- IV glucose w/o fat induces EFA deficiency w/ accompanying symptomatology
- Hydrogenated coconut oil and tallow are used to induce EFA deficiency in lab animals
- PUFA induced NAFLD seems to be dependent on what mouse model is being used, for example, diabetic prone mice already have deranged EFA metabolism, as a result EFA would be implicated much like cholesterol is implicated in various disease states but interventions fail, flawed logic, do you biology? LOL.
- Symptoms of EFA deficiency take weeks not years to appear (even when nutrition is adequate)
- Reversal of EFA deficiencies with sources of LA and ALA largely resolve acute symptomatology within weeks not years, the idea it takes years to deplete PUFA stores is unrealistic
- Common symptoms of chronic EFA deficiency are hair loss, increased shedding, and skin abnormalities, hair and skin is one of the most metabolically active tissues, the idea that EFAs slow metabolism is an unrealistic mechanism; same for improvements in skin quality
- LA and ALA seem to spare the B vitamins and vice versa
- Symptoms of EFA deficiency are reminiscent of hypothyroidism (thinning of hair, thinning of outer eyebrows)
- EFAs are required for proper epithelial differentiation and proliferation, this not only has implications for hair and skin but ALL epithelial cells including the GI tract along with gut permeability
- EFA deficient animals manifest with slowed wound healing, this is a problem as the longer a wound takes to heal the more susceptible one is to infection and scarring
- The immune system requires LA and ALA to function properly, immune cells hoard EFAs and use the peroxides generated from EFAs to disable viruses and bacteria
- EFAs are required for the proper metabolism of saturated fatty acids (the mechanism is not clear yet)
- EFAs are required for myofibrillar and sarcoplasmic hypertrophy
- EFAs are required for some hormone production, especially some of the stress hormones, a failure in the production of stress hormones would inhibit the stress response, thus adaptation, leading to maladaptive and degenerative state
- EFA deficiencies manifest psychologically with the following traits: depression, aggression, hostility, changes in attention, motivation, changes in reactivity to stimuli and reward, general personality disorders such as obsessive compulsive behavior, apathy, and eating disorders
- EFAs required for proper sex organ function and development in both males and females
- EFA metabolism is complex, supplemental EFAs can resolve EFA symptomatology in most cases, however, perturbations of desaturase and elongase activity such as those seen different disease phenotypes can prove difficult to treat though because the underlying machinery is deranged
- EFA derangement is seen in the following conditions, alloxan and streptozotocin treated diabetic rats, diabetes, vitamin E and selenium deficiencies, cystic fibrosis, copper deficiency, Kwashiorkor, adult respiratory distress syndrome, chronic and acute carbon tetrachloride poisoning, multiple sclerosis, most chronic and acute neurological diseases, LEC rat models of fulminant hepatitis, hepatic cancer, Wilson’s disease, sudden cardiac death, beta-Thalassaemia major, abnormal umbilical cord blood cells
- Mead acid is increased during EFA deficiency, the largest reservoir of mead acid is the cartilage, after stores of oleic acid are exhausted soft tissues particularly in the joints are robbed of mead acid stores, it is plausible this can lead to joint degeneration, stiffening of joints, loss of flexibility, calcification of joints
- LA and ALA are the only known essential fatty acids (in humans, mice have different available desaturase and elongase enzymes, as do other species along with varying capacities), other fatty acids sometimes associated with EFAs such as DHA, EPA, AA, are what are known as ‘conditional essential fatty acids’
- Contrary to the antioxidant hypothesis, Vitamin E may not be involved with stabilizing polyunsaturated fat i.e. reducing its proneness towards oxidation, rather Vitamin E is involved with the function of desaturation ezymes, which of course is a more plausible mechanism
- LA probably is an important part of the mammalian antioxidant system
- There are sex differences in EFA metabolism that are proportional to muscle mass
P.S. I can ABSOLUTELY tell you without a doubt B6 won’t fix that. LOL.Bold claim? Nope. Demonstrated in 1938.
These results show that rats may develop acrodynia-like dermatitis if the diet is free from fat even when moderately large amounts of B6 are given. The possibility that the disease observed by Burr and Burr might be due to a low intake of vitamin B6 is ruled out by the finding that even with 10 times the minimum curative dose, unsaturated fatty acid is necessary for normal health and growth. The fatty acid factor is, therefore, an essential constituent of the diet for rats.
This has probably been the longest I’ve sat with one topic, but as it stands the saga continues, this bit of information is something I’ve been sitting on for quite a while, but I came across it again in another paper and had to post.
P.S. I can ABSOLUTELY tell you without a doubt B6 won’t fix that. LOL.
As the title implies there is a lot to cover. For now, I wanted to post that paper from the previous post.
Best wishes, Edward
Everybody loves a little click bait. And this is click bait. As part of my ongoing “Unifying biology” series I had planned to do a post on essential fatty acids. It was one of the first things I planned on covering. Initially, as you can see below I have a good start. But then I got side tracked by other things I wanted to cover and because the more I read about EFA’s and the history of their research and their relationship with B vitamins the more I realized this particular topic was not going to be easy to neatly fold and place in the drawer. The truth is while I have been silent on the necessity of the classical essential fatty acids, I have been quite adamant of my position on polyunsaturated fats. Essential fatty acids have always been a sort of moot point for me, my assumption was always that if you are eating animal products you are going to get some depending on your favorite animal. That is true. But it turns out there is a story to be told. Stay tuned for the next post in my “Unifying biology” series.
I have a pathological proclivity leaning towards disenchantment with extremes. Yet, at the same time I cannot help myself, I spend a great deal of my research time exploring extremes in biology. I largely see extremes as sources of inspiration. I do give myself a chance to allow that inspiration to provoke new questions. Sometimes off the wall questions, I’m sure my peers over the years would agree. Sometimes I have posed off the wall questions to my peers just to see what kind of person I am dealing with. Is this a person who is seeking truth or is this a person seeking compliance?
But I mainly direct these off the wall questions to myself, bias is a problem in any scientific discipline, and one of the ways you can limit the bias is by trying to dethrone yourself. I have dethroned myself many times over the years and any internally consistent person truly seeking some element of truth should be comfortable with consuming the proverbial foot or two. I have eaten many pairs of feet.
The truth is I don’t see extremes as outliers, and I don’t see outliers as extremes. I see outliers and extremes as unifiers. I have mentioned in the past that individual ideology can leak into your scientific perspective. This is true for me. My ideology of placing emphasis on the individual as unique and valuable leaks into everything I do. That is a hard pill for some to swallow, even if I fundamentally disagree with you, I still think you are unique and valuable. At the end of the day you are a human. We have that in common. That is all I need. In fact, the people I value the most are the people who challenge my thoughts and ideas. This is where learning occurs.
One of the questions I asked myself years ago is: Why does our physiology produce ketones when we restrict carbohydrate? Now, before you rattle off in your brain all the circumstances under which we produce ketones, read the question: Why do we produce ketones?
One of the central tenants of my hypothesis as I stated in my previous blog post is that we produce ketones when we are hypoxic, whether it be at the cellular level, the tissue level, the organ level, system level or organism level. In other words, when your cells can not utilize oxygen OR there is a lack of oxygen your physiology will produce ketones.
What do I mean by “your cells can not utilize oxygen”? For example, you can be under normal oxygen levels but for a variety of reasons your cells fail to utilize oxygen. Maybe your mitochondria are broken. Similarly, oxygen levels can be lower but maybe you have unbroken mitochondria and you can use oxygen more efficiently. The later would make you more resistant to stress and the former would make you more sensitive to stress.
There are a variety of circumstances under which ketones are produced, ketones are produced in elevated amounts after birth, ketones are produced after exercise, ketones are produced during sleep, ketones are produced during nutritional ketosis, ketones are produced at altitude, ketones are produced during metabolic ketoacidosis, and under many more circumstances.
If you are sharp, you’ll notice that ketones are produced physiologically such as after birth, after exercise, during sleep, and at altitude. You’ll also notice that ketones are sometimes produced in association with different disease pathologies, diabetic ketoacidosis being the most familiar example. Then there are the compounds that can induce hypoxia by interfering with oxygen utilization and ketones are produced. For example, hydrogen cyanide and alcohol.
The one thing all those things have in common whether physiological or pathological or induced is that all those states are states in which oxygen use is limited in some way.
When hypoxia is present so are ketones. In fact, the ketogenic pathways are very ancient even water bears (Tardigrade) make ketones. Interesting.
What other things can elevate ketones? Well we know for sure that by restricting carbohydrate that we can self-induce ketone production and if the production of ketones indicates hypoxia perhaps that might not be an ideal state to be in?
What about fructose? Can fructose increase ketone production? That was one of the off the wall questions I dared to ask myself.
For the purpose of this blog post which serves as an introduction to this concept I will be posting clips from papers, over the next few articles I will provide the citations, for now I want to just cover the basics and tell you a story.
Let’s start with this:
Fructose it seems can induce ketogenesis and if we accept that ketones are an indication of hypoxia and we consider the implications of chronic hypoxia and that it precipitates all disease, all the sudden we have a very plausible explanation for the association of fructose with different disease states.
In the above paper they are validating this:
This group did their homework, they said this is interesting, does this occur under physiological levels? Right? Because we want to know, does this have practical relevance.
Then during the same era, we have this:
One of the interesting things about this paper is the mention that the glycogen content of the liver increased. It is well known that fructose not only increases gluconeogenesis but that fructose in fact inhibits glycogenolysis. What is not well known in some circles is that the elevated gluconeogenesis is a response to the fructose, but at the same time while there is an increase in glycogen formation there is inhibited breakdown of glycogen. Now we have a very good partial mechanism to explain why, while fructose has no need for insulin, why there are transient increases in fasting blood glucose and fasting insulin. This is part of the reason why diabetics often have distended livers. Because glycogenolysis is inhibited glycogen continues to be deposited in the liver, it is an under reported complication of diabetes and can be confused with nonalcoholic fatty liver disease unless a biopsy is done, and a PAS stain ordered.
There are more. But for now, it seems like fructose can induce ketogenesis. The reason for this is because fructose is inducing internal metabollic hypoxia. But that is only if you accept the idea that ketones are generated under conditions of lowered oxygen or inefficient oxygen use. So, is that true?
This was an observation made in the 1930’s. I know some of you like old papers. It was the first observation of its kind. And it was verified by another group in the same era.
Translation as oxygen tension increases BHB is converted back to acetoacetic acid when oxygen decreases acetoacetic acid is converted to BHB.
In the beginning of this short post I mentioned that I have a pathological proclivity leaning towards disenchantment with extremes. In that context, those extremes I am referring to are the polarized cults on both sides of the fence who refuse to consider the arguments each side makes AND the evidence both sides bring to the table. Everybody seems to hate each other these days but what if I told you that there were arguments on both sides that were partially correct and arguments on both sides that are absolutely wrong and that there is a hill in the middle that explains both sides more adequately than each extreme can account for with their own dogma?
So how does this apply practically? Is it a simple matter of avoiding things that cause hypoxia and thus ketogenesis? Do we avoid fructose like it is the Black Plague? Is it really that black and white? Not at all, it’s more elegant than that as we shall see. Much more elegant. No spoilers.
One of the questions I’ve been trying to develop an intellectually satisfying answer to for the past decade is: Why did Kwasniewski and Lutz seem to advise against ketosis, was it empirical or esoteric?
I find the hypoxic in utero environment of the fetus and subsequent metabolic transition of the neonate to a normoxic environment and eventual metabolic transformation fascinating. After gestation interesting things are occurring metabolically, increases in lactate, increases in ketogenesis and gluconeogenesis. The scant number of tracer studies looking at infant metabolism seem to indicate that exogenous lactose from breast milk and endogenous glucose as a result of gluconeogenesis is being shunted towards biosynthetic pathways and glucose is metabolically spared. In breast fed infants, glucose concentrations increase cyclically maintaining normoglycaemia. In contrast, infants administered oral solutions of glucose develop cyclical hypoglycemia.
I suspect there are morphological and functional differences between infant and adult mitochondria. There are reasons for this suspicion. Infants administered glucose less than 1 month after gestation present with glucose intolerance and glucose tolerance subsequently increases over the following months of development; additionally, the metabolic substrate profile points in that direction.
Infants have generous amounts of adipose tissue and as the infant transitions to a toddler and child, adipose tissue declines. I would suggest this is a result of maturing mitochondrial morphology and function; and that elevated lactate and ketones reflects fatty acid oxidation (FAO) capacity. This physiological metabolic transition is a result of adapting to an externally normoxic environment. Interestingly, for every 1000 meter increase in elevation there is a reduction in neonate mass and an increase in the incidence of fetal death.
One of the central tenets of my hypothesis is that ketone formation indicates hypoxia be it a histophysiological adaptation to external environmental conditions and physiological stimuli or; a pathophysiological disorder resulting from chronic exposure to compounds and energy substrates that interfere with or block normal histophysiological adaptations. In other words, anything that chronically interferes or blocks normal homeostatic processes produces a maladapted and eventually, unadaptive state, leading to entropy i.e. degeneration and death.
There is a beautiful cyclical metabolic signature from conception to death reflecting our ability to deal with oxygen and lack thereof; the energy substrates that build and prepare us for an oxygenated environment are eventually the same energy substrates that kill us. We develop in a hypoxic in utero environment and adapt to an oxygen rich environment. After birth and in the presence of oxygen our physiology matures and develops reflecting the external environmental conditions. As our mitochondria learn how to breathe, we slowly loose the ketogenic capacity present during early stages of life and transition to a reliance on fatty acids and develop the capacity to rely on glucose, fructose, and ketones when intermittent hypoxia is present. When intermittent hypoxia is present our mitochondria temporarily uncouple and become physiologically insulin sensitive and glucose is used to facilitate adaptation via biosynthetic pathways.
As we age our ketogenic capacity continues to decline along with a diminishing fatty acid oxidation capacity. In the context of this decline, not only do we lose the ability to produce adequate ketones to continually adapt to intermittent hypoxia, our mitochondria degenerate losing the ability to metabolize fatty acids and our physiology becomes more and more reliant on glucose as a metabolic substrate and as a result we lose the ability to maintain physiological insulin resistance. Slowly the adaptive state of intermittent physiological insulin sensitivity becomes pathophysiological and we lose the physiological insulin resistance of our youth.
As I have reflected on in the past, glucose is a primitive energy substrate, a glucose driven metabolism, contrasted with glucose used as a biosynthetic substrate in the context of a fatty acid driven metabolism, will drive primitive histophysiology and the subsequent degeneration of the orchestra. Every day the orchestra slowly goes out of tune and eventually the musicians slowly start disappearing, eventually the conductor has no musicians and he will turn to the audience, take a bow, and you will take your last breath.
In the end you will suffocate to death.
Why did Kwasniewski and Lutz seem to advise against ketosis?
- Whether they knew better or not, chronic ketosis indicates hypoxia.
- The conservative amount of glucose needed to stay out of deep chronic ketosis facilitates physiological insulin resistance and supports adaptive physiological insulin sensitivity during intermittent hypoxia.
- Ketosis reflects fatty acid oxidation capacity.
This is an aside but worth talking about.
Typically, we talk about heme and nonheme iron when we are going to discuss iron in biology. And one of the reasons I don’t worry about my hemochromatosis too much even though heme iron is more “bioavailable” and I like red meat is because the heme iron, the kind found in meat, is bound to a hemeprotein. That I eat red meat is contrarian.
In the case of hemoglobin this hemeprotein functions somewhat like a “conditional loop”, when pH is low and carbon dioxide is high (as in hypoxia i.e. generally a lack of oxygen to cells, tissues, organs, and the organism) hemoglobin will “release” oxygen to surrounding tissues.
When the situation is reversed higher pH and low carbon dioxide hemoglobin will “up take” oxygen. It is a controlled situation and hypoxia inducible factors seem to mediate part of this controlled situation.
My suspicion is that under normal atmospheric conditions being metabolically hypoxic (intake of significant amounts of fructose at sea level under normoxia) can be problematic and partially explains why sea level diabetics often have relief of symptoms at altitude. [This is a dynamic interaction with many environmental conditions to include energy substrates, the picture being painted will become clear as this series progresses.]
Fructose can chelate with inorganic iron. Ingested nonheme iron needs to be reduced to be absorbed and used appropriately which our intestinal cells can do. Prior to that conversion iron can react with compounds such as ascorbic acid or fructose.
In parallel, fructose tends to cause hemoglobin to release its bound iron and reduce oxygen affinity of hemoglobin and this is probably why we see iron implicated in many different phenotypical states (disease states), while the total picture is more complex than a single variable, iron is an important nexus to facilitate understanding. This unbound iron can do damage in the right contexts.
In diabetic-like phenotypes, fructose in erythrocytes (red blood cells) is about 3-4 times higher than it is in non-diabetic phenotypes. When hemoglobin is incubated with fructose, fructated hemoglobin forms (similar to glycated hemoglobin but with fructose instead of glucose). When ferrozine is added to a solution containing ferrous iron, the ferrozine binds with ferrous iron and produces a magenta colored solution. This is something you would do if you want to confirm that fructated hemoglobin is releasing its iron. Indeed, when ferrozine is added to a medium containing fructated hemoglobin it turns magenta reflecting the level of fructosylation/fructation, proportionally.
We know that fructose fructates hemoglobin, and we know it disrupts the heme protein causing an increase in free iron and this partly explains the interference with oxygen affinity. One other interesting thing to point out regarding iron containing protein complexes is that cytochrome p450 is an iron containing protein. Cytochrome p450 is involved with steroid hormone synthesis, xenobiotic and polyunsaturated fatty acid metabolism.
All cells are constantly turning over heme which is facilitated by heme oxygenase (HO) to produce carbon monoxide, ferrous iron (Fe2+) and biliverdin/bilirubin. Bilirubin binds to albumin and is transported to the liver where it binds with glucuronate and is excreted (glucuronidation). This is normal physiology.
In fructose induced nonalcoholic fatty liver states there is an increase in deposited iron that is attenuated by heme oxygenase. Heme oxygenase requires oxygen, protons (H+), and NADPH and increases superoxide dismutase activity. Acutely, our physiology can handle this when we are at our baseline phenotype. Chronically this reaction cannot sustain, and this is for several reasons, most importantly, failure of oxygen delivery inhibits palmitic acid driven mitochondrial oxidative phosphorylation and increases the reliance on glycolytic energy metabolism. One of the other over looked aspects of a reliance on glycolytic energy pathways is that the mitochondria participate in the generation of steroid hormones and normal cellular function, you need palmitic driven OXPHOS for this occur. The question is, which comes first disrupted oxygen delivery or inhibited OXPHOS by fructose? Or are they in parallel?
At sea level and in the context of sufficient sources of heme iron and saturated fatty acids hemoglobin is saturated with oxygen and oxygen transport occurs normally and is partially under the control of hypoxia inducible factors (HIF).
However, in the context of excessive fructose in conjunction with nonheme iron as well as fructose interfering with in situ hemoglobin causing iron release and affecting oxygen affinity (and interfering with cellular respiration as a result), fructose and liberated iron from hemoglobin will potentially react with the excess iron and oxygen released from these reactions as well as the oxygen delivered from organism level respiration (breathing) further interfering with oxygen delivery.
In essence—excess fructose in a higher oxygen environment not only disrupts in situ function of hemoglobin but also reacts with unbound nonheme iron and interferes with HO producing a hypoxic phenotype. Until fructose concentrations fall this is a vicious cycle that affects the protein, lipid, and carbohydrate structures of intact cells. Again, acutely we are equipped for such insults. Chronically this leads to accelerated degeneration.
For the past year or so, I’ve been attempting to develop a hypothesis that unifies a lot of concepts in biology. My primary interest is understanding respiration at the cellular level and at the organism level; understanding the interplay between the two; and how that interplay, manifests as observable physiology, pathology, and psychology.
Just uttering the word unify in scientific circles if you are keen enough to notice, draws a target on your back, and rightfully so. There is no shortage of hair brained drain circling ideas out there. Criticism is welcome.
Though I work in the field of pathology, more specifically histology, I generally prefer the somewhat out of fashion term histophysiology to describe the things that interest me. Here is why:
Histophysiology: a branch of physiology concerned with the function and activities of tissues; structural and functional tissue organization.
Pathology: the study of the essential nature of diseases and especially of the structural and functional changes produced by them; something abnormal; the structural and functional deviations from the normal that constitute disease or characterize a particular disease.
Physiology: a branch of biology that deals with the functions and activities of life or of living matter (such as organs, tissues, or cells) and of the physical and chemical phenomena involved.
Pathophysiology: the physiology of abnormal states.
Histology: a branch of anatomy that deals with the minute structure of animal and plant tissues as discernible with the microscope; tissue structure or organization.
Its more useful from my perspective to understand how cells work rather than deviation from normal, as normal is subjective. I am more comfortable with classifying various diseases and pathologies as dynamic phenotypes.
This is important to me for several reasons. First, classifying various pathologies as phenotypes allows us to understand, at least in thinking, that a disease is an adaptation (bear in mind that adaptation does not necessarily mean the adaptation is subjectively beneficial). The abnormal (phenotype), if you will, is the dynamic response of the cell to dynamic conditions.
The problem with the word disease, with the way we perceive disease, is that it implies that the cell is responding irrationally and independent of the environment when in fact the cell is responding very rationally and quite dependently on the environment.
From a philosophical perspective it is a misunderstanding to say when environmental conditions produce abnormal phenotypes that the environment is somehow defected. In one sense this is true, but only in the sense of how we perceive what normal is. Cells respond to the environment and adapt to the conditions of the environment, rationally. Cells don’t respond independently of their environment for our sake.
While that may sound like semantics it is necessary.
There is a dynamic relationship that the cell has with its environment to include energy substrates. Certain types of cells prefer different kinds of energy substrates. And on a bigger scale, groups of cells that compose larger structures like tissue, control their local environment to ensure they receive proper energy substrates.
When the internal environment of a tissue type no longer has access to a preferred energy substrate the cell/tissue can intermittently physiologically adapt to another energy substrate. However, a chronic shift to an unpreferred energy substrate will eventually cause a shift in the cellular phenotype and through proliferation, eventually affect tissue structure and function. That may or may not be subjectively beneficial.
While cells certainly respond to the conditions of their environment, a group of cells can also generate an internal environment to support their group level goals by using other energy substrates via in situ structure to generate a gradient barrier. The generated gradient barrier that protects the group level preferred environment and access to the tissues preferred energy substrates is called an organ.
Via structure, energy substrates can then be routed to various locations and the preferred mixtures of energy substrates can be taken up by different cells and tissue types that have different requirements to maintain their preferred internal environment to support their overall structure and functionality. It is important to understand that this preferred functionality is interdependent on other tissues/organs behaving in their preferred manner and maintaining their preferred internal environment. The saying: One man’s trash is another man’s treasure applies. When all cells/tissues/organs are interdependently in concert we call this an organism.
When conditions change and a tissue can no longer access its preferred energy substrate, an intermittent physiological switch to another energy substrate occurs, if the access to the preferred energy substrate is chronically bottlenecked, the internal environment of a group of cells fundamentally changes. When this occurs this affects the energy substrate supply to other groups of tissues because the concert is over. A systemic phenotypical shift begins.
If the phenotypical shift is chronic, there is then deviation from the baseline phenotype, this deviation fundamentally alters tissue structure and function and the concert is now playing another piece which you may or may not enjoy.
As humans we strive to keep the original concert going. The piece we enjoy. The piece we call I ormyself. We all sense when something is out of tune. Sometimes its just one violinist others its the whole section and at our worst the whole orchestra is out of tune or no longer playing our favorite piece.
The question is how do we ensure the internal environment stays in concert playing I for as long as possible so you can adapt and respond appropriately to the external environment consciously and unconsciously.
This past week I’ve been spending quite a bit of time thinking about L. reuteri. One of the interesting things I’ve mentioned in the past and why I think that this particular strain is interesting out of all the other different species is because L. reuteri was a dominant species in the human gut in the middle twentieth century according to literature and samplings done during that time period. Present day this seems to not be the case. In fact, it seems to be quite rare.
One of the interesting things about L. reuteri is that the antimicrobial compound it produces, reuterin, is produced in the presence of glycerol. Glycerol as you know forms the backbone of triglycerides i.e. fat. In the lab, reuterin can be synthesized simply by culturing L. reuteri with glycerol. L. reuteri is unique in that it will thrive in 16:0 and 18:0 i.e palmitic and stearic acid growth medium.
It’s growth however, can be inhibited by excess consumption of polyunsaturated fat and in particular 18:2 or linoleic acid. While some strains have been shown to mutate in the presence of LA and evolve defense mechanisms to protect itself from LA, they don’t thrive as much as they do when LA is low. In other words LA is bactericidal/bacteriostatic. A bactericidal compound literally kills bacteria whereas a bacteriostatic compound simple inhibits growth. The effect that LA has on bacteria has been known since the early 20th century.If we take a look at these figures for sources of LA in the diet we can see that LA has dramatically increased mostly from increased soybean oil and poultry consumption.
If we take a look at these figures for sources of LA in the diet we can see that LA has dramatically increased mostly from increased soybean oil and poultry consumption.
That is a very interesting coincidence along with the falls in palmitic and stearic acid.
When bile is released it breaks down triglycerides into it’s basic components, free glycerol and 3 free fatty acids. The free glycerol would have provided substrates for L. reuteri to produce reuterin and the free fatty acids would have provided the approperiate energy substrates for L. reuteri to continue to thrive and remain dominant.
However, with declining saturated fat and meat intake and the increase in 18:2 since the middle part of the 20th century, this would have proved unhospitable to L. reuteri thus destroying any benefit to a symbiotic relationship. No more free lunch.While most bacterial strains can thrive with a variety of different energy substrates, they proliferate and dominate when they are provided with the right energy substrates that allow them to effectively compete. When you remove those things and simultaneously introduce a hostile environment they vacate.
Given the long evolutionary history we have seemed to have had with L. reuteri and the increasing amounts of carbohydrate and LA in the human diet and the decreasing prevalence of L. reuteri, I’d venture to say that this particular species is well suited to thrive in a diet low in carbohydrate and rich in fat. In other words it doesn’t need carbohydrate to thrive. I’ve often thought of the gut biomass as only being relevant in the context of diets that contain elevated amounts of ruffage. Clearly this is not always the case as L. reuteri likes glycerol, amino acids, and saturated fat, and doesn’t like LA, so as far as I’m concerned me and L. reuteri can be friends.
Given that L. reuteri thrives at physiological temperatures, culturing at 37C probably is fine.
L. reuteri produces a broad spectrum antibiotic compound called reuterin. The principle effect of reuterin is to kill off competing strains of bacteria and parasites. While reuterin is classed as an antibiotic the designation is somewhat misleading because it implies that L. reuteri is producing reuterin for the benefit of the host. In reality, it is produced for the benefit of itself; the benefit to the host is a convenient side effect. In other words, L. reuteri is killing off other strains of gut bacteria to plow the field for its own colonization i.e. a bit of slash and burn. While I have reason to believe the antibiotic side effect is beneficial overall, I don’t think it is without consequence if your gut is colonized by pathogens that are susceptible to reuterin.
The situational scenario I see happening is L. reuteri entering the GI tract and then opportunistically producing reuterin to kill off competitors, in response to this, the competing bacteria then release their own set of defensive chemicals, e.g. bacteriocins, endotoxin/lipopolysaccharides/lipoglycans. It is completely plausible that this thermonuclear war can lead to host discomfort with accompanying symptomology.
In my anecdotal experience with taking L. reuteri for a month, 1-2 tablets a day with meals, I had minor symptomology indicative of such a scenario. In the first week I did have one day where my stools were loose as a goose, and I intermittently had cold feet indicative of subclinical “endotoxemia”.
The second week, I had symptoms of some sort of modulatory effect on my thyroid hormone axis, feeling a little anxious and some feelings of agitation reminiscent of the times I supplemented with thyroid hormone but those feelings never overwhelmingly became my modus operandi.
By the end of the second and into the third and fourth week I had somewhat increased mucous production or the feeling of a film in my mouth and throat. I also had wild cravings. Wild cravings which I indulged in.
At the end of the fourth week the thyroid symptoms which were intermittent resolved and the mucous production most likely due to the biofilm L. reuteri establishes interacting with my own mucus production had normalized and the cravings winded down.
All throughout the experience I did notice that my digestion improved and that bloating wasn’t an issue by the 3rd and 4th week although bloating was intermittent the first and second week.
Regarding thyroid hormone, while it is possible for a direct effect on the thyroid hormone axis, in my opinion, the effect is likely indirect and a consequence of modulating the microbiome—as in—reducing the bacterial count of bacterial strains that produce chemical species that have an inhibitory effect on the thyroid hormone axis below a physiologically relevant amount.
I do think that this indirect effect is the most likely the route that L. reuteri sustains the more “youthful” hormonal pattern evidenced in the literature and is more in line with a symbiotic relationship rather than a direct effect.
All of the symptoms I had were minor compared to some of the things reported by others who have taken L. reuteri. I want to emphasize that I also spent the beginning of my life into my twenties on antibiotics and that may be why my symptoms were minor, so it is possible I simply had less harmful strains colonized in my GI tract and thus less overall harmful biomass to reduce. Do I think L. reuteri killed all those harmful strains? Not at all, I think it is more likely it reduced bacterial counts and consequently the harmful chemical species they produce below the physiological amounts required to produce symptomology. I do think those potentially harmful species are there, but now I feel they are probably low enough to avoid negative symptoms and perhaps relevantly high enough to produce a hormetic effect on the immune “system” which I view as ideal.
I do think I have been colonized by L. reuteri as the perceived benefits have continued to persist. The literature alludes to the fact that overtime counts of L. reuteri can fall requiring a “booster” after several months but I’m somewhat skeptical of this and think it probably depends on overall eating habits. Since L. reuteri seems to be found naturally in dairy and meat before we cook it, it superficially appears that that should be enough to maintain populations without “boosters”. We shall see how things develop over the coming months.
Overall, I feel happier and more exploratory and patient and I can eat more of the foods I like when I care to have them. To me that is a quality of life improvement and for some of you it might be worth exploring.
A member of my Discord server asked a very good question that I haven’t really addressed, here is part of the answer.
I think the speculation that there is a sweet spot is correct as at either extreme of temperature ATP production becomes unstable.
I do remember seeing posts of people claiming they were hypothyroid right around the time Paul Jaminet introduced the Perfect Health Diet. I also remember some of the more extreme people saying the chilliness people where experiencing was a sign that they were doing things right. LOL.
I’m not sure who originated the idea that ketosis was causal in thyroid dysfunction/low T3 except that, very consistently, lower T3 is associated ketosis type diets and starvation and further I’m not quite sure where the idea even comes from as far as being “harmful” as the effect ON SERUM is expected. Not very many of them provided evidence for this, so I’m not sure if it was based on signs and symptoms or symptoms alone. But the effect is physiological not pathological; at least initially.
Regardless, across species there is an inverse correlation between T3 and longevity and like with temperature there probably is a sweet spot for T3 as well but serum measurements are highly variable. What is important is local tissue levels which we don’t have commercial tests for; but we can do this in the lab with PCR, which I have done when I was researching the effects that viruses have on cellular thyroid hormone metabolism.
I’ve mentioned in the past that when cells are provided with the correct energy substrates that hormones are background. There is normal circadian oscillation for catabolic and anabolic processes but in a situation where appropriate energy substrates are used hormones remain in the background.
Lifecycle oscillations of thyroid hormone are also orchestrated by physiological processes such as in utero and during birth, stress, cold, the death of a family member or a bad breakup. In healthy adults, there also is an postive association between T3 and waist size that nobody seems to want to address. Indeed, T3 administration above physiological amounts causes diabetes to develop.
As well, during illness thyroid hormone levels decrease, adjuvant therapy with thyroid hormone during these situations tends to exacerbate the illness pointing in the direction that fluctuation in thyroid hormones is an adaptive process.
Thyroid hormones are catabolic, sometimes they appear anabolic but this is only because during catabolism, anabolic parameters also increase.
Increased T3 is a symptom of hypoxia both at the cellular, tissue, and organism level and the level of hypoxia in vivo is largely an effect of 2 things 1) the predominant metabolic substrates being provided to your cells and 2) the external availability of oxygen.
When does thyroid hormone increase? Under carbohydrate load and under anaerobic/hypoxic conditions. Given that thyroid hormone is catabolic this makes sense, as the increased local thyroid hormone concentration is secondary symptom of anaerobic/carbohydrate metabolism.
Excess carbohydrates in a normoxic environment is maladaptive, as I’ve pointed out in the past in my energy and structure blog posts, carbohydrates are a primitive fuel source this is why high-level organisms utilize fatty acids for their basal metabolism unless the situation is such that they are in a hypoxic environment. Even in naked mole rats although serum levels of thyroid hormones are low, ultrastructurally (cellular and tissue level) there is increased secretion of the hormones.
One of the functions of thyroid hormones is to orchestrate “form”, what this means is that through very carefully controlled fluctuations in cellular respiration you can change the phenotype of a cell, you can also kill cells with thyroid hormones which is part of their function as well in organisms that go through metamorphosis. For example, in tadpoles as the frog develops thyroid hormones increase to supraphysiological levels at the posterior-proximal junction of the tadpole tail, ROS and autophagy increases and the tail essentially cauterizes off.
Thyroid hormones are a necessary to “keep form”, thyroid hormones activate during carbohydrate/hypoxic situations in order to keep the cells utilizing carbohydrates from degenerating into more primitive cell types, for example, cancer. When this mechanism fails, for any number of reasons, whether it be fueling the basal metabolism with primitive energy substrates, external hypoxia, internal hypoxia from antimetabolic compounds, at the end of the day thyroid hormones help to maintain “form”, structure, and function. In a very real sense not only is thyroid hormone catabolic, it is protective and can be better classified as a stress hormone. It is an organizer.
One of the things that happens during Paleo style diets with all the PUFA, nuts, antinutrients, excess protein, etc., is that all of these things have an inhibiting effect on respiration. While serum levels of thyroid hormones fall, it is only because ultrastructural levels of thyroid hormone increase, that is, more is being used than can be produced, hence the nuclear blast of unsavory symptoms.
So your last point:
“This was the main reason I always steered clear of ketogenic diets. What do you make of that? Could it be simply the cumulative inhibitory effect of PUFA, since these people were probably not discriminating againsts those fat sources? Could it be the compounding of these diets + exercise that causes this? Excessive protein elevating cortisol and that in turn suppressing thyroid function?”
You hit the nail on the head exactly. Lower serum = higher ultrastructural levels = emergency = maintaining form because of the hypoxia induced from Paleo style diets is more important than thermoregulation. Your physiology is redirecting ATP and H+ pools to maintain form to survive verses cozy metabolically generated warmth.
Saturated fat does not do this. I steer clear of ketosis. Ketones are a symptom of hypoxia. We are indeed omnivores, glucose is essential for optimal health, people who say well, we have gluconeogenesis and ketones aren’t thinking about things in the broader context. It’s like, we have those pathways as evidence that yes, some glucose is required and probably optimal, we do not have the high output gluconeogenic pathways that true carnivores have. And when are those pathways active? Hmmm.
I hope that that answers at least part of your question. Ask any follow up questions and I’ll be sure to address them. This is a good topic.
Aside: One of the interesting things to look at is that RPF folks can sometimes initially loose weight, that is a function of elevated thyroid hormones trying to rescue the metabolism, but if they continue and ignore all shitty symptoms all of the sudden they blow the fuck up whether it is weight gain or worsening problems such as panic attacks, helplessness, social avoidance, etc. These of course are all symptoms of hypoxia … unless they start taking thyroid hormone. I prefer the advice “… let us avoid the problem to begin with …” the situation with the folks on the RPF is first physiological then pathological. Yikes.
This post stems from a question on Discord about why I’ve moved away from drinking milk (and if you haven’t joined my Discord server, please do, there are a lot of smart people on there with lots of different experiences).
This is going to be a bit all over.
Most of the benefits of milk are from the milkfat and some of the more exotic lipids contained in the milkfat.
The galactose is beneficial in certain contexts because over the long term if your cells have a diabetic like phenotype or a hypoxic phenotype (dare I say they are basically the same thing), galactose will shift the cell state to increase OXPHOS increasing ATP and oxygen consumption, glucose doesn’t seem to be able to shift the cell metabolic phenotype in a positive direction except to maintain whatever state the mitochondria are in and potentially worsen it if cells are in an already diabetic like phenotype and glucose isn’t being directed properly. Fructose definitely can in the right contexts.
Glucose is not a good metabolic substrate to rely on predominately if you are an organism that relies on palmitic acid driven OXPHOS and like to breathe oxygen; and I would distinguish between a basal and peripheral metabolism here. From my experiences you can have quite a bit of potatoes and still have room to breathe.
It’s important to note that acute exposure to galactose will not cause this shift, cells have to be exposed chronically (environmentally) for the shift to occur permanently. Once the steady state is restored cells will happily burn palmitic acid and a nice physiological insulin resistant state can be restored.
When I think about milk and in particular the galactose and ketones increasing at altitude it’s not hard to imagine that milk is the input which produces the desired metabolic output i.e. moving from a hypoxic to normoxic environment. Not too much different than fructose driven glycolysis in low oxygen environments.
When I think about ketones and their ability to “prevent” or “reduce” the consequences of hypoxia I think given how high they are in human babies that mitochondria are still developing oxidative capacity and the internal “atmospheric conditions” are being buffered if not facilitated by lactate.
Tissue unsaturation does increase as one climbs in altitude and this may account for the higher rates of skin cancer and so do ketones.
All energy substrates have “innate”, yikes, pros and cons that will make your life adaptive or miserable as internal and external environmental factors change. One prediction would be that as oxygen becomes less available there is more reliance on glucose as a suitable energy substrate along with raises in ketones and lactate. And in some cases fructose. When exogenous glucose is not available fat serves the ketone lunch.
This is why ketosis is not appropriate in my opinion except as an intervention. Ketosis is a side effect, the benefits come from SFAs.
And while the intervention can resolve symptoms, it does not as far as I can tell “cure” things, it just keeps life going but you still slowly fall apart.
To cure things, you have to provide stimulus that can rebuild structure. And so, this builds on my energy and structure post.
So why don’t we want to drink milk all the time if it has the benefits of restoring OXPHOS? Restoring is the key word here. Well when I drank milk all the time I found that my diet was quite limited and I’m a guy who likes variety and thinks monotherapy diets are interventions not cures and tend to think they predispose people to orthorexia and a host of other psychological problems.
Eventually you get tired of milk and want a bit of substance. I tend to pay attention to what I’m hungry for, I tend to trust that, maybe a bit too much for some people, maybe not enough, I’m cautious and there is some logic behind how I judge whether or not a craving is a real need verses something more psychological. That doesn’t mean you shouldn’t eat something for psychological reasons and there is definitely some interplay in which a psychological craving might have overall benefit. But let’s not get too spooky here.
When you get to the point where your like, I’d like to chew on something, it’s probably a good sign that you need to chew on something besides the meat in your meat and milk diet.
For those of you who understand my cryptologic you’ll know that I’m not a fan of fruits and vegetables, but I am a fan at the same time because I like a little NERF ball. That is Nuclear factor (erythroid-derived 2)-like 2 or NRF2.
I think, though this is working through some higher level signaling (not everyone can conceptualize the implications of metabolic substrates and NRF2 is a good place to have that dialog), that this is one of the ways antioxidants work, it’s not because they are functionally benefiting the system, it’s because they are assaulting the system and whittling out adaptation by increasing our own mammalian antioxidant system (this explains the dose bell curve of antioxidants as well), since exercise, antioxidants, and other stressors (psychological stress) hit NRF2 it is a good common ground and the proverbial point in which “cures” as differentiated from “interventions” happen or can happen.
Once OXPHOS is stable, how do you approach making it antifragile? You begin by coming off your monotherapy diet and stress testing it. Not much different than a baby. You start by gently exposing it to the environment. If you protect your baby too much it will be maladapted and if you stress it too much it will be maladapted. You want that sweet spot or zone of proximal development a psychological concept which originated with Lev Vygotsky which I think applies to physiology or is a good way to conceptualize physiology.
And that is the beginning to a long process. I started off with herbs and spices and a bit of starch. Even herbs and spices were a bit uncomfortable at first much like the first time you pick up a weight or attempt a long walk or a short jog. But it starts there. And for now, that’s were we’ll end.
I was born by cesarean section. My mother was in labor with me for over 36 hours before they decided to do the procedure. From the time I was born till the time I moved out of my parents’ house I was sick all the time. Right from the get go I had trouble breathing and was sick with pneumonia every 3-4 weeks. At first, they thought I might have cystic fibrosis and after ruling out other possible diseases and environmental factors they diagnosed me with severe chronic asthma. I missed a lot of school and spent those every 3-4 weeks in hospitals around the country hooked up to IVs and monitoring equipment, I grew up on steroid inhalers, breathing treatments, and antibiotics. On top of that because of my father’s culture, he believed that crying babies just want attention so from the very get go if I was to cry at night because I was hungry he would not let my mother feed me (or so the story goes) so I was starved during preweaning period of my life (whether it was my father’s or mother’s doing). Despite those things, I was always intensely curious about how things worked, by the time I was 2 I had already taken apart my first radio and put it back together, socially I was maladapted, and had to repeat kindergarten because I was too quiet, really I just was in the habit of keeping my mouth shut and very much liked to observe things intensely i.e. watch and learn.
Socialpsychologically the environment I grew up in was very stressful, my Dad was never easy on us, he never hit us, but he didn’t make life easy, if we had a question which I always did he’d be like go look it up in a book or some other informational resource, answers never came easy without due effort, and so from a very young age I was incredibly resourceful and knowledgeable, Dad would say don’t waste my time with your curiosity if it really means something to you figure it out because I’m busy providing a roof over your head and putting food on the table (to his credit he did initially show us and tell us where we could find answers). The health problems and the stressful environment went on till I graduated high school. Shortly after which I moved out of my parents out and went out on my own. After I did that most things in life became quite easy as long as I had interest in them and my health problems miraculously disappeared till I started fiddling with my diet. I guess you kind of learn what’s important after you almost suffocate a couple times and your O2 saturation goes to subhuman levels, and you learn to look on the bright side, to be happy with just being able to wake up in the morning and breathe, and I learned those things at a very young age, which allowed me to see through the bullshit parts of life and culture.
One of the things I learned in the military when I was considering cross training into psychology was working with PTSD patients in group therapy settings. PTSD patients all somehow see their tragedy or make their tragedy worse than the other person telling their story to one up the next person and try to invoke sympathy and attention, it usually isn’t as sinister as that (sometimes it is), but the interesting thing is that while there maybe be stories that are objectively worse than another person’s story, they all perceive their tragedy individually as worse than the next person’s, but the perspective pain/and physiological manifestations are real and it is just as worse as the next guy’s story in the pain the person feels. That is a real. The feelings are genuine. So you learn in treating people with PTSD that all pain is perspectively equivalent to other’s even though objectively seeing your friends shot is something a bit different than being shell shocked or having a substance abuse problem. What is different though is the objective tolerance a person has when exposed to future traumatic events. And you pay attention to that, because those are the ones who can cave for the most ridiculous reasons, though they are not ridiculous in that person’s mind, and turn around a shoot you just for being a little insensitive or cutting you off in traffic, etc.
There is a perspective problem in the nutritional world on various 1st world forums, it’s like, you know maybe you can’t tolerate certain foods, I looked at Polish Hunter’s Stew and am like man that looks fucking delicious, but that cabbage looks like it is going to rip a crater through my intestines and produce enough atomic gas to reach escape velocity and send me to the moon, but I’m not going to lose sleep over it because objectively there are people starving to death every day. I’m going to be happy with what I can eat, push the boundaries when I can and if the boundaries recede and make me fart, give me acne, or make me bloated, I’m going to be glad that that is all I have to concern myself with, is that I have a choice.
I call that ^ The Dirty Russian Meatball but really it’s just a modified Salisbury steak recipe. To make that beauty you will need a pound of mince preferably an 80/20 blend or do a beef/pork mix. You are also going to need parsley, salt, pepper, an egg, garlic powder and onion powder, Worcestershire sauce, beef broth concentrate, butter, lard, a large onion and sour cream.
Mix the beef with parsley, salt, pepper, the egg, garlic and onion powder, and a splash (maybe a tablespoon of Worcestershire sauce and a smidgen of beef broth concentrate (use your judgment as to the amounts of dry spices). Mix well. Divide into the portion sizes you want and bake in the oven at 190C for 15-20 minutes, check with a meat thermometer. I try to aim for 52-54C which after a short rest will yield a medium to medium-well finish.
While you’re baking your Russian Meatball, melt 2 knobs of butter in a pan with 2 to 3 tablespoons of lard, add to that a diced large onion. You want to caramelize those onions well (I used a sweet onion, but yellow works). Around the time your Russian Meatball is finished should be about the time your onions are nicely browned, turn the heat to low/off, add some splashes of Worcestershire sauce, a smidge of beef broth concentrate and warm water, and a few spoonfuls of sour cream. Mix well. Don’t break the sauce.
Plate your Russian Meatball then spoon the sauce over, there, your Russian Meatball is Dirty.
Wrapping things up around here at home, we’ll be picking up the our Airstream travel trailer sometime at the beginning of January. We are looking forward to the new adventure. I also am looking forward to doing more with the blog and writing more. In the interim I’ve added Discord support, you should be able to join the server using the widget on the right sidebar.
If for some reason you can not connect to Discord, leave a comment, or send me an email and I’ll send you an invite.
As always, best wishes, Ed.
Sometimes for whatever reason WordPress doesn’t send me comment notifications and I logged in today to see a bunch of them from the previous post. I’ll get to those sometime soon. In the meantime this is some homemade pizza using a dough recipe I’ve returned to tweaking the past few days. The dough is simple: flour, water, yeast, and salt. The sauce is simple: Tomato, garlic, oregano, crushed red pepper, salt, and 1 tsp of coconut oil, and sugar. The cheese is the real deal, not that low moisture part skim mozzarella bullshit. There are few pepperoni on there but the flavor of the sauce and cheese really is good enough. It’s really easy to make 8, 200g balls of dough (throw them in the fridge), make enough sauce and have fresh mozz on hand, and have pizza and soda for dinner for a week and be quite the happy camper. Oh, and the sugar in the sauce, this is the difference between the pizza you love and the over seasoned “healthy” pizza that never quite satisfies. If you skip the pepperoni, virtually no PUFA, after all that isn’t whole grain flour :)
Good evening, ah, ah, ah, just finished having 2 cheeseburgers and coke and a craft ginger ale. It’s heavy squatting season again and experience has taught me that during that type of maximal training even a calorically restricted diet of cheeseburgers and coke is far superior to any amount of rice and lean meat I might be able to shove down my throat both taste wise and recovery wise. I prefer the Ivan Abadjiev diet while engaged in lifting.
Ivan is an interesting guy if you can get past the steroids, then again I think a fair percentage of the Ray Peat forum has dabbled in banned substances. He seemed to have a good grasp on physiology in a practical way and in my opinion a better understanding of stress than Peat as far as how Peat frames stress. In fact he has a view of stress much like my views.
It’s funny I was listening to a podcast with Ray Peat, and sometimes I get the distinct impression that if he is not a communist he at least is a sympathizer. Ideology has a funny way of setting up the framework through which you synthesize information.
I set up this blog more for myself than anyone else to track my own changes, changes in the way I researched topics and changes in my views, when you are writing in the present and with no money to make from it, you can look back, see where you have gone right and see where you have gone wrong. I like that. I like that I can change my mind about things and not feel bad about it.
I’ve come back to a way of eating that tries to avoid PUFA (not that that ever changed outside of some childhood favorites I craved every once and a while), but I don’t deemphasize carbohydrate as much as I used to, I’m quite liberal with them especially sucrose. I eat carbohydrate to taste and fats of the saturated sort to taste and protein to taste, it ends up being my macro ratios are pretty balanced between one another (and incidentally when they are the most palatable). I tend to like the idea of a little bit of physiological insulin resistance promoted by saturated fat so that glucose is shunted to hepatic glycogen and muscle glycogen stores.
I’ve changed my views on things like aspirin. The so called blood thinners and blood thinning effect I think we tend to think of that literally like thinning paint but when I factored in structured water my views changed.
I think carbohydrates are pretty damned individual as far as sucrose verses starch, there are certainly ways of preparing starch that seem to be more healthful but some people seem to tolerate starch regardless of the preparation.
Endotoxin has always been interesting to me, Vodka seems to work fine as a mouth wash and eternal internal cleanser, just don’t go overboard :) a cigarette can also modulate the vagus nerve as well, as for the hot gas, if your pulmonary alveoli are saturated not sure the gas is hot enough to raise the saturated lipids to their smoke point as for the tar and other stuff I’ll take my chances.
I’ve never been a fruit kind of guy, I tried the filtered OJ way back in the day and recently I found some high quality OJ that I tried for a while, you know because it is supposed to be better, I strongly disagree with the reasoning on that and I think there are good reasons to avoid it. I love craft soda and I think the lack of “nutrients” tends to guide cravings a little more accurately.
I drink milk on occasion but for the most part tend to favor cream.
Over the past few months I’ve experimented extensively with topical supplements. Pregnenolone, DHEA, Progesterone, T3, T3/T4, the fat soluable vitamins, etc. I will say that all of them seem to be much more effective topically. They are useful sometimes but can, for most, be a tripping point, if you aren’t approaching their use systemically.
Just a note. The same diabetic mentioned previously also suffers from elevated glucose in the morning said that she had the fermented pasta for dinner with a tomato and pork based sauce around 7:00pm. Normally she eats a small protein snack before bed to help control morning blood glucose. This time she did not. Her morning glucose was 113. Normally after regular pasta and a small protein snack around bedtime morning blood glucose is 130-140.
N=2 Fermented pasta seems to not blow your blood glucose through the roof
A couple of interesting updates. I have a friend who is diabetic and on metformin but not insulin and no statins. I told her about the fermented pasta I’ve been eating and told her there is some literature that suggests fermented wheat won’t blow your glucose through the roof (it doesn’t mine but regular pasta does). So, I gave her a small sample to try. I got a text message from her and she said that normally when she has pasta by 5pm her glucose is 140. She said this time at 5pm her glucose was 92.
Moving to nomad land
My wife and I (who by the way I met on the Ray Peat forum, married for 3 years) are both Histotechnologists. We recently purchased an Airstream and are planning on hitting the road full time doing contract work. The arrangement will allow us to work 6-7 months out of the year and play off the grid the rest of the year.
I will be doing some contract work and doing some graduate work in the investigations field in the way of crime scene investigation/criminal justice as a one of the subspecialties in histotechnology is forensic histotechnology. I don’t know if I’ll ever do anything with it but it is something to do and can’t hurt.
Our Airstream build is scheduled, I estimate that it will be January/February when it is finished. I plan on doing a lot more with this blog around that time.
That’s all for now. Cheers.
Greetings, have been enjoying the comments and responding when I can, working on a post and as always, always, planning on posting more. Too busy with histology at the moment. But will be back soon :)
In the meantime have been eating pasta: http://pastafermentata.com
Saturated fat recipes to come :)
It’s kind of funny how I have changed as I’ve gotten older. I just turned 34 last month and despite oscillations over the years the trend since I’ve been born is linear improvement. I feel better than I felt last year and so on. The funny part is that I eat just about everything these days and the only thing that has stayed universally consistent over the years is my general avoidance of polyunsaturated fat and more recently my willingness to embrace childhood favorites on a regular basis including things like Doritos, commercial pizza and cheeseburgers. A paradox I know—but that’s about it.
There are a couple of things that you might find interesting as well.
I come from the band camp that sings the tune that a high metabolism is not the same thing as an efficient metabolism. Now efficiency i.e. “achieving maximum productivity with minimum wasted effort or expense” is what gives a person the ability to eat less than another despite matched efforts. And depending on what is going on this could mean a person is producing more ATP per log of wood thrown onto the fire or a person is using ATP more—how do I say this proper—more soundly. Or both.
Bottom line if you can’t go without food for a day there is something wrong. You might want to upgrade from a bonfire to a wood burning stove. Or from two sticks to a match. Or from wet sticks to dry sticks. Ha.
For myself, I eat the bulk of my calories after work. Sometimes I’ll bring something “small” to work like Creepy Uncle Ed’s 6-yolk hot chocolate (have lost interesting coffee for some time) or I’ll pick one up at the coffee shop (sadly no yolks in that), and sometimes a few 1 gram salt tablets during the day mostly preemptive preparation for my evening weightlifting.
I eat all of the macronutrients in any combination that I am hungry for. The only rule I follow is to avoid polyunsaturated fat. Now avoid doesn’t mean always. When I’m in Rome (traveling), I do as the Romans do, and indulge in a bit of pro-oxidative behavior. For example, recently I was up in Chicago and ate the local cuisine. If I happen to be hungry for some childhood favorites such as Doritos which seem to be magical in instances I do so.
I even eat wheat things, like pancakes, using un-crapified wheat flour. Basically unbleached, unbrominated, unenriched flour. Enriched flours acutely bother me. So I’ve been baking a little more as of late even have made my own sandwich bread which I use for cheese burgers. You could live off cheeseburgers and milkshakes by the way and only lack in potassium so take your pick, banana split or fries (air fried or cooked in coconut oil or peanut oil—Five Guys Cajun fries anyone?)
One of the most interesting accidental discoveries I made this year was after I purchased a pressure cooker. Starch gelatinization on digestibility is pretty incredible, rice and potatoes no longer bother me.
I smoke off and on though less then I used to and I drink off and on as well sometimes excessively other times nothing. I sleep when I’m tired although increased tobacco use and moderate alcohol consumption seems to improve my sleeping patterns to acceptable societal norms whereas without those things I tend to have irregular sleeping patterns like when I was growing up.
On workdays, Monday through Friday I tend to eat less calories on average then on the weekend.
Not much in the way of supplements, maybe a quarter tablet of Aspirin on occasion, salt tablets pretty regularly (I sweat a lot, as in puddles on the lifting platform when I work out), and infrequently magnesium, I just took some the other day last time I took it was in December. I’ve never taken any single supplement on a regular basis without having some sort of eventual negative effect. Sometimes I take 12.5 mcg of Cynomel.
Aspirin, Benadryl, Cynomel, and magnesium all reduce my maximal strength. A small amount of Benadryl (1/4 to 1/2 a tablet) is enough to knock my maximum efforts down 10-15kg for 24-36 hours. 12.5 mcg of Cynomel will increase my strength for 6 hours but subsequently reduce it for the next 24 hours. A steady dose of ¼ a tablet of Aspirin will eventually cause difficulty in breathing—eosinophilia. A steady dose of 500mg of magnesium per day also reduces my strength although not as predictably as the other supplements. Whey protein, I essentially have completely negative effects with. It essentially interferes with my vision temporarily which is interesting, not willing to fuck around with that since I have better than perfect vision yet.
Essentially, I eat things I want and justify those crappy foods I grew up with as beneficial pro-oxidants. Isn’t that fucked up?
I had a good laugh the other day about ancestral eating because I was watching a fictional show on TV where they were preparing an old-fashioned meal—a stew of some sort—and then a few scenes later burning a witch at the stake. There was something cosmically hysterical about that to me.
I remember back in the early days of the ancestral eating movement how there was this kind of fairy tale idea that our ancestors where healthier than us.
The entire idea of “diseases of affluence” is on shaky ground as far as I’m concerned. It’s more so that diseases come and go and/or are “born” depending on numerous environmental and sociological factors and the “fitness” of a given population.
So said person doesn’t have diabetes and isn’t overweight but burns people. I’ll take the diabetic over the plantation owners.
Sanity should be considered.
For long time readers of this blog you will of course know that I was banned from the Ray Peat Forum in October of 2013. When I left the forum I basically started writing here and I guess I have achieved “legend” status as every now and then since then if I’m mentioned on the forum I will occasionally get emails from people saying as much. And when others have been banned I sometimes have gotten emails from them as well.
Today I received an email with the following quote:
I documented my original banishment into exile here. I did enjoy my time contributing to the community, and I was “a helpful, peaceful, loving member” but I think a large part of me since then has blossomed into something more promising.
This quote just never set well with me:
“The forum was created specifically for people to come and discuss the work of Ray Peat – not to debate it, to discuss it, share insights about it and work together to understand it while gaining their health through the practical use of his information.” ~Charlie
I’m just not into manufacturing consent. I know a lot about manufacturing consent. It happens every day all around you and I do my best to avoid it. Although I don’t get to post a lot on here I do have loyal readers and people who send emails asking how I’m doing, post interesting comments that are sometimes funny, sometimes challenging to my own ideas, but always thoughtful.
There is something very sexy about truth even though she can be ugly sometimes. She isn’t always attractive, but she never lies.
And finally a quote from the good book (NIV):
“Do not give dogs what is sacred; do not throw your pearls to pigs. If you do, they may trample them under their feet, and turn and tear you to pieces.” ~Matthew 7:6
Monday I start work again at new job as a supervisory histotechnologist but back in the clinical setting. I’m pretty excited about it.
This past year has seen it’s ups and downs in terms of what I’ve been eating, I never strayed to far from the saturated fat but I did experiment with my fair share of carbohydrate in the form of starch and sugar.
I did put on some weight for sure probably a mix of muscle and fat, but nothing approaching obesity and big surpise sucrose was the primary driving factor. Like in the past it was just enough weight to where I felt a bit uncomfortable with the road I was going down.
But the lengthy “experiment” because I never tracked any parameters was interesting in the effect it had on my mood and my neurotic tendencies and highlights a statement I made a few years ago in my private work regarding the ability of diet to change behavior:
“I’ve seen people who have never picked up a book in their life—do so—I’ve seen creative happy people spiral into a stagnant depression, I’ve seen rational thinking people turn into basket cases, I’ve seen non-religious people become so, and the vice versa for all these examples. Just with changes in diet.”
There is nothing groundbreaking about that observation its a really simple concept that translated to jargon simply means changes in respiration manifest as different observable behaviors.
Dancing with the devil was however freeing of any doubts I may have had over the years to my approach and conclusions. And now I realize I was right the first time, so right, and so I’m back to my meat and milk and occasional sweet potatoes and honey.
The transition back was painless, the slimming effortless, the clarity priceless, the sanity beautiful. It’s just too easy for me to eat like that, it took effort to eat a lot of carbohydrate and it never felt quite right.
When you get down to a low level eating saturated fat as a primary way to fuel metabolism not only is supported on a number of levels, but even when considering structured water of the cells, eating saturated fat makes a great deal of sense. And I like things that mesh up like that.
Until the next solar eclipse,
P.S. One small change, although there is not enough data to completely support the idea of A2 milk I have switched to it and not only does it taste better but I do notice a difference.
I’ve heard it said in some arguments that the activity of refining a carbohydrate in ancestral times e.g. wood pulp to make it edible (yes, that is a thing) or other plant-like crap was because when people are hungry that they are processing a said food for the sake of energy density or something like that. I’m probably remembering the exact explanation wrong.
To be fair there are some reasons why that might be true and there some reasons that perhaps raise more nuanced questions.
Nuanced questions can be exhausting depending on your disposition, how old you are, etc. Some folks settle on an idea, fully well knowing there is more to the story, but because the question is so exhausting to explore and there are so many interacting variables, the question is laid to rest and an assumption is made. And we are all guilty of that.
I largely find that behavior a symptom of aging or energy deficit. But some people will say well I don’t have time to think about such things, so I’m just going to continue on standing on that soapbox and promoting it as something good for the general public because it works for me. And I’m cool with that (the part where you do your own thing), except, then if you are going to be like that then you need to not be judgmental. Or if you are going to be judgmental which is your right, then STFU about it and tender some evidence.
Sometimes you see that in fanatical religious people, the world is changing around them, becoming more complicated, yet there is this disconnect and simple-minded resistance against recognizing that the world is changing around them and fossilizing their ideas. Which in the end means they are wrong and for those types is like hell-on-earth, but they’d probably admit that, which would lead to a conversation about heaven.
Now if I’m starving to death, I’m going to either be hunting for food or digging for food, then I’m going to light it on fire, cook it and eat it. Processing food can be very labor intensive. And in the case of processing wood pulp, can take 2-3 days before it’s finally edible. It also takes a group of people. A labor force of sorts. And so those folks are going to be expending a lot of energy and maybe they might need to eat more. So what would be the point of all that.
Maybe partly for security. Like job security except for food. Because maybe digging for der ders isn’t always a reliable source of food. You know how it is you go to your job you work, you might not like it that much or maybe you do, but you do it anyway because you know at the end of it, you’ll get your paycheck, and you’ll get your reliable source of food, your PS4, cable TV, and Internets. And according to some you’ll get obesity along with it. And that is a pretty sweet deal when you get to have this kind of guaranteed relaxation; even for diabetics. And because of that relaxation time some curious chap had the time to think about things and make some medicine that the diabetics could take to prolong their life for a while longer, even if in the end the medicine ends up killing them, it did allow them to prolong their habits for better or worse, got to die of something (lets not miss the overall point of that please).
Then you have these folks saying it is healthier and more evolutionary appropriate to go out sweat and look for food, expend energy, have irregular sleep patterns, maybe eat a poisonous root mistaken for a potato, or raped by a bear, etc., in a modern day context.
And maybe if that was the only thing you were doing you would be healthy and “happy” if you were lucky enough to avoid disaster. But that is like pulling the rat out of his cage that I mentioned in a previous post where you take a group who is in one context very healthy and drop them into another. Probably not going to have good results but who knows you might. There was a big experiment done called Paleo, and it’s still ongoing in various forms.
Because some people decided to promote this thing called Paleo. I’m talking about the low carbohydrate version which is probably on version 99 right now. And for some they say it worked and (in another post we are going to explore the term “worked” and what that entails) made their blood markers improve, made them loose weight, got them off medications, etc.
However, overall the general trend has moved back towards the argument of having carbohydrate despite those beneficial things (which tells me that at best restricting carbohydrate it is an effective intervention therapy for some that somewhat makes static, depending on how you look at it, or “reverses” in the sense of symptom relief, but not cures, a overall declining physiological state). First it was things like sweet der ders, der ders, rices, taro, etc., I think that started with Paul Jaminet and safe starches years back.
And now even though I don’t really pay attention anymore it seems like people have gravitated towards more of a whole foods type thing that seems pretty balanced. But the battle scars are there. I see a lot people who are now worse off. For example, a few months back someone posted a recent picture on Twitter where there were some notable Paleo folks sitting down around a table having steaks and salads. And the steaks I’ve got no problem with really, I have meat when I’m hungry for it. But they are were all balding to various degrees and they didn’t start that way. But hey, that way of eating is supposed to promote the image that fertile women are attracted to. Now they might talk about genetics and such and hey maybe people who are going to eventually be bald self-select for Paleo, but I don’t really buy into all that.
Just recently because I’ve been busy and under a rock I heard about this thing called Plant Paleo. I went into listening to the Podcast thinking this was going to be like a diet made mostly of starch and regular consumption of animal products just with the emphasis placed on carbohydrate. But it ended up being like not even a egg a day, low in animal protein, a lot of raw veggies, scheduled feasts, and a totally ridiculous bucket of horseshit. But it seemed to work for the guy, got him ripped and made him happy. That’s cool. I dig that. You are doing what works for you and gives the image for a male that is currently acceptable to our culture. I’m sorry but I prefer the softer looking appearance on males and females. If you are so ripped that I can see your internal organs it probably means you are useful for little else.
Like the first book I read close to a decade ago now was Weston Price’s, and for all it’s flaws the one thing I did not notice was the regular consumption of raw vegetables. But then there were other books I read like The Old Way and there too there was no impression that these folks were eating raw vegetables to maintain health.
And scheduled feasts, like that to me is just a reach around to again try to recreate some sort of fairy tale associated with good times and good health. I’m not into that and I feel it’s maladaptive and conducive to eating disorders.
I think the biggest lesson out of everything we learned about nutrition over the past decade is that industrial polyunsaturated fat should be avoided. Cholesterol is: who cares. And butter is good. And I say that being fully aware of some 90+ year olds and 100+ year olds had plenty of PUFA in their diet over their lifespan and where fine if we are ONLY considering longevity and not other factors that contribute to quality of life (such as sharpness of mind, mobility, etc.). And I have some interesting speculations as to why. And that same argument could be made against a lot of things to convince us that any risk when it comes to our diet is best avoided. But then that more often then not causes problems as well.
So the idea that carbohydrate was o.k. for our ancestors because they were looking for energy density and processed their carbohydrate for the sake of energy density makes little sense to me. Maybe they just wanted some pure ass, nutrient void carbohydrate, so that when they were out hunting the guy throwing the stone tip stick didn’t fall over because he got a cramp from all the fiber he ate and thus fail to bring home some food for his crew.
I often look at high level athletes for patterns and eating behaviors especially some of the differences between males and females, because I think performance, good performance dictates some important lessons (1) athletes often have some strange eating rituals, almost superstitious, instead of viewing this as some psychosomatic voodoo I’ve always taken the overall theme at face value and that athlete is eating what makes him feel well when he performs and when he is doing hard training which allows him to (a) perform, (b) recover and (c) wake up and do it again the next day because if (d) he can’t then he fails at whatever he is trying to accomplish. And I think we can extend some of those concepts to regular folks like you and me and apply them to life.
The whole paradigm of Paleo, or LCHF, started as a good thing not because it is the ultimate truth, but because it caused us to pause and reflect and look at things more carefully much the same way that for some Dr. Peat was and is an inspiration. But Dr. Peat went a step beyond and inspired some to go down a road that was less traveled and inspire meaningful thought and curiosity which in the end I believe is more health giving and enriching then rigid guidelines and inflexible eating frameworks and in reality just another case of herd mentality. Dr. Peat’s contributions are not about sugar and PUFA his main contribution in my opinion is having some balls. He demonstrates his ability to evolve with the ever changing scientific literature all while maintaining an overall consistency. That’s a beautiful thing. Having a big pair of balls i.e. the ability to think for yourself is increasingly important (not that it ever wasn’t). Being consistent does not mean you are biased. Being biased usually means you are inconsistent.
Where Paleo and LCHF fails now in my opinion, and for a long time now, is that they are becoming exactly what they criticized rushing to conclusions too quickly. And then you have those bundles of sticks that are o.k. with sugar taxes, WTF. Like seriously, WTF. Why don’t you first figure how to make food affordable before you start imposing more taxes, that go to who exactly?, healthcare costs?, sounds like wishful thinking to me. What a bunch of tools. How such a “free thinking” and “critical” crowd can think more authoritarianism is conducive to better health because we are too stupid to know better is somehow the solution to ANY problem is beyond my simple mind. Why don’t we just allow people free access to published research show students how to access it preferably before college and teach them basic science and math and statistics so they can read it informed and let them and future generations draw their own conclusions.
I often get emails from people who are sick and they ask for advice. I usually respond with more questions or I engage the person in a way that offers support to their situation rather than answers. Because I don’t have the answers, I’m just a dude with a blog, anybody can do this, I just think in a way about things that sometimes makes people feel free to ask questions, there are lots of people out there like that. I’m not a Doctor, please stop sending me lists of symptoms and asking “What should I do?”. I think unless you are dying or have a GSW to the chest, that the helplessness and hopelessness that you feel is because you are looking for answers, stop looking for answers, look to ask the right questions and then SEEK the answer, that order is important.
Maybe our ancestors processed carbohydrate simply because they didn’t want a belly ache.
Maybe it’s a mixture of both energy density and not wanting a belly ache and security. But for sure it’s not simply energy density because I’m starving.
I’m very excited to type this post on my new full sized bilingual English/Russian keyboard, my tiny laptop was cramping my fingers, and because I’ve been learning Russian I need a keyboard with Cyrillic characters. My reason for learning Russian? I have always wanted to, I love the way it sounds, I love the way Cyrillic characters look, I love pronouncing it, I want to visit one day, and I want to be able to read some Russian science. Yeah Russian science, they do some cool shit over there when you can get a hold of the translations. Plus anything Russian including some of their traditional foods are cool.
I wanted to take a moment to clarify, in the case it was missed, the main point of the last post I wrote on bread. The post was about an experience and this blog will be moving towards more of a mixture of me sharing my experiences in life my expertise in my career field, blended with science, speculation, and sarcasm and “common sense”. There is so much that can be learned from each other by sharing experiences and the telling of stories. Any ultimately a lot more can be retained and learned from life which is in itself applied science (discovered or not) by weaving it into everyday experiences.
As such, let it be clear that the point of the last post was not to say that if we all slow fermented our bread the gluten problem would be solved. Instead, the post served to exercise two points: (1) my experience and (2) the fact that the gluten free fad is far from cut and dry. It’s more complicated than that. For instance, one of things I learned in my adventures in researching bread chemistry is that gluten and gliadin both are hydrolyzed and depolymerized during slow fermentation and also that the carbohydrate content drops. That’s kind of a big detail to explore. After all a lot of generations ate bread and seemed to do o.k. I mean we are still here right? Barely. Just kidding.
Humans aren’t stupid, the obesity epidemic is a modern problem, that’s not to say there weren’t obese people in the old days there were, but not on this scale, we need to move away from looking at the here and now context and explore the “human existence” pattern as best as we can with the caveat of being honest about what we can and can’t know i.e. rational thinking.
It’s been said there is no such thing as a dumb question, true to some extent, but there is such a thing when exploring a complex topic, of not asking the right questions that could have a big impact on whether or not a given data set holds any weight at all and whether or not it is applicable to anyone.
Note: More pictures to come!
Bread has always been an interesting topic for me and there is a past post where I talked about bread and butter and the idea that around the time we started removing the butter from our fridges and counters we started seeing more gluten intolerance.
When I was a kid I would pilfer butter and bread in the moonlight while everyone was sleeping. Bare chested I would take a plain slice of Wonder bread, spread a thick layer of butter on it, fold it in half and smash it together, and eat it.
[A superior butter transport is in fact raisin bread which allows 2 sometimes 3 layers of butter before caving in under structural stress. I studied this. The raisins act as miniature tension rods.]
Sometime in my 20’s I did this diet where I eliminated bread from my diet. I read things about gluten, gliadin, schizophrenia, gluten ataxia, various autoimmune disorders, etc., and decided to throw my main butter transport ship out the window. I most certainly ate less butter as a result.
This past year I really began to branch out in experimenting with various sources of carbohydrate. I largely avoided wheat before that, aside from the occasional sprinkle in stews and gravy. So I decided to spread my cheeks and blow a nice medium winded gluten free fart over the Internets gluten dusted bible and investigate it’s pages further. I started looking for plain breads that were made with no oils. I’ll give you a dollar for each loaf of bread I found without oil (feel free to laugh and/or cry on that one).
I finally found some local artisan bread (artisan is short for hippies in garages charging high quality prices for low quality shit) at Whole Foods, had it sliced and began to nibble on it with butter. I made some grilled cheeses, some garlic bread at one point, etc. It was good, I was excited, but after a while I lost interest, it didn’t rekindle my childhood memories of bread and butter, and I’m definitely not the type of guy who wants good bread to sit down and eat a loaf of it, I just need a proper transport. And honestly I’ve never found in all these years a suitable alternative to bread and I’m not the type of guy to settle for anything but the best. So I went without it. I moved on and began to look at approaching the bread problem myself, got a book, did research, figured out the problem, and then never followed through because of work related activities. But my plan was to work on my own starter and use long fermentation times. Stuff like that takes a lot of time to work on.
I was on Netflix one day looking for something interesting to watch and saw the Cooked documentary up there. See I really hate food documentaries, they give me reflux. But I couldn’t find anything, so I bit my brain tongue, turned it on, and prepared myself to be transformed. It turned out it was 4 episodes. I watched them all and was pretty impressed.
I liked all the episodes but the episode where they featured the Berkshire Mountain Bakery caught my eye, this guy did shit the right way and the one thing he said that I could experimentally test was the “spit test”. He said essentially that with fake bread you always have to have something to wash it down (I would agree), and that real bread causes your mouth to produce saliva as it begins the digestive process. So I looked to see where his bakery was and boy was I a happy camper when I found out he was only a few hours away.
There were two locations within 30 minutes of each other. One was like a pizza slash cafe type deal and the other was were the magic happened and the main bakery.
The town the place is located in was small and reminded me more of how New England is supposed to feel whereas Connecticut seems more like a ghetto the size of a state. I grew up in a conservative religious family and my father was essentially a fanatic. When you grow up that way and your brain develops and starts thinking freely you develop this kind of weird sixth sense. You know those small towns were everybody is polite and nice but you know they are engaging in candle lit cannibalism? Yeah that kind of town where even the hippies are conservative. I can detect that 10 miles out. I can’t be sure if it’s some type of electric field I’m tuned into or the faint smell of witches burning in the air.
The purpose of this trip was the spit test to see if this bread made my mouth salivate and to decide whether or not we would place a bigger order online to store in our freezer. We tried some samples, and holy shit, not only was my mouth salivating and producing an abundance of spit, but for 30 minutes after it was like my mouth was watering. We bought some raisin bread, various different named breads, a chocolate croissant, and some other things Elyse picked out. Everything was priced much less then what I’d expect for such a labor intensive product.
We then went over to their pizza and cafe place. Ordered a cheese pizza and waited about 15 minutes. It smelled wonderful. At first when we opened it was kind of strange seeing actual real mozzarella on a pizza as real mozzarella when melted has almost a wet rubbery appearance that can be off putting. So we went out in the car to try it while we were driving home. Holy crap, easily the best pizza I’ve had in my life and growing up I’ve had pizza from all the major pizza regions. The pizza crust was done the same way, slow fermentation, it caused elevated spit production, and there was not lead ball sitting in my stomach after eating it.
The entire experience was enlightening, stimulating, and the kind of thing I associate with curiosity and that curiosity eventually took us on this adventure. That is the way life should be, for better or worse, an adventure.
Beyond the butter, there is the bread, and if the bread sucks it ruins the butter and that is not a good thing. There are things that happen during slow fermentation that don’t happen with manufactured starters and other methods that are used to speed up the bread making process. I think there is good reason to believe that something is fundamentally changed when bread is done right and I think there are very few people who are reading this who have ever had a real piece of bread and felt the sensation, the tangy taste, the light spongy moist texture, and the pleasure of a proper butter transport.
[Europe your bread is better then America’s but this isolated bakery just beat you with a stick.]
In my past post I talked about how when we stopped putting butter on our bread it seemed like we started having an elevation in gluten intolerance and allergies. Not only did we stop eating butter on our bread we stopped making bread right.
If your feeling dangerous give it a try if you can. They have a $50 order minimum but it can be frozen. If you are in search of a butter battle ship this is the one, see on you on the starboard side, look for the guy having the left over roast beef sandwich.
The first paragraph in the Wikipedia Nutrition article sings the following tune:
“Nutrition is the science that interprets the interaction of nutrients and other substances in food (e.g. phytonutrients, anthocyanins, tannins, etc.) in relation to maintenance, growth, reproduction, health and disease of an organism. It includes food intake, absorption, assimilation, biosynthesis, catabolism and excretion.”
I think the person singing that song is a bit out of tune. I think the definition promotes a sort of thinking that is conducive to an idea that we are black boxes. That given a rigid set of nutritional parameters, we can expect a sort of uniform response from the organism. Like a rat study where you have caged animals and the experiment group gets fed one thing and the other group gets fed another and they uniformly have on average the same weight gain or lack thereof in their respective experimental groups. For example, feed a group of mice the Western diet, they get fat, while the chow fed control group stays slim.
But what is wrong with the experimental design is that it fails to simulate a natural mouse-like environment. And I think most would acknowledge that. However, to get them to be honest about the implications might prove more difficult.
The evidence of this phenomena can be experienced just by pulling the blinders back, stepping outside, and taking a look around. Take a look at the culture you live in, you’ll notice that generally people tend to follow the “when in Rome” mentality adapting the lifestyle and eating habits of the natives. Yet you’ll see polar reactions, some seem to thrive while others seem to have nothing but problems.
Or in a different way you can take a group of people with the same beliefs, eating habits and sense of community and you’ll see that they generally react in the same way as the mice in the cage. Pluck one out take them to a new geographic location and things change.
Those observations point to a point I made in a previous comment that the physiological reaction of a organism depends on the context where the organism is present. And this points to the idea that there is a very intimate interaction with an organism and it’s environment.
I have no doubt that people eat in various ways to combat health problems with great success, you have COPD, eat some butter, you sneeze or feel congested or have wheat belly after eating wheat, you avoid wheat. But while those things might provide symptom relief, the question then becomes, have you solved the problem? And how can you know that you solved the problem? What is the litmus test? It’s very tempting for people to say well wheat is like antifreeze for me, people who drink antifreeze die, so I should avoid it.
But most people including those who live long and healthy lives often eat wheat, so the question should be why can’t I eat wheat, what is broken, how did I break it, was it simple cause and effect; I ate a lot of wheat and I broke my wheat digestive powers?
Do I care if I can’t eat wheat? Will I have anxiety about not being able to eat wheat for the rest of my life? Will I burden society as a whole with an International gluten-free campaign so that I can get everyone off gluten so that I can feel normal?
Will I be Paleo, sign-up for CrossFit and start a blog with a selfie showing my hot abs or ass, and try to convince everybody else that this is the right way and the rest of us sinners are going to hell (even though most likely those are opportunistic photos taken when I’m not feeling like shit)?
H/T to those of you who really don’t feel like shit.
Meanwhile the sinners are quietly eating their cheeseburgers.
To think that the way you eat is right for everyone is at the root the thinking of an authoritarian control freak who is the poster child for a person suffering the delusion that they are in control of their life. When most likely that person is anything but in control of their life, feeding into a self-fulfilling delusion that the more variables they can control in their life the more they can skirt the issue of actually having a life, living their life, and enjoying their life.
This post has been overdue, as for the past year I’ve been experiencing paradigm shifts in my thinking as a approach the world in a more honest way. And approaching the world with peeled back blinders is always a good thing even if you have to put a foot or two in your mouth. I am not content with fossils.
“Possessing opinions is like possessing fish, assuming one has a fish pond. One has to go fishing and needs some luck—then one has one’s own fish, one’s own opinions. I am speaking of live opinions, of live fish. Others are satisfied if they own a cabinet of fossils—and in their heads, ‘convictions.’” ~Nietzsche
Although my cabinet of PUFA fossils is well intact aside from flirtations with animal products that tend to contain higher amounts of them :)
Over the next few months or whatever I’ll be plucking out old blog posts and updating things based on new information and why I’ve changed my mind (but the old blog posts will stay up for illustrative purposes). It shouldn’t be too hard as my views on saturated fat and polyunsaturated fat are still the same and I still am metabolically focused. But some of my views on carbohydrate have changed dramatically. Bear in mind that my blog is personal, everything I do is not 100% transferable to empty vessels, but I hope it still can provoke the asking of questions and generate criticism good or bad.
More to follow soon. Thank you for the continued questions and comments during these dark times. Till then have fun!
Note: This post is going to be greatly expanded at the moment I’m having trouble with my citation manager.
Immunohistochemistry (IHC) and immunocytochemistry (ICC) are examples of two immunohistochemical methods where a tissue sample is incubated with antibodies (Ab) to detect the presence of an antigen. The logic behind this method stems from immunology–that specific Abs bind to specific antigens e.g. proteins, chemokines, cytokines, receptors, membrane associated proteins, pathogens, etc. The pertinent difference between IHC and ICC is that in IHC you are working with cells that have been sliced open and in ICC you are working with whole cells which sometimes you permeabilize to allow Ab penetration into the cell.
The assumption behind IHC and ICC is that cells maintain their intra- and extra- cellular organization throughout the process of executing an IHC/ICC experiment and that antigens keep their position within the cell post fixation thus yielding valid data. Given that cells are composed of a mixture of proteins, lipids, and carbohydrates, as well as structured H2O and other complex molecules this is a troubling assumption.
[I doubt it’s an assumption in the true sense as most histologists and pathologists are aware that tissue morphology is altered during fixation. But the lack of attention to this issue in the literature and the amount of published data using immunohistochemical methods without confirming its validity leads me to call it an assumption.]
As a histologist you are trained in a variety of disciplines and you are trained to think about what is going on with the tissue you are processing at a low level as you expose it to different chemical agents. For some technologists techniques are developed and improved on by observation and trial and error. For other technologists a more evidenced based approach is taken where you consider the mechanics of a technique at the biochemical level to experimentally drive the techniques you are developing. The former is more likely to occur with diagnostic histotechs.
For example during fixation tissue samples can be dramatically altered. Most histologists should be familiar with the idea of fixation artifacts and the effects that different fixatives have on tissue morphology and that some fixatives can dramatically change the results of a special stain or IHC. The practice of antigen retrieval should be a clue to the chemical impact a fixative can have on cellular proteins.
Over the years there has been a consensus reached as to what fixatives are appropriate for various special stains and IHC/ICC. To say there is no logic behind this consensus would be misleading but to say that we know exactly how and why fixatives affect cells and overall morphology would also be misleading. Some of the science behind the choice of a fixative is evidence based but a good portion is observational and traditional and usually subjective.
The evidence behind that observation can be witnessed from the thousands of different histochemical techniques that histologists use to demonstrate structures within a tissue or cell. There is this phenomena that two laboratories can use the same histochemical technique and achieve different results. To compound that further two histologists can follow the same procedure and get different results. This is an anecdotal clue alluding to the fact that we really don’t have a precise and standardized approach when it comes to examining tissues using histochemical methods. There is some standardization and oversight, however, a lot of techniques are subjective. At the biochemical level thousands of variables come into play when developing an IHC/ICC e.g. purity and quality of reagents, the clone of the Ab, temperature, humidity, pH of reagents, etc. And the same is true with special stains.
While these things I’ve mentioned are the tip of the iceberg the real question is should we still rely on IHC/ICC in research and diagnostics to generate data? The answer is: it depends and requires consideration. I think to say immunohistochemical techniques are completely invalid would be an extreme overstatement. I also tend to think it depends on what type of antigen you are looking for. For example, is the antigen a chemokine or cytokine or is it a receptor or membrane bound protein.
In the future this area no doubt needs more research. We need more specific positive and negative controls and we need to be cautious in how we interpret results in IHC/ICC and in general any tissue that is processed with a histochemical method. When a histologist is trying to detect an antigen close attention should be paid to the nature of it and whether or not results can be affected by using different fixatives and the differences in cellular staining between whole cells in ICC and tissue sections in IHC where cells are cut open. For example, in ICC if you have intracellular perinuclear staining but in IHC you extracellular and non-specific staining using the same Ab one should indeed pause to think at a lower level. Questions such as: Is the fixative I’m using preserving the lipids of the cell or is the Tween 20 in my buffer causing a dissociation of the lipids from the cell structure?
There is no straightforward answer to any of these questions at this point. In the next post I will review some of the literature that addresses some of these concerns. At this point it is a unpopular topic so the list is short.
“Everyone in nutrition is influenced, more-or-less unscientifically, by their own dietary choices or those of their culture. On the one hand we have a clique of mandarins who were “born on second base and think that they’ve hit a home run” with regard to diet and metabolic health. On the other hand we have people such as Tim Noakes, on trial for his opinions as I write, who have overcome metabolic disadvantages with the help of diets that have included the prohibited elements. By any objective test, the second narrative should be the more convincing, but perhaps not in a society that worships unearned success. It is obvious enough that the selection and appreciation of evidence in the DGAC process is distorted by unthinking acceptance of the first narrative. We owe a real debt to Nina Teicholz for bringing this out to be debated in the public domain.” ~George Henderson
“In a community where everyone has a divergent opinion on what’s healthy and what’s not, what’s obesogenic and what’s not, which diet is best for which people, under which circumstances, etc., I can’t help but wonder if the nutrition and metabolism community might be better suited to follow the path of the aforementioned 12% minority [of physicists], and just shut up and calculate. Forget about what we think we know, and just focus our attention, instead of on ideals, on generating better, more generalizable data, utilizing solid statistical methods, carefully avoiding common missteps (like overemphasizing p-values, running too many significance tests, and using relative risk ratios rather than absolute risk and NNT, among other things), making all the data available for objective re-computation, analyzing quantifiable changes in biochemical assays, and more.” ~Ian Lane
“One thing’s for sure, it takes a curious blend of ignorance, cognitive dissonance and confirmation bias to become convinced that salted-sugared skim milk and OJ is the ‘best’ way to attain the highest possible level of health.” ~Shane
Can you hear the crickets chirping on this blog? I have things to write, but life has gotten in the way of regular posting. Just started a new job about a month ago at the Plum Island Animal Disease Center, and have been consumed with research lately. That has turned out to be useful with my own personal interests regarding respiration. Viral hijacking of cells is an interesting way to look at respiration, hint, somewhere along the line they are manipulating local cellular energetics (glycolysis/OXPHOS) to generate an environment which they can replicate in.
As a sign of good faith that I will eventually resume posting, I’m posting a recipe, hopefully you’ll eat it in all it’s goodness, and it will distract you from the chirping.
You’ll need a big stock pot.
3-4 pounds of fattiest chuck roast you can find, cube it, to the size you desire, and salt and pepper those bitches. I like bigger pieces. Have your stock pot on medium heat with 2-3 knobs of butter.
AGE your meat (brown it). Cook it in batches and set the seared pieces of meat aside.
Once you’ve done that, cut 2 medium onions in half, and then into fourths. Put those on top of the brown bits with a few splashes of balsamic vinegar. I happen to have some apple balsamic vinegar right now, but what ever you desire is fine. The vinegar is going to lift the brown bits off the bottom of the pan and you are going to cook the onions down a bit, but not too much.
Next put the beef back in. Pour in two cups of beef or chicken stock, then 2 cups of red wine (whatever you like), and 2 cups of water.
Mix it a bit. Put in 6-7 cloves of garlic with the skins on (don’t crush them), a bay leaf, a generous pinch of thyme, and 1-2 tablespoons of tomato paste. And before I forget, a tablespoon or so of flour. Oh shit. Just opened a can of worms. You can use arrowhead powder or some type of dry starch powder if you so desire. No pussyfooting around on this, use something.
Put the lid on and bring to a simmer.
About 45 minutes in put in 3-4 inch chunks of carrot (I usually throw in 3-4 carrots worth, but whatever you like, just make it look pretty as far as distribution) and cube a potato or two and toss those in. Cook for another 30-45 minutes until the chunks of starch reach your desired consistency. Fingerling potatoes work well too, poke through the skin with a fork for those before you toss them in. If using whole potatoes I favor the smaller red variety which I typically peel if I’m not feeling lazy.
Total cook time 1 hour 15-30 minutes.
Serve in a bowl with sour cream if you wish and some fresh parsley for garnish. Milk or your favorite alcoholic beverage goes well.
If you have room afterwards, desert is whipped cream and berries and a if you are feeling dangerous a splash of vodka and lemon juice. OR some high cheesecake of the low carbohydrate variety.
Eat, drink and be merry.
I was reading Danny Roddy’s latest post about a fish tank or something (just kidding Danny, I Love You) which I thought was quite good and remembered this thread from a while back.
Gosh, were we all so immature in those days. The growth we’ve all experienced over the years has been amazing.
This naturally brings me to Dr. Peat. I once wrote quite a bit on the Ray Peat Forums, eventually was banned and moved on to grow into addressing problems I deemed more important. The thing that annoyed me with the cult like Peat following was that they reminded me too much of religious people. They interpreted his work as if it was biblical scripture, and when something didn’t fit they would endlessly try to justify their position or just ignore it or say that you don’t truly understand his work. Not much different then groups of church people and their endless interpretations of biblical scripture that pit themselves against each other.
What initially attracted me to Dr. Peat in the early days was his view that energy and structure are interdependent, something which at the time as I was studying mitochondria, struck a chord with me and gave me the confidence that the way I was thinking about things was something worth pursuing. My armchair background in physics and other sciences, and as Danny Roddy put it in his article in so many words, a pursuit for a universal theory, whirl-winded me away from the cult-life and towards synergizing my own ideas most of which aren’t published publicly. There are some people who I confided in and shared a portion of my work with who were also Peat “followers” who said in so many words “that this is the light at the end of the tunnel”, the thing that will bring everything full circle. That was a few years ago.
Such compliments scare the shit out me. And after which, I became reclusive to examine the finer details. Exceptions and outliers are my kryptonite. It is all too easy to generalize and miss something. Which is why to this day I haven’t published my general theory on the nature of nature.
Recently I was listening to the KMUD interview with the makers of “On the Back of a Tiger” and Dr. Peat. There were a lot of good and positive things said. But the one thing that bothered me was that the host kept asking what Dr. Peat thought, asking for an opinion is not a sin, but my impression was that the host wanted verification for the work that others have dedicated the majority of their lives studying, annoyingly so, as if in one swift word Dr. Peat could invalidate their work. I find that mentality troubling.
That mentality is the antithesis of Dr. Peats work. It is the opposite of thinking, the opposite of stimulating the organism. It is authoritarianism.
This might be confusing for some as Dr. Peat is definitely is anti-authority. To illustrate what I mean here is an excerpt from my work about the concept I’m trying to convey:
“Entrenching is not the new idea but rather the aversion to self-confessing an error approaching things in a new way. The conflict does not arise out of the new idea but arises out of the individual. These individuals place too much power in words and ideas. These people are the real dangers in society—not the originators of new ideas. It takes much more than an individual to do anything with a dangerous idea just as it takes much more than an individual to do something with a useful idea. Ideas have to be stated and different people must implement them to become a useful or dangerous reality.”
In other words, it is the followers the perpetuate dogma. Not the originator of the idea. That is, the state of the sciences and its application is not the result of authoritarianism per se, it is the complacency of people that facilitates authoritarianism. Governments and institutions become authoritative because people are poor consumers. They are poor consumers because they have no self-confidence, have a lack of curiosity, and/or they lack the belief that they can think for and figure things out for themselves. This mentality is self-reinforcing and over time systems in place become more and more authoritative and resistant to change. But the solution is not to destroy, the solution is to evolve. Nothing good really comes from destruction, usually repetitive cycles between the garden of Eden and Doomsday.
Once a follower understands that it is they who facilitate dogma, they are faced with a multiple dilemmas:
“What is difficult for the entrenched individual is not the new shift, but the shift that points to years or a life wasted and genuine interests forsaken. There is a saying: “You can’t teach an old dog a new trick.” Few people are so downright stubborn. But these defining qualities are common enough that most of us are familiar with these individuals.”
“And what follows is a revolution in cultural knowledge to try and rationalize why we did things the way we did in the past and why it is justified to change things for the future. Radicals entrenched in their beliefs usually, but not always, die in these shifts of thinking; literally or sacrificing the personality. Being a martyr for a particular paradigm has never been a personally natural inclination. When the individual is cornered and experience is conflicted with lacquered beliefs, the individual is faced with options of entrenching themselves behind belief or taking steps to evolve in another direction. It is the collateral damage of opposing extreme views in groups of people that often drive cultural evolution. At some point we must put aside belief and continue moving forward. A fight to the death is not a viable option except for the delusional.”
The proverbial foot in mouth is not an easy situation for anyone. Easier for some harder for others. Once somebody is convinced they are on to something and build a model around it for their livelihood they are doomed to confirmation bias. They themselves become the antithesis of life. It is why to this day I refuse to put a price tag on sharing information and ideas. It is crookery. Dishonest. And egotistical. It is what got us into this mess in the first place. It’s like the FDA, maybe the founding intentions were good, but it evolved into a completely different monster, that is the nature of trying to protect people and/or inform them, bias almost always follows, and where there is bias there is destruction.
A lot of people who should be scientists and have the charisma and passion to change things don’t become them because they are disenchanted with the system in place. What cowards. If you want to change something you have to participate and help the system to evolve. You do your small part and help to change things for the future. Being reclusive from that hostile environment only demonstrates the compliant temperament to bowing down to authority.
Being critical and passive demonstrates one thing, it demonstrates the type of energy flowing through you. An energized organism is resistant and resilient to stress, thrives, and has the ability to fundamentally change things, be it themselves or their environment. For example, Dan Wich noted my ability to levitate chairs with large amounts of saturated fat.
For years I thought that avoiding stress was healthy, to my surprise, the opposite occurred and was demonstrated to me over and over again, during the most supposedly stress free portions of my life I suffered from the most debilitating health issues. But as I began to participate in life more and more, confronting adversity, my health, my spunk, my problem solving abilities, etc., all rebounded regardless of my diet, regardless of how much sleep I got, regardless of everything just short of exhausting myself, stress (thinking is stress for example) gives life purpose.
I began to question the “positives” of caffeine when I was reading combination therapy studies where caffeine alone was not effective but caffeine plus a therapy was more effective than the therapy alone. That raised an eyebrow for me. Perhaps it is useful to know how compounds exert their effects before we say something is good for you.
Caffeine as are most methylxanthines are potent inhibitors of respiration. There are also a number of negative hormonal side effects with the digestive system leading me to wonder e.g. if some perceived food intolerances are caused by heavy chronic coffee consumption.
When I see a compound inhibit respiration and a shift towards glycolysis I automatically think insulin. Caffeine effectively increases insulin. This would have the effect of suppressing beta-oxidation to some extent causing a stress response which would temporarily increase the RMR. Anytime respiration is suppressed acutely there is a temporary increase in the RMR to restore NAD+/NADH ratios. Caffeine probably inhibits respiration by shifting the cells towards glycolysis increasing NADH which essentially creates the Crabtree effect. It happens that the Crabtree effect causes cells to uptake calcium which eventually causes apoptosis. In cancer this would be useful. Essentially the caffeine is stressing the cell making the pharmaceutical therapy more potent.
Some people report that when they give up coffee there is a period of time where they feel excessively tired. My opinion is that when chronic stress is reduced this symptom is to be expected.
Dr. Peat mentions caffeine being an “adaptogen” he is somewhat correct in the sense that acute caffeine consumption would cause a temporary increase in RMR (stress response) causing weaker damaged cells to follow through to apoptosis. Caffeine does stimulate autophagy. Basically a sort of ripple effect through the organism i.e. a window cleaning with a squeegee. When insulin increases the thyroid hormones tend to increase as the thyroid hormones participate in degrading insulin thus restoring organization through increased beta-oxidation of fatty acids.
But chronic consumption could be maladaptive. On the surface there seems to be a loss of heavy caffeine consumers in centenarian pools. Fat, nicotine, chocolate, and alcohol (although heavy alcohol consumption does as well skew NAD+/NADH ratios) seems to be far more common with coffee consumption being a cup or two a day for those that do drink it and happen to make past their 90’s. But that observation is probably biased because I haven’t looked that hard.
Chocolate also contains methylxanthines but the stearic acid and other SFAs probably offset the negative consequences.
For those who look at metabolic rates, there are a lot of compounds that increase the metabolic rate. A lot of lethal substances are on that list. I think that it is important to look at the context when recommending chronic consumption of said substances as an adaptive stress response is something quite different then a chronically induced state of hypermetabolism. Animals that live long such as the naked mole rat have low RQs, are insulin resistant, and Vitamin D deficient. During hypoxia (e.g. altitude or underground) humans react physiologically, fatty oxidation increases and ketones increase. Fatty acids, lactate, and ketones are protective in low oxygen environments.
Then there are those who are better or worse at metabolizing caffeine and other xenobiotic compounds, I would guess this would determine tolerance to such compounds as well as what “dose” would mediate a beneficial hormetic response.
In the beginning I mentioned that I began to question the “positives” of caffeine. I want to define “positives”. Because the idea is not to recommend that you should axe coffee the idea is that just because we see good evidence of a substance with benefits doesn’t mean we turn off our brains and forget to ask why are there these benefits, how does the substance mediate its effects, how can I best use this substance without interfering in general with my enjoyment of a substance which possibly could be a double edged sword.
So having a cup or two of coffee a day is probably adaptive, but if you are drinking “50 cups of coffee per day” there is probably something extremely wrong with you.
There is this idea out there that blows my mind. It’s the idea that somehow being a baby is stressful or harmful.
That a rapidly growing and developing baby who is in ketosis and is consuming a protein-restricted-low-carbohydrate-diet i.e. breast milk is somehow in a state of stress. That if a baby never weaned after some magical age from breast milk that eventually they would go from a healthy growing thriving baby to developing the following symptoms:
- Gastrointestinal disturbances (diarrhea, vomiting, nausea, constipation, GER)
- Inflammation risk
- Thinning hair/hair loss
- Kidney stones
- Muscle cramps or weakness
- Low platelet count
- Impaired concentration/cognition
- Impaired mood
- Renal tubular acidosis
- Nutrient deficiency
- Disordered mineral metabolism
- Poor growth in children
- Skeletal fracture
- Increased bruising
- Sepsis, infection, bacteria overgrowth
- Acute pancreatitis
- Long QT intervals
- Shift towards atherogenic lipid profiles (including hypercholesterolemia and hypertriglyceridemia)
- Heart arrhythmia
- Myocardial infarction
- Menstrual irregularities and amenorrhea
If you are to believe the high-carbohydrate-low-fat people and their interpretation of physiology that is the implication at the end of the day. That somehow after weaning we fundamentally transform into an organism which once had a metabolism that predominantly utilized saturated fat, ketones, and lactate to a metabolism that to be in its optimal state post weaning should now utilize primarily sugar.
It’s like a bad joke. I’m not into the habit of believing that we are screwed before we can walk if we can’t find and climb an orange tree. Typically it is us who give ourselves the reach arounds.
Somebody skipped the part where saturated fat, ketones and lactate support rapid growth and in fact are necessary for normal development.
Anyway enough with that crap (I originally wrote this post without the symptom list and then came across that ridiculous post).
Some people get all tickled when you say you are doing it wrong. I’m not in the habit of saying your doing it wrong but clearly babies are doing it right. Shrug. I dunno.
Curiosity, movement, abstract thinking, problem solving, and imagination support brain development, idleness retards it (lowered stress). Anything that puts a demand on energy is stress.
People view stress as a bad thing, it is chronically, but I think of the organism more like a “muscle” much like exercising the neurons in the brain leads to improvements in cognitive functions. Perhaps we should look at acute stress more like “exercise”. After all it would be a more intuitive paradigm.
In the past few days two people have asked me what my thoughts on protein are. And one person asked about my caloric intake. I am particularly active and considering that context I thought I’d cover my reasoning on why I restrict protein. Honestly I’m past the restrict part I tend to eat low protein easily because I hate that overly full feeling like there is a ball of lead in my stomach after a larger-than-life-everything-is-bigger-in-America-steak.
My rationale comes from two angles, the first one considers the mitochondria and respiration and the second angle being growth and metabolism.
The most intense period of growth and metabolism during our lives is when we are babies. The brain is developing, organ systems are developing, etc. It’s actually quite amazing to think about. And I say actually because I think a lot of people don’t consider how amazing that stage of life is. A lot can go wrong.
What are the primary exogenous metabolic substrates in growing babies? For simplicities sake: saturated fat, a sprinkle of polyunsaturated fat, a sprinkle of protein and carbohydrate. There are some other exotic lipids in breast milk and some bacteria but again we are just going to do a surface overview.
From those raw materials the baby develops. And thinking about that is a trip. Babies that are breastfed from birth to 2-5 years old continue to rapidly develop and I think it is fairly well established that breastfed babies have a leg up in a lot of different areas regarding the ability to cope with stress, having higher potential IQ’s (although nurture can ruin that), being resistant to disease later in life, the list is a long one. But wean a baby early or feed them formula and all the sudden you start to see negative consequences.Digestive issues, retarded growth, underdeveloped brains, allergies, mood swings (I’ve always found the disposition of breast fed babies compared to early weaned babies interesting).
Those points there should if anything cause one to pause when thinking about macronutrient ratios and growth and metabolism. Especially in the circles that focus on having high metabolisms. There I must point out that babies have low respiratory quotients, elevated ketones, elevated lactate, etc. I should also point out that breastfed babies are more symmetrical.
The most intense period of growth and the period in life when our metabolisms are probably at their peak are when we are babies.
Now lets think about all the fat on babies. Around 30-35% give or take after a few months. Muscle mass? Not much. But parents who breastfed their babies know that babies are impressively strong for their size and surprisingly coordinated when one considers what kind of coordination it takes to walk upright. We tend to not think of walking or crawling as something impressive but that is only because as adults we take it for granted.
Strength in my opinion is more so a CNS issue. If you watch Olympic lifting especially the feather weight classes what you see is something pretty impressive. You see stick figures lifting 2 or 3 times their body weight over their heads depending on the movement. How is that possible? My opinion is that for the most part strength is a measure of the efficiency of the CNS to fire muscle fibers in a coordinated and explosive fashion. The more accurate the CNS is with activating muscle fibers the greater the strength.
In general you have sarcoplasmic and myofibrillar hypertrophy. Sarcoplasmic hypertrophy is probably stressful to the body whereas myofibrillar hypertrophy is adaptive. In general when cells take up excess water it’s probably a negative thing. This is why in endurance athletes you often see enlarged hearts and after a while they drop dead.
If you watch kids play in a natural setting it’s almost always myofibrillar hypertrophy that is occurring.
Protein is more dense than water and babies almost always feel heavier than they appear.
So as babies we are growing and are getting strong due to myofibrillar hypertrophy. Strong despite the fact that when we are breast feeding our protein is lower than what we’d expect from adult studies on protein intake. Yet protein synthesis is still obviously occurring and we are still growing and still developing.
Again the body fat percentage in general for babies is around 30-35%. Strength is a measure of the accuracy of the CNS. And increasing strength primarily develops from myofibrillar hypertrophy. Yet the protein content of breast milk is low.
So there a few questions you have to ask yourself. Do these things regarding strength and protein intake agree or disagree with the literature on adults? Has anybody actually shown that increasing protein intake (alone) correlates with increased strength in a dose dependent manner (obviously protein intake does need to be adequate but outside of that the question is interesting)? Why is it that the strongest people in the world almost always look fat? Is there a shredded beast under there? Or is their strength a function of their body fat percentage and more importantly the body fat composition (cough, of the saturated sort) and the ability of their CNS to recruit their muscle fibers? Would they be as strong if they shed the fat? Would the longevity of their careers increase or decrease with leanness or increasing body fat?
If at the end of the day you believe that protein intake (outside of adequate) has nothing to do with the ability to increase one’s strength then you are left to look at the first angle, respiration and/or cellular generation of energy, which is without a doubt going to in part determine the ability of your CNS to fire your muscles, whether it be saturated fatty acids, lactate, creatine phosphate, etc.
A misconception is that the cell is a bag filled with water and all the organelles are just floating around and that the cellular membrane is basically all lipid. I would say a lot of scientists recognize the gel like nature of the cell but at this point we just haven’t gotten to the point where people are making a big deal about it, but the evidence is there. If you look at electron micrographs of cells you can see that this is actually not the case, cells are protein rich. In fact the cellular membrane is to a great degree made of proteins. I’ve seen some extremely varying estimates on the protein content of cells but at this point I’m more comfortable with saying that the cell is not a bag.
The next question then is if that is true (cells are made of a lot of proteins) and a growing baby is indeed growing and is on a low protein diet where is all the protein coming from? Where are the raw materials for protein synthesis coming from? Is the protein in breast milk enough? I would say it is enough and I would bet the farm that outside of adequate protein intake more is not better.
That is my line of thinking. I start there. Essentially looking at things from a functionality point of view rather than theoretical needs or aesthetic goals. The ability of excess amino acids to feed into the TCA cycle concerns me in the sense that I want saturated fat in my mitochondria, or maybe some ketones, or maybe some lactate or glucose were needed (Peter knows more about that than I do). I don’t like the idea of swollen mitochondria.
It does seem to be true that high meat diets can be conducive to leanness (so can vegetarian diets) but when I see things like that I see more of a starving to death syndrome, the undesirable substrates cause fat loss because the mitochondria are trying to maintain respiration and from the organism view, trying to maintain form. And I would say to some extent that the thermogenic quality of eating excess meat probably is at least in part due to elevated fatty acid oxidation which might be okay in the short term but long term I don’t like the idea. There is nothing wrong with having a high body fat percentage if it is the right kind of fat. It’s beneficial and you’ll probably feel better. We’ve all seen babies, we’ve seen some babies that are fat in a bad way (formula fed) and babies that are fat in a good way (breastfed), the breastfed babies fat is of a different quality.
Aside: This post is geared towards flesh meat, I have yet to think about whether protein is protein, or if denaturing proteins e.g. fermentation makes a difference. I also did not consider in this post the ability of the gut bacteria to ferment amino acids.
That’s all for now.
“Adult female Sprague-Dawley rats were fed isocaloric semipurified diets containing a high content of either polyunsaturated (P) or saturated (S) fatty acids; these diets were nutritionally adequate, providing for all known essential nutrient requirements. On day 3 after beginning S or P, one group of animals was exposed to a single 6-Gy dose of abdominal radiation, and the other half was sham irradiated. S or P diets were continued for a further 14 days. Brush-border membrane purification and sucrase-specific activities were unaffected by diet or by abdominal irradiation. In rats fed P, irradiation was associated with an increase in jejunal brush-border membrane total phospholipid and the ratio of phospholipid to cholesterol; these changes were not observed in animals fed S. In irradiated rats, ileal brush-border membrane phospholipid per cholesterol was high in animals fed S compared with P. In irradiated animals fed P, there was reduced jejunal and ileal uptake of several medium- and long-chain saturated and unsaturated fatty acids and cholesterol, and the ileal uptake of higher concentrations of glucose was reduced in irradiated animals fed P. In contrast, lipid uptake was similar in control and irradiated animals fed S except for cholesterol uptake, which was reduced. Ileal uptake of higher concentrations of glucose was increased in irradiated animals fed S. Quantitative autoradiography failed to demonstrate any change in the distribution of leucine or lysine transport sites along the villus 1 or 2 wk after abdominal irradiation or in response to feeding S or P. Also, these differences in transport achieved by feeding S to radiated animals were not explained by variations in the animals’ food consumption or intestinal mucosal surface area. Thus the use of short-term feeding with a saturated fatty acid diet in the prevention of acute irradiation damage to the intestine warrants further investigation in humans.”
Thomson, a B., Keelan, M., Lam, T., Cheeseman, C. I., Walker, K., & Clandinin, M. T. (1989). Saturated fatty acid diet prevents radiation-associated decline in intestinal uptake. The American Journal of Physiology, 256, G178–G187. Retrieved from http://ajpgi.physiology.org/content/ajpgi/256/1/G178.full.pdf
I wish you all a happy winter solstice no matter what variation theme you subscribe to.
It seems fitting to write about cravings. With the New Year around the corner there will be plenty written about cutting calories, losing weight, exercise, colon cleanses, juicing, coffee enemas, and all that Bah Humbug!
I am in the middle of writing a post on the Crabtree effect and in the process I started thinking about cravings.
I’m always thinking about the mitochondria.
We often say that certain energy substrates are addicting. That might be so, but I find the explanation unsatisfying. Feeding a human and/or a lab animal sucrose and noticing addictive behavior and showing an fMRI of a brain lit like a Christmas tree demonstrates cause and effect but it does not answer the question: Why?
I believe the brain can be loosely described as a blend between a psychopath and sociopath. It will whittle your body away in the name of itself while you grow tumors on your arms and legs. It will keep you up at night if you didn’t eat enough. It will send signals to hormone secreting sites on your body to increase this or decrease that. It will make you feel bouts of mania and it will make you depressed. It’s all very exhausting. It brings me back to the point in an earlier post that hormones are background until inefficient energy substrates are introduced AND/OR the organism is put into a context where there is a need for an acute response due to increased energy needs e.g. physical stress, psychological stress, injury, etc.
But what mechanism is responsible for this, what signal is the brain receiving that causes all of these symptoms? I believe the answer at the end of the day is simply inhibited mitochondrial respiration i.e. hypoxia and that the brain senses this. That is another key, that the brain senses this, although it can be quite selective in acknowledging it with its psychopath/sociopath mentality.
I think it is fair to say that the brain can sense inhibited respiration globally and locally. Local inflammation is an indicator that the brain really is aware that a toe is a toe and that when you get kicked in the balls your balls hurt not your eyes, although they probably will water a bit. Why do your eyes water when you get kicked in the balls? I don’t know but I think it is a good indicator that although we are amazing creatures we aren’t perfect. I think there are examples of other organisms with more accurate nervous systems. We’ll get there though eventually if we don’t kill ourselves first.
But you have to ask yourself why is it that if I cut off my arm my whole body feels the pain and not just the site where the arm is cut off? Is it because your brain senses a possibility of death or is it because your brain knows that you will have one less hand to stuff your face with?
If you think about that for a moment it’s quite amazing. If we assume that cravings are a result of inhibited mitochondrial respiration we can then begin to explore the cause of cravings and perhaps why certain cravings are prevalent.
Fat is all around us in the Western world. So are carbohydrates. In our culture we associate carbohydrates with energy. I witness this conditioning on a day-to-day basis with my coworkers who ask: “If you don’t eat carbohydrates where do you get your energy from?”
When I explain to them I get my energy from fat they are baffled. “Isn’t that bad for your heart?” Contrast that with traditional times where fat was a prized resource.
When you consider that then you can begin to contemplate cravings. I don’t believe that menstruating women in artic cultures craved chocolate. I don’t know maybe during menstruation the women had secret stashes of berries.
Silly isn’t it.
So why do we crave sucrose? Because there is strong enough of a cultural convention and an association with carbohydrates and energy that during stress this is what we reach for naturally. If that association was different we’d reach for the butter.
However, the difference is that butter maintains respiration. Sucrose does not, in fact over time it reduces mitochondrial density and respiration so that a craving for sucrose produces a perpetual addiction in the name of trying to maintain respiration.
For so many years we have believed that butter and fat were a guilty pleasure, we forgot that in reality it was a superior energy substrate. So we ate it when we “caved” but believed at the same time it was clogging our arteries. We slowly conditioned out of ourselves our fat loving selves by believing that it was bad for us and thus losing the association between fat and energy and stability.
Now we believe that sucrose is good for us, we believe that the swings between hypo- and hyperglycemia are normal and all the peculiar behaviors associated with it. We believe that no matter how depressed or fatigued we feel that that is part of life and it is acceptable so long as we don’t die of a heart attack. In effect, because we fear death by heart attack we have allowed ourselves to be conditioned into believing carbohydrates are healthy even while we proverbially attach electrodes to our nipples every time we drink a bottle of Coke.
When you start thinking about respiration and the Crabtree effect you start believing that the idea of “moderation” is a last ditch effort by commercial enterprises to perpetuate a legacy. I believe that people in the Western world are unsatisfied, they might not know it consciously yet, but I think the flux of TV cooking shows where Chefs prepare real food is a sign that people are hungry for something real. They just don’t know why and they have forgotten how to cook. All they know is that it fat dripping off of charred meat looks good. But I would see things in a “mystical way” like that. After all I’m a Jungian and I subscribe to Sheldrake’s morphic fields. “We” want to survive.
An addiction can loosely be defined as a failure of a substance to solve the underlying problem of restoring respiration.
Off topic. I read some posts on the pseudonutritionosphere that triggered some early memories and thoughts.
Thinking back I was always an active child, both mentally and physically. And both seemed to enhance each other. Experiences like that can help a grown man make sense of things sometimes. In my teenage years I played a lot of recreational basketball on the weekends. I also played baseball. I also did a lot of cycling, and there was a period I remember in middle school where I would run around the track during recess. I never really fit in with the physical types and I never really fit in with the mental types. In high school, I went to football camp in my freshman year, and then played on the football team for most of the season but quit towards the end. I was also in the choir from elementary school through high school. If I recall correctly I stopped singing at the end of 11th grade. Then I got a guitar. Fast forwarding a little bit into the time while I was in the military I had a small studio set up and I recorded a lot of music. Eventually I found the drums. I like the drums. In my mid-twenties I was a marathoner for several years before I discovered lifting weights.
You see although I was physical and into doing physical activities, I was not into the sports culture. I did those things because there was an element of challenge that stimulated me. So if you asked me the rules or what is what I still don’t know, I’ve never had an interest in those aspects of “sports”. My thoughts were just give me the ball and I’ll do what I need to do. I think things like that are good.
After that I discovered Olympic weightlifting. I’m almost 32 now and still do the Olympic lifts everyday, sometimes twice.
In the old days Olympic weightlifting was an old mans hobby. Looking back I can see why. It requires a certain amount of patience that is hard to ingrain into a twerp without having a lot of supervision. And that is not a bad thing, you have to repress curiosity and introduce structure for a child to do something so mindless because at that point Olympic weightlifting seems rather pointless.
When most people think of weightlifting they think of crossfit (I’m not going to even legitimize that with a capital letter) and bodybuilding.
Those things are not Olympic weightlifting. At least not to me. And because this is an opinionated post it’s probably wise to keep that fact in mind.
I think Olympic weightlifting is one of the healthiest physical hobbies you can engage in. Why? No scientific studies here, not that there aren’t any, but because it’s not important. So why is it one of the healthiest activities besides drinking wine, eating chocolate, and smoking or Snus? Or eating beef ribs? Because it makes me feel healthy. That’s why. That is all there is to it.
Now for you it might be reading a book, or going for a stroll in the park, or injecting a dose of insulin. Fair enough.
When I was growing up, and I’m not old by any means, children still had hobbies. We started things on fire, we played in the swamp, we were outside past the time the street lamps came on, we burned slugs in gasoline, climbed roofs, jumped out of our windows at night, we wrestled, and we still did a lot of things that are typically associated with the golden age of American culture. A lot of stupid shit. To be fair, I was on the tail end of that, right as we began to transition from board games to their digital counterparts. So even though my friends typically had hobbies there were also a lot of children who were just learning to mold the couch to their asses.
I write a bit, o.k. mostly about material things like saturated fatty acids, graspable things you can hold in your hand to improve your life. And while those things can go a long way to improve your life. The recipe will never be complete without some missing ingredients:
Getting a life.
I have part of a book sitting on my hard drive collecting digital dust. The book as far as I can tell is my most original idea, I’m just not ready to finish it yet. I’m still testing it. So far it has stood up to several years of new data. As I’ve said before, I’m curious about exceptions, and because my idea is important to me I want to cherish it a bit, and if it should happen I’m wrong, then I will let it go and will never publish it. I think in one of my posts on PUFA that I never finished the second part to I even eluded to the fact that some people seem to do fine and live a long time with it, or get away with it. Of course that is only happening because they are maintaining normoglycemia. Are they lucky? Yes of course in their eyes. But I see something else at play something very material and explainable.
That is what the book is mostly about, not how to get a life, but why having a life matters tremendously.
If you spend a lot of time arguing on the Internet, it’s time for you to stop. Why not start your own blog and share your ideas with others. One of two things are going to happen, either a) you’ll loose interest and realize that the only reason you are on the Internet is because you like to argue with people or b) you’ll start exploring things on your own and be more likely to discover solutions to your problems that will give real change in your life. You’ll become a scientist in your own right specializing in the study of you. Perhaps you might make some breakthroughs instead of using other peoples paradigms on yourself.
Do you know what being sedentary does to oxidative stress markers? And I’m not just speaking of being physically sedentary I’m talking about an idle unfulfilled brain more concerned with arguments instead of exploration.
May the force be with you.
You’ll notice around here that I sometimes post papers on the usefulness of ketones yet I rarely talk about ketosis. The reason is that I think ketosis is secondary to the main point. The main point being: run your metabolism off of saturated fatty acids. I do not think that the benefits of a high fat diet stem from being ketotic I think the benefit comes from running your metabolism on fat, even high fat PUFA rats do better than low fat rats when we are speaking of longevity. And I think that I’ve been consistent about that, the saturated fat bit, to the point of ignoring a lot of other things people seem to care about, which I do on purpose because I think it really doesn’t matter.
It’s useful to think of the word “metabolism” and what it really means. I think we can compare this to Cogito ergo sum, “I think, therefore I am” or “I am thinking, therefore I exist”. Do you really think that if you are eating a high carbohydrate diet that “you” exist? What exists in that state is your hyperglycemic self and your hypoglycemic self. Somewhere in the middle you exist, that is where you exist in pure form, that is where your metabolism lies, an efficient one at that. The balancing act between hyper- and hypo- glycemia is amazing. It’s what helps to maintain “form” i.e. you. The things your physiology does to try to maintain OXPHOS and suppress the Crabtree effect thus preventing you from degenerating into giant mass of primitive cells is not appropriately appreciated.
When free fatty acids rise during stress or during sickness or when anything bad happens that is a signal, a good one, that your physiology is trying to maintain form, trying to maintain you, if that doesn’t happen or you block it, degeneration follows, much like when you take statins to try to lower cholesterol. This way of thinking, that because this or that rises during stress or bad times therefore this is bad is completely ignoring the mechanisms that caused the flux in the first place.
It’s like saying the ball dropped because I opened my hand and let it go, without considering gravity and the impact it has if you opened your hand in zero gravity or on another planet. It goes right back to the cause and correlation thinking that a lot of people spend their time pointing out and arguing against.
Judging by comments and walking around the web I think that some people have this idea that if your cells are not running off of glucose then your cells are running off of ketones. The misunderstanding being that if you aren’t feeding your cells glucose that you are eating a lot of fat or glucose deprived and then, that fat (dietary or stored), is being converted into ketones and then being oxidized by your mitochondria. That is a misguided black and white understanding of metabolism.
Your cells prefer to burn saturated fat. End of story. They are happy that way. Every cell in the body that has mitochondria can and does prefer to burn saturated fat. End of story.
If you think “high fat diet” and then automatically think “ketones” you’re missing the point.
Ketones are not a dose dependent fuel source i.e. the more you have floating around the better. I detect a level of lipid hypothesis trains of thoughts when people talk about ketones. For example, some people still believe that low cholestorol is good and that more is bad, without considering what is actually causing the flux. The same is true I think when people are thinking about ketones, the context is not considered.
A while ago I wrote my thoughts on aspirin.
Recently, Joe asked: “If a large part of a chimpanzee’s diet is fructose, why are they not dying from any heart or aneurysms?”
It’s a good question. But I would ask in return how do we know they aren’t?
In the wild animals get sick and die just like we do. Only we are less likely to take notice because they have no newspapers with obituaries or anyone to do autopsies on a regular basis so we can investigate the cause of death. I would guess primates die all the time and are left behind where they return to the earth. I would also say that sick animals that are burdensome to the group would be left behind as well. The San people did this as well if I am recalling The Old Way correctly.
Because of the lack of autopsy reports done on Chimpanzees in the wild it would be hard to know either way. But we do have Zoos. And autopsies are done there on occasion. Still we might say that the diet is a bit different from what a certain animal might eat in the wild. True. However, I think fructose is uniquely harmful. And I think that animals who eat a lot of fruit will have some of the same problems humans do with fructose.
But then we have the diet thing. The diet we feed them in the Zoo and then the diet they would eat in the wild. That’s a problem. But really, we can kind of work around this by say comparing the Chimpanzee to other animals say the Gorilla or Sheep which both ferment their food to short chain fatty acids. So perhaps we can compare animals that live in captivity to see a difference.
I have a couple papers on this topic. But I want to look at the pathology which is the most revealing. Lets start with the Chimpanzee:
O.k. tea and milk? I doubt Chimpanzees are brewing tea in the bush. Nonetheless, I would think these food choices are something Dr. Peat would agree with. Nix the tea.
Interesting. Now lets move to the other animals that eat a lot of leaves and grass and other roughage and convert it into fat.
Interesting. What about a sheep? Those are probably fed pretty “normally” even in captivity.
So we have one Chimpanzee, one Gorilla, and 122 Sheep. Is this enough data to get a realistic look into what is happening in the wild? Maybe for the sheep it is a better sample size.
I don’t base the harmfulness of fructose totally on macroscopic studies. I’m thinking more at the cellular level i.e. Crabtree effect. And thinking like that, this paper is convenient and fits with my bias.
But we have other omnivorous species of monkeys as well that tend to eat what a lot of folks would consider healthy.
Day, C. E. (Ed.). (1976). Atherosclerosis Drug Discovery (Vol. 67). Boston, MA: Springer US. doi:10.1007/978-1-4614-4618-7
Kavanagh, K., Wylie, A. T., Tucker, K. L., Hamp, T. J., Gharaibeh, R. Z., Fodor, A. A., & Cullen, J. M. C. (2013). Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates. The American Journal of Clinical Nutrition, 98(2), 349–57. doi:10.3945/ajcn.112.057331
Muldoon, M. F., Kaplan, J. R., Manuck, S. B., & Mann, J. J. (1992). Effects of a low-fat diet on brain serotonergic responsivity in cynomolgus monkeys. Biological Psychiatry, 31(7), 739–42. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1599991
Stehbens, W. E. (1963). Cerebral aneurysms of animals other than man. The Journal of Pathology and Bacteriology, 86(1), 161–168. doi:10.1002/path.1700860120
First, I’m always surprised that people read my blog, I don’t get a lot of traffic and there are a lot of people who are smarter than me and have fascinating ideas. True, I only read their blogs because they happen to draw similar conclusions or confirm my own ideas but they are miles ahead in their concrete understanding while I’m left to daydream and theorize.
I thank those who have commented and asked questions it only goes further to deepen all of our understandings, both directions.
I respect your privacy, however, I dislike anonymous comments or comments with your name as an organization or business and comments with fake email addresses and websites. I give you my name and details of my personal experiences (see “About” page) and you can freely contact me. I dislike off point comments or comments that don’t contribute. I dislike argumentative claims that aren’t cited.
I want to encourage “realness” here. Use your name (capitalize the first letter), you only need your first, I want a more personal experience. I want you to be an individual and stand by your comments or expressions or questions. I want to know the people who read here. I want as human an experience as possible while masked behind fancy studies and carefully thought out words and phrases. Take pride in your comment, stand by it, cite it if it is needed, punctuate and use the spell checker, make your ideas and comments accessible to everyone. Cumulative knowledge.
A person I deeply respect once said in so many words “information is information good or bad, both sets help you to draw meaningful conclusions”. You know who you are.
A few years ago I came across this letter (Kasper, Schonborn, & Rabast, 1975). I was still in Germany at the time and still fiddling with carbohydrates. I knew at the time that saturated fat increased thyroid hormone production and promoted an optimal metabolism because I was outside in the cold doing a lot of running and when my carbohydrates got a bit higher than normal I wouldn’t be able to run in freezing weather with shorts, no I’d have to put the thermal tights on thus reducing me to a grade B bad ass instead of grade A.
I remember this bit catching my attention at the time:
I filed it away in my brain.
Shortly after I remember coming across this paper that proposed that iodine deficiency may be caused by an increase in carbohydrates (Kopp, 2004). This seemed to fit in with the theme: those energy substrates that are efficient AND optimal are so because they require less overall cofactors to be oxidized and because they are the exact type of resource “desired” by the mitochondria. Typically efficiency is the ratio of useful output to the total input in a system. Sure mitochondria can oxidize other substrates, however, what you find is that those substrates namely the polyunsaturated fats and carbohydrates tax the entire organism bringing into the picture those hormones that otherwise would be background which typically increase the need for more energy. That bit there—that hormones are background until undesirable energy substrates are brought into the picture—is a key point to remember for future posts.
Recently I came across this paper (Yoshimura, Hori, & Yoshimura, 1972):
I’ve come across several papers looking at the effects of macronutrients on thyroid hormones. The pattern is that fat has the greatest impact on thyroid hormone production and that carbohydrate while it can temporarily increase T3; the increase in T3 caused by increased carbohydrate consumption is actually a protective measure, a symptom. A symptom that I think is best to avoid. Interestingly fat reduces anxiety when compared to the other macronutrients which in my opinion points to stable thyroid hormone production (Prasad & Prasad, 1996).
It has been shown that carbohydrate can increase RQ. Though this is often not clear cut it is the general trend that RQ increases with carbohydrate consumption. This is in my opinion a result of the Crabtree effect.
When carbohydrates are consumed T3 increases which results in an increase in fatty acid oxidation. This is curious because one might be so inclined to expect an increase in glucose oxidation. Instead what happens is that fatty acid oxidation increases and so does DNL. Essentially carbohydrates are being converted to fatty acids, insulin is raised and the surplus of fatty acids is being stored, T3 if it can stay elevated long enough tries to bring back energy balance by burning fatty acids. Of course overtime this breaks (pathological insulin resistance coupled with thyroid disorder probably leads to ketoacidosis) and results in metabolic derangement not unlike how the pancreas breaks after a few decades of hyperglycemia. The solution to this problem is to eat in a way that prevents the problem in the first place.
T3 also happens to stimulate mitochondrial uncoupling, the uncoupling effect is partially indirect and the result of burning fatty acids. Uncoupling is for another time.
I think that when you base your diet off of saturated fat that ketones and glucose are spared in the right amounts for the tissues that desire them, much like in neonates. I think that aging is mainly a defect in fatty acid metabolism not glucose metabolism. I think this is why our risk for cancer increases as we age, again Crabtree effect. Thyroid hormones keep the body organized i.e. saturated fat as the predominate energy substrate keeps the body functioning properly, carbohydrates cause disorganization. For the most part people who live a long time like their fat, and when you see an exception my opinion is that they are going the naked mole rat route, they are eating carbohydrate but are actually fermenting it all to fatty acids and like the naked mole rat are physiologically insulin resistant.
Kasper, H., Schonborn, J., & Rabast, U. (1975). Letter: Behavior of body weight under a low carbohydrate, high fat diet. The American Journal of …, 28(8), 800–801. Retrieved from http://ajcn.nutrition.org/content/28/8/800.short
Kopp, W. (2004). Nutrition, evolution and thyroid hormone levels – a link to iodine deficiency disorders? Medical Hypotheses, 62(6), 871–5. doi:10.1016/j.mehy.2004.02.033
Prasad, A., & Prasad, C. (1996). Short-term consumption of a diet rich in fat decreases anxiety response in adult male rats. Physiology & Behavior, 60(3), 1039–42. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8873290
Yoshimura, M., Hori, S., & Yoshimura, H. (1972). Effect of high-fat diet on thermal acclimation with special reference to thyroid activity. The Japanese Journal of Physiology, 22(5), 517–31. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/4539646
It’s been a while, I do have a back log of posts waiting to be finished on mitochondrial uncoupling, hormones, ketones, and diatomic hydrogen, they are all separate posts but they fit together.
Work has been busy, so has life, but thinking about what I think about never stops. And I constantly flagellate myself for not keeping up with writing.
Since I have limited time I thought I’d write a bit about what I eat for those that are curious or confused by some previous posts.
In the mornings I usually have about half a pint of cream (which is pastured), there is coffee somewhere in there (a French roast made in the press). I do drink this throughout the morning, it’s not a contest.
For lunch or somewhere around that time I like cream cheese which is imported from France (hat tip to Whole Foods for managing that one), cream cheese is made from cream not milk, so it has tiny amounts of protein and although the label says there are no carbohydrates I bet there are a few molecules in there somewhere.
After lunch I usually have a cup or two of Bulgarian yogurt which is made from whole milk. I sometimes have that in the morning as well. It’s pretty common for me to go through at least 3 cups of that a day.
Dinner is usually beef (which is pastured and I go very very out of my way to get it from a specific farmer… the fat still tastes sweet… that’s fresh), although I don’t always eat meat every day, when I do I make up for it. I like beef short ribs, beef shank, marrow bones, oxtails, and that sort of thing. Love roasts. I don’t know how much beef I eat but probably approaching 1 pound or so on average which sometimes includes the weight of the bones other times not.
Somewhere between lunch and dinner I usually work in the other half pint of cream, and in the evenings I’ve been known to have up to 2 quarts of milk accompanied with cream cheese. But that is rare.
I rarely use anything more but salt, and even then I usually don’t use it, I salt to taste when needed. Needless to say I have no problem with using spices and the like and/or veggies when I have a hankering for them. My taste buds are unspoiled I guess.
I do lift heavy weights every single day, not for health reasons but because I enjoy that type of thing, much like the other things I do in my life.
That’s about it. Some days I have only cream and yogurt, some days I’m not hungry in the morning and don’t eat till dinner, you get the picture.
Oh, I do have butter milk on occasion or mix it with my milk, I like the sour taste.
“Dairy products derived from the milk of cows fed in pastures are characterised by higher amounts of conjugated linoleic acid and α-linolenic acid (ALA), and several studies have shown their ability to reduce cardiovascular risk. However, their specific metabolic effects compared with standard dairy in a high-fat diet (HFD) context remain largely unknown; this is what we determined in the present study with a focus on the metabolic and intestinal parameters. The experimental animals were fed for 12 weeks a HFD containing 20 % fat in the form of a pasture dairy cream (PDC) or a standard dairy cream (SDC). Samples of plasma, liver, white adipose tissue, duodenum, jejunum and colon were analysed. The PDC mice, despite a higher food intake, exhibited lower fat mass, plasma and hepatic TAG concentrations, and inflammation in the adipose tissue than the SDC mice. Furthermore, they exhibited a higher expression of hepatic PPARα mRNA and adipose tissue uncoupling protein 2 mRNA, suggesting an enhanced oxidative activity of the tissues. These results might be explained, in part, by the higher amounts of ALA in the PDC diet and in the liver and adipose tissue of the PDC mice. Moreover, the PDC diet was found to increase the proportions of two strategic cell populations involved in the protective function of the intestinal epithelium, namely Paneth and goblet cells in the small intestine and colon, compared with the SDC diet. In conclusion, a PDC HFD leads to improved metabolic outcomes and to a stronger gut barrier compared with a SDC HFD. This may be due, at least in part, to the protective mechanisms induced by specific lipids.”
Benoit, B., Plaisancié, P., Géloën, A., Estienne, M., Debard, C., Meugnier, E., … Michalski, M.-C. (2014). Pasture v. standard dairy cream in high-fat diet-fed mice: improved metabolic outcomes and stronger intestinal barrier. The British Journal of Nutrition, 112(4), 520–35. doi:10.1017/S0007114514001172
The Congo Red stain is a special stain used in histology to aid in the diagnosis of amyloidosis. A polarizing filter will highlight amyloid an “green apple” color. This is modified version of the stain I developed for use in our laboratory:
Counterstain the slides in Harris hematoxylin for 15 minutes, dip in acid alcohol 1 to 2 times, rise in tap water. Blue in 0.3% ammonium hydroxide. Rinse in tap water. Incubate slides in Congo Red at room temperature for 30 to 60 minutes. Rinse in tap water, then dip the slides in 80% alkaline alcohol 1 to 2 dips. Dehydrate, clear, and coverslip.
I once had a white rabbit named Clariece. Her and my Turkish Van cat, Chuck, used to sit and look at each other for long periods of time. They shared the litter box. If you know anything about rabbits, you know that sweet potatoes and other starchy things can be lethal.
Rabbits are herbivores.
Rabbits use hindgut fermentation.
One day many moons ago when sweet potato was something I ingested quite frequently because it tasted good, some fresh sweet potato fresh from the market was left on a low shelf (not by me) within a rabbits paw reach of my fluffy white rabbit Clariece.
A day later I noticed Clariece looked puffy. Very puffy. And quite hard. Then I noticed she was sitting very still for long periods of time in the corner. Something was wrong.
Later that day when I went to cook sweet potato I noticed that half of one was gone.
My forensic investigation of the sweet potato revealed fluffy white rabbit teeth marks.
I continued to watch over her and tried to keep her comfortable hoping for the best. Her last hops were her hoping over to the litter box climbing inside to take her last breath of cat piss.
I’m sure the sweet potatoes tasted quite good to her.
Liver tastes like shit.
I wanted to do a short post quickly before I start packing my apartment to move early this week. Here I just want to look at RQ as a measurement and what it can tell us. I will write more about RMR and how it relates to RQ including different physiological states that influence RQ such as birth, what happens to RQ at the start of breast feeding, how thyroid hormones effect RQ, etc. once I get into my new apartment.
There can be a problem when reading papers as to what it exactly means to have a “high metabolism”. The phrase is loosely defined. But some people, including Dr. Peat, define the strength of the metabolism based on the RQ (respiratory quotient). The RQ is essentially the ratio of carbon dioxide eliminated to oxygen consumed.
RQ = C02 eliminated / O2 consumed
A RQ closer to 1 typically means more carbohydrate is being burned and a value closer to 0.7 typically means fat is being burned.
For some reason there is the idea that a high RQ closer to 1 is the same thing as a “high metabolism”. I don’t really know how RQ became associated with the rate of the metabolism. RQ tells you essentially what fuel you are burning, nothing about the rate of your metabolism.
“On a normal diet, his weight was 152 pounds, and his metabolic rate was from 9% to 12% below normal, but after six months on the diet it had increased to 2% below normal. After three months on the sugar and milk diet, his weight leveled off at 138 pounds. After being on the diet, when he ate 2000 calories of sugar and milk within two hours, his respiratory quotient would exceed 1.0, but on his normal diet his maximum respiratory quotient following those foods was less than 1.0.
The effect of diabetes is to keep the respiratory quotient low, since a respiratory quotient of one corresponds to the oxidation of pure carbohydrate, and extreme diabetics oxidize fat in preference to carbohydrate, and may have a quotient just a little above 0.7.” ~Dr. Peat
“His respiratory quotient increased (producing more carbon dioxide), as well as his rate of resting metabolism.” ~Dr. Peat
“Maintaining a high rate of oxidative metabolism, without calorie restriction, retards the accumulation of PUFA, and a high metabolic rate is associated with longevity. An adequate amount of sugar maintains both a high rate of metabolism, and a high respiratory quotient, i.e., high production of carbon dioxide.” ~Dr. Peat
“At high altitude, or when taking a carbonic anhydrase inhibitor, there is more carbon dioxide in the blood, and the serum phosphate is lower; sucrose and fructose increase the respiratory quotient and carbon dioxide production, and this is probably a factor in lowering the serum phosphate.” ~Dr. Peat
Needless to say, the only point with which I agree with from above is that carbohydrate increases RQ and fructose is effective at the task. The literature supports that.
It seems that as we age RQ increases and if you believe that a higher RQ is a measure of the rate of metabolism this can lead to some paradoxical conclusions. If that is what you think, you don’t have to do anything, your RQ will increase without any dietary intervention.
In obesity and diabetes it is observed that RQs tend to be higher (more towards 1). Aging, disease, and other metabolic derangements at the end of the day all basically stem from hypoxia (Douglas & Haddad, 2008).
“Similarly, individuals with a high 24-hour respiratory quotient (RQ) are more likely to gain weight than those with a low RQ.” (Ravussin, 1995)
“Over a 7-year period, mean unadjusted and adjusted 24-hour RQ increased (p < 0.01). Cross-sectional data analysis showed that both the unadjusted (r = 0.19, p < 0.03) and adjusted (r = 0.19, p < 0.03) 24-hour RQ correlated with increasing age while adjusted BMR (r = -0.21, p < 0.02) correlated inversely with age.” (Rising, Tataranni, Snitker, & Ravussin, 1996)
“Subjects with higher 24-h RQ (90th percentile) independent of 24-h energy expenditure were at 2.5 times higher risk of gaining greater than or equal to 5 kg body weight than those with lower 24-h RQ (10th percentile).” (Zurlo et al., 1990)
“In contrast obese patients who succeeded to retain the weight loss achieved initially by the VLCD at 2-yr follow-up (weight losers) or those who did not exhibit weight fluctuations (weight noncyclers) were characterized by a significantly lower RQ.” (Hainer, Kunesova, & Parizkova, 1999)
“High nonsleeping RQ (NSRQ) predicted 2-year change in FM independently of energy balance, circulating insulin, and insulin sensitivity. This observation suggests that low postprandial fat oxidation may uniquely predispose obesity-prone individuals to accrual of adipose tissue.” (Ellis, Hyatt, Hunter, & Gower, 2010)
Now a high RQ is not always associated with weight gain, this is why RQ really should not be associated with the rate of metabolism. If you are into calorie counting, you can have a high RQ on a high carbohydrate diet without gaining weight. But DNL is going to be very active. You’ll be burning fat just as quickly as you make it. Your triglycerides will probably increase, but they might not if you are taking thyroid. which is going to enhance fatty acid oxidation.
Aside: Thyroid hormone itself stimulates DNL. DNL is reduced in hypothyroidism and treatment with T3 increases DNL.
T3 also decreases the RQ (Barbe et al., 2001).
Of course long term you are going to run into a lot of side effects as DNL will eventually not be able to supply the demand T3 places on fatty acid oxidation. This is speculative, but I think a reasonable partial explanation for why a lot of people on a low-fat-high-carbohydrate-diet taking thyroid probably feel better when they eat more saturated fat.
Barbe, P., Larrouy, D., Boulanger, C., Chevillotte, E., Viguerie, N., Thalamas, C., … Langin, D. (2001). Triiodothyronine-mediated up-regulation of UCP2 and UCP3 mRNA expression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 15(1), 13–15. doi:10.1096/fj.00-0502fje
Douglas, R. M., & Haddad, G. G. (2008). Can O2 dysregulation induce premature aging? Physiology (Bethesda, Md.), 23, 333–49. doi:10.1152/physiol.00023.2008
Ellis, A. C., Hyatt, T. C., Hunter, G. R., & Gower, B. a. (2010). Respiratory quotient predicts fat mass gain in premenopausal women. Obesity (Silver Spring, Md.), 18(12), 2255–9. doi:10.1038/oby.2010.96
Hainer, V., Kunesova, M., & Parizkova, J. (1999). Respiratory quotient in obesity: its association with an ability to retain weight loss and with parental obesity. Sbornik …, 101(1), 99–104. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10953639
Ravussin, E. (1995). Metabolic differences and the development of obesity. Metabolism: Clinical and Experimental, 44(9 Suppl 3), 12–4. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7674909
Rising, R., Tataranni, P. A., Snitker, S., & Ravussin, E. (1996). Decreased ratio of fat to carbohydrate oxidation with increasing age in Pima Indians. Journal of the American College of Nutrition, 15(3), 309–12. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8935448
Zurlo, F., Lillioja, S., Esposito-Del Puente, A., Nyomba, B. L., Raz, I., Saad, M. F., … Ravussin, E. (1990). Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ. The American Journal of Physiology, 259(5 Pt 1), E650–7. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/2240203
“When something out of the ordinary happens, it is ridiculous to say that it is a mystery or a portent of something to come. Eclipses of the sun and moon, comets, clouds that flutter like flags, snow in the fifth month, lightning in the twelfth month, and so on, are all things that occur every fifty or one hundred years. They occur according to the evolution of Yin and Yang. The fact that the sun rises in the east and sets in the west would be a mystery, too, if it were not an everyday occurrence. It is not dissimilar. Furthermore, the fact that something bad always happens in the world when strange phenomena occur is due to people seeing something like fluttering clouds and thinking that something is going to happen. The mystery is created in their minds, and by waiting for the disaster, it is from their very minds that it occurs. The occurrence of mysteries is always by word of mouth.” ~Yamamoto Tsunetomo
It’s interesting how words, phrases, ideas, and behavior go through multiple stages of metamorphosis within the context of a culture, subculture, and individual level.
Metamorphosis in insects ends with a self-sufficient organism able to consume energy and reproduce. After reproduction, the insect soon dies leaving it’s offspring to fulfill both an environmental and reproductive purpose. But metamorphosis is a linear process; there is a beginning and an end. What emerges from the cocoon is something refined for a specific purpose. Words, phrases, ideas, and behavior tend to have a linear development, but follow circular patterns of refinement until their meaning becomes either precise or meaningless.
Nutrition is difficult to define. For some it is lists of safe foods. For others it’s all about having energy to do what one wants to do in life for as long as possible. And there are a majority of people who don’t concern themselves with defining it.
It is the commercialization of nutrition and my interest in psychology that eventually interested me (besides my own self-experimentation and observations) in the psychological impact of nutrition, pre- and post-, on behavior.
I have found, in observation, that an idea a culture is attempting to define follows a process with patterns that can be developed into behavioral frameworks, which predicts the refinement process. It is the process of refining the definition of an idea that isolates or unites different groups of people. This process is similar to Max Weber’s idea of “rationalization” in the context of religion.
One cannot be down on people who are led to and fro by different dietary paradigms. This process is a consequence of rationalization driven by the unconscious. Likewise, one cannot be down on an entire culture defined by its government officials or religion. Its nature is what has allowed us to survive without the interconnection that now defines our world. Developed personality and individuality in the Jungian sense is a unique occurrence.
In the modern world there is less need for reliance on others. But there is still a need for passing on of knowledge, tradition, and wisdom, suitable for survival, social interactions, and going about daily activities. Science and the Internet are impacting cultural instinct, traditions, and wisdom through exposure. I view this exposure neutrally. Complete confidence on what others deem as fact is often a mistake just as being overly self-reliant and reinventing the wheel again is inefficient. There is a cautious balance to be struck, especially in a time when there is a shift in consciousness and the process of cultural diffusion is active.
An intelligent, thinking, and reasoning being must strike a balance between the two. It is this balancing act that allows cultural evolution to occur and new paradigms to develop which will be tested by successive generations. What works stays, what doesn’t work leaves; better ways of doing things slowly filter out older ways of doing things. New ways of thinking philosophize old traditions and religions. For example: Thomas Aquinas, applying Greek philosophy to biblical texts, or Martin Luther, nailing his grievances to the Catholic cathedral door.
These events happen when there is a shift in unconsciousness. And what follows is a revolution in cultural knowledge to try and rationalize why we did things the way we did in the past and why it is justified to change things for the future. Radicals entrenched in their beliefs usually, but not always, die in these shifts of thinking; literally or by sacrificing the personality. Being a martyr for a particular paradigm has never been a personally natural inclination. When the individual is cornered and experience is conflicted with lacquered beliefs, the individual is faced with options of entrenching themselves behind belief or taking steps to evolve in another direction. It is the collateral damage of opposing extreme views in groups of people that often drive cultural evolution. At some point we must put aside belief and continue moving forward. A fight to the death is not a viable option except for the delusional.
“We should not let ourselves be burnt for our opinions: we are not that sure of them. But perhaps for this: that we may have and change our opinions.” ~Nietzsche
What is difficult for the entrenched individual is not the new shift, but the shift that points to years or a life wasted and genuine interests forsaken. There is a saying: “You can’t teach an old dog new tricks.” Few people are so downright stubborn. But these defining qualities are common enough that most of us are familiar with these individuals.
Entrenching is not the new idea but rather the aversion to self-confessing an error approaching things in a new way. The conflict does not arise out of the new idea but arises out of the individual. These individuals place too much power in words and ideas. These people are the real dangers in society—not the originators of new ideas. It takes much more than an individual to do anything with a dangerous idea, just as it takes much more than an individual to do something with a useful idea. Ideas have to be stated and different people must implement them before they can become a useful or dangerous reality.
Despite modern man’s large brain, the rational portion seems atrophied in most. This allows erroneous thought to pervade in popular culture and society, causing harm. Capitalistic, mechanistic, and authoritarian thinking makes this easy to do.
Some ideas tend to have cyclical natures occurring and reoccurring throughout history, often shifted or changed slightly but still keeping their original essence or philosophy. Observations have personally demonstrated that ideas are cyclical simply because what is current is not satisfying and causes gas and bloating. When enough people smell the stink they become uneasy and start to look for new solutions.
People try old ideas, not simply for the sake of the new, but for the promise of something better (or curing chronic boredom).
Old ideas come and go and are cyclical for many reasons. One reason assumes there is validity to the idea, yet for whatever reason remains underdeveloped in that period of time. There have been plenty of ideas left undeveloped because of a requirement for a different field of science. Later, some of these ideas ended up being game changers in the modern era.
Another reason is simply that the idea was not valid. When people do try old, invalid ideas in their life, you will often find that these people are constantly trying to justify the validity of their dug up treasure. Foolishness is the virtue of the wise.
There is nothing vain about exploring history through a modern perspective and trying old approaches when modern and fringe approaches fail. Trying is one thing. Trying is not miserably “riding it out”. Loosely illustrated, trying means taking an interest in the cello and with every passing lesson there is improvement in both technical aspects and style; persistently trying means taking up the cello and despite best efforts never being able to complete the first lesson, despite trying for several weeks, months, or years. For those, the cello, despite intense interest, will always remain just an interest.
When something does not work for you, be bold, ask questions and seek answers.
“Possessing opinions is like possessing fish, assuming one has a fish pond. One has to go fishing and needs some luck—then one has one’s own fish, one’s own opinions. I am speaking of live opinions, of live fish. Others are satisfied if they own a cabinet of fossils—and in their heads, convictions.” ~Nietzsche
Filip left a comment asking about aspirin, this was another one of those comments turned into post type deals.
So speaking of aspirin. There are some dots to connect here, and definitely some different trains of thought that you can ride, but have a look at the following articles and follow the paper trail.
Paterson, J. R., Baxter, G., Dreyer, J. S., Halket, J. M., Flynn, R., & Lawrence, J. R. (2008). Salicylic acid sans aspirin in animals and man: persistence in fasting and biosynthesis from benzoic acid. Journal of Agricultural and Food Chemistry, 56(24), 11648–52. doi:10.1021/jf800974z
“To examine the possibility of a gastrointestinal bacterial source for SA, two small groups of germ-free mice were assayed for SA. The pooled serum from six mice treated with neomycin, 100 mg/kg/day, for 4 days before sacrifice had a slightly higher concentration of SA in serum (0.309 μmol/L) than the pooled serum sample from six untreated animals (0.268 μmol/L). Another germ-free animal model studied was the Sprague−Dawley rat delivered by caesarean section, reared in a sterile environment, and fed sterilized food. A group of eight such germ-free animals had a pooled serum SA level of 0.166 μmol/L, approximately 2.5 times greater than the pooled serum salicylic acid level of 0.069 μmol/L from a group of control animals. The net effect of minimizing or eliminating a contribution from colonic bacteria in these animal models was therefore enhancement of serum SA levels in the host animal.”
“Results of SA levels in a large variety of animals showed that those species regarded as primarily carnivorous had levels comparable to those measured in herbivores. Some bacteria, notably mycobacterial, yersinia, and pseudomonas species, synthesize SA to enhance iron chelation, so there was a possibility that gut, particularly colonic, bacteria might be the source of SA not readily explicable by lack of dietary exposure. However, preliminary study of two germ-free animal models reported here showed the net effect of minimizing or eliminating a contribution from colonic bacteria was, in fact, an increase in serum SA levels.”
A review of the literature by Heiby cites an interesting experiment on rat that perhaps shed some light on the risk of stomach bleeding. Aspirin was far more toxic to rats fed a high carbohydrate diet than it was to rats fed a high protein diet. A deficiency of magnesium increased this toxicity, especially in pregnant animals. Gastric ulceration in non-pregnant rats was very severe on the high carbohydrate diet (14, p. 255). On the basis of these animal studies, it is interesting to speculate that the apparent increase over the last half-century in the risk of stomach bleeding due to aspirin use may be the result of the large increase in dietary carbohydrate during the same period.
I originally came across that here. But as it is written there, there are differences in the in-text citations and I was not able to track down a paper to verify that observation.
And Peter mentions this (there is also a bit on coconut oil in the following paragraph if you follow the link, for the few that asked about that):
Anyone reading Chris or Emma’s blogs will realise that aspirin, and possibly other related salycilates from plants, cause the pancreas the secrete extra insulin. Avoid. Gluten and wheat germ agglutinin (both from wheat, barley and rye) are (or contain) insulin mimetics, avoid. Casein stimulates insulin secretion, avoid. Pharmaceutical NSAID probably do the same as salycilates, avoid if possible.
O.k. Now for some of my thoughts.
As for daily use, I don’t know. In general, I like things that uncouple the mitochondria. However, to speculate, there is a difference between an energy substrate that uncouples mitochondria and a compound that uncouples mitochondria. I think that the latter can deplete ATP to an extent that is undesirable (which would be dose dependent)., but I can also think of some situations where that type of uncoupling would confer some desired effects. In my endotoxin and fructose post I talked about depleted ATP impacting tight-junction (occluding junctions or zonulae occludentes) integrity. Which makes this interesting. Whereas some saturated fat (e.g. palmitic acid) which also uncouples the mitochondria maintains tight-junction integrity.
Speculating some more, a lot of people get nosebleeds from aspirin use. When you get a nose bleed, you notice it, blood dripping out of your nose, that to me is like a rupture. You don’t notice one or two blood cells on your upper lip, you notice a good amount of blood coming out. That is a tremendous failure in the integrity of the tight-junctions in capillaries. Now imagine consuming some fructose (which is depleting ATP too and probably weakening tight-junctions). It is hardening your arteries and when they are nice and calcified, lets say you take some aspirin and one of your calcified capillaries “fractures”, but see now your blood is thin and blood comes spouting out. Sounds quite like an aneurysm.
Because fructose isn’t going to calcify your vascular system overnight, I’m sure little microscopic breaks happen here and there in the tight-junctions which get clotted. Imagine a wooden handrail that thousands of people have run their hands across, some parts keep their shine, other parts chip off and loose their luster. It’s a handrail with character. Or have you ever filled a balloon up and over time you notice certain parts of it are thin and thick as the air diffuses out? Between the clotting and inflammation, I’d say damaged parts of the vascular system might swell much like the thick and thin sections of a balloon under uneven pressure caused by variations in thinness and thickness of vascular/capillary walls. Have you ever untied a worn out balloon that has been sitting in the sun and tried to blow it back up again? It’s never quite the same, and I would imagine the brittleness from the deteriorated rubber would be an interesting way to think about the pathophysiology of a nose bleed or aneurysm. It just fractures at a weak point and pops if you blow it up big enough e.g. a sudden increase in heart rate.
O.k. now this brings me back to aspirin. Sometimes when I’m writing with an old fashioned pencil the tip breaks off in a way where you can kind of fit it back into the pencil and continue writing with it. That of course is not very versatile because you almost always have to write with less pressure and kind of turn the angle of the pencil where the lead broke to keep the bit of lead in. If you have some clots just waiting to break off it would make sense to lower the viscosity of your blood so as not to disturb them. I would say aspirin would be pretty useful for that.
Anyway, I think aspirin might be useful to solve some acute symptoms. And hey, maybe a low-dose aspirin is legit. But don’t forget about the first paper. Like I said, there are a few different trains of thought to ride. Preventing an “aspirin deficiency” would be a better bet. At least that is what I think.
“What was it Oscar Wilde said? ‘The well-bred contradict other people, the wise contradict themselves.’ If you have insight into a body of knowledge, you are going to discover science that contradicts your view. You either modify your model, which if it is sound will survive and benefit from such adjustments, or you put on well-bred airs.
This is the distinction between science, where you are interested in learning new things, and wise enough to contradict yourself as a result, and dogma, accepting which will force you to contradict others (or indeed censor them) unless they agree with you.” ~George Henderson
There was a time when I had a fairly liberal view on the issue of sugar. Sugar resurged when people seemed to be having all kinds of problems with low carbohydrate diets. And to a great many people sugar seemed to resolve some issues. I cannot debate that. I also cannot vouch for the pros or cons of long-term use of liberal amounts of sugar in other people. Some people claim it has helped them to their surprise, others have claimed it has destroyed their health. It is a paradox.
However, I can vouch for myself and a few other people that sugar without a doubt had an absolute negative impact on my/their health in the long-term. Sugar can be useful in some instances e.g. emergency medicine. No doubt that in a calorically malnourished individual sugar can have seemingly positive effects. Despite that, I think there are better and safer ways, lest you want to risk re-feeding syndrome.
But here I want to discuss something briefly that I’ve observed. A quick browse around Ray Peat centered forums and you find that a lot of people have digestive issues. They eat sugar, and if they only eat sugar they seem to do o.k. for a while until they start to introduce new food. Foods that I would consider quite normal. I’m sure there are people who claim that sugar improved their digestion. Fair enough.
I’ve always found the issue of endotoxin intriguing especially when it comes to “leaky gut”. The entire issue of endotoxin is an interesting one. In the end we probably die from sepsis and hypoxia, if something else doesn’t get you first. Yet endotoxin seems to play an important role in immune health. It’s the kind of thing where you want to be in control of it. You don’t want none and you don’t want too much for too long. And of course somewhere in one on my posts I’m quite sure I linked to a study discussing the possibility of a hormonal role for endotoxin.
Endotoxin is not really something that I worry about. Saturated fat is quite good at keeping the tight junctions healthy and functioning. There are a few people around the web who have discussed this. So I’m not going to rehash.
Anyway, there are people whose digestive problems get worse when they eat sugar. There are host of reasons and angles really to look at this. But I want to focus on the effect of fructose. Fructose is quite effective at depleting ATP (Mayes, 1993). That is not a good thing considering that when ATP is depleted, the cells will enter a stressed state. No ATP=comprised cell function. This would have a ripple effect throughout an organism long-term causing all kinds of systematic symptoms which essentially stems from inefficient or inhibited respiration.
I would imagine that depleted ATP would compromise tight junction function. Something which would probably lead to endotoxin “leaking” everywhere. So here you have a situation where when tight junction function is compromised, you literally have LPS poisoning tissue. On the other side of the coin you also have the effect where fructose seems to “tighten” capillaries (Chakir, 1998; Yuan et al., 2007). Some people have viewed this as a good thing. I view it negatively. I want my capillaries to maintain their elasticity and permeability. I want my tissues to always be able to have efficient gas exchange and waste removal. One can easily see how tightened capillaries can cause hypoxia in peripheral tissues. Which of course is something we see in diabetics, not to mention hypertension. As well, I would imagine this could increase systematically serum levels of endotoxin.
You want to maintain the elasticity of the vascular system. You want it to be able to “breathe” properly. One of the sites of endotoxin detoxification is in the lungs. If your capillaries are hardened, detoxification of endotoxin is compromised. Once again, a feature of diabetes induced by fructose is endotoxemia (Kavanagh et al., 2013).
Another feature of fructose feeding is also hyperinsulinemia/insulin resistence (of the wrong sort) (Chakir, 1998). Fructose probably hardens the arteries. If you eat sugar (which is fructose and glucose), fructose will eventually have the effect of hardening the arteries, thus blocking insulin from transporting the glucose bit to where it belongs.
I would say for me personally it is impossible to maintain a liberal disposition with fructose, I can definitely see some cases where small amounts of it could have a potential hormetic effect. But in the long term I think liberal use of fructose is unwise.
Aside: It is interesting to note that some lactic acid bacteria strains protect from endotoxin (Nanji, Khettry, & Sadrzadeh, 1994).
Chakir, M. (1998). Reduction of Capillary Permeability in the Fructose-Induced Hypertensive Rat. American Journal of Hypertension, 11(5), 563–569. doi:10.1016/S0895-7061(97)00411-1
Impaired insulin transcapillary transport and the subsequent decrease in insulin delivery to target organs have been suggested to play a role in insulin resistance. These defects were studied in fructose-fed rats, an animal model with insulin resistance. For this study, male Sprague-Dawley rats were fed with either a 60% fructose enriched (F) or a standard chow diet (N) for a total of 2, 4, or 8 weeks. Capillary permeability to albumin was assessed at the end of each dietary period by quantifying the extravasation of albumin-bound Evans blue (EB) dye in different organs. Unanesthetized animals were injected with Evans blue dye (20 mg/kg) in the caudal vein 10 min before being killed and EB dye was extracted by formamide from selected organs collected after exsanguination. As expected, rats had an increase in blood pressure upon feeding with fructose at 4 and 8 weeks (F, 149 +/- 3 mm Hg; N, 139 +/- 3 mm Hg; P < .05). Using this technique, we showed a 56% and a 51% reduction in capillary permeability in skeletal muscles at 4 and 8 weeks of fructose feeding, respectively (4 weeks: N, 44.5 +/- 5.0 microg/g of dry tissue; F, 19.8 +/- 4.2 microg/g of dry tissue; P < .01 and 8 weeks: N, 23.3 +/- 3.7 microg/g of dry tissue; F, 11.3 +/- 4.0 microg/g of dry tissue; P < .05). Similar changes were observed at 4 weeks in the thoracic aorta (N, 82.8 +/- 8.8 microg/g of dry tissue; F, 53.0 +/- 5.1 microg/g of dry tissue; P < .02) and skin (N, 36.0 +/- 5.3 microg of dry tissue; F, 15.0 +/- 2.3 microg/g of dry tissue; P < .02) and at 8 weeks in the liver (N, 107.5 +/- 4.3 microg/g of dry tissue; F, 80.9 +/- 3.2 microg/g of dry tissue; P < .01). In conclusion, fructose feeding is accompanied by a significant and selective reduction of Evans blue leakage primarily in skeletal muscle and liver, and transiently in the skin and aorta, consistent with a role for decreased tissue insulin delivery in insulin resistance.
Kavanagh, K., Wylie, A. T., Tucker, K. L., Hamp, T. J., Gharaibeh, R. Z., Fodor, A. A., & Cullen, J. M. C. (2013). Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates. The American journal of clinical nutrition, 98(2), 349–57. doi:10.3945/ajcn.112.057331
BACKGROUND: Controversy exists regarding the causative role of dietary fructose in obesity and fatty liver diseases. Clinical trials have indicated that negative health consequences may occur only when fructose is consumed within excess calories. Animal studies have suggested that fructose impairs intestinal integrity and leads to hepatic steatosis (HS). OBJECTIVES: We assessed nonhuman primates after chronic ad libitum and short-term calorically controlled consumption of a high-fructose (HFr), low-fat diet (24% of calories). Microbial translocation (MT), microbiome, and metabolic health indexes were evaluated. DESIGN: Seventeen monkeys fed 0.3–7 y of an HFr ad libitum diet were compared with 10 monkeys fed a low-fructose, low-fat diet (control). Ten middle-aged, weight-stable, fructose-naive monkeys were stratified into HFr and control groups fed for 6 wk at caloric amounts required to maintain weight stability. Metabolic endpoints, feces, liver, small and large intestinal biopsies, and portal blood samples were collected. RESULTS: Monkeys allowed ad libitum HFr developed HS in contrast to the control diet, and the extent of ectopic fat was related to the duration of feeding. Diabetes incidence also increased. Monkeys that consumed calorically controlled HFr showed significant increases in biomarkers of liver damage, endotoxemia, and MT indexes and a trend for greater hepatitis that was related to MT; however, HS did not develop. CONCLUSIONS: Even in the absence of weight gain, fructose rapidly causes liver damage that we suggest is secondary to endotoxemia and MT. HS relates to the duration of fructose consumption and total calories consumed. These data support fructose inducing both MT and ectopic fat deposition in primates.
Mayes, P. A. (1993). Intermediary metabolism of fructose. The American journal of clinical nutrition, 58(5 Suppl), 754S–765S. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8213607
Most of the metabolic effects of fructose are due to its rapid utilization by the liver and it by-passing the phosphofructokinase regulatory step in glycolysis, leading to far reaching consequences to carbohydrate and lipid metabolism. These consequences include immediate hepatic increases in pyruvate and lactate production, activation of pyruvate dehydrogenase, and a shift in balance from oxidation to esterification of nonesterified fatty acids, resulting in increased secretion of very-low-density-lipoprotein (VLDL). These effects are augmented by long-term absorption of fructose, which causes enzyme adaptations that increase lipogenesis and VLDL secretion, leading to triglyceridemia, decreased glucose tolerance, and hyperinsulinemia. Acute loading of the liver with fructose causes sequestration of inorganic phosphate in fructose-1-phosphate and diminished ATP synthesis. Consequently, the inhibition by ATP of the enzymes of adenine nucleotide degradation is removed and uric acid formation accelerates with consequent hyperuricemia. These effects are of particular significance to potentially hypertriglyceridemic or hyperuricemic individuals.
Nanji, A. A., Khettry, U., & Sadrzadeh, S. M. H. (1994). Lactobacillus Feeding Reduces Endotoxemia and Severity of Experimental Alcoholic Liver (Disease). Experimental Biology and Medicine, 205(3), 243–247. doi:10.3181/00379727-205-43703
We have previously shown a relationship between plasma endotoxin levels and severity of alcoholic liver injury in the intragastric feeding rat model. We attempted to reduce both circulating endotoxin and liver injury in this model by administering a lactobacillus strain (species GG) which survives for prolonged periods in the gastrointestinal tract. Male Wistar rats were fed ethanol and liquid diet containing corn oil (CO+E). Another group of animals (CO+E+L) received the diet containing ethanol plus a daily bolus of lactobacilli GG concentrate (10(10) CFU). All animals were sacrificed after one month. All animals had plasma endotoxin measurements and evaluation of severity of pathologic changes in the liver. The weight gain and blood alcohol levels were similar in both groups. The mean +/- SE of the pathology score was significantly higher (3.4 +/- 0.85) in the CO+E group compared to the CO+E+L group (0.5 +/- 0.3, P < 0.01). The virtual absence of pathologic changes in the latter group was accompanied by significantly lower endotoxin levels (8.4 +/- 2.9 pg/ml in CO+E+L group vs 48.3 +/- 7.8 pg/ml in CO+E group, P < 0.01). Feeding of strains of lactobacilli that survive in the gastrointestinal tract reduces endotoxemia and alcohol-induced liver injury in the rat. Lactobacillus species GG provides a potential nontoxic form of therapy for both endotoxemia and alcoholic liver disease.
Yuan, S. Y., Breslin, J. W., Perrin, R., Gaudreault, N., Guo, M., Kargozaran, H., & Wu, M. H. (2007). Microvascular permeability in diabetes and insulin resistance. Microcirculation (New York, N.Y. : 1994), 14(4-5), 363–73. doi:10.1080/10739680701283091
Microvascular barrier injury has been implicated in the initiation and progress of end organ complications of diabetic mellitus. Plasma leakage and fluid retention are seen in various tissues of diabetic patients or animals at the early stages of the disease before structural microangiopathy can be detected. Clinical and experimental evidence suggests that hyperglycemia, often accompanied with insulin deficiency or insulin resistance, causes impaired autoregulation and increased permeability in microvessels. Multiple molecular pathways have been identified as contributors to the altered fluid homeostasis, including increased polyol flux that promotes oxidative stress, advanced glycation that leads to carbonyl stress, and excessive glucose metabolism that results in protein kinase C activation. These abnormal metabolic activities are associated with the production of pro-inflammatory cytokines and growth factors, which can stimulate an array of signaling reactions and structural changes at the endothelial barrier and ultimately cause microvascular leakage. Interventions that manipulate these metabolic and inflammatory pathways have demonstrated efficacy in delaying the progress of diabetic microvascular complications; however, their direct effects and mechanisms of action on the microcirculation remain elusive. A deeper understanding of the molecular basis of diabetes-induced endothelial barrier dysfunction will provide a framework for the development of new therapeutic targets to treat this chronic and debilitating disease process.
“Of the eighteen elements of which the human body is composed, all of which are presumably essential, several are needed in very small quantities. A few are required in liberal quantities. The normal adult needs to receive from the foods eaten one-half to one gram of calcium or lime per day. Few people receive more than one-half of the minerals present in the food. The requirements of phosphorus are approximately twice this amount. Of iron we need from one-seventh to one-third of a gram per day. Smaller amounts than these are required of several other elements. In order to utilize these minerals, and to build and maintain the functions of various organs, definite quantities of various organic catalysts which act as activating substances are needed. These include the known and unknown vitamins.”
Interesting that Price observed calcium to phosphorus ratio of 1:2 in healthy traditional tribes. Undoubtedly it would be hard to flip this ratio unless you were a dairy herding tribe.
Price, W. A. (2008). Nutrition and physical degeneration. La Mesa, CA: Price-Pottenger Nutrition Foundation.
One of things that many find difficult with Dr. Peat is that you can read pages and pages of his ideas and at the end of it you basically are left guessing what it is that you are going to eat. Never mind the inaccuracies. People like Danny Roddy and forums like Peatarian, Ray Peat forum and Co. have attempted to make recommendations through their interpretations. There are some interesting graphics and the sort all around the web, based on those ideas.
I’m all for theory and all that jazz and cool diagrams and inverted pyramids, but really, like I have written before in various places, most people are interested in nutrition because they are sick, not because they want to become nutritionists. They just want to get better and get on with their lives. In that sense I believe in something practical.
My unimpressive advice is to source your diet from cattle. This means eating things like steaks, roasted bones (the marrow), liver, oxtails, suet, tallow, (insert whatever part of the cow you fancy here). Those things are good to eat cooked however you like. This also means that all dairy such as cheese (fresh or aged), yogurt of any type e.g. Kefir, FAGE, (insert any type of plain full fat yogurt here), sour cream, whole milk, cream, half and half, butter, etc. Although I’m using the cow here, as a specific example, really, any ruminant animal and their milk and milk products are good to eat e.g. sheep, bison, goat, etc.
Eat till you are full and drink as much milk as you like. Suet is useful for a lot of things, a lot of people like to use coconut oil, but suet is cheaper in most cases and I think it is better to use along with butter. I don’t recommend coconut oil.
There is no doubt that you can carve out a fine existence living off of those things.
Things to minimize: starch and sugar. Non-starchy vegetables are a fine and welcome addition to any stew as well as whatever spices and seasonings you like. For example, carrots, celery, leek, garlic, onion, (those are just random vegetables, no, there is no reason for me mentioning them, and no they do not hold magical power), all of these things you will find in hearty stews, as well as seasonings for your meat which adds wonderful flavor. Boiled greens are also good to eat, they can be boiled in water with a pinch of salt, cooked until they have a pleasant taste, drained, and then covered with a bit of cream or butter.
The major source of CHO will be coming from dairy. There is no magic number of carbohydrates I recommend I just recommend that you drink a fair amount of milk something like 1.5-2+ quarts per day. Lactose in milk is sufficient to supply the amount of glucose you need. Galactose is also unique in that it enhances OXPHOS and reverses the inhibitive effect on respiration caused by glucose and fructose (Aguer et al., 2011; Chico, Olavarría, & de Castro, 1978; Diaz-Ruiz, Rigoulet, & Devin, 2011; Dott, Mistry, Wright, Cain, & Herbert, 2014; Marroquin, Hynes, Dykens, Jamieson, & Will, 2007; Sussman, Erecińska, & Wilson, 1980).
Eat till you feel satisfied, eat when you are hungry, and don’t count anything, don’t worry about phosphate (Hettleman, Sabina, Drezner, Holmes, & Swain, 1983), don’t worry about trying to get a certain number of this or that. Focus on getting creative with the infinite amount of dishes you can prepare with these rich ingredients.
Coffee, chocolate, beer, wine, and tea, are always welcome, and I think nicotine is useful.
Salt your food to taste (MENEELY, TUCKER, & DARBY, 1952; MENEELY, TUCKER, DARBY, & AUERBACH, 1953).
Aguer, C., Gambarotta, D., Mailloux, R. J., Moffat, C., Dent, R., McPherson, R., & Harper, M.-E. (2011). Galactose enhances oxidative metabolism and reveals mitochondrial dysfunction in human primary muscle cells. PloS one, 6(12), e28536. doi:10.1371/journal.pone.0028536
BACKGROUND: Human primary myotubes are highly glycolytic when cultured in high glucose medium rendering it difficult to study mitochondrial dysfunction. Galactose is known to enhance mitochondrial metabolism and could be an excellent model to study mitochondrial dysfunction in human primary myotubes. The aim of the present study was to 1) characterize the effect of differentiating healthy human myoblasts in galactose on oxidative metabolism and 2) determine whether galactose can pinpoint a mitochondrial malfunction in post-diabetic myotubes. METHODOLOGY/PRINCIPAL FINDINGS: Oxygen consumption rate (OCR), lactate levels, mitochondrial content, citrate synthase and cytochrome C oxidase activities, and AMPK phosphorylation were determined in healthy myotubes differentiated in different sources/concentrations of carbohydrates: 25 mM glucose (high glucose (HG)), 5 mM glucose (low glucose (LG)) or 10 mM galactose (GAL). Effect of carbohydrates on OCR was also determined in myotubes derived from post-diabetic patients and matched obese non-diabetic subjects. OCR was significantly increased whereas anaerobic glycolysis was significantly decreased in GAL myotubes compared to LG or HG myotubes. This increased OCR in GAL myotubes occurred in conjunction with increased cytochrome C oxidase activity and expression, as well as increased AMPK phosphorylation. OCR of post-diabetic myotubes was not different than that of obese non-diabetic myotubes when differentiated in LG or HG. However, whereas GAL increased OCR in obese non-diabetic myotubes, it did not affect OCR in post-diabetic myotubes, leading to a significant difference in OCR between groups. The lack of an increase in OCR in post-diabetic myotubes differentiated in GAL was in relation with unaltered cytochrome C oxidase activity levels or AMPK phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our results indicate that differentiating human primary myoblasts in GAL enhances aerobic metabolism. Because this cell culture model elicited an abnormal response in cells from post-diabetic patients, it may be useful in further studies of the molecular mechanisms of mitochondrial dysfunction.
Chico, E., Olavarría, J. S., & de Castro, I. N. (1978). Crabtree effect induced by fructose in isolated hepatocytes from fed rats. Biochemical and biophysical research communications, 83(4), 1422–9. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/29632
Diaz-Ruiz, R., Rigoulet, M., & Devin, A. (2011). The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression. Biochimica et biophysica acta, 1807(6), 568–76. doi:10.1016/j.bbabio.2010.08.010
During the last decades a considerable amount of research has been focused on cancer. Recently, tumor cell metabolism has been considered as a possible target for cancer therapy. It is widely accepted that tumors display enhanced glycolytic activity and impaired oxidative phosphorylation (Warburg effect). Therefore, it seems reasonable that disruption of glycolysis might be a promising candidate for specific anti-cancer therapy. Nevertheless, the concept of aerobic glycolysis as the paradigm of tumor cell metabolism has been challenged, as some tumor cells exhibit high rates of oxidative phosphorylation. Mitochondrial physiology in cancer cells is linked to the Warburg effect. Besides, its central role in apoptosis makes this organelle a promising “dual hit target” to selectively eliminate tumor cells. From a metabolic point of view, the fermenting yeast Saccharomyces cerevisiae and tumor cells share several features. In this paper we will review these common metabolic properties as well as the possible origins of the Crabtree and Warburg effects.
Dott, W., Mistry, P., Wright, J., Cain, K., & Herbert, K. E. (2014). Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity. Redox biology, 2, 224–33. doi:10.1016/j.redox.2013.12.028
Mitochondrial toxicity is increasingly being implicated as a contributing factor to many xenobiotic-induced organ toxicities, including skeletal muscle toxicity. This has necessitated the need for predictive in vitro models that are able to sensitively detect mitochondrial toxicity of chemical entities early in the research and development process. One such cell model involves substituting galactose for glucose in the culture media. Since cells cultured in galactose are unable to generate sufficient ATP from glycolysis they are forced to rely on mitochondrial oxidative phosphorylation for ATP generation and consequently are more sensitive to mitochondrial perturbation than cells grown in glucose. The aim of this study was to characterise cellular growth, bioenergetics and mitochondrial toxicity of the L6 rat skeletal muscle cell line cultured in either high glucose or galactose media. L6 myoblasts proliferated more slowly when cultured in galactose media, although they maintained similar levels of ATP. Galactose cultured L6 cells were significantly more sensitive to classical mitochondrial toxicants than glucose-cultured cells, confirming the cells had adapted to galactose media. Analysis of bioenergetic function with the XF Seahorse extracellular flux analyser demonstrated that oxygen consumption rate (OCR) was significantly increased whereas extracellular acidification rate (ECAR), a measure of glycolysis, was decreased in cells grown in galactose. Mitochondria operated closer to state 3 respiration and had a lower mitochondrial membrane potential and basal mitochondrial O2 (•-) level compared to cells in the glucose model. An antimycin A (AA) dose response revealed that there was no difference in the sensitivity of OCR to AA inhibition between glucose and galactose cells. Importantly, cells in glucose were able to up-regulate glycolysis, while galactose cells were not. These results confirm that L6 cells are able to adapt to growth in a galactose media model and are consequently more susceptible to mitochondrial toxicants.
Hettleman, B. D., Sabina, R. L., Drezner, M. K., Holmes, E. W., & Swain, J. L. (1983). Defective adenosine triphosphate synthesis. An explanation for skeletal muscle dysfunction in phosphate-deficient mice. The Journal of clinical investigation, 72(2), 582–9. doi:10.1172/JCI111006
The basis for skeletal muscle dysfunction in phosphate-deficient patients and animals is not known, but it is hypothesized that intracellular phosphate deficiency leads to a defect in ATP synthesis. To test this hypothesis, changes in muscle function and nucleotide metabolism were studied in an animal model of hypophosphatemia. Mice were made hypophosphatemic through restriction of dietary phosphate intake. Gastrocnemius function was assessed in situ by recording isometric tension developed after stimulation of the nerve innervating this muscle. Changes in purine nucleotide, nucleoside, and base content of the muscle were quantitated at several time points during stimulation and recovery. Serum concentration and skeletal muscle content of phosphorous are reduced by 55 and 45%, respectively, in the dietary restricted animals. The gastrocnemius muscle of the phosphate-deficient mice fatigues more rapidly compared with control mice. ATP and creatine phosphate content fall to a comparable extent during fatigue in the muscle from both groups of animals; AMP, inosine, and hypoxanthine (indices of ATP catabolism) appear in higher concentration in the muscle of phosphate-deficient animals. Since total ATP use in contracting muscle is closely linked to total developed tension, we conclude that the comparable drop in ATP content in association with a more rapid loss of tension is best explained by a slower rate of ATP synthesis in the muscle of phosphate-deficient animals. During the period of recovery after muscle stimulation, ATP use for contraction is minimal, since the muscle is at rest. In the recovery period, ATP content returns to resting levels more slowly in the phosphate-deficient than in the control animals. In association with the slower rate of ATP repletion, the precursors inosine monophosphate and AMP remain elevated for a longer period of time in the muscle of phosphate-deficient animals. The slower rate of ATP repletion correlates with delayed return of normal muscle contractility in the phosphate-deficient mice. These studies suggest that the slower rate of repletion of the ATP pool may be the consequence of a slower rate of ATP synthesis and this is in part responsible for the delayed recovery of normal muscle contractility.
Marroquin, L. D., Hynes, J., Dykens, J. A., Jamieson, J. D., & Will, Y. (2007). Circumventing the Crabtree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants. Toxicological sciences : an official journal of the Society of Toxicology, 97(2), 539–47. doi:10.1093/toxsci/kfm052
Many highly proliferative cells generate almost all ATP via glycolysis despite abundant O(2) and a normal complement of fully functional mitochondria, a circumstance known as the Crabtree effect. Such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, such as the inhibitors rotenone, antimycin, oligomycin, and compounds like carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), that uncouple the respiratory electron transfer system from phosphorylation. These cells are also resistant to the toxicity of many drugs whose deleterious side effect profiles are either caused, or exacerbated, by impairment of mitochondrial function. Drug-induced mitochondrial toxicity is shown by members of important drug classes, including the thiazolidinediones, statins, fibrates, antivirals, antibiotics, and anticancer agents. To increase detection of drug-induced mitochondrial effects in a preclinical cell-based assay, HepG2 cells were forced to rely on mitochondrial oxidative phosphorylation rather than glycolysis by substituting galactose for glucose in the growth media. Oxygen consumption doubles in galactose-grown HepG2 cells and their susceptibility to canonical mitochondrial toxicants correspondingly increases. Similarly, toxicity of several drugs with known mitochondrial liabilities is more readily apparent in aerobically poised HepG2 cells compared to glucose-grown cells. Some drugs were equally toxic to both glucose- and galactose-grown cells, suggesting that mitochondrial impairment is likely secondary to other cytotoxic mechanisms.
MENEELY, G. R., TUCKER, R. G., & DARBY, W. J. (1952). Chronic sodium chloride toxicity in the albino rat. I. Growth on a purified diet containing various levels of sodium chloride. The Journal of nutrition, 48(4), 489–98. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/13000527
MENEELY, G. R., TUCKER, R. G., DARBY, W. J., & AUERBACH, S. H. (1953). Chronic sodium chloride toxicity in the albino rat. II. Occurrence of hypertension and of a syndrome of edema and renal failure. The Journal of experimental medicine, 98(1), 71–80. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2136278&tool=pmcentrez&rendertype=abstract
Sustained arterial hypertension developed in male, albino rats chronically fed diets rich in sodium chloride with demineralized drinking water available ad libitum. After 12 months of the experimental regimen a positive, linear correlation (r = 0.91) was found between the systolic blood pressure and the concentration of sodium chloride in the diet. A syndrome of edema and renal failure was observed in 18 per cent of the group fed at the level of 7.0 to 9.8 per cent of sodium chloride. Significant histologic changes occurred in the kidneys and certain other organs in rats consuming rations containing these levels of NaCl. The relative volume of the radiosodium space was increased in the rat by high dietary sodium chloride.
Sussman, I., Erecińska, M., & Wilson, D. F. (1980). Regulation of cellular energy metabolism: the Crabtree effect. Biochimica et biophysica acta, 591(2), 209–23. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7397121
The Crabtree effect (inhibition of respiration by glycolysis) is observed in cells with approximately equal glycolytic and respiratory capacities for ATP synthesis. Addition of glucose to aerobic suspensions of glucose-starved cells (Sarcoma 180 ascites tumor cells) causes a burst of respiration and lactate production due to ATP utilization for glucose phosphorylation by hexokinase and phosphofructokinase. This burst of activity is followed by inhibition of both respiration and glycolysis, the former to below the value before glucose addition (Crabtree effect). Both the respiratory rate and the glycolytic flux appear to be regulated by the cytosolic [ATP]/[ADP][Pi] albeit by completely different mechanisms. Respiration is regulated by the free energy of hydrolysis of ATP, such that the rate increases as the [ATP]/[ADP][Pi] decreases and decreases as the [ATP]/[adp][Pi] increases. The regulatory enzymes of glycolysis are activated by ADP (AMP) and Pi and inhibited by ATP. Thus both respiration and glycolysis increase or decrease as the [ATP]/[ADP][Pi] decreases or increases. The parallel regulation of both ATP-producing pathways by this common metabolite ratio is consistent with the cytoplasmic [ATP]/[ADP][Pi] being an important determinant of homeostatic regulation of cellular energy metabolism.
Another shorter one.
As we can see, low phosphorus makes people miserable (De Lorenzo, Hargreaves, & Kakkar, 1998; Land et al., 1993; Laroche, 2001).
There are some mentions of oral supplements and such but I think it is best just to eat meat. And continue eating your dairy.
De Lorenzo, F., Hargreaves, J., & Kakkar, V. V. (1998). Phosphate diabetes in patients with chronic fatigue syndrome. Postgraduate medical journal, 74(870), 229–32. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2360873&tool=pmcentrez&rendertype=abstract
Phosphate depletion is associated with neuromuscular dysfunction due to changes in mitochondrial respiration that result in a defect of intracellular oxidative metabolism. Phosphate diabetes causes phosphate depletion due to abnormal renal re-absorption of phosphate be the proximal renal tubule. Most of the symptoms presented by patients with phosphate diabetes such as myalgia, fatigue and mild depression, are also common in patients with chronic fatigue syndrome, but this differential diagnosis has not been considered. We investigated the possible association between chronic fatigue syndrome and phosphate diabetes in 87 patients who fulfilled the criteria for chronic fatigue syndrome. Control subjects were 37 volunteers, who explicitly denied fatigue and chronic illness on a screening questionnaire. Re-absorption of phosphate by the proximal renal tubule, phosphate clearance and renal threshold phosphate concentration were the main outcome measures in both groups. Of the 87 patients with chronic fatigue syndrome, nine also fulfilled the diagnostic criteria for phosphate diabetes. In conclusion, we report a previously undefined relationship between chronic fatigue syndrome and phosphate diabetes. Phosphate diabetes should be considered in differential diagnosis with chronic fatigue syndrome; further studies are needed to investigate the incidence of phosphate diabetes in patients with chronic fatigue syndrome and the possible beneficial effect of vitamin D and oral phosphate supplements.
Land, J. M., Kemp, G. J., Taylor, D. J., Standing, S. J., Radda, G. K., & Rajagopalan, B. (1993). Oral phosphate supplements reverse skeletal muscle abnormalities in a case of chronic fatigue with idiopathic renal hypophosphatemia. Neuromuscular disorders : NMD, 3(3), 223–5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8400863
A 57-yr-old man presented with a long history of undiagnosed fatigue but no evidence of bone disease. He was noted to have hypophosphatemia due to an idiopathic phosphaturia. Marked abnormalities of exercising skeletal muscle detected by phosphorus magnetic resonance spectroscopy and by plasma metabolite measurements were consistent with mitochondrial dysfunction. Oral phosphate supplements restored plasma phosphate concentration and muscle biochemistry to normal and produced considerable improvement in symptoms and exercise tolerance, although the phosphate concentration in muscle was only marginally low and increased little by treatment. We conclude that hypophosphatemia should be excluded in unexplained fatigue.
Laroche, M. (2001). Phosphate, the renal tubule, and the musculoskeletal system. Joint, bone, spine : revue du rhumatisme, 68(3), 211–5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11394620
A component of ATP, phosphate is at the hub of the energy-related mechanisms operative in muscle cells. Together with calcium, phosphate is involved in bone tissue mineralization: thus, a chronic alteration in the metabolism of phosphate can induce bone and joint disorders. Diagnosis of chronic hypophosphatemia. Serum phosphate, calcium, and creatinine should be assayed simultaneously. Serum calcium is increased in hypophosphatemia caused by hyperparathyroidism and decreased in osteomalacia. Urinary phosphate excretion should be measured in patients with a normal serum calcium level and a serum phosphate level lower than 0.80 mmol/L. A decrease in urinary phosphate excretion to less than 10 mmol/24 h strongly suggests a gastrointestinal disorder, such as malabsorption, antacid use, or chronic alcohol abuse. In patients with a urinary phosphate excretion greater than 20 mmol/24 h, the maximal rate of tubular reabsorption of phosphate (TmPO4) and the ratio of TmPO4 over glomerular filtration rate (GFR) should be determined to look for phosphate diabetes. Manifestations and causes of phosphate diabetes in adults. Moderately severe phosphate diabetes in adults manifests as chronic fatigue, depression, spinal pain, and polyarthralgia, with osteoporosis ascribable to increased bone resorption. Although many cases are idiopathic, investigations should be done to look for X-linked vitamin D-resistant rickets missed during childhood, a mesenchymatous tumor, or Fanconi’s syndrome with renal wasting of phosphate, glucose, and amino acids. Management of phosphate diabetes. Phosphate supplementation and, in patients with normal urinary calcium excretion, calcitriol produce some improvement in the symptoms and increase the bone mineral density. Whether dipyramidole is clinically effective remains unclear.
Ah, phosphorus. Sounds like the name of a Greek mythology character. Before I discuss glucose and carbon dioxide in response to some comments on the last post, I wanted to discuss a bit about phosphorus.
Meat is good, especially ruminant meat, all the bits you love and all the bits that induce a gag reflex, especially when you can get a hold of the grass fed sorts.
Phosphorus is important.
ATP is good. Adenosine triphosphate.
A lot of readers who read this blog are concerned about calcium and phosphorus. There is this thought pattern that less phosphate is better, which leads to phosphate is harmful, which eventually leads to a less is more type of mentality i.e. restriction.
Your ability to produce ATP is pretty important. You don’t just consume glucose and then phosphate appears from nowhere. It has to come from somewhere. Bad things happen when you eat a lot of carbohydrate and there is a lack of phosphorous in the diet, as carbohydrate places a demand on hexokinase, which requires phosphate to bind glucose to phosphate (glucose-6-phosphate) during glycolysis.
What happens when you are fed a phosphorus deficient diet? (Hettleman, Sabina, Drezner, Holmes, & Swain, 1983; Kilic, Demirkol, Ucsel, Citak, & Karabocuoglu, 2012)
Since the amount of phosphorous in your food is going to have an impact on ATP production, and ATP is the energy currency of cells, you can expect that a deficiency is going to systematically effect the entire organism. Indeed that is what we see in hypophosphatemia: weakness, bone pain, increased susceptibility to infection, numbness and tingling of the extremities, appetite suppression, cold extremities, difficulty swallowing, and a host of other “hypo” like symptoms.
Aside: Fructose is particularly effective at wasting phosphorus as well as inhibiting the absorption of calcium (Bergstra, Lemmens, & Beynen, 1993; Burch et al., 1980; Douard et al., 2010, 2013; Kizhner & Werman, 2002).
Bergstra, A. E., Lemmens, A. G., & Beynen, A. C. (1993). Dietary fructose vs. glucose stimulates nephrocalcinogenesis in female rats. The Journal of nutrition, 123(7), 1320–7. Retrieved from http://europepmc.org/abstract/MED/8320569
The effect of dietary fructose vs. glucose on kidney calcification (nephrocalcinosis) was studied in female rats. Fructose or glucose was incorporated into purified diets formulated either according to the nutrient requirements of rats or made nephrocalcinogenic by the addition of phosphorus (19.4 instead of 12.9 mmol/100 g diet) or by restriction of magnesium (0.8 instead of 1.6 mmol/100 g diet). Irrespective of the background composition of the diet, fructose consistently produced higher kidney calcium concentrations than did glucose. Fructose also raised kidney weight, expressed either as wet weight relative to body weight or as absolute dry weight; this greater kidney weight was not explained by the extra calcium. Fructose generally induced greater urinary concentrations of phosphorus and magnesium and lowered urinary pH compared with glucose. The greater urinary phosphorus concentrations in rats fed fructose may be responsible for the nephrocalcinogenic activity of this monosaccharide. Fructose stimulated the absorption of phosphorus and magnesium, which explains the higher concentrations of these minerals in the urine.
Burch, H. B., Choi, S., Dence, C. N., Alvey, T. R., Cole, B. R., & Lowry, O. H. (1980). Metabolic effects of large fructose loads in different parts of the rat nephron. The Journal of biological chemistry, 255(17), 8239–44. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/6773936
Rats were given large parenteral loads of fructose and the different segments of single nephrons then analyzed for fructose metabolites, fructose metabolizing enzymes, and nucleotide high energy phosphates. Fructokinase and fructose-1-P aldolase activities, and all the major metabolite and nucleotide effects, were confined to the proximal tubule. The proximal straight segment had the highest fructokinase and suffered the greatest changes. In this segment, fructose-1-P rose to 60 mmol/kg (dry weight basis) and glycerol-3-P and glucose-6-P reached 8 and 12 mmol/kg, respectively. ATP fell 80% and GTP (judging from the changes in GTP plus GDP) fell by the same percentage, but UTP was less affected. Total adenylate decreased 50%. In the proximal convoluted tubule, where fructokinase was lower and fructose-1-P aldolase higher than in the straight segment, fructose-1-P rose ony one-fourth as much and glucose-6-P was almost unchanged. In contrast, glycerol-3-P rose more, reaching 16 mmol/kg. Other substances measured along the nephron were glycerol-3-P dehydrogenase, fructose-1,6-bisphosphate aldolase, fructose, glucose, fructose bisphosphate, triose phosphate, and 6-P-gluconate. Control ATP levels were found to be highest in the distal tubule.
Douard, V., Asgerally, A., Sabbagh, Y., Sugiura, S., Shapses, S. A., Casirola, D., & Ferraris, R. P. (2010). Dietary fructose inhibits intestinal calcium absorption and induces vitamin D insufficiency in CKD. Journal of the American Society of Nephrology : JASN, 21(2), 261–71. doi:10.1681/ASN.2009080795
Renal disease leads to perturbations in calcium and phosphate homeostasis and vitamin D metabolism. Dietary fructose aggravates chronic kidney disease (CKD), but whether it also worsens CKD-induced derangements in calcium and phosphate homeostasis is unknown. Here, we fed rats diets containing 60% glucose or fructose for 1 mo beginning 6 wk after 5/6 nephrectomy or sham operation. Nephrectomized rats had markedly greater kidney weight, blood urea nitrogen, and serum levels of creatinine, phosphate, and calcium-phosphate product; dietary fructose significantly exacerbated all of these outcomes. Expression and activity of intestinal phosphate transporter, which did not change after nephrectomy or dietary fructose, did not correlate with hyperphosphatemia in 5/6-nephrectomized rats. Intestinal transport of calcium, however, decreased with dietary fructose, probably because of fructose-mediated downregulation of calbindin 9k. Serum calcium levels, however, were unaffected by nephrectomy and diet. Finally, only 5/6-nephrectomized rats that received dietary fructose demonstrated marked reductions in 25-hydroxyvitamin D(3) and 1,25-dihydroxyvitamin D(3) levels, despite upregulation of 1alpha-hydroxylase. In summary, excess dietary fructose inhibits intestinal calcium absorption, induces marked vitamin D insufficiency in CKD, and exacerbates other classical symptoms of the disease. Future studies should evaluate the relevance of monitoring fructose consumption in patients with CKD.
Douard, V., Sabbagh, Y., Lee, J., Patel, C., Kemp, F. W., Bogden, J. D., … Ferraris, R. P. (2013). Excessive fructose intake causes 1,25-(OH)(2)D(3)-dependent inhibition of intestinal and renal calcium transport in growing rats. American journal of physiology. Endocrinology and metabolism, 304(12), E1303–13. doi:10.1152/ajpendo.00582.2012
We recently discovered that chronic high fructose intake by lactating rats prevented adaptive increases in rates of active intestinal Ca(2+) transport and in levels of 1,25-(OH)2D3, the active form of vitamin D. Since sufficient Ca(2+) absorption is essential for skeletal growth, our discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25-(OH)2D3 mediates the inhibitory effect of excessive fructose intake on active Ca(2+) transport. First, compared with those fed glucose or starch, growing rats fed fructose for 4 wk had a marked reduction in intestinal Ca(2+) transport rate as well as in expression of intestinal and renal Ca(2+) transporters that was tightly associated with decreases in circulating levels of 1,25-(OH)2D3, bone length, and total bone ash weight but not with serum parathyroid hormone (PTH). Dietary fructose increased the expression of 24-hydroxylase (CYP24A1) and decreased that of 1α-hydroxylase (CYP27B1), suggesting that fructose might enhance the renal catabolism and impair the synthesis, respectively, of 1,25-(OH)2D3. Serum FGF23, which is secreted by osteocytes and inhibits CYP27B1 expression, was upregulated, suggesting a potential role of bone in mediating the fructose effects on 1,25-(OH)2D3 synthesis. Second, 1,25-(OH)2D3 treatment rescued the fructose effect and normalized intestinal and renal Ca(2+) transporter expression. The mechanism underlying the deleterious effect of excessive fructose intake on intestinal and renal Ca(2+) transporters is a reduction in serum levels of 1,25-(OH)2D3. This finding is significant because of the large amounts of fructose now consumed by Americans increasingly vulnerable to Ca(2+) and vitamin D deficiency.
Hettleman, B. D., Sabina, R. L., Drezner, M. K., Holmes, E. W., & Swain, J. L. (1983). Defective adenosine triphosphate synthesis. An explanation for skeletal muscle dysfunction in phosphate-deficient mice. The Journal of clinical investigation, 72(2), 582–9. doi:10.1172/JCI111006
The basis for skeletal muscle dysfunction in phosphate-deficient patients and animals is not known, but it is hypothesized that intracellular phosphate deficiency leads to a defect in ATP synthesis. To test this hypothesis, changes in muscle function and nucleotide metabolism were studied in an animal model of hypophosphatemia. Mice were made hypophosphatemic through restriction of dietary phosphate intake. Gastrocnemius function was assessed in situ by recording isometric tension developed after stimulation of the nerve innervating this muscle. Changes in purine nucleotide, nucleoside, and base content of the muscle were quantitated at several time points during stimulation and recovery. Serum concentration and skeletal muscle content of phosphorous are reduced by 55 and 45%, respectively, in the dietary restricted animals. The gastrocnemius muscle of the phosphate-deficient mice fatigues more rapidly compared with control mice. ATP and creatine phosphate content fall to a comparable extent during fatigue in the muscle from both groups of animals; AMP, inosine, and hypoxanthine (indices of ATP catabolism) appear in higher concentration in the muscle of phosphate-deficient animals. Since total ATP use in contracting muscle is closely linked to total developed tension, we conclude that the comparable drop in ATP content in association with a more rapid loss of tension is best explained by a slower rate of ATP synthesis in the muscle of phosphate-deficient animals. During the period of recovery after muscle stimulation, ATP use for contraction is minimal, since the muscle is at rest. In the recovery period, ATP content returns to resting levels more slowly in the phosphate-deficient than in the control animals. In association with the slower rate of ATP repletion, the precursors inosine monophosphate and AMP remain elevated for a longer period of time in the muscle of phosphate-deficient animals. The slower rate of ATP repletion correlates with delayed return of normal muscle contractility in the phosphate-deficient mice. These studies suggest that the slower rate of repletion of the ATP pool may be the consequence of a slower rate of ATP synthesis and this is in part responsible for the delayed recovery of normal muscle contractility.
Kilic, O., Demirkol, D., Ucsel, R., Citak, A., & Karabocuoglu, M. (2012). Hypophosphatemia and its clinical implications in critically ill children: a retrospective study. Journal of critical care, 27(5), 474–9. doi:10.1016/j.jcrc.2012.03.005
PURPOSE: The aims of this study were to determine the prevalence of hypophosphatemia and to discuss the clinical implications of hypophosphatemia in critically ill children. MATERIALS AND METHODS: A retrospective review of the medical records of children admitted to the pediatric intensive care unit from December 2006 to December 2007 was conducted. RESULTS: In 60.2% (n = 71) of the patients, any serum phosphorous level at admission and at the third day or seventh day after admission to pediatric intensive care unit was in hypophosphatemic range. Sepsis was present in 22.9% (n = 27) of the children studied and was associated with hypophosphatemia (P = .02). Hypophosphatemia was also associated with use of furosemide (P = .04), use of steroid (P = .04), use of β(2) agonist (P = .026), and use of an H(2) blocker (P = .004). There was a significant association between hypophosphatemia and the rate to attain target caloric requirements by enteral route (P = .007). The median time to attain target caloric requirements by enteral route was 2.9 ± 1.9 (0.2-10) days in the normophosphatemic group and 4.4 ± 2.8 (0.3-12) days in the hypophosphatemic group. In the multiple regression model, solely the rate to attain the target caloric requirements by enteral route demonstrated independent association with hypophosphatemia (P = .006; β = .27; 95% confidence interval, 0.02-0.09). Significant association was found between hypophosphatemia and the duration of mechanical ventilation and between hypophosphatemia and pediatric intensive care unit length of stay (P = .02 and P = .001, respectively). CONCLUSIONS: Critically ill pediatric patients are prone to hypophosphatemia, especially if they cannot be fed early by enteral route. Hypophosphatemia is associated with an increased duration of mechanical ventilation and increased length of stay in the pediatric intensive care unit, suggesting that active repletion might improve these parameters.
Kizhner, T., & Werman, M. J. (2002). Long-term fructose intake: biochemical consequences and altered renal histology in the male rat. Metabolism: clinical and experimental, 51(12), 1538–47. doi:10.1053/meta.2002.36306
The use of fructose as a pure sugar has considerably increased in the last 3 decades, especially as a sweetener in carbonated beverages. Our previous studies showed that long-term fructose intake adversely affected several age-related metabolic parameters. The purpose of the present study was to compare the consequences of long-term fructose intake with those of glucose or sucrose on renal morphology and on several biochemical parameters used to estimate renal function. Male rats were fed a commercial diet for 16 months, and had free access either to water (control) or to 250 g/L solutions of fructose, glucose, or sucrose. Fructose-drinking rats exhibited higher liver weights compare to the other dietary groups. Control rats excreted significantly less urinary output than all sugar groups, which did not differ from each other. No differences were observed in fasting plasma fructose, glucose, and creatinine levels, or in urinary glucose levels. Fructose consumption resulted in elevated urinary fructose levels, higher creatinine clearance, and marked proteinuria. The tested sugars had influence on the molecular weight distribution of urinary proteins in the ranges of 10 to 16, 25 to 35, and 75 to 85 kd. Histological examination revealed that fructose consumption led to the formation of foci of cortical tubular necrosis with chronic inflammatory infiltrate, accumulation of tubular hyaline casts, thickening of the Bowman’s capsule, mesangial thickening due to collagen deposits, and the occurrence of hemosiderin in tubular cells. These data suggest that fructose has a negative impact on kidney function and morphology. Further research is required to elucidate the precise mechanisms by which long-term fructose consumption hampers renal metabolism.
Before we can talk about how an organism functions, we need to understand its gross organization and have the ability to visualize it. We need language to create an analogy, we need an analogy to visualize things. Recently, I had a conversation with a someone on why I view saturated fat as a superior energy substrate. But before I could explain why, I had to explain how I view the organism. Below is our conversation. This will serve as a introduction through which to interpret the rest of the of the information I write about.
(7:06:07 PM) Anonymous: so, having been looking into Peat’s work for so long and coming around to seeing his ideas as logical
(7:07:27 PM) Anonymous: this leaves me not entirely sure of some things when approaching a “low carb” diet (at least as far as macro-ratios goes)
(7:09:50 PM) Anonymous: things like how this approach relates to blood sugar, sugar=anti stress, sugar needed for T4>T3, cells running on sugar etc.
(7:11:59 PM) Edward: oh man… big question… where to start…
(7:12:03 PM) Edward: o.k. so
(7:12:24 PM) Anonymous: haha
(7:12:47 PM) Edward: If me and Dr. Peat were to agree on one thing it would be that energy and structure are interdependent
(7:13:09 PM) Edward: and quite frankly that is not a new biological concept, it is older then he is
(7:14:05 PM) Edward: however, the difference between myself and Peat is the function of structure…
(7:15:29 PM) Edward: I think that structure, which is a invention of evolution is in place to deliver energy, because I think the structure exists to support the organization of the organism
(7:16:47 PM) Edward: he looks at it a bit differently inherently if he is promoting sugar which is a primitive fuel source… in other words there is no structure needed to deliver glucose to a cell
(7:18:50 PM) Edward: does that make sense what i said so far
(7:19:01 PM) Edward: at least what we disagree on
(7:19:28 PM) Anonymous: yeah
(7:19:37 PM) Edward: I need to full screen this chat window it’s getting serious in here
(7:19:53 PM) Anonymous: i did that a little while ago ;)
(7:19:57 PM) Edward: o.k. evidence of this is the vascular system, the CNS, the lymphatic system, etc
(7:20:06 PM) Edward: at least on a big scale
(7:20:23 PM) Edward: for a single celled organism we don’t need all that
(7:20:42 PM) Edward: it is happy eating sugar
(7:21:25 PM) Edward: those systems are “structure”… in biology we say cells, tissue, organs, organ system so on when we talk about structure
(7:21:36 PM) Edward: the entire digestive system is “structure”
(7:22:23 PM) Edward: that “structure” is designed to deliver nutrients and the such to all of the cells, tissue, organs, etc… in the body
(7:23:07 PM) Edward: now obviously i argue that saturated fat is a superior energy source
(7:26:25 PM) Edward: o.k. so in the body there are the different organs, the brain, the balls, the ovaries, the muscles, the heart, etc…
(7:26:42 PM) Edward: all of these require a different energy substrate…
(7:27:02 PM) Edward: for example, your balls like citrate
(7:27:47 PM) Edward: your brain likes lactate/a bit of glucose/a bit of ketones/and some specific kinds of fat
(7:28:10 PM) Edward: the muscles at rest and during most activity burn fat
(7:28:15 PM) Edward: the heart prefers it
(7:28:58 PM) Edward: the blood… ahh the blood… the blood cells have no mitochondria
(7:29:13 PM) Edward: guess where the brains gets part of it’s lactate from
(7:29:16 PM) Edward: ?
(7:29:28 PM) Edward: The anaerobic metabolism of the red blood cells
(7:30:18 PM) Edward: the colon likes butyric acid
(7:30:33 PM) Edward: so you see each part of the body likes something different
(7:31:04 PM) Edward: how is it possible to support those fuel demands?
(7:31:44 PM) Edward: you have to have structure, the vascular system, the lymphatic system, the CNS, the GI system, etc.
(7:32:27 PM) Edward: when we look at breast milk what do we see…
(7:32:42 PM) Edward: first we see percentages of all the different saturated fat chain lengths
(7:32:54 PM) Edward: short, medium, long, very long, etc
(7:33:00 PM) Edward: and then we see protein
7:33:09 PM) Edward: a splash of lactose
(7:33:23 PM) Edward: we also see some branched chain fatty acids
(7:33:37 PM) Edward: and a very tiny tiny bit of polyunsaturated fat
(7:34:08 PM) Edward: there are no ketones in milk at least not that i am aware of… and this is the hooker
(7:34:29 PM) Edward: a baby needs ketones… if a baby does not have ketones it will either die or be retarded
(7:34:57 PM) Edward: ketones serve as a cholesterol precursor and also serve as a precursor for some of the special lipids in the brain
(7:35:31 PM) Edward: give a baby glucose instead of breast feeding and it develops tumors on the brain
(7:35:52 PM) Edward: so how does the baby get the ketones it needs
(7:36:06 PM) Edward: via “structure”
(7:36:52 PM) Edward: the liver and brain can make ketones locally and delivers them to the brain… that is structure at play (ketones are probably produced elsewhere as well)
(7:37:09 PM) Edward: so remember… structure is essentially a group of cells that perform a specialized function
(7:37:24 PM) Edward: each individual cell does not have structure not in the sense we are talking about here
(7:38:02 PM) Edward: so the ketones are delivered to each cell via structure because the individual cell itself can not do this because it serves a different function
(7:38:15 PM) Edward: same with lactate
(7:38:42 PM) Edward: babies need lactate and so does the brain… the brain itself can’t do this
(7:39:08 PM) Edward: it has to be delivered by the anaerobic metabolism of the red blood cells and locally in the brain in the astrocyctes
(7:39:34 PM) Edward: does that make sense so far?
(7:40:44 PM) Anonymous: yeah, although i’m not aware of the astrocyctes
(7:41:12 PM) Edward: oh well, there are about a dozen or more different types of cells in the brain
(7:43:53 PM) Edward: o.k. glucose is a primitive fuel source it is “anti-structure” and so are polyunsatured fats but here it we have to make perfectly clear that the polyunsaturated fats are anti-structure as a fuel source, but the brain is indeed made of polyunsatured fat… that is structure… in this case the polyunsatured fats serve electric functions
(7:43:58 PM) Edward: does that make sense
(7:44:46 PM) Edward: so as a fuel polyunsaturated fast are anti-structure but that does not mean they can not be built by the body to serve a functional/structural purpose
(7:44:50 PM) Edward: ?
(7:44:58 PM) Anonymous: yep
(7:45:04 PM) Edward: cool
(7:45:35 PM) Edward: glucose can basically be absorbed through a gradient anywhere in the body
(7:46:51 PM) Edward: if you eat it it goes in your mouth, your mouth cells, your esophagus cells, your stomach, everywhere… you can make a glucose solution and inject it in your arm and your cells will use it you can squirt some up your ass and your colon cells will use it, you can put it on your skin, etc…
(7:47:29 PM) Edward: there is absolutely no structure required for any type of cell to use it
(7:47:50 PM) Edward: so the cells are intelligent
(7:47:54 PM) Edward: “intelligent”
(7:48:06 PM) Edward: they sense their environment
(7:48:20 PM) Edward: what happens when you are queuing?
(7:49:28 PM) Anonymous: as in waiting in line?
(7:49:46 PM) Edward: yes waiting in line
(7:50:08 PM) Edward: o.k. so walk through me on this
(7:50:33 PM) Edward: what is the sort of place in the UK where you’d have to queue?
(7:52:02 PM) Anonymous: bank
(7:52:20 PM) Edward: o.k. the bank… now why would you be going to the bank?
(7:53:16 PM) Edward: bare with me on this…
(7:53:45 PM) Anonymous: you want me to pick one reason?
(7:53:48 PM) Edward: yes
(7:53:51 PM) Edward: one reason
(7:54:07 PM) Anonymous: to extract money from my account
(7:56:40 PM) Edward: this is a lose analogy
(7:56:42 PM) Edward: anyway
(7:56:56 PM) Edward: you all are standing in line
(7:57:06 PM) Edward: each person walks up gets what they need and leaves
(7:57:35 PM) Edward: what happens if you don’t stand in line? Like in Germany were they all crowd around like animals?
(7:57:57 PM) Anonymous: haha!
(7:59:22 PM) Anonymous: i guess it would be hard to discern who should be seen first by the assistant at the bank
(7:59:40 PM) Anonymous: and perhaps there would be fighting between those in line…?
(7:59:53 PM) Edward: yes, they would be all fighting for the resource they came to get
(8:00:24 PM) Edward: so some people would get their money before others and others would be waiting or pushed out of the way right?
(8:00:36 PM) Anonymous: yeah
(8:00:53 PM) Edward: congratulations you now understand why we get cancer
(8:01:17 PM) Edward: and this is why structure is so important
(8:01:42 PM) Edward: when you need something you know when you need it, you go to the bank, wait in line, and you get what you need
(8:01:54 PM) Edward: money = energy substrates
(8:02:57 PM) Edward: when you have no structure or you fill your body with a fuel that requires no structure you create an environment in the body where literally the first cell to absorb the the glucose wins at the expense of it’s sister cell
(8:03:03 PM) Edward: even if it is in the same organ
(8:03:32 PM) Edward: people who don’t wait in line and crowd around like in Germany they act like animals not civilized and chaos develops
(8:03:45 PM) Edward: this is very similar to what happens in the body
(8:04:40 PM) Edward: cancer and disease really is proof that we are made up of a group of primitive (individual) cells all working together
(8:05:27 PM) Edward: when a bunch of money drops from the sky the people scatter and fight for it, they don’t all put it in a pile and then split it equally right?
(8:05:42 PM) Anonymous: mmhmm
(8:06:03 PM) Edward: and as much as it seriously pains me to use this analogy gov’t is a good analogy to use for structure
(8:06:56 PM) Edward: obviously some gov’t are better than others and as a result each individual has a better life… some gov’t suck and then the individuals (the cells) have shitty lives
(8:07:25 PM) Edward: they starve, don’t have food, get disease
(8:07:27 PM) Edward: etc
(8:08:22 PM) Edward: does all that make sense
(8:08:23 PM) Edward: ?
(8:08:33 PM) Anonymous: yep
(8:08:42 PM) Edward: are light bulbs turning on?
(8:09:01 PM) Anonymous: lol
(8:09:04 PM) Anonymous: yeah
(8:09:44 PM) Edward: o.k. break time for a moment…
This post is going to serve as a sort of summary for the posts that I will be writing on the relationship between thyroid hormones and saturated fat. I’ve been working on ways to make things understandable and trying to develop some analogies so we can get a visual in the brain.
The first concepts I will be covering is the behavior of T3 alone, what it does to your metabolism and how it functions. I hope to dissolve some myths concerning the type of metabolism T3 promotes and why perhaps taking T3 on a low fat diet might be a mistake which can increase stress as well as making one more sensitive to stress.
From there I will work into the behavior of saturated fat alone, what it does to your metabolism, and how it functions. I hope to dissolve some myths concerning the type of metabolism that saturated fat promotes. I also hope to make it perfectly clear that there is a difference between a high saturated fat diet and a high fat diet that is high in polyunsaturated fats. And I also hope to make clear the difference between free saturated fatty acids and free polyunsaturated fatty acids.
At that point some light bulbs should be turning on and I will compare the similarities between the thyroid hormones and saturated fat. I will use that post as a jumping off point to make some predictions about things we should see in reality and the literature if this concept is true which I will follow up with examples and supporting literature.
Then I will write posts on longevity, metabolic rate, disease, and dovetail all of these concepts together. I was struggling with either wanting to write one large article or a series. I decided on writing a series because it will allow me to manage my time a little better with my work schedule. Plus I am getting ready to transfer to a hospital in Connecticut so with that pending move there might be some delays here and there. But the delays will give you a chance to start digging around yourself and poke holes in things that I may have overlooked. It is important to be vigilant. I have been very thorough in looking to find exceptions but I am only one person, and the literature is massive, and maybe you will look at things a little differently. And that is o.k., all we are after is answers to questions, and questioning assumptions.
Finally, always look for exceptions. It leads to great questions.
A few years ago I started looking at the mechanisms through which T3 works. In my brain when I’m developing a model in my head, it needs to resemble a gently moving mobile; you know those things over a baby crib. It has to make sense, it has to look beautiful. I’ve always pictured everything in nature almost as a fractal.
I had noticed in some personal experiments that T3 reminded me of eating butter. A lot of the same symptoms T3 seemed to solve where the same symptoms butter seemed to solve. Things like that make me incredibly curious.
When you are looking at hormones it becomes tempting to read so much about the positive benefits of one hormone that you convince yourself that actually taking that hormone is a good idea. It is easy to look at the positive benefits of a substance and quickly forget to ask the question what is causing a flux in this particular hormone to begin with?
It is very easy to forget the flux and the balance. I picture in my head a glass full of different colored dyes all remaining separate yet blended together at their edges in beautiful gradients.
Even more important is that when you look at hormones, you can’t just look at the flux of different hormones to understand them. One hormone is always pushing or pulling another through a cascade. To really get down to the understanding of hormones and their function, you have to get down to the microscopic level where organization starts. What is it about multicellular organisms that makes all of the cells organize, what makes them work together, how do they know where to go? How does a blood cell know it is a blood cell, how does muscle cell know it belongs in your muscle instead of your brain. How come your toenails grow straight out instead of curling under and growing back into your toe? How come sperm cells know to attach to the egg instead of attaching to an epithelial cell?
Everyday curious minds are working on solving these mysteries. It is fascinating how much we know really. Utterly staggering. Almost every question I’ve ever cared to ask at one point or another has been studied in some form or fashion, or at least part of the question has been studied.
These days what we are lacking most of all are creative people who can move objects in space in their brains. These days people are super concerned with data points instead of prediction power. Prediction power is the ultimate test for any theory. And as I’ve said many times if you don’t have prediction power or if your model can’t predict an exception then it’s time to go back to the drawing board.
You have to constantly back check everything from the microscopic to the macroscopic. You can never be too careful in coming to conclusions. Especially when it comes to your own health.
As I said, it made me incredibly curious when I noticed that T3 solved the same problems butter seemed to solve. So I began looking for a connection. I have a lot of posts I’m supposed to be writing and for now they will be put on hold. From here on out I will be focusing on writing about the connection between T3 and butter.
Lanni, a., Moreno, M., Lombardi, A., & Goglia, F. (2003). Thyroid hormone and uncoupling proteins. FEBS letters, 543(1-3), 5–10. doi:10.1016/S0014-5793(03)00320-X
Thyroid hormone (TH/T3) exerts many of its effects on energy metabolism by affecting gene transcription. However, although this is an important target for T3, only a limited number of T3-responsive genes have been identified and studied. Among these, the genes for uncoupling proteins (UCPs) have attracted the interest of scientists. Although the role of UCP1 seems quite well established, uncertainty surrounds the physiological function of the recently discovered UCP1 analogs, UCP2 and UCP3. The literature suggests that T3 affects both the expression and the activity of each of these UCPs but further studies are needed to establish whether the mechanisms activated by the hormone are the same. Recently, because of their larger range of expression, much attention has been devoted to UCP2 and UCP3. Most detailed studies on the involvement of these proteins as mediators of the effects of T3 on metabolism have focused on UCP3 because of its expression in skeletal muscle. T3 seems to be unique in having the ability to stimulate the expression and activity of UCP3 and this may be related to the capacity of T3 to activate the integrated biochemical processes linked to UCP activity, such as those related to fatty acids, coenzyme Q and free radicals.
Nicotine uncouples the mitochondria via UCP1 (uncoupling protein 1, or thermogenin). It upregulates BAT thermogensis (brown adipose tissue) and increases in BAT thermogenesis is associated with increased longevity. I could see nicotine, aside from butter, promoting longevity.
Mattson, M. P. (2010). Perspective: Does brown fat protect against diseases of aging? Ageing research reviews, 9(1), 69–76. doi:10.1016/j.arr.2009.11.004
The most commonly studied laboratory rodents possess a specialized form of fat called brown adipose tissue (BAT) that generates heat to help maintain body temperature in cold environments. In humans, BAT is abundant during embryonic and early postnatal development, but is absent or present in relatively small amounts in adults where it is located in paracervical and supraclavicular regions. BAT cells can “burn” fatty acid energy substrates to generate heat because they possess large numbers of mitochondria in which oxidative phosphorylation is uncoupled from ATP production as a result of a transmembrane proton leak mediated by uncoupling protein 1 (UCP1). Studies of rodents in which BAT levels are either increased or decreased have revealed a role for BAT in protection against diet-induced obesity. Data suggest that individuals with low levels of BAT are prone to obesity, insulin resistance and cardiovascular disease, whereas those with higher levels of BAT maintain lower body weights and exhibit superior health as they age. BAT levels decrease during aging, and dietary energy restriction increases BAT activity and protects multiple organ systems including the nervous system against age-related dysfunction and degeneration. Future studies in which the effects of specific manipulations of BAT levels and thermogenic activity on disease processes in animal models (diabetes, cardiovascular disease, cancers, neurodegenerative diseases) are determined will establish if and how BAT affects the development and progression of age-related diseases. Data from animal studies suggest that BAT and mitochondrial uncoupling can be targeted for interventions to prevent and treat obesity and age-related diseases. Examples include: diet and lifestyle changes; specific regimens of mild intermittent stress; drugs that stimulate BAT formation and activity; induction of brown adipose cell progenitors in muscle and other tissues; and transplantation of brown adipose cells.
Yoshida, T., Yoshioka, K., Hiraoka, N., & Kondo, M. (1990). Effect of nicotine on norepinephrine turnover and thermogenesis in brown adipose tissue and metabolic rate in MSG obese mice. Journal of nutritional science and vitaminology, 36(2), 123–30. Retrieved from http://europepmc.org/abstract/MED/2388096
To clarify whether nicotine stimulates the sympathetic nervous system (SNS) and thermogenesis in brown adipose tissue (BAT) and whether it promotes the resting metabolic rate (RMR), with resulting mitigation of obesity, we measured norepinephrine (NE) turnover (an indicator of SNS activity), guanosine-5’-diphosphate (GDP) binding (a thermogenic indicator), oxygen consumption in BAT, and RMR in monosodium-L-glutamate (MSG) obese and saline control mice after 2 weeks treatment with nicotine. Nicotine significantly increased NE turnover, GDP binding, oxygen consumption in BAT, and RMR, and significantly reduced body weight in MSG obese mice as well as in control mice without affecting food intake. These results suggest that nicotine stimulates NE turnover and thermogenesis in BAT, and promotes RMR, all of which contribute to the mitigation of obesity.
Romestaing, C., Piquet, M.-A., Bedu, E., Rouleau, V., Dautresme, M., Hourmand-Ollivier, I., … Sibille, B. (2007). Long term highly saturated fat diet does not induce NASH in Wistar rats. Nutrition & metabolism, 4, 4. doi:10.1186/1743-7075-4-4
BACKGROUND: Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. METHODS: 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. RESULTS: MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption) or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25-28% vs standard). CONCLUSION: Long term high saturated fat feeding led to increased “peripheral” fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH.
Di Paola, M., & Lorusso, M. (2006). Interaction of free fatty acids with mitochondria: coupling, uncoupling and permeability transition. Biochimica et biophysica acta, 1757(9-10), 1330–7. doi:10.1016/j.bbabio.2006.03.024
Long chain free fatty acids (FFA) exert, according to their actual concentration, different effects on the energy conserving system of mitochondria. Sub-micromolar concentrations of arachidonic acid (AA) rescue DeltapH-dependent depression of the proton pumping activity of the bc1 complex. This effect appears to be due to a direct interaction of AA with the proton-input mouth of the pump. At micromolar concentrations FFA increase the proton conductance of the inner membrane acting as protonophores. FFA can act as natural uncouplers, causing a mild uncoupling, which prevents reactive oxygen species production in the respiratory resting state. When Ca(2+)-loaded mitochondria are exposed to micromolar concentrations of FFA, the permeability of the inner membrane increases, resulting in matrix swelling, rupture of the outer membrane and release of intermembrane pro-apoptotic proteins. The characteristics of AA-induced swelling appear markedly different in mitochondria isolated from heart or liver. While in the latter it presents the canonical features of the classical permeability transition (PT), in heart mitochondria substantial differences are observed concerning CsA sensitivity, DeltaPsi dependence, reversibility by BSA and specificity for the activating divalent cation. In heart mitochondria, the AA-dependent increase of the inner membrane permeability is affected by ANT ligands such as adenine nucleotides and atractyloside. AA apparently causes a Ca2+-mediated conversion of ANT from a translocator to a channel system. Upon diamide treatment of heart mitochondria, the Ca2+/AA-induced CsA insensitive channel is converted into the classical PT pore. The relevance of these observations in terms of tissue-specific components of the putative PTP and heart ischemic and post-ischemic process is discussed.
At least until the CHO breaks you…
Dennis, N. a, Browndyke, J. N., Stokes, J., Need, A., Burke, J. R., Welsh-Bohmer, K. a, & Cabeza, R. (2010). Temporal lobe functional activity and connectivity in young adult APOE varepsilon4 carriers. Alzheimer’s & dementia : the journal of the Alzheimer’s Association, 6(4), 303–11. doi:10.1016/j.jalz.2009.07.003
BACKGROUND: We sought to determine if the APOE epsilon4 allele influences both the functional activation and connectivity of the medial temporal lobes (MTLs) during successful memory encoding in young adults. METHODS: Twenty-four healthy young adults, i.e., 12 carriers and 12 noncarriers of the APOE epsilon4 allele, were scanned in a subsequent-memory paradigm, using event-related functional magnetic resonance imaging. The neuroanatomic correlates of successful encoding were measured as greater neural activity for subsequently remembered versus forgotten task items, or in short, encoding success activity (ESA). Group differences in ESA within the MTLs, as well as whole-brain functional connectivity with the MTLs, were assessed. RESULTS: In the absence of demographic or performance differences, APOE epsilon4 allele carriers exhibited greater bilateral MTL activity relative to noncarriers while accomplishing the same encoding task. Moreover, whereas epsilon4 carriers demonstrated a greater functional connectivity of ESA-related MTL activity with the posterior cingulate and other peri-limbic regions, reductions in overall connectivity were found across the anterior and posterior cortices. CONCLUSIONS: These results suggest that the APOE varepsilon4 allele may influence not only functional activations within the MTL, but functional connectivity of the MTLs to other regions implicated in memory encoding. Enhanced functional connectivity of the MTLs with the posterior cingulate in young adult epsilon4 carriers suggests that APOE may be expressed early in brain regions known to be involved in Alzheimer’s disease, long before late-onset dementia is a practical risk or consideration. These functional connectivity differences may also reflect pleiotropic effects of APOE during early development.
Evans, S., Gray, M. A., Dowell, N. G., Tabet, N., Tofts, P. S., King, S. L., & Rusted, J. M. (2013). APOE E4 Carriers show prospective memory enhancement under nicotine, and evidence for specialisation within medial BA10. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 38(4), 655–63. doi:10.1038/npp.2012.230
There is evidence to suggest that the APOE ɛ4 allele (which confers an increased risk of developing dementia) might be associated with cognitive advantages earlier in life. Further, nicotine might selectively benefit ɛ4 carriers. We used fMRI to explore performance on a prospective memory (PM) task in young adults (age 18-30) with and without nicotine using a within-subjects design. Participants performed an ongoing task while retaining a PM instruction to respond to specific stimuli embedded in the task. Nicotine effects varied according to APOE status. Reaction times to the PM cue were improved under nicotine in ɛ4 carriers, but not in ɛ3 carriers. In an event-related analysis, extrastriate responses to PM trials were enhanced by nicotine only in ɛ4 carriers. These differences in early visual processing may contribute to the behavioral findings. Activity in medial BA10 (previously implicated in PM) differentiated ɛ4 from ɛ3 carriers. One BA10 subregion showed greater deactivation in ɛ4 carriers during PM trials. Activity in other BA10 subregions was modulated by PM reaction time, pointing to region-specific effects within medial BA10. In addition, activity in right hippocampal formation was only seen in ɛ4 carriers receiving nicotine. These results demonstrate that cognitive enhancement by nicotine can selectively benefit APOE ɛ4 carriers, and point to genotype-specific differences in neural activity during PM. In addition, these results show that the role of medial BA10 in PM likely involves varying contributions from functionally specific subregions.
Filippini, N., MacIntosh, B. J., Hough, M. G., Goodwin, G. M., Frisoni, G. B., Smith, S. M., … Mackay, C. E. (2009). Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proceedings of the National Academy of Sciences of the United States of America, 106(17), 7209–14. doi:10.1073/pnas.0811879106
The APOE epsilon4 allele is a risk factor for late-life pathological changes that is also associated with anatomical and functional brain changes in middle-aged and elderly healthy subjects. We investigated structural and functional effects of the APOE polymorphism in 18 young healthy APOE epsilon4-carriers and 18 matched noncarriers (age range: 20-35 years). Brain activity was studied both at rest and during an encoding memory paradigm using blood oxygen level-dependent fMRI. Resting fMRI revealed increased “default mode network” (involving retrosplenial, medial temporal, and medial-prefrontal cortical areas) coactivation in epsilon4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in epsilon4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The APOE epsilon4 allele modulates brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.
Mondadori, C. R. A., de Quervain, D. J.-F., Buchmann, A., Mustovic, H., Wollmer, M. A., Schmidt, C. F., … Henke, K. (2007). Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers. Cerebral cortex (New York, N.Y. : 1991), 17(8), 1934–47. doi:10.1093/cercor/bhl103
The apolipoprotein E (APOE) epsilon4 allele is the major genetic risk factor for Alzheimer’s disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE epsilon4 with better episodic memory compared with APOE epsilon2 and epsilon3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas epsilon2 and epsilon3 carriers increased activity. This smaller neural investment of epsilon4 carriers into learning reappeared during retrieval: epsilon4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE epsilon4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy humans.
Moreau, P.-H., Bott, J.-B., Zerbinatti, C., Renger, J. J., Kelche, C., Cassel, J.-C., & Mathis, C. (2013). ApoE4 confers better spatial memory than apoE3 in young adult hAPP-Yac/apoE-TR mice. Behavioural brain research, 243, 1–5. doi:10.1016/j.bbr.2012.12.043
The APOE-ɛ4 allele is associated with increased cognitive decline during normal aging and Alzheimer’s disease. However, several studies intriguingly found a beneficial effect on cognition in young adult human APOE-ɛ4 carriers. Here, we show that 3-month old bigenic hAPP-Yac/apoE4-TR mice outperformed their hAPP-Yac/apoE3-TR counterparts on learning and memory performances in the highly hippocampus-dependent, hidden-platform version of the Morris water maze task. The two mouse lines did not differ in a non-spatial visible-platform version of the task. This hAPP-Yac/apoE-TR model may thus provide a useful tool to study the mechanisms involved in the antagonistic pleiotropic effects of APOE-ɛ4 on cognitive functions.
Rusted, J. M., Evans, S. L., King, S. L., Dowell, N., Tabet, N., & Tofts, P. S. (2013). APOE e4 polymorphism in young adults is associated with improved attention and indexed by distinct neural signatures. NeuroImage, 65, 364–73. doi:10.1016/j.neuroimage.2012.10.010
The APOE e4 allele, which confers an increased risk of developing dementia in older adulthood, has been associated with enhanced cognitive performance in younger adults. An objective of the current study was to compare task-related behavioural and neural signatures for e4 carriers (e4+) and non-e4 carriers (e4-) to help elucidate potential mechanisms behind such cognitive differences. On two measures of attention, we recorded clear behavioural advantages in young adult e4+ relative to e4-, suggesting that e4+ performed these tasks with a wider field of attention. Behavioural advantages were associated with increased task-related brain activations detected by fMRI (BOLD). In addition, behavioural measures correlated with structural measures derived from a former DTI analysis of white matter integrity in our cohort. These data provide clear support for an antagonistic pleiotropy hypothesis–that the e4 allele confers some cognitive advantage in early life despite adverse consequences in old age. The data implicate differences in both structural and functional signatures as complementary mediators of the behavioural advantage.
The presence of the E4 allele of apolipoprotein E (apoE) is the strongest known genetic risk factor for sporadic Alzheimer’s disease (AD). Other risk factors for developing AD have been identified, including lifestyle such as dietary habits. The present study was designed to explore the impact of the interaction between variant human apoE isoforms and a high carbohydrate diet (HCD) on mechanisms behind learning and memory retention. As an investigative model, we compared young apoE3 and apoE4 target replacement mice fed on a HCD for 6 months. Our results indicate that HCD compromises memory processes in apoE4 mice. ApoE4 mice on HCD showed decreased activity-regulated cytoskeletal-associated protein (Arc) and brain derived neurotrophic factor (BDNF) levels, as well as decreased BDNF signaling in the hippocampus. In contrast, apoE3 mice were resistant to the deleterious effects of HCD on both behavior and memory-related proteins. Our results support the hypothesis that already in mid-life, genetic, and environmental risk factors act together on the mechanisms behind cognitive impairment.
Maioli, S., Puerta, E., Merino-Serrais, P., Fusari, L., Gil-Bea, F., Rimondini, R., & Cedazo-Minguez, A. (2012). Combination of apolipoprotein E4 and high carbohydrate diet reduces hippocampal BDNF and arc levels and impairs memory in young mice. Journal of Alzheimer’s disease : JAD, 32(2), 341–55. doi:10.3233/JAD-2012-120697
Alzheimer’s disease (AD) is a common, progressive, neurodegenerative disease that primarily afflicts the elderly. A well-defined risk factor for late onset AD is possession of one or more alleles of the epsilon-4 variant (E4) of the apolipoprotein E gene. Meta-analysis of allele frequencies has found that E4 is rare in populations with long historical exposure to agriculture, suggesting that consumption of a high carbohydrate (HC) diet may have selected against E4 carriers. The apoE4 protein alters lipid metabolism in a manner similar to a HC diet, suggesting a common mechanism for the etiology of AD. Evolutionarily discordant HC diets are proposed to be the primary cause of AD by two general mechanisms. (1) Disturbances in lipid metabolism within the central nervous system inhibits the function of membrane proteins such as glucose transporters and the amyloid precursor protein. (2) Prolonged excessive insulin/IGF signaling accelerates cellular damage in cerebral neurons. These two factors ultimately lead to the clinical and pathological course of AD. This hypothesis also suggests several preventative and treatment strategies. A change in diet emphasizing decreasing dietary carbohydrates
and increasing essential fatty acids (EFA) may effectively prevent AD. Interventions that restore lipid homeostasis may treat the disease, including drugs that increase fatty acid metabolism, EFA repletion therapy, and ketone body treatment.
Henderson, S. T. (2004). High carbohydrate diets and Alzheimer’s disease. Medical hypotheses, 62(5), 689–700. doi:10.1016/j.mehy.2003.11.028
Wanted to add this little clip from Homo Optimus as an addition to my comment regarding DOMS.
I did indeed. There is a leading football team in Poland for the players of which, some time ago, I recommended correct nutrition. They are resistant to fatigue, play aggressively, and typically score goals in the second half when their opposition is falling apart. And one more important detail – they do not have muscle cramps, and suffer injuries much less often than other players.
Not sure how well the Polish team referenced here play or which one it is; more interested in the lack of muscle cramps.
I have been reading through Jan Kwasniewski’s book Homo Optimus and came across this bit:
Those who are not interested can skip the next few lines, but I would like to explain these processes which lead to advantageous or harmful changes in our bodies. Unsaturated fats, we are told – essential unsaturated fats – are present in mother’s milk at the concentration of 0.4%. No one can dispute that mother’s milk is the ideal nutrition, as far as the biochemical composition is concerned. It contains 3 to [illegible] grams of fat per 1 gram of protein. The conclusion is obvious – if Nature included such a minute quantity of that constituent in such a wonder food, then we should respect it. Meanwhile, people are being persuaded that plant-derived fats containing polyunsaturated fatty acids which do not exist in mother’s milk, are healthy. Nothing is more misleading – in the body they participate in reaction by binding oxygen. Peroxides, superoxides, various other poisons accelerating the formation of atherosclerosis are formed; aging of tissues, mechanical damage, cancer formation occurs. Some time ago, experiments were conducted investigating the effects of the replacement in a diet of saturated fat with unsaturated fats. What was concluded? Patients who were fed unsaturated fats were getting cancer 3-4, even 5 times more often than patients on the same proportion of saturated fats. Its is obvious why. Peroxides, which I have already mentioned, induce inflammations in the body, disease states, they simply degenerate tissues and whole organs. This concerns polyunsaturated fats only, those not present in butter, but instead present in plant-derived oils. That is not the end to it. In the bodies nourished with polyunsaturated fat the chemical compound called malate aldehyde is formed – terrible stuff. Technical gases such as ethane and pentane are also formed, excreted by the body, defending itself against the poisoning. However, together with these gases we also excrete hydrogen – the best fuel for our tissues.
I like that he mentions the aldehydes produced when polyunsaturated fats are oxidized. As he says, “terrible stuff”.
This is one of the most useful tips I’ve come across for getting perfect soft-boiled eggs with a pan and water. This method makes a huge difference in repeatable consistency. If you keep your eggs on the counter at room temperature (which was something I picked up when living in Germany) the cooking times will be about a minute to a minute and a half shorter depending on the consistency you like. I have been happy with 6 minutes and then a quick rinse in cold water, not too long in the cold water because I like the yolk to still have a creamy warm texture. A superior cooking method would be Sous-vide.
I think that this website is interesting considering the endosymbiotic theory of the origin of mitochondria is the explanation usually given for the origin of the organelle (the other is the autogenic one). And now it seems the origin of the peroxisome might get the same canned answer for its origin.
I remember the first time I read about the idea that mitochondria were essentially prokaryotic cells that took up residency in eukaryotic cells. The story I read seemed rather fairy-tale like.
“The lactic acid bacteria are themselves anti-inflammatory, but if they live in the upper intestine (because of hypothyroidism) they might be able to convert sugar to lactic acid, which would be stressful for the liver. Any lactic acid can promote inflammation, but bacterial DL-lactic acid is worse, so it shouldn’t be used in large amounts.” ~Dr. Peat via e-mail
Lactic acid bacteria seem to be anti-inflammatory. There are several isomers of lactate/lactic acid and they have differing physiological effects. The literature is supportive of the anti-inflammatory effects of lactic acid bacteria, and anecdotal and historical accounts support the literature. The literature also seems to support a positive effect for the lactic acid produced by lactic acid bacteria, which contrasts with Dr. Peat.
In the meantime have a look through the literature below and a look at Lactated Ringer’s Solution.
Time to eat.
De Luis, D. A., Varela, C., de La Calle, H., Cantón, R., de Argila, C. M., San Roman, A. L., & Boixeda, D. (1998). Helicobacter pylori infection is markedly increased in patients with autoimmune atrophic thyroiditis. Journal of clinical gastroenterology, 26(4), 259–63. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9649006
Infection by viral or bacterial pathogens has been suspected in playing a role in the development of autoimmune thyroid disease. Because Helicobacter pylori might be involved in the development of nongastrointestinal conditions such as rosacea, ischemic heart disease, and diabetes mellitus, we evaluated the prevalence of H. pylori infection in patients with autoimmune thyroid disease. Fifty-nine patients with autoimmune thyroid disease were included: autoimmune atrophic thyroiditis (n=21), Hashimoto’s thyroiditis (n=18), and Graves’ disease (n=20). Twenty patients with nontoxic multinodular goiter served as controls for nonautoimmune thyroid disease, and 11 patients with Addison’s disease served as controls for nonthyroid endocrine autoimmune disease. The levels of anti-H. pylori immunoglobulin G (IgG) were determined, and a radiolabeled urea breath test were performed. The prevalence of H. pylori infection was markedly increased in the patients with autoimmune atrophic thyroiditis (85.7%), compared with the controls with nontoxic multinodular goiter (40%) and Addison’s disease (45.4%). Infection by H. pylori resulted in increased levels of gastrin, pepsinogen I, and pepsinogen II in the H. pylori-positive groups, compared with the H. pylori-negative groups. A positive linear regression was found between the levels of microsomal autoantibodies and those of anti-H. pylori IgG in patients with autoimmune atrophic thyroiditis (n=21; r=0.79; p < 0.01). Finally, and although the overall prevalence of H. pylori infection was not increased, the anti-H. pylori IgG levels and the results from the breath test were higher in the patients with Graves’ disease and Hashimoto’s thyroiditis patients than in the controls. Clearly, the prevalence of H. pylori infection is increased in autoimmune atrophic thyroiditis and results in abnormalities of gastric secretory function. The strong relation between the levels of anti-H. pylori IgG and the levels of microsomal antibodies suggests that H. pylori antigens might be involved in the development of autoimmune atrophic thyroiditis or that autoimmune function in autoimmune atrophic thyroiditis may increase the likelihood of H. pylori infection.
Midolo, P. D. D., Lambert, J. R. R., Hull, R., Luo, F., & Grayson, M. L. L. (1995). In vitro inhibition of Helicobacter pylori NCTC 11637 by organic acids and lactic acid bacteria. The Journal of applied bacteriology, 79(4), 475–479. doi:10.1111/j.1365-2672.1995.tb03164.x
In this study the effects of both pH and organic acids on Helicobacter pylori NCTC 11637 were tested. Lactobacillus acidophilus, Lact. casei, Lact. bulgaricus, Pediococcus pentosaceus and Bifidobacterium bifidus were assayed for their lactic acid production, pH and inhibition of H. pylori growth. A standard antimicrobial plate well diffusion assay was employed to examine inhibitory effects. Lactic, acetic and hydrochloric acids demonstrated inhibition of H. pylori growth in a concentration-dependent manner with the lactic acid demonstrating the greatest inhibition. This inhibition was due both to the pH of the solution and its concentration. Six strains of Lact. acidophilus and one strain of Lact. casei subsp. rhamnosus inhibited H. pylori growth where as Bifidobacterium bifidus, Ped. pentosaceus and Lact. bulgaricus did not. Concentrations of lactic acid produced by these strains ranged from 50 to 156 mmol l-1 and correlated with H. pylori inhibition. The role of probiotic organisms and their metabolic by-products in the eradication of H. pylori in vivo remains to be determined.
Ohashi, Y., Nakai, S., Tsukamoto, T., Masumori, N., Akaza, H., Miyanaga, N., … Aso, Y. (2002). Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Urologia internationalis, 68(4), 273–80. doi:58450
INTRODUCTION: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota, shows antitumor activity in experimental animals. One clinical trial using L. casei showed a significant decrease in the recurrence of superficial bladder cancer. So, to Ohashi, Y., Nakai, S., Tsukamoto, T., Masumori, N., Akaza, H., Miyanaga, N., … Aso, Y. (2002). Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Urologia internationalis, 68(4), 273–80. doi:58450 INTRODUCTION: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota, shows antitumor activity in experimental animals. One clinical trial using L. casei showed a significant decrease in the recurrence of superficial bladder cancer. So, to assess the preventive effect of the intake of L. casei, widely taken as fermented milk products in Japan, against bladder cancer, we conducted a case-control study. METHODS: A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR). RESULTS: The OR of smoking was 1.61 (95% confidence interval: 1.10-2.36). Those of previous (10-15 years ago) intake of fermented milk products were 0.46 (0.27-0.79) for 1-2 times/week and 0.61 (0.38-0.99) for 3-4 or more times/week, respectively. CONCLUSION: It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.assess the preventive effect of the intake of L. casei, widely taken as fermented milk products in Japan, against bladder cancer, we conducted a case-control study. METHODS: A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR). RESULTS: The OR of smoking was 1.61 (95% confidence interval: 1.10-2.36). Those of previous (10-15 years ago) intake of fermented milk products were 0.46 (0.27-0.79) for 1-2 times/week and 0.61 (0.38-0.99) for 3-4 or more times/week, respectively. CONCLUSION: It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.
Sgouras, D., Maragkoudakis, P., Petraki, K., Martinez-Gonzalez, B., Eriotou, E., Michopoulos, S., … Mentis, A. (2004). In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei strain Shirota. Applied and environmental microbiology, 70(1), 518–26. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=321236&tool=pmcentrez&rendertype=abstract
We studied the potential inhibitory effect of Lactobacillus casei strain Shirota (from the fermented milk product Yakult [Yakult Ltd., Tokyo, Japan]) on Helicobacter pylori by using (i) in vitro inhibition assays with H. pylori SS1 (Sydney strain 1) and nine H. pylori clinical isolates and (ii) the in vivo H. pylori SS1 mouse model of infection over a period of 9 months. In vitro activity against H. pylori SS1 and all of the clinical isolates was observed in the presence of viable L. casei strain Shirota cells but not in the cell-free culture supernatant, although there was profound inhibition of urease activity. In vivo experiments were performed by oral administration of L. casei strain Shirota in the water supply over a period of 9 months to 6-week-old C57BL/6 mice previously infected with H. pylori SS1 (study group; n = 25). Appropriate control groups of H. pylori-infected but untreated animals (n = 25) and uninfected animals given L. casei strain Shirota (n = 25) also were included in the study. H. pylori colonization and development of gastritis were assessed at 1, 2, 3, 6, and 9 months postinfection. A significant reduction in the levels of H. pylori colonization was observed in the antrum and body mucosa in vivo in the lactobacillus-treated study group, as assessed by viable cultures, compared to the levels in the H. pylori-infected control group. This reduction was accompanied by a significant decline in the associated chronic and active gastric mucosal inflammation observed at each time point throughout the observation period. A trend toward a decrease in the anti-H. pylori immunoglobulin G response was measured in the serum of the animals treated with lactobacillus, although this decrease was not significant.
Cats, A., Kuipers, E. J., Bosschaert, M. A. R., Pot, R. G. J., Vandenbroucke-Grauls, C. M. J. E., & Kusters, J. G. (2003). Effect of frequent consumption of a Lactobacillus casei-containing milk drink in Helicobacter pylori-colonized subjects. Alimentary pharmacology & therapeutics, 17(3), 429–35. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12562457
BACKGROUND: Several studies have reported inhibitory effects of lactic acid bacteria on bacterial pathogens. AIM: To test whether a drink containing Lactobacillus casei strain Shirota inhibits Helicobacter pylori growth. METHODS: The in vitro growth inhibition of H. pylori was studied when L. casei was added to plates previously inoculated with H. pylori reference strain NCTC 11637. In an intervention study, 14 H. pylori-positive subjects were given Yakult drink (10(8) colony-forming units/mL L. casei) thrice daily during meals for 3 weeks. Six untreated H. pylori-positive subjects served as controls. H. pylori bacterial loads were determined using the 13C-urea breath test, which was performed before and 3 weeks after the start of L. casei supplementation. RESULTS: In vitro, L. casei inhibits H. pylori growth. This effect was stronger with L. casei grown in milk solution than in DeMan-Rogosa-Sharpe medium. No growth inhibition was shown with medium inoculated with lactic acid, Escherichia coli strain DH5alpha or uninoculated medium. Filtration of L. casei culture before incubation with H. pylori completely abolished the inhibitory effect. Urease activity decreased in nine of the 14 (64%) subjects with L. casei supplementation and in two of the six (33%) controls (P = 0.22). CONCLUSIONS: Viable L. casei are required for H. pylori growth inhibition. This does not result from changes in lactic acid concentration. In addition, a slight, but non-significant, trend towards a suppressive effect of L. casei on H. pylori in vivo may exist.
James I always appreciate your comments.
There are reliable reports on the Maasai/Masai. For further exploration: Peter Dobromylskyj, Stephan Guyenet, Chris Masterjohn have all written on the Maasai. Ray Peat has also commented on the health of the Maasai:
“Many people advocate a low protein diet, specifically to prevent or treat osteoporosis, but the cultures that traditionally have had extremely high protein diets, such as the Masai, are very healthy.” (Peat, n.d.)
There are also interesting studies isolating the impacts of different types of fat in mice (Horn, Laver, & Wood, 1981; MacQueen, 2011).
The question of healthy, healthier, and healthiest is relative. There are many optimums in health and there is plenty of observational evidence to support this position; in the literature and anecdotal.
If I am in Europe and then go to the United States and see that the average population of Europe is healthier than the average population of the United States-clearly Europe is doing something different to achieve those results. Is Europe’s approach optimal, not necessarily, but one could argue that it is a step towards something better (a degree of improvement towards something optimal). If I am in an area of the world that has a high concentration of 90+ year old inhabitants and then move to an area where the phenomena is absent–regardless of the factors–if longevity is your goal, then in my opinion it is worth further exploration.
Another example: If I look at the longest lived and see that sucrose is relatively low, and I see evidence in the literature that sucrose is healthful, then the next question to be asked is if sucrose is a negative, neutral, or positive contributing factor to longevity and good health. If I see that some people who live a long time eat relatively little sugar and I see that some people also live long lives eating more sucrose, then I can see that there are apparently two different paradigms at work that perhaps achieve the same results. You can look at a pattern and develop a theory, but as soon as the pattern is broken it means the foundation on which the theory is based is flawed.
A comical example is if someone tells me that bacon is unhealthful and that industrial bacon is even more unhealthful. We walk away thinking bacon is unhealthful but industrial bacon is worse. But then we find a woman who is 100+ years old who gives responsibility of her longevity to the high quantities of bacon she eats that is more than likely less than pastured. So not only is she eating “harmful” bacon, she is eating the worst of the worst. Is there a protective factor that protects from the negative factors of bacon? Or is it such that bacon, regardless of the source, is either a neutral or positive factor towards longevity?
Good health is usually a balance between the concepts of security and freedom.
“I’m a bit skeptic about inferring that a habit or food is good based upon the apparent health of a population.”
However, the question I am raising is not a matter of health, it is a matter of toxicity. When a food dominates a particular diet and the population is in good health and it is claimed that same food is harmful, there is an irregularity. For example, if smoking is harmful and/or toxic, and the oldest person on earth smoked (as well as others in the record books) there is an irregularity. Either the toxin is indeed harmful and there is a protective factor or the toxin is not harmful; or the mechanism for harmfulness is incorrect or there are contextual considerations. A further example would be fatty acids such as those found in breast milk and coconut oil that are ketogenic. These fatty acids are ketogenic in their nature. If we agree that breast milk and coconut oil are good even though they produce ketones (or in the case of breast milk which enhances ketogenesis) then there are now at least two contexts for ketosis. One that is stimulated by metabolic substrates, and one that is produced in certain physiological situations (self-induced or as a result of disease). In a baby who is in ketosis we do not say that ketones are harmful, yet ketoacidosis in a diabetic is harmful. Clearly ketones are protective. But the context (physiological states) in which they are measured might lead some people to throw out the baby with the bath water. My opinion is that lactic acid and lactate have different contexts as well.
Your last question:
“But Ray Peat seems to think carb (esp. sugar – but let’s leave alone the debate on starch and endotoxin for now) is needed for good thyroid even once in good health – do you disagree and if so why?”
I think glucose is probably wise. How much is required for good health and stress resistance? I don’t know, but I think the requirement is rather low. I have a post on this topic that I have not yet had a chance to finish. Fresh meat contains glycogen which indeed is a source of glucose. That is something that I think is important which most miss when gauging carbohydrate requirements. Even then I have no idea how much glycogen is available in fresh meat.
Personally I recovered predominately on a high saturated fat diet similar to the Maasai pattern (I suppose a “what do I eat?” type of post is overdue). In my toolbox, however, were varying amounts of sugars and thyroid along the way (Cynoplus and Cynomel I no longer need, and my CO2 always falls somewhere between 29-32 mEq/L). Another kind of quirky thing about me is that the only carbohydrates I trust are those produced from animals. Namely those found in milk and honey. Maybe that is silly, maybe not. How much of the sugars we actually use after gut fermentation from milk is questionable. How much sugar? I have no idea but overall rather low, sometimes I put sucrose or honey in my coffee or tea sometimes I don’t. I like the occasional scoop of vanilla ice cream with bits of chocolate or if I’m feeling wild chocolate syrup. I also like cheesecake. I usually have absolutely no sweet cravings. But there were periods where I attempted to force feed myself large amounts of fruit. Virgin coconut oil was useful for slimming down at some points but refined was not. Sometimes I gently melt the coconut oil down and pour it over a bit of ice cream to make the chocolate syrup I make crispy.
My body temperatures are rock solid stable on high saturated fat 98.6-99 F. If I get a little wild with the sugars my body temperatures get wild as well which tends to agree with this.
On another note:
There is also another post I have in the pipes about mucin deficiency, which some have said is a lack of glucose in certain low carbohydrate promoting circles, whereas I believe it to be a deficiency of certain amino acids in the context of a diet that is high in muscle meats-namely glycine, which mucin is partly made up of.
Another topic I plan on writing about is methionine restriction. Obviously in some animals methionine restriction leads to increased lifespan, but I haven’t seen anything that would convince me that outright restriction in humans would have the same effect, and I think it is because there are certain species of gut bacteria that digest methionine. In fact there is some evidence to suggest that methionine deficiency causes gray hair. Anecdotally when I was in Santa Fe, NM at altitude there is a large vegetarian population there, and I noticed that a lot of young vegetarians 30-50 years old had rich gray hair.
Horn, P. L., Laver, J. J., & Wood, J. T. (1981). Changes of aging parameters among rats on diets differing in fat quantity and quality. Journal of Gerontology, 36(3), 285–93. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7229275
MacQueen, H. A. (2011). Age-Related Biomarkers Can be Modulated by Diet in the Rat. Food and Nutrition Sciences, 02(08), 884–890. doi:10.4236/fns.2011.28120
Peat, R. (n.d.). Calcium and Disease: Hypertension, organ calcification, & shock, vs. respiratory energy. Retrieved March 29, 2014, from http://raypeat.com/articles/articles/calcium.shtml
I consume a lot of full fat dairy. A good half of it—probably more—is fermented in some bacterial cocktail. In some places there has been resurgence in the idea of drinking lots of milk. I think anything coming from a cow is healthy. But some people believe that the lactic acid in fermented bacterial cocktails is harmful.
As well, people talk about how much milk the Maasai drank. Now the Maasai and other dairy herding cultures are healthy. Thriving off of cows and their milk and the products produced from their milk no doubt is a high saturated fat diet. I think dairy, as far as food sources go, is probably the best and safest food source. I think the rest of the cow is good, too. But with how bad fermented foods are supposed to be and limiting yourself to maybe two tablespoons of yogurt, well that sounds rather…
Thriving off of cows and their dairy is like extended breast feeding…
Babies seem healthy to me and they seem to like breast milk. How dare a mother poison her baby with lactic acid producing bacteria (Martín et al., 2003).
I’m a big believer that a theory should—if it has any ounce of credibility—reflect what we see in reality. Most of the milk drank by the Maasai was fermented. There is a problem there. Given their good health and the fact they smoke a lot gives us a couple of angles to work from. No science required, just a little logic and common sense. First, the traditional Maasai were healthy. Second they smoked a lot. In modern culture we view smoking and/or nicotine as unhealthy, so if the Maasai have an unhealthy lifestyle factor then they must be protected by something in their diet (or some other factor). But we’ll avoid the complexity of those other factors for now and focus on the diet. So the Maasai smoked, and according to those who believe that lactic acid is harmful, that is also another risk factor for disaster.
The real question is: if lactic acid is harmful despite the fact that the lactic acid producing bacteria modulate endotoxin (Schiffrin, Rochat, Link-Amster, Aeschlimann, & Donnet-Hughes, 1995), and if smoking is harmful despite the fact that nicotine modulates endotoxin (Wittebole et al., 2007), well then…we have a big problem considering that most of the calories in the traditional Maasai diet are coming from fermented milk. These guys, according to some paradigms, are literally waiting to burst giant lactic acid secreting tumors out of their eye sockets, earholes and rectums. But they don’t. Of course, we could forever go down the road of different arguments, but really the simplest answer, and an answer that agrees with other traditional healthy cultures that ate fermented dairy, is simple: lactic acid is not harmful. Much like people who eat more saturated fat tend to be healthier. Yes, people who eat butter are healthier, faster, and stronger.
Of course, what is more interesting about fermented dairy is some of the special properties those bacteria provide us with. For example, Lactobacillus plantarum found in some fermented dairy products (but mostly in fermented plant concoctions) converts linoleic acid to CLA (Kishino, Ogawa, Yokozeki, & Shimizu, 2009; Ogawa et al., 2005). Of course, CLA is useful (Belury, 2002).
I don’t know. If you are eating a low PUFA diet and you are worried about PUFA, I kind of like the idea of a little flora mopping up what I can’t humanly avoid and turning it into something useful and probably healthful.
Belury, M. A. (2002). Inhibition of Carcinogenesis by Conjugated Linoleic Acid: Potential Mechanisms of Action. J. Nutr., 132(10), 2995–2998. Retrieved from http://jn.nutrition.org/content/132/10/2995.full
Kishino, S., Ogawa, J., Yokozeki, K., & Shimizu, S. (2009). Metabolic diversity in biohydrogenation of polyunsaturated fatty acids by lactic acid bacteria involving conjugated fatty acid production. Applied Microbiology and Biotechnology, 84(1), 87–97. doi:10.1007/s00253-009-1949-0
Martín, R., Langa, S., Reviriego, C., Jimínez, E., Marín, M. L., Xaus, J., … Rodríguez, J. M. (2003). Human milk is a source of lactic acid bacteria for the infant gut. The Journal of Pediatrics, 143(6), 754–8. doi:10.1016/j.jpeds.2003.09.028
Ogawa, J., Kishino, S., Ando, A., Sugimoto, S., Mihara, K., & Shimizu, S. (2005). Production of conjugated fatty acids by lactic acid bacteria. Journal of Bioscience and Bioengineering, 100(4), 355–64. doi:10.1263/jbb.100.355
Schiffrin, E. J., Rochat, F., Link-Amster, H., Aeschlimann, J. M., & Donnet-Hughes, a. (1995). Immunomodulation of human blood cells following the ingestion of lactic acid bacteria. Journal of Dairy Science, 78(3), 491–7. doi:10.3168/jds.S0022-0302(95)76659-0
Wittebole, X., Hahm, S., Coyle, S. M., Kumar, A., Calvano, S. E., & Lowry, S. F. (2007). Nicotine exposure alters in vivo human responses to endotoxin. Clinical and Experimental Immunology, 147(1), 28–34. doi:10.1111/j.1365-2249.2006.03248.x
Triiodothyronine (T3) increases mitochondrial respiration and promotes, in rodents, the uncoupling between oxygen consumption and ATP synthesis. The T3 effect is mediated partly through transcriptional control of genes encoding mitochondrial proteins. Here, we determined the effect of T3 on mRNA levels of uncoupling proteins (UCP) and proteins involved in the biogenesis of the respiratory chain in human skeletal muscle and on UCP2 mRNA expression in adipose tissue.
“T3 is also known to stimulate fatty acid oxidation. The decrease in respiratory quotient observed in our study suggests that T3 treatment induced an increase in fatty acid oxidation.”
Just moved to New York. Getting settled in etc., once things are settled will resume writing. For the time being came across some things I found worth reading.
This one is a post on low-dose radiation coming from Stan’s blog.
The rest are interesting papers:
Galo, M. G., Uñates, L. E., & Farías, R. N. (1981). Effect of membrane fatty acid composition on the action of thyroid hormones on (Ca2+ + Mg2+)-adenosine triphosphatase from rat erythrocyte. The Journal of biological chemistry, 256(14), 7113–4. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/6114093
The action of L-triiodothyronine, L-thyroxine, and their analogues on the (Ca2+ + Mg2+)-ATPase of erythrocytes from rats fed with two different fat-supplemented diets has been studied. It was found that only L-triiodothyronine and L-thyroxine have effects on the (Ca2+ + Mg2+)-ATPase of both groups, producing inhibition in rats fed with corn oil and activation in rats fed with lard-supplemented diets. The half-maximal effect for L-triiodothyronine and L-thyroxine are, respectively, on the order of 10(-10) and 10(-8) M. These changes were not obtained with analogues of the hormones. It is suggested that the response of this enzymatic system to the hormonal action is conditioned by the fatty acid composition of membrane-bound lipids. This observation is novel in the hormonal research area.
Ortiz-Caro, J., Montiel, F., Pascual, A., & Aranda, A. (1986). Modulation of thyroid hormone nuclear receptors by short-chain fatty acids in glial C6 cells. Role of histone acetylation. J. Biol. Chem., 261(30), 13997–14004. Retrieved from http://www.jbc.org/content/261/30/13997.short
Mitsuhashi, T., Uchimura, H., & Takaku, F. (1987). n-Butyrate increases the level of thyroid hormone nuclear receptor in non-pituitary cultured cells. J. Biol. Chem., 262(9), 3993–3999. Retrieved from http://www.jbc.org/content/262/9/3993.short
The blog is still alive, I’ve just come back stateside for a job in New York. Posting will resume shortly.
I don’t think humans are idiots. That is a problem.
It’s a problem because people who pledge themselves to cult like eating habits assume humans are idiots.
I find the concerns surrounding wheat fascinating. When I come across a study like this one. It makes me think.
If you take away the butter what is left? The bread.
I find it interesting that right around the time butter, cream, and milk became unhealthful foods people started becoming allergic to their bread.
If a person discovers they feel like the plague after eating bread and they stop eating it and it helps that is good. If that same person and their friends say that wheat is a problem and that the entire human species is verging on mass suicide by eating wheat that is delusional.
Perhaps that person and their friends just need to eat more butter.
You don’t need to speculate what people ate eons ago, 100 to 200 years back is all that is really needed. People prepared and consumed foods in specific ways for a reason. Who eats bread without butter?
I don’t think humans (our species) are idiots. Insanity is doing the same thing over and over again and expecting different results. I don’t think humans (our species) are insane.
This morning I came across this thread on ketosis and tissue unsaturation. I still watch the the Ray Peat forum because there are some curious people who ask interesting questions and they get smacked with wooden spoons. What is unfortunate is that those holding the spoon(s) are grossly mistaken.
This thread reminded me of a recent email exchange with Dr. Peat, in which he wrote the following in response to a brief summary I wrote on polyunsaturated fats, that summary is the basis for my recent post(s) on polyunsaturated fats:
That’s my interpretation too, it seems that we are perfectly adapted to a very warm planet with a lot of CO2 and with fats unsaturated according to the effects on structure and electronic behavior needed for special functions. I think our body temperature keeps our enzymes from evolving into the cold-blooded pattern, keeping us ready to handle the n-9 based fats when things improve.
Which brings me to the misunderstanding/misinterpretation some people have regarding PUFA. It is exogenous (dietary) polyunsaturated fats that are problematic born from the essential fatty acid doctrine. The body indeed produces it’s own unsaturated fatty acids such as those found in the brain for structure and special functions to the degree that they are needed when the body is fed appropriately.
Lactate seems to be able to produce C02 efficiently, at least in the context of the early postnatal period. What is interesting is that blood lactate doesn’t seem to be elevated. Yet it is being oxidized preferentially over glucose. Glucose seems to be being spared for specialized precursors. It is also interesting that lactate doesn’t seem to be going through the Cori cycle but straight to the Krebs (Medina, 1985), which is interesting because it might mean these early adaptive responses are not in the same stressful context such as working muscles? Much like producing ketones from ketogenic fatty acids is not stressful.
Dombrowski, G. J., Swiatek, K. R., & Chao, K. L. (1989). Lactate, 3-hydroxybutyrate, and glucose as substrates for the early postnatal rat brain. Neurochemical research, 14(7), 667–75. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/2779727
The dependence of cerebral energy metabolism upon glucose, 3-hydroxybutyrate, and lactate as fuel sources during the postnatal period was investigated. The brain of 6 day old suckling pups used very little glucose, but by the 15th postnatal day glucose was the major catabolite. Hydroxybutyrate was not a major brain fuel at either 6 or 15 days of age. Its utilization accounted for only 19% of the brain’s total energy needs at 15 days of age, even through blood ketone concentrations are near maximal at this time. Seventy percent of the cerebral metabolic requirements were met by lactate in animals aged 6 days. The major role played by lactate as a substrate for brain metabolism in young pups was not a result of abnormally elevated blood lactate concentrations. The slow catabolism of glucose in young brain can not be explained by low rates of influx or inadequate enzymatic capacity.
Fernández, E., & Medina, J. M. (1986). Lactate utilization by the neonatal rat brain in vitro. Competition with glucose and 3-hydroxybutyrate. The Biochemical journal, 234(2), 489–92. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1146593&tool=pmcentrez&rendertype=abstract
The maximum rates of lactate oxidation and lipogenesis from lactate by early-neonatal brain slices were considerably greater than those for utilization of glucose and 3-hydroxybutyrate at physiological concentrations. Lactate inhibited glucose utilization, but enhanced 3-hydroxybutyrate utilization. 3-Hydroxybutyrate inhibited lactate and glucose utilization. Glucose slightly inhibited oxidation of lactate and 3-hydroxybutyrate, but scarcely enhanced lipogenesis from these substrates.
Holmgren, C. D., Mukhtarov, M., Malkov, A. E., Popova, I. Y., Bregestovski, P., & Zilberter, Y. (2010). Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro. Journal of neurochemistry, 112(4), 900–12. doi:10.1111/j.1471-4159.2009.06506.x
While the ultimate dependence of brain function on its energy supply is evident, how basic neuronal parameters and network activity respond to energy metabolism deviations is unresolved. The resting membrane potential (E(m)) and reversal potential of GABA-induced anionic currents (E(GABA)) are among the most fundamental parameters controlling neuronal excitability. However, alterations of E(m) and E(GABA) under conditions of metabolic stress are not sufficiently documented, although it is well known that metabolic crisis may lead to neuronal hyper-excitability and aberrant neuronal network activities. In this work, we show that in slices, availability of energy substrates determines whether GABA signaling displays an inhibitory or excitatory mode, both in neonatal neocortex and hippocampus. We demonstrate that in the neonatal brain, E(m) and E(GABA) strongly depend on composition of the energy substrate pool. Complementing glucose with ketone bodies, pyruvate or lactate resulted in a significant hyperpolarization of both E(m) and E(GABA), and induced a radical shift in the mode of GABAergic synaptic transmission towards network inhibition. Generation of giant depolarizing potentials, currently regarded as the hallmark of spontaneous neonatal network activity in vitro, was strongly inhibited both in neocortex and hippocampus in the energy substrate enriched solution. Based on these results we suggest the composition of the artificial cerebrospinal fluid, which bears a closer resemblance to the in vivo energy substrate pool. Our results suggest that energy deficits induce unfavorable changes in E(m) and E(GABA), leading to neuronal hyperactivity that may initiate a cascade of pathological events.
Medina, J. M. (1985). The role of lactate as an energy substrate for the brain during the early neonatal period. Biology of the neonate, 48(4), 237–44. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/3904842
The role played by lactate as an energy substrate for the newborn rat during the early neonatal period was studied. Plasma lactate is mostly removed within the first 2 h after delivery, i.e. during the presuckling period. Lactate removal was enhanced by hyperoxia but strongly inhibited by hypoxia, showing a direct correlation with blood oxygen concentrations. Lactate was not converted into glucose during the presuckling period, gluconeogenesis being insignificant in these circumstances; instead it was rapidly oxidized through the tricarboxylic acid cycle. Likewise, lactate was significantly oxidized by brain slices from newborns at birth. At physiological concentrations, lactate oxidation by brain slices was 10- and 3-fold higher than that of glucose and 3-hydroxybutyrate, respectively. In the same circumstances, lipogenesis de novo from lactate was 2- and 5-fold higher than from glucose and 3-hydroxybutyrate, respectively. The results suggest that lactate is the main metabolic fuel for the brain during the early neonatal period.
Vicario, C., Arizmendi, C., Malloch, G., Clark, J. B., & Medina, J. M. (1991). Lactate utilization by isolated cells from early neonatal rat brain. Journal of neurochemistry, 57(5), 1700–7. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1919582
The utilization of lactate, glucose, 3-hydroxybutyrate, and glutamine has been studied in isolated brain cells from early newborn rats. Isolated brain cells actively utilized these substrates, showing saturation at concentrations near physiological levels during the perinatal period. The rate of lactate utilization was 2.5-fold greater than that observed for glucose, 3-hydroxybutyrate, or glutamine, suggesting that lactate is the main metabolic substrate for the brain immediately after birth. The apparent Km for glucose utilization suggested that this process is limited by the activity of hexokinase. However, lactate, 3-hydroxybutyrate, and glutamine utilization seems to be limited by their transport through the plasma membrane. The presence of fatty acid-free bovine serum albumin (BSA) in the incubation medium significantly increased the rate of lipogenesis from lactate or 3-hydroxybutyrate, although this was balanced by the decrease in their rates of oxidation in the same circumstances. BSA did not affect the rate of glucose utilization. The effect of BSA was due not to the removal of free fatty acid, but possibly to the binding of long-chain acyl-CoA, resulting in the disinhibition of acetyl-CoA carboxylase and citrate carrier.
Vicario, C., & Medina, J. M. (1992). Metabolism of lactate in the rat brain during the early neonatal period. Journal of neurochemistry, 59(1), 32–40. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1613508
The metabolism of lactate in isolated cells from early neonatal rat brain has been studied. In these circumstances, lactate was mainly oxidized to CO2, although a significant portion was incorporated into lipids (78% sterols, 4% phosphatidylcholine, 2% phosphatidylethanolamine, and 1% phosphatidylserine). The rate of lactate incorporation into CO2 and lipids was higher than those found for glucose and 3-hydroxybutyrate. Lactate strongly inhibited glucose oxidation through the pyruvate dehydrogenase-catalyzed reaction and the tricarboxylic acid cycle while scarcely affecting glucose utilization by the pentose phosphate pathway. Lipogenesis from glucose was strongly inhibited by lactate without relevant changes in the rate of glycerol phosphate synthesis. These results suggest that lactate inhibits glucose utilization at the level of the pyruvate dehydrogenase-catalyzed reaction, which may be a mechanism to spare glucose for glycerol and NADPH synthesis. The effect of 3-hydroxybutyrate inhibiting lactate utilization only at high concentrations of 3-hydroxybutyrate suggests that before ketogenesis becomes active, lactate may be the major fuel for the neonatal brain. (-)-Hydroxycitrate and aminooxyacetate markedly inhibited lipogenesis from lactate, suggesting that the transfer of lactate carbons through the mitochondrial membrane is accomplished by the translocation of both citrate and N-acetylaspartate.
Adam, P. A., Räihä, N., Rahiala, E. L., & Kekomäki, M. (1975). Oxidation of glucose and D-B-OH-butyrate by the early human fetal brain. Acta paediatrica Scandinavica, 64(1), 17–24. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1114894
The isolated brains of 12 previable human fetuses obtained at 12 to 21 weeks’ gestation, were perfused through the interval carotid artery with glucose (3 mM) and/or DL-B-OH-butyrate (DL-BOHB), 4.5 MM, plus tracer quantities of either glucose-6-14C (G6-14C) or beta-OH-butyrate-3-14C (BOHB3-14C). Oxidative metabolism was demonstrated by serial collection of gaseous 14CO2 from the closed perfusion system, and from the recirculating medium. Glucose and BOHB were utilized at physiological rates as indicated (mean plus or minus SEM): G6-14C at 0.10 plus or minus 0.01 mumoles/min g brain (n equal 7) or 17.5 plus or minus 1.9 mumoles/min kg fetus; and BOHB3-14C at 0.16 plus or minus 0.05 mumoles/min g (n equal to 5) or 27.3 plus or minus 7.4 mumoles/min kg. Based on fetal weight, glucose metabolism by brain apparently accounted for about 1/3 of basal glucose utilization in the fetus. On a molar basis BOHB3-14C was taken up at 1.47 times the rate of G6-14C. Both BOHB3-14C and G6 14C were converted to 14CO2. The rate of BOHB3-14C conversion to 14CO2 was equal to its rate of consumption, and exceeded the conversion of glucose to CO2 because 45% of the G6-14C was incorporated into lactate-14C. Accordingly, both substrates support oxidative metabolism by brain; and BOHB is a major potential alternate fuel which can replace glucose early in human development.
Freinkel, N., Cockroft, D. L., Lewis, N. J., Gorman, L., Akazawa, S., Phillips, L. S., & Shambaugh, G. E. (1986). The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture. The American journal of clinical nutrition, 44(6), 986–95. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/3788845
Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.
Nishii, Y., Ichikawa, K., Miyamoto, T., Takeda, T., Kobayashi, M., Suzuki, S., … Hashizume, K. (1993). n-Butyrate enhances induction of thyroid hormone-responsive nuclear protein. Endocrine journal, 40(5), 515–21. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7951517
Effects of n-butyrate on nuclear thyroid hormone receptors and on thyroid hormone-responsive nuclear protein were investigated by means of a perfusion system in rat liver. Treatment with 5 mM n-butyrate resulted in an increase (150%) in the maximal binding capacity of 3,5,3’-L-triiodothyronine (T3) nuclear receptors without altering the affinity of receptor for T3. However, further perfusion for 4 h decreased the number of the receptors to the control level. n-Butyrate increased the amount of acetylated histone H4. The ability of nuclear T3 receptors to bind to core histones was diminished by acetylation of the core histones. Thyroid hormone-responsive nuclear protein (n protein) was increased by T3. The induction of the n protein by T3 was augmented by n-butyrate. These results suggested that n-butyrate modulates thyroid hormone-responsive gene expression in rat liver via the increased number of nuclear receptors or changes in the chromatin constitution.
Some people in nutritional science are aware that the polyunsaturated fats such as those found in industrial vegetable oils can be harmful. But few people that I’ve read seem to illustrate why PUFA are harmful in a way that gives a logical understanding. When someone says something is harmful they are merely stating something. It does not mean they actually understand the “why”. A person might read a study and the study might be correct and that person may regurgitate what was in the study. Though the person may be informed they lack the visual pictures painted in the mind that helps to form a basis from which other conclusions can be drawn. In other words, they have no real understanding. That phenomenon is rampant in nutritional science. From a practical standpoint that approach may work, but for a person who is in a complicated situation or trying to understand more than that, the approach is limited, and taking shots in the dark could have negative consequences.
In order to understand the world around us, we cannot just memorize facts and connect dots. It leads to superficial understanding.
Many people have said that polyunsaturated fats are harmful and have provided evidence for why by putting together pieces of their effects in different contexts. But that does nothing in the end to help us to predict upstream and downstream effects, in that approach we are without prediction power for making rational choices.
In your body you have different lipid-like hormones and nutrients. A lot of these hormones and nutrients are unsaturated. In other words, they resemble the polyunsaturated fatty acids. In a body that doesn’t have bottles of corn oil floating around, these unsaturated hormones and nutrients bind to the cells as they should, like putting a key into a keyhole. Though that is a rather mechanical way of thinking about it, the analogy is useful. When you consume polyunsaturated fats they in effect bind to the same places your hormones would normally bind. As long as the body remains fairly unstressed this poses minimal problems in the short term.
Under stress, however, the body releases the protective hormones. If the body is saturated with the polyunsaturated fats, the unsaturated hormones can no longer bind. Over time, the body can no longer respond to stress efficiently because the protective hormones can no longer function, in effect, the polyunsaturated fats are mimicking the binding of unsaturated hormones blocking the protective hormones from functioning.
Over time, as we age, we gradually lose the ability to respond to stress because of this process. In other words, resistance to stress is the ability to respond to stress efficiently. As we lose the efficiency to respond to stress, we age because we are unable to repair the damage caused by stress. In other words, aging is a feature of the body not being able to respond to stress efficiently and completely. Stasis must shift to maintain balance. It is the shifting process that can be problematic.
In the cell there is an organelle called the peroxisome. The peroxisomes break down lipid like substances or xenobiotic compounds. In other words, they protect the cell from foreign compounds. That seems to be one of their primary functions.
What is interesting here is that the mitochondria work in a similar parallel when they metabolize oxygen.
I had known from prior research that the polyunsaturated fats cause problems with cellular respiration by reducing the efficiency of the mitochondria, thus overall efficiency of the cell, in a sense turning the mitochondria into “mush”. Different fuel substrates have differing efficiency, so I needed something more, something that pointed to a problem with the nature of polyunsaturated fats themselves.
When a cell is exposed to PUFA the peroxisomes proliferate or increase in number rapidly. Peroxisomes are especially sensitive to the unsaturated fatty acids. In the laboratory, fish oil is commonly used in their study. Interestingly, the saturated fats do not cause proliferation in most cases. It is also interesting that cholesterol lowering drugs also cause peroxisome proliferation. Remember: peroxisomes proliferate when exposed to harmful substances.
So the cells can, to some extent, protect themselves from PUFA by breaking them down. Given that, why can’t we consume PUFA with a clear conscious? And why do some people seem to be able to eat more than others?
Part 2 shortly.
Bergamo, P., Gogliettino, M., Palmieri, G., Cocca, E., Maurano, F., Stefanile, R., … Rossi, M. (2011). Conjugated linoleic acid protects against gliadin-induced depletion of intestinal defenses. Molecular nutrition & food research, 55 Suppl 2, S248–56. doi:10.1002/mnfr.201100295
SCOPE: The involvement of oxidative stress in gluten-induced toxicity has been evidenced in vitro and in clinical studies but has never been examined in vivo. We recently demonstrated the protective activity of conjugated linoleic acid (CLA), which functions by the activation of nuclear factor erythroid 2-related factor2 (Nrf2), a key transcription factor for the synthesis of antioxidant and detoxifying enzymes (phase 2). Here, we evaluate the involvement of nuclear factor erythroid 2-related factor2 in gliadin-mediated toxicity in human Caco-2 intestinal cells and in gliadin-sensitive human leukocyte antigen-DQ8 transgenic mice (DQ8) and the protective activity of CLA.
METHODS AND RESULTS: Gliadin effects in differentiated Caco-2 cells and in DQ8 mice, fed with a gliadin-containing diet with or without CLA supplementation, were evaluated by combining enzymatic, immunochemical, immunohistochemical, and quantitative real-time PCR (qRT-PCR) assays. Gliadin toxicity was accompanied by downregulation of phase 2 and elevates proteasome-acylpeptide hydrolase activities in vitro and in vivo. Notably, gliadin was unable to generate severe oxidative stress extent or pathological consequences in DQ8 mice intestine comparable to those found in celiac patients and the alterations produced were hampered by CLA.
CONCLUSION: The beneficial effects of CLA against the depletion of crucial intestinal cytoprotective defenses indicates a novel nutritional approach for the treatment of intestinal disease associated with altered redox homeostasis.
Effective now all future posts will be at this address: http://thebittercitizen.wordpress.com/
As of now there is no system to what I’ve been posting, I prefer to write on a whim and post whatever I happen to be thinking about (it keeps my stress hormones down) but I expect things to become more organized and hopefully more useful as time progresses because there does seem to be people who are reading my opinions. There will also be another author writing posts as well giving a female perspective on different topics.
Ultimately my goal is to get people thinking about how the body works in different contexts and learn how to adapt to the adaptations the body makes throughout our lifespans. I don’t know all the answers. But I always welcome questions and comments.
Once I solve hosting issues the site will then have a seamless move to thebittercitizen.com
The lactate shuttle theory has been around for a couple of decades. Essentially, it is associated with the idea that the brain prefers lactate as an energy substrate, but lactate shuttle theory is actually describing a (proposed) mechanism, not the implications. I had been aware of the idea, but was not sure of the context of functionality. From some prior research I had found that the brain stores glycogen.
Peter has a brief post on this.
You always find a high concentration of GLUTx transporters in high energy organs. Having a high concentration of GLUTx transporters points to earlier times and to some interesting ideas.
The fact that ROS (reactive oxygen species) from glucose causes problems in the brain has always seemed strange to me given the common idea that the brain prefers glucose. Bypassing glucose metabolism with either fructose 1,6-bisphosphate or ketones has anticonvulsant activity. Given the composition of the fatty acids in the brain ROS seems like a really really bad idea, and it is probably the reason that if ROS is reduced things start working better.
When I started researching neonatal ketosis, I saw that besides the elevated ketones in neonates, lactate was also elevated. Ketones and lactate seem to be essential for a developing brain. Here are some papers on lactate below that can be tied in with the neonatal ketosis post.
So given this, the question is why? Why in neonates are ketones and lactate elevated? Does the status of a neonate represent an optimal status that we as adults should mimic, or is the status of the neonate a contextual adaptation? I have my own ideas as to why. What are some of your thoughts?
Gladden, L. B. (2008). A lactatic perspective on metabolism. Medicine and science in sports and exercise, 40(3), 477–85. doi:10.1249/MSS.0b013e31815fa580
Hashimoto, T., & Brooks, G. A. (2008). Mitochondrial lactate oxidation complex and an adaptive role for lactate production. Medicine and science in sports and exercise, 40(3), 486–94. doi:10.1249/MSS.0b013e31815fcb04
Holmgren, C. D., Mukhtarov, M., Malkov, A. E., Popova, I. Y., Bregestovski, P., & Zilberter, Y. (2010). Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro. Journal of neurochemistry, 112(4), 900–12. doi:10.1111/j.1471-4159.2009.06506.x
Kasischke, K. (2011). Lactate fuels the neonatal brain. Frontiers in neuroenergetics, 3(June), 4. doi:10.3389/fnene.2011.00004
Philp, A., Macdonald, A. L., & Watt, P. W. (2005). Lactate–a signal coordinating cell and systemic function. The Journal of experimental biology, 208(Pt 24), 4561–75. doi:10.1242/jeb.01961
Tyzio, R., Allene, C., Nardou, R., Picardo, M. A., Yamamoto, S., Sivakumaran, S., … Ben-Ari, Y. (2011). Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(1), 34–45. doi:10.1523/JNEUROSCI.3314-10.2011
Wyss, M. T., Jolivet, R., Buck, A., Magistretti, P. J., & Weber, B. (2011). In vivo evidence for lactate as a neuronal energy source. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(20), 7477–85. doi:10.1523/JNEUROSCI.0415-11.2011
Zilberter, Y., Zilberter, T., & Bregestovski, P. (2010). Neuronal activity in vitro and the in vivo reality: the role of energy homeostasis. Trends in pharmacological sciences, 31(9), 394–401. doi:10.1016/j.tips.2010.06.005
Jean, C., Fromentin, G., Tomé, D., & Larue-Achagiotis, C. (2002). Wistar rats allowed to self-select macronutrients from weaning to maturity choose a high-protein, high-lipid diet. Physiology & behavior, 76(1), 65–73. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12175590
The aim of this work was to study the evolution of rat food choice in relation to their age and metabolic parameters. Eighty Wistar rats were studied from birth to 13 weeks of age. At weaning, six litters were fed on a macronutrient self-selecting diet and four on a standard diet. In self-selecting males, protein intake was maximal at Week 7 of age and then plateaued (Week 13), whereas in females, protein consumption peaked at Week 7 and then steadily decreased. Females showed a strong and early preference for fat, which increased continuously with age. Males and females ingested their total energy intake during the dark period (respectively, 79% and 70%). Simple meals (composed of one item) were mainly ingested during the light phase, while mixed meals (at least two items) were ingested during the night. In males, most mixed meals began with carbohydrate bouts and finished with proteins, while in females no particular choice was observed at the beginning of meals, but most of them ended with protein bouts. Body weights of either male and female self-selecting or control fed rats were not significantly different at the end of the experiment. Differences between dietary groups in body fat mass were not observed with the exception of higher subcutaneous fat found in self-selecting rats. Moreover, insulinemia was lower in both male and female self-selecting rats. The high-protein, high-fat diet chosen by the self-selecting rats could be linked to a prevention of the age-related insulin resistance.
- Came across this interesting omnivorous animal this morning on “The High-fat Hep C Diet” blog. One of the more interesting things I’ve come across this year.
- This fence building spider was interesting as well. Is the pole in the middle for tether ball (kidding)?
- Food for thought, er, worms for vitamin C? Interesting idea.
- Is it the yogurt or honey? The brain seems to like lactate. The brain can also store glycogen and it probably converts it to lactate (whether or not that is a good thing I don’t know, but healthy babies have elevated lactate levels besides the ketones, nonetheless it is still not clear whether lactate is an emergency substrate or preferred) However, the main components in different honey are fairly similar, the glucose and fructose part. If two different brands of honey have different effects, then we can more than likely eliminate the sugar component and look at other properties of various kinds of honey. Different kinds of honey have different antimicrobial properties and contaminants. A little hormesis to improve sleep? How does endotoxin impact sleep? (Personally, honey ruins my sleep even in tiny amounts and so does sugar. Sugar also negatively impacts my typing tests.)
Stewart, W. K., & Fleming, L. W. (1973). Features of a successful therapeutic fast of 382 days’ duration. Postgraduate medical journal, 49(569), 203–9. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2495396&tool=pmcentrez&rendertype=abstract
A 27-year-old male patient fasted under supervision for 382 days and has subsequently maintained his normal weight. Blood glucose concentrations around 30 mg/100 ml were recorded consistently during the last 8 months, although the patient was ambulant and attending as an out-patient. Responses to glucose and tolbutamide tolerance tests remained normal. The hyperglycaemic response to glucagon was reduced and latterly absent, but promptly returned to normal during carbohydrate refeeding. After an initial decrease was corrected, plasma potassium levels remained normal without supplementation. A temporary period of hypercalcaemia occurred towards the end of the fast. Decreased plasma magnesium concentrations were a consistent feature from the first month onwards. After 100 days of fasting there was a marked and persistent increase in the excretion of urinary cations and inorganic phosphate, which until then had been minimal. These increases may be due to dissolution of excessive soft tissue and skeletal mass. Prolonged fasting in this patient had no ill-effects.
Devasagayam, T. P., Kamat, J. P., Mohan, H., & Kesavan, P. C. (1996). Caffeine as an antioxidant: inhibition of lipid peroxidation induced by reactive oxygen species. Biochimica et biophysica acta, 1282(1), 63–70. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8679661
Caffeine (1,3,7-trimethyl xanthine), an ingredient of coffee, has been investigated for its potential antioxidant activity against oxidative damage to rat liver microsomes. Such damage was induced by three reactive oxygen species of cardinal importance in causing membrane damage in vivo namely hydroxyl radical (.OH), peroxyl radical (ROO.) and singlet oxygen (1O2). The results obtained showed that caffeine was an effective inhibitor of lipid peroxidation, at millimolar concentrations, against all the three reactive species. The extent of inhibition was high against peroxidation induced by .OH, medium against 1O2 and low against ROO. In general, the antioxidant ability of caffeine was similar to that of the established biological antioxidant glutathione and significantly higher than ascorbic acid. Investigations into the possible mechanisms involved in the observed antioxidant effect reveal that the quenching of these reactive species by caffeine may be one of the possible factor responsible. The rate constant of caffeine with .OH was 7.3 x 10(9) M-1 s-1 and with 1O2 it was 2.9 x 10(7) M-1 s-1. Considering their potential for damage, half-life estimates and generation in biological systems, the ability of caffeine to inhibit oxidative damage induced by these reactive species in membranes suggest one more positive attribute of caffeine, whose daily intake as coffee may be considerable in most populations.
Onodera, Y., Nam, J.-M., & Bissell, M. J. (2013). Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. The Journal of clinical investigation, 124(1). doi:10.1172/JCI63146
There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. Unexpectedly and importantly, we found that unlike reported literature, in 3D the differences between “normal” and malignant phenotypes could not be explained by HIF-1α/2α, AMPK, or mTOR pathways. Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics.
Møller, P., Vogel, U., Pedersen, A., Dragsted, L. O., Sandström, B., & Loft, S. (2003). No effect of 600 grams fruit and vegetables per day on oxidative DNA damage and repair in healthy nonsmokers. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 12(10), 1016–22. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/14578137
In several epidemiological studies, high intakes of fruits and vegetables have been associated with a lower incidence of cancer. Theoretically, intake of antioxidants by consumption of fruits and vegetables should protect against reactive oxygen species and decrease the formation of oxidative DNA damage. We set up a parallel 24-day dietary placebo-controlled intervention study in which 43 subjects were randomized into three groups receiving an antioxidant-free basal diet and 600 g of fruits and vegetables, or a supplement containing the corresponding amounts of vitamins and minerals, or placebo. Blood and urine samples were collected before, once a week, and 4 weeks after the intervention period. The level of strand breaks, endonuclease III sites, formamidopyrimidine sites, and sensitivity to hydrogen peroxide was assessed in mononuclear blood cells by the comet assay. Excretion of 7-hydro-8-oxo-2’-deoxyguanine was measured in urine. The expressions of oxoguanine glycosylase 1 and excision repair cross complementing 1 DNA repair genes, determined by real-time reverse transcription-PCR of mRNAs, were investigated in leukocytes. Consumption of fruits and vegetables or vitamins and minerals had no effect on oxidative DNA damage measured in mononuclear cell DNA or urine. Hydrogen peroxide sensitivity, detected by the comet assay, did not differ between the groups. Expression of excision repair cross complementing 1 and oxoguanine glycosylase 1 in leukocytes was not related to the diet consumed. Our results show that after 24 days of complete depletion of fruits and vegetables, or daily ingestion of 600 g of fruit and vegetables, or the corresponding amount of vitamins and minerals, the level of oxidative DNA damage was unchanged. This suggests that the inherent antioxidant defense mechanisms are sufficient to protect circulating mononuclear blood cells from reactive oxygen species.
Andersen, I. M., Tengesdal, G., Lie, B. A., Boberg, K. M., Karlsen, T. H., & Hov, J. R. (2013). Effects of Coffee Consumption, Smoking, and Hormones on Risk for Primary Sclerosing Cholangitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. doi:10.1016/j.cgh.2013.09.024
BACKGROUND & AIMS: Little is known about nongenetic risk factors for primary sclerosing cholangitis (PSC), except a possible protective effect of smoking. We investigated the relationship between environmental risk factors and susceptibility to PSC. METHODS: A questionnaire was distributed to patients with PSC, recruited from Oslo University Hospital Rikshospitalet in Norway through 2011, and randomly chosen individuals from the Norwegian Bone Marrow Donor Registry (control subjects). Data were analyzed from 240 patients with PSC and 245 control subjects, matched for gender and age. RESULTS: A lower proportion of patients with PSC were daily coffee drinkers than control subjects, both currently (76% vs 86%; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.32-0.82; P = .006) and at the age of 18 years (35% vs 49%; OR, 0.58; 95% CI, 0.40-0.83; P = .003). The associations were mainly attributed to differences observed in men. Twenty percent of the patients were ever (current or former) daily smokers compared with 43% of control subjects (OR, 0.33; 95% CI, 0.22-0.50; P < .001). Ever daily smoking before PSC diagnosis was associated with older age at diagnosis (42 years vs 32 years; P < .001). Ever daily smoking (P < .001) and being a coffee drinker at the age of 18 years (P = .048) were independently and negatively associated with PSC. Fewer female patients with PSC than control subjects reported ever use of hormonal contraception (51% vs 85%; P < .001). Among female patients, there was a strong correlation between increasing number of children before the diagnosis of PSC and increasing age at diagnosis (r = 0.63; P < .001). CONCLUSIONS: Coffee consumption and smoking might protect against development of PSC. In women, the disease might be influenced by hormonal factors.
Maalouf, M., Sullivan, P. G. G., Davis, L., Kim, D. Y. Y., & Rho, J. M. M. (2007). Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience, 145(1), 256–64. doi:10.1016/j.neuroscience.2006.11.065
Dietary protocols that increase serum levels of ketones, such as calorie restriction and the ketogenic diet, offer robust protection against a multitude of acute and chronic neurological diseases. The underlying mechanisms, however, remain unclear. Previous studies have suggested that the ketogenic diet may reduce free radical levels in the brain. Thus, one possibility is that ketones may mediate neuroprotection through antioxidant activity. In the present study, we examined the effects of the ketones beta-hydroxybutyrate and acetoacetate on acutely dissociated rat neocortical neurons subjected to glutamate excitotoxicity using cellular electrophysiological and single-cell fluorescence imaging techniques. Further, we explored the effects of ketones on acutely isolated mitochondria exposed to high levels of calcium. A combination of beta-hydroxybutyrate and acetoacetate (1 mM each) decreased neuronal death and prevented changes in neuronal membrane properties induced by 10 microM glutamate. Ketones also significantly decreased mitochondrial production of reactive oxygen species and the associated excitotoxic changes by increasing NADH oxidation in the mitochondrial respiratory chain, but did not affect levels of the endogenous antioxidant glutathione. In conclusion, we demonstrate that ketones reduce glutamate-induced free radical formation by increasing the NAD+/NADH ratio and enhancing mitochondrial respiration in neocortical neurons. This mechanism may, in part, contribute to the neuroprotective activity of ketones by restoring normal bioenergetic function in the face of oxidative stress.
Yukiko, H., Takashi, K., & Takashi, S. (1967). Fatty liver induced by injection of l-tryptophan. Biochimica et Biophysica Acta (BBA) – Lipids and Lipid Metabolism, 144(2), 233–241. Retrieved from http://www.sciencedirect.com/science/article/pii/0005276067901531
l-Tryptophan caused the accumulation of neutral lipids in liver within 2.5 h after its intraperitoneal injection into rats. This accumulation of neutral lipids continued for about 24 h. Peripheral fatty liver was diagnosed histologically by Sudan III staining. The minimal effective dose was 0.5 mg/g of body weight. The level of cholesterol and phospholipids in liver did not alter. 3-Hydroxyanthranilic acid and l-kynurenine were as effective as l-tryptophan in inducing the accumulation of neutral lipids, but other metabolites of tryptophan, kynurenic acid, anthranilic acid, quinolinic acid, nicotinic acid and nicotinamide did not produce the lipid accumulation. The administration of other amino acids, such as l-leucine, l-lysine, l-tyrosine, l-threonine and l-methionine, did not increase the amount of total lipids in liver. Simultaneous administration of ATP, ADP, AMP, adenosine or folic acid with l-tryptophan prevented the fatty liver. A marked decrease in the concentration of ATP in the liver was shown by the administration of l-tryptophan or l-kynurenine. These observations support the concept that l-tryptophan-induced fatty liver is due to the decreased level of ATP. A possible mechanism of ATP depression by administered l-tryptophan is discussed.
Kang, J. X., Xiao, Y. F., & Leaf, A. (1995). Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes. Proceedings of the National Academy of Sciences, 92(9), 3997–4001. doi:10.1073/pnas.92.9.3997
Because previous studies showed that polyunsaturated fatty acids can reduce the contraction rate of spontaneously beating heart cells and have antiarrhythmic effects, we examined the effects of the fatty acids on the electrophysiology of the cardiac cycle in isolated neonatal rat cardiac myocytes. Exposure of cardiomyocytes to 10 microM eicosapentaenoic acid for 2-5 min markedly increased the strength of the depolarizing current required to elicit an action potential (from 18.0 +/- 2.4 pA to 26.8 +/- 2.7 pA, P < 0.01) and the cycle length of excitability (from 525 ms to 1225 ms, delta = 700 +/- 212, P < 0.05). These changes were due to an increase in the threshold for action potential (from -52 mV to -43 mV, delta = 9 +/- 3, P < 0.05) and a more negative resting membrane potential (from -52 mV to -57 mV, delta = 5 +/- 1, P < 0.05). There was a progressive prolongation of intervals between spontaneous action potentials and a slowed rate of phase 4 depolarization. Other polyunsaturated fatty acids–including docosahexaenoic acid, linolenic acid, linoleic acid, arachidonic acid, and its nonmetabolizable analog eicosatetraynoic acid, but neither the monounsaturated oleic acid nor the saturated stearic acid–had similar effects. The effects of the fatty acids could be reversed by washing with fatty acid-free bovine serum albumin. These results show that free polyunsaturated fatty acids can reduce membrane electrical excitability of heart cells and provide an electrophysiological basis for the antiarrhythmic effects of these fatty acids.
It’s something I don’t really understand. It’s like saying, you have a diet of higher fat that is not conducive to high metabolic rate, but you add in a few hormones and it’s fixed. But if the fat diet provided enough energy, why do these hormones naturally decline in the first place? How can hormones compensate for an energy problem?
I think Edward must have a good explanation for this, because his posts have hinted about good thyroid not being incompatible with higher fat ratio.
The underlying explanation is that there is a difference between saturated free fatty acids and polyunsaturated free fatty acids. Essentially you self-induce mitochondrial diseases with polyunsaturated free fatty acids; you can’t do that with saturated free fatty acids. There is a longer post here but sadly no time. Sometime after the 16th.
Glasauer, A., Sena, L. A., Diebold, L. P., Mazar, A. P., & Chandel, N. S. (2013). Targeting SOD1 reduces experimental non-small-cell lung cancer. The Journal of clinical investigation, 124(1). doi:10.1172/JCI71714
Approximately 85% of lung cancers are non-small-cell lung cancers (NSCLCs), which are often diagnosed at an advanced stage and associated with poor prognosis. Currently, there are very few therapies available for NSCLCs due to the recalcitrant nature of this cancer. Mutations that activate the small GTPase KRAS are found in 20% to 30% of NSCLCs. Here, we report that inhibition of superoxide dismutase 1 (SOD1) by the small molecule ATN-224 induced cell death in various NSCLC cells, including those harboring KRAS mutations. ATN-224-dependent SOD1 inhibition increased superoxide, which diminished enzyme activity of the antioxidant glutathione peroxidase, leading to an increase in intracellular hydrogen peroxide (H2O2) levels. We found that ATN-224-induced cell death was mediated through H2O2-dependent activation of P38 MAPK and that P38 activation led to a decrease in the antiapoptotic factor MCL1, which is often upregulated in NSCLC. Treatment with both ATN-224 and ABT-263, an inhibitor of the apoptosis regulators BCL2/BCLXL, augmented cell death. Furthermore, we demonstrate that ATN-224 reduced tumor burden in a mouse model of NSCLC. Our results indicate that antioxidant inhibition by ATN-224 has potential clinical applications as a single agent, or in combination with other drugs, for the treatment of patients with various forms of NSCLC, including KRAS-driven cancers.