“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.