Essential Fatty Acids: There Is a Lot to Explain

Nutritional adequacy is a relationship between what an organism can obtain and what its circumstances require. I used to think about essential fatty acids as though establishing their presence in the diet settled that relationship. If you ate animal products, you would get some. Depending on the animal, perhaps more, perhaps less. The practical question appeared to have been answered.

It was a reassuring conclusion for a calculation I hadn’t actually done.

In 2019, when I published the first post in my essential fatty acid series, I had already been running self-experiments for a number of years. I had expected this particular subject to be relatively easy to cover. What complicated it was the recognition that I had thought much more about the presence of a nutrient than about the conditions governing its adequacy. I knew to ask what was in the food. I had been less attentive to what was being asked of the organism eating it.

Over several years, I conducted a comprehensive review of the essential fatty acid literature, following almost a century of research from the early Burr and Burr experiments through relatively recent work. The notes I eventually published were the residue of that review: compressed entries marking discussions I intended to develop individually. Intravenous feeding. Skin. Wound healing. Vitamin interactions. Behavior. On the page, they could look like unrelated curiosities. In the research, they kept returning me to the same problem: how an organism meets the material demands of maintaining itself under changing conditions.

This essay is an introduction to that larger story.

It has a personal history as well. I’ve been deliberately seeking out and consuming sources of linoleic acid for close to a decade, and doing so became a vital part of my own health. That experience gave the subject a practical importance I couldn’t dismiss. The literature supplied the experimental history through which I could think more carefully about it. Both mattered, though they answered different kinds of questions.

The change in my thinking was fundamentally ecological. An organism lives under conditions that place demands on it, and those demands affect what counts as adequate. Maintenance, repair, and adaptation have material costs. A diet’s composition tells us something about the resources entering the system; understanding sufficiency also requires an account of the work the system is doing.

Severe injury makes the distinction unusually clear. Tissue has to be repaired, and the metabolic circumstances under which that repair occurs have changed. Even nutrients already stored in the body may be less accessible under particular feeding conditions. The presence of a reserve and the ability to draw on it are separate facts. [1]

I began applying that way of thinking to a longer history. How had the conditions of life changed over a hundred years, two hundred years, and beyond? Modernity can make food more accessible while introducing demands that are persistent, unfamiliar, or difficult to recover from. My interest was in how those changing conditions might alter the requirements for adaptation. Extending the clinical principle to everyday stress is part of the broader ecological argument I hope to develop over time.

That led me into the economics of seed oil production. The growth of demand for oils and the increasing complexity of civilization began to look like parts of a discussion that nutrition tends to divide into separate departments. Producing food, transporting it, and keeping it usable have economic costs. Living within the arrangements that make those things possible has physiological costs. Civilization is generous with conveniences; the invoice is less conspicuous.

I think the essential fatty acid literature I reviewed, from Burr and Burr onward, contains substantial direct and indirect evidence relevant to that account of stress and adaptation. The larger interpretation still requires its connections to be made explicitly. An increase in oil consumption cannot, on its own, establish an increase in biological need. It can, however, make us examine what we mean by supply and demand when both the food system and the organisms within it are changing.

The supply side contained an assumption of its own. With seed oils so abundant, I had barely considered whether essential fatty acid deficiency could remain a practical possibility. The abundance seemed to settle the matter before the physiology had been invited into the room.

Then I considered what was happening to the oils.

High-oleic varieties are a particularly useful example. Increasing oleic acid at the expense of polyunsaturated fatty acids can improve an oil’s stability during frying. That is a meaningful advantage for the people producing and using it. The same change also alters its nutritional composition. A familiar crop name can therefore conceal a substantially different mixture of fatty acids. The label has continuity; the chemistry may not. [2]

The history reaches back to high-oleic sunflower breeding in the 1970s, near the period when obesity began increasing markedly in the United States. That proximity deserves a careful chronology. It also presents a familiar temptation: to make dates perform the work of a mechanism. A variety must be developed, adopted, and consumed in quantities that change intake before a claim about its population effects can be evaluated. Each step belongs in the account. [3]

There is a more immediate implication for the way food availability is estimated. If an oil’s composition changes while a dataset continues to assign it an older fatty acid profile, the resulting estimate of available linoleic acid can be wrong even when the total quantity of oil is recorded correctly. Establishing whether a particular dataset has this problem requires checking its methods, the varieties being sold, and their market share. The inference follows from the composition change; its importance in any actual food supply has to be measured.

My original confidence in animal foods brought the issue back around. The animal had a diet too. In pigs, altering the dietary fat can alter the fatty acid composition of the pork. An animal product is therefore part of the same ecological and agricultural history I had been treating as someone else’s problem. [4]

By then, the question had expanded in both directions. The environment could change the demands placed on the organism, while production and feeding practices could change what reached it. Between supply and need lay another set of conditions: whether a nutrient could be mobilized, transported, and used. This was the setting in which the deficiency experiments began to make considerably more sense.

They are also where the story becomes pleasantly inconvenient.

In studies of continuous, fat-free feeding, people supplied with adequate calories developed biochemical signs of essential fatty acid deficiency within days to weeks. A simple account based on gradually exhausting all body-fat reserves has difficulty with that time course. The measurements did not establish that every reserve had disappeared. They showed a response under a particular nutritional regimen, which made the regimen itself part of the explanation.

Changing the feeding conditions changed the picture. In a small study of surgical patients given amino acids without glucose or fat, stored linoleic acid was mobilized and biochemical deficiency did not develop during the short observation period. Set beside the continuous glucose–amino acid feeding studies, this makes the distinction between possession and availability difficult to ignore. [5]

A reserve is useful only insofar as it can supply the work being done. That is a modest statement, but it complicates a great deal of nutritional reasoning. We can count what enters the body and still miss the conditions that determine whether it reaches its destination. We can also count what remains stored and mistake that inventory for an explanation of tissue function.

The blood measurements deserve the same scrutiny. Mead acid appears repeatedly in this literature as a marker of essential fatty acid deficiency. The phrase is familiar enough to conceal the interesting part: how did a particular molecule acquire that meaning?

In 1956, Mead and Slaton isolated it from fat-deficient rats. Holman subsequently varied the linoleic acid supplied in rat diets and measured the response in tissue fatty acids. As dietary linoleate increased, trienoic acids declined while tetraenoic acids increased toward a plateau. Their ratio condensed a response to changing supply into a measurement that could be used to assess adequacy. The marker had an experimental history before it acquired the apparent inevitability of a laboratory result. [6]

There is a mechanism behind the pattern. When essential fatty acids are scarce, the body can synthesize Mead acid from oleic acid, using enzymes that also participate in processing essential fatty acids. A rise in Mead acid alongside a fall in arachidonic acid therefore reflects an altered metabolic situation. The organism is responding to the conditions in which it finds itself.

Recognizing that response opens a second question: what does the response do?

Mead acid has effects of its own. In rats whose diets already supplied sufficient essential fatty acids, adding Mead acid changed the production of an inflammatory signal by stimulated immune cells. That experimental separation matters. It allows an effect of the molecule to be examined without requiring the entire state of deficiency to accompany it. [7]

A deficiency, a compensatory response, and a symptom can occur together without being interchangeable explanations. Some consequences may arise from what is missing; others may involve what the organism produces under those circumstances. Assigning all of them to whichever molecule happens to be elevated is an efficient way to acquire certainty. It is a less efficient way to understand the experiment.

This is also where the discussion of Mead acid, cartilage, and joint function belongs. The biochemical findings provide a foundation for examining proposed connections with joint deterioration. The proposed connections have to earn their place through evidence about the tissue and its function. An elevated measurement cannot carry the whole argument by itself.

Following the evidence into tissues changes the scale of the discussion. Skin gives us a visible consequence, but visibility does not necessarily simplify the explanation. A patient can be deficient in more than one nutrient, and a successful intervention can restore several things at once. The result is real even when its attribution remains incomplete. [8]

Hair and skin changes occupied several entries in my notes, including their resemblance to changes associated with impaired thyroid function. That resemblance creates a question about mechanisms: what produces a similar appearance under different conditions? From there, the discussion reaches epithelial maintenance more broadly, including the intestinal lining. A phrase such as “gut permeability” becomes more useful when we can explain what the cells forming the barrier are doing and what they require to keep doing it.

Wound healing brings maintenance into a more demanding setting. Damaged tissue has to be rebuilt, and the sequence includes the inflammatory response as well as the eventual repair. The notes on impaired healing in deficient animals were points of entry into that sequence: how closure proceeds, what quality of tissue is restored, and how the response is coordinated. Immunity enters as part of the work already under discussion.

So does oxidation, a word that has acquired rather more moral authority than a chemical process should be asked to carry.

The relevant questions concern the molecules being produced, their location, their targets, and the means available to control their effects. Without those details, a discussion can drift between treating oxidation as intrinsically destructive and treating an immune response as intrinsically desirable. The organism has to manage the actual chemistry, which is less accommodating of slogans.

Vitamin E gives us a concrete example of how nutritional conditions can alter the outcome. In mice lacking a particular defense against lipid peroxidation in liver cells, a vitamin E-enriched diet allowed survival under circumstances that otherwise produced severe liver degeneration and early death. The meaning of the fatty acid environment depends partly on the system’s capacity to manage it. [9]

The B vitamins and selenium belong in this account because the fatty acids do not act in nutritional isolation. My notes marked several relationships I wanted to explain, including those involving the desaturases and elongases that modify fatty acids. Supply alone cannot describe a process whose outcome also depends on the machinery receiving that supply. The next part of the story therefore concerns what happens when that machinery has already been altered.

Disease models make this problem especially clear. Before accepting a broad conclusion about a fat fed to a diabetic mouse, I want to know how the diabetes was produced, what had changed in the animal’s metabolism, how much fat was supplied, and what it replaced. These details determine the meaning of the result. They are sometimes treated as administrative clutter on the way to a conclusion about dinner.

The mouse, unfortunately, has retained its medical history.

Diabetes, liver disease, and neurological conditions appeared in the notes because they offered distinct settings in which to examine the handling of fatty acids. A changed profile might contribute to dysfunction, result from it, or reflect an attempt to accommodate it. Following the sequence allows us to ask which explanation fits a particular case. Combining every altered profile into a single dietary verdict discards the very differences that make the experiments informative.

The same concern extends through growth and reproduction. Muscle development, sex differences, and the production of stress hormones were among the topics I had set aside for fuller treatment. Each returns us to the material requirements of a response. An organism may receive a signal to adapt while lacking some part of what is needed to complete the adaptation. My interest is in the conditions that allow the process to proceed, and the points at which it fails.

Behavior brings that concern to the scale at which we encounter the whole organism. Attention, motivation, mood, reactivity: the notes compressed these subjects into a few lines, but their experimental contexts require much more room. The relationship between cellular function and observable behavior has been central to my thinking throughout this work. These topics belong here because they extend the story from the handling of a nutrient to the way an organism responds to its world.

That is the continuity I want to recover from the notes. What began as a casual assumption about animal foods developed into a question about the conditions under which an organism can maintain itself. The path passed through agricultural production, access to stored nutrients, compensatory metabolism, tissue repair, and the ability to carry an adaptive response through. The recent essays give that concern a more explicit language of energy, structure, and adaptation. This series will give the underlying research room to be seen.

The comprehensive review is behind this discussion. The work ahead is to unfold it, with enough attention to the experiments that the connections remain visible and the attractive explanations remain answerable to what was actually observed.

We’ll begin with Burr and Burr: the diets, the animals, the deterioration, and the restoration of growth and health. I once expected to dispose of the subject in a fairly short post. Nearly a century of research proved resistant to that editorial decision.

Evidence and sources