Polyunsaturated Fat Intake: What About Humans?

Now we know how to raise a healthy pig or rat: balance omega-6 linoleic acid (LA) and omega-3 alpha-linolenic acid (LNA) and keep both relatively low. LA and LNA are the most basic (and shortest) forms of omega-6 and omega-3 fats. They are the only fats the body can't make on its own. They're found in plant foods, and animal foods to a lesser extent. Animals convert them to longer-chain fats like arachidonic acid (AA; omega-6), EPA (omega-3) and DHA (omega-3). These long-chain, animal PUFA are involved in a dizzying array of cellular processes. They participate directly as well as being further elongated to form eicosanoids, a large class of very influential signaling molecules.

AA is the precursor of a number of inflammatory eicosanoids, while omega-3-derived eicosanoids tend to be less inflammatory and participate in long-term repair processes. A plausible explanation for the negative health effects of LA-rich vegetable oils is the fact that they lead to an imbalance in cellular signaling by increasing the formation of AA and decreasing the formation of EPA and DHA. Both inflammatory and anti-inflammatory signaling are necessary in the proper context, but they must be in balance for optimal function. Many modern diseases involve excess inflammation. LA also promotes oxidative and nitrosative damage to organs, as explained in the last post. This is an enormous oversimplification, but I'll skip over the details (most of which I don't know) because they could fill a stack of textbooks.

How do we raise a healthy human? Although I think pigs are a decent model organism for studying diet and health as it relates to humans, they don't have as much of a carnivorous history as we do. You would expect them to be more efficient at converting plant nutrients to their animal counterparts: carotenes to vitamin A, vitamin K1 to K2, and perhaps short-chain polyunsaturated fats (PUFA) to long-chain fats like AA, EPA and DHA. I mention it simply to point out that what goes for a pig may not necessarily go for a human when it comes to fatty acid conversion.

I've dug up a few papers exploring this question. I don't intend this post to be comprehensive but I think it's enough to get a flavor of what's going on. The first paper is an intervention trial comparing the effect of flax oil and fish oil supplementation on the fat composition of red blood cells. Investigators gave volunteers either 1.2 g, 2.4 g or 3.6 g (one teaspoon) flax oil per day; or 0.6 g or 1.2 g fish oil per day. The volunteers were U.S. firefighters, who otherwise ate their typical diet rich in omega-6. Flax oil supplementation at the two higher doses increased EPA, but did not increase DHA or decrease AA significantly. This suggests that humans can indeed convert some ALA to long-chain omega-3 fats, but adding ALA to a diet that is already high in omega-6 does not reduce AA or increase the all-important DHA.

The fish oil supplement, even at one-sixth the highest flax oil dose, increased EPA and DHA to a greater extent than flax oil, and also decreased AA. This shows that fish oil has a greater effect than flax oil on the fat profile of red blood cells in the context of a diet rich in omega-6. Another study also found that ALA intake is not associated with EPA or DHA in blood plasma. This could suggest either that humans aren't very good at converting ALA to longer n-3 fats, that the pathways are blocked by excessive LA or some other factor (a number of things block conversion of omega-3 fats), or that our bodies are already converting sufficient omega-3 and fish oil is overkill.

What happens when you reduce omega-6 consumption while increasing omega-3? In one study, participants were put on a "high LA" or "low LA" (3.8% of calories) diet. The first had an omega-6 : omega-3 ratio of 10.1, while the second had a ratio of 4.0. As in the previous intervention study, EPA was higher on the low LA diet. Here's where it gets interesting: DHA levels fell precipitously throughout the study, regardless of which diet the participants were eating. This has to do with a special requirement of the study diet: participants were not allowed to eat seafood. This shows that most of the DHA in the blood is obtained by eating DHA from animal fat, rather than elongating it from ALA such as flax oil. This agrees with the finding that strict vegetarians (vegans) have a low level of DHA in blood plasma.

In another intervention study, researchers achieved a better omega-6 : omega-3 ratio, with participants going from a baseline ratio of 32.2 to an experimental ratio of 2.2 for 10 weeks. The change in ratio was mostly from increasing omega-3, rather than decreasing omega-6. This caused an increase in serum EPA and DHA, although the DHA did not quite reach statistical significance (p= 0.06). In this study, participants were encouraged to eat fish 3 times per week, which is probably the reason their DHA rose. Participants saw a metabolic shift to fat burning, and an increase in insulin sensitivity that was on the cusp of statistical significance (p= 0.07).

I think what the data suggest is that humans can convert short-chain omega-3 (ALA) to EPA, but we don't efficiently elongate it to DHA. At least in the context of a high LA intake. Another thing to keep in mind is that serum PUFA are partially determined by what's in fat tissue. Modern Americans have an abnormally high proportion of LA in their fat tissue, sometimes over 20%. This contributes to a higher proportion of omega-6 and its derivatives in all tissues. "Wild" humans, including our paleolithic ancestors, would probably have values in the lower single digits. LA in fat tissue has a half-life of about 2 years, so restoring balance is a long-term process. Omega-3 fats do not accumulate to the same degree as LA, typically comprising about 1% of fat tissue. At this point, one could rightly ask: we know how diet affects blood polyunsaturated fats, but what's the relevance to health? There are multiple lines of evidence, all of which point in generally the same direction in my opinion.

There are strong, consistent associations between omega-6 intake (from vegetable oils), low omega-3 intake, and a number of health and psychiatric problems. Another line of evidence comes from intervention trials. The Lyon diet-heart study was one of the most successful intervention trials of all time. The experimental group increased their intake of fish, poultry, root vegetables, green vegetables, bread and fruit, while decreasing intake of red meat and dairy fat. A key difference between this study and other intervention trials is that participants were encouraged to eat a margarine rich in omega-3 ALA. In sum, participants decreased their total PUFA intake, decreased omega-6 intake and increased intake of ALA and long-chain omega-3s. After an average of 27 months, total mortality was 70% lower in the intervention group than in the control group eating the typical diet! This effect was not seen in trials that encouraged vegetable and grain consumption, discouraged red meat and dairy fat consumption, but didn't alter PUFA intake or the omega-6 : omega-3 ratio, such as the Women's Health Initiative.

As usual, the most important line of evidence comes from healthy non-industrial cultures that did not suffer from modern non-communicable diseases. They invariably consumed very little omega-6 LA (3% of calories or less), ate a roughly balanced amount of omega-6 and omega-3, and had a source of long-chain (animal) omega-3. They did not eat much omega-3 from plant sources (such as flax), as concentrated sources are rare in nature. Dr. Weston Price observed that cultures throughout the world sought out seafood if available, sometimes going to great lengths to obtain it. Here's an exerpt from Nutrition and Physical Degeneration about Fiji islanders:

Since Viti Levu, one of the islands of this group, is one of the larger islands of the Pacific Ocean, I had hoped to find on it a district far enough from the sea to make it necessary for the natives to have lived entirely on land foods. Accordingly, with the assistance of the government officials and by using a recently opened government road I was able to get well into the interior of the island by motor vehicle, and from this point to proceed farther inland on foot with two guides. I was not able, however, to get beyond the piles of sea shells which had been carried into the interior. My guide told me that it had always been essential, as it is today, for the people of the interior to obtain some food from the sea, and that even during the times of most bitter warfare between the inland or hill tribes and the coast tribes, those of the interior would bring down during the night choice plant foods from the mountain areas and place them in caches and return the following night and obtain the sea foods that had been placed in those depositories by the shore tribes. The individuals who carried these foods were never molested, not even during active warfare. He told me further that they require food from the sea at least every three months, even to this day. This was a matter of keen interest, and at the same time disappointment since one of the purposes of the expedition to the South Seas was to find, if possible, plants or fruits which together, without the use of animal products, were capable of providing all of the requirements of the body for growth and for maintenance of good health and a high state of physical efficiency.

Price searched for, but did not find, vegetarian groups that were free of the diseases of civilization. What he found were healthy cultures that put a strong emphasis on nutrient-dense animal foods, particularly seafoods when available. I think all this information together suggests that the optimum, while being a fairly broad range, is a low intake of omega-6 LA (less than 3% of calories) and a modest intake of animal omega-3 for DHA.

I believe the most critical element is reducing omega-6 LA by eliminating industrial vegetable oils (soybean, corn, cottonseed, etc.) and the foods that contain them from the diet. Fats from pasture-raised ruminants (butter, beef, lamb etc.) and wild fish are naturally balanced. We no longer commonly eat the most concentrated land source of DHA, brain, so I think it's wise to eat seafood sometimes. According to the first study I cited, 1/4 teaspoon of fish oil (or cod liver oil) per day is enough to elevate plasma DHA quite significantly. This amount of omega-3 could be obtained by eating seafood weekly.

Polyunsaturated Fat Intake: Effects on the Heart and Brain

I'm revisiting the topic of the omega-6/omega-3 balance and total polyunsaturated fat (PUFA) intake because of some interesting studies I've gotten a hold of lately (thanks Robert). Two of the studies are in pigs, which I feel are a decent model organism for studying the effect of diet on health as it relates to humans. Pigs are omnivorous (although more slanted toward plant foods), have a similar digestive system to humans (although sturdier), are of similar size and fat composition to humans, and have been eating grains for about the same amount of time as humans.

In the last post on the omega-6/omega-3 balance, I came to the conclusion that a roughly balanced but relatively low intake of omega-6 and omega-3 fats is consistent with the diets of healthy non-industrial cultures. There were a few cultures that had a fairly high long-chain omega-3 intake from seafood (10% of calories), but none ate much omega-6.

The first study explores the effect of omega-6 and omega-3 fats on heart function. Dr. Sheila Innis and her group fed young male pigs three different diets:

1. An unbalanced, low PUFA diet. Pig chow with 1.2% linoleic acid (LA; the main omega-6 plant fat) and 0.06% alpha linolenic acid (ALA; the main omega-3 plant fat).
   
2. A balanced, low PUFA diet. Pig chow with 1.4% LA and 1.2% ALA.
3. An unbalanced, but better-than-average, "modern diet". Pig chow with 11.6% LA and 1.2% ALA.

After 30 days, they took a look at the pigs' hearts. Pigs from the first and third (unbalanced) groups contained more "pro-inflammatory" fats (arachidonic acid; AA) and less "anti-inflammatory" fats (EPA and DHA) than the second group. The first and third groups also experienced an excessive activation of "pro-inflammatory" proteins, such as COX-2, the enzyme inhibited by aspirin, ibuprofen and other NSAIDs.

The most striking finding of all was the difference in lipid peroxidation between groups. Lipid peroxidation is a measure of oxidative damage to cellular fats. In the balanced diet hearts, peroxidation was half the level found in the first group, and one-third the level found in the third group! This shows that omega-3 fats exert a powerful anti-oxidant effect that can be more than counteracted by excessive omega-6. Nitrosative stress, another type of damage, tracked with n-6 intake regardless of n-3, with the third group almost tripling the first two. I think this result is highly relevant to the long-term development of cardiac problems, and perhaps cardiovascular disease in general.

In another study with the same lead author Sanjoy Ghosh, rats fed a diet enriched in omega-6 from sunflower oil showed an increase in nitrosative damage, damage to mitochondrial DNA, and a decrease in maximum cardiac work capacity (i.e., their hearts were weaker). This is consistent with the previous study and shows that the mammalian heart does not like too much omega-6! The amount of sunflower oil these rats were eating (20% food by weight) is not far off from the amount of industrial oil the average American eats.

A third paper by Dr. Sheila Innis' group studied the effect of the omega-6 : omega-3 balance on the brain fat composition of pigs, and the development of neurons in vitro (in a culture dish). There were four diets, the first three similar to those in the first study:

1. Deficient. 1.2% LA and 0.05% ALA.
2. Contemporary. 10.7% LA and 1.1% ALA.
   
3. Evolutionary. 1.2% LA and 1.1% ALA.
4. Supplemented. The contemporary diet plus 0.3% AA and 0.3% DHA.

The first thing they looked at was the ability of the animals to convert ALA to DHA and concentrate it in the brain. DHA is critical for brain and eye development and maintenance. The evolutionary diet was most effective at putting DHA in the brain, with the supplemented diet a close second and the other three lagging behind. The evolutionary diet was the only one capable of elevating EPA, another important fatty acid derived from ALA. If typical fish oil rather than isolated DHA and AA had been given as the supplement, that may not have been the case. Overall, the fatty acid composition of the brain was quite different in the evolutionary group than the other three groups, which will certainly translate into a variety of effects on brain function.

The researchers then cultured neurons and showed that they require DHA to develop properly in culture, and that long-chain omega-6 fats are a poor substitute. Overall, the paper shows that the modern diet causes a major fatty acid imbalance in the brain, which is expected to lead to developmental problems and probably others as well. This can be partially corrected by supplementing with fish oil.

Together, these studies are a small glimpse of the countless effects we are having on every organ system, by eating fats that are unfamiliar to our pre-industrial bodies. In the next post, I'll put this information into the context of the modern human diet.

Health is Multi-Factorial

Thanks to commenter Brock for pointing me to this very interesting paper, "Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor-alpha in rats with sucrose-induced metabolic syndrome". As we know, sugar gives rats metabolic syndrome when it's added to regular rat chow, probably the same thing it does to humans when added to a processed food diet.

One thing has always puzzled me about sugar. It doesn't appear to cause major metabolic problems when added to an otherwise healthy diet, yet it wreaks havoc in other contexts. One example of the former situation is the Kuna, who are part hunter-gatherer, part agricultural. They eat a lot of refined sugar, but in the context of chocolate, coconut, fish, plantains, root vegetables and limited grains and beans, they are relatively healthy. Perhaps not quite on the same level as hunter-gatherer groups, but healthier than the average modernized person from the point of view of the diseases of civilization.

This paper really sheds light on the matter. The researchers gave a large group of rats access to drinking water containing 30% sucrose, in addition to their normal rat chow, for 21 weeks. The rats drank 4/5 of their calories in the form of sugar water. There's no doubt that this is an extreme treatment. They subsequently developed metabolic syndrome, including abdominal obesity, elevated blood pressure, elevated fasting insulin, elevated triglycerides, elevated total cholesterol and LDL, lowered HDL, greatly increased serum uric acid, greatly elevated liver enzymes suggestive of liver damage, and increased tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a hormone secreted by visceral (abdominal) fat tissue that may play a role in promoting insulin resistance.

After this initial 12-week treatment, they divided the metabolic syndrome rats into two groups:

• One that continued the sugar treatment, along with a diet enriched in corn and canola oil (increased omega-6).
• A second that continued the sugar treatment, along with a diet enriched in fish oil (increased omega-3).

The two diets contained the same total amount of polyunsaturated fat (PUFA), but had very different omega-6 : omega-3 ratios. The first had a ratio of 9.3 (still better than the average American), while the second had a ratio of 0.02, with most of the omega-3 in the second group coming from EPA and DHA (long-chain, animal omega-3s). The second diet also contained four times as much saturated fat as the first, mostly in the form of palmitic acid.

Compared to the vegetable oil group, the fish oil group had lower fasting insulin, lower blood pressure, lower triglycerides, lower cholesterol, and lower LDL. As a matter of fact, the fish oil group looked as good or better on all these parameters than a non-sugar fed control group receiving the extra vegetable oil alone (although the control group isn't perfect because it inevitably ate more vegetable oil-containing chow to make up for the calories it wasn't consuming in sugar). The only things reducing vegetable oil and increasing fish oil didn't fix were the weight and the elevated TNF-alpha, although they didn't report the level of liver enzymes in these groups. The TNF-alpha finding is not surprising, since it's secreted by visceral fat, which did not decrease in the fish oil group.

I think this is a powerful result. It may have been done in rats, but the evidence is there for a similar mechanism in humans. The Kuna have a very favorable omega-6 : omega-3 ratio, with most of their fat coming from highly saturated coconut and cocoa. This may protect them from their high sugar intake. The Kitavans also have a very favorable omega-6 : omega-3 ratio, with most of their fat coming from coconuts and fish. They don't eat refined sugar, but they do eat a tremendous amount of starch and a generous amount of fruit.

The paper also suggests that the metabolic syndrome is largely reversible.

I believe that both excessive sugar and excessive omega-6 from modern vegetable oils are a problem individually. But if you want to have a much bigger problem, try combining them!

Real Food X: Roasted Marrow Bones

Bone marrow is a food that has been prized throughout history-- from hunter-gatherer tribes to haute cuisine chefs. It's not hard to understand why, once you've tasted it. It's delicate, meaty and fatty. It's also rich in fat-soluble vitamins, including vitamins K1 and K2, although this will depend on what the animal has eaten.

Roasted marrow bones make a simple appetizer. Beef bones are the best because of their size. Select wide bones that are cut about three inches long. They should be from the femur or the humerus, called the "shank bones". These are sometimes available in the frozen meats section of a grocery store, otherwise a butcher can procure them. If you have access to a farmer's market that sells meats, vendors will typically have bones cut for you if you request it.

Recipe

1. Preheat oven to 450 F (230 C).
2. Place bones, cut side up, in a baking dish or oven-proof skillet.
3. Bake for about 15 minutes, until the marrow begins to separate from the bone, but not much longer because it will turn to mush.
4. Scoop out and eat the marrow by itself, on sourdough rye toast or however you please.
5. Make soup stock from the leftover bones.

Vitamin K2 in Marrow

I'm always on the lookout for foods rich in vitamin K2 MK-4, because it's so important and so rare in the modern food system. I heard some internet rumors that marrow might be rich in fat-soluble vitamins. Google let me down, so I decided to look through the rat studies on K2 MK-4 in which they looked at its tissue distribution.

I found one that looked at the K2 MK-4 content in different tissues of rats fed vitamin K1. Marrow was rich in K2, along with testes. It contains 10-20 times more MK-4 than liver by weight, and more than any of the other organs they tested (serum, liver, spleen, kidney, heart, testes, marrow, brain) except testes. They didn't include values for salivary gland and pancreas, the two richest sources.

If we assume beef marrow has the same amount of MK-4 as rat marrow per weight (I have no idea if this is really the case, but it's probably in the ballpark), two ounces of beef marrow would contain about 10 micrograms MK-4. Not a huge source, but significant nevertheless.

Bone marrow was a prized food in many hunter-gatherer societies. Let's see what Dr. Weston Price has to say about it (from Nutrition and Physical Degeneration):

For the Indians living inside the Rocky Mountain Range in the far North of Canada, the successful nutrition for nine months of the year was largely limited to wild game, chiefly moose and caribou. During the summer months the Indians were able to use growing plants. During the winter some use was made of bark and buds of trees. I found the Indians putting great emphasis upon the eating of the organs of the animals, including the wall of parts of the digestive tract. Much of the muscle meat of the animals was fed to the dogs. It is important that skeletons are rarely found where large game animals have been slaughtered by the Indians of the North. The skeletal remains are found as piles of finely broken bone chips or splinters that have been cracked up to obtain as much as possible of the marrow and nutritive qualities of the bones. These Indians obtain their fat-soluble vitamins and also most of their minerals from the organs of the animals. An important part of the nutrition of the children consisted in various preparations of bone marrow, both as a substitute for milk and as a special dietary ration.

Here's a bit more about these same groups, also from Nutrition and Physical Degeneration:

The condition of the teeth, and the shape of the dental arches and the facial form, were superb. Indeed, in several groups examined not a single tooth was found that had ever been attacked by tooth decay. In an examination of eighty-seven individuals having 2,464 teeth only four teeth were found that had ever been attacked by dental caries. This is equivalent to 0.16 per cent. As we came back to civilization and studied, successively, different groups with increasing amounts of contact with modern civilization, we found dental caries increased progressively, reaching 25.5 per cent of all of the teeth examined at Telegraph Creek, the point of contact with the white man's foods. As we came down the Stikine River to the Alaskan frontier towns, the dental caries problem increased to 40 per cent of all of the teeth.

Evidently, the traditionally-living groups were doing something right.

The Fructose Index is the New Glycemic Index

I stumbled upon an interesting editorial recently in the American Journal of Clinical Nutrition from Dr. Richard Johnson's group, entitled "How Safe is Fructose for Persons With or Without Diabetes?" It was a response to a meta-analysis in the same journal pronouncing fructose safe up to 90 grams per day. That's the amount in eight apples or four cans of soda. Not quite what our hunter-gatherer ancestors were eating! The editorial outlined the case against excessive fructose, which I feel is quite strong. That led me to another, more comprehensive paper from Dr. Johnson's group, which argues that the amount of fructose found in a food, which they call the "fructose index", is more relevant to health than the food's glycemic index.

The glycemic index is a measure of the blood sugar response to a fixed amount of carbohydrate from a particular food. For example, white bread has a high glycemic index because it raises blood sugar more than another food containing the same amount of carbohydrate, say, lentils. Since chronically elevated blood sugar and its natural partner, insulin resistance, are part of the metabolic syndrome, it made sense that the glycemic index would be a good predictor of the metabolic effect of a food. I believed this myself for a long time.

My faith in the concept began to erode when I learned more about the diets of healthy traditional cultures. For example, the Kitavans get 69% of their calories from high-glycemic index carbohydrates (mostly starchy root vegetables), with little added fat-- that's a lot of fast-digesting carbohydrate! Overweight, elevated insulin and other symptoms of the metabolic syndrome are essentially nonexistent. Throughout Africa, healthy cultures make dishes from grains or starchy tubers that are soaked, pounded, fermented and then cooked. The result is a pile of mush that is very easily absorbed by the digestive tract, which is exactly the point of going through all the trouble.

The more I thought about the glycemic index and its relationship to insulin resistance and the metabolic syndrome, the more I realized there is a disconnect in the logic: elevated post-meal glucose and insulin do not necessarily lead to chronically elevated glucose and insulin. Here's what Dr. Mark Segal from Dr. Johnson's group had to say:

We suggest that the [glycemic index] is better aimed at identifying foods that stimulate insulin secretion rather than foods that stimulate insulin resistance. The underlying concept is based on the principle that it is the ingestion of foods that induce insulin resistance that carries the increased risk for obesity and cardiovascular disease and not eating foods that stimulate insulin secretion.

Well said! I decided to take a look through the literature to see if there had been any trials on the relationship between a diet's glycemic index and its ability to cause satiety (fullness) and affect weight. I found a meta-analysis from 2007. Two things are clear from the paper: 1) in the short term, given an equal amount of carbohydrate, a diet with a low glycemic index is more satiating (filling) than one with a high glycemic index, leading to a lower intake of calories. 2) this effect disappears in the long-term, and the three trials (1, 2, 3) lasting 10 weeks or longer found no consistent effect on caloric intake or weight*. As a matter of fact, the only statistically significant (p less than 0.001) weight difference was a greater weight loss in one of the high-glycemic index groups!

As I've said many times, the body has mechanisms for maintaining weight and caloric intake where they should be in the long term. As long as those mechanisms are working properly, weight and caloric intake will be appropriate. The big question is, how does the modern lifestyle derail those mechanisms?

Dr. Johnson believes fructose is a major contributor. Table sugar, fruit, high-fructose corn syrup and honey are all roughly 50% fructose by calories. Total fructose consumption has increased about 19% in the U.S. since 1970, currently accounting for almost one eighth of our total calorie intake (total sugars account for one quarter!). That's the average, so many people actually consume more.

Fructose, but not starch or its component sugar glucose, causes insulin resistance, elevated serum uric acid (think gout and kidney stones), poorer blood glucose control, increased triglycerides and LDL cholesterol in animal studies and controlled human trials. All of these effects relate to the liver, which clearly does not like excessive fructose (or omega-6 oils). Some of these trials were conducted using doses that are near the average U.S. intake. The effect seems to compound over time both in humans and animals. The overweight, the elderly and the physically unfit are particularly vulnerable. I find this pretty damning.

Drs. Johnson and Segal recommend limiting fructose to 15-40 grams per day, which is the equivalent of about two apples or one soda (choose the apples!). They also recommend temporarily eliminating fructose for two weeks, to allow the body to recover from the negative long-term metabolic adaptation that can persist even when intake is low. I think this makes good sense.

The glycemic index may still be a useful tool for people with poor glucose control, like type II diabetics, but I'm not sure how much it adds to simply restricting carbohydrate. Reducing fructose may be a more effective way to address insulin resistance than eating a low glycemic index diet.


*Here was the author's way of putting it in the abstract: "Because of the increasing number of confounding variables in the available long-term studies, it is not possible to conclude that low-glycaemic diets mediate a health benefit based on body weight regulation. The difficulty of demonstrating the long-term health benefit of a satietogenic food or diet may constitute an obstacle to the recognition of associated claims." In other words, the data not supporting our favorite hypothesis is an obstacle to its recognition. You don't say?

Is Vitamin A Toxicity a Concern?

Several commenters have asked for my opinion on recent statements by prominent health researchers that many Americans are suffering from unrecognized vitamin A toxicity. Dr. John Cannell of the Vitamin D Council is perhaps the most familiar of them. Dr. Cannell's mission is to convey the benefits of vitamin D to the public. The Vitamin D Council's website is a great resource.

Vitamin A is a very important nutrient. Like vitamin D, it has its own nuclear receptors which alter the transcription of a number of genes in a wide variety of tissues. Thus, it is a very fundamental nutrient to health. It's necessary for proper development, vision, mineral metabolism, bone health, immune function, the integrity of skin and mucous membranes, and many other things. Vitamin A is a fat-soluble vitamin, and as such, it is possible to overdose. So far, everyone is in agreement.

The question of optimal intake is where opinions begin to diverge. Hunter-gatherers and healthy non-industrial cultures, who almost invariably had excellent dental and skeletal development and health, often had a very high intake of vitamin A (according to Dr. Weston Price and others). This is not surprising, considering their fondness for organ meats. A meager 2 ounces of beef liver contains about 9,500 IU, or almost 200% of your U.S. and Canadian recommended daily allowance (RDA). Kidney and eye are rich in vitamin A, as are many of the marine oils consumed by the Inuit and other arctic groups.

If we can extrapolate from historical hunter-gatherers, our ancestors didn't waste organs. In fact, in times of plenty, some groups discarded the muscle tissue and ate the organs and fat. Carnivorous animals often eat the organs first, because they know exactly where the nutrients are. Zookeepers know that if you feed a lion nothing but muscle, it does not thrive.

This is the background against which we must consider the question of vitamin A toxicity. Claims of toxicity must be reconciled with the fact that healthy cultures often consumed large amounts of vitamin A without any ill effects. Well, you might be surprised to hear me say that I do believe some Americans and Europeans suffer from what you might call vitamin A toxicity. There is a fairly consistent association between vitamin A intake and bone mineral density, osteoporosis and fracture risk. It holds true across cultures and sources of vitamin A. Chris Masterjohn reviewed the epidemiology here. I recommend reading his very thorough article if you want more detail. The optimum intake in some studies is 2-3,000 IU, corresponding to about 50% of the RDA. People who eat more or less than this amount tend to suffer from poorer bone health. This is where Dr. Cannell and others are coming from when they say vitamin A toxicity is common.

The only problem is, this position ignores the interactions between fat-soluble vitamins. Vitamin D strongly protects agains vitamin A toxicity and vice versa. As a matter of fact, "vitamin A toxicity" is almost certainly a relative deficiency of vitamin D. Vitamin D deficiency is also tightly correlated with low bone mineral density, osteoporosis and fracture risk. A high vitamin A intake requires vitamin D to balance it. The epidemiological studies showing an association between high-normal vitamin A intake and reduced bone health all sported populations that were moderately to severely vitamin D deficient on average. At optimal vitamin D levels, 40-70 ng/mL 25(OH)D, it would take a whopping dose of vitamin A to induce toxicity. You might get there if you eat nothing but beef liver for a week or two.

The experiment hasn't been done under controlled conditions in humans, but if you believe the animal studies, the optimal intake for bone mineral density is a high intake of both vitamins A and D. And guess what? A high intake of vitamins A and D also increases the need for vitamin K2. That's because they work together. For example, vitamin D3 increases the secretion of matrix Gla protein and vitamin K2 activates it. Is it any surprise that the optimal proportions of A, D and K occur effortlessly in a lifestyle that includes outdoor activity and whole, natural animal foods? This is the blind spot of the researchers who have warned of vitamin A toxicity: uncontrolled reductionism. Vitamins do not act in a vacuum; they interact with one another. If your theory doesn't agree with empirical observations from healthy cultures, it's back to the drawing board.

High-vitamin cod liver oil is an excellent source of vitamins A and D because it contains a balanced amount of both. Unfortunately, many brands use processing methods that reduce the amount of one or more vitamins. See the Weston Price foundation's recommendations for the highest quality cod liver oils. They also happen to be the cheapest per dose. I order Green Pasture high-vitamin cod liver oil through Live Superfoods (it's cheaper than ordering directly).

This suggests that vitamin A toxicity may be less of a concern when vitamin D status is good.