Wednesday, December 3, 2008

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 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.

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