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.

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.

Google Flu Trends

I just discovered a wonderful new tool from Google.org, Google Flu Trends. Google.org is the philanthropic branch of Google. Flu Trends gives you real-time data on flu incidence in your U.S. state, as well as for the country as a whole. Here's how it works:

We've found that certain search terms are good indicators of flu activity. Google Flu Trends uses aggregated Google search data to estimate flu activity in your state up to two weeks faster than traditional flu surveillance systems.

Each week, millions of users around the world search for online health information. As you might expect, there are more flu-related searches during flu season, more allergy-related searches during allergy season, and more sunburn-related searches during the summer.

Google's data match up well with U.S. Centers for Disease Control and Prevention (CDC) data on flu incidence, but are available 1-2 weeks before CDC data. Here's a comparison of Flu Trends and CDC data for previous years. Plus, Google makes the information easily accessible and user-friendly.

I think this a fantastic use of the massive amount of raw information on the internet. It's amazing what a person can do with a brain and an internet connection these days.

Can Vitamin K2 Reverse Arterial Calcification?

It certainly can in rats. In April 2007, Dr. Cees Vermeer and his group published a paper on the effect of vitamin K on arterial calcification (the accumulation of calcium in the arteries). As I mentioned two posts ago, arterial calcification is tightly associated with the risk of heart attack and death. Warfarin-treated rats are an established model of arterial calcification. Warfarin also causes calcification in humans. The drug is a "blood thinner" that inhibits vitamin K recycling, and inhibits the conversion of vitamin K1 (phylloquinone) to K2 MK-4 (menaquinone-4). This latter property turns out to be the critical one in the calcification process.

Rats are able to convert vitamin K1 to K2 MK-4, whereas humans don't seem to convert well. Conversion efficiency varies between species. Dr. Vermeer's group treated rats with warfarin for 6 weeks, during which they developed extensive arterial calcification. They also received vitamin K1 to keep their blood clotting properly. At 6 weeks, the warfarin-treated rats were broken up into several groups:

• One continued on the warfarin and K1 diet
• One was placed on a diet containing a normal amount of K1 (no warfarin)
  
• One was placed on a high K1 diet (no warfarin)
• The last was placed on a high K2 MK-4 diet (no warfarin)
  

After 6 more weeks, the first two groups developed even more calcification, while the third and fourth groups lost about 40% of their arterial calcium. The high vitamin K groups also saw a decrease in cell death in the artery wall, a decrease in uncarboxylated (inactive) MGP, and an increase in arterial elasticity. They also measured the vitamin K content of aortas from each group. The group that received the 12-week warfarin treatment had a huge amount of K1 accumulation in the aorta, but no K2 MK-4. This is expected because warfarin inhibits the conversion of K1 to K2 MK-4. It's notable that when conversion to K2 was blocked, K1 alone was totally ineffective at activating MGP and preventing calcification.

In the group fed high K1 but no warfarin, there was about three times more K2 MK-4 in the aortas than K1, suggesting that they had converted it effectively and that vascular tissue selectively accumulates K2 MK-4. A high K1 intake was required for this effect, however, since the normal K1 diet did not reverse calcification. The rats fed high K2 MK-4 had only K2 MK-4 in their aortas, as expected.

What does this mean for us? K2 MK-4 appears to be the form of vitamin K that arteries prefer (although not enough is known about the longer menaquinones, such as MK-7, to rule out a possible effect). Humans don't seem to be very good at making the conversion from K1 to K2 MK-4 (at normal intakes; there are suggestions that at artificially large doses we can do it). That means we need to ensure an adequate K2 MK-4 intake to prevent or reverse arterial calcification; eating K1-rich greens won't cut it. It's worth noting that the amounts of K1 and K2 used in the paper were very large, far beyond what is obtainable through food. But the regression took only 6 weeks, so it's possible that a smaller amount of K2 MK-4 over a longer period could have the same effect in humans.

K2 MK-4 (and perhaps other menaquinones like MK-7) may turn out to be an effective treatment for arterial calcification and cardiovascular disease in general. It's extremely effective at preventing osteoporosis-related fractures in humans. That's a highly significant fact. Osteoporosis and arterial calcification often come hand-in-hand. Thus, they are not a result of insufficient or excessive calcium, but of a failure to use the available calcium effectively. In the warfarin-treated rats described above, the serum (blood) calcium concentration was the same in all groups. Osteoporosis and arterial calcification are two sides of the same coin, and the fact that one can be addressed with K2 MK-4 means that the other may be as well.

Both osteoporosis and arterial calcification may turn out to be symptoms of vitamin K2 deficiency, resulting from the modern fear of animal fats and organs, and the deterioration of traditional animal husbandry practices. So eat your pastured dairy, organs, fish roe and shellfish! And if you have arterial calcification, as judged by a heart scan, you may want to consider supplementing with additional K2 MK-4 (also called menaquinone-4 and menatetrenone).

The osteoporosis studies were done with 45 milligrams per day, which was well tolerated but seems excessive to me. Smaller doses were not tested. From the limited information available on the K2 content of foods, 1 milligram of K2 MK-4 per day seems like the upper limit of what you can get from food. That's about 40 times more than the average person eats. Anything more and you're outside your body's operating parameters. Make sure you're getting adequate vitamin D3 and A if you supplement with K2. Vitamin D3 in particular increases the secretion of MGP, so the two work in concert.

Cardiovascular Disease and Vitamin K2

Vitamin K2 is intimately involved in calcium metabolism. Matrix Gla-protein (MGP) is a vitamin K-dependent protein that is secreted in cartilage, lung, heart, kidney and arteries. MGP prefers the MK-4 form of vitamin K2, the type that occurs almost exclusively in animal foods. Mice lacking MGP develop extensive arterial and soft tissue calcification (accumulation of calcium, as in bone). Same for humans with naturally occurring mutations in MGP (Keutel syndrome). It also happens in rats treated with warfarin, which inhibits vitamin K recycling. Let's hear what Dr. Cees Vermeer and his group have to say about MGP:

Among the proteins involved in vascular calcium metabolism, the vitamin K-dependent matrix Gla-protein (MGP) plays a dominant role. Although on a molecular level its mechanism of action is not completely understood, it is generally accepted that MGP is a potent inhibitor of arterial calcification. Its pivotal importance for vascular health is demonstrated by the fact that there seems to be no effective alternative mechanism for calcification inhibition in the vasculature. An optimal vitamin K intake is therefore important to maintain the risk and rate of calcification as low as possible.

So why do we care about vessel calcification? It associates strongly with the risk of heart attack and total mortality, better than traditional markers like the Framingham risk index*. That's because it's actually a measure of the disease process, rather than a marker with an unclear connection to it.

In my post on vitamin K2, I mentioned the Rotterdam study, which found that vitamin K2 intake is strongly associated with a lower risk of cardiovascular and total mortality. Vitamin K1, which is the type found in plants, was not associated with reduced mortality. I just came across another study in women selected from the PROSPECT cohort that showed something similar. Women with the highest K2 intake had the lowest level of coronary calcification. There was no association with K1. This suggests, yet again, that humans aren't very good at making the conversion from K1 to K2 MK-4. This is probably because during evolution, we always had a ready source of K2, so efficient conversion became unnecessary. Vitamin K2 MK-4 is found almost exclusively in animal foods.

Notably absent from the main text body is a discussion of where the K2 is coming from. It's tucked away in one sentence of the methods section: "cheese contributed 54%, milk products 22% and meat 15% of menaquinone intake." Oops! These are the foods that are supposed to cause heart disease! And do you remember where the K2 is? In the fat-- double oops! Yet another important nutrient that's found in animal fat.

Keep in mind that these Dutch women have an intake of K2 that is probably lower than what we would have eaten as hunter-gatherers. Most people in modern societies are verifiably K2 deficient. A focus on the organs (brain, pancreas) and fats of wild animals, shellfish, fish eggs and insects would have assured hunter-gatherers a high intake of vitamin K2 MK-4. This is precisely what Weston Price found in Nutrition and Physical Degeneration. He refers to vitamin K2 MK-4 as "activator X" in the book. In modern times, our most readily available source of vitamin K2 MK-4 is actually not a paleolithic food at all, it's butter from pasture-raised cows. It's how we can get away with not eating brain, pancreas and bugs.


*I plugged my numbers into this Framingham risk index calculator and it gave me the message "Please go back and enter an HDL value in the range of 20-100."!! I can imagine if you follow NCEP dietary guidelines your HDL would never break 100 mg/dL!

Winterize Your Diet

As winter approaches, there are steps you can take to preserve your health and well-being. Here's a list of things I find useful:

-Eat in season. Root vegetables like beets, turnips, rutabagas and potatoes are in season and make a satisfying dish. Try baked beets with raw garlic, sage and butter. Winter squash are tasty, nutritious and colorful. They make excellent soups and mashes, and can be baked or steamed. My favorite varieties are butternut, kabochas, delicata and gold nugget. They pair well with sage or nutmeg. In some places, hardy greens such as kale and collards are available in winter. Many fruits such as apples, pears and citrus are in season during the winter (or stored from fall).

-Prepare soup stocks. There's nothing like a long-simmered bone broth to drive away the winter chill. They are also rich in minerals and gelatin, which aids digestion and soothes the digestive tract.

-Make sauerkraut or other fermented vegetables. Fermentation was once used as a means to preserve flavor and nutrition for the winter. Fermented vegetables are a powerful digestive aid. After the first frost, cabbage is at its sweetest. Sweet cabbage makes the best kraut.

-Keep your vitamin D level high. This may protect against the typical winter ills, including flu and seasonal depression. Unless you live in a warm climate and spend time outside in the winter regularly, it's wise to seek out vitamin D. High-vitamin cod liver oil, pasture-raised animal fats, shellfish and fatty fish are good sources. Some people may wish to supplement with vitamin D3.