Dairy Fat and Diabetes

Introduction

Having access to embargoed news from the Annals of Internal Medicine is really fun. I get to report on important studies at the same time as the news media. But this week, I got my hands on a study that I'm not sure will be widely reported (Mozaffarian et al. Trans-palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in US Adults. Ann Internal Med. 2010). Why? Because it suggests that dairy fat may protect against diabetes.

The lead author is Dr. Dariush Mozaffarian, whose meta-analysis of diet-heart controlled trials I recently criticized (1). I think this is a good opportunity for me to acknowledge that Dr. Mozaffarian and his colleagues have published some brave papers in the past that challenged conventional wisdom. For example, in a 2005 study, they found that postmenopausal women who ate the most saturated fat had the slowest rate of narrowing of their coronary arteries over time (2). It wasn't a popular finding but he has defended it. His colleague Dr. Walter Willett thinks dietary fat is fine (although he favors corn oil), whole eggs can be part of a healthy diet, and there are worse things than eating coconut from time to time. Dr. Willett is also a strong advocate of unrefined foods and home cooking, which I believe are two of the main pillars of healthy eating.

Let's hit the data

Investigators collected two measures of dairy fat intake in 3,736 Americans:

1. 24 hour dietary recall questionnaires, six times. This records volunteers' food intake at the beginning of the study.
2. Blood (plasma phospholipid) content of trans-palmitoleate. Dairy fat and red meat fat are virtually the only sources of this fatty acid, so it reflects the intake of these foods. Most of the trans-palmitoleate came from dairy in this study, although red meat was also a significant source.

After adjustment for confounding factors, trans-palmitoleate levels were associated with a smaller waist circumference, higher HDL cholesterol, lower serum triglycerides, lower C-reactive protein, lower fasting insulin and lower calculated insulin resistance. Furthermore, people with the highest trans-palmitoleate levels had 1/3 the risk of developing diabetes over the three years volunteers were followed. Keep in mind, however, that this is an observational study and does not prove that dairy fat prevents diabetes.

Even though certain blood fatty acids partially represent food intake, they can also represent metabolic conditions. For example, people on their way to type II diabetes tend to have more saturated blood lipids, independent of diet (3, 4)*. So it's reassuring to see that dietary trans-palmitoleate intake was closely related to the serum level. The investigators also noted that "greater whole-fat dairy consumption was associated with lower risk for diabetes," which increases my confidence that serum trans-palmitoleate is actually measuring dairy fat intake to some degree. However, in the end, I think the striking association they observed was partially due to dairy fat intake, but mostly due to metabolic factors that had nothing to do with dairy fat**.

Here's a nice quote:

Our findings support potential metabolic benefits of dairy consumption and suggest that trans-palmitoleate may mediate these effects***. They also suggest that efforts to promote exclusive consumption of low-fat and nonfat dairy products, which would lower population exposure to trans-palmitoleate, may be premature until the mediators of the health effects of dairy consumption are better established.

*Probably due to uncontrolled de novo lipogenesis because of insulin resistance. Many studies find that serum saturated fatty acids are higher in those with metabolic dysfunction, independent of diet. They sometimes interpret that as showing that people are lying about their diet, rather than that serum saturated fatty acids don't reflect diet very well. For example, in one study I cited, investigators found no relationship between dietary saturated fat and diabetes risk, but they did find a relationship between serum saturated fatty acids and diabetes risk (5). They then proceeded to refer to the serum measurements as "objective measurements" that can tease apart "important associations with diabetes incidence that may be missed when assessed by [food questionnaires]." They go on to say that serum fatty acids are "useful as biomarkers for fatty acid intake," which is true for some fatty acids but not remotely for most of the saturated ones, according to their data.

**Why do I say that? Because mathematically adjusting for dairy and meat fat intake did not substantially weaken the association between phospholipid trans-palmitoleate and reduced diabetes risk (Table 4). In other words, if you believe their math, dairy/meat fat intake only accounted for a small part of the protective association. That implies that healthy people maintain a higher serum phospholipid trans-palmitoleate level than unhealthy people, even if both groups eat the same amount of trans-palmitoleate. If they hadn't mentioned that full-fat dairy fat intake was directly associated with a lower risk of diabetes, I would not find the study very interesting because I'd have my doubts that it was relevant to diet.

***I find it highly doubtful that trans-palmitoleate entirely mediates the positive health outcomes associated with dairy fat intake. I think it's more likely to simply be a marker of milk fat, which contains a number of potentially protective substances such as CLA, vitamin K2, butyric acid, and the natural trans fats including trans-palmitoleate. In addition, dairy fat is low in omega-6 polyunsaturated fat. I find it unlikely that their fancy math was able to tease those factors apart, because those substances all travel together in dairy fat. trans-palmitoleate pills are not going to replace butter.

Dr. Mellanby's Tooth Decay Reversal Diet

I have a lot of admiration for Drs. Edward and May Mellanby. A husband-and-wife team, they discovered vitamin D, and determined that rickets is caused by poor calcium (or phosphorus) status, typically due to vitamin D deficiency. They believed that an ideal diet is omnivorous, based on whole foods, and offers an adequate supply of fat-soluble vitamins and easily absorbed minerals. They also felt that grain intake should be modest, as their research showed that unsoaked whole grains antagonize the effect of vitamins D and A.

Not only did the Mellanbys discover vitamin D and end the rickets epidemic that was devastating Western cities at the time, they also discovered a cure for early-stage tooth decay that has been gathering dust in medical libraries throughout the world since 1924.

It was in that year that Dr. May Mellanby published a summary of the results of the Mellanby tooth decay reversal studies in the British Medical Journal, titled "Remarks on the Influence of a Cereal-free Diet Rich in Vitamin D and Calcium on Dental Caries in Children". Last year, I had to specially request this article from the basement of the University of Washington medical library (1). Thanks to the magic of the internet, the full version of the paper is now freely available online (2).

You don't need my help to read the study, but in this post I offer a little background, a summary and my interpretation.

In previous studies, the Mellanbys used dogs to define the dietary factors that influence tooth development and repair. They identified three, which together made the difference between excellent and poor dental health (from Nutrition and Disease):

1. The diet's mineral content, particularly calcium and phosphorus
2. The diet's fat-soluble vitamin content, chiefly vitamin D
3. The diet's content of inhibitors of mineral absorption, primarily phytic acid

Once they had defined these factors, they set about testing their hypotheses in humans. They performed eight trials, each one in children in an institutionalized setting where diet could be completely controlled. The number of cavities in each child's mouth was noted at the beginning and end of the period. I'll only discuss the three most informative, and only the most successful in detail. First, the results:

I'll start with diet 1. Children on this diet ate the typical fare, plus extra oatmeal. Oatmeal is typically eaten as an unsoaked whole grain (and soaking it isn't very effective in any case), and so it is high in phytic acid, which effectively inhibits the absorption of a number of minerals including calcium. These children formed 5.8 cavities each and healed virtually none-- not good!

Diet number 2 was similar to diet 1, except there was no extra oatmeal and the children received a large supplemental dose of vitamin D. Over 28 weeks, only 1 cavity per child developed or worsened, while 3.9 healed. Thus, simply adding vitamin D to a reasonable diet allowed most of their cavities to heal.

Diet number 3 was the most effective. This was a grain-free diet plus supplemental vitamin D. Over 26 weeks, children in this group saw an average of only 0.4 cavities form or worsen, while 4.7 healed. The Mellanbys considered that they had essentially found a cure for this disorder in its early stages.

What exactly was this diet? Here's how it was described in the paper (note: cereals = grains):

...instead of cereals- for example, bread, oatmeal, rice, and tapioca- an increased allowance of potatoes and other vegetables, milk, fat, meat, and eggs was given. The total sugar, jam, and syrup intake was the same as before. Vitamin D was present in abundance in either cod-liver oil or irradiated ergosterol, and in egg yolk, butter, milk, etc. The diet of these children was thus rich in those factors, especially vitamin D and calcium, which experimental evidence has shown to assist calcification, and was devoid of those factors- namely, cereals- which interfere with the process.

Carbohydrate intake was reduced by almost half. Bread and oatmeal were replaced by potatoes, milk, meat, fish, eggs, butter and vegetables. The diet is reminiscent of what Dr. Weston Price used to reverse tooth decay in his dental clinic in Cleveland, although Price's diet did include rolls made from freshly ground whole wheat. Price also identified the fat-soluble vitamin K2 MK-4 as another important factor in tooth decay reversal, which would have been abundant in Mellanby's studies due to the dairy. The Mellanbys and Price were contemporaries and had parallel and complementary findings. The Mellanbys did not understand the role of vitamin K2 in mineral metabolism, and Price did not seem to appreciate the role of phytic acid from unsoaked whole grains in preventing mineral absorption.

Here are two sample meals provided in Dr. Mellanby's paper. I believe the word "dinner" refers to the noon meal, and "supper" refers to the evening meal:

Breakfast- Omelette, cocoa, with milk.
Lunch- Milk.
Dinner- Potatoes, steamed minced meat, carrots, stewed fruit, milk.
Tea- Fresh fruit salad, cocoa made with milk.
Supper- Fish and potatoes fried in dripping, milk.

Breakfast- Scrambled egg, milk, fresh salad.
Dinner- Irish stew, potatoes, cabbage, stewed fruit, milk.
Tea- Minced meat warmed with bovril, green salad, milk.
Supper- Thick potato soup made with milk.

In addition, children received vitamin D daily. Here's Dr. Mellanby's summary of their findings:

The tests do not indicate that in order to prevent dental caries children must live on a cereal-free diet, but in association with the results of the other investigations on animals and children they do indicate that the amount of cereal eaten should be reduced, particularly during infancy and in the earlier years of life, and should be replaced by an increased consumption of milk, eggs, butter, potatoes, and other vegetables. They also indicate that a sufficiency of vitamin D and calcium should be given from birth, and before birth, by supplying a suitable diet to the pregnant mother. The teeth of the children would be well formed and more resistant to dental caries instead of being hypoplastic and badly calcified, as were those in this investigation.

If I could add something to this program, I would recommend daily tooth brushing and flossing, avoiding sugar, and rinsing the mouth with water after each meal.

This diet is capable of reversing early stage tooth decay. It will not reverse advanced decay, which requires professional dental treatment as soon as possible. It is not a substitute for dental care in general, and if you try using diet to reverse your own tooth decay, please do it under the supervision of a dentist. And while you're there, tell her about Edward and May Mellanby!

Preventing Tooth Decay
Reversing Tooth Decay
Images of Tooth Decay Healing due to an Improved Diet
Dental Anecdotes

Pastured Dairy may Prevent Heart Attacks

Not all dairy is created equal. Dairy from grain-fed and pasture-fed cows differs in a number of ways. Pastured dairy contains more fat-soluble nutrients such as vitamin K2, vitamin A, vitamin E, carotenes and omega-3 fatty acids. It also contains more conjugated linoleic acid, a fat-soluble molecule that has been under intense study due to its ability to inhibit obesity and cancer in animals. The findings in human supplementation trials have been mixed, some confirming the animal studies and others not. In feeding experiments in cows, Dr. T. R. Dhiman and colleagues found the following (1):

Cows grazing pasture and receiving no supplemental feed had 500% more conjugated linoleic acid in milk fat than cows fed typical dairy diets.

Fat from ruminants such as cows, sheep and goats is the main source of CLA in the human diet. CLA is fat-soluble. Therefore, skim milk doesn't contain any. It's also present in human body fat in proportion to dietary intake. This can come from dairy or flesh.

In a recent article from the AJCN, Dr. Liesbeth Smit and colleagues examined the level of CLA in the body fat of Costa Rican adults who had suffered a heart attack, and compared it to another group who had not (a case-control study, for the aficionados). People with the highest level of CLA in their body fat were 49% less likely to have had a heart attack, compared to those with the lowest level (2).

Since dairy was the main source of CLA in this population, the association between CLA and heart attack risk is inextricable from the other components in pastured dairy fat. In other words, CLA is simply a marker of pastured dairy fat intake in this population, and the (possible) benefit could just as easily have come from vitamin K2 or something else in the fat.

This study isn't the first one to suggest that pastured dairy fat may be uniquely protective. The Rotterdam and EPIC studies found that a higher vitamin K2 intake is associated with a lower risk of heart attack, cancer and overall mortality (3, 4, 5). In the 1940s, Dr. Weston Price estimated that pastured dairy contains up to 50 times more vitamin K2 than grain-fed dairy. He summarized his findings in the classic book Nutrition and Physical Degeneration. This finding has not been repeated in recent times, but I have a little hunch that may change soon...

Vitamin K2
Cardiovascular Disease and Vitamin K2
Can Vitamin K2 Reverse Arterial Calcification?

Full-fat Dairy for Cardiovascular Health??

[2013 update: a few colleagues and I have published a comprehensive review paper on the association between full-fat dairy consumption and obesity, metabolic health, and cardiovascular disease.  You can find it here.]

I just saw a paper in the AJCN titled "Dairy consumption and patterns of mortality of
Australian adults". It's a prospective study with a 15-year follow-up period. Here's a quote from the abstract:

There was no consistent and significant association between total dairy intake and total or cause-specific mortality. However, compared with those with the lowest intake of full-fat dairy, participants with the highest intake (median intake 339 g/day) had reduced death due to CVD (HR: 0.31; 95% confidence interval (CI): 0.12–0.79; P for trend = 0.04) after adjustment for calcium intake and other confounders. Intakes of low-fat dairy, specific dairy foods, calcium and vitamin D showed no consistent associations.

People who ate the most full-fat dairy had a 69% lower risk of cardiovascular death than those who ate the least. Otherwise stated, people who mostly avoided dairy or consumed low-fat dairy had more than three times the risk of dying of coronary heart disease or stroke than people who ate the most full-fat diary.  This result is an outlier, and also observational so difficult to interpret, but it certainly is difficult to reconcile with the idea that dairy fat is a significant contributor to cardiovascular disease.

Contrary to popular belief, full-fat dairy, including milk, butter and cheese, has never been convincingly linked to cardiovascular disease. What has been linked to cardiovascular disease is milk fat's replacement, margarine. In the Rotterdam study, high vitamin K2 intake was linked to a lower risk of fatal heart attack, aortic calcification and all-cause mortality. Most of the K2 came from full-fat cheese.

From a 2005 literature review on milk and cardiovascular disease in the EJCN:

In total, 10 studies were identified. Their results show a high degree of consistency in the reported risk for heart disease and stroke, all but one study suggesting a relative risk of less than one in subjects with the highest intakes of milk.

...the studies, taken together, suggest that milk drinking may be associated with a small but worthwhile reduction in heart disease and stroke risk.

...All the cohort studies in the present review had, however, been set up at times when reduced-fat milks were unavailable, or scarce.

Magnesium and Vitamin D Metabolism

Ted Hutchinson posted a link in the comments section of my last post, pointing to a page on the Vitamin D Council's website where Dr. John Cannell discusses cofactors required for proper vitamin D metabolism. It's actually the site's home page, highlighting how important he feels this matter is. In this case, 'cofactor' simply means another nutrient that's required for the efficient production and use of vitamin D. They include:

• Magnesium
• Zinc
• Vitamin K2
• Vitamin A
• Boron

And probably others we aren't yet aware of. On another page, Dr. Cannell links to two papers that review the critical interaction between magnesium status and vitamin D metabolism (1, 2). Here's a quote from the abstract of the second paper:

Magnesium... is essential for the normal function of the parathyroid glands, metabolism of vitamin D and adequate sensitivity of target tissues to [parathyroid hormone] and active vitamin D metabolites. Magnesium deficit is usually associated with hypoparathyroidism, low production of active vitamin D metabolites, in particular 1,25(OH)2 vitamin D3 and resistance to PTH and vitamin D. On the contrary, magnesium excess, similar to calcium, inhibits PTH secretion. Bone metabolism is impaired under positive as well as under negative magnesium balance.

Magnesium status is critical for normal vitamin D metabolism, insulin sensitivity, and overall health. Supplemental magnesium blocks atherosclerosis in multiple animal models (3, 4). Most Americans don't get enough magnesium (5).

The bottom line is that no nutrient acts in a vacuum. The effect of every part of one's diet and lifestyle is dependent on every other part. I often talk about single nutrients on this blog, but my core philosophy is that a proper diet focuses on Real Food, not nutrients. Tinkering with nutritional status using supplements is potentially problematic. Despite what some people might tell you, our understanding of nutrition and human health is currently rather crude-- so it's best to respect the accumulated wisdom of cultures that don't get the diseases we're trying to avoid.

Interesting Articles in the AJCN

I just received an RSS alert for the American Journal of Clinical Nutrition's latest articles. This upcoming issue is full of very interesting material:

1. Dr. Neil D. Barnard reviews food consumption patterns in the US from 1909 to 2007 (1). This is something I've written about a number of times. The most notable change is that industrial seed oil use has increased by more than 3-fold in the last 40 years, and even more in the last 100 although he doesn't provide those numbers. Butter and lard use declined sharply. Meat consumption is up, but the increase comes exclusively from poultry because we're eating the same amount of red meat we always have. Grain consumption is down, although it peaked around 1900 so it may not be a fair comparison with today:

In the late 1800s, wheat flours became more popular and available due to the introduction of new [high-gluten] wheat varieties, [low extraction] milling techniques, and transport methods, and during this time new breakfast cereals were introduced by John Harvey Kellogg, CW Post, and the Quaker Oats Company. Thereafter, however, per capita availability of flour and cereal products gradually dropped as increased prosperity, improved mechanization, and transport (eg, refrigerated railway cars) increased competition from other food groups. [Then they partially rebounded in the last 40 years]

2. Dr. S.C. Larsson published a paper showing that in Sweden, multivitamin use is associated with a slightly higher risk of breast cancer (2).

3. Soy protein and isoflavones, which have been proposed to do everything from increase bone mineral density to fight cancer, are slowly falling out of favor. Dr. Z.M. Liu and colleagues show that soy protein and/or isoflavone supplementation has no effect on insulin sensitivity or glucose tolerance in a 6 month trial (3). This follows a recent trial showing that isoflavones have no effect on bone mineral density.

4. Dr. Ines Birlouez-Aragon and colleagues showed that high-heat cooked (fried and sauteed) foods increase risk factors for diabetes and cardiovascular disease (insulin resistance, cholesterol, triglycerides), compared to low-heat cooked foods (steamed, stewed) in a one-month trial (4). The high-heat diet also reduced serum levels of long-chain omega-3 fatty acids and vitamins C and E.

5. Dr. Katharina Nimptsch and colleagues showed that higher menaquinone (vitamin K2) intake is associated with a lower cancer incidence and lower cancer mortality in Europeans (5). Most of their K2 came from cheese.

6. And finally, Dr. Zhaoping Li and colleagues showed that cooking meat with an herb and spice blend reduced the levels of oxidized fat during cooking, and reduced serum and urinary markers of lipid oxidation in people eating the meat (6).

Butyric Acid: an Ancient Controller of Metabolism, Inflammation and Stress Resistance?

An Interesting Finding

Susceptible strains of rodents fed high-fat diets overeat, gain fat and become profoundly insulin resistant. Dr. Jianping Ye's group recently published a paper showing that the harmful metabolic effects of a high-fat diet (lard and soybean oil) on mice can be prevented, and even reversed, using a short-chain saturated fatty acid called butyric acid (hereafter, butyrate). Here's a graph of the percent body fat over time of the two groups:

The butyrate-fed mice remained lean and avoided metabolic problems. Butyrate increased their energy expenditure by increasing body heat production and modestly increasing physical activity. It also massively increased the function of their mitochondria, the tiny power plants of the cell.

Butyrate lowered their blood cholesterol by approximately 25 percent, and their triglycerides by nearly 50 percent. It lowered their fasting insulin by nearly 50 percent, and increased their insulin sensitivity by nearly 300 percent*. The investigators concluded:

Butyrate and its derivatives may have potential application in the prevention and treatment of metabolic syndrome in humans.

There's one caveat, however: the butyrate group at less food. Something about the butyrate treatment caused their food intake to decline after 3 weeks, dropping roughly 20% by 10 weeks. The investigators cleverly tried to hide this by normalizing food intake to body weight, making it look like the food intake of the comparison group was dropping as well (when actually it was staying the same as this group was gaining weight).  This does cast some doubt on the health-promoting effects of high-dose butyrate.

I found this study thought-provoking, so I looked into butyrate further.

Butyrate Suppresses Inflammation in the Gut and Other Tissues

In most animals, the highest concentration of butyrate is found in the gut. That's because it's produced by intestinal bacteria from carbohydrate that the host cannot digest, such as cellulose and pectin. Indigestible carbohydrate is the main form of dietary fiber.

It turns out, butyrate has been around in the mammalian gut for so long that the lining of our large intestine has evolved to use it as its primary source of energy. It does more than just feed the bowel, however. It also has potent anti-inflammatory and anti-cancer effects. So much so, that investigators are using oral butyrate supplements and butyrate enemas to treat inflammatory bowel diseases such as Crohn's and ulcerative colitis. Some investigators are also suggesting that inflammatory bowel disorders may be caused or exacerbated by a deficiency of butyrate in the first place.

Butyrate, and other short-chain fatty acids produced by gut bacteria**, has a remarkable effect on intestinal permeability. In tissue culture and live rats, short-chain fatty acids cause a large and rapid decrease in intestinal permeability. Butyrate, or dietary fiber, prevents the loss of intestinal permeability in rat models of ulcerative colitis. This shows that short-chain fatty acids, including butyrate, play an important role in the maintenance of gut barrier integrity. Impaired gut barrier integrity is associated with many diseases, including fatty liver, heart failure and autoimmune diseases (thanks to Pedro Bastos for this information-- I'll be covering the topic in more detail later).

Butyrate's role doesn't end in the gut. It's absorbed into the circulation, and may exert effects on the rest of the body as well. In human blood immune cells, butyrate is potently anti-inflammatory***.

Butyrate Increases Resistance to Metabolic and Physical Stress

Certain types of fiber reduce atherosclerosis in animal models, and this effect may be due to butyrate production produced when the fiber is fermented. Fiber intake was associated with lower blood markers of inflammation in the Women's Health Initiative study, and has been repeatedly associated with lower heart attack risk and reduced progression of atherosclerosis in humans. Butyrate also sharply reduces the harmful effects of type 1 diabetes in rats, as does dietary fiber to a lesser extent.

Butyrate increases the function and survival of mice with certain neurodegenerative diseases. Polyglutamine diseases, which are the most common class of genetic neurodegenerative diseases, are delayed in mice treated with butyrate (1, 2, 3). Many of you have probably heard of Huntington's disease, which is the most common of the class. I did my thesis on a polyglutamine disease called SCA7, and this is the first suggestion I've seen that diet may be able to modify its course.

Yet another interesting finding in the first paper I discussed: mice treated with butyrate were more cold-resistant than the comparison group. When they were both placed in a cold room, body temperature dropped quite a bit in the comparison group, while it remained relatively stable in the butyrate group, despite the fact that the butyrate group was leaner****. This was due to increased heat production in the butyrate group.

Due to the potent effect butyrate has on a number of bodily processes, it may be a fundamental controller of metabolism, stress resistance and the immune system in mammals.

An Ancient Line of Communication Between Symbiotic Organisms

Why does butyrate have so much control over inflammation? Let's think about where it comes from. Bacteria in the gut produce it. It's a source of energy, so our bodies take it up readily. It's one of the main molecules that passes from the symbiotic (helpful) bacteria in the gut to the rest of the body. Could it be that the body receives butyrate as a signal that there's a thriving colony of symbiotic bacteria in the gut, inducing immune tolerance to them? The body may alter its immune response (inflammation) in order to permit a mutually beneficial relationship between itself and its symbionts.

Sources of Butyrate

There are two main ways to get butyrate and other short-chain fatty acids. The first is to eat fiber and let your intestinal bacteria do the rest. Whole plant foods such as sweet potatoes, properly prepared whole grains, beans, vegetables, fruit and nuts are good sources of fiber. Refined foods such as white flour, white rice and sugar are very low in fiber. Clinical trials have shown that increasing dietary fiber increases butyrate production, and decreasing fiber decreases it (free full text).

Butyrate also occurs in significant amounts in food. What foods contain butyrate? Hmm, I wonder where the name BUTYR-ate came from? Butter perhaps? Butter is 3-4 percent butyrate, the richest known source. But everyone knows butter is bad for you, right?

After thinking about it, I've decided that butyrate may have been a principal component of Dr. Weston Price's legendary butter oil. Price used this oil in conjunction with high-vitamin cod liver oil to heal tooth decay and a number of other ailments in his patients. The method he used to produce it would have concentrated fats with a low melting temperature, including butyrate, in addition to vitamin K2*****. Thus, the combination of high-vitamin cod liver oil and butter oil would have provided a potent cocktail of fat-soluble vitamins (A, D3, K2), omega-3 fatty acids and butyrate. It's no wonder it was so effective in his patients.


* According to insulin tolerance test.

** Acetate (acetic acid, the main acid in vinegar), propionate and butyrate are the primary three fatty acids produced by intestinal fermentation.

*** The lowest concentration used in this study, 30 micromolar, is probably higher than the concentration in peripheral serum under normal circumstances. Human serum butyrate is in the range of 4 micromolar in British adults, and 29 micromolar in the hepatic portal vein which brings fats from the digestive tract to the liver (ref). This would likely be at least two-fold higher in populations eating high-fiber diets.

**** Due to higher mitochondrial density in brown fat and more mitochondrial uncoupling.

***** Slow crystallization, which selectively concentrates triglycerides with a low melting point.

Malocclusion: Disease of Civilization, Part IX

A Summary

For those who didn't want to wade through the entire nerd safari, I offer a simple summary.

Our ancestors had straight teeth, and their wisdom teeth came in without any problem. The same continues to be true of a few non-industrial cultures today, but it's becoming rare. Wild animals also rarely suffer from orthodontic problems.

Today, the majority of people in the US and other affluent nations have some type of malocclusion, whether it's crooked teeth, overbite, open bite or a number of other possibilities.

There are three main factors that I believe contribute to malocclusion in modern societies:

1. Maternal nutrition during the first trimester of pregnancy. Vitamin K2, found in organs, pastured dairy and eggs, is particularly important. We may also make small amounts from the K1 found in green vegetables.
2. Sucking habits from birth to age four. Breast feeding protects against malocclusion. Bottle feeding, pacifiers and finger sucking probably increase the risk of malocclusion. Cup feeding and orthodontic pacifiers are probably acceptable alternatives.
3. Food toughness. The jaws probably require stress from tough food to develop correctly. This can contribute to the widening of the dental arch until roughly age 17. Beef jerky, raw vegetables, raw fruit, tough cuts of meat and nuts are all good ways to exercise the jaws.
   

And now, an example from the dental literature to motivate you. In 1976, Dr. H. L. Eirew published an interesting paper in the British Dental Journal. He took two 12-year old identical twins, with identical class I malocclusions (crowded incisors), and gave them two different orthodontic treatments. Here's a picture of both girls before the treatment:


In one, he made more space in her jaws by extracting teeth. In the other, he put in an apparatus that broadened her dental arch, which roughly mimics the natural process of arch growth during childhood and adolescence. This had profound effects on the girls' subsequent occlusion and facial structure:

The girl on the left had teeth extracted, while the girl on the right had her arch broadened. Under ideal circumstances, this is what should happen naturally during development. Notice any differences?

Thanks to the Weston A Price foundation's recent newsletter for the study reference.

Malocclusion: Disease of Civilization, Part V

Prenatal Development of the Face and Jaws

The structures of the face and jaws take shape during the first trimester of pregnancy. The 5th to 11th weeks of pregnancy are particularly crucial for occlusion, because this is when the jaws, nasal septum and other cranial structures form. The nasal septum is the piece of cartilage that forms the structure of the nose and separates the two air passages as they enter the nostrils.

Maternal Nutritional Status Affects Fetal Development

Abnormal nutrient status can lead to several types of birth defects. Vitamin A is an essential signaling molecule during development. Both deficiency and excess can cause birth defects, with the effects predominantly targeting the cranium and nervous system, respectively. Folic acid deficiency causes birth defects of the brain and spine. Other nutrients such as vitamin B12 may influence the risk of birth defects as well*.

The Role of Vitamin K

As early as the 1970s, physicians began noting characteristic developmental abnormalities in infants whose mothers took the blood-thinning drug warfarin (coumadin) during the first trimester of pregnancy. These infants showed an underdevelopment of the nasal septum, the maxilla (upper jaw), small or absent sinuses, and a characteristic "dished" face. This eventually resulted in narrow dental arches, severe malocclusion and tooth crowding**. The whole spectrum was called Binder's syndrome, or warfarin embryopathy.

Warfarin works by inhibiting vitamin K recycling, thus depleting a nutrient necessary for normal blood clotting. It's now clear that Binder's syndrome can result from anything that interferes with vitamin K status during the first trimester of pregnancy. This includes warfarin, certain anti-epilepsy drugs, certain antibiotics, genetic mutations that interfere with vitamin K status, and celiac disease (intestinal damage due to gluten).

Why is vitamin K important for the development of the jaws and face of the fetus? Vitamin K is required to activate a protein called matrix gla protein (MGP), which prevents unwanted calcification of the nasal septum in the developing fetus (among other things). If this protein isn't activated by vitamin K during the critical developmental window, calcium deposits form in the nasal septum, stunting its growth and also stunting the growth of the maxilla and sinuses. Low activity of MGP appears to be largely responsible for Binder's syndrome, since the syndrome can be caused by genetic mutations in MGP in humans. Small or absent sinuses are common in the general population.

One of the interesting things about MGP is its apparent preference for vitamin K2 over vitamin K1. Vitamin K1 is found predominantly in green vegetables, and is sufficient to activate blood clotting factors and probably some other vitamin K-dependent proteins. "Vitamin K2" refers to a collection of molecules known as menaquinones. These are denoted as "MK", followed by a number indicating the length of the side chain attached to the quinone ring.

Biologically important menaquinones are MK-4 through MK-12 or so. MK-4 is the form that animals synthesize from vitamin K1 for their own use. Certain organs (brain, pancreas, salivary gland, arteries) preferentially accumulate K2 MK-4, and certain cellular processes are also selective for K2 MK-4 (MGP activation, PKA-dependent transcriptional effects). Vitamin K2 MK-4 is found almost exclusively in animal foods, particularly pastured butter, organs and eggs. It is always found in foods designed to nourish growing animals, such as eggs and milk.

Humans have the ability to convert K1 to K2 when K1 is ingested in artificially large amounts. However, due to the limited absorption of normal dietary sources of K1 and the unknown conversion efficiency, it's unclear how much green vegetables contribute to K2 status. Serum vitamin K1 reaches a plateau at about 200 micrograms per day of dietary K1 intake, the equivalent of 1/4 cup of cooked spinach (see figure 1 of this paper). Still, I think eating green vegetables regularly is a good idea, and may contribute to K2 status. Other menaquinones such as MK-7 (found in natto) may contribute to K2 status as well, but this question has not been resolved.

Severe vitamin K deficiency clearly impacts occlusion. Could more subtle deficiency lead to a less pronounced form of the same developmental syndrome? Here are a few facts about vitamin K relevant to this question:

• In industrial societies, newborns are typically vitamin K deficient. This is reflected by the fact that in the US, nearly all newborns are given vitamin K1 at birth to prevent potentially fatal hemorrhage. In Japan, infants are given vitamin K2 MK-4, which is equally effective at preventing hemmorhage.
• Fetuses generally have low vitamin K status, as measured by the activity of their clotting factors.
  
• The human placenta transports vitamin K across the placental barrier and accumulates it. This transport mechanism is highly selective for vitamin K2 MK-4 over K1.
• The concentration of K1 in maternal blood is much higher than its concentration in umbilical cord blood, whereas the concentration of K2 in maternal blood is similar to the concentration in cord blood. Vitamin K2 MK-7 is undetectable in cord blood, even when supplemented, suggesting that MK-7 is not an adequate substitute for MK-4 during pregnancy.
  
• In rat experiments, arterial calcification due to warfarin was inhibited by vitamin K2 MK-4, but not vitamin K1. This is probably due to K2's ability to activate MGP, the same protein required for the normal development of the human face and jaws.
  
• The human mammary gland appears to be the most capable organ at converting vitamin K1 to K2 MK-4.
  

Together, this suggests that in industrial societies, fetuses and infants are vitamin K deficient, to the point of being susceptible to fatal hemorrhage. It also suggests that vitamin K2 MK-4 plays a critical role in fetal and early postnatal development. Could subclinical vitamin K2 deficiency be contributing to the high prevalence of malocclusion in modern societies?

An Ounce of Prevention

Vitamin A, folic acid, vitamin D and vitamin K2 are all nutrients with a long turnover time. Body stores of these nutrients depend on long-term intake. Thus, the nutritional status of the fetus during the first trimester reflects what the mother has been eating for several months before conception.

Dr. Weston Price noted that a number of the traditional societies he visited prepared women of childbearing age for healthy pregnancies by giving them special foods rich in fat-soluble vitamins. This allowed them to gestate and rear healthy, well-formed children. Nutrient-dense animal foods and green vegetables are a good idea before, during and after pregnancy.


* Liver is the richest source of vitamin A, folic acid and B12.

** Affected individuals may show class I, II, or III malocclusion.

Dihydro-Vitamin K1

Step right up ladies and gents; I have a new miracle vitamin for you. Totally unknown to our ignorant pre-industrial ancestors, it's called dihydro-vitamin K1. It's formed during the oil hydrogenation process, so the richest sources are hydrogenated fats like margarine, shortening and commercial deep fry oil. Some of its benefits may include:

• Inhibiting vitamin K2 metabolism
• Reducing bone mineral density
  
• Causing organ damage and inhibiting platelet formation in animal models
• Dramatically increasing the death rate of spontaneously hypertensive rats

Dihydro-vitamin K1 accounts for roughly 30% of the vitamin K intake of American children, and a substantial portion of adult intake as well. Over 99 percent of Americans have it in their diet. Research on dihydro-vitamin K1 is in its infancy at this point, so no one has a very solid idea of its effects on the body beyond some preliminary and disturbing suggestions from animal experiments and brief human trials.

This could be another mechanism by which industrially processed vegetable oils degrade health. It's also another example of why it's not a good idea to chemically alter food. We don't understand food, or our bodies, well enough to know the long-term consequences of foods that have been recently introduced to the human diet. I believe these foods should be avoided on principle.

Pastured Eggs

Eggs are an exceptionally nutritious food. It's not surprising, considering they contain everything necessary to build a chick! But all eggs are not created equal. Anyone who has seen the tall, orange yolk, viscous white, and tough shell of a true pastured egg knows they're profoundly different. So has anyone who's tasted one. This has been vigorously denied by the American Egg Board and the Egg Nutrition Council, primarily representing conventional egg farmers, which assert that eggs from giant smelly barns are nutritionally equal to their pastured counterparts.

In 2007, the magazine Mother Earth News decided to test that claim. They sent for pastured eggs from 14 farms around the U.S., tested them for a number of nutrients, and compared them to the figures listed in the USDA Nutrient Database for conventional eggs. Here are the results per 100 grams for conventional eggs, the average of all the pastured eggs, and eggs from Skagit River Ranch, which sells at my farmer's market:

Vitamin A:

• Conventional: 487 IU
• Pastured avg: 792 IU
• Skagit Ranch: 1013 IU
  

Vitamin D:

• Conventional: 34 IU
  
• Pastured avg: 136 - 204 IU
  
• Skagit Ranch: not determined
  

Vitamin E:

• Conventional: 0.97 mg
• Pastured avg: 3.73 mg
  
• Skagit Ranch: 4.02 mg

Beta-carotene:

• Conventional: 10 mcg
  
• Pastured avg: 79 mcg
  
• Skagit Ranch: 100 mcg
  

Omega-3 fatty acids:

• Conventional: 0.22 g
  
• Pastured avg: 0.66 g
  
• Skagit Ranch: 0.74 g
  

Looks like the American Egg Board and the Egg Nutrition Council have some egg on their faces...

Eggs also contain vitamin K2, with the amount varying substantially according to the hen's diet. Guess where the A, D, K2, beta-carotene and omega-3 fatty acids are? In the yolk of course. Throwing the yolk away turns this powerhouse into a bland, nutritionally unimpressive food.

It's important to note that "free range" supermarket eggs are nutritionally similar to conventional eggs. The reason pastured eggs are so nutritious is that the chickens get to supplement their diets with abundant fresh plants and insects. Having little doors on the side of a giant smelly barn just doesn't replicate that.

Dental Anecdotes

Here are a few anecdotes gleaned from past comments that describe improvements in oral health due to a change in diet. Please feel free to add your own (positive or negative) experience to the comments. I may add it to the post.

Stan: My teeth stopped decaying and some breakage (broken tooth due to mechanical damage, 5 years ago) begun sealing itself with new enamel on my high animal fat, low carb diet of the last 10 years. I still have all my teeth including wisdom teeth. My teeth no longer develop plaque/scale and thus no need to descale, and I no longer develop cold sores on my gums. I haven't been to a dentist since 1999 (I am 53). [From another comment] I can fully confirm the astounding effect of a diet very high in animal produce and low in plants, on my teeth. My tooth decay has totally stopped! I wrote about that before but it is worth repeating: - my teeth would not decay even if mechanically damaged, broken in half etc. The broken exposed parts of a tooth, even if the core is open, just seals itself over time.

Dave: Our family has had similar experiences. In particular, my daughter had a poorly formed molar (she was a spring baby, before we started Vitamin D, hmmmm). The tooth had quite a large crater in it. I put her on D3 and cod liver oil/butter oil. We finally got a dentist she'd cooperate with enough for X-rays. The result was exactly as described above: a thick layer of dentin had formed. The dentist was thoroughly puzzled, which I enjoyed immensely :-)

Arnoud: For years my dentist has been insisting on more frequent and more aggressive cleaning techniques.... to no avail. Last year I started Vitamin D supplementation, and a more Paleo style of diet, and the 'chronic' inflammation of my gums resolved themselves within days, literally. My dentist claims it is a coincidence. I think not!

Martin: Once I changed my diet to one close to what is listed in this entry, and added a vitamin D3 supplement, my dental health greatly improved. No more cavities, and beyond that, no more rapid build-up of dental plaque. To prevent gum problems, I used to have to get my teeth cleaned four times a year, now, once a year is enough, and it seems to me, even that might not be necessary.

Thresshold: I am a cavity-every-six-months person, who arrested decay for 3 years by going on a Protein Power-like diet. No limit on non-starchy veggies, lots of meat-- turkey, beef --lots of nuts, olive oil, egg a day. No grains. Very little fruit, no sugar. Plenty of supplemented vitamin A and D, E, C, Bs, some dolomite.

Jeff: I just had a dentist visit, first in almost 3 years. No cavities for the first time in a while. Your advice and a Paleo diet are the reason, in my mind.

Dr. Dan: Before paleo I had bleeding gums and sore teeth. Now that I have been on it I have not had them and my flatmate just commented how white my teeth are looking.

Cheeseslave: I have also eliminated cavities since I changed the way I eat. I avoid all phytic acid (I try to only eat sprouted bread or naturally fermented sourdough) and I soak or sprout all my grains, legumes, nuts and seeds. I also take cod liver oil, and eat a nutrient-dense diet consisting of mostly meat and dairy.

Dr. B. G.: Myself, I had periodontal disease (esp immed after pregnancy and lactation -- wonder W-H-Y ??!) however at the last check up -- I have no more pockets of '5' and am released to come in only 2x annually instead of all the extra (painful) de-planing and cleanings. This was improved by: vitamin A, vitamin D 5000 IU every am, high dose fish oil, flaxseed and egg yolks and saturated fats and some K2 supplements. [From another comment] I have to admit -- my dental problems reversed prior to total Paleo eating (eg, wheat-free). On vitamin D and fish oil alone my cavities sealed. In fact I had gone back to see the DDS but he couldn't find one tiny 'sticky' spot. When he decided to fill it irregardless (and I was an idiot to not walk out b/c who knew that cavities could heal/seal...on their own??), then I had to leave him. At that point, the dental hygienist had already let me return to a 'normal' insured 2 cleanings/yr schedule, instead of the $$ 4/year (where 2 were out-of-pocket). With going 100% wheat-free, vits ADEK and adding a little (fresh highquality) flaxseed oil, my gums are super healthy and no throbbing at all for the last 9mos!

Brock: When I went to my dentist for the first time in a while last September I was told I had six cavities. My dentist told me to schedule to get them filled in, but I never did. I just had the intuitive feeling that the human body ought to be able to heal itself, and that for some reason my dentist just didn't know how. So, I started Googling. My search lead me here and to the Weston Price Foundation. I bought Dr. Price's book and changed by diet months ago. I eat mostly paleo but mainly just focus on avoiding wheat, corn, sugar and n6 fats. I supplement with Vitamins A, C, D, E and K2. Long story short, my six cavities have closed up and my teeth have noticeably improved in color and "feel". Swelling in my gums is down. I can often go for weeks now without brushing my teeth without any noticeable side effects. It's great.

Andrew S.:I had a lot of cavities growing up, and as a young adult. I started up a new company, didn't have health insurance, and didn't go to the dentist in a while -- and started eating whole, natural foods, with a bit of supplementation (mostly cod liver oil). I was surprised when I visited the dentist for the first time in years to not have any decay.

Robert Andrew Brown: I too have gone from regular cavities, indifferent gum health, sensitive teeth, and a host of dental work to prove it, to none since balancing the Omega 3s and 6s, and regular 'industrial' cod liver oil. Small carries that were sensitive and on the list for restorative work have re mineralised and skinned over but not refilled. I have only recently started seriously increasing vitamin D and reintroducing grass fed butter.

Reversing Tooth Decay

In the last post, I discussed the research of Drs. Edward and May Mellanby on the nutritional factors affecting tooth formation. Dr. Mellanby is the man who discovered vitamin D and identified the cause of rickets. Nutrition has a profound effect on tooth structure, and well-formed teeth are inherently resistant to decay. But is there anything you can do if your teeth are already formed?

Teeth are able to heal themselves. That's one reason why traditional cultures such as the Inuit can wear their teeth down to the pulp due to chewing leather and sand-covered dried fish, yet still have an exceptionally low rate of tooth decay. It's also how the African Wakamba tribe could traditionally file their front teeth into sharp points without causing decay. Both cultures lost their resistance to tooth decay after adopting nutrient-poor Western foods such as white flour and sugar.

Teeth are made of four layers. Enamel is the hardest, most mineralized outer shell. Dentin is another protective mineralized layer that's below the enamel. Below the dentin is the pulp, which contains blood vessels and nerves. The roots are coated with cementum, another mineralized tissue.

When enamel is poorly formed and/or the diet isn't adequate, enamel demineralizes and decay sets in. Tooth decay is an opportunistic infection that takes advantage of poorly developed or maintained teeth. If the diet remains inadequate, the tooth has to be filled or removed, or the person risks more serious complications.

Fortunately, a decaying or broken tooth has the ability to heal itself if the diet is good, including by remineralizing enamel and dentin, and/or forming a limited quantity of new dentin. This new dentin is deposited by specialized cells called odontoblasts. Here's what Dr. Edward Mellanby had to say about his wife's research on the subject. This is taken from Nutrition and Disease:

Since the days of John Hunter it has been known that when the enamel and dentine are injured by attrition or caries, teeth do not remain passive but respond to the injury by producing a reaction of the odontoblasts in the dental pulp in an area generally corresponding to the damaged tissue and resulting in a laying down of what is known as secondary dentine. In 1922 M. Mellanby proceeded to investigate this phenomenon under varying nutritional conditions and found that she could control the secondary dentine laid down in the teeth of animals as a reaction to attrition both in quality and quantity, independently of the original structure of the tooth. Thus, when a diet of high calci­fying qualities, ie., one rich in vitamin D, calcium and phosphorus was given to the dogs during the period of attrition, the new secondary dentine laid down was abundant and well formed whether the original structure of the teeth was good or bad. On the other hand, a diet rich in cereals and poor in vitamin D resulted in the production of secondary dentine either small in amount or poorly calcified, and this happened even if the primary dentine was well formed.

Thus, in dogs, the factors that affect tooth healing are the same factors that affect tooth development:

1. The mineral content of the diet, particularly calcium and phosphorus
2. The fat-soluble vitamin content of the diet, chiefly vitamin D
3. The availability of minerals for absorption, determined largely by the diet's phytic acid content (prevents mineral absorption)

What about humans? Drs. Mellanby set out to see if they could use their dietary principles to cure tooth decay that was already established. They divided 62 children with cavities into three different diet groups for 6 months. Group 1 ate their normal diet plus oatmeal (rich in phytic acid). Group 2 ate their normal diet plus vitamin D. Group 3 ate a grain-free diet and took vitamin D.

In group 1, oatmeal prevented healing and encouraged new cavities, presumably due to its ability to prevent mineral absorption. In group 2, simply adding vitamin D to the diet caused most cavities to heal and fewer to form. The most striking effect was in group 3, the group eating a grain-free diet plus vitamin D, in which nearly all cavities healed and very few new cavities developed. Grains are the main source of phytic acid in the modern diet, although we can't rule out the possibility that grains were promoting tooth decay through another mechanism as well.

Dr. Mellanby was quick to point out that diet 3 contained some carbohydrate (~45% reduction) and was not low in sugar: "Although [diet 3] contained no bread, porridge or other cereals, it included a moderate amount of carbohydrates, for plenty of milk, jam, sugar, potatoes and vegetables were eaten by this group of children." This study was published in the British Medical Journal (1) and the British Dental journal. Here's Dr. Edward Mellanby again:

The hardening of carious areas that takes place in the teeth of children fed on diets of high calcifying value indicates the arrest of the active process and may result in “healing” of the infected area. As might be surmised, this phenomenon is accompanied by a laying down of a thick barrier of well-formed secondary denture... Summing up these results it will be clear that the clinical deductions made on the basis of the animal experiments have been justified, and that it is now known how to diminish the spread of caries and even to stop the active carious process in many affected teeth.

Dr. Mellanby first began publishing studies showing the reversal of cavities in humans using diet in 1924. Why has such a major medical finding, published in high-impact peer-reviewed journals, faded into obscurity?

Dr. Weston Price also had success curing tooth decay using a similar diet. He fed poor children one very nutritious meal a day and monitored their dental health. From Nutrition and Physical Degeneration (p. 290):

About four ounces of tomato juice or orange juice and a teaspoonful of a mixture of equal parts of a very high vitamin natural cod liver oil and an especially high vitamin butter was given at the beginning of the meal. They then received a bowl containing approximately a pint of a very rich vegetable and meat stew, made largely from bone marrow and fine cuts of tender meat: the meat was usually broiled separately to retain its juice and then chopped very fine and added to the bone marrow meat soup which always contained finely chopped vegetables and plenty of very yellow carrots; for the next course they had cooked fruit, with very little sweetening, and rolls made from freshly ground whole wheat, which were spread with the high-vitamin butter. The wheat for the rolls was ground fresh every day in a motor driven coffee mill. Each child was also given two glasses of fresh whole milk. The menu was varied from day to day by substituting for the meat stew, fish chowder or organs of animals.

Dr. Price provides before and after X-rays showing re-calcification of cavity-ridden teeth on this program. His intervention was not exactly the same as Drs. Mellanby, but it was similar in many ways. Both diets were high in minerals, rich in fat-soluble vitamins (including D), and low in phytic acid.

Price's diet was not grain-free, but used rolls made from freshly ground whole wheat. Freshly ground whole wheat has a high phytase (the enzyme that degrades phytic acid) activity, thus in conjunction with the long yeast rises common in Price's time, it would have broken down nearly all of its own phytic acid. This would have made it a source of minerals rather than a sink for them. He also used high-vitamin pastured butter in conjunction with cod liver oil. We now know that the vitamin K2 in pastured butter is important for bone and tooth development and maintenance. This was something that Dr. Mellanby did not understand at the time, but modern research has corroborated Price's finding that K2 is synergistic with vitamin D in promoting skeletal and dental health.

If I were to design the ultimate dietary program to heal cavities that incorporates the successes of both doctors, it would look something like this:

• Rich in animal foods, particularly full-fat pastured dairy products (if tolerated) and bone broths. Also meat, organs, fish, and eggs.
• Fermented grains only; no unfermented grains such as oatmeal, breakfast cereal, crackers, etc. No breads except true sourdough (ingredients should not list lactic acid). Or even better, no grains at all.
• Limited nuts; beans in moderation, only if they're soaked overnight or longer prior to cooking (due to the phytic acid).
• Starchy vegetables such as potatoes and sweet potatoes.
• A limited quantity of fruit (one piece per day or less), but no refined sweets.
• Cooked and raw vegetables.
• Sunlight, high-vitamin cod liver oil, or vitamin D3 supplements.
• Pastured butter.
• No industrially processed food.

This diet would maximize mineral absorption while providing abundant fat-soluble vitamins. It probably isn't necessary to follow it strictly. For example, if you eat more mineral-rich foods such as dairy and bone broths, you can probably get away with more phytic acid. Or you might be able to heal cavities eating like this for only one or two meals a day, as Dr. Price demonstrated. 

This post is focused on diet, but obviously oral hygiene also matters.  Brushing your teeth, flossing, and rinsing your mouth out after meals will also reduce dental risks.  

The technique described above is applicable to early-stage, small cavities, not necessarily to advanced decay.  If you try to heal your own cavities using diet, please do it under the supervision of a dentist.  

Latest Study on Vitamin K and Coronary Heart Disease

A Dutch group led by Dr. Yvonne T. van der Schouw recently published a paper examining the link between vitamin K intake and heart attack (thanks Robert). They followed 16,057 women ages 49-70 years for an average of 8.1 years, collecting data on their diet and incidence of heart attack.

They found no relationship between K1 intake and heart attack incidence. K1 is the form found in leafy greens and other plant foods. They found that each 10 microgram increase in daily vitamin K2 consumption was associated with a 9% lower incidence of heart attack. Participants consumed an average of 29 micrograms K2 per day, with a range of 0.9 to 128 micrograms. That means that participants with the highest intake had a very much reduced incidence of heart attack on average. Vitamin K2 comes from animal foods (especially organs and pastured dairy)and fermented foods such as cheese, sauerkraut, miso and natto. Vitamin K is fat-soluble, so low-fat animal foods contain less of it. Animal foods contain the MK-4 subtype while fermentation produces longer menaquinones, MK-5 through MK-14.

There's quite a bit of evidence to support the idea that vitamin K2 inhibits and possibly reverses arterial calcification, which is possibly the best overall measure of heart attack risk. It began with the observations of Dr. Weston Price, who noticed an inverse relationship between the K2 MK-4 content of butter and deaths from coronary heart disease and pneumonia in several regions of the U.S. You can find those graphs in Nutrition and Physical Degeneration.

The 25% of participants eating the most vitamin K2 (and with the lowest heart attack risk) also had the highest saturated fat, cholesterol, protein and calcium intake. They were much less likely to have elevated cholesterol, but were more likely to be diabetic.

Here's where the paper gets strange. They analyzed the different K2 subtypes individually (MK-4 through MK-9). MK-7 and MK-6 had the strongest association with reduced heart attack risk per microgram consumed, while MK-4 had no significant relationship. MK-8 and MK-9 had a weak but significant protective relationship.

There are a few things that make me skeptical about this result. First of all, the studies showing prevention/reversal of arterial calcification in rats were done with MK-4. MK-4 inhibits vascular calcification in rats whereas I don't believe the longer menaquinones have been tested. Furthermore, they attribute a protective effect to MK-7 in this study, but the average daily intake was only 0.4 micrograms! You could get that amount of K2 if a Japanese person who had eaten natto last week sneezed on your food. I can't imagine that amount of MK-7 is biologically significant. That, among other things, makes me skeptical of what they're really observing.

I'm not convinced of their ability to parse the effect into the different K2 subtypes. They mentioned in the methods section that their diet survey wasn't very accurate at estimating the individual K2 subtypes. Combine that with the fact that the K2 content of foods varies quite a bit by animal husbandry practice and type of cheese, and you have a lot of variability in your data. Add to that the well-recognized variability inherent in these food questionnaires, and you have even more variabiltiy.

I'm open to the idea that longer menaquinones (K2 MK-5 and longer, including MK-7) play a role in preventing cardiovascular disease, but I don't find the evidence sufficient yet. MK-4 is the form of K2 that's made by animals, for animals. Mammals produce it in their breast milk and other animals produce it in eggs all the way down to invertebrates. I think we can assume they make MK-4, and not the longer menaquinones, for a reason.

MK-4 is able to play all the roles of vitamin K in the body, including activating blood clotting factors, a role traditionally assigned to vitamin K1. This is obvious because K2 MK-4 is the only significant source of vitamin K in the diet of infants before weaning. No one knows whether the longer menaquinones are able to perform all the functions of MK-4; it hasn't been tested and I don't know how you could ever be sure. MK-7 is capable of performing at least some of these functions, such as activating osteocalcin and clotting factors.

I do think it's worth noting that the livers of certain animals contain longer menaquinones, including MK-7. So it is possible that we're adapted to eating some of the longer menaquinones. Many cultures also have a tradition of fermented food (probably a relatively recent addition to the human diet), which could further increase the intake of longer menaquinones. The true "optimum", if there is one, may be to eat a combination of forms of K2, including MK-4 and the longer forms. But babies and healthy traditional cultures such as the Masai seem to do quite well on a diet heavily weighted toward MK-4, so the longer forms probably aren't strictly necessary.

Well if you've made it this far, you're a hero (or a nerd)! Now for some humor. From the paper:

The concept of proposing beneficial effects to vitamin K2 seems to have different basis as for vitamin K1. Vitamin K1 has been associated with a heart-healthy dietary pattern in the earlier work in the USA and this attenuated their associations with CHD. Vitamin K2 has different sources and relate to different dietary patterns than vitamin K1. This suggests that the risk reduction with vitamin K2 is not driven by dietary patterns, but through biological effects.

They seem confused by the fact that people who ate foods high in saturated fat and cholesterol had less CHD, yet people consuming green vegetables didn't.  Here's more:

Thus, although our findings may have important practical implications on CVD prevention, it is important to mention that in order to increase the intake of vitamin K2, increasing the portion vitamin K2 rich foods in daily life might not be a good idea. Vitamin K2 might be, for instance more relevant in the form of a supplement or in low-fat dairy. More research into this is necessary.

Translation: "People who ate the most cheese, milk and meat had the lowest heart attack rate, but be careful not to eat those things because they might give you a heart attack. Get your K2 from low-fat dairy (barely contains any) and supplements."

Vitamin K2 and Cranial Development

One of the things Dr. Weston Price noticed about healthy traditional cultures worldwide is their characteristically broad faces, broad dental arches and wide nostrils. Due to the breadth of their dental arches, they invariably had straight teeth and enough room for wisdom teeth. As soon as these same groups adopted white flour and sugar, the next generation to be born grew up with narrow faces, narrow dental arches, crowded teeth, pinched nostrils and a characteristic underdevelopment of the middle third of the face.

Here's an excerpt from Nutrition and Physical Degeneration, about traditional and modernized Swiss groups. Keep in mind these are Europeans we're talking about (although he found the same thing in all the races he studied):

The reader will scarcely believe it possible that such marked differences in facial form, in the shape of the dental arches, and in the health condition of the teeth as are to be noted when passing from the highly modernized lower valleys and plains country in Switzerland to the isolated high valleys can exist. Fig. 3 shows four girls with typically broad dental arches and regular arrangement of the teeth. They have been born and raised in the Loetschental Valley or other isolated valleys of Switzerland which provide the excellent nutrition that we have been reviewing.
Another change that is seen in passing from the isolated groups with their more nearly normal facial developments, to the groups of the lower valleys, is the marked irregularity of the teeth with narrowing of the arches and other facial features... While in the isolated groups not a single case of a typical mouth breather was found, many were seen among the children of the lower-plains group. The children studied were from ten to sixteen years of age.

Price attributed this physical change to a lack of minerals and the fat-soluble vitamins necessary to make good use of them: vitamin A, vitamin D and what he called "activator X"-- now known to be vitamin K2 MK-4. The healthy cultures he studied all had an adequate source of vitamin K2, but many ate very little K1 (which comes mostly from vegetables). Inhabitants of the Loetschental valley ate green vegetables only in summer, due to the valley's harsh climate. The rest of the year, the diet was limited chiefly to whole grain sourdough rye bread and pastured dairy products.

The dietary transitions Price observed were typically from mineral- and vitamin-rich whole foods to refined modern foods, predominantly white flour and sugar. The villagers of the Loetschental valley obtained their fat-soluble vitamins from pastured dairy, which is particularly rich in vitamin K2 MK-4.

In a modern society like the U.S., most people exhibit signs of poor cranial development. How many people do you know with perfectly straight teeth who never required braces? How many people do you know whose wisdom teeth erupted normally?

The archaeological record shows that our hunter-gatherer ancestors generally didn't have crooked teeth. Humans evolved to have dental arches in proportion to their tooth size, like all animals. Take a look at these chompers. That skull is from an archaeological site in the Sahara desert that predates agriculture in the region. Those beautiful teeth are typical of paleolithic humans and modern hunter-gatherers. Crooked teeth and impacted wisdom teeth are only as old as agriculture. However, Price found that with care, certain traditional cultures were able to build well-formed skulls on an agricultural diet.

So was Price on to something, or was he just cherry picking individuals that supported his hypothesis? It turns out there's a developmental syndrome in the literature that might shed some light on this. It's called Binder's syndrome. Here's a description from a review paper about Binder's syndrome (emphasis mine):

The essential features of maxillo-nasal dysplasia were initially described by Noyes in 1939, although it was Binder who first defined it as a distinct clinical syndrome. He reported on three cases and recorded six specific characteristics:⁵

• Arhinoid face.
• Abnormal position of nasal bones.
• Inter-maxillary hypoplasia with associated malocclusion.
• Reduced or absent anterior nasal spine.
• Atrophy of nasal mucosa.
• Absence of frontal sinus (not obligatory).

Individuals with Binder's syndrome have a characteristic appearance that is easily recognizable.⁶ The mid-face profile is hypoplastic, the nose is flattened, the upper lip is convex with a broad philtrum, the nostrils are typically crescent or semi-lunar in shape due to the short collumela, and a deep fold or fossa occurs between the upper lip and the nose, resulting in an acute nasolabial angle.

Allow me to translate: in Binder's patients, the middle third of the face is underdeveloped, they have narrow dental arches and crowded teeth, small nostrils and abnormally small sinuses (sometimes resulting in mouth breathing). Sound familiar? So what causes Binder's syndrome? I'll give you a hint: it can be caused by prenatal exposure to warfarin (coumadin).

Warfarin is rat poison. It kills rats by causing them to lose their ability to form blood clots, resulting in massive hemmorhage. It does this by depleting vitamin K, which is necessary for the proper functioning of blood clotting factors. It's used (in small doses) in humans to thin the blood as a treatment for abnormal blood clots. As it turns out, Binder's syndrome can be caused by a number of things that interfere with vitamin K metabolism. The sensitive period for humans is the first trimester. I think we're getting warmer...

Another name for Binder's syndrome is "warfarin embryopathy". There happens to be a rat model of it. Dr. Bill Webster's group at the University of Sydney injected rats daily with warfarin for up to 12 weeks, beginning on the day they were born (rats have a different developmental timeline than humans). They also administered large doses of vitamin K1 along with it. This is to ensure the rats continue to clot normally, rather than hemorrhaging. Another notable property of warfarin that I've mentioned before is its ability to inhibit the conversion of vitamin K1 to vitamin K2 MK-4. Here's what they had to say about the rats:

The warfarin-treated rats developed a marked maxillonasal hypoplasia associated with a 11-13% reduction in the length of the nasal bones compared with controls... It is proposed that (1) the facial features of the human warfarin embryopathy are caused by reduced growth of the embryonic nasal septum, and (2) the septal growth retardation occurs because the warfarin-induced extrahepatic vitamin K deficiency prevents the normal formation of the vitamin K-dependent matrix gla protein in the embryo.

"Maxillonasal hypoplasia" means underdevelopment of the jaws and nasal region. Proper development of this region requires fully active matrix gla protein (MGP), which I've written about before in the context of vascular calcification. MGP requires vitamin K to activate it, and it seems to prefer K2 MK-4 to K1, at least in the vasculature. Administering K2 MK-4 along with warfarin prevents warfarin's ability to cause arterial calcification (thought to be an MGP-dependent mechanism), whereas administering K1 does not.
Here are a few quotes from a review paper by Dr. Webster's group. I have to post the whole abstract because it's a gem:

The normal vitamin K status of the human embryo appears to be close to deficiency [I would argue in most cases the embryo is actually deficient, as are most adults in industrial societies]. Maternal dietary deficiency or use of a number of therapeutic drugs during pregnancy, may result in frank vitamin K deficiency in the embryo. First trimester deficiency results in maxillonasal hypoplasia in the neonate with subsequent facial and orthodontic implications. A rat model of the vitamin K deficiency embryopathy shows that the facial dysmorphology is preceded by uncontrolled calcification in the normally uncalcified nasal septal cartilage, and decreased longitudinal growth of the cartilage, resulting in maxillonasal hypoplasia. The developing septal cartilage is normally rich in the vitamin K-dependent protein matrix gla protein (MGP). It is proposed that functional MGP is necessary to maintain growing cartilage in a non-calcified state. Developing teeth contain both MGP and a second vitamin K-dependent protein, bone gla protein (BGP). It has been postulated that these proteins have a functional role in tooth mineralization. As yet this function has not been established and abnormalities in tooth formation have not been observed under conditions where BGP and MGP should be formed in a non-functional form.

Could vitamin K insufficiency be related to underdeveloped facial structure in industrialized cultures?  Price felt that to ensure the proper development of their children, mothers should eat a diet rich in fat-soluble vitamins both before and during pregnancy. This makes sense in light of what we now know. There is a pool of vitamin K2 MK-4 in the organs that turns over very slowly, in addition to a pool in the blood that turns over rapidly. Entering pregnancy with a full store means a greater chance of having enough of the vitamin for the growing fetus. Healthy traditional cultures often fed special foods rich in fat-soluble vitamins to women of childbearing age and expectant mothers, thus ensuring beautiful and robust progeny.