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

Tropical Plant Fats: Palm Oil

A Fatal Case of Nutritionism

The concept of 'nutritionism' was developed by Dr. Gyorgy Scrinis and popularized by the food writer Michael Pollan. It states that the health value of a food can be guessed by the sum of the nutrients it contains. Pollan argues, I think rightfully, that nutritionism is a reductionist philosophy that assumes we know more about food composition and the human body than we actually do. You can find varying degrees of this philosophy in most mainstream discussions of diet and health*.

One conspicuous way nutritionism manifests is in the idea that saturated fat is harmful. Any fat rich in saturated fatty acids is typically assumed to be unhealthy, regardless of its other constituents. There is also apparently no need to directly test that assumption, or even to look through the literature to see if the assumption has already been tested. In this manner, 'saturated' tropical plant fats such as palm oil and coconut oil have been labeled unhealthy, despite essentially no direct evidence that they're harmful. As we'll see, there is actually quite a bit of evidence, both indirect and direct, that their unrefined forms are not harmful and perhaps even beneficial.

Palm Oil and Heart Disease

Long-time readers may recall a post I wrote a while back titled Ischemic Heart Attacks: Disease of Civilization (1). I described a study from 1964 in which investigators looked for signs of heart attacks in thousands of consecutive autopsies in the US and Africa, among other places. They found virtually none in hearts from Nigeria and Uganda (3 non-fatal among more than 4,500 hearts), while Americans of the same age had very high rates (up to 1/3 of hearts).

What do they eat in Nigeria? Typical Nigerian food involves home-processed grains, starchy root vegetables, beans, fruit, vegetables, peanuts, red palm oil, and a bit of dairy, fish and meat**. The oil palm Elaeis guineensis originated in West Africa and remains one of the main dietary fats throughout the region.

To extract the oil, palm fruit are steamed, and the oily flesh is removed and pressed. It's similar to olive oil in that it is extracted gently from an oil-rich fruit, rather than harshly from an oil-poor seed (e.g., corn or soy oil). The oil that results is deep red and is perhaps the most nutrient-rich fat on the planet. The red color comes from carotenes, but red palm oil also contains a large amount of vitamin E (mostly tocotrienols), vitamin K1, coenzyme Q10 and assorted other fat-soluble constituents. This adds up to a very high concentration of fat-soluble antioxidants, which are needed to protect the fat from rancidity in hot and sunny West Africa. Some of these make it into the body when it's ingested, where they appear to protect the body's own fats from oxidation.

Mainstream nutrition authorities state that palm oil should be avoided due to the fact that it's approximately half saturated. This is actually one of the main reasons palm oil was replaced by hydrogenated seed oils in the processed food industry. Saturated fat raises blood cholesterol, which increases the risk of heart disease. Doesn't it? Let's see what the studies have to say.

Most of the studies were done using refined palm oil, unfortunately. Besides only being relevant to processed foods, this method also introduces a new variable because palm oil can be refined and oxidized to varying degrees. However, a few studies were done with red palm oil, and one even compared it to refined palm oil. Dr. Suzanna Scholtz and colleagues put 59 volunteers on diets predominating in sunflower oil, refined palm oil or red palm oil for 4 weeks. LDL cholesterol was not different between the sunflower oil and red palm oil groups, however the red palm oil group saw a significant increase in HDL. LDL and HDL both increased in the refined palm oil group relative to the sunflower oil group (2).

Although the evidence is conflicting, most studies have not been able to replicate the finding that refined palm oil increases LDL relative to less saturated oils (3, 4). This is consistent with studies in a variety of species showing that saturated fat generally doesn't raise LDL compared to monounsaturated fat in the long term, unless a large amount of purified cholesterol is added to the diet (5).

Investigators have also explored the ability of palm oil to promote atherosclerosis, or hardening and thickening of the arteries, in animals. Not only does palm oil not promote atherosclerosis relative to monounsaturated fats (e.g., olive oil), but in its unrefined state it actually protects against atherosclerosis (6, 7). A study in humans hinted at a possible explanation: compared to a monounsaturated oil***, palm oil greatly reduced oxidized LDL (8). As a matter of fact, I've never seen a dietary intervention reduce oxLDL to that degree (69%). oxLDL is a major risk factor for cardiovascular disease, and a much better predictor of risk than the typically measured LDL cholesterol (9). The paper didn't state whether or not the palm oil was refined. I suspect it was lightly refined, but still rich in vitamin E and CoQ10.

As I discussed in my recent interview with Jimmy Moore, atherosclerosis is only one factor in heart attack risk (10). Several other factors are also major determinants of risk: clotting tendency, plaque stability, and susceptibility to arrhythmia. Another factor that I haven't discussed is how resistant the heart muscle is to hypoxia, or loss of oxygen. If the coronary arteries are temporarily blocked-- a frequent occurrence in modern people-- the heart muscle can be damaged. Dietary factors determine the degree of damage that results. For example, in rodents, nitrites derived from green vegetables protect the heart from hypoxia damage (11). It turns out that red palm oil is also protective (12, 13). Red palm oil also protects against high blood pressure in rats, an effect attributed to its ability to reduce oxidative stress (14, 15).

Together, the evidence suggests that red palm oil does not contribute to heart disease risk, and in fact is likely to be protective. The benefits of red palm oil probably come mostly from its minor constituents, i.e. the substances besides its fatty acids. Several studies have shown that a red palm oil extract called palmvitee lowers serum lipids in humans (16, 17). The minor constituents are precisely what are removed during the refining process.

Palm Oil and the Immune System

Red palm oil also has beneficial effects on the immune system in rodents. It protects against bacterial infection when compared with soybean oil (18). It also protects against certain cancers, compared to other oils (19, 20). This may be in part due to its lower content of omega-6 linoleic acid (roughly 10%), and minor constituents.

The Verdict

Yet again, nutritionism has gotten itself into trouble by underestimating the biological complexity of a whole food. Rather than being harmful to human health, red palm oil, an ancient and delicious food, is likely to be protective. It's also one of the cheapest oils available worldwide, due to the oil palm's high productivity. It has a good shelf life and does not require refrigeration. Its strong, savory flavor goes well in stews, particularly meat stews. It isn't available in most grocery stores, but you can find it on the internet. Make sure not to confuse it with refined palm oil or palm kernel oil.


* The approach that Pollan and I favor is a simpler, more empirical one: eat foods that have successfully sustained healthy cultures.

** Some Nigerians are also pastoralists that subsist primarily on dairy.

*** High oleic sunflower oil, from a type of sunflower bred to be high in monounsaturated fat and low in linoleic acid. I think it's probably among the least harmful refined oils. I use it sometimes to make mayonnaise. It's often available in grocery stores, just check the label.

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.

Low Vitamin D: Cause or Result of Disease?

Don Matesz at Primal Wisdom put up a post a few days ago that I think is worth reading. It follows an e-mail discussion between us concerning a paper on magnesium restriction in rats (executive summary: moderate Mg restriction reduces the hormone form of vitamin D by half and promotes osteoporosis). In his post, Don cites several papers showing that vitamin D metabolism is influenced by more than just vitamin D intake from the diet and synthesis in the skin.

Celiac disease patients have low 25(OH)D3, the circulating storage form of vitamin D, which spontaneously corrects on a gluten-free diet. There are numerous suggestions in the medical literature that overweight and sickness cause low vitamin D, potentially confounding the interpretation of studies that find lower levels of illness among people with low vitamin D levels.

Don't get me wrong, I still think vitamin D is important in preventing disease. But it does lead me to question the idea that we should force down huge doses of supplemental vitamin D to get our 25(OH)D3 up to 60, 70 or even 80 ng/mL. When the dosage of supplemental D goes beyond what a tan Caucasian could conceivably make on a day at the beach (4,000 IU?), that's when I start becoming skeptical. Check out Don's post for more.

Vitamin D May Prevent Flu and Asthma

The AJCN just published a new controlled trial evaluating the effectiveness of vitamin D supplements on flu and asthma (1). Dr. Hiroyuki Ida's group gave Japanese schoolchildren (10 years average age) 1,200 IU of vitamin D3 or placebo per day from December through March. They found that children taking vitamin D had a significantly lower incidence of influenza A but not influenza B. These are two strains of flu that each accounted for roughly half the flu incidence in this population. Sadly, if you add the total flu incidence for A and B together (which the authors don't do in their tables), vitamin D supplementation didn't reduce total flu incidence significantly.

They also found that in the subset of children not already taking vitamin D supplements, the effect was greater, with unsupplemented children contracting nearly three times as many influenza A infections as children receiving vitamin D. They didn't analyze the influenza B or total influenza incidence in that way, so we don't know if prior supplementation makes a difference there.

The most striking finding of the paper is that the vitamin D group suffered from 6 times fewer asthma attacks than the placebo group. This needs to be repeated but it's consistent with other data and I find it very encouraging.

The paper did have some limitations. They didn't measure vitamin D status so they have no way to know exactly how effective their pill-based supplements were.

Another problem is that they began collecting data immediately after beginning supplementation. Vitamin D is a fat-soluble vitamin that can take 3 months to reach maximum concentration in the body following supplementation. By the time the children were reaching their maximum serum concentration of vitamin D, the trial was over. It would be nice to see the next trial begin supplementation in the fall and look at flu incidence in the winter.

This paper comes on the heels of another showing that vitamin D is necessary for the activation of an immune cell called the killer T cell (2). These are important for resistance to infections and cancer. Overall, these papers add to the accumulating evidence that vitamin D is important for the proper functioning of the human immune system. However, mice may not be the best model for use in studying vitamin D biology. From the first paper:

The evolution of different mechanisms for the regulation of PLC-γ1 activity in human and mouse T cells parallels the development of divergent VDR-dependent and VDR-independent antimicrobial pathways in human and mouse macrophages31, respectively, and may reflect the fact that mice are nocturnal animals with fur and humans are daytime creatures that synthesize vitamin D in the skin after exposure to ultraviolet light.

In other words, mice don't use vitamin D in the same way as humans because they have a different evolutionary relationship to it.

The Body Fat Setpoint, Part IV: Changing the Setpoint

Prevention is Easier than Cure

Experiments in animals have confirmed what common sense suggests: it's easier to prevent health problems than to reverse them. Still, many health conditions can be improved, and in some cases reversed, through lifestyle interventions. It's important to have realistic expectations and to be kind to oneself. Cultivating a drill sergeant mentality will not improve quality of life, and isn't likely to be sustainable.

Fat Loss: a New Approach

If there's one thing that's consistent in the medical literature, it's that telling people to eat fewer calories isn't a very effective fat loss strategy, despite the fact that it works if strictly adhered to. Many people who use this strategy see transient fat loss, followed by fat regain and a feeling of defeat. There's a simple reason for it: the body doesn't want to lose weight. It can be difficult to fight the fat mass setpoint, and the body will use every tool it has to maintain its preferred level of fat: hunger, increased interest in food, reduced body temperature, higher muscle efficiency (i.e., less energy is expended for the same movement), lethargy, lowered immune function, et cetera.

Therefore, what we need for sustainable fat loss is not starvation; we need a treatment that lowers the fat mass setpoint. There are several criteria that this treatment will have to meet to qualify:

1. It must cause fat loss
2. It must not involve deliberate calorie restriction
3. It must maintain fat loss over a long period of time
4. It must not be harmful to overall health

I also prefer strategies that make sense from the perspective of human evolution.

Strategies: Diet Pattern

One treatment that fits my criteria is low-carbohydrate dieting. Overweight people eating low-carbohydrate diets generally lose some fat and spontaneously reduce their calorie intake. In fact, in several diet studies, investigators compared an all-you-can-eat low-carbohydrate diet with a calorie-restricted low-fat diet. The low-carbohydrate dieters generally reduced their calorie intake and body fat to a similar or greater degree than the low-fat dieters, despite the fact that they ate all the calories they wanted (1). This may suggest that their fat mass setpoint had changed. At this point, I think moderate carbohydrate restriction may be preferable to strict carbohydrate restriction for some people, due to the increasing number of reports I've read of people doing poorly in the long run on extremely low-carbohydrate diets.  Furthermore, controlled trials of low-carb diets show that the long-term weight loss, despite being greater than low-fat diets, is not that impressive for the "average person".  Some people find it highly effective, while most people find it moderately effective or even ineffective.

Another strategy that appears preferable is the "paleolithic" diet. In Dr. Staffan Lindeberg's 2007 diet study, overweight volunteers with heart disease lost fat and reduced their calorie intake to a remarkable degree while eating a diet consistent with our hunter-gatherer heritage (3). This result is consistent with another diet trial of the paleolithic diet in diabetics (4). In post hoc analysis, Dr. Lindeberg's group showed that the reduction in weight was apparently independent of changes in carbohydrate intake*. This suggests that the paleolithic diet has health benefits that are independent of carbohydrate intake.

Strategies: Gastrointestinal Health

Since the gastrointestinal (GI) tract is so intimately involved in body fat metabolism and overall health (see the former post), the next strategy is to improve GI health. There are a number of ways to do this, but they all center around four things:

1. Don't eat food that encourages the growth of harmful bacteria
2. Eat food that encourages the growth of good bacteria
3. Don't eat food that impairs gut barrier function
4. Eat food that promotes gut barrier health

The first one is pretty easy in theory: avoid fermentable substances of which you're intolerant.  This can include lactose (milk) and certain polysaccharides, and a number of other FODMAPs.  For the second and fourth points, make sure to eat fermentable fiber. In one trial, oligofructose supplements led to sustained fat loss, without any other changes in diet (5). This is consistent with experiments in rodents showing improvements in gut bacteria profile, gut barrier health, glucose tolerance and body fat mass with oligofructose supplementation (6, 7, 8).  However, oligofructose is a FODMAP and therefore will be poorly tolerated by a subset of people.

The colon is packed with symbiotic bacteria, and is the site of most intestinal fermentation. The small intestine contains fewer bacteria, but gut barrier function there is critical as well. The small intestine is where the GI doctor will take a biopsy to look for celiac disease. Celiac disease is a degeneration of the small intestinal lining due to an autoimmune reaction caused by gluten (in wheat, barley and rye). This brings us to one of the most important elements of maintaining gut barrier health: avoiding food sensitivities. Gluten and casein (in dairy protein) are the two most common offenders. Gluten sensitivity is more common than most people realize; just under 1% of young adults and the prevalence increases with age.

Eating raw fermented foods such as sauerkraut, kimchi, yogurt and half-sour pickles also helps maintain the integrity of the upper GI tract. I doubt these have any effect on the colon, given the huge number of bacteria already present.

Strategies: Miscellaneous

Anecdotally, many people have had success using intermittent fasting (IF) for fat loss. There's some evidence in the scientific literature that IF and related approaches may be helpful (14). There are different approaches to IF, but a common and effective method is to do two complete 24-hour fasts per week. It's important to note that IF isn't about restricting calories, it's about resetting the fat mass setpoint. After a fast, allow yourself to eat quality food until you're no longer hungry.

Insufficient sleep has been strongly and repeatedly linked to obesity. Whether it's a cause or consequence of obesity I can't say for sure, but in any case it's important for health to sleep until you feel rested. If your sleep quality is poor due to psychological stress, meditating before bedtime may help. I find that meditation has a remarkable effect on my sleep quality. Due to the poor development of oral and nasal structures in industrial nations, many people do not breathe effectively and may suffer from conditions such as sleep apnea that reduce sleep quality. Overweight also contributes to these problems.


* Since reducing carbohydrate intake wasn't part of the intervention, this result is observational.

The Body Fat Setpoint, Part III: Dietary Causes of Obesity

[2013 update: I've edited this post to remove elements that I feel were poorly supported.  I now think that changes in the setpoint are at least partially secondary to passive overconsumption of calories, particularly low quality calories]

What Caused the Setpoint to Change?

We have two criteria to narrow our search for the cause of modern fat gain:

1. It has to be new to the human environment
2. At some point, it has to cause leptin resistance or otherwise disturb the setpoint

Although I believe that exercise is part of a healthy lifestyle, and can help prevent fat gain and to some degree treat overweight, it probably can't explain the recent increase in fat mass in modern nations. This is because exercise doesn't appear to have declined. There are various other possible explanations, such as industrial pollutants, a lack of sleep and psychological stress, which may play a role. But I feel that diet is likely to be the primary cause. When you're drinking 20 oz Cokes, bisphenol-A contamination is the least of your worries.

In the last post, I described two mechanisms that may contribute to elevating the body fat set point by causing leptin resistance: inflammation in the hypothalamus, and impaired leptin transport into the brain due to elevated triglycerides. After more reading and discussing it with my mentor, I've decided that the triglyceride hypothesis is on shaky ground*. Nevertheless, it is consistent with certain observations:

• Fibrate drugs that lower triglycerides can lower fat mass in rodents and humans
• Low-carbohydrate diets are somewhat effective for fat loss and lower triglycerides
• Fructose can cause leptin resistance in rodents and it elevates triglycerides (1)
• Fish oil reduces triglycerides. Some but not all studies have shown that fish oil aids fat loss (2)

Inflammation in the hypothalamus, with accompanying resistance to leptin signaling, has been reported in a number of animal studies of diet-induced obesity. I feel it's likely to occur in humans as well, although the dietary causes are probably different for humans. The hypothalamus is the primary site where leptin acts to regulate fat mass (3). Importantly, preventing inflammation in the brain prevents leptin resistance and obesity in diet-induced obese mice (3.1). The hypothalamus is likely to be the most important site of action. Research is underway on this.

The Role of Digestive Health

What causes inflammation in the hypothalamus? One of the most interesting hypotheses is that increased intestinal permeability allows inflammatory substances to cross into the circulation from the gut, irritating a number of tissues including the hypothalamus.

Dr. Remy Burcelin and his group have spearheaded this research. They've shown that high-fat diets cause obesity in mice, and that they also increase the level of an inflammatory substance called lipopolysaccharide (LPS) in the blood. LPS is produced by gram-negative bacteria in the gut and is one of the main factors that activates the immune system during an infection. Antibiotics that kill gram-negative bacteria in the gut prevent the negative consequences of high-fat feeding in mice.

Burcelin's group showed that infusing LPS into mice on a low-fat chow diet causes them to become obese and insulin resistant just like high-fat fed mice (4). Furthermore, adding 10% of the soluble fiber oligofructose to the high-fat diet prevented the increase in intestinal permeability and also largely prevented the body fat gain and insulin resistance from high-fat feeding (5). Oligofructose is food for friendly gut bacteria and ends up being converted to butyrate and other short-chain fatty acids in the colon. This results in lower intestinal permeability to toxins such as LPS. This is particularly interesting because oligofructose supplements cause fat loss in humans (6).

A recent study showed that blood LPS levels are correlated with body fat, elevated cholesterol and triglycerides, and insulin resistance in humans (7). However, a separate study didn't come to the same conclusion (8). The discrepancy may be due to the fact that LPS isn't the only inflammatory substance to cross the gut lining-- other substances may also be involved. Anything in the blood that shouldn't be there is potentially inflammatory.

Overall, I think gut dysfunction could play a role in obesity and other modern metabolic problems.
Exiting the Niche

I believe that we have strayed too far from our species' ecological niche, and our health is suffering. One manifestation of that is body fat gain. Many factors probably contribute, but I believe that diet is the most important. A diet heavy in nutrient-poor refined carbohydrates and industrial omega-6 oils, high in gut irritating substances such as gluten and sugar, and a lack of direct sunlight, have caused us to lose the robust digestion and good micronutrient status that characterized our distant ancestors. I believe that one consequence has been the dysregulation of the system that maintains the fat mass "setpoint". This has resulted in an increase in body fat in 20th century affluent nations, and other cultures eating our industrial food products.

In the next post, I'll discuss my thoughts on how to reset the body fat setpoint.

* The ratio of leptin in the serum to leptin in the brain is diminished in obesity, but given that serum leptin is very high in the obese, the absolute level of leptin in the brain is typically not lower than a lean person. Leptin is transported into the brain by a transport mechanism that saturates when serum leptin is not that much higher than the normal level for a lean person. Therefore, the fact that the ratio of serum to brain leptin is higher in the obese does not necessarily reflect a defect in transport, but rather the fact that the mechanism that transports leptin is already at full capacity.

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.

The Diet-Heart Hypothesis: Oxidized LDL, Part I

In my reading about lipoprotein particles (LDL, HDL, etc.) and how they associate with cardiac risk, I've come across three LDL-related markers that associate with risk: LDL cholesterol, LDL particle number, and LDL size/density. Is this a coincidence, or is there a reason for it?

The first marker, LDL cholesterol, is probably nothing more than a crude approximation of particle number. But LDL particle number and size/density are related to something else, that probably actually causes atherosclerosis rather than simply being associated with it: oxidized LDL (oxLDL).

oxLDL is formed when the lipids in LDL particles react with oxygen and break down. This happens specifically to the unsaturated fats in LDL, because saturated fats, by their chemical nature, are very resistant to oxidative damage. Polyunsaturated fats are much more susceptible to oxidative damage than saturated or monounsaturated fats. Linoleic acid (the omega-6 fatty acid found abundantly in industrial seed oils) is the main polyunsaturated fatty acid in LDL.

LDL is packaged with antioxidants in the liver, primarily vitamin E and coenzyme Q10 (CoQ10), to prevent its oxidation. However, the more time it spends in the blood, the more likely it is to exhaust its antioxidant store and become oxidized. Also, the smaller the LDL particle, the more likely it is to become trapped in the vessel wall and become oxidized there.

Oxidized LDL Correlates Tightly with Cardiac Risk

oxLDL has turned out to be a very sensitive marker of cardiac risk, surpassing traditional markers like LDL, HDL, and triglycerides in most studies to date. Since the discovery of sensitive assays that detect oxidized LDL drawn directly from patient blood, a number of studies have been published supporting its ability to detect atherosclerosis (plaque buildup in the arteries), heart attack risk and even the metabolic syndrome.

Holovet and colleagues published a study comparing the ability of oxLDL and a traditional risk factor assessment to detect coronary artery disease. The traditional method is called the Global Risk Factor Assessment Score (GRAS), and includes age, total cholesterol, HDL, blood pressure, diabetes and smoking status. It's similar to the commonly used Framingham risk score (which, interestingly enough, doesn't include LDL).

GRAS was able to correctly differentiate a healthy person from a person with coronary artery disease 49% of the time, while oxLDL was correct 82% of the time. Thus, oxLDL by itself was far more accurate than a whole battery of traditional cholesterol and cardiac markers. Coronary patients had more than twice the level of circulating oxLDL than the healthy comparison group.

In a large prospective study by Meisinger and colleagues, participants with high oxLDL had a 4.25 higher risk of heart attack than patients with lower oxLDL. oxLDL blew away all other blood lipid markers by nearly a factor of two. From the abstract:

Plasma oxLDL was the strongest predictor of CHD events compared with a conventional lipoprotein profile and other traditional risk factors for CHD.

Oxidized LDL Makes Sense

 Regular, non-oxidized LDL has few properties that would make it a suspect in atherosclerosis. It's just a little particle carrying cholesterol and fats from the liver to other organs. As soon as it oxidizes, however, it becomes pro-inflammatory, immunogenic, damaging to the vessel wall, and most importantly, capable of transforming immune cells called macrophages into foam cells, a major constituent of arterial plaque.

Researchers have been interested in the plaque-generating properties of oxLDL for over three decades, and quite a bit of data have accumulated. They've identified cellular receptors that allow macrophages to ingest oxLDL (CD36 and SR-A). These receptors are specific for oxLDL and do not recognize normal LDL to a significant degree. Mice whose macrophages lack either of these two receptors have the same amount of circulating LDL as normal mice, yet have 60 to 70 percent less atherosclerosis when fed a plaque-forming diet (1, 2). Shorter-term studies have not always been consistent however, suggesting that there are alternative mechanisms. I'll expand on this more later.

Another line of evidence comes from the ability of LDL-borne antioxidants to prevent atherosclerosis in animal models. The powerful synthetic antioxidant probucol greatly reduces atherosclerosis in a number of animal models. It also reduces the extremely high cholesterol rodents and herbivorous animals get when they eat a high-cholesterol "atherogenic diet", but several studies have concluded that the majority of probucol's effect is due to its antioxidant ability rather than its ability to reduce cholesterol (ref).

Vitamin E and CoQ10 are two other LDL-borne antioxidants that can reduce atherosclerosis in animal models, particularly in combination with one another. Vitamin E alone is not as effective, and in some studies totally ineffective, which is one possible explanation for the equivocal results of vitamin E cardiovascular trials in humans. The most effective combination of antioxidants is probably the one provided by a nutrient-dense diet.

In Summary

Multiple lines of evidence suggest that oxidized LDL plays a dominant role in atherosclerosis. Not only is it associated with cardiovascular risk, there's also a large body of evidence suggesting it actually directly contributes to it. 

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.

Nutrition and Infectious Disease

Dr. Edward Mellanby's book Nutrition and Disease contains a chapter titled "Nutrition and Infection". It begins:

There is general agreement among medical men that the susceptibility of mankind to many types of infection is closely related to the state of nutrition. The difficulty arises, when closer examination is given to this general proposition, as to what constitutes good and bad nutrition, and the problem is not rendered easier by recent advances in nutritional science.

Dr. Mellanby was primarily concerned with the effect of fat-soluble vitamins on infectious disease, particularly vitamins A and D. One of his earliest observations was that butter protected against pneumonia in his laboratory dogs. He eventually identified vitamin A as the primary protective factor. He found that by placing rats on a diet deficient in vitamin A, they developed numerous infectious lesions, most often in the urogenital tract, the eyes, the intestine, the middle ear and the lungs. This was prevented by adding vitamin A or cabbage (a source of beta-carotene, which the rats converted to vitamin A) to the diet. Mellanby and his colleagues subsequently dubbed vitamin A the "anti-infective vitamin".

Dr. Mellanby was unsure whether the animal results would apply to humans, due to "the difficulty in believing that diets even of poor people were as deficient in vitamin A and carotene as the experimental diets." However, their colleagues had previously noted marked differences in the infection rate of largely vegetarian African tribes versus their carnivorous counterparts. The following quote from Nutrition and Disease refers to two tribes which, by coincidence, Dr. Weston Price also described in Nutrition and Physical Degeneration:

The high incidence of bronchitis, pneumonia, tropical ulcers and phthisis among the Kikuyu tribe who live on a diet mainly of cereals as compared with the low incidence of these diseases among their neighbours the Masai who live on meat, milk and raw blood (Orr and Gilks), probably has a similar or related nutritional explanation. The differences in distribution of infective disease found by these workers in the two tribes are most impressive. Thus in the cereal-eating tribe, bronchitis and pneumonia accounted for 31 per cent of all cases of sickness, tropical ulcers for 33 per cent, and phthisis for 6 per cent. The corresponding figures for the meat, milk and raw blood tribe were 4 per cent, 3 per cent and 1 per cent.

So they set out to test the theory under controlled conditions. Their first target: puerperal sepsis. This is an infection of the uterus that occurs after childbirth. They divided 550 women into two groups: one received vitamins A and D during the last month of pregnancy, and the other received nothing. Neither group was given instructions to change diet, and neither group was given vitamins during their hospital stay. The result, quoted from Nutrition and Disease:

The morbidity rate in the puerperium using the [British Medical Association] standard was 1.1 per cent in the vitamin group and 4.7 in the control group, a difference of 3.6 per cent which is twice the standard error (1.4), and therefore statistically significant.

This experiment didn't differentiate between the effects of vitamin A and D, but it did establish that fat-soluble vitamins are important for resistance to bacterial infection. The next experiment Dr. Mellanby undertook was a more difficult one. This time, he targeted puerperal septicemia. This is a more advanced stage of puerperal sepsis, in which the infection spreads into the bloodstream. In this experiment, he treated women who had already contracted the infection. This trial was not as tightly controlled as the previous one. Here's a description of the intervention, from Nutrition and Disease:

...all patients received when possible a diet rich not only in vitamin A but also of high biological quality. This diet included much milk, eggs, green vegetables, etc., as well as the vitamin A supplement. For controls we had to use the cases treated in previous years by the same obstetricians and gynecologists as the test cases.

In the two years prior to this investigation, the mortality rate for puerperal septicemia in 18 patients was 92%. In 1929, Dr. Mellanby fed 18 patients in the same hospital his special diet, and the mortality rate was 22%. This is a remarkable treatment for an infection that was almost invariably fatal at the time.

Dr. Mellanby was a man with a lot of perspective. He was not a reductionist; he knew that a good diet is more than the sum of its parts. Here's another quote from Nutrition and Disease:

It is probable that, as in the case of vitamin D and rickets, the question is not simple and that it will ultimately be found that vitamin A works in harmony with some dietetic factors, such as milk proteins and other proteins of high biological value, to promote resistance of mucous membranes and epithelial cells to invasion by micro-organisms, while other factors such as cereals, antagonise its influence. The effect of increasing the green vegetable and reducing the cereal intake on the resistance of herbivorous animals to infection is undoubted (Glenny and Allen, Boock and Trevan) and may well indicate a reaction in which the increased carotene of the vegetable plays only a part, but an important part.

P.S.- I have to apologize, I forgot to copy down the primary literature references for this post before returning the book to the library. So for the skeptics out there, you'll either have to take my word for it, or find a copy of the book yourself.

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 the diet isn't adequate, enamel demineralizes and decay sets in. Tooth decay is an opportunistic infection that takes advantage of poorly built 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. Pulp contains cells called odontoblasts, which form new dentin if the diet is good. 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 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 in warm water (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 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.

Preventing Tooth Decay

Meet Sir Edward Mellanby, the man who discovered vitamin D. Along with his wife, Dr. May Mellanby, he identified dietary factors that control the formation and repair of teeth and bones. He also identified the primary cause of rickets (vitamin D deficiency) and the effect of phytic acid on mineral absorption. Truly a great man! This research began in the 1910s and continued through the 1940s.

What he discovered about tooth and bone formation is profound, disarmingly simple, and largely forgotten. I remember going to the dentist as a child. He told me I had good teeth. I informed him that I tried to eat well and stay away from sweets. He explained to me that I had good teeth because of genetics, not my diet. I was skeptical at the time, and rightly so.

Tooth structure is primarily determined during growth. Well-formed teeth are highly resistant to decay, while poorly-formed teeth are cavity-prone. Drs. Mellanby demonstrated this by showing a strong correlation between tooth enamel defects and cavities in British children. The following graph is drawn from several studies he compiled in the book Nutrition and Disease (1934). "Hypoplastic" refers to enamel that's poorly formed on a microscopic level.
The graph is confusing, so don't worry if you're having a hard time interpreting it. If you look at the blue bar representing children with well-formed teeth, you can see that 77% of them have no cavities, and only 7.5% have severe cavities (a "3" on the X axis). Looking at the green bar, only 6% of children with the worst enamel structure are without cavities, while 74% have severe cavities. Enamel structure is VERY strongly related to cavity prevalence.

What determines enamel structure during growth? Drs. Mellanby identified three dominant factors:

1. The mineral content of the diet
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

Teeth and bones are a mineralized protein scaffold. Vitamin D influences the quality of the protein scaffold that's laid down, and the handling of the elements that mineralize it. For the scaffold to mineralize, the diet has to contain enough minerals, primarily calcium and phosphorus. Vitamin D allows the digestive system to absorb the minerals, but it can only absorb them if they aren't bound by phytic acid. Phytic acid is an anti-nutrient found primarily in unfermented seeds such as grains. So the process depends on getting minerals (sufficient minerals in the diet and low phytic acid) and putting them in the right place (fat-soluble vitamins).

Optimal tooth and bone formation occurs only on a diet that is sufficient in minerals, fat-soluble vitamins, and low in phytic acid. Drs. Mellanby used dogs in their experiments, which it turns out are a good model for tooth formation in humans for a reason I'll explain later. From Nutrition and Disease:

Thus, if growing puppies are given a limited amount of separated [skim] milk together with cereals, lean meat, orange juice, and yeast (i.e., a diet containing sufficient energy value and also sufficient proteins, carbohydrates, vitamins B and C, and salts), defectively formed teeth will result. If some rich source of vitamin D be added, such as cod-liver oil or egg-yolk, the structure of the teeth will be greatly improved, while the addition of oils such as olive... leaves the teeth as badly formed as when the basal diet only is given... If, when the vitamin D intake is deficient, the cereal part of the diet is increased, or if wheat germ [high in phytic acid] replaces white flour, or, again, if oatmeal [high in phytic acid] is substituted for white flour, then the teeth tend to be worse in structure, but if, under these conditions, the calcium intake is increased, then calcification [the deposition of calcium in the teeth] is improved.

Other researchers initially disputed the Mellanbys' results because they weren't able to replicate the findings in rats. It turns out, rats produce the phytic acid-degrading enzyme phytase in their small intestine, so they can extract minerals from unfermented grains better than dogs. Humans also produce phytase, but at levels so low they don't significantly degrade phytic acid. The small intestine of rats has about 30 times the phytase activity of the human small intestine, again demonstrating that humans are not well adapted to eating grains. Our ability to extract minerals from seeds is comparable to that of dogs, which shows that the Mellanbys' results are more applicable to humans than those in rats.

Drs. Mellanby found that the same three factors determine bone quality in dogs as well, which I may discuss in another post.

Is there anything someone with fully formed enamel can do to prevent tooth decay? Drs. Mellanby showed (in humans this time) that not only can tooth decay be prevented by a good diet, it can be almost completely reversed even if it's already present. Dr. Weston Price used a similar method to reverse tooth decay as well. I'll discuss that in my next post.

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."