Tuesday, January 27, 2009

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.

Sunday, January 25, 2009

The Tokelau Island Migrant Study: The Final Word

Over the course of the last month, I've outlined some of the major findings of the Tokelau Island Migrant study. It's one of the most comprehensive studies I've found of a traditional culture transitioning to a modern diet and lifestyle. It traces the health of the inhabitants of the Pacific island Tokelau over time, as well as the health of Tokelauan migrants to New Zealand.

Unfortunately, the study began after the introduction of modern foods. We will never know for sure what Tokelauan health was like when their diet was completely traditional. To get some idea, we have to look at other traditional Pacific islanders such as the Kitavans.

What we can say is that an increase in the consumption of modern foods on Tokelau, chiefly white wheat flour and refined sugar, correlated with an increase in several non-communicable disorders, including overweight, diabetes and severe tooth decay. Further modernization as Tokelauans migrated to New Zealand corresponded with an increase in nearly every disorder measured, including heart disease, weight gain, diabetes, asthma and gout. These are all "diseases of civilization", which are not observed in hunter-gatherers and certain non-industrial populations throughout the world.

One of the most interesting things about Tokelauans is their extreme saturated fat intake, 40- 50% of calories. That's more than any other population I'm aware of. Yet Tokelauans appear to have a low incidence of heart attacks, lower than their New Zealand- dwelling relatives who eat half as much saturated fat. This should not be buried in the scientific literature; it should be common knowledge.

Overall, I believe the Tokelau Island Migrant study (among others) shows us that partially replacing nourishing traditional foods with modern foods such as processed wheat and sugar, is enough to cause a broad range of disorders not seen in hunter-gatherers but typical of modern societies. Changes in lifestyle between Tokelau and New Zealand may have also played a role.
The Tokelau Island Migrant Study: Background and Overview
The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain
The Tokelau Island Migrant Study: Diabetes
The Tokelau Island Migrant Study: Asthma

Saturday, January 24, 2009

The Tokelau Island Migrant Study: Gout

Gout is a disorder in which uric acid crystals form in the joints, causing intense pain. The body forms uric acid as a by-product of purine metabolism. Purines are a building block of DNA, among other things. Uric acid is normally excreted into the urine, hence the name.

On Tokelau between 1971 and 1982, gout prevalence fell slightly. In migrants to New Zealand, gout prevalence began at the same level as on Tokelau but increased rapidly over the same time period. Here are the prevalence data for men, from Migration and Health in a Small Society: the Case of Tokelau (I don't have data for women):

This paper found that the age-standardized risk of developing gout was 9 times higher in New Zealand than on Tokelau for men, and 2.7 times higher for women.

The Tokelau Island Migrant Study: Background and Overview
The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain
The Tokelau Island Migrant Study: Diabetes
The Tokelau Island Migrant Study: Asthma

Wednesday, January 21, 2009

The Tokelau Island Migrant Study: Asthma

Asthma may be another "disease of civilization", uncommon in non-industrial cultures. Between 1980 and 2001, its prevalence more than doubled in American children 17 years and younger. The trend is showing no sign of slowing down (CDC NHANES surveys).



The age-standardized asthma prevalence in Tokelauan migrants to New Zealand age 15 and older, was 2 - 6 times higher than in non-migrants from 1976 to 1982, depending on gender and year. The highest prevalence was in New Zealand migrant women in 1976, at 6.8%. The lowest was in Tokelauan men in 1976 at 1.1%.

A skeptic might suggest it's because these adults grew up around certain types of pollen or other antigens, and were exposed to new ones later in life. However, even migrant children in the 0-4 age group, who were most likely born in NZ, had more asthma than on Tokelau.

What could contribute to the increased asthma prevalence upon modernization? I'm not particularly knowledgeable about the mechanisms of asthma, but it seems likely to involve a chronic over-activation of the immune system ("inflammation").

The Tokelau Island Migrant Study: Background and Overview
The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain
The Tokelau Island Migrant Study: Diabetes

The Tokelau Island Migrant Study data in this post come from the book Migration and Health in a Small Society: The Case of Tokelau.

Thanks to the EPA and Wikipedia for the graph image (public domain).

Monday, January 19, 2009

The Tokelau Island Migrant Study: Diabetes

This post will be short and sweet. Diabetes is a disease of civilization. As Tokelauans adopted Western industrial foods, their diabetes prevalence increased. At any given time point, age-standardized diabetes prevalence was higher in migrants to New Zealand than those who remained on Tokelau:


This is not a difference in diagnosis. Tokelauans were examined for diabetes by the same group of physicians, using the same criteria. It's also not a difference in average age, sice the numbers are age-standardized. On Tokelau, diabetes prevalence doubled in a decade. Migrants to New Zealand in 1981 had roughly three times the prevalence of diabetes that Tokelauans did in 1971. I can only imagine the prevalence is even higher in 2008.

We don't know what the prevalence was in Tokelauans when their diet was completely traditional, but I would expect it to be low like other traditional Pacific island societies. I'm looking at a table right now of age-standardized diabetes prevalence on 11 different Pacific islands. There is quite a bit of variation, but the pattern is clear: the more modernized, the higher the diabetes rate. In several cases, the table has placed two values side-by-side: one value for rural inhabitants of an island, and another for urban inhabitants of the same island. In every case, the prevalence of diabetes is higher in the urban group. In some cases, the difference is as large as four-fold.

The lowest value goes to the New Caledonians of Touho, who are also considered the least modernized on the table (although even their diet is not completely traditional). Men have an age-standardized diabetes prevalence of 1.8%, women 1.4%. At the other extreme are the Micronesians of Nauru, affluent due to phosphate resources, who have a prevalence of 33.4% for men and 32.1% for women. They subsist mostly on imported food and are extremely obese.

The same patterns can be seen in Africa, the Arctic and probably everywhere that has adopted processed Western foods. White rice alone (compared with the combination of wheat flour and sugar) does not seem to have this effect.

The data in this post are from the book Migration and Health in a Small Society: the Case of Tokelau.

The Tokelau Island Migrant Study: Background and Overview

The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain