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.

Impressions of Hawai'i

I recently went to Hawai'i for the American Society of Human Genetics meeting in Waikiki, followed by a one-week vacation on Kaua'i with friends. It was my first time in Hawai'i and I really enjoyed it. The Hawai'ians I encountered were kind and generous people.

Early European explorers remarked on the beauty, strength, good nature and exellent physical development of the native Hawai'ians. The traditional Hawai'ian diet consisted mostly of taro root, sweet potatoes, yams, breadfruit, coconut, fish, occasional pork, fowl including chicken, taro leaves, seaweed and a few sweet fruits. It would have been very low (but adequate) in omega-6, because there simply isn't much of it available in this environment. Root crops and most fruit are virtually devoid of fat; seafood and coconut contain very little omega-6; and even the pork and chicken would have been low in omega-6 due to their diets. Omega-3 would have been plentiful from marine foods, and saturated fats would have come from coconut. All foods were fresh and unrefined. Abundant exercise and sunlight would have completed their salubrious lifestyle.

The traditional Hawai'ian diet was rich in easily digested starch, mainly in the form of poi, which is fermented mashed taro. I ate poi a number of times while I was on Kaua'i, and really liked it. It's mild, similar to mashed potatoes, but with a slightly sticky consistency and a purple color (due to the particular variety of taro that's traditionally used to make it).

I had the opportunity to try a number of traditional Polynesian foods while I was on Kaua'i. One plant that particularly impressed me is breadfruit. It's a big tree that makes cantaloupe-sized starchy green fruit. Breadfruit is incredibly versatile, because it can be used at different stages of ripeness for different purposes. Very young, it's like a vegetable, at full size, it's a bland starch, and fully ripe it's starchy and sweet like a sweet potato. It can be baked, boiled, fried and even dried for later use. It has a mild flavor and a texture similar to soft white bread. It's satisfying and fairly rich in micronutrients. On the right are breadfruit, coconut and sugarcane, three traditional Hawai'ian foods.

I find perennial staple crops such as breadfruit very interesting, because they're much less destructive to soil quality than annual crops, and they're a breeze to maintain. I could walk into the backyard of the apartment I was renting and pick a breadfruit, soak it, throw it in the oven and I had something nutritious to eat in just over an hour. It's like picking a bag of potatoes right off a tree. Insects and birds didn't seem to like it at all, possibly because the raw fruit exudes a bitter, rubbery sap when damaged. Unfortunatley, breadfruit is a tropical plant. Temperate starchy staples that were exploited by native North Americans include the majestic American chestnut in the Appalachians, and acorns in the West. These are both more work than breadfruit to prepare, particularly acorns which must be extensively soaked to remove bitter tannins.

One of the foods Polynesian settlers brought to Hawai'i was sugar cane. I had the opportunity to try fresh sugar cane for the first time while I was on Kaua'i. You cut off the outer skin, then cut it into strips and chew to get the sweet juice. It was mild but tasty. I don't know if it was a coincidence or not, but I ended up feeling unwell after eating several pieces. It may simply have been too much sugar for me.

Modern Hawai'i is a hunter-gatherer's dream. There are fruit trees everywhere, including papayas, wild and cultivated guavas, mangoes, avocados, passion fruit, breadfruit, bananas, citrus fruits and many others. Many of those fruits did not predate European contact however. Even pineapples were introduced to Hawai'i after European contact. Coconuts are everywhere, and we could pick one up for a drink and snack on almost any beach. The forests are full of wild chickens (such as the one at left) and pigs, both having resulted from the escape and subsequent mixing of Polynesian and European breeds. Kaua'ians frequently hunt the pigs, which are environmentally damaging due to their habit of rooting through topsoil for food. Large areas of forest on Kaua'i look like they've been ploughed due to the pigs' rooting. Humans are their only predators and their food is abundant.

While I was on Kaua'i, I ate mostly seafood (including delicious raw tuna poke), poi, breadfruit, coconut and sweet fruits-- a real Polynesian style hunter-gatherer diet! I swam every day, hiked in the lovely interior, and kayaked. It was a great trip, and I hope to return someday.

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Butter vs. Margarine

I came across an interesting study the other day, courtesy of Dr. John Briffa's blog. It's titled "Margarine Intake and Subsequent Coronary Heart Disease in Men", by Dr. William P. Castelli's group. It followed participants of the Framingham Heart study for 20 years, and recorded heart attack incidence*. Keep in mind that 20 years is an unusually long follow-up period.

The really cool thing about this study is they also tracked butter consumption.  Here's a graph of the overall results, by teaspoons of butter or margarine eaten per day:

Heart attack incidence increased with increasing margarine consumption (statistically significant) and decreased slightly with increasing butter consumption (not statistically significant). 

It gets more interesting. Let's have a look at some of the participant characteristics, broken down by margarine consumption:

People who ate the least margarine had the highest prevalence of glucose intolerance (pre-diabetes), smoked the most cigarettes, drank the most alcohol, and ate the most saturated fat and butter. These were the people who cared the least about their health. Yet they had the fewest heart attacks. The investigators corrected for the factors listed above in their assessment of the contribution of margarine to disease risk, however, the fact remains that the group eating the least margarine was the least health conscious. This affects disease risk in many ways, measurable or not. I've written about that before, here and here.

The investigators broke down the data into two halves: the first ten years, and the second ten. In the first ten years, there was no significant association between margarine intake and heart attack incidence. In the second ten, the group eating the most margarine had 77% more heart attacks than the group eating none:

So it appears that margarine takes a while to work its magic.

They didn't publish a breakdown of heart attack incidence with butter consumption over the two periods. The Framingham study fits in perfectly with most other observational studies showing that full-fat dairy intake is not associated with heart attack and stroke risk. 

It's worth mentioning that this study was conducted from the late 1960s until the late 1980s. Artificial trans fat labeling laws were still decades away in the U.S., and margarine contained more trans fat than it does today. Currently, margarine can contain up to 0.5 grams of trans fat per serving and still be labeled "0 g trans fat" in the U.S. The high trans fat content of the older margarines probably had something to do with the result of this study.

That does not make today's margarine healthy, however. Margarine remains an industrially processed pseudo-food. I'm just waiting for the next study showing that some ingredient in the new margarines (plant sterols? dihydro vitamin K1?) is the new trans fat.

Butter, Margarine and Heart Disease
The Coronary Heart Disease Epidemic


* More precisely, "coronary heart disease events", which includes infarction, sudden cardiac death, angina, and coronary insufficiency.

A Little Hiatus

I'm going to a conference next week, followed by a little vacation. I've written two posts that will publish automatically while I'm gone. I may or may not respond to comments for the next two weeks. I probably won't respond to e-mails. I'll resume the malocclusion series when I get back.

Malocclusion: Disease of Civilization, Part IV

There are three periods during the development of the face and jaws that are uniquely sensitive to environmental influences such as nutrition and muscle activity patterns.

1: Prenatal Period

The major structures of the human face and jaws develop during the first trimester of pregnancy. The maxilla (upper jaw) takes form between the 7th and 10th week after conception. The mandible (lower jaw) begins two weeks earlier. The nasal septum, which is the piece of cartilage that forms the structure of the nose and divides the nostrils, appears at week seven and grows most rapidly from weeks 8 to 11. Any disturbance of this developmental window can have major consequences for later occlusion.

2: Early Postnatal Period

The largest postnatal increment in face and jaw growth occurs from birth until age 4. During this period, the deciduous (baby) teeth erupt, and the activity patterns of the jaw and tongue influence the size and shape of the maxilla and the mandible as they grow. The relationship of the jaws to one another is mostly determined during this period, although it can still change later in development.

During this period, the dental arch widens from its center, called the midpalatal suture. This ensures that the jaws are the correct size and shape to eventually accept the permanent teeth without crowding them.

3: Adolescence

The third major developmental period occurs between ages 11 and 16, depending on the gender and individual, and happens roughly at the same time as the growth spurt in height. The dental arch continues to widen, reaching its final size and shape. Under ideal circumstances, at the end of this period the arch should be large enough to accommodate all teeth, including the third molars (wisdom teeth), without crowding. Narrow dental arches cause malocclusion and third molar crowding.

Growth of the Dental Arch Over Time

The following graph shows the widening of the dental arch over time*. The dotted line represents arch growth while the solid line represents growth in body height. You can see that arch development slows down after 6 years old, resumes around 11, and finally ends at about 18 years. This graph represents the average of many children, so not all children will see these changes at the age indicated. The numbers are in millimeters per year, but keep in mind that the difference between a narrow arch and a broad one is only a few millimeters.

In the next few posts, I'll describe the factors that I believe influence jaw and face structure during the three critical periods of development.


* These data represent many years of measurements collected by Dr. Arne Bjork, who used metallic implants in the maxilla to make precise measurements of arch growth over time in Danish youths. The graph is reproduced from the book A Synopsis of Craniofacial Growth, by Dr. Don M. Ranly. Data come from Dr. Bjork's findings published in the book Postnatal Growth and Development of the Maxillary Complex. You can see some of Dr. Bjork's data in the paper "Sutural Growth of the Upper Face Studied by the Implant Method" (free full text).

Malocclusion: Disease of Civilization, Part III

Normal Human Occlusion

In 1967, a team of geneticists and anthropologists published an extensive study of a population of Brazilian hunter-gatherers called the Xavante (1). They made a large number of physical measurements, including of the skull and jaws. Of 146 Xavante examined, 95% had "ideal" occlusion, while the 5% with malocclusion had nothing more than mild crowding of the incisors (front teeth). The authors wrote:

Characteristically, the Xavante adults exhibited broad dental arches, almost perfectly aligned teeth, end-to-end bite, and extensive dental attrition [tooth wear].

In the same paper, the author presents occlusion statistics for three other cultures. According to the papers he cites, in Japan, the prevalence of malocclusion was 59%, and in the US (Utah), it was 64%. He also mentions another native group living near the Xavante, part of the Bakairi tribe, living at a government post and presumably eating processed food. The prevalence of malocclusion was 45% in this group.

In 1998, Dr. Brian Palmer (DDS) published a paper describing some of the collections of historical skulls he had examined over the years (2):

...I reviewed an additional twenty prehistoric skulls, some dated at 70,000 years old and stored in the Anthropology Department at the University of Kansas. Those skulls also exhibited positive [good] occlusions, minimal decay, broad hard palates, and "U-shaped" arches.

The final evaluations were of 370 skulls preserved at the Smithsonian Institution in Washington, D.C. The skulls were those of prehistoric North American plains Indians and more contemporary American skulls dating from the 1920s to 1940s. The prehistoric skulls exhibited the same features as mentioned above, whereas a significant destruction and collapse of the oral cavity were evident in the collection of the more recent skulls. Many of these more recent skulls revealed severe periodontal disease, malocclusions, missing teeth, and some dentures. This was not the case in the skulls from the prehistoric periods...

The arch is the part of the upper jaw inside the "U" formed by the teeth. Narrow dental arches are a characteristic feature of malocclusion-prone societies. The importance of arch development is something that I'll be coming back to repeatedly. Dr. Palmer's paper includes the following example of prehistoric (L) and modern (R) arches:


Dr. Palmer used an extreme example of a modern arch to illustrate his point, however, arches of this width are not uncommon today. Milder forms of this narrowing affect the majority of the population in industrial nations.

In 1962, Dr. D.H. Goose published a study of 403 British skulls from four historical periods: Romano-British, Saxon, medieval and modern (3). He found that the arches of modern skulls were less broad than at any previous time in history. This followed an earlier study showing that modern British skulls had more frequent malocclusion than historical skulls (4). Goose stated that:

Although irregularities of the teeth can occur in earlier populations, for example in the Saxon skulls studied by Smyth (1934), the narrowing of the palate seems to have occurred in too short a period to be an evolutionary change. Hooton (1946) thinks it is a speeding up of an already long standing change under conditions of city life.

Dr. Robert Corruccini published several papers documenting narrowed arches in one generation of dietary change, or in genetically similar populations living rural or urban lifestyles (reviewed in reference #5). One was a study of Caucasians in Kentucky, in which a change from a traditional subsistence diet to modern industrial food habits accompanied a marked narrowing of arches and increase in malocclusion in one generation. Another study examined older and younger generations of Pima Native Americans, which again showed a reduction in arch width in one generation. A third compared rural and urban Indians living in the vicinity of Chandigarh, showing marked differences in arch breadth and the prevalence of malocclusion between the two genetically similar populations. Corruccini states:

In Chandigarh, processed food predominates, while in the country coarse millet and locally grown vegetables are staples. Raw sugar cane is widely chewed for enjoyment rurally [interestingly, the rural group had the lowest incidence of tooth decay], and in the country dental care is lacking, being replaced by chewing on acacia boughs which clean the teeth and are considered medicinal.

Dr. Weston Price came to the same conclusion examining prehistoric skulls from South America, Australia and New Zealand, as well as their living counterparts throughout the world that had adhered to traditional cultures and foodways. From Nutrition and Physical Degeneration:

In a study of several hundred skulls taken from the burial mounds of southern Florida, the incidence of tooth decay was so low as to constitute an immunity of apparently one hundred per cent, since in several hundred skulls not a single tooth was found to have been attacked by tooth decay. Dental arch deformity and the typical change in facial form due to an inadequate nutrition were also completely absent, all dental arches having a form and interdental relationship [occlusion] such as to bring them into the classification of normal.

Price found that the modern descendants of this culture, eating processed food, suffered from malocclusion and narrow arches, while another group from the same culture living traditionally did not. Here's one of Dr. Price's images from Nutrition and Physical Degeneration (p. 212). This skull is from a prehistoric New Zealand Maori hunter-gatherer:


Note the well-formed third molars (wisdom teeth) in both of the prehistoric skulls I've posted. These people had ample room for them in their broad arches. Third molar crowding is a mild form of modern face/jaw deformity, and affects the majority of modern populations. It's the reason people have their wisdom teeth removed. Urban Nigerians in Lagos have 10 times more third molar crowding than rural Nigerians in the same state (10.7% of molars vs. 1.1%, reference #6).

Straight teeth and good occlusion are the human evolutionary norm. They're also accompanied by a wide dental arch and ample room for third molars in many traditionally-living cultures. The combination of narrow arches, malocclusion, third molar crowding, small or absent sinuses, and a characteristic underdevelopment of the middle third of the face, are part of a developmental syndrome that predominantly afflicts industrially living cultures.

(1) Am. J. Hum. Genet. 19(4):543. 1967. (free full text)
(2) J. Hum. Lact. 14(2):93. 1998
(3) Arch. Oral Biol. 7:343. 1962
(4) Brash, J.C.: The Aetiology of Irregularity and Malocclusion of the Teeth. Dental Board of the United Kingdom, London, 1929.
(5) Am J. Orthod. 86(5):419
(6) Odonto-Stomatologie Tropicale. 90:25. (free full text)

Malocclusion: Disease of Civilization, Part II

The Nature of the Problem

In 1973, the US Centers for Disease Control and Prevention (CDC) published the results of a National Health Survey in which it examined the dental health of American youths nationwide. The following description was published in a special issue of the journal Pediatric Dentistry (1):

The 1973 National Health Survey reported 75% of children, ages 6 to 11 years, and 89% of youths, ages 12 to 17 years, have some degree of occlusal disharmony [malocclusion]; 8.7% of children and 13% of youth had what was considered a severe handicapping malocclusion for which treatment was highly desirable and 5.5% of children and 16% of youth had a severe handicapping malocclusion that required mandatory treatment.

89% of youths had some degree of malocclusion, and 29% had a severe handicapping malocclusion for which treatment was either highly desirable or mandatory. Fortunately, many of these received orthodontics so the malocclusion didn't persist into adulthood.

This is consistent with another survey conducted in 1977, in which 38% of American youths showed definite or severe malocclusion. 46% had occlusion that the authors deemed "ideal or acceptable" (2).

The trend continues. The CDC National Health and Nutrition Examination Survey III (NHANES III) found in 1988-1991 that approximately three fourths of Americans age 12 to 50 years had some degree of malocclusion (3).

The same holds true for Caucasian-Americans, African-Americans and Native Americans in the US, as well as other industrial nations around the world. Typically, only 1/3 to 1/2 of the population shows good (but not necessarily perfect) occlusion (4- 8).

In the next post, I'll review some of the data from non-industrial and transitioning populations.


Malocclusion: Disease of Civilization


1. Pediatr. Dent. 17(6):1-6. 1995-1996
2. USPHS Vital and Health Statistics Ser. 11, no 162. 1977
3. J. Dent. Res. Special issue. 75:706. 1996. Pubmed link.
4. The Evaluation of Canadian Dental Health. 1959. Describes Canadian occlusion.
5. The Effects of Inbreeding on Japanese Children. 1965. Contains data on Japanese occlusion.
6. J. Dent. Res. 35:115. 1956. Contains data on both industrial and non-industrial cultures (Pukapuka, Fiji, New Guinea, U.S.A. and New Zealand).
7. J. Dent. Res. 44:947. 1965 (free full text). Contains data on Caucasian-Americans and African-Americans living in several U.S. regions, as well as data from two regions of Germany. Only includes data on Angle classifications, not other types of malocclusion such as crossbite and open bite (i.e., the data underestimate the total prevalence of malocclusion).
8. J. Dent. Res. 47:302. 1968 (free full text). Contains data on Chippewa Native Americans in the U.S., whose occlusion was particularly bad, especially when compared to previous generations.