Magnesium and Insulin Sensitivity

From a paper based on US NHANES nutrition and health survey data (1):

During 1999–2000, the diet of a large proportion of the U.S. population did not contain adequate magnesium... Furthermore, racial or ethnic differences in magnesium persist and may contribute to some health disparities.... Because magnesium intake is low among many people in the United States and inadequate magnesium status is associated with increased risk of acute and chronic conditions, an urgent need exists to perform a current survey to assess the physiologic status of magnesium in the U.S. population.

Magnesium is an essential mineral that's slowly disappearing from the modern diet, as industrial agriculture and industrial food processing increasingly dominate our food choices. One of the many things it's necessary for in mammals is proper insulin sensitivity and glucose control. A loss of glucose control due to insulin resistance can eventually lead to diabetes and all its complications.

Magnesium status is associated with insulin sensitivity (2, 3), and a low magnesium intake predicts the development of type II diabetes in most studies (4, 5) but not all (6). Magnesium supplements largely prevent diabetes in a rat model* (7). Interestingly, excess blood glucose and insulin themselves seem to reduce magnesium status, possibly creating a vicious cycle.

In a 1993 trial, a low-magnesium diet reduced insulin sensitivity in healthy volunteers by 25% in just four weeks (8). It also increased urinary thromboxane concentration, a potential concern for cardiovascular health**.

At least three trials have shown that magnesium supplementation increases insulin sensitivity in insulin-resistant diabetics and non-diabetics (9, 10, 11). In some cases, the results were remarkable. In type II diabetics, 16 weeks of magnesium supplementation improved fasting glucose, calculated insulin sensitivity and HbA1c*** (12). HbA1c dropped by 22 percent.

In insulin resistant volunteers with low blood magnesium, magnesium supplementation for four months reduced estimated insulin resistance by 43 percent and decreased fasting insulin by 32 percent (13). This suggests to me that magnesium deficiency was probably one of the main reasons they were insulin resistant in the first place. But the study had another very interesting finding: magnesium improved the subjects' blood lipid profile remarkably. Total cholesterol decreased, LDL decreased, HDL increased and triglycerides decreased by a whopping 39 percent. The same thing had been reported in the medical literature decades earlier when doctors used magnesium injections to treat heart disease, and also in animals treated with magnesium. Magnesium supplementation also suppresses atherosclerosis (thickening and hardening of the arteries) in animal models, a fact that I may discuss in more detail at some point (14, 15).

In the previous study, participants were given 2.5 g magnesium chloride (MgCl2) per day. That's a bit more than the USDA recommended daily allowance (MgCl2 is mostly chloride by weight), in addition to what they were already getting from their diet. Most of a person's magnesium is in their bones, so correcting a deficiency by eating a nutritious diet may take a while.

Speaking of nutritious diets, how does one get magnesium? Good sources include halibut, leafy greens, chocolate and nuts. Bone broths are also an excellent source of highly absorbable magnesium. Whole grains and beans are also fairly good sources, while refined grains lack most of the magnesium in the whole grain. Organic foods, particularly artisanally produced foods from a farmer's market, are richer in magnesium because they grow on better soil and often use older varieties that are more nutritious.

The problem with seeds such as grains, beans and nuts is that they also contain phytic acid which prevents the absorption of magnesium and other minerals (16). Healthy non-industrial societies that relied on grains took great care in their preparation: they soaked them, often fermented them, and also frequently removed a portion of the bran before cooking (17). These steps all served to reduce the level of phytic acid and other anti-nutrients. I've posted a method for effectively reducing the amount of phytic acid in brown rice (18). Beans should ideally be soaked for 24 hours before cooking, preferably in warm water.

Industrial agriculture has systematically depleted our soil of many minerals, due to high-yield crop varieties and the fact that synthetic fertilizers only replace a few minerals. The mineral content of foods in the US, including magnesium, has dropped sharply in the last 50 years. The reason we need to use fertilizers in the first place is that we've broken the natural nutrient cycle in which minerals always return to the soil in the same place they were removed. In 21st century America, minerals are removed from the soil, pass through our toilets, and end up in the landfill or in waste water. This will continue until we find an acceptable way to return human feces and urine to agricultural soil, as many cultures do to this day****.

I believe that an adequate magnesium intake is critical for proper insulin sensitivity and overall health.


* Zucker rats that lack leptin signaling

** Thromboxane A2 is an omega-6 derived eicosanoid that potently constricts blood vessels and promotes blood clotting. It's interesting that magnesium has such a strong effect on it. It indicates that fatty acid balance is not the only major influence on eicosanoid production.

*** Glycated hemoglobin. A measure of the average blood glucose level over the past few weeks.

**** Anyone interested in further reading on this should look up The Humanure Handbook

Dissolve Away those Pesky Bones with Corn Oil

I just read an interesting paper from Gabriel Fernandes's group at the University of Texas. It's titled "High fat diet-induced animal model of age-associated obesity and osteoporosis". I was expecting this to be the usual "we fed mice industrial lard for 60% of calories and they got sick" paper, but I was pleasantly surprised. From the introduction:

CO [corn oil] is known to promote bone loss, obesity, impaired glucose tolerance, insulin resistance and thus represents a useful model for studying the early stages in the development of obesity, hyperglycemia, Type 2 diabetes [23] and osteoporosis. We have used omega-6 fatty acids enriched diet as a fat source which is commonly observed in today's Western diets basically responsible for the pathogenesis of many diseases [24].

Just 10% of the diet as corn oil (roughly 20% of calories), with no added omega-3, on top of an otherwise poor laboratory diet, caused:

• Obesity
• Osteoporosis
• The replacement of bone marrow with fat cells
  
• Diabetes
• Insulin resistance
  
• Generalized inflammation
• Elevated liver weight (possibly indicating fatty liver)
  

Hmm, some of these sound familiar... We can add them to the findings that omega-6 also promotes various types of cancer in rodents (1).

20% fat is less than the amount it typically takes to make a rodent this sick. This leads me to conclude that corn oil is particularly good at causing mouse versions of some of the most common facets of the "diseases of civilization". It's exceptionally high in omega-6 (linoleic acid) with virtually no omega-3.

Make sure to eat your heart-healthy corn oil! It's made in the USA, dirt cheap and it even lowers cholesterol!

Lindeberg on Obesity

I'm currently reading Dr. Staffan Lindeberg's magnum opus Food and Western Disease, recently published in English for the first time. Dr. Lindeberg is one of the world's leading experts on the health and diet of non-industrial cultures, particularly in Papua New Guinea. The book contains 2,034 references. It's also full of quotable statements. Here's what he has to say about obesity:

Middle-age spread is a normal phenomenon - assuming you live in the West. Few people are able to maintain their [youthful] waistline after age 50. The usual explanation - too little exercise and too much food - does not fully take into account the situation among traditional populations. Such people are usually not as physically active as you may think, and they usually eat large quantities of food.

Overweight has been extremely rare among hunter-gatherers and other traditional cultures [18 references]. This simple fact has been quickly apparent to all foreign visitors...

The Kitava study measured height, weight, waist circumference, subcutaneous fat thickness at the back of the upper arm (triceps skinfold) and upper arm circumference on 272 persons ages 4-86 years. Overweight and obesity were absent and average [body mass index] was low across all age groups. ...no one was larger around their waist than around their hips.

...The circumference of the upper arm [mostly indicating muscle mass] was only negligibly smaller on Kitava [compared with Sweden], which indicates that there was no malnutrition. It is obvious from our investigations that lack of food is an unknown concept, and that the surplus of fruits and vegetables regularly rots or is eaten by dogs.

The Population of Kitava occupies a unique position in the world in terms of the negligible effect that the Western lifestyle has had on the island.

The only obese Kitavans Dr. Lindeberg observed were two people who had spent several years off the island living a modern, urban lifestyle, and were back on Kitava for a visit.

I'd recommend this book to anyone who has a scholarly interest in health and nutrition, and somewhat of a background in science and medicine. It's extremely well referenced, which makes it much more valuable.

Saturated Fat and Insulin Sensitivity

Insulin sensitivity is a measure of the tissue response to insulin. Typically, it refers to insulin's ability to cause tissues to absorb glucose from the blood. A loss of insulin sensitivity, also called insulin resistance, is a core part of the metabolic disorder that affects many people in industrial nations.

I don't know how many times I've seen the claim in journal articles and on the internet that saturated fat reduces insulin sensitivity. The idea is that saturated fat reduces the body's ability to handle glucose effectively, placing people on the road to diabetes, obesity and heart disease. Given the "selective citation disorder" that plagues the diet-health literature, perhaps this particular claim deserves a closer look.

The Evidence

I found a review article from 2008 that addressed this question (1). I like this review because it only includes high-quality trials that used reliable methods of determining insulin sensitivity*.

On to the meat of it. There were 5 studies in which non-diabetic people were fed diets rich in saturated fat, and compared with a group eating a diet rich in monounsaturated (like olive oil) or polyunsaturated (like corn oil) fat. They ranged in duration from one week to 3 months. Four of the five studies found that fat quality did not affect insulin sensitivity, including one of the 3-month studies.

The fifth study, which is the one that's nearly always cited in the diet-health literature, requires some discussion. This was the KANWU study (2). Over the course of three months, investigators fed 163 volunteers a diet rich in either saturated fat or monounsaturated fat.

The SAFA diet included butter and a table margarine containing a relatively high proportion of SAFAs. The MUFA diet included a spread and a margarine containing high proportions of oleic acid derived from high-oleic sunflower oil and negligible amounts of trans fatty acids and n-3 fatty acids and olive oil.

Yummy. After three months of these diets, there was no significant difference in insulin sensitivity between the saturated fat group and the monounsaturated fat group. Yes, you read that right. Even the study that's selectively cited as evidence that saturated fat causes insulin resistance found no significant difference between the diets. You might not get this by reading the misleading abstract. I'll be generous and acknowledge that the (small) difference was almost statistically significant (p = 0.053).

What the authors decided to focus on instead is the fact that insulin sensitivity declined slightly but significantly on the saturated fat diet compared with the pre-diet baseline. That's why this study is cited as evidence that saturated fat impairs insulin sensitivity. But anyone who has a basic science background will see where this reasoning is flawed (warning: nerd attack. skip the rest of the paragraph if you're not interested). You need a control group for comparison, to take into account normal fluctuations caused by such things as the season, eating mostly cafeteria food, and having a doctor hooking you up to machines. That control group was the group eating monounsaturated fat. The comparison between diet groups was the 'primary outcome', in statistics lingo. That's the comparison that matters, and it wasn't significant. To interpret the study otherwise is to ignore the basic conventions of statistics, which the authors were happy to do. There's a name for it: 'moving the goalpost'. The reviewers shouldn't have let this kind of shenanigans slide.

So we have five studies through 2008, none of which support the idea that saturated fat reduces insulin sensitivity in non-diabetics. Since the review paper was published, I know of one subsequent study that asked the same question (3). Susan J. van Dijk and colleagues fed volunteers with abdominal overweight (beer gut) a diet rich in either saturated fat or monounsaturated fat. I e-mailed the senior author and she said the saturated fat diet was "mostly butter". The specific fats used in the diets weren't mentioned anywhere in the paper, which is a major omission**. In any case, after 8 weeks, insulin sensitivity was virtually identical between the two groups. This study appeared well controlled and used the gold standard method for assessing insulin sensitivity, called the euglycemic-hyperinsulinemic clamp technique***.

The evidence from controlled trials is rather consistent that saturated fat has no appreciable effect on insulin sensitivity.

Why Are We so Focused on Saturated Fat?

Answer: because it's the nutrient everyone loves to hate. As an exercise in completeness, I'm going to mention three dietary factors that actually reduce insulin sensitivity, and get a lot less air time than saturated fat.

#1: Caffeine. That's right, controlled trials show that your favorite murky beverage reduces insulin sensitivity (4, 5). Is it actually relevant to real life? I doubt it. The doses used were large and the studies short-term.

#2: Magnesium deficiency. A low-magnesium diet reduced insulin sensitivity by 25% over the course of three weeks (6). I think this is probably relevant to long-term insulin sensitivity and overall health, although it would be good to have longer-term data. Magnesium deficiency is widespread in industrial nations, due to our over-reliance on refined foods such as sugar, white flour and oils.

#3: Sugar. Fructose reduces insulin sensitivity in humans, along with many other harmful effects (7).

As long as we continue to focus our energy on indicting saturated fat, it will continue distracting us from the real causes of disease.


* For the nerds: euglycemic-hyperinsulinemic clamp (the gold standard), insulin suppression test, or intravenous glucose tolerance test with Minimal Model. They didn't include studies that reported HOMA as their only measure, because it's not very accurate.

** There's this idea that pervades the diet-health literature that all saturated fats are roughly equivalent, all monounsaturated fats are equivalent, etc., therefore it doesn't matter what the source was. This is beyond absurd and reflects our cultural obsession with saturated fat. It really irks me that the reviewers didn't demand this information.

*** They did find that markers of inflammation in fat tissue were higher after the saturated fat diet.

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 does not help them lose weight in the long term. Gary Taubes has written about this at length in his book Good Calories, Bad Calories, and in his upcoming book on body fat. 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's extremely difficult to fight the fat mass setpoint, and the body will use every tool it has to maintain its preferred level of fat: hunger, 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

The most obvious treatment that fits all of my criteria is low-carbohydrate dieting. Overweight people eating low-carbohydrate diets generally lose 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 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 (2).

Another strategy that appears effective 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: avoid refined sugar, refined carbohydrate in general, and lactose if you're lactose intolerant. 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).

Oligofructose is similar to inulin, a fiber that occurs naturally in a wide variety of plants. Good sources are jerusalem artichokes, jicama, artichokes, onions, leeks, burdock and chicory root. Certain non-industrial cultures had a high intake of inulin. There are some caveats to inulin, however: inulin and oligofructose can cause gas, and can also exacerbate gastroesophageal reflux disorder (9). So don't eat a big plate of jerusalem artichokes before that important date.

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 widespread and typically undiagnosed (10).

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. Other important factors in gut barrier health are keeping the ratio of omega-6 to omega-3 fats in balance, eating nutrient-dense food, and avoiding the questionable chemical additives in processed food. If triglycerides are important for leptin sensitivity, then avoiding sugar and ensuring a regular source of omega-3 should aid weight loss as well.

Strategies: Micronutrients

As I discussed in the last post, micronutrient deficiency probably plays a role in obesity, both in ways that we understand and ways that we (or I) don't. Eating a diet that has a high nutrient density and ensuring a good vitamin D status will help any sustainable fat loss strategy. The easiest way to do this is to eliminate industrially processed foods such as white flour, sugar and seed oils. These constitute more than 50% of calories for the average Westerner.

After that, you can further increase your diet's nutrient density by learning to properly prepare grains and legumes to maximize their nutritional value and digestibility (11, 12; or by avoiding grains and legumes altogether if you wish), selecting organic and/or pasture-raised foods if possible, and eating seafood including seaweed. One of the problems with extremely low-carbohydrate diets is that they may be low in water-soluble micronutrients, although this isn't necessarily the case.

Strategies: Miscellaneous

In general, exercise isn't necessarily helpful for fat loss. However, there is one type of exercise that clearly is: high-intensity intermittent training (HIIT). It's basically a fancy name for sprints. They can be done on a track, on a stationary bicycle, using weight training circuits, or any other way that allows sufficient intensity. The key is to achieve maximal exertion for several brief periods, separated by rest. This type of exercise is not about burning calories through exertion: it's about increasing hormone sensitivity using an intense, brief stressor (hormesis). Even a ridiculously short period of time spent training HIIT each week can result in significant fat loss, despite no change in diet or calorie intake (13).

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.

I'm sure there are other useful strategies, but that's all I have for now. If you have something to add, please put it in the comments.


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

New Saturated Fat Review Article by Dr. Ronald Krauss

I never thought I'd see the day when one of the most prominent lipid researchers in the world did an honest review of the observational studies evaluating the link between saturated fat and cardiovascular disease. Dr. Ronald Krauss's group has published a review article titled "Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease". As anyone with two eyes and access to the medical literature would conclude (including myself), they found no association whatsoever between saturated fat intake and heart disease or stroke:

A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD.

Bravo, Dr. Krauss. That was a brave move.

Thanks to Peter for pointing out this article.

The Body Fat Setpoint, Part II: Mechanisms of Fat Gain

The Timeline of Fat Gain

Modern humans are unusual mammals in that fat mass varies greatly between individuals. Some animals carry a large amount of fat for a specific purpose, such as hibernation or migration. But all individuals of the same sex and social position will carry approximately the same amount of fat at any given time of year. Likewise, in hunter-gatherer societies worldwide, there isn't much variation in body weight-- nearly everyone is lean. Not necessarily lean like Usain Bolt, but not overweight.

Although overweight and obesity occurred forty years ago in the U.S. and U.K., they were much less common than today, particularly in children. Here are data from the U.S. Centers for Disease Control NHANES surveys (from this post):

Together, this shows that a) leanness is the most natural condition for the human body, and b) something about our changing environment, not our genes, has caused our body fat to grow.

Fat Mass is Regulated by a Feedback Circuit Between Fat Tissue and the Brain

In the last post, I described how the body regulates fat mass, attempting to keep it within a narrow window or "setpoint". Body fat produces a hormone called leptin, which signals to the brain and other organs to decrease appetite, increase the metabolic rate and increase physical activity. More fat means more leptin, which then causes the extra fat to be burned. The little glitch is that some people become resistant to leptin, so that their brain doesn't hear the fat tissue screaming that it's already full. Leptin resistance nearly always accompanies obesity, because it's a precondition of significant fat gain. If a person weren't leptin resistant, he wouldn't have the ability to gain more than a few pounds of fat without heroic overeating (which is very very unpleasant when your brain is telling you to stop). Animal models of leptin resistance develop something that resembles human metabolic syndrome (abdominal obesity, blood lipid abnormalities, insulin resistance, high blood pressure).

The Role of the Hypothalamus

The hypothalamus is on the underside of the brain connected to the pituitary gland. It's the main site of leptin action in the brain, and it controls the majority of leptin's effects on appetite, energy expenditure and insulin sensitivity. Most of the known gene variations that are associated with overweight in humans influence the function of the hypothalamus in some way (1). Not surprisingly, leptin resistance in the hypothalamus has been proposed as a cause of obesity. It's been shown in rats and mice that hypothalamic leptin resistance occurs in diet-induced obesity, and it's almost certainly the case in humans as well. What's causing leptin resistance in the hypothalamus?

There are three leading explanations at this point that are not mutually exclusive. One is cellular stress in the endoplasmic reticulum, a structure inside the cell that's used for protein synthesis and folding. I've read the most recent paper on this in detail, and I found it unconvincing (2). I'm open to the idea, but it needs more rigorous support.

A second explanation is inflammation in the hypothalamus. Inflammation inhibits leptin and insulin signaling in a variety of cell types. At least two studies have shown that diet-induced obesity in rodents leads to inflammation in the hypothalamus (3, 4)*. If leptin is getting to the hypothalamus, but the hypothalamus is insensitive to it, it will require more leptin to get the same signal, and fat mass will creep up until it reaches a higher setpoint.

The other possibility is that leptin simply isn't reaching the hypothalamus. The brain is a unique organ. It's enclosed by the blood-brain barrier (BBB), which greatly restricts what can enter and leave it. Both insulin and leptin are actively transported across the BBB. It's been known for a decade that obesity in rodents is associated with a lower rate of leptin transport across the BBB (5, 6).

What causes a decrease in leptin transport across the BBB? Triglycerides are a major factor. These are circulating fats going from the liver and the digestive tract to other tissues. They're one of the blood lipid measurements the doctor makes when he draws your blood. Several studies in rodents have shown that high triglycerides cause a reduction in leptin transport across the BBB, and reducing triglycerides allows greater leptin transport and fat loss (7, 8). In support of this theory, the triglyceride-reducing drug gemfibrozil also causes weight loss in humans (9)**. Guess what else reduces triglycerides and causes weight loss? Low-carbohydrate diets, and avoiding sugar and refined carbohydrates in particular.

In the next post, I'll get more specific about what factors could be causing hypothalamic inflammation and/or reduced leptin transport across the BBB. I'll also discuss some ideas on how to reduce leptin resistance sustainably through diet and exercise.


* This is accomplished by feeding them sad little pellets that look like greasy chalk. They're made up mostly of lard, soybean oil, casein, maltodextrin or cornstarch, sugar, vitamins and minerals (this is a link to the the most commonly used diet for inducing obesity in rodents). Food doesn't get any more refined than this stuff, and adding just about anything to it, from fiber to fruit extracts, makes it less damaging.

** Fibrates are PPAR agonists, so the weight loss could also be due to something besides the reduction in triglycerides.

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

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. It has to cause leptin resistance or otherwise disturb the setpoint
   

Although I believe that exercise is part of a healthy lifestyle, it probably can't explain the increase in fat mass in modern nations. I've written about that here and here. 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 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 probably plays a major role in obesity and other modern metabolic problems. Insufficient dietary fiber, micronutrient deficiencies, excessive gut irritating substances such as gluten, abnormal bacterial growth due to refined carbohydrates (particularly sugar), and omega-6:3 imbalance may all contribute to abnormal gut bacteria and increased gut permeability.

The Role of Fatty Acids and Micronutrients

Any time a disease involves inflammation, the first thing that comes to my mind is the balance between omega-6 and omega-3 fats. The modern Western diet is heavily weighted toward omega-6, which are the precursors to some very inflammatory substances (as well as a few that are anti-inflammatory). These substances are essential for health in the correct amounts, but they need to be balanced with omega-3 to prevent excessive and uncontrolled inflammatory responses. Animal models have repeatedly shown that omega-3 deficiency contributes to the fat gain and insulin resistance they develop when fed high-fat diets (9, 10, 11).

As a matter of fact, most of the papers claiming "saturated fat causes this or that in rodents" are actually studying omega-3 deficiency. The "saturated fats" that are typically used in high-fat rodent diets are refined fats from conventionally raised animals, which are very low in omega-3. If you add a bit of omega-3 to these diets, suddenly they don't cause the same metabolic problems, and are generally superior to refined seed oils, even in rodents (12, 13).

I believe that micronutrient deficiency also plays a role. Inadequate vitamin and mineral status can contribute to inflammation and weight gain. Obese people typically show deficiencies in several vitamins and minerals. The problem is that we don't know whether the deficiencies caused the obesity or vice versa. Refined carbohydrates and refined oils are the worst offenders because they're almost completely devoid of micronutrients.

Vitamin D in particular plays an important role in immune responses (including inflammation), and also appears to influence body fat mass. Vitamin D status is associated with body fat and insulin sensitivity in humans (14, 15, 16). More convincingly, genetic differences in the vitamin D receptor gene are also associated with body fat mass (17, 18), and vitamin D intake predicts future fat gain (19).

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.

The Body Fat Setpoint

One pound of human fat contains about 3,500 calories. That represents roughly 40 slices of toast. So if you were to eat one extra slice of toast every day, you would gain just under a pound of fat per month. Conversely, if you were to eat one fewer slice per day, you'd lose a pound a month. Right? Not quite.

How is it that most peoples' body fat mass stays relatively stable over long periods of time, when an imbalance of as little as 5% of calories should lead to rapid changes in weight? Is it because we do complicated calculations in our heads every day, factoring in basal metabolic rate and exercise, to make sure our energy intake precisely matches expenditure? Of course not. We're gifted with a sophisticated system of hormones and brain regions that do the calculations for us unconsciously*.

When it's working properly, this system precisely matches energy intake to expenditure, ensuring a stable and healthy fat mass. It does this by controlling food seeking behaviors, feelings of fullness and even energy expenditure by heat production and physical movements. If you eat a little bit more than usual at a meal, a properly functioning system will say "let's eat a little bit less next time, and also burn some of it off." This is why animals in their natural habitat are nearly always at an appropriate weight, barring starvation. The only time wild animals are overweight enough to compromise maximum physical performance is when it serves an important purpose, such as preparing for hibernation.

I recently came across a classic study that illustrates these principles nicely in humans, titled "Metabolic Response to Experimental Overfeeding in Lean and Overweight Healthy Volunteers", by Dr. Erik O. Diaz and colleagues (1). They overfed lean and modestly overweight volunteers 50% more calories than they naturally consume, under controlled conditions where the investigators could be confident of food intake. Macronutrient composition was 12-42-46 % protein-fat-carbohydrate.

After 6 weeks of massive overfeeding, both lean and overweight subjects gained an average of 10 lb (4.6 kg) of fat mass and 6.6 lb (3 kg) of lean mass. Consistent with what one would expect if the body were trying to burn off excess calories and return to baseline fat mass, the metabolic rate and body heat production of the subjects increased.

Following overfeeding, subjects were allowed to eat however much they wanted for 6 weeks. Both lean and overweight volunteers promptly lost 6.2 of the 10 lb they had gained in fat mass (61% of fat gained), and 1.5 of the 6.6 lb they had gained in lean mass (23%). Here is a graph showing changes in fat mass for each individual that completed the study:

We don't know if they would have lost the remaining fat mass in the following weeks because they were only followed for 6 weeks after overfeeding, although it did appear that they were reaching a plateau slightly above their original body weight. Thus, nearly all subjects "defended" their original body fat mass irrespective of their starting point. Underfeeding studies have shown the same phenomenon: whether lean or overweight, people tend to return to their original fat mass after underfeeding is over. Again, this supports the idea that the body has a body fat mass "set point" that it attempts to defend against changes in either direction. It's one of many systems in the body that attempt to maintain homeostasis.

OK, so why do we care?

We care because this has some very important implications for human obesity. With such a powerful system in place to keep body fat mass in a narrow range, a major departure from that range implies that the system isn't functioning correctly. In other words, obesity has to result from a defect in the system that regulates body fat, because a properly functioning system would not have allowed that degree of fat gain in the first place.

So yes, we are gaining weight because we eat too many calories relative to energy expended. But why are we eating too many calories? Because the system that should be defending a low fat mass is now defending a high fat mass. Therefore, the solution is not simply to restrict calories, or burn more calories through exercise, but to try to "reset" the system that decides what fat mass to defend. Restricting calories isn't necessarily a good solution because the body will attempt to defend its setpoint, whether high or low, by increasing hunger and decreasing its metabolic rate. That's why low-calorie diets, and most diets in general, typically fail in the long term. It's miserable to fight hunger every day.

This raises two questions:

1. What caused the system to defend a high fat mass?
2. Is it possible to reset the fat mass setpoint, and how would one go about it?
   

Given the fact that body fat mass is much higher in many affluent nations than it has ever been in human history, the increase must be due to factors that have changed in modern times. I can only speculate what these factors may be, because research has not identified them to my knowledge, at least not in humans. But I have my guesses. I'll expand on this in the next post.


* The hormone leptin and the hypothalamus are the ringleaders, although there are many other elements involved, such as numerous gut-derived peptides, insulin, and a number of other brain regions.

Rabbits on a High-Saturated Fat Diet Without Added Cholesterol

I just saw another study that supports my previous post Animal Models of Atherosclerosis: LDL. The hypothesis is that in the absence of excessive added dietary cholesterol, saturated fat does not influence LDL or atherosclerosis in animal models, relative to other fats (although omega-6 polyunsaturated oils do lower LDL in some animal models). This appears to be consistent with what we see in humans.

In this study, they fed four groups of rabbits different diets:

1. Regular low-fat rabbit chow
2. Regular low-fat rabbit chow plus 0.5 g cholesterol per day
3. High-fat diet with 30% calories as coconut oil (saturated) and no added cholesterol
   
4. High-fat diet with 30% calories as sunflower oil (polyunsaturated) and no added cholesterol
   

LDL at 6 months was the same in groups 1, 3 and 4, but was increased more than 20-fold in group 2. It's not the fat, it's the fact that they're overloading herbivores with dietary cholesterol!

Total cholesterol was also the same between all groups except the cholesterol-fed group. TBARS, a measure of lipid oxidation in the blood, was elevated in the cholesterol and sunflower oil groups but not in the chow or coconut groups. Oxidation of blood lipids is one of the major factors in atherosclerosis, the vascular disease that narrows arteries and increases the risk of having a heart attack. Serum vitamin C was lower in the cholesterol-fed groups but not the others.

This supports the idea that saturated fat does not inherently increase LDL, and in fact in most animals it does not. This appears to be the case in humans as well, where long-term trials have shown no difference in LDL between people eating more saturated fat and people eating less, on timescales of one year or more (some short trials show a modest LDL-raising effect, but even this appears to be due to an increase in particle size rather than particle number). Since these trials represent the average of many people, they may hide some individual variability: it may actually increase LDL in some people and decrease it in others.

Merry Christmas!

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

An Interesting Finding

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

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

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

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

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

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

Butyrate Suppresses Inflammation in the Gut and Other Tissues

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

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

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

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

Butyrate Increases Resistance to Metabolic and Physical Stress

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

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

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

Due to the potent effect butyrate has on a number of bodily processes, I believe it may be a fundamental controller of metabolism, stress resistance and the immune system in mammals, similar to omega-6:3 balance.

An Ancient Line of Communication Between Symbiotic Organisms

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

A Change of Heart

Butyrate has caused me to re-think my position on fiber-- which was formerly that it's irrelevant at best. I felt that fiber came along with nutrient-dense whole plant foods, but was not beneficial per se. I believed that the associations between fiber intake and a lower risk of a number of diseases were probably due to the fact that wealthier, more educated, healthier people tend to buy more whole grains, fruit and vegetables. In other words, I believed that fiber intake was associated with better health, but did not contribute to it. I now feel, based on further reading about fiber and short-chain fatty acids like butyrate, that the associations represent a true cause-and-effect relationship.

I also didn't fully appreciate the caloric contribution of fiber to the human diet. In industrialized countries, fiber may contribute 5 to 10 percent of total calorie intake, due to its conversion to short-chain fatty acids like butyrate in the large intestine (free full text). This figure is probably at least twice as high in cultures consuming high-fiber diets. It's interesting to think that "high-carbohydrate" cultures may be getting easily 15 percent of their calories from short-chain fats. Since that isn't recorded in dietary surveys, they may appear more dependent on carbohydrate than they actually are. The Kitavans may be getting more than 30 percent of their total calories from fat, despite the fact that their food is only 21 percent fat when it passes their lips. Their calorie intake may be underestimated as well.

Sources of Butyrate

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

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

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


* According to insulin tolerance test.

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

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

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

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

Malocclusion: Disease of Civilization, Part IX

A Summary

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

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

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

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

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

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


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

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

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

Malocclusion: Disease of Civilization, Part VIII

Three Case Studies in Occlusion

In this post, I'll review three cultures with different degrees of malocclusion over time, and try to explain how the factors I've discussed may have played a role.

The Xavante of Simoes Lopes

In 1966, Dr. Jerry D. Niswander published a paper titled "The Oral Status of the Xavantes of Simoes Lopes", describing the dental health and occlusion of 166 Brazilian hunter-gatherers from the Xavante tribe (free full text). This tribe was living predominantly according to tradition, although they had begun trading with the post at Simoes Lopes for some foods. They made little effort to clean their teeth. They were mostly but not entirely free of dental cavities:

Approximately 33% of the Xavantes at Simoes Lopes were caries free. Neel et al. (1964) noted almost complete absence of dental caries in the Xavante village at Sao Domingos. The difference in the two villages may at least in part be accounted for by the fact that, for some five years, the Simoes Lopes Xavante have had access to sugar cane, whereas none was grown at Sao Domingos. It would appear that, although these Xavantes still enjoy relative freedom from dental caries, this advantage is disappearing after only six years of permanent contact with a post of the Indian Protective Service.

The most striking thing about these data is the occlusion of the Xavante. 95 percent had ideal occlusion. The remaining 5 percent had nothing more than a mild crowding of the incisors (front teeth). Niswander didn't observe a single case of underbite or overbite. This would have been truly exceptional in an industrial population. Niswander continues:

Characteristically, the Xavante adults exhibited broad dental arches, almost perfectly aligned teeth, end-to-end bite, and extensive dental attrition. At 18-20 years of age, the teeth were so worn as to almost totally obliterate the cusp patterns, leaving flat chewing surfaces.

The Xavante were clearly hard on their teeth, and their predominantly hunter-gatherer lifestyle demanded it. They practiced a bit of "rudimentary agriculture" of corn, beans and squash, which would sustain them for a short period of the year devoted to ceremonies. Dr. James V. Neel describes their diet (free full text):

Despite a rudimentary agriculture, the Xavante depend very heavily on the wild products which they gather. They eat numerous varieties of roots in large quantities, which provide a nourishing, if starchy, diet. These roots are available all year but are particularly important in the Xavante diet from April to June in the first half of the dry season when there are no more fruits. The maize harvest does not last long and is usually saved for a period of ceremonies. Until the second harvest of beans and pumpkins, the Xavante subsist largely on roots and palmito (Chamacrops sp.), their year-round staples.

From late August until mid-February, there are also plenty of nuts and fruits available. The earliest and most important in their diet is the carob or ceretona (Ceretona sp.), sometimes known as St. John's bread. Later come the fruits of the buriti palm (Mauritia sp.) and the piqui (Caryocar sp.). These are the basis of the food supply throughout the rainy season. Other fruits, such as mangoes, genipapo (Genipa americana), and a number of still unidentified varieties are also available.

The casual observer could easily be misled into thinking that the Xavante "live on meat." Certainly they talk a great deal about meat, which is the most highly esteemed food among them, in some respects the only commodity which they really consider "food" at all... They do not eat meat every day and may go without meat for several days at a stretch, but the gathered products of the region are always available for consumption in the community.

Recently, the Xavante have begun to eat large quantities of fish.

The Xavante are an example of humans living an ancestral lifestyle, and their occlusion shows it. They have the best occlusion of any living population I've encountered so far. Here's why I think that's the case:

• A nutrient-rich, whole foods diet, presumably including organs.
  
• On-demand breast feeding for two or more years.
• No bottle-feeding or modern pacifiers.
• Tough foods on a regular basis.
  

I don't have any information on how the Xavante have changed over time, but Niswander did present data on another nearby (and genetically similar) tribe called the Bakairi that had been using a substantial amount of modern foods for some time. The Bakairi, living right next to the Xavante but eating modern foods from the trading post, had 9 times more malocclusion and nearly 10 times more cavities than the Xavante. Here's what Niswander had to say:

Severe abrasion was not apparent among the Bakairi, and the dental arches did not appear as broad and massive as in the Xavantes. Dental caries and malocclusion were strikingly more prevalent; and, although not recorded systematically, the Bakairi also showed considerably more periodontal disease. If it can be assumed that the Bakairi once enjoyed a freedom from dental disease and malocclusion equal to that now exhibited by the Xavantes, the available data suggest that the changes in occlusal patterns as well as caries and periodontal disease have been too rapid to be accounted for by an hypothesis involving relaxed [genetic] selection.

The Masai of Kenya

The Masai are traditionally a pastoral people who live almost exclusively from their cattle. In 1945, and again in 1952, Dr. J. Schwartz examined the teeth of 408 and 273 Masai, respectively (#1 free full text; #2 ref). In the first study, he found that 8 percent of Masai showed some form of malocclusion, while in the second study, only 0.4 percent of Masai were maloccluded. Although we don't know what his precise criteria were for diagnosing malocclusion, these are still very low numbers.

In both studies, 4 percent of Masai had cavities. Between the two studies, Schwartz found 67 cavities in 21,792 teeth, or 0.3 percent of teeth affected. This is almost exactly what Dr. Weston Price found when he visited them in 1935. From Nutrition and Physical Degeneration, page 138:

In the Masai tribe, a study of 2,516 teeth in eighty-eight individuals distributed through several widely separated manyatas showed only four individuals with caries. These had a total of ten carious teeth, or only 0.4 per cent of the teeth attacked by tooth decay.

Dr. Schwartz describes their diet:

The principal food of the Masai is milk, meat and blood, the latter obtained by bleeding their cattle... The Masai have ample means with which to get maize meal and fresh vegetables but these foodstuffs are known only to those who work in town. It is impossible to induce a Masai to plant their own maize or vegetables near their huts.

This is essentially the same description Price gave during his visit. The Masai were not hunter-gatherers, but their traditional lifestyle was close enough to allow good occlusion. Here's why I think the Masai had good occlusion:

• A nutrient-dense diet rich in protein and fat-soluble vitamins from pastured dairy.
• On-demand breast feeding for two or more years.
• No bottle feeding or modern pacifiers.
  

The one factor they lack is tough food. Their diet, composed mainly of milk and blood, is predominantly liquid. Although I think food toughness is a factor, this shows that good occlusion is not entirely dependent on tough food.

Sadly, the lifestyle and occlusion of the Masai has changed in the intervening decades. A paper from 1992 described their modern diet:

The main articles of diet were white maize, [presumably heavily sweetened] tea, milk, [white] rice, and beans. Traditional items were rarely eaten... Milk... was not mentioned by 30% of mothers.

A paper from 1993 described the occlusion of 235 young Masai attending rural and peri-urban schools. Nearly all showed some degree of malocclusion, with open bite alone affecting 18 percent.

Rural Caucasians in Kentucky

It's always difficult to find examples of Caucasian populations living traditional lifestyles, because most Caucasian populations adopted the industrial lifestyle long ago. That's why I was grateful to find a study by Dr. Robert S. Corruccini, published in 1981, titled "Occlusal Variation in a Rural Kentucky Community" (ref).

This study examined a group of isolated Caucasians living in the Mammoth Cave region of Kentucky, USA. Corruccini arrived during a time of transition between traditional and modern foodways. He describes the traditional lifestyle as follows:

Much of the traditional way of life of these people (all white) has been maintained, but two major changes have been the movement of industry and mechanized farming into the area in the last 25 years. Traditionally, tobacco (the only cash crop), gardens, and orchards were grown by each family. Apples, pears, cherries, plums, peaches, potatoes, corn, green beans, peas, squash, peppers, cucumbers, and onions were grown for consumption, and fruits and nuts, grapes, and teas were gathered by individuals. In the diet of these people, dried pork and fried [presumably in lard], thick-crust cornbread (which were important winter staples) provided consistently stressful chewing. Hunting is still very common in the area.

Although it isn't mentioned in the paper, this group, like nearly all traditionally-living populations, probably did not waste the organs or bones of the animals it ate. Altogether, it appears to be an excellent and varied diet, based on whole foods, and containing all the elements necessary for good occlusion and overall health.

The older generation of this population has the best occlusion of any Caucasian population I've ever seen, rivaling some hunter-gatherer groups. This shows that Caucasians are not genetically doomed to malocclusion. The younger generation, living on more modern foods, shows very poor occlusion, among the worst I've seen. They also show narrowed arches, a characteristic feature of deteriorating occlusion. One generation is all it takes. Corruccini found that a higher malocclusion score was associated with softer, more industrial foods.

Here are the reasons I believe this group of Caucasians in Kentucky had good occlusion:

• A nutrient-rich, whole foods diet, presumably including organs.
  
• Prolonged breast feeding.
• No bottle-feeding or modern pacifiers.
• Tough foods on a regular basis.
  

Common Ground

I hope you can see that populations with excellent teeth do certain things in common, and that straying from those principles puts the next generation at a high risk of malocclusion. Malocclusion is a serious problem that has major implications for health, well-being and finances. In the next post, I'll give a simplified summary of everything I've covered in this series. Then it's back to our regularly scheduled programming.

Malocclusion: Disease of Civilization, Part VII

Jaw Development During Adolescence

Beginning at about age 11, the skull undergoes a growth spurt. This corresponds roughly with the growth spurt in the rest of the body, with the precise timing depending on gender and other factors. Growth continues until about age 17, when the last skull sutures cease growing and slowly fuse. One of these sutures runs along the center of the maxillary arch (the arch in the upper jaw), and contributes to the widening of the upper arch*:

This growth process involves MGP and osteocalcin, both vitamin K-dependent proteins. At the end of adolescence, the jaws have reached their final size and shape, and should be large enough to accommodate all teeth without crowding. This includes the third molars, or wisdom teeth, which will erupt shortly after this period.

Reduced Food Toughness Correlates with Malocclusion in Humans

When Dr. Robert Corruccini published his seminal paper in 1984 documenting rapid changes in occlusion in cultures around the world adopting modern foodways and lifestyles (see this post), he presented the theory that occlusion is influenced by chewing stress. In other words, the jaws require good exercise on a regular basis during growth to develop normal-sized bones and muscles. Although Dr. Corruccini wasn't the first to come up with the idea, he has probably done more than anyone else to advance it over the years.

Dr. Corruccini's paper is based on years of research in transitioning cultures, much of which he conducted personally. In 1981, he published a study of a rural Kentucky community in the process of adopting the modern diet and lifestyle. Their traditional diet was predominantly dried pork, cornbread fried in lard, game meat and home-grown fruit, vegetables and nuts. The older generation, raised on traditional foods, had much better occlusion than the younger generation, which had transitioned to softer and less nutritious modern foods. Dr. Corruccini found that food toughness correlated with proper occlusion in this population.

In another study published in 1985, Dr. Corruccini studied rural and urban Bengali youths. After collecting a variety of diet and socioeconomic information, he found that food toughness was the single best predictor of occlusion. Individuals who ate the toughest food had the best teeth. The second strongest association was a history of thumb sucking, which was associated with a higher prevalence of malocclusion**. Interestingly, twice as many urban youths had a history of thumb sucking as rural youths.

Not only do hunter-gatherers eat tough foods on a regular basis, they also often use their jaws as tools. For example, the anthropologist and arctic explorer Vilhjalmur Stefansson described how the Inuit chewed their leather boots and jackets nearly every day to soften them or prepare them for sewing. This is reflected in the extreme tooth wear of traditional Inuit and other hunter-gatherers.

Soft Food Causes Malocclusion in Animals

Now we have a bunch of associations that may or may not represent a cause-effect relationship. However, Dr. Corruccini and others have shown in a variety of animal models that soft food can produce malocclusion, independent of nutrition.

The first study was conducted in 1951. Investigators fed rats typical dry chow pellets, or the same pellets that had been crushed and softened in water. Rats fed the softened food during growth developed narrow arches and small mandibles (lower jaws) relative to rats fed dry pellets.

Other research groups have since repeated the findings in rodents, pigs and several species of primates (squirrel monkeys, baboons, and macaques). Animals typically developed narrow arches, a central aspect of malocclusion in modern humans. Some of the primates fed soft foods showed other malocclusions highly reminiscent of modern humans as well, such as crowded incisors and impacted third molars. These traits are exceptionally rare in wild primates.

One criticism of these studies is that they used extremely soft foods that are softer than the typical modern diet. This is how science works: you go for the extreme effects first. Then, if you see something, you refine your experiments. One of the most refined experiments I've seen so far was published by Dr. Daniel E. Leiberman of Harvard's anthropology department. They used the rock hyrax, an animal with a skull that bears some similarities to the human skull***.

Instead of feeding the animals hard food vs. mush, they fed them raw and dried food vs. cooked. This is closer to the situation in humans, where food is soft but still has some consistency. Hyrax fed cooked food showed a mild jaw underdevelopment reminiscent of modern humans. The underdeveloped areas were precisely those that received less strain during chewing.

Implications and Practical Considerations

Besides the direct implications for the developing jaws and face, I think this also suggests that physical stress may influence the development of other parts of the skeleton. Hunter-gatherers generally have thicker bones, larger joints, and more consistently well-developed shoulders and hips than modern humans. Physical stress is part of the human evolutionary template, and is probably critical for the normal development of the skeleton.

I think it's likely that food consistency influences occlusion in humans. In my opinion, it's a good idea to regularly include tough foods in a child's diet as soon as she is able to chew them properly and safely. This probably means waiting at least until the deciduous (baby) molars have erupted fully. Jerky, raw vegetables and fruit, tough cuts of meat, nuts, dry sausages, dried fruit, chicken bones and roasted corn are a few things that should stress the muscles and bones of the jaws and face enough to encourage normal 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).

** I don't know if this was statistically significant at p less than 0.05. Dr. Corruccini uses a cutoff point of p less than 0.01 throughout the paper. He's a tough guy when it comes to statistics!

*** Retrognathic.