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.

It's Time to Let Go of The Glycemic Index

The glycemic index (GI) is a measure of how much an individual food elevates blood sugar when it's eaten. To measure it, investigators feed a person a food that contains a fixed amount of carbohydrate, and measure their blood glucose response over time. Then they determine the area under the glucose curve and compare it to a standard quickly digesting food such as white bread or pure glucose.

Each food must contain the same total amount of carbohydrate, so you might have to eat a big plate of carrots to compare with a slice of bread. You end up with a number that reflects the food's ability to elevate glucose when eaten in isolation. It typically depends on how quickly the carbohydrate is absorbed, with higher numbers usually resulting from faster absorption.

The GI is a standby of modern nutritional advice. It's easy to believe in because processed foods tend to have a higher glycemic index than minimally processed foods, high blood sugar is bad, and chronically high insulin is bad. But many people have criticized the concept, and rightly so.

Blood sugar responses to a carbohydrate-containing foods vary greatly from person to person. For example, I can eat a medium potato and a big slice of white bread (roughly 60 g carbohydrate) with nothing else and only see a modest spike in my blood sugar. I barely break 100 mg/dL and I'm back at fasting glucose levels within an hour and a half. You can see a graph of this experiment here. That's what happens when you have a well-functioning pancreas and insulin-sensitive tissues. Your body shunts glucose into the tissues almost as rapidly as it enters the bloodstream. Someone with impaired glucose tolerance might have gone up to 170 mg/dL for two and a half hours on the same meal.

The other factor is that foods aren't eaten in isolation. Fat, protein, acidity and other factors slow carbohydrate absorption in the context of a normal meal, to the point where the GI of the individual foods become much less pronounced.

It's time to put my money where my mouth is. Researchers have conducted a number of controlled trials comparing low-GI diets to high-GI diets. I've done an informal literature review to see what the overall findings are. I'm only interested in long-term studies-- 10 weeks or longer-- and I've excluded studies using subjects with metabolic disorders such as diabetes.

The question I'm asking with this review is, what are the health effects of a low-glycemic index diet on a healthy normal-weight or overweight person? I found a total of seven studies on PubMed in which investigators varied GI while keeping total carbohydrate about the same, for 10 weeks or longer. I'll present them out of chronological order because they flow better that way.

Study #1. Investigators put overweight women on a 12-week diet of either high-GI or low-GI foods with an equal amount of total carbohydrate. Both were unrestricted in calories. Body composition and total food intake were the same on both diets. The reason became apparent when they measured the subjects' glucose and insulin response to the high- and low-GI meals, and found that they were the same!

Study #2. Investigators divided 129 overweight young adults into four different diet groups for 12 weeks. Diet #1: high GI, high carbohydrate (60%). Diet #2: low GI, high carbohydrate. Diet #3: high GI, high-protein (28%). Diet #4: low GI, high protein. The high-protein diets were also a bit higher in fat. Although the differences were small and mostly not statistically significant, participants on diet #3 improved the most overall in my opinion. They lost the most weight, and had the greatest decrease in fasting insulin and calculated insulin resistance. Diet #2 came out modestly ahead of diet #1 on fat loss and fasting insulin.

Study #3. At 18 months, this is by far the longest trial. Investigators assigned 203 healthy Brazilian women to either a low-GI or high-GI energy-restricted diet. The difference in GI between the two diets was very large; the high-GI diet was double the low-GI diet. Weight loss was a meager 1/3 pound greater in the low-GI group, a difference that was not statistically significant at 18 months. Insulin resistance and fasting insulin decreased in the high-GI group but increased in the low-GI group, also not statistically significant.

Study #4. The FUNGENUT study. In this 12-week intervention, investigators divided 47 subjects with the metabolic syndrome into two diet groups. One was a high-glycemic, high-wheat group; the other was a low-glycemic, high-rye group. After 12 weeks, there was an improvement in the insulinogenic index (a marker of early insulin secretion in response to carbohydrate) in the rye group but not the wheat group. Glucose tolerance was essentially the same in both groups.

What makes this study unique is they went on to look at changes in gene expression in subcutaneous fat tissue before and after the diets. They found a decrease in the expression of stress and inflammation-related genes in the rye group, and an increase in stress and inflammation genes in the wheat group. They interpreted this as being the result of the different GIs of the two diets.

I have a different interpretation. I believe wheat is a uniquely unhealthy food, that promotes inflammation and general metabolic havoc over a long period of time. This probably relates at least in part to its gluten content, which is double that of rye. Dr. William Davis has had great success with his cardiac patients by counseling them to eliminate wheat. He agrees based on his clinical experience that wheat has uniquely damaging effects on the metabolism that other sources of starch do not have.

Study #5. This one is really bizarre. Investigators divided 18 subjects with elevated cardiovascular disease risk markers into two diets differing in their GI. In the abstract, they claim that only the low-GI group lost weight. If you look at their data table, it shows that actually the high-GI group lost much more weight than the low-GI group. The high-GI group lost body fat while the low-GI group gained fat. The other variables they measured stayed essentially the same. I don't understand how they got the numbers in their abstract from the numbers in their table. If anyone can figure this out I would be grateful.

Study #6. 45 overweight females were divided between high-GI and low-GI diets for 10 weeks. The low-GI group lost a small amount more fat than the high-GI group, but the difference wasn't significant. The low-GI group also had a 10% drop in LDL cholesterol.

Study #7. This was the second-longest trial, at 4 months. 34 subjects with impaired glucose tolerance were divided into three diet groups. Diet #1: high-carbohydrate (60%), high-GI. Diet #2: high-carbohydrate, low-GI. Diet #3: "low-carbohydrate" (49%), "high-fat" (monounsaturated from olive and canola oil). The diet #1 group lost the most weight, followed by diet #2, while diet #3 gained weight. The differences were small but statistically significant. The insulin and triglyceride response to a test meal improved in diet group #1 but not #2. The insulin response also improved in group #3. The high-GI group came out looking pretty good.

Overall, these studies do not support the idea that lowering the glycemic index of carbohydrate foods is useful for weight loss, insulin or glucose control, or anything else besides complicating your life. If anything, the longest two studies support the alternate hypothesis: that high-GI carbohydrates are superior to low-GI carbohydrates. Why might this be? I'll speculate in my next post.

Further reading:

The Fructose Index is the New Glycemic Index

How to Eat Grains

Our story begins in East Africa in 1935, with two Bantu tribes called the Kikuyu and the Wakamba. Their traditional diets were mostly vegetarian and consisted of sweet potatoes, corn, beans, plantains, millet, sorghum, wild mushrooms and small amounts of dairy, small animals and insects. Their food was agricultural, high in carbohydrate and low in fat.

Dr. Weston Price found them in good health, with well-formed faces and dental arches, and a dental cavity rate of roughly 6% of teeth. Although not as robust or as resistant to tooth decay as their more carnivorous neighbors, the "diseases of civilization" such as cardiovascular disease and obesity were nevertheless rare among them. South African Bantu eating a similar diet have a low prevalence of atherosclerosis, and a measurable but low incidence of death from coronary heart disease, even in old age.

How do we reconcile this with the archaeological data showing a general decline in human health upon the adoption of agriculture? Humans did not evolve to tolerate the toxins, anti-nutrients and large amounts of fiber in grains and legumes. Our digestive system is designed to handle a high-quality omnivorous diet. By high-quality, I mean one that has a high ratio of calories to indigestible material (fiber). Our species is very good at skimming off the highest quality food in nearly any ecological niche. Animals that are accustomed to high-fiber diets, such as cows and gorillas, have much larger, more robust and more fermentative digestive systems.

One factor that reconciles the Bantu data with the archaeological data is that much of the Kikuyu and Wakamba diet came from non-grain sources. Sweet potatoes and plantains are similar to the starchy wild plants our ancestors have been eating for nearly two million years, since the invention of fire (the time frame is debated but I think everyone agrees it's been a long time). Root vegetables and starchy fruit have a higher nutrient bioavailibility than grains and legumes due to their lower content of anti-nutrients and fiber.

The second factor that's often overlooked is food preparation techniques. These tribes did not eat their grains and legumes haphazardly! This is a factor that was overlooked by Dr. Price himself, but has been emphasized by Sally Fallon. Healthy grain-based African cultures typically soaked, ground and fermented their grains before cooking, creating a sour porridge that's nutritionally superior to unfermented grains. The bran was removed from corn and millet during processing, if possible. Legumes were always soaked prior to cooking.

These traditional food processing techniques have a very important effect on grains and legumes that brings them closer in line with the "paleolithic" foods our bodies are designed to digest. They reduce or eliminate toxins such as lectins and tannins, greatly reduce anti-nutrients such as phytic acid and protease inhibitors, and improve vitamin content and amino acid profile. Fermentation is particularly effective in this regard. One has to wonder how long it took the first agriculturalists to discover fermentation, and whether poor food preparation techniques or the exclusion of animal foods could account for their poor health.

I recently discovered a paper that illustrates these principles: "Influence of Germination and Fermentation on Bioaccessibility of Zinc and Iron from Food Grains". It's published by Indian researchers who wanted to study the nutritional qualities of traditional fermented foods. One of the foods they studied was idli, a South Indian steamed "muffin" made from rice and beans. Idlis happen to be one of my favorite foods.

The amount of minerals your digestive system can extract from a food depends in part on the food's phytic acid content. Phytic acid is a molecule that traps certain minerals (iron, zinc, magnesium, calcium), preventing their absorption. Raw grains and legumes contain a lot of it, meaning you can only absorb a fraction of the minerals present in them.

In this study, soaking had a modest effect on the phytic acid content of the grains and legumes examined (although it's generally more effective). Fermentation, on the other hand, completely broke down the phytic acid in the idli batter, resulting in 71% more bioavailable zinc and 277% more bioavailable iron. It's safe to assume that fermentation also increased the bioavailability of magnesium, calcium and other phytic acid-bound minerals.

Fermenting the idli batter also completely eliminated its tannin content. Tannins are a class of molecules found in many plants that are toxins and anti-nutrients. They reduce feed efficiency and growth rate in a variety of species.

Lectins are another toxin that's frequently mentioned in the paleolithic diet community. They are blamed for everything from digestive problems to autoimmune disease, probably with good reason. One of the things people like to overlook in this community is that traditional processing techniques such as soaking, sprouting, fermentation and cooking, greatly reduce or eliminate lectins from grains and legumes. One notable exception is gluten, which survives all but the longest fermentation and is not broken down by cooking.

Soaking, sprouting, fermenting, grinding and cooking are the techniques by which traditional cultures have been making the most of grain and legume-based diets for thousands of years. We ignore these time-honored traditions at our own peril.

Sugar, Hydrogen, Bacteria and Maldigestion

There are several ways to cause a nutrient deficiency. The first is to eat too little of a nutrient. Another way is to burn through your body's nutrient stores at an accelerated rate, for example, what omega-6 vegetable oils do to vitamin E, and what wheat bran does to vitamin D. A third way is to eat enough nutrients but fail to absorb them efficiently.

A good way to reduce your absorption of nutrients is to lower your stomach's acidity. This will protect you from those pesky nutrients protein, vitamin B12, and iron (and probably others as well). The stomach is one tough organ. When it receives food, a healthy stomach lowers its pH to roughly 2.0 by secreting hydrochloric acid. That's more acidic than lemon juice and more than 10 times more acidic than vinegar. This begins to break food down, and will kill most bacteria and other pathogens. Stomach acidity is basically the body's way of "cooking" food before further digestion. At the same time, the stomach secretes pepsin, which is an acid-stable enzyme that digests protein.

Insufficient stomach acidity promotes bacterial overgrowth in the small intestine and allows undigested proteins into the intestine. The gastrin knockout mouse, which is incapable of producing stomach acid, suffers from bacterial overgrowth, inflammation, damage and precancerous polyps in its intestines. The same thing happens when you treat mice with a drug that inhibits stomach acidification.

There are a few different ways to reduce your stomach's acidity level. The most straightforward is to take an antacid, or any number of drugs that lower stomach acidity (as in the mouse study above). But can we do it naturally? Sure, all it takes is a little Helicobacter pylori infection! Luckily, most people already have one.

H. pylori is a bacterium that's the main proximal cause of stomach ulcers. Antibiotics are now the standard treatment for ulcers, and they're effective. Treating an asymptomatic H. pylori infection with antibiotics increases stomach acidity, suggesting that H. pylori is capable of suppressing the secretion of stomach acid. In another study, eradicating H. pylori with antibiotics improved nearly all patients suffering from hypochlorhydria (insufficient stomach acid).

Like any organism, H. pylori likes to stay well-fed. Its favorite food is hydrogen gas (H2), and the more it gets, the more it grows. It's not the only bacterium to like H2. Salmonella, of food poisoning fame, requires H2 to become pathogenic. Clostridium bacteria are also associated with elevated H2. H2 is produced by the fermentation of food by bacteria in the digestive tract. It's very small so it diffuses around the body, reaching the stomach lining where it's eagerly gobbled up by H. pylori. It may be equally good food for a number of other parasites around the body.

Now let's stop beating around the bush and get to the meat of this post. It's all summed up in a beautiful title: Fructose Intake at Current Levels in the United States May Cause Gastrointestinal Distress in Normal Adults. Dr. Richard W. McCallum et al. fed doses of isolated fructose to 15 normal adults. Can I say it any better than the abstract?

More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose... Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people.

Here's where it gets really interesting. One of the measures of malabsorption they used was H2 on the breath. Both the 25g and the 50g doses caused a large increase in H2, especially the 50g dose (5-fold increase). This is the same thing you see in people who are lactose intolerant. Bacterial fermentation is the only significant source of H2 in the human body. That means the fructose was hanging around in the small intestine for long enough to be decomposed by the local bacteria, who took advantage of it to proliferate.

Certain types of fiber also promote H2 production. Resistant starch, as well as certain non-caloric sweeteners, are readily fermented into H2 in some people. Cellulose, the predominant fiber in vegetables and grains, does not increase H2. The large difference in fiber content of rural vs. urban Mexican diets doesn't seem to correlate with H2 production by intestinal bacteria. Interestingly, both white and whole wheat bread increase H2 production.

Let's put those doses of fructose into perspective. One medium banana contains about 7 grams. A 16-ounce bottle of apple juice contains about 30 grams. A slice of cake contains about 12. One "child-size" 12 ounce cup of Coca-Cola from McDonald's contains 17 grams (as long as you don't get a refill!). One large 32 ounce Coca-Cola contains 47 grams. Your H. pylori will be VERY pleased if you drink one of those, especially if you use it to wash down the white flour bun on your hamburger.

I do think it's important to mention that the study described above used isolated fructose. It's not clear that other sources of fructose would behave the same. For example, the presence of glucose enhances fructose absorption. Fruit, table sugar and high-fructose corn syrup all contain glucose. It's also not clear what the effect would be of eating fructose with a meal rather than in isolation. None of this has been studied to my knowledge, so we're left extrapolating from studies that used pure fructose.

Now let's connect the dots. Excessive fructose, certain types of fiber, and wheat cause bacterial overgrowth and H2 production (if you believe the fructose-H2 connection). Elevated H2 causes overgrowth of H. pylori and possibly other pathogenic bacteria in the body. H. pylori lowers stomach acid, causing further overgrowth of bacteria in the small intestine. This causes inflammation and increases the risk for digestive cancers.

Decreased stomach acid also causes malabsorption of protein, B12, iron and perhaps other nutrients. It allows undigested protein to travel into the small intestine. This could potentially be very important. For example, many people are allergic to the casein in milk. It's one of the two most common alleriges, along with gluten. Both casein and gluten are proteins. A normally functioning stomach at the proper pH should completely digest casein. You can't be allergic to casein if there's none around. I don't know if the same applies to gluten.

Robust digestion may explain why many healthy non-industrial groups do very well eating dairy, sometimes to the exclusion of nearly everything else, yet many people in modern societies do better without dairy protein (butter is typically well tolerated). This phenomenon could also go a long way toward explaining the fact that allergies are becoming more and more common in industrial nations as we consume more sugar.

Thanks to Peter and Matt Stone for some of the ideas I incorporated into this post. Thanks to pbo31 for the CC photo.

Gluten Sensitivity: Celiac Disease is the Tip of the Iceberg

Celiac disease is a degeneration of the lining of the small intestine caused by a sensitivity to gluten. Gluten is the protein portion of wheat, rye, barley, and wheat relatives (spelt, kamut, emmer, einkorn and triticale). I found an interesting paper recently on the impact of celiac disease on nutrient status and bone density. Researchers compared 54 Northern Italian children with untreated celiac disease to 60 presumably healthy children. The celiac patients had extremely poor vitamin D status, with a deficiency rate of 35.18% compared to 5% in the control group. This was using the lenient cut-off point of 20 ng/mL. Average serum 25(OH)D3 in celiac patients was less than half the level of the control group. The celiac patients also had low serum calcium and magnesium, and elevated parathyroid hormone. Celiac children had lower bone mineral density. All parameters returned to normal after 6 months on a gluten-free diet.

This confirms what has been shown numerous times before: celiac disease interferes with nutrient status, including the all-important fat-soluble vitamins. It's not surprising, since it flattens the villi, finger-like structures necessary for efficient nutrient absorption in the small intestine. But wait, the overwhelming majority of our vitamin D comes from the effect of sunlight on our skin, not through our small intestine! So gluten sensitivity must be doing something besides just flattening villi. Perhaps it does. Feeding wheat bran to "healthy" volunteers caused them to burn through their vitamin D reserves at an accelerated rate. I think this underlines what I've come to believe about wheat: it's problematic for a large proportion of the population, perhaps the majority.

Approximately 12% of Americans can be diagnosed as gluten sensitive using blood antibody tests (anti-gliadin IgA or IgG). A subset of these have full-blown celiac disease. The vast, vast majority are undiagnosed. Gluten sensitivity associates with a dizzying array of diseases, including autoimmune disorders, cancer, and neurological problems. The problem with the blood tests is they aren't very sensitive. The most common blood tests for celiac disease look for a class of antibody called IgA. IgA is produced by the mucosa, including the gut. Unless gut damage is already extensive, the majority of IgA stays in the gut. This may cause the assay to overlook many cases of gluten sensitivity. A negative blood antibody test does not rule out gluten sensitivity!

I recently discovered the work of Dr. Kenneth Fine of EnteroLab. He has developed an assay that detects anti-gliadin IgA in stool. Gliadin is one of the problematic proteins in gluten that is implicated in gluten sensitivity. Dr. Fine has been conducting informal research using his fecal anti-gliadin IgA test (data here). He has found that:

• 100% of untreated celiac patients are antigliadin IgA positive by fecal test, compared to only 76% by blood (n= 17).
• 76% of microscopic colitis (a type of chronic diarrhea) patients are positive by the fecal test, compared to 9% by blood (n= 57).
• 57% of symptomatic people (digestive problems?) are positive by the fecal test, compared to 12% by blood (n= 58).
• 62% of people with autoimmune disease are positive by the fecal test.
• 29% of asymptomatic (healthy) people are positive by the fecal test, compared to 11-12% by blood (n= 240).
• Baby and cow feces are 0% positive by the stool assay.

It gets worse. Gluten sensitivity is determined in large part by genetics. A gene called HLA-DQ is intimately involved. It encodes a protein that is expressed on the surface of cells, that serves to activate immune cells when certain foreign substances are present. Different versions of the gene are activated by different substances. HLA-DQ2 and HLA-DQ8 are classically associated with celiac disease. Roughly 42% of the US population carries DQ2 or DQ8. According to Dr. Fine, every allele except DQ4 has some association with gluten-related problems! Only 0.4% of the U.S. population carries HLA-DQ4 and no other allele.

Not everyone who is genetically susceptible will end up developing health problems due to gluten, but it's impossible to estimate how many of the problems we attribute to other causes are in fact caused or exacerbated by gluten.

The immune system can be divided into two parts: innate and adaptive. The innate immune system is a nonspecific, first-line reaction to a perceived threat. The adaptive immune system is a more sophisticated, but slower system that produces a powerful response by particular cell types to a very specific threat. Antibody production is part of the adaptive immune system. Thus, if your gluten sensitivity test is looking for antibodies, it could still be missing an immune reaction to gluten mediated by the innate immune system!

This question has been addressed in a preliminary study. Researchers took gut biopsies from celiac patients and asymptomatic controls. Five out of six asymptomatic controls showed elevated interleukin-15, a marker of innate immune activation, upon exposure to gliadin. An activated innate immune system (commonly called 'inflammation') is associated with a wide array of chronic diseases, from obesity to cancer to cardiovascular disease. Inflammatory cytokines are elevated in celiac patients and may play a role in their bone pathology. What I would like to see is some negative controls-- would the gut biopsies have produced interleukin-15 in response to benign foods or is it truly specific to gluten?

I don't intend to imply that everyone has gluten sensitivity, but I do think the totality of the data are thought-provoking. They also include the association between the introduction of wheat to non-industrial populations and the development of widespread health problems. Another thing to keep in mind is that traditional sourdough fermentation breaks down a portion of gluten, possibly explaining the rise in gluten sensitivity that has paralleled a shift to quick-rise yeast breads. I believe that gluten sensitivity is behind many modern ills, and should be on the short list of suspects in the case of unexplained health problems. This is particularly true of digestive, autoimmune and neurological disorders. Gluten sensitivity is easy to address: stop eating gluten for a few weeks. See how you feel. Reintroduce gluten and see what happens. You might learn something about yourself.

Book Review: Dangerous Grains

Dangerous Grains is about the health hazards of gluten grains. It's co-written by James Braly, an M.D. who specializes in food allergies, and Ron Hoggan, a celiac patient who has written widely on the subject.

Celiac disease is a degeneration of the intestinal lining caused by exposure to gluten. Gluten sensitivity is a broader term that encompasses any of the numerous symptoms that can occur throughout the body when susceptible people eat gluten. The term gluten sensitivity includes celiac disease. Gluten is a protein found in wheat, its close relatives (kamut, spelt, triticale), barley and rye. Wheat is the most concentrated source.

Dangerous Grains is a good overview of the mountain of data on celiac disease and gluten sensitivity that few people outside the field are familiar with. For example, did you know:

• An estimated one percent of the U.S. population suffers from celiac disease.
• Approximately 12 percent of the US population suffers from gluten sensitivity.
• Gluten can damage nearly any part of the body, including the brain, the digestive tract, the skin and the pancreas. Sometimes gastrointestinal symptoms are absent.
  
• Both celiac and other forms of gluten sensitivity increase the risk of a large number of diseases, such as type 1 diabetes and cancer, often dramatically.
• The majority of people with gluten sensitivity are not diagnosed.
• Most doctors don't realize how common gluten sensitivity is, so they rarely test for it.
  
• Celiac disease and other symptoms of gluten sensitivity are easily reversed by avoiding gluten.

Twelve percent of Americans have gluten sensitivity! That's an enormous disease burden coming from a single type of food. I suspect the true incidence may actually be higher. There are preliminary data suggesting that most people may mount an immune response to gluten that does not require antibodies (through the innate immune system). This type of gluten sensitivity would be overlooked by the typical antibody tests, but could still result in damage.

Dangerous Grains also discusses the opioid-like peptides released from gluten during digestion. Opioids are powerful drugs, such as heroin and morphine, that were originally derived from the poppy seed pod. They are strong suppressors of the immune system and quite addictive. There are no data that conclusively prove the opioid-like peptides in gluten cause immune suppression or addiction to wheat, but there are some interesting coincidences and anecdotes. Celiac patients are at an increased risk of cancer, particularly digestive tract cancer, which suggests that the immune system is compromised. Heroin addicts are also at increased risk of cancer. Furthermore, celiac patients often suffer from abnormal food cravings. From my reading, I believe that wheat causes excessive eating, perhaps through a drug-like mechanism, and many people report withdrawal-like symptoms and cravings after eliminating wheat.

I know several people who have benefited greatly from removing gluten from their diets. Anyone who has digestive problems, from gas to acid reflux, or any other mysterious health problem, owes it to themselves to try a gluten-free diet for a month. Gluten consumption has increased quite a bit in the U.S. in the last 30 years, mostly due to an increase in the consumption of processed wheat snacks. I believe it's partly to blame for our declining health. Wheat has more gluten than any other grain. Avoiding wheat and all its derivatives is a keystone of my health philosophy.

Another notable change that Sally Fallon and others have pointed out is that today's bread isn't made the same way our grandparents made it. Quick-rise yeast allows bread to be fermented for as little as 3 hours, whereas it was formerly fermented for 8 hours or more. This allowed the gluten to be partially broken down by the microorganisms in the dough. Some gluten-sensitive people report that they can eat well-fermented sourdough wheat bread without symptoms. I think these ideas are plausible, but they remain anecdotes to me at this point. Until research shows that gluten-sensitive people can do well eating sourdough wheat bread in the long term, I'll be avoiding it. I have no reason to believe I'm gluten sensitive myself, but through my reading I've been convinced that wheat, at least how we eat it today, is probably not healthy for anyone.

I'm not aware of any truly healthy traditional culture that eats wheat as a staple. As a matter of fact, white wheat flour has left a trail of destruction around the globe wherever it has gone. Polished rice does not have such a destructive effect, so it's not simply the fact that it's a refined carbohydrate. Hundreds, if not thousands of cultures throughout the world have lost their robust good health upon abandoning their traditional foods in favor of white flour and sugar. The medical and anthropological literature are peppered with these stories. I'm aware of one healthy culture that traditionally ate sourdough-fermented whole grain rye bread, the Swiss villagers of the Loetschental valley described in Nutrition and Physical Degeneration.

Overall, the book is well written and accessible to a broad audience. I recommend it to anyone who has health problems or who is healthy and wants to stay that way!

Rats on Junk Food

If diet composition causes hyperphagia, we should be able to see it in animals. I just came across a great study from the lab of Dr. Neil Stickland that explored this in rats. They took two groups of pregnant rats and fed them two different diets ad libitum, meaning the rats could eat as much as they wanted. Here's what the diets looked like:

The animals were fed two types of diet throughout the study. They were fed either RM3 rodent chow alone ad libitum (SDS Ltd, Betchworth, Surrey, UK) or with a junk food diet, also known as cafeteria diet, which consisted of eight different types of palatable foods, purchased from a British supermarket. The palatable food included biscuits, marshmallows, cheese, jam doughnuts, chocolate chip muffins, butter flapjacks, potato crisps and caramel/chocolate bars.

It's important to note that the junk food-fed rats had access to rat chow as well. Now here's where it gets interesting. Rats with access to junk food in addition to rat chow ate 56% more calories than the chow-only group! Here's what they had to say about it:

These results clearly show that pregnant rats, given ad libitum access to junk food, exhibited hyperphagia characterised by a marked preference for foods rich in fat, sucrose and salt at the expense of protein-rich foods, when compared with rats that only had access to rodent chow. Although the body mass of dams was comparable among all groups at the start of the experiment, the increased energy intake in the junk food group throughout gestation was accompanied by an increase in body mass at G20 [gestational day 20] with the junk food-fed dams being 13 % heavier than those fed chow alone.

Hmm, this is remarkably reminiscent of what's happening to a certain group of humans in North America right now: give them access to food made mostly of refined grains, sugar, and industrially processed vegetable oil. They will prefer it to healthier food, to the point of overeating. The junk food then drives hyperphagia by interfering with the body's feedback loops that normally keep feeding behaviors and body fat within the optimal range. These data support the hypothesis that metabolic damage is the cause of, not the result of, "super-sized" food portions and other similar cultural phenomena.

The rest of the paper is interesting as well. Pups born to mothers who ate junk food while pregnant and lactating had a greater tendency to eat junk than pups born to mothers who ate rat chow during the same period. This underscores the idea that poor nutrition can set a child up for a lifetime of problems.

Hyperphagia

One of the things I didn't mention in the last post is that Americans are eating more calories than ever before. According to Centers for Disease Control NHANES data, in 2000, men ate about 160 more calories per day, and women ate about 340 more than in 1971. That's a change of 7% and 22%, respectively. The extra calories come almost exclusively from refined grains, with the largest single contribution coming from white wheat flour (correction: the largest single contribution comes from corn sweeteners, followed by white wheat flour).

Some people will see those data and decide the increase in calories is the explanation for the expanding American waistline. I don't think that's incorrect, but I do think it misses the point. The relevant question is "why are we eating more calories now than we were in 1971?"

We weren't exactly starving in 1971. And average energy expenditure, if anything, has actually increased. So why are we eating more? I believe that our increased food intake, or hyperphagia, is the result of metabolic disturbances, rather than the cause of them.

Humans, like all animals, have a sophisticated system of hormones and brain regions whose function is to maintain a proper energy balance. Part of the system's job is to keep fat mass at an appropriate level. With a properly functioning system, feedback loops inhibit hunger once fat mass has reached a certain level, and also increase resting metabolic rate to burn excess calories. If the system is working properly, it's very difficult to gain weight. There have been a number of overfeeding studies in which subjects have consumed huge amounts of excess calories. Some people gain weight, many don't.

The fact that fat mass is hormonally regulated can be easily seen in other mammals. When was the last time you saw a fat squirrel in the springtime? When was the last time you saw a thin squirrel in the fall? These events are regulated by hormones. A squirrel in captivity will put on weight in the fall, even if its daily food intake is not changed.

A key hormone in this process is leptin. Leptin levels are proportional to fat mass, and serve to inhibit hunger and eating behaviors. Under normal conditions, the more fat tissue a person has, the more leptin they will produce, and the less they will eat until the fat mass has reached the body's preferred 'set-point'. The problem is that overweight Westerners are almost invariably leptin-resistant, meaning their body doesn't respond to the signal to stop eating!

Leptin resistance leads to hyperphagia, overweight and the metabolic syndrome (a common cluster of symptoms that implies profound metabolic disturbance). It typically precedes insulin resistance during the downward slide towards metabolic syndrome.

I suspect that wheat, sugar and perhaps other processed foods cause hyperphagia. It's the same thing you see when wheat is first introduced to a culture, even if it's replacing another refined carbohydrate. I believe hyperphagia is secondary to a disturbed metabolism. There's something about the combination of refined wheat, sugar, processed vegetable oils and other industrial foods that reached a critical mass in the mid-70s. The shift in diet composition disturbed our normal hormonal profile (even more than it was already disturbed), and sent us into a tailspin of excessive eating and unprecedented weight gain.

Grains and Human Evolution

You've heard me say that I believe grains aren't an ideal food for humans. Part of the reason rests on the assertion that we have not been eating grains for long enough to have adapted to them. In this post, I'll go over what I know about the human diet before and after agriculture, and the timeline of our shift to a grain-based diet. I'm not an archaeologist so I won't claim that all these numbers are exact, but I think they are close enough to make my point.

As hunter-gatherers, we ate some combination of the following: land mammals (including organs, fat and marrow), cooked tubers, seafood (fish, mammals, shellfish, seaweed), eggs, nuts, fruit, honey, "vegetables" (stems, leaves, etc.), mushrooms, assorted land animals, birds and insects. The proportion of each food varied widely between groups and even seasons. This is pretty much what we've been living on since we evolved as a species, and even before, for a total of 1.5 million years or so (this number is controversial but is supported by multiple lines of evidence). There are minor exceptions, including the use of wild grains in a few areas, but for the most part, that's it.

The first evidence of a calorically important domesticated crop I'm aware of was about 11,500 years ago in the fertile crescent. They were cultivating an early ancestor of wheat called emmer. Other grains popped up independently in what is now China (rice; ~10,000 years ago), and central America (corn; ~9,000 years ago). That's why people say humans have been eating grains for about 10,000 years.

The story is more complicated than the dates suggest, however. Although wheat had its origin 11,500 years ago, it didn't become widespread in Western Europe for another 4,500 years. So if you're of European descent, your ancestors have been eating grains for roughly 7,000 years. Corn was domesticated 9,000 years ago, but according to the carbon ratios of human teeth, it didn't become a major source of calories until about 1,200 years ago! Many American groups did not adopt a grain-based diet until 100-300 years ago, and in a few cases they still have not. If you are of African descent, your ancestors have been eating grains for 9,000 to 0 years, depending on your heritage. The change to grains was accompanied by a marked decrease in dental health that shows up clearly in the archaeological record.

Practically every plant food contains some kind of toxin, but grains produce a number of nasty ones that humans are not well adapted to. Grains contain a large amount of phytic acid for example, which strongly inhibits the absorption of a number of important minerals. Tubers, which were our main carbohydrate source for about 1.5 million years before agriculture, contain less of it. This may have been a major reason why stature decreased when humans adopted grain-based agriculture. There are a number of toxins that occur in grains but not in tubers, such as certain heat-resistant lectins.

Non-industrial cultures often treated their seeds, including grains, differently than we do today. They used soaking, sprouting and long fermentation to decrease the amount of toxins found in grains, making them more nutritious and digestible. Most grain staples are not treated in this way today, and so we bear the brunt of their toxins even more than our ancestors did.

From an evolutionary standpoint, even 11,500 years is the blink of an eye. Add to that the fact that many people descend from groups that have been eating grains for far less time than that, and you begin to see the problem. There is no doubt that we have begun adapting genetically to grains. All you have to do to understand this is look back at the archaeological record, to see the severe selective pressure (read: disease) that grains placed on its early adopters. But the question is, have we had time to adapt sufficiently to make it a healthy food? I would argue the answer is no.

There are a few genetic adaptations I'm aware of that might pertain to grains: the duplication of the salivary amylase gene, and polymorphisms in the angiotensin-converting enzyme (ACE) and apolipoprotein B genes. Some groups duplicated a gene that secretes the enzyme amylase into the saliva, increasing its production. Amylase breaks down starch, indicating a possible increase in its consumption. The problem is that we were getting starch from tubers before we got it from grains, so it doesn't really argue for either side in my opinion. The ACE and apolipoprotein B genes may be more pertinent, because they relate to blood pressure and LDL cholesterol. Blood pressure and blood cholesterol are both factors that respond well to low-carbohydrate (and thus low-grain) diets, suggesting that the polymorphisms may be a protective adaptation against the cardiovascular effects of grains.

The fact that up to 1% of people of European descent may have full-blown celiac disease attests to the fact that 7,000 years have not been enough time to fully adapt to wheat on a population level. Add to that the fact that nearly half of genetic Europeans carry genes that are associated with celiac, and you can see that we haven't been weeded out thoroughly enough to tolerate wheat, the oldest grain!

Based on my reading, discussions and observations, I believe that rice is the least problematic grain, wheat is the worst, and everything else is somewhere in between. If you want to eat grains, it's best to soak, sprout or ferment them. This activates enzymes that break down most of the toxins. You can soak rice, barley and other grains overnight before cooking them. Sourdough bread is better than normal white bread. Unfermented, unsprouted whole wheat bread may actually be the worst of all.

Another China Tidbit

A final note about the Chinese study in the previous post: the overweight vegetable-eaters (read: wheat eaters) exercised more than their non-vegetable-eating, thin neighbors. So although their average calorie intake was a bit higher, their expenditure was as well. So much for 'calories in, calories out'...

Although I speculated in the last post that affluent people might be eating more wheat and fresh vegetables, the data don't support that. Participants with the highest income level actually adhered to the wheat and vegetable-rich pattern the least, while low-income participants were most likely to eat this way.

Interestingly, education showed a (weaker) trend in the opposite direction. More educated participants were more likely to eat the wheat-vegetable pattern, while the opposite was true of less educated participants. Thus, it looks like wheat makes people more educated. Just kidding, that's exactly the logic we have to avoid when interpreting this type of study!

Wheat is Invading China

Dr. Michael Eades linked to an interesting study yesterday on his Health and Nutrition blog. It's entitled "Vegetable-Rich Food Pattern is Related to Obesity in China."

It's one of these epidemiological studies where they try to divide subjects into different categories of eating patterns and see how health problems associate with each one. They identified four patterns: the 'macho' diet high in meat and alcohol; the 'traditional' diet high in rice and vegetables; the 'sweet tooth' pattern high in cake, dairy and various drinks; and the 'vegetable rich' diet high in wheat, vegetables, fruit and tofu. The only pattern that associated with obesity was the vegetable-rich diet. The 25% of people eating closest to the vegetable-rich pattern were more than twice as likely to be obese as the 25% adhering the least.

The authors of the paper try to blame the increased obesity on a higher intake of vegetable oil from stir-frying the vegetables, but that explanation is juvenile and misleading. A cursory glance at table 3 reveals that the vegetable-eaters weren't eating any more fat than their thinner neighbors. Dr. Eades suggests that their higher carbohydrate intake (+10%) and higher calorie intake (+120 kcal/day) are responsible for the weight gain, but I wasn't satisfied with that explanation so I took a closer look.

One of the most striking elements of the 'vegetable-rich' food pattern is its replacement of rice with wheat flour. The 25% of the study population that adhered the least to the vegetable-rich food pattern ate 7.3 times more rice than wheat, whereas the 25% sticking most closely to the vegetable-rich pattern ate 1.2 times more wheat than rice! In other words, wheat flour had replaced rice as their single largest source of calories. This association was much stronger than the increase in vegetable consumption itself!

All of a sudden, the data make perfect sense. Wheat seems to destroy the metabolism of cultures wherever it goes. I think the reason we don't see the same type of association in American epidemiological studies is that everyone eats wheat. Only in a culture that has a true diversity of diet can you find a robust association like this. The replacement of rice with wheat may have caused the increase in calorie intake as well, subsequent to metabolic dysfunction. Clinical trials of low-carbohydrate diets as well as 'paleolithic diets' have shown good metabolic outcomes from wheat avoidance, although one can't be sure that wheat is the only culprit from those data.

I don't think the vegetables had anything to do with the weight gain, they were just incidentally associated with wheat consumption. But I do think these data argue against the commonly-held idea that vegetables protect against overweight.

Celiac and Fat-Soluble Vitamins

One of the things I've been thinking about lately is the possibility that intestinal damage due to gluten grains (primarily wheat) contributes to the diseases of civilization by inhibiting the absorption of fat-soluble vitamins. If it were a contributing factor, we would expect to see a higher incidence of the common chronic diseases in newly-diagnosed celiac patients, who are often deficient in fat-soluble vitamins. We might also see a resolution of chronic disease in celiac patients who have been adhering faithfully to a long-term, gluten-free diet.

One thing that definitely associates with celiac disease is bone and tooth problems. Celiac patients often present with osteoporosis, osteopenia (thin bones), cavities or tooth enamel abnormalities (thanks Peter).

An Italian study showed that among 642 heart transplant candidates, 1.9% had anti-endomyosal antibodies (a feature of celiac), compared with 0.35% of controls. That's more than a 5-fold enrichment! The majority of those patients were presumably unaware of their celiac disease, so they were not eating a gluten-free diet.

Interestingly, celiac doesn't seem to cause obesity; to the contrary. That's one facet of modern health problems that it definitely does not cause.

The relationship between cancer and celiac disease is very interesting. The largest study I came across was conducted in Sweden using retrospective data from 12,000 celiac patients. They found that adult celiac patients have a higher overall risk of cancer, but that the extra risk disappears with age. The drop in cancer incidence may reflect dropping gluten following a celiac diagnosis. Here's another study showing that the elevated cancer risk occurs mostly in the first year after diagnosis, suggesting that eliminating gluten solves the problem. Interestingly, celiac patients have a greatly elevated risk of lymphoma, but a lower risk of breast cancer.

There's a very strong link between celiac and type I diabetes. In a large study, 1 in 8 type I diabetic children had celiac disease. This doesn't necessarily tell us much since celiac and type I diabetes are both autoimmune disorders.

One last study to add a nail to the coffin. Up to this point, all the studies I've mentioned have been purely observational, not able to establish a causal relationship. I came across a small study recently which examined the effect of a high-fiber diet on vitamin D metabolism in healthy (presumably non-celiac) adults. They broke the cohort up into two groups, and fed one group 20g of bran in addition to their normal diet. The other group got nothing extra. The bran-fed group had a vitamin D elimination half-life of 19.5 days, compared to 27.5 for the control group. In other words, for whatever reason, the group eating extra bran was burning through their vitamin D reserves 30% faster than the control group.

Unfortunately, the paper doesn't say what kind of bran it was, but it was probably wheat or oat (**Update- it's wheat bran**). This is important because it would determine if gluten was involved. Either way, it shows that something in grains can interfere with fat-soluble vitamin status, which is consistent with the staggering negative effect of wheat products on healthy non-industrialized cultures.

Add to this the possibility that most people may have some degree of gluten sensitivity, and you start to see a big problem. All together, the data are consistent with gluten grains interfering with fat-soluble vitamin status. As I discussed earlier, this could strongly contribute to the diseases of civilization. These data don't prove anything conclusively, but I do find them thought-provoking.

Thanks to Dudua for the CC photo

Vitamin Deficiency

I'm going to do some speculating today. More than usual. What are some of the deficiency symptoms of A, D and K2? Another way of putting the question is, what problems can you prevent or cure by giving people the right fat-soluble vitamins? If you read my last post, you know that cardiovascular disease, osteoporosis (and resulting fractures) and tooth decay are all strongly linked to fat-soluble vitamin status, probably in a causal way. There's also a strong suggestion that they could be involved in diabetes, kidney stones, resistance to infection and cancer. Well, we've just about covered all the major modern health problems, haven't we?

What if the 'disease of civilization' is simply a deficiency of fat-soluble vitamins? What if the only reason we haven't realized it yet is because we haven't understood the critical importance of K2 MK-4, and its synergy with A and D? I'm not totally convinced it's true, but it does make sense. I'm interested to hear other peoples' opinions on this.

There are two mechanisms that could cause deficiency. The first is the obvious: reduced intake. In general, we have a lower intake of A, D (from sunlight) and especially K2 than non-industrial populations past and present that did not suffer from the disease of civilization. Most Westerners fall short of optimal serum vitamin D, and K2 deficiency is nearly ubiquitous.

Reading Nutrition and Physical Degeneration, as well as other accounts of non-industrial groups transitioning from their traditional diets to a more Westernized one, it struck me how badly these people were being affected. Even when they were still eating some nutrient-dense traditional foods, their development and health suffered tremendously. I asked myself this question: could the Western food they were eating have actively interfered with their vitamin status, and could it be doing the same to us?

The most common foods that replaced traditional diets in Weston Price's studies were white wheat flour and sugar. Wheat contains a lot of gluten, which in some people causes celiac disease. Celiac is an immune response to gluten that causes the degeneration of the intestinal lining, which is responsible for absorbing nutrients, among other things. Celiac patients are often deficient in many nutrients, including fat-soluble vitamins. So there's clearly a link between gluten damage and fat-soluble vitamin status.

The interesting thing about celiac is it may actually be a spectrum, with nearly everyone showing some degree of gluten damage, but only severe cases being diagnosed. The diagnosis involves looking for antibodies against gluten, but there is evidence that some people may mount an immune response without producing antibodies (through the innate immune system). Peter pointed this out a while back.

So the hypothesis goes: the disease of civilization is caused by a deficiency of fat-soluble vitamins, due to both a lower intake and inefficient absorption through a damaged intestinal lining. Comments?