High-Fat Dairy, Obesity, Metabolic Health and Cardiovascular Disease.

New Review Paper by Yours Truly: High-Fat Dairy, Obesity, Metabolic Health and Cardiovascular Disease

My colleagues Drs. Mario Kratz, Ton Baars, and I just published a paper in the European Journal of Nutrition titled "The Relationship Between High-Fat Dairy Consumption and Obesity, Cardiovascular, and Metabolic Disease".  Mario is a nutrition researcher at the Fred Hutchinson Cancer Research Center here in Seattle, and friend of mine.  He's doing some very interesting research on nutrition and health (with an interest in ancestral diets), and I'm confident that we'll be getting some major insights from his research group in the near future.  Mario specializes in tightly controlled human feeding trials.  Ton is an agricultural scientist at the University of Kassel in Germany, who specializes in the effect of animal husbandry practices (e.g., grass vs. grain feeding) on the nutritional composition of dairy.  None of us have any connection to the dairy industry or any other conflicts of interest.

The paper is organized into three sections:

1. A comprehensive review of the observational studies that have examined the relationship between high-fat dairy and/or dairy fat consumption and obesity, metabolic health, diabetes, and cardiovascular disease.
2. A discussion of the possible mechanisms that could underlie the observational findings.
3. Differences between pasture-fed and conventional dairy, and the potential health implications of these differences.

 We wrote this paper because after reviewing the evidence, we found it to be surprising and fairly contradictory to conventional ideas on nutrition and health.  I wrote the sections on obesity, metabolic health and diabetes, Mario wrote the sections on cardiovascular disease and fatty acids, and Ton wrote the section on husbandry practices and dairy fat composition.  Mario was the lead author and did most of the editing/formatting, submitted the manuscript, etc.  Our paper went through a rigorous peer review process.

Here are our basic findings:

• High-fat dairy consumption is not associated with obesity, in fact, 11 out of 16 studies found that higher dairy fat intake is associated with lower body fat and/or less fat gain over time.  None identified an association between high-fat dairy consumption and fat gain, although some did find an association between low-fat dairy consumption and fat gain.
• High-fat dairy consumption is not associated with poorer metabolic health.  Six of 11 studies found that higher high-fat dairy consumption is associated with better metabolic health, while only one found that it was associated with one marker of poorer metabolic health (and this study used an odd design). 
• The association between high-fat dairy intake and diabetes risk is inconsistent.  Zero of eight studies found that high-fat dairy consumption is associated with diabetes risk, and three found that it was protective.  However, three studies also found that low-fat dairy intake was inversely associated with diabetes risk, compared to no association with high-fat dairy, suggesting by inference that the fat content of the dairy could be harmful.  These studies all adjusted for body fatness.  Since body fatness is a key risk factor for diabetes, and dairy fat intake is inversely associated with body fatness, this is obviously a major confound.  We discussed this and other potential confounds in the paper.
• The evidence on cardiovascular disease is inconsistent, with a number of studies suggesting a protective association, a few suggesting a harmful one, and several suggesting no association.
• Dairy fat is a complex substance.  There are major differences in the fatty acid composition of dairy from pasture-raised vs. conventionally raised cows, and many of these fatty acids are bioactive and could influence human health.
• We also discuss the limitations of observational studies in some detail, and many other issues that I won't touch on here.

What This Paper Means 

This is the first comprehensive review of studies on the association between high-fat dairy intake and obesity, metabolic, and cardiovascular health.  Typical dietary advice includes the recommendation to eat low-fat or skim dairy products.  This is based on the hypothesis that avoiding the (mostly saturated) fat in dairy will reduce the risk of obesity, metabolic problems, and cardiovascular disease.  This idea is logical, but not every idea that is logical is correct when tested scientifically, particularly when it pertains to a complex natural food.  We asked the question "what does the evidence say about this hypothesis?"

The research to date suggests that high-fat dairy overall does not have a negative impact on obesity risk, metabolic problems, diabetes risk, or cardiovascular disease.  In fact, these studies offer fairly strong support to the hypothesis that high-fat dairy may protect against obesity.  However, there was variability between studies and this may be explained by factors such as a) differences in the quality of dairy products between countries/regions, b) the form in which dairy is consumed (e.g., traditional cheeses vs. ice cream and pizza), and c) other confounding factors discussed in the paper. 

Please keep in mind that these studies are observational and therefore can not establish cause and effect. They're best viewed as a springboard for future research.

What This Paper Doesn't Mean

I want to be very clear about this.  This paper does not mean that adding butter to all your food will make you lose fat or become healthier.  In fact, if you do that you will most likely gain fat and become less healthy.  Say what??  The studies we reviewed examined the role of high-fat dairy in the context of normal varied diet patterns.  They did not compare people eating normally to people who put extra butter on everything, which is an excellent way to increase your calorie intake.  Essentially they compared people eating high-fat dairy to people eating other types of fats as part of a mixed diet.  The difference is subtle but critical to understand: addition vs. replacement. 

So does this mean that replacing other types of fats with dairy fat (pasture-raised in particular), in the context of a normal varied diet, could lead to less fat gain and perhaps even better health over time?  Perhaps.  That is what the studies suggest overall.  But again, these are observational studies with major limitations, so we'll have to wait for more evidence before we can hang our hats on the idea.  In the meantime, it's clear that typical dietary recommendations to favor low-fat dairy over high-fat dairy are on thin ice.

Cancer and the Immune System

Cancer and the Immune System

My understanding of cancer has changed radically over the past few months. I used to think of it as an inevitable consequence of aging, a stochastic certainty. The human body is made of about 50 trillion cells, many of which replicate their DNA and divide regularly. It's only a matter of time until one of those cells randomly accumulates the wrong set of mutations, and loses the molecular brakes that restrict uncontrolled growth. 

Strictly speaking, the idea is correct. That is how cancer begins. However, there's another check in place that operates outside the cancer cell itself: the immune system. A properly functioning immune system can recognize and destroy cancerous cells before they become dangerous to the organism. In fact, your immune system has probably already controlled or destroyed a number of them in your lifetime. 

I recently read a fascinating account of some preliminary findings from the lab of Dr. Zheng Cui at Wake Forest university. His group took blood samples from 100 people and purified a type of immune cell called the granulocyte. They then evaluated the granulocytes' ability to kill cervical cancer cells in a cell culture dish. They found that it varied dramatically from one individual to another. One person's granulocytes killed 97% of the cancer cells in 24 hours, while another person's killed 2%. 

They found some important trends. Granulocytes from people over 50 years old had a reduced ability to kill cancer cells, as did granulocytes from people with cancer. This raises the possibility that cancer is not simply the result of getting too old, but a very specific weakening of the immune system.

The most important finding, however, was that the granulocytes' kung-fu grip declined dramatically during the winter months. Here's Dr. Cui:

Nobody seems to have any cancer-killing ability during the
winter months from November to April.

Hmm, I wonder why that could be?? Vitamin D anyone??

Cancer Among the Inuit

Cancer Among the Inuit

I remember coming across a table in the book Eat, Drink and Be Healthy (by Dr. Walter Willett) a few years back. Included were data taken from Dr. Ancel Keys' "Seven Countries Study". It showed the cancer rates for three industrialized nations: the US, Greece and Japan. Although specific cancers differed, the overall rate was remarkably similar for all three: about 90 cancers per 100,000 people per year. Life expectancy was also similar, with Greece leading the pack by 4 years (the data are from the 60s). 

The conclusion I drew at the time was that lifestyle did not affect the likelihood of developing cancer. It was easy to see from the same table that heart disease was largely preventable, since the US had a rate of 189 per 100,000 per year, compared to Japan's 34. Especially since I also knew that Japanese-Americans who eat an American diet get heart disease just like European-Americans. 

I fell prey to the same logic that is so pervasive today: the idea that you will eventually die of cancer if no other disease gets you first. It's easy to believe, since the epidemiology seems to tell us that lifestyle doesn't affect overall cancer rates very much. There's only one little glitch... those epidemiological studies compare the sick to the sicker. 

Here's the critical fact that modern medicine seems to have forgotten: hunter-gatherers and numerous non-industrial populations throughout the world have unusually low cancer rates. This idea was widely accepted in the 19th century and the early 20th, but has somehow managed to fade into obscurity.  Allow me to explain. 

I recently read Cancer, Disease of Civilization by Vilhjalmur Stefansson (thanks Peter). Stefansson was an anthropologist and arctic explorer who participated in the search for cancer among the Canadian and Alaskan Inuit. Traditionally, most Inuit groups were mostly carnivorous, eating a diet of raw and cooked meat and fish almost exclusively. Their calories came primarily from fat. They alternated between seasons of low and high physical activity, typically enjoyed an abundant food supply yet also periodically faced famines. 

Field physicians in the arctic noted that the Inuit were a remarkably healthy people. While they suffered from a tragic susceptibility to European communicable diseases, they did not develop the chronic diseases we now view as part of being human: tooth decay, overweight, heart attacks, appendicitis, constipation, diabetes and cancer. When word reached American and European physicians that the Inuit did not develop cancer, a number of them decided to mount an active search for it. This search began in the 1850s and tapered off in the 1920s, as traditionally-living Inuit became difficult to find. 

One of these physicians was captain George B. Leavitt. He actively searched for cancer among the traditionally-living Inuit from 1885 to 1907. Along with his staff, he claims to have performed tens of thousands of examinations. He did not find a single case of cancer. At the same time, he was regularly diagnosing cancers among the crews of whaling ships and other Westernized populations. It's important to note two relevant facts about Inuit culture: first, their habit of going shirtless indoors. This would make visual inspection for external cancers very easy. Second, the Inuit generally had great faith in Western doctors and would consult them even for minor problems. Therefore, doctors in the arctic had ample opportunity to inspect them for cancer. 

A study was published in 1934 by F.S. Fellows in the US Treasury's Public Health Reports entitled "Mortality in the Native Races of the Territory of Alaska, With Special Reference to Tuberculosis". It contained a table of cancer mortality deaths for several Alaskan regions, all of them Westernized to some degree. However, some were more Westernized than others. In descending order of Westernization, the percent of deaths from cancer were as follows:


Keep in mind that all four of the Inuit populations in this table were somewhat Westernized. It's clear that cancer incidence tracks well with Westernization, although other factors could be involved in producing this result (such as poorer diagnosis in less Westernized regions). By "Westernization", what I mean mostly is the adoption of European food habits, including wheat flour, sugar, canned goods and vegetable oil. Later, most groups also adopted Western-style houses, which incidentally were not at all suited to their harsh climate. 

In the next post, I'll address the classic counter-argument that hunter-gatherers were free of cancer because they didn't live long enough to develop it.

Mortality and Lifespan of the Inuit

Mortality and Lifespan of the Inuit

One of the classic counter-arguments that's used to discredit accounts of healthy hunter-gatherers is the fallacy that they were short-lived, and thus did not have time to develop diseases of old age like cancer. While the life expectancy of hunter-gatherers was not as high as ours today, most groups had a significant number of elderly individuals, who sometimes lived to 80 years and beyond. Mortality came mostly from accidents, warfare and infectious disease rather than chronic disease. 

I found a a mortality table from the records of a Russian mission in Alaska (compiled by Veniaminov, taken from Cancer, Disease of Civilization), which recorded the ages of death of a traditionally-living Inuit population during the years 1822 to 1836. Here's a plot of the raw data:

Here's the data re-plotted in another way. I changed the "bin size" of the bars to 10 year spans each (rather than the bins above, which vary from 3 to 20 years). This allows us to get a better picture of the number of deaths over time. I took some liberties with the data to do this, breaking up a large bin equally into two smaller bins. I also left out the infant mortality data, which are interesting but not relevant to this post: 

Excluding infant mortality, about 25% of their population lived past 60. Based on these data, the approximate life expectancy (excluding infant mortality) of this Inuit population was 43.5 years. It's possible that life expectancy would have been higher before contact with the Russians, since they introduced a number of nasty diseases to which the Inuit were not resistant. Keep in mind that the Westerners who were developing cancer alongside them probably had a similar life expectancy at the time. Here's the data plotted in yet another way, showing the number of individuals surviving at each age, out of the total deaths recorded:

It's remarkably linear. Here's the percent chance of death at each age:


In the next post, I'll briefly summarize cancer data from several traditionally-living cultures other than the Inuit.

Sunscreen and Melanoma

Sunscreen and Melanoma

Melanoma is the most deadly type of skin cancer, accounting for most skin cancer deaths in the US. As Ross pointed out in the comments section of the last post, there is an association between severe sunburn at a young age and later development of melanoma. Darker-skinned people are also more resistant to melanoma. The association isn't complete, however, since melanoma sometimes occurs on the soles of the feet and even in the intestine. This may be due to the fact that there are several types of melanoma, potentially with different causes. 

Another thing that associates with melanoma is the use of sunscreen above a latitude of 40 degrees from the equator. In the Northern hemisphere, 40 degrees draws a line between New York city and Beijing. A recent meta-analysis found consistently that sunscreen users above 40 degrees are at a higher risk of melanoma than people who don't use sunscreen, even when differences in skin color are taken into account. Wearing sunscreen decreased melanoma risk in studies closer to the equator. It sounds confusing, but it makes sense once you know a little bit more about UV rays, sunscreen and the biology of melanoma. 

The UV light that reaches the Earth's surface is composed of UVA (longer) and UVB (shorter) wavelengths. UVB causes sunburn, while they both cause tanning. Sunscreen blocks UVB, preventing burns, but most brands only weakly block UVA. Sunscreen allows a person to spend more time in the sun than they would otherwise, and attenuates tanning. Tanning is a protective response (among several) by the skin that protects it against both UVA and UVB. Burning is a protective response that tells you to get out of the sun. The result of diminishing both is that sunblock tends to increase a person's exposure to UVA rays. 

It turns out that UVA rays are more closely associated with melanoma than UVB rays, and typical sunscreen fails to prevent melanoma in laboratory animals. It's also worth mentioning that sunscreendoes prevent more common (and less lethal) types of skin cancer. 

Modern tanning beds produce a lot of UVA and not much UVB, in an attempt to deliver the maximum tan without causing a burn. Putting on sunscreen essentially does the same thing: gives you a large dose of UVA without much UVB. 

The authors of the meta-analysis suggest an explanation for the fact that the association changes at 40 degrees of latitude: populations further from the equator tend to have lighter skin. Melanin blocks UVA very effectively, and the pre-tan melanin of someone with olive skin is enough to block most of the UVA that sunscreen lets through. The fair-skinned among us don't have that luxury, so our melanocytes get bombarded by UVA, leading to melanoma. This may explain the incredible rise in melanoma incidence in the US in the last 35 years, as people have also increased the use of sunscreen. It may also have to do with tanning beds, since melanoma incidence has risen particularly in women. 

In my opinion, the best way to treat your skin is to tan gradually, without burning. Use clothing and a wide-brimmed hat if you think you'll be in the sun past your burn threshold. If you want to use sunscreen, make sure it blocks UVA effectively. Don't rely on the manufacturer's word; look at the ingredients list. It should contain at least one of the following: titanium dioxide, zinc oxide, avobenzone (Parsol 1789), Mexoryl SX (Tinosorb). It's best if it's also paraben-free. 

Fortunately, as an external cancer, melanoma is easy to diagnose. If caught early, it can be removed without any trouble. If caught a bit later, surgeons may have to remove lymph nodes, which makes your face look like John McCain's. Later than that and you're probably a goner. If you have any questions about a growth, especially one with irregular borders that's getting larger, ask your doctor about it immediately!

The Inuit: Lessons from the Arctic

The Inuit: Lessons from the Arctic

The Inuit (also called Eskimo) are a group of hunter-gatherer cultures who inhabit the arctic regions of Alaska, Canada and Greenland. They are a true testament to the toughness, adaptability and ingenuity of the human species. Their unique lifestyle has a lot of information to offer us about the boundaries of the human ecological niche. Weston Price was fascinated by their excellent teeth, good nature and overall robust health. Here's an excerpt from Nutrition and Physical Degeneration:

"In his primitive state he has provided an example of physical excellence and dental perfection such as has seldom been excelled by any race in the past or present...we are also deeply concerned to know the formula of his nutrition in order that we may learn from it the secrets that will not only aid in the unfortunate modern or so-called civilized races, but will also, if possible, provide means for assisting in their preservation."

The Inuit are cold-hardy hunters whose traditional diet consists of a variety of sea mammals, fish, land mammals and birds. They invented some very sophisticated tools, including the kayak, whose basic design has remained essentially unchanged to this day. Most groups ate virtually no plant food. Their calories came primarily from fat, up to 75%, with almost no calories coming from carbohydrate. Children were breast-fed for about three years, and had solid food in their diet almost from birth. As with most hunter-gatherer groups, they were free from chronic disease while living a traditional lifestyle, even in old age. Here's a quote from Observations on the Western Eskimo and the Country they Inhabit; from Notes taken During two Years [1852-54] at Point Barrow, by Dr. John Simpson:

These people [the Inuit] are robust, muscular and active, inclining rather to spareness [leanness] than corpulence [overweight], presenting a markedly healthy appearance. The expression of the countenance is one of habitual good humor. The physical constitution of both sexes is strong. Extreme longevity is probably not unknown among them; but as they take no heed to number the years as they pass they can form no guess of their own ages.

One of the common counterpoints I hear to the idea that high-fat hunter-gatherer diets are healthy, is that exercise protects them from the ravages of fat. The Inuit can help us get to the bottom of this debate. Here's a quote from Cancer, Disease of Civilization (1960, Vilhjalmur Stefansson):

"They are large eaters, some of them, especially the women, eating all the time..." ...during the winter the Barrow women stirred around very little, did little heavy work, and yet "inclined more to be sparse than corpulent" [quotes are the anthropologist Dr. John Murdoch, reproduced by Stefansson].

Another argument I sometimes hear is that the Inuit are genetically adapted to their high-fat diet, and the same food would kill a European. This appears not to be the case. The anthropologist and arctic explorer Vilhjalmur Stefansson spent several years living with the Inuit in the early 20th century. He and his fellow Europeans and Americans thrived on the Inuit diet. American doctors were so incredulous that they defied him and a fellow explorer to live on a diet of fatty meat only for one year, under the supervision of the American Medical Association. To the doctors' dismay, they remained healthy, showing no signs of scurvy or any other deficiency (JAMA 1929;93:20–2).

Yet another amazing thing about the Inuit was their social structure. Here's Dr. John Murdoch again (quoted from Cancer, Disease of Civilization): 

The women appear to stand on a footing of perfect equality with the men, both in the family and the community. The wife is the constant and trusted companion of the man in everything except the hunt, and her opinion is sought in every bargain or other important undertaking... The affection of parents for their children is extreme, and the children seem to be thoroughly worthy of it. They show hardly a trace of fretfulness or petulance so common among civilized children, and though indulged to an extreme extent are remarkably obedient. Corporal punishment appears to be absolutely unknown, and children are rarely chided or punished in any way.

Unfortunately, those days are long gone. Since adopting a modern processed-food diet, the health and social structure of the Inuit has deteriorated dramatically. This had already happened to most groups by Weston Price's time, and is virtually complete today. Here's Price:

In the various groups in the lower Kuskokwim seventy-two individuals who were living exclusively on native foods had in their 2,138 teeth only two teeth or 0.09 per cent that had ever been attacked by tooth decay. In this district eighty-one individuals were studied who had been living in part or in considerable part on modern foods, and of their 2, 254 teeth 394 or 13 per cent had been attacked by dental caries. This represents an increase in dental caries of 144 fold.... When these adult Eskimos exchange their foods for our modern foods..., they often have very extensive tooth decay and suffer severely.... Their plight often becomes tragic since there are no dentists in these districts.

Modern Inuit also suffer from very high rates of diabetes and overweight. This has been linked to changes in diet, particularly the use of white flour, sugar and processed oils. 

Overall, the unique lifestyle and diet of the Inuit have a lot to teach us. First, that some humans are capable of being healthy eating mostly animal foods. Second, that some humans are able to thrive on a high-fat diet. Third, that humans are capable of living well in extremely harsh and diverse environments. Fourth, that the shift from natural foods to processed foods, rather than changes in macronutrient composition, is the true cause of the diseases of civilization.

Corn Oil and Cancer??

Corn Oil and Cancer?

The benefits of corn oil keep rolling in. In a new study by Stephen Freedland's group at Duke, feeding mice a diet rich in butter and lard didn't promote the growth of transplanted human prostate cancer cells any more than a low-fat diet (1).

Why do we care? Because other studies, including one from the same investigators, show that corn oil and other industrial seed oils strongly promote prostate cancer cell growth and increase mortality in similar models (2, 3).

From the discussion section:

Current results combined with our prior results suggest that lowering the fat content of a primarily saturated fat diet offers little survival benefit in an intact or castrated LAPC-4 xenograft model. In contrast to the findings when omega-6 fats are used, these results raise the possibility that fat type may be as important as fat amount or perhaps even more important.

There's a large body of evidence implicating excess omega-6 fat in a number of cancer models. Reducing omega-6 to below 4% of calories has a dramatic effect on cancer incidence and progression*. In fact, there have even been several experiments showing that butter and other animal fats promote cancer growth to a lesser degree than margarine and omega-6-rich seed oils. I discussed that here.


* The average American eats 7-8% omega-6 by calories. This means it will be difficult to see a relationship between omega-6 intake and cancer (or heart disease, or most things) in observational studies in the US or other industrial nations, because we virtually all eat more than 4% of calories as omega-6. Until the 20th century, omega-6 intake was below 4%, and usually closer to 2%, in some traditional societies. That's where it remains in contemporary traditional societies unaffected by industrial food habits, such as Kitava.

Pastured Dairy may Prevent Heart Attacks

Pastured Dairy may Prevent Heart Attacks

Not all dairy is created equal. Dairy from grain-fed and pasture-fed cows differs in a number of ways. Pastured dairy contains more fat-soluble nutrients such as vitamin K2, vitamin A, vitamin E, carotenes and omega-3 fatty acids. It also contains more conjugated linoleic acid, a fat-soluble molecule that has been under intense study due to its ability to inhibit obesity and cancer in animals. The findings in human supplementation trials have been mixed, some confirming the animal studies and others not. In feeding experiments in cows, Dr. T. R. Dhiman and colleagues found the following (1):

Cows grazing pasture and receiving no supplemental feed had 500% more conjugated linoleic acid in milk fat than cows fed typical dairy diets.

Fat from ruminants such as cows, sheep and goats is the main source of CLA in the human diet. CLA is fat-soluble. Therefore, skim milk doesn't contain any. It's also present in human body fat in proportion to dietary intake. This can come from dairy or flesh.

In a recent article from the AJCN, Dr. Liesbeth Smit and colleagues examined the level of CLA in the body fat of Costa Rican adults who had suffered a heart attack, and compared it to another group who had not (a case-control study, for the aficionados). People with the highest level of CLA in their body fat were 49% less likely to have had a heart attack, compared to those with the lowest level (2).

Since dairy was the main source of CLA in this population, the association between CLA and heart attack risk is inextricable from the other components in pastured dairy fat. In other words, CLA is simply a marker of pastured dairy fat intake in this population, and the (possible) benefit could just as easily have come from vitamin K2 or something else in the fat.

This study isn't the first one to suggest that pastured dairy fat may be uniquely protective. The Rotterdam and EPIC studies found that a higher vitamin K2 intake is associated with a lower risk of heart attack, cancer and overall mortality (3, 4, 5). In the 1940s, Dr. Weston Price estimated that pastured dairy contains up to 50 times more vitamin K2 than grain-fed dairy. He summarized his findings in the classic book Nutrition and Physical Degeneration. This finding has not been repeated in recent times, but I have a little hunch that may change soon...

Vitamin K2
Cardiovascular Disease and Vitamin K2
Can Vitamin K2 Reverse Arterial Calcification?

Nitrate: a Protective Factor in Leafy Greens

Nitrate: a Protective Factor in Leafy Greens

Cancer Link and Food Sources

Nitrate (NO3) is a molecule that has received a lot of bad press over the years. It is thought to promote digestive cancers, in part due to its ability to form carcinogens when used as a preservative for processed meat. Because of this (1), nitrate was viewed with suspicion and a number of countries imposed strict limits on its use as a food additive.

But what if I told you that by far the greatest source of nitrate in the modern diet isn't processed meat-- but vegetables, particularly leafy greens (2)? And that the evidence linking exposure to nitrate itself has largely failed to materialize? For example, one study found no difference in the incidence of gastric cancer between nitrate fertilizer plant workers and the general population (3). Most other studies in animals and humans have not supported the hypothesis that nitrate itself is carcinogenic (4, 5, 6), but rather that they are only carcinogenic in the context of processed meats due to the formation of carcinogenic nitrosamines. This, combined with recent findings on nitrate biology, has changed the way we think about this molecule in recent years.

A New Example of Human Symbiosis

In 2003, Dr. K. Cosby and colleagues showed that nitrite (NO2; not the same as nitrate) dilates blood vessels in humans when infused into the blood (7). Investigators subsequently uncovered an amazing new example of human-bacteria symbiosis: dietary nitrate (NO3) is absorbed from the gut into the bloodstream and picked up by the salivary glands. It's then secreted into saliva, where oral bacteria use it as an energy source, converting it to nitrite (NO2). After swallowing, the nitrite is reabsorbed into the bloodstream (8). Humans and oral bacteria may have co-evolved to take advantage of this process. Antibacterial mouthwash prevents it.

Nitrate Protects the Cardiovascular System

In 2008, Dr. Andrew J. Webb and colleagues showed that nitrate in the form of 1/2 liter of beet juice (equivalent in volume to about 1.5 soda cans) substantially lowers blood pressure in healthy volunteers for over 24 hours. It also preserved blood vessel performance after brief oxygen deprivation, and reduced the tendency of the blood to clot (9). These are all changes that one would expect to protect against cardiovascular disease. Another group showed that in monkeys, the ability of nitrite to lower blood pressure did not diminish after two weeks, showing that the animals did not develop a tolerance to it on this timescale (10).

Subsequent studies showed that dietary nitrite reduces blood vessel dysfunction and inflammation (CRP) in cholesterol-fed mice (11). Low doses of nitrite also dramatically reduce tissue death in the hearts of mice exposed to conditions mimicking a heart attack, as well as protecting other tissues against oxygen deprivation damage (12). The doses used in this study were the equivalent of a human eating a large serving (100 g; roughly 1/4 lb) of lettuce or spinach.

Mechanism

Nitrite is thought to protect the cardiovascular system by serving as a precursor for nitric oxide (NO), one of the most potent anti-inflammatory and blood vessel-dilating compounds in the body (13). A decrease in blood vessel nitric oxide is probably one of the mechanisms of diet-induced atherosclerosis and increased clotting tendency, and it is likely an early consequence of eating a poor diet (14).

The Long View

Leafy greens were one of the "protective foods" emphasized by the nutrition giant Sir Edward Mellanby (15), along with eggs and high-quality full-fat dairy. There are many reasons to believe greens are an excellent contribution to the human diet, and what researchers have recently learned about nitrate biology certainly reinforces that notion. Leafy greens may be particularly useful for the prevention and reversal of cardiovascular disease, but are likely to have positive effects on other organ systems both in health and disease. It's ironic that a molecule suspected to be the harmful factor in processed meats is turning out to be one of the major protective factors in vegetables.

Malocclusion: Disease of Civilization, Part III

Malocclusion: Disease of Civilization, Part III

Normal Human Occlusion 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Paleopathology at the Origins of Agriculture

Paleopathology at the Origins of Agriculture

In April of 1982, archaeologists from around the globe converged on Plattsburgh, New York for a research symposium. Their goal:

...[to use] data from human skeletal analysis and paleopathology [the study of ancient diseases] to measure the impact on human health of the Neolithic Revolution and antecedent changes in prehistoric hunter-gatherer food economies. The symposium developed out of our perception that many widely debated theories about the origins of agriculture had testable but untested implications concerning human health and nutrition and our belief that recent advances in techniques of skeletal analysis, and the recent explosive increase in data available in this field, permitted valid tests of many of these propositions.

In other words, they got together to see what happened to human health as populations adopted agriculture. They were kind enough to publish the data presented at the symposium in the bookPaleopathology at the Origins of Agriculture, edited by the erudite Drs. Mark Nathan Cohen and George J. Armelagos. It appears to be out of print, but luckily I have access to an excellent university library.

There are some major limitations to studying human health by looking at bones. The most obvious is that any soft tissue pathology will have been erased by time. Nevertheless, you can learn a lot from a skeleton. Here are the main health indicators discussed in the book:

• Mortality. Archaeologists are able to judge a person's approximate age at death, and if the number of skeletons is large enough, they can paint a rough picture of the life expectancy and infant mortality of a population.
• General growth. Total height, bone thickness, dental crowding, and pelvic and skull shape are all indicators of relative nutrition and health. This is particularly true in a genetically stable population. Pelvic depth is sensitive to nutrition and determines the size of the birth canal in women.
• Episodic stress. Bones and teeth carry markers of temporary "stress", most often due to starvation or malnutrition. Enamel hypoplasia, horizontal bands of thinned enamel on the teeth, is probably the most reliable marker. Harris lines, bands of increased density in long bones that may be caused by temporary growth arrest, are another type.
• Porotic hyperostosis and cribra orbitalia. These are both skull deformities that are caused by iron deficiency anemia, and are rather creepy to look at. They're typically caused by malnutrition, but can also result from parasites.
• Periosteal reactions. These are bone lesions resulting from infections.
• Physical trauma, such as fractures.
• Degenerative bone conditions, such as arthritis.
• Isotopes and trace elements. These can sometimes yield information about the nutritional status, diet composition and diet quality of populations.
• Dental pathology. My favorite! This category includes cavities, periodontal disease, missing teeth, abscesses, tooth wear, and excessive dental plaque.

The book presents data from 19 regions of the globe, representing Africa, Asia, the Middle East, Europe, South America, with a particular focus on North America. I'll kick things off with a fairly representative description of health in the upper Paleolithic in the Eastern Mediterranean. The term "Paleolithic" refers to the period from the invention of stone tools by hominids 2.5 million years ago, to the invention of agriculture roughly 10,000 years ago. The upper Paleolithic lasted from about 40,000 to 10,000 years ago. From page 59:

In Upper Paleolithic times nutritional health was excellent. The evidence consists of extremely tall stature from plentiful calories and protein (and some microevolutionary selection?); maximum skull base height from plentiful protein, vitamin D, and sunlight in early childhood; and very good teeth and large pelvic depth from adequate protein and vitamins in later childhood and adolescence...
Adult longevity, at 35 years for males and 30 years for females, implies fair to good general health...
There is no clear evidence for any endemic disease.

The level of skeletal (including cranial and pelvic) development Paleolithic groups exhibited has remained unmatched throughout the history of agriculture. There may be exceptions but the trend is clear. Cranial capacity was 11% higher in the upper Paleolithic. You can see the pelvic data in this table taken from Paleopathology at the Origins of Agriculture. 

There's so much information in this book, the best I can do is quote pieces of the editor's summary and add a few remarks of my own. One of the most interesting things I learned from the book is that the diet of many hunter-gatherer groups changed at the end of the upper Paleolithic, foreshadowing the shift to agriculture. From pages 566-568:

During the upper Paleolithic stage, subsistence seems focused on relatively easily available foods of high nutritional value, such as large herd animals and migratory fish. Some plant foods seem to have been eaten, but they appear not to have been quantitatively important in the diet. Storage of foods appears early in many sequences, even during the Paleolithic, apparently to save seasonal surpluses for consumption during seasons of low productivity.

As hunting and gathering economies evolve during the Mesolithic [period of transition between hunting/gathering and agriculture], subsistence is expanded by exploitation of increasing numbers of species and by increasingly heavy exploitation of the more abundant and productive plant species. The inclusion of significant amounts of plant food in prehistoric diets seems to correlate with increased use of food processing tools, apparently to improve their taste and digestibility. As [Dr. Mark Nathan] Cohen suggests, there is an increasing focus through time on a few starchy plants of high productivity and storability. This process of subsistence intensification occurs even in regions where native agriculture never developed. In California, for example, as hunting-gathering populations grew, subsistence changed from an early pattern of reliance on game and varied plant resources to to one with increasing emphasis on collection of a few species of starchy seeds and nuts.

...As [Dr. Cohen] predicts, evolutionary change in prehistoric subsistence has moved in the direction of higher carrying capacity foods, not toward foods of higher-quality nutrition or greater reliability. Early nonagricultural diets appear to have been high in minerals, protein, vitamins, and trace nutrients, but relatively low in starch. In the development toward agriculture there is a growing emphasis on starchy, highly caloric food of high productivity and storability, changes that are not favorable to nutritional quality but that would have acted to increase carrying capacity, as Cohen's theory suggests.

Very interesting.

One of the interesting things I learned from the book is that Mesolithic populations, groups that were halfway between farming and hunting-gathering, were generally as healthy as hunter-gatherers: 

...it seems clear that seasonal and periodic physiological stress regularly affected most prehistoric hunting-gathering populations, as evidenced by the presence of enamel hypoplasias and Harris lines. What also seems clear is that severe and chronic stress, with high frequency of hypoplasias, infectious disease lesions, pathologies related to iron-deficiency anemia, and high mortality rates, is not characteristic of these early populations. There is no evidence of frequent, severe malnutrition, so the diet must have been adequate in calories and other nutrients most of the time. During the Mesolithic, the proportion of starch in the diet rose, to judge from the increased occurrence of certain dental diseases [with exceptions to be noted later], but not enough to create an impoverished diet... There is a possible slight tendency for Paleolithic people to be healthier and taller than Mesolithic people, but there is no apparent trend toward increasing physiological stress during the mesolithic.

Cultures that adopted intensive agriculture typically showed a marked decline in health indicators. This is particularly true of dental health, which usually became quite poor.

Stress, however, does not seem to have become common and widespread until after the development of high degrees of sedentism, population density, and reliance on intensive agriculture. At this stage in all regions the incidence of physiological stress increases greatly, and average mortality rates increase appreciably. Most of these agricultural populations have high frequencies of porotic hyperostosis and cribra orbitalia, and there is a substantial increase in the number and severity of enamel hypoplasias and pathologies associated with infectious disease. Stature in many populations appears to have been considerably lower than would be expected if genetically-determined maxima had been reached, which suggests that the growth arrests documented by pathologies were causing stunting... Incidence of carbohydrate-related tooth disease increases, apparently because subsistence by this time is characterized by a heavy emphasis on a few starchy food crops.

Infectious disease increased upon agricultural intensification:

Most [studies] conclude that infection was a more common and more serious problem for farmers than for their hunting and gathering forebears; and most suggest that this resulted from some combination of increasing sedentism, larger population aggregates, and the well-established synergism between infection and malnutrition.

There are some apparent exceptions to the trend of declining health with the adoption of intensive agriculture. In my observation, they fall into two general categories. In the first, health improves upon the transition to agriculture because the hunter-gatherer population was unhealthy to begin with. This is due to living in a marginal environment or eating a diet with a high proportion of wild plant seeds. In the second category, the culture adopted rice. Rice is associated with less of a decline in health, and in some cases an increase in overall health, than other grains such as wheat and corn. In chapter 21 of the book Ancient Health: Bioarchaeological Interpretations of the Human Past, Drs. Michelle T Douglas and Michael Pietrusewsky state that "rice appears to be less cariogenic [cavity-promoting] than other grains such as maize [corn]."

One pathology that seems to have decreased with the adoption of agriculture is arthritis. The authors speculate that it may have more to do with strenuous activity than other aspects of the lifestyle such as diet. Another interpretation is that the hunter-gatherers appeared to have a higher arthritis rate because of their longer lifespans:

The arthritis data are also complicated by the fact that the hunter-gatherers discussed commonly displayed higher average ages at death than did the farming populations from the same region. The hunter-gatherers would therefore be expected to display more arthritis as a function of age even if their workloads were comparable [to farmers].

In any case, it appears arthritis is normal for human beings and not a modern degenerative disease. 

And the final word:

Taken as a whole, these indicators fairly clearly suggest an overall decline in the quality-- and probably in the length-- of human life associated with the adoption of agriculture.

Life Expectancy and Growth of Paleolithic vs. Neolithic Humans

Life Expectancy and Growth of Paleolithic vs. Neolithic Humans

If paleolithic people were healthier than us due to their hunter-gatherer lifestyle, why did they have a shorter life expectancy than we do today? I was just reminded by Scott over at Modern Forager about some data on paleolithic (pre-agriculture) vs. neolithic (post-agriculture) life expectancy and growth characteristics. Here's a link to the table, which is derived from an article in the text Paleopathology at the Origins of Agriculture. 

The reason the table is so interesting is it allows us to ask the right question. Instead of "why did paleolithic people have a shorter life expectancy than we do today?", we should ask "how did the life expectancy of paleolithic people compare to that of pre-industrial neolithic people?" That's what will allow us to tease the effects of lifestyle apart from the effects of modern medicine. 

The data come from age estimates of skeletons from various archaeological sites representing a variety of time periods in the Mediterranean region. Paleolithic skeletons indicated a life expectancy of 35.4 years for men and 30.0 years for women, which includes a high rate of infant mortality. This is consistent with data from the Inuit that I posted a while back (life expectancy excluding infant mortality = 43.5 years). With modest fluctuations, the life expectancy of humans in this Mediterranean region remained similar from paleolithic times until the last century. I suspect the paleolithic people died most often from warfare, accidents and infectious disease, while the neolithic people died mostly from chronic disease, and infectious diseases that evolved along with the domestication of animals (zoonotic diseases). But I'm just speculating based on what I know about modern populations, so you can take that at face value.

The most interesting part of the table is actually not the life expectancy data. It also contains numbers for average stature and pelvic inlet depth. These are both markers of nutritional status during development. Pelvic inlet depth is a measure of the size of the pelvic canal through which a baby would pass during birth. It can be measured in men and women, but obviously its implications for birth only apply to women. As you can see in the table, stature and pelvic inlet depth declined quite a bit with the adoption of agriculture, and still have not reached paleolithic levels to this day. 

The idea that a grain-based diet interferes with normal skeletal development isn't new. It's well-accepted in the field of archaeology that the adoption of grains coincided with a shortening of stature, thinner bones and crooked, cavity-ridden teeth. This fact is so well accepted that these sorts of skeletal changes are sometimes used as evidence that grains were adopted in a particular region historically. Weston Price saw similar changes in the populations he studied, as they transitioned from traditional diets to processed-food diets rich in white wheat flour, sweets and other processed foods. 

The change in pelvic inlet depth is also very telling. Modern childbirth is so difficult, it makes you wonder why our bodies have evolved to make it so drawn-out and lethal. Without the aid of modern medicine, many of the women who now get C-sections and other birth interventions would not make it. My feeling is that we didn't evolve to make childbirth so lethal. It's more difficult in modern times, at least partially because we have a narrower pelvic inlet than our ancestors. Another thing Weston Price commented on was the relative ease of childbirth in many of the traditional societies he visited. Here's an exerpt from Nutrition and Physical Degeneration:

A similar impressive comment was made to me by Dr. Romig, the superintendent of the government hospital for Eskimos and Indians at Anchorage, Alaska. He stated that in his thirty-six years among the Eskimos, he had never been able to arrive in time to see a normal birth by a primitive Eskimo woman. But conditions have changed materially with the new generation of Eskimo girls, born after their parents began to use foods of modern civilization. Many of them are carried to his hospital after they had been in labor for several days. One Eskimo woman who had married twice, her last husband being a white man, reported to Dr. Romig and myself that she had given birth to twenty-six children and that several of them had been born during the night and that she had not bothered to waken her husband, but had introduced him to the new baby in the morning.

Now that's what I call fertility!

Grains and Human Evolution

Grains and Human Evolution

[Update 8/2011: as I've learned more about human genetics and evolution, I've come to appreciate that many Europeans actually descend from early adopters of agriculture more than they descend from the hunter-gatherers that previously occupied Europe.  Also, 10,000 years has been long enough for significant genetic adaptation.  Read The 10,000 Year Explosion for more information].

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.