Saturday, December 27, 2008

Butter, Margarine and Heart Disease

Shortly after World War II, margarine replaced butter in the U.S. food supply. Margarine consumption exceeded butter in the 1950s. By 1975, we were eating one-fourth the amount of butter eaten in 1900 and ten times the amount of margarine. Margarine was made primarily of hydrogenated vegetable oils, as many still are today. This makes it one of our primary sources of trans fat. The consumption of trans fats from other sources also likely tracked closely with margarine intake.

Coronary heart disease (CHD) resulting in a loss of blood flow to the heart (heart attack), was first described in detail in 1912 by Dr. James B. Herrick. Sudden cardiac death due to CHD was considered rare in the 19th century, although other forms of heart disease were diagnosed regularly by symptoms and autopsies. They remain rare in many non-industrial cultures today. This could not have resulted from massive underdiagnosis because heart attacks have characteristic symptoms, such as chest pain that extends along the arm or neck. Physicians up to that time were regularly diagnosing heart conditions other than CHD. The following graph is of total heart disease mortality in the U.S. from 1900 to 2005. It represents all types of heart disease mortality, including 'heart failure', which are non-CHD disorders like arrhythmia and myocarditis.

The graph above is not age-adjusted, meaning it doesn't reflect the fact that lifespan has increased since 1900. I couldn't compile the raw data myself without a lot of effort, but the age-adjusted graph is here. It looks similar to the one above, just a bit less pronounced. I think it's interesting to note the close similarity between the graph of margarine intake and the graph of heart disease deaths. The butter intake graph is also essentially the inverse of the heart disease graph.

Here's where it gets really interesting. The U.S. Centers for Disease Control has also been tracking CHD deaths specifically since 1900. Again, it would be a lot of work for me to compile the raw data, but it can be found here and a graph is in Anthony Colpo's book The Great Cholesterol Con. Here's the jist of it: there was essentially no CHD mortality until 1925, at which point it skyrocketed until about 1970, becoming the leading cause of death. After that, it began to fall due to improved medical care. There are some discontinuities in the data due to changes in diagnostic criteria, but even subtracting those, the pattern is crystal clear.

The age-adjusted heart disease death rate (all forms of heart disease) has been falling since the 1950s, largely due to improved medical treatment. Heart disease incidence has not declined substantially, according to the Framingham Heart study. We're better at keeping people alive in the 21st century, but we haven't successfully addressed the root cause of heart disease.

Was the shift from butter to margarine involved in the CHD epidemic? We can't make any firm conclusions from these data, because they're purely correlations. But there are nevertheless mechanisms that support a protective role for butter, and a detrimental one for margarine. Butter from pastured cows is one of the richest known sources of vitamin K2. Vitamin K2 plays a central role in protecting against arterial calcification, which is an integral part of arterial plaque and the best single predictor of cardiovascular death risk. In the early 20th century, butter was typically from pastured cows.

Margarine is a major source of trans fat. Trans fat is typically found in vegetable oil that has been hydrogenated, rendering it solid at room temperature. Hydrogenation is a chemical reaction that is truly disgusting. It involves heat, oil, hydrogen gas and a metal catalyst. I hope you give a wide berth to any food that says "hydrogenated" anywhere in the ingredients. Some modern margarine is supposedly free of trans fats, but in the U.S., less than 0.5 grams per serving can be rounded down so the nutrition label is not a reliable guide. Only by looking at the ingredients can you be sure that the oils haven't been hydrogenated. Even if they aren't, I still don't recommend margarine, which is an industrially processed pseudo-food.

One of the strongest explanations of CHD is the oxidized LDL hypothesis. The idea is that LDL lipoprotein particles ("LDL cholesterol") become oxidized and stick to the vessel walls, creating an inflammatory cascade that results in plaque formation. Chris Masterjohn wrote a nice explanation of the theory here. Several things influence the amount of oxidized LDL in the blood, including the total amount of LDL in the blood, the antioxidant content of the particle, the polyunsaturated fat content of LDL (more PUFA = more oxidation), and the size of the LDL particles. Small LDL is considered more easily oxidized than large LDL. Small LDL is also associated with elevated CHD mortality. Trans fat shrinks your LDL compared to butter.

In my opinion, it's likely that both the decrease in butter consumption and the increase in trans fat consumption contributed to the massive incidence of CHD seen in the U.S. and other industrial nations today. I think it's worth noting that France has the highest per-capita dairy fat consumption of any industrial nation, along with a comparatively low intake of hydrogenated fat, and also has the second-lowest rate of CHD, behind Japan.

Friday, December 26, 2008

Leptin Resistance and Sugar

Leptin is a major hormone regulator of fat mass in vertebrates. It's a frequent topic on this blog because I believe it's central to overweight and modern metabolic disorders. Here's how it works. Leptin is secreted by fat tissue, and its blood levels are proportional to fat mass. The more fat tissue, the more leptin. Leptin reduces appetite, increases fat release from fat tissue and increases the metabolic rate. Normally, this creates a "feedback loop" that keeps fat mass within a fairly narrow range. Any increase in fat tissue causes an increase in leptin, which burns fat tissue at an accelerated rate. This continues until fat mass has decreased enough to return leptin to its original level.

Leptin was first identified through research on the "obese" mutant mouse. The obese strain arose by a spontaneous mutation, and is extremely fat. The mutation turned out to be in a protein investigators dubbed leptin. When researchers first discovered leptin, they speculated that it could be the "obesity gene", and supplemental leptin a potential treatment for obesity. They later discovered (to their great chagrin) that obese people produce much more leptin than thin people, so a defeciency of leptin was clearly not the problem, as it was in the obese mouse. They subsequently found that obese people scarcely respond to injected leptin by reducing their food intake, as thin people do. They are leptin resistant. This makes sense if you think about it. The only way a person can gain significant fat mass is if the leptin feedback loop isn't working correctly.

Another rodent model of leptin resistance arose later, the "Zucker fatty" rat. Zucker rats have a mutation in the leptin receptor gene. They secrete leptin just fine, but they don't respond to it because they have no functional receptor. This makes them an excellent model of complete leptin resistance. What happens to Zucker rats? They become obese, hypometabolic, hyperphagic, hypertensive, insulin resistant, and they develop blood lipid disturbances. It should sound familiar; it's the metabolic syndrome and it affects 24% of Americans (CDC NHANES III). Guess what's the first symptom of impending metabolic syndrome in humans, even before insulin resistance and obesity? Leptin resistance. This makes leptin an excellent contender for the keystone position in overweight and other metabolic disorders.

I've mentioned before that the two most commonly used animal models of the metabolic syndrome are both sugar-fed rats. Fructose, which accounts for 50% of table sugar and 55% of high-fructose corn syrup, is probably the culprit. Glucose, which is the remainder of table sugar and high-fructose corn syrup, and the product of starch digestion, does not have the same effects. I think it's also relevant that refined sugar contains no vitamins or minerals whatsoever. Sweetener consumption in the U.S. has increased from virtually nothing in 1850, to 84 pounds per year in 1909, to 119 pounds in 1970, to 142 pounds in 2005 (source).

In a recent paper, Dr. Philip Scarpace's group (in collaboration with Dr. Richard Johnson), showed that a high-fructose diet causes leptin resistance in rats. The diet was 60% fructose, which is extreme by any standards, but it caused a complete resistance to the effect of leptin on food intake. Normally, leptin binds receptors in a brain region called the hypothalamus, which is responsible for food intake behaviors (including in humans). This accounts for leptin's ability to reduce food consumption. Fructose-fed rats did not reduce their food intake at all when injected with leptin, while rats on a normal diet did. When subsequently put on a high-fat diet (60% lard), rats that started off on the fructose diet gained more weight.

I think it's worth mentionong that rodents don't respond to high-fat diets in the same way as humans, as judged by the efficacy of low-carbohydrate diets for weight loss. Industrial lard also has a very poor ratio of omega-6 to omega-3 fats (especially if it's hydrogenated), which may also contribute to the observed weight gain.

Fructose-fed rats had higher cholesterol and twice the triglycerides of control-fed rats. Fructose increases triglycerides because it goes straight to the liver, which makes it into fat that's subsequently exported into the bloodstream. Elevated triglycerides impair leptin transport from the blood to the hypothalamus across the blood-brain barrier, which separates the central nervous system from the rest of the body. Fructose also impaired the response of the hypothalamus to the leptin that did reach it. Both effects may contribute to the leptin resistance Dr. Scarpace's group observed.

Just four weeks of fructose feeding in humans (1.5g per kg body weight) increased leptin levels by 48%. Body weight did not change during the study, indicating that more leptin was required to maintain the same level of fat mass. This may be the beginning of leptin resistance.

Thursday, December 25, 2008

The Fundamentals

I heard an interview of Michael Pollan yesterday on Talk of the Nation. He made some important points about nutrition that bear repeating. He's fond of saying "don't eat anything your grandmother wouldn't recognize as food". That doesn't mean your grandmother specifically, but anyone's grandmother, whether she was Japanese, American or African. The point is that commercial food processing has taken us away from the foods, and traditional food preparation methods, on which our bodies evolved to thrive. At this point, we don't know enough about health to design a healthy synthetic diet. Diet and health are too complex for reductionism at our current level of understanding. For that reason, any departure from natural foods and traditional food processing techniques is suspect.

Mainstream nutrition science has repeatedly contradicted itself and led us down the wrong path. This means that traditional cultures still have something to teach us about health. Hunter-gatherers and certain other non-industrial cultures are still the healthiest people on Earth, from the perspective of non-communicable disease. Pollan used the example of butter. First we thought it was healthy, then we were told it contains too much saturated fat and should be replaced with hydrogenated vegetable margarine. Now we learn that trans fats are unhealthy, so we're making new margarines that are low in trans fats, but are still industrially processed pseudo-foods. How long will it take to show these new fats are harmful? What will be the next industrial fat to replace them? This game can be played forever as the latest unproven processed food replaces the previous one, and it will never result in something as healthy as real butter.

The last point of Pollan's I'll mention is that the world contains (or contained) a diversity of different cultures, living in dramatically different ways, many of which do not suffer from degenerative disease. These range from carnivores like the Inuit, to plant-heavy agriculturalists like the Kitavans, to pastoralists like the Masai. The human body is adapted to a wide variety of foodways, but the one it doesn't seem to like is the modern Western diet.

Pollan's new book is In Defense of Food. I haven't read it, but I think it would be a good introduction to the health, ethical and environmental issues that surround food choices. He's a clear and accessible writer.

Merry Christmas, happy Hanukkah, and happy holidays to everyone!

Friday, December 19, 2008

Omega-6 Linoleic Acid Suppresses Thyroid Signaling

The thyroid gland controls the body's metabolic rate, among other things. It does this by secreting the thyroid hormones triiodothyronine (T3) and thyroxine (T4). As with any other hormone, the tissue response depends on the amount of hormone and the tissue's sensitivity to the hormone.

For example, in type I diabetes, the pancreas doesn't produce enough insulin to move glucose from the blood into tissues. In type II diabetes, often the tissues are so resistant to the action of insulin that glucose is not effectively transported from the blood into tissues, despite high levels of insulin. Both result in excessively high blood glucose after a meal containing carbohydrate.

In the last post, I discussed a study in which rats on different diets, fed equal amounts of calories and omega-3, gained weight in proportion to the omega-6 linoleic acid content of their diets. 1960s men fed a diet high in linoleic acid also gained weight relative to a more typical control diet containing the same number of calories. Rats deficient in linoleic acid develop an abnormally high metabolic rate. This suggests that the metabolic rate may be supressed by linoleic acid, and leads us to the question: does linoleic acid suppress thyroid signaling?

I was first introduced to the idea by Dr. Ray Peat, who suggests that all polyunsaturated fats (PUFA) suppress thyroid signaling (and should be avoided as much as possible). I couldn't find any credible references in his articles, so I went digging around PubMed myself. It turns out, he's right, and it's been known since at least the 1970s.

The first thing I searched for is whether or not linoleic acid reduces the secretion of T3 or T4 by the thyroid gland. It doesn't seem to, although one study I found used Crisco as the "saturated fat" control group (I'm not making this up!). Next, I looked for studies that evaluated the effect of linoleic acid on tissue sensitivity to thyroid hormones. Here's what I found:
  • A corn oil diet greatly suppresses the liver's response to T4 when compared with an equal amount of lard (5% by weight).
  • A safflower oil diet suppresses the liver's response to T3 when compared with an equal amount of beef tallow (10% by weight).
  • A diet high in linoleic acid (undisclosed source) suppresses the response of brown fat and liver to T3.
This is highly significant, since the liver is one of the major sites of thyroid hormone-responsive heat production. The liver and other visceral organs generate heat largely by activating a pump that pushes ions back and forth across the cell membrane, called the sodium-potassium ATPase. It's basically a way to create heat from chemical energy, like rubbing your hands together.

In another study, investigators showed that rats eating a diet containing 20% beef tallow ad libitum ate more, weighed less and carried less fat than rats eating 20% safflower oil. The
liver sodium-potassium ATPase activity of the safflower group was 26% lower, although the result was not considered statistically significant. Serum leptin was much higher in the safflower oil group. High leptin plus low energy expenditure suggests leptin resistance. The safflower group was eating less food, and gaining more weight, probably because linoleic acid was suppressing its ability to generate heat. This may be partly due to inhibition of the sodium-potassium ATPase, as well as the effects of leptin resistance.

In the 1970s, linoleic acid was
being considered as a treatment for hyperthyroidism:
Further studies should reveal the extent to which observed effects of excess thyroid hormone are amenable to control by dietary polyunsaturated fat.
Linoleic acid may interfere with thyroid signaling by inhibiting thyroid hormone binding to its receptor. Not all PUFA are equal in their ability to promote weight gain. Growing mice fed 15% corn oil develop more fat mass than mice fed 10% corn oil plus 5% perilla oil (rich in omega-3 alpha-linolenic acid). The effect can be blocked by knocking out the prostacyclin receptor, which shows that omega-6 derived eicosanoid signaling is responsible for the "excessive adipose [fat] tissue development" in growing mice. This mechanism is different from thyroid signaling.

Add gluten-induced autoimmune hypothyroidism, goitrogens (thyroid inhibitors) in soy, and endocrine disruptors from plastic like bispheonl-A, and you have potent brew that may strongly promote obesity in Western industrial nations.

The treatment? Dump the vegetable oil, wheat, soy, sugar and processed food in favor of the things the human body is equipped to handle: animal fats, root vegetables, vegetables, fruit, meats, organs, seafood, eggs, nuts and soaked or fermented non-gluten grains and legumes. Throw in some bugs if you're feeling adventurous.

Coconut oil can be particularly helpful because it's almost exclusively saturated, so it doesn't interfere with thyroid signaling. That may be why it increases energy expenditure and aids weight loss. Coconut has a long history of use by healthy non-industrial cultures in tropical areas. The medical literature likes to use the euphemism "medium-chain triglycerides" when referring to the saturated fat in coconut oil because it conceals the fact that it's saturated. Low-carbohydrate diets are also very helpful for weight loss, but I'm not sure it's really due to the carbohydrate itself rather than restricting wheat and sugar. I discussed that concept in this post.

Thanks to Wikipedia for the CC photo.

Tuesday, December 16, 2008

Vegetable Oil and Weight Gain

In the last post, I stated that the three largest changes in the American diet since 1970 (a time during which the obesity rate doubled) were an increase in refined grain consumption, an increase in sweetener consumption, and the replacement of animal fats with industrial vegetable fats. I'm always on the lookout for mechanisms that could link these changes to metabolic dysregulation. I suspect wheat is a major player, possibly due to its ability to cause inflammation and overeating. Sugar is also an obvious culprit, since it contributes to insulin resistance and other elements of the metabolic syndrome. Vegetable oil is clearly involved in many of the diseases of civilization. Are there any data that suggest it's involved in weight gain? I believe I've found convincing evidence that it is.

Vegetable oil is truly an "external factor", something in our environment that has changed dramatically in the last 100 years (as opposed to our genes, which are essentially the same). A century ago, nearly all fats eaten in the U.S. came from animals. That's how it's been for humans since the beginning of time, with the exception of
seasonal nuts and oily seeds for some groups. Polyunsaturated fat (PUFA) consumption in the US has more than tripled in the last 100 years, with the increase coming almost solely from omega-6 linoleic acid-rich seed oils like soybean and corn oil (source): This amount of linoleic acid is totally foreign to the human body. It causes countless detrimental effects to many, if not all organ systems. And it's exactly what mainstream health authorities have been telling us to eat for the last 50 years. You may have noticed that the recommendations have changed recently to focus on monounsaturated oils like olive oil. They are backpedaling in the face of an avalanche of studies demonstrating the detrimental effects of linoleic acid on health.

I found a well-controlled study in which investigators put rats on three different isocaloric, high-fat diets. Each one contained an identical amount of total fat, protein, carbohydrate, omega-3 alpha-linolenic acid (from flax oil), and variable amounts of omega-6 linoleic acid:
  • 59% of calories from beef tallow, for a total n-6 of 4.4% of calories.
  • 59% of calories from olive oil, for a total n-6 of 7.7% of calories.
  • 59% of calories from safflower oil, for a total n-6 of 36.6% of calories.
All rats gained weight on the high-fat diet, but their body fat composition differed. Fat tissue in the tallow group was 10.3% linoleic acid, 15.2% in the olive oil group and 54.5% in the safflower group. Relative to the tallow group, rats in the olive oil group saw a 7.5% increase in total body weight, and the safflower group saw a 12.3% increase. The latter is the equivalent of an average American gaining 21 lbs (9.5 kg). All rats were eating the exact same number of calories. The most straightforward explanation is that the rats' metabolism was slowed in direct proportion to the linoleic acid content of the diet.

This effect seems to be specific to mammals, because linoleic acid does not cause weight gain in birds. I think it's worth noting that homemade tallow from beef suet is only 2.4% linoleic acid, far lower than the 7.4% (as a percentage of total fat) fed to the tallow group in this experiment.

Weight gain occurred even at 4.4% of calories from linoleic acid. We don't know what they would have looked like on less linoleic acid under the same conditions. However, rats fed a high-fat diet rich in coconut oil or butter (low n-6)
do not gain weight, despite a greatly increased caloric intake (although they do gain some fat mass). It's also worth mentioning that rats in the tallow group had higher tissue concentrations of omega-3 fatty acids, though they had an identical intake to the other two groups. This suggests that linoleic acid somehow drives omega-3 out of the tissues, and is consistent with studies showing a precipitous drop in muscle concentration of omega-3 in cows fed grains and soybeans in a feedlot.

Time to back this up with human data. When I'm digging for studies, I typically look at the oldest ones first. They are often the most informative. In this case, I had another reason as well. In the 1960s, Americans ate about half the linoleic acid we do today, and our body fat linoleic acid stores were also about half as big (although still high). What happens when you feed a 1960s American man with a diet high in linoleic acid-rich vegetable oils?
He gains weight as his body fat stores of linoleic acid increase, just like the rats above. It's like putting your body fat in a time machine and beaming it to 2008!

They don't design studies like this anymore. 782 elderly men were placed on isocaloric controlled diets for 5 years, one group eating a typical "high-saturated fat" diet and the other eating a diet in which total energy, fat, carbohydrate and protein intake were identical to the first group, but linoleic acid-rich vegetable oils were substituted for animal fats. This study is unique in its long duration, large number of participants, specific isolation of the effects of linoleic acid, and the fact that it was conducted when body fat stores of linoleic acid were lower than today.

In the beginning, the body fat of both groups was 11% linoleic acid. By one year on the diet, the unsaturated group had risen to just over 20%. This is where the weight gain began. Between year one and three, the two groups diverged by just under 5% body weight, or about 8 pounds (3.6 kg). This is an estimate based on the graph provided, because they didn't include the raw data. If you compare these numbers to the body fat/weight gain statistics for the rat study above, they are quite similar.

At five years, body fat in the unsaturated group was 32% linoleic acid, and the weight difference between groups remained the same as it was at 3 years. Hunter-gatherers almost certainly have values in the low single digits (possibly less than 1% for some groups), putting this completely outside the range of our natural fat composition.
The body fat of Americans is currently hovering between 15 and 25% omega-6 linoleic acid, due mostly to a high intake of industrial vegetable oils.

If you believe the studies I presented above, Americans and other industrial cultures throughout the world are in the range where excess linoleic acid causes the accumulation of body fat. According to the human study, adding more linoleic acid to body fat after about 20% may not cause further weight gain. That means any similar study in the last 20 years could be confounded by excess stored linoleic acid. The half-life of fat tissue turnover is about 2 years, so restoring balance is a long-term process.

In both the rat and human experiments above, "low"-linoleic and high-linoleic groups ate the same number of calories, yet the high-linoleic groups gained more weight. How could that be? In the next post, I'll describe what I believe is the mechanism. Any guesses?

Sunday, December 14, 2008

U.S. Weight, Lifestyle and Diet Trends, 1970- 2007

For this post, I compiled statistics on U.S. weight, health and lifestyle trends, and graphed them as consistently as possible. They span the period from 1970 to 2007, during which the obesity rate doubled. The data come from the National Health and Nutrition Examination Survey (NHANES), the Behavioral Risk Factor Surveillance System (BRFSS), and the U.S. Department of Agriculture (USDA). Some of the graphs are incomplete, either because the data don't exist, or because I wasn't able to find them. Obesity is defined as a body mass index (BMI) of 30+; overweight is a BMI of 25+. Yes, it's frightening. It has affected adults and children (NHANES).
The percentage of Americans who report exercising in their spare time has actually increased since 1988 (BRFSS).
We're eating about 250 more calories per day, according to NHANES.
The 250 extra calories are coming from carbohydrate (NHANES).

We're eating more vegetables and fruit (USDA).
We're eating more meat by weight, although calories from meat have probably gone down because the meat has gotten leaner (USDA). This graph represents red meat, fish and poultry. The increase comes mostly from poultry. Boneless, skinless chicken breasts anyone?
We're eating more sugar (USDA). The scale of the graph doesn't allow you to fully appreciate that sweetener consumption had increased by a full 100 calories per day by 1999, although it has dropped a bit since then. This is based on food disappearance data. In other words, the amount consumed is estimated using the amount sold domestically, minus a percentage that approximates waste. High-fructose corn syrup has seized nearly 50% of the sweetener market since 1970.
Again, the scale of the graph doesn't allow you to fully appreciate the magnitude of the change here. In 2000, we ate approximately 2.5 ounces, or 280 calories, more processed grains per day than in 1970 (USDA). That has since decreased slightly (34 calories). You might be saying to yourself right now "hey, that plus the 100 calories from sugar adds up to more of an increase than the NHANES data show!" Yes, and I think that points to the fact that the data sets are not directly comparable. NHANES data are self-reported whereas USDA data are collected from vendors. Regardless of the absolute numbers, our processed grain consumption has gone way up since 1970.

Wheat is still king. Although we grow a lot of corn in this country, most of it gets fed to animals. We prefer eating wheat without first feeding it to an intermediary. In absolute quantity, wheat consumption has increased more than any other grain (not including corn syrup).
Bye bye whole milk. Hello skim milk (USDA).

This graph represents "added fats", as opposed to fats that occur naturally in meat or milk (the USDA does not track the latter). Added fats include salad oil, cooking oil, deep fry oil, butter, lard, tallow, etc. We are eating a lot more vegetable oil than we were in 1970. It comes chiefly from the industrial, omega-6 rich oils such as soybean, corn and canola. Added animal fats have increased slightly, but it's pretty insignificant in terms of calories.

There is an artifact in this graph that I have to point out. In 2000, the USDA changed the way it gathered vegetable oil data. This led to an abrupt, apparent increase in its consumption that is obvious on the graph. So it's difficult to make any quantitative conclusions, but I think it's clear nevertheless that vegetable oil intake has increased considerably.

Between 1970 and 1980, something changed in the U.S. that caused a massive increase in obesity and other health problems. Some combination of factors reached a critical mass that our metabolism could no longer tolerate. The three biggest changes in the American diet since 1970:
  • An increase in cereal grain consumption, particularly wheat.
  • An increase in sweetener consumption
  • The replacement of meat and milk fat with industrial vegetable oils, with total fat intake remaining the same.
Mainstream America has done to itself what it did to native American and other indigenous cultures worldwide, with the same result.

Saturday, December 13, 2008

The Myth of the High-Protein Diet

The phrase "low-carbohydrate diet" is a no-no in some circles, because it implies that a diet is high in fat. Often, the euphemism "high-protein diet" is used to avoid the mental image of a stick of butter wrapped in bacon. It's purely a semantic game, because there is no such thing as a diet in which the majority of calories come from protein. The ability of the human body to metabolize protein ends at about 1/3 of calories (1, 2), and the long-term optimum may be lower still. Low-carbohydrate diets (yes, the ones that are highly effective for weight loss and general health) are high-fat diets.

Healthy cultures around the world tend to consume roughly 10 to 20% of calories from protein:

Masai - 19%
Kitava - 10%

Tokelau - 12%
Inuit - 20%, according to Stefansson
Kuna - 12%
Sweden - 12%
United States - 15%
Human milk - 6%

The balance comes from fat and carbohydrate. Ask a traditional Inuit. If there's no fat on your meat, you may as well starve. Literally. "Rabbit starvation" was a term coined by American explorers who quickly realized that living on lean game is somewhere between unhealthy and fatal.

In the early 1900s, anthropologist and explorer Vilhjalmur Stefansson lived for several years among completely isolated Canadian Inuit (Eskimo) who had never seen a white person before. They were literally a stone-age culture, completely uninfluenced by the modern world. They are representative of how some of our paleolithic ancestors would have lived. Here's Stefansson, quoted from My Life With the Eskimo (1913):
In certain places and in certain years, rabbits are an important article of diet, but even when there is an abundance of this animal, the Indians consider themselves starving if they get nothing else, - and fairly enough, as my own party can testify, for any one who is compelled in winter to live for a period of several weeks on lean meat will actually starve, in this sense: that there are lacking from his diet certain necessary elements, notably fat, and it makes no difference how much he eats, he will be hungry at the end of each meal, and eventually he will lose strength or become actually ill. The Eskimo who have provided themselves in summer with bags of seal oil can carry them into a rabbit country and can live on rabbits satisfactorily for months.
Dr. Loren Cordain, in his excellent paper "Plant-Animal Subsistence Ratios and Macronutrient Energy Estimations in Worldwide Hunter-Gatherer Diets", argues based on calculated estimates that historical hunter-gatherers generally consumed between 19 and 35% of calories from protein:
This high reliance on animal-based foods coupled with the relatively low carbohydrate content of wild plant foods produces universally characteristic macronutrient composition ratios in which protein is elevated (19- 35% of energy) at the expense of carbohydrates (22- 40% of energy).
Later, he states that the most plausible range of fat intakes is 28- 58%. I agree with his assertion that hunter-gatherer diets tended to be relatively high in protein compared with contemporary diets, but I think his protein numbers are a bit high. Why? Because he calculates macronutrient composition based on the whole-carcass fat content of "representative" animals such as deer.

It's clear from the anthropological literature that hunter-gatherers did not go after representative animals. They went after the fattest animals they could find. They knew exactly which animals were fattest in which seasons, which individuals were likely to be fattest within a herd, and which bodyparts were fattest on an individual animal. For example, Stefansson describes how the Inuit relied on (extremely fat) seal in the spring, wolf in the summer, and caribou and bear in the fall and early winter. If necessary, they would discard lean meat in favor of tongue, marrow, internal organs, back fat and other fat-rich bodyparts. This was in order to obtain a minimum of 65% of calories from fat.

Hunter-gatherers would sometimes even provision themselves with enough fat in advance to last a lean season or two. This was true for dozens of tribes along the Northwest coast of North America that relied chiefly on animal foods. Here's another excerpt from My Life With the Eskimo:
...[spring] is the season which the Eskimo give up to the accumulation of blubber for the coming year. Fresh oil is not nearly so palatable or digestible as oil that has been allowed to ferment in a sealskin bag through the summer, and besides that it is difficult often to get seals in the fall... Each family will in the spring be able to lay away from three to seven bags of oil. Such a bag consists of the whole skin of the common seal... This makes a bag which will hold about three hundred pounds of blubber, so that a single family's store of oil for the fall will run from nine hundred to two thousand pounds.
That's a lot of oil! Some of it would have been used to light oil lamps, but much of it would have been eaten. I think Cordain's estimate of the protein intake of hunter-gatherers is a bit high due to his underestimating fat intake. His paper shows that if you break historical hunter-gatherer cultures into 10 groups based on their reliance on animal foods, the most numerous group (46 out of 229) obtained 85- 100% of their food from animal sources. In other words, approximately 20% of historical hunter-gatherers were carnivorous or nearly so. If the human protein ceiling is 35% of calories, that means roughly one fifth of hunter-gatherers ate 65% or more of their calories as fat. It also means carnivory and high-fat diets are not just anomalies, they are part of the human ecological niche. Zero out of 229 groups obtained less than 16% of calories from animal foods. Vegetarianism is not part of our niche.

Further, although the human body can theoretically tolerate up to 35% protein by calories, even that amount is probably not optimal in the long term. I think that's suggested by the fact that diverse cultures tend to find a source of fat and/or carbohydrate that keeps their protein intake roughly between 10 and 20%. I think it's fine to eat plenty of protein, and there's no need to deliberately restrict it, because your tastes will tell you if you're eating too much. However, "high-protein diet" as a euphemism for low-carbohydrate diet is a misnomer. Low-carbohydrate diets are, and have always been, high-fat diets.

Monday, December 8, 2008

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.

Saturday, December 6, 2008

Peripheral vs. Ectopic Fat

I went to an interesting presentation the other day by Dr. George Ioannou of the University of Washington, on obesity and liver disease. He made an interesting distinction between the health effects of two types of body fat. The first is called subcutaneous fat (or peripheral fat). It accumulates right under the skin and is evenly distributed over the body's surface area, including extremities. The second is called ectopic fat. Ectopic means "not where it's supposed to be". It accumulates in the abdominal region (beer belly), the liver, muscle tissue including the heart, the pancreas, and perhaps in lipid-rich deposits in the arteries. Subcutaneous fat can be measured by taking skinfold thickness in different places on the body, or sometimes by measuring arm or leg circumference. Ectopic fat can be measured by taking waist circumference.

It's an absolutely critical distinction, because ectopic fat associates with poor health outcomes while subcutaneous fat does not. In
this recent study, waist circumference was associated with increased risk of death while arm and leg circumference were associated with a reduced risk of death. I think the limb circumference association in this particular study is probably confounded by muscle mass, but other studies have also shown a strong, consistent association between ectopic fat and risk of death, but not subcutaneous fat. The same goes for dementia and a number of other diseases. I think it's more than an epidemiological asssociation. Surgically removing the abdominal fat from mice prevents insulin resistance and prolongs their lifespan.

People with excess visceral fat are also
much more likely to have fatty liver and cirrhosis. It makes sense if you think of them both as manifestations of ectopic fat. There's a spectrum of disorders that goes along with excess visceral fat and fatty liver: it's called the metabolic syndrome, and it affects a quarter of Americans (NHANES III). We already have a pretty good idea of what causes fatty liver, at least in lab animals: industrial vegetable oils and sugar. What's the most widely used animal model of metabolic syndrome? The sugar-fed rat. What are two of the main foods whose consumption has increased in recent decades? Vegetable oil and sugar. Hmm... Fatty liver is capable of causing insulin resistance and diabetes, according to a transgenic mouse that expresses a hepatitis C protein in its liver.

You want to keep your liver happy. All those blood tests they do in the doctor's office to see if you're healthy-- cholesterol levels, triglycerides, insulin, glucose--
reflect liver function to varying degrees.

Abdominal fat is a sign of ectopic fat distribution throughout the body, and its associated metabolic consequences. I think we know it's unhealthy on a subconscious level, because belly fat is not attractive whereas nicely distributed subcutaneous fat can be. If you have excess visceral fat, take it as a sign that your body does not like your current lifestyle. It might be time to think about changing your diet and exercise regime.
Here are some ideas.

Wednesday, December 3, 2008

Polyunsaturated Fat Intake: What About Humans?

Now we know how to raise a healthy pig or rat: balance omega-6 linoleic acid (LA) and omega-3 alpha-linolenic acid (LNA) and keep both relatively low. LA and LNA are the most basic (and shortest) forms of omega-6 and omega-3 fats. They are the only fats the body can't make on its own. They're found in plant foods, and animal foods to a lesser extent. Animals convert them to longer-chain fats like arachidonic acid (AA; omega-6), EPA (omega-3) and DHA (omega-3). These long-chain, animal PUFA are involved in a dizzying array of cellular processes. They participate directly as well as being further elongated to form eicosanoids, a large class of very influential signaling molecules.

AA is the precursor of a number of inflammatory eicosanoids, while omega-3-derived eicosanoids tend to be less inflammatory and participate in long-term repair processes. A plausible explanation for the negative health effects of LA-rich vegetable oils is the fact that they lead to an imbalance in cellular signaling by increasing the formation of AA and decreasing the formation of EPA and DHA. Both inflammatory and anti-inflammatory signaling are necessary in the proper context, but they must be in balance for optimal function. Many modern diseases involve excess inflammation. LA also promotes oxidative and nitrosative damage to organs, as explained in the last post. This is an enormous oversimplification, but I'll skip over the details (most of which I don't know) because they could fill a stack of textbooks.

How do we raise a healthy human? Although I think pigs are a decent model organism for studying diet and health as it relates to humans, they don't have as much of a carnivorous history as we do. You would expect them to be more efficient at converting plant nutrients to their animal counterparts: carotenes to vitamin A, vitamin K1 to K2, and perhaps short-chain polyunsaturated fats (PUFA) to long-chain fats like AA, EPA and DHA. I mention it simply to point out that what goes for a pig may not necessarily go for a human when it comes to fatty acid conversion.

I've dug up a few papers exploring this question. I don't intend this post to be comprehensive but I think it's enough to get a flavor of what's going on. The first paper is an intervention trial comparing the effect of flax oil and fish oil supplementation on the fat composition of red blood cells. Investigators gave volunteers either 1.2 g, 2.4 g or 3.6 g (one teaspoon) flax oil per day; or 0.6 g or 1.2 g fish oil per day. The volunteers were U.S. firefighters, who otherwise ate their typical diet rich in omega-6. Flax oil supplementation at the two higher doses increased EPA, but did not increase DHA or decrease AA significantly. This suggests that humans can indeed convert some ALA to long-chain omega-3 fats, but adding ALA to a diet that is already high in omega-6 does not reduce AA or increase the all-important DHA.

The fish oil supplement, even at one-sixth the highest flax oil dose, increased EPA and DHA to a greater extent than flax oil, and also decreased AA. This shows that fish oil has a greater effect than flax oil on the fat profile of red blood cells in the context of a diet rich in omega-6. Another study also found that ALA intake is not associated with EPA or DHA in blood plasma. This could suggest either that humans aren't very good at converting ALA to longer n-3 fats, that the pathways are blocked by excessive LA or some other factor (a number of things block conversion of omega-3 fats), or that our bodies are already converting sufficient omega-3 and fish oil is overkill.

What happens when you reduce omega-6 consumption while increasing omega-3? In one study, participants were put on a "high LA" or "low LA" (3.8% of calories) diet. The first had an omega-6 : omega-3 ratio of 10.1, while the second had a ratio of 4.0. As in the previous intervention study, EPA was higher on the low LA diet. Here's where it gets interesting: DHA levels fell precipitously throughout the study, regardless of which diet the participants were eating. This has to do with a special requirement of the study diet: participants were not allowed to eat seafood. This shows that most of the DHA in the blood is obtained by eating DHA from animal fat, rather than elongating it from ALA such as flax oil. This agrees with the finding that strict vegetarians (vegans) have a low level of DHA in blood plasma.

In another intervention study, researchers achieved a better omega-6 : omega-3 ratio, with participants going from a baseline ratio of 32.2 to an experimental ratio of 2.2 for 10 weeks. The change in ratio was mostly from increasing omega-3, rather than decreasing omega-6. This caused an increase in serum EPA and DHA, although the DHA did not quite reach statistical significance (p= 0.06). In this study, participants were encouraged to eat fish 3 times per week, which is probably the reason their DHA rose. Participants saw a metabolic shift to fat burning, and an increase in insulin sensitivity that was on the cusp of statistical significance (p= 0.07).

I think what the data suggest is that humans can convert short-chain omega-3 (ALA) to EPA, but we don't efficiently elongate it to DHA. At least in the context of a high LA intake. Another thing to keep in mind is that serum PUFA are partially determined by what's in fat tissue. Modern Americans have an abnormally high proportion of LA in their fat tissue, sometimes over 20%. This contributes to a higher proportion of omega-6 and its derivatives in all tissues. "Wild" humans, including our paleolithic ancestors, would probably have values in the lower single digits. LA in fat tissue has a half-life of about 2 years, so restoring balance is a long-term process. Omega-3 fats do not accumulate to the same degree as LA, typically comprising about 1% of fat tissue. At this point, one could rightly ask: we know how diet affects blood polyunsaturated fats, but what's the relevance to health? There are multiple lines of evidence, all of which point in generally the same direction in my opinion.

There are strong, consistent associations between omega-6 intake (from vegetable oils), low omega-3 intake, and a number of health and psychiatric problems. Another line of evidence comes from intervention trials. The Lyon diet-heart study was one of the most successful intervention trials of all time. The experimental group increased their intake of fish, poultry, root vegetables, green vegetables, bread and fruit, while decreasing intake of red meat and dairy fat. A key difference between this study and other intervention trials is that participants were encouraged to eat a margarine rich in omega-3 ALA. In sum, participants decreased their total PUFA intake, decreased omega-6 intake and increased intake of ALA and long-chain omega-3s. After an average of 27 months, total mortality was 70% lower in the intervention group than in the control group eating the typical diet! This effect was not seen in trials that encouraged vegetable and grain consumption, discouraged red meat and dairy fat consumption, but didn't alter PUFA intake or the omega-6 : omega-3 ratio, such as the Women's Health Initiative.

As usual, the most important line of evidence comes from healthy non-industrial cultures that did not suffer from modern non-communicable diseases. They invariably consumed very little omega-6 LA (3% of calories or less), ate a roughly balanced amount of omega-6 and omega-3, and had a source of long-chain (animal) omega-3. They did not eat much omega-3 from plant sources (such as flax), as concentrated sources are rare in nature. Dr. Weston Price observed that cultures throughout the world sought out seafood if available, sometimes going to great lengths to obtain it. Here's an exerpt from Nutrition and Physical Degeneration about Fiji islanders:
Since Viti Levu, one of the islands of this group, is one of the larger islands of the Pacific Ocean, I had hoped to find on it a district far enough from the sea to make it necessary for the natives to have lived entirely on land foods. Accordingly, with the assistance of the government officials and by using a recently opened government road I was able to get well into the interior of the island by motor vehicle, and from this point to proceed farther inland on foot with two guides. I was not able, however, to get beyond the piles of sea shells which had been carried into the interior. My guide told me that it had always been essential, as it is today, for the people of the interior to obtain some food from the sea, and that even during the times of most bitter warfare between the inland or hill tribes and the coast tribes, those of the interior would bring down during the night choice plant foods from the mountain areas and place them in caches and return the following night and obtain the sea foods that had been placed in those depositories by the shore tribes. The individuals who carried these foods were never molested, not even during active warfare. He told me further that they require food from the sea at least every three months, even to this day. This was a matter of keen interest, and at the same time disappointment since one of the purposes of the expedition to the South Seas was to find, if possible, plants or fruits which together, without the use of animal products, were capable of providing all of the requirements of the body for growth and for maintenance of good health and a high state of physical efficiency.
Price searched for, but did not find, vegetarian groups that were free of the diseases of civilization. What he found were healthy cultures that put a strong emphasis on nutrient-dense animal foods, particularly seafoods when available. I think all this information together suggests that the optimum, while being a fairly broad range, is a low intake of omega-6 LA (less than 3% of calories) and a modest intake of animal omega-3 for DHA.

I believe the most critical element is reducing omega-6 LA by eliminating industrial vegetable oils (soybean, corn, cottonseed, etc.) and the foods that contain them from the diet. Fats from pasture-raised ruminants (butter, beef, lamb etc.) and wild fish are naturally balanced. We no longer commonly eat the most concentrated land source of DHA, brain, so I think it's wise to eat seafood sometimes. According to the first study I cited, 1/4 teaspoon of fish oil (or cod liver oil) per day is enough to elevate plasma DHA quite significantly. This amount of omega-3 could be obtained by eating seafood weekly.