Monday, November 29, 2010

Choline and Fatty Liver

I've been writing about non-alcoholic fatty liver disorder (NAFLD) since the early days of this blog, because it's an alarmingly common disorder (roughly a quarter of Americans affected) that is typically undiagnosed. It often progresses into its more serious cousin non-alcoholic steatohepatitis (NASH), an inflammatory condition that causes liver damage and can progress to cancer. In a number of previous posts, I pinpointed excess sugar and seed oil consumption as culprits in NAFLD and NASH (1, 2, 3, 4, 5).

Chris Masterjohn recently published two very informative posts on NAFLD/NASH that add a major additional factor to the equation: choline (6, 7). Choline is an essential nutrient that's required for the transport of fat out of the liver (8). NAFLD can be caused, and cured, simply by removing or adding dietary choline, and it appears to be dominant over other dietary factors including fat, sugar and alcohol. Apparently, certain researchers have been aware of this for some time, but it hasn't entered into the mainstream consciousness.

Could that be because the richest dietary sources are liver and eggs*? Choline is also found in smaller amounts in a variety of whole animal and plant foods. Most people don't get the officially recommended amount. From a recent review article (9):
Mean choline intakes for older children, men, women, and pregnant women are far below the adequate intake level established by the [Institute of Medicine]. Given the importance of choline in a wide range of critical functions in the human body, coupled with less-than-optimal intakes among the population, dietary guidance should be developed to encourage the intake of choline-rich foods.
I've dubbed beef liver the Most Nutritious Food in the World, Nature's Multivitamin, and I'll probably invent other titles for it in the future. Add yours to the comments.

Head over to Chris's blog and read about the classic studies he unearthed. And add The Daily Lipid to your RSS reader, because there's more interesting material to come!

The Sweet Truth about Liver and Egg Yolks
Does Choline Deficiency Contribute to Fatty Liver in Humans?

* For the brave: brain is actually the richest source of choline.

Sunday, November 28, 2010

HealthCorrelator for Excel 1.0 (HCE): Call for beta testers

This call is closed. Beta testing has been successfully completed. HealthCorrelator for Excel (HCE) is now publicly available for download and use on a free trial basis. For those users who decide to buy it after trying, licenses are available for individuals and organizations.

To download a free trial version – as well as get the User Manual, view demo YouTube videos, and download and try sample datasets – visit the web site.

Monday, November 22, 2010

Human traits are distributed along bell curves: You need to know yourself, and HCE can help

Most human traits (e.g., body fat percentage, blood pressure, propensity toward depression) are influenced by our genes; some more than others. The vast majority of traits are also influenced by environmental factors, the “nurture” part of the “nature-nurture” equation. Very few traits are “innate”, such as blood type.

This means that manipulating environmental factors, such as diet and lifestyle, can strongly influence how the traits are finally expressed in humans. But each individual tends to respond differently to diet and lifestyle changes, because each individual is unique in terms of his or her combination of “nature” and “nurture”. Even identical twins are different in that respect.

When plotted, traits that are influenced by our genes are distributed along a bell-shaped curve. For example, a trait like body fat percentage, when measured in a population of 1000 individuals, will yield a distribution of values that will look like a bell-shaped distribution. This type of distribution is also known in statistics as a “normal” distribution.

Why is that?

The additive effect of genes and the bell curve

The reason is purely mathematical. A measurable trait, like body fat percentage, is usually influenced by several genes. (Sometimes individual genes have a very marked effect, as in genes that “switch on or off” other genes.) Those genes appear at random in a population, and their various combinations spread in response to selection pressures. Selection pressures usually cause a narrowing of the bell-shaped curve distributions of traits in populations.

The genes interact with environmental influences, which also have a certain degree of randomness. The result is a massive combined randomness. It is this massive randomness that leads to the bell-curve distribution. The bell curve itself is not random at all, which is a fascinating aspect of this phenomenon. From “chaos” comes “order”. A bell curve is a well-defined curve that is associated with a function, the probability density function.

The underlying mathematical reason for the bell shape is the central limit theorem. The genes are combined in different individuals as combinations of alleles, where each allele is a variation (or mutation) of a gene. An allele set, for genes in different locations of the human DNA, forms a particular allele combination, called a genotype. The alleles combine their effects, usually in an additive fashion, to influence a trait.

Here is a simple illustration. Let us say one generates 1000 random variables, each storing 10 random values going from 0 to 1. Then the values stored in each of the 1000 random variables are added. This mimics the additive effect of 10 genes with random allele combinations. The result are numbers ranging from 1 to 10, in a population of 1000 individuals; each number is analogous to an allele combination. The resulting histogram, which plots the frequency of each allele combination (or genotype) in the population, is shown on the figure bellow. Each allele configuration will “push for” a particular trait range, making the trait distribution also have the same bell-shaped form.

The bell curve, research studies, and what they mean for you

Studies of the effects of diet and exercise on health variables usually report their results in terms of average responses in a group of participants. Frequently two groups are used, one control and one treatment. For example, in a diet-related study the control group may follow the Standard American Diet, and the treatment group may follow a low carbohydrate diet.

However, you are not the average person; the average person is an abstraction. Research on bell curve distributions tells us that there is about a 68 percentage chance that you will fall within a 1 standard deviation from the average, to the left or the right of the “middle” of the bell curve. Still, even a 0.5 standard deviation above the average is not the average. And, there is approximately a 32 percent chance that you will not be within the larger -1 to 1 standard deviation range. If this is the case, the average results reported may be close to irrelevant for you.

Average results reported in studies are a good starting point for people who are similar to the studies’ participants. But you need to generate your own data, with the goal of “knowing yourself through numbers” by progressively analyzing it. This is akin to building a “numeric diary”. It is not exactly an “N=1” experiment, as some like to say, because you can generate multiple data points (e.g., N=200) on how your body alone responds to diet and lifestyle changes over time.

HealthCorrelator for Excel (HCE)

I think I have finally been able to develop a software tool that can help people do that. I have been using it myself for years, initially as a prototype. You can see the results of my transformation on this post. The challenge for me was to generate a tool that was simple enough to use, and yet powerful enough to give people good insights on what is going on with their body.

The software tool is called HealthCorrelator for Excel (HCE). It runs on Excel, and generates coefficients of association (correlations, which range from -1 to 1) among variables and graphs at the click of a button.

This 5-minute YouTube video shows how the software works in general, and this 10-minute video goes into more detail on how the software can be used to manage a specific health variable. These two videos build on a very small sample dataset, and their focus is on HDL cholesterol management. Nevertheless, the software can be used in the management of just about any health-related variable – e.g., blood glucose, triglycerides, muscle strength, muscle mass, depression episodes etc.

You have to enter data about yourself, and then the software will generate coefficients of association and graphs at the click of a button. As you can see from the videos above, it is very simple. The interpretation of the results is straightforward in most cases, and a bit more complicated in a smaller number of cases. Some results will probably surprise users, and their doctors.

For example, a user who is a patient may be able to show to a doctor that, in the user’s specific case, a diet change influences a particular variable (e.g., triglycerides) much more strongly than a prescription drug or a supplement. More posts will be coming in the future on this blog about these and other related issues.

Saturday, November 20, 2010

Glucose Tolerance in Non-industrial Cultures


Glucose is the predominant blood sugar and one of the body's two main fuel sources (the other is fatty acids). Glucose, in one form or another, is also the main form of digestible dietary carbohydrate in nearly all human diets. Starch is made of long chains of glucose molecules, which are rapidly liberated and absorbed during digestion. Sucrose, or table sugar, is made of one glucose and one fructose molecule, which are separated before absorption.

Blood glucose is essential for life, but it can also be damaging if there is too much of it. Therefore, the body tries to keep it within a relatively tight range. Normal fasting glucose is roughly between 70 and 90 mg/dL*, but in the same individual it's usually within about 5 mg/dL on any given day. Sustained glucose above 160 mg/dL or so causes damage to multiple organ systems. Some people would put that number closer to 140 mg/dL.

The amount of glucose contained in a potato far exceeds the amount contained in the blood, so if all that glucose were to enter the blood at once, it would lead to a highly damaging blood glucose level. Fortunately, the body has a hormone designed to keep this from happening: insulin. Insulin tells cells to internalize glucose from the blood, and suppresses glucose release by the liver. It's released by the pancreas in response to eating carbohydrate, and protein to a lesser extent. The amount of insulin released is proportional to the amount of carbohydrate ingested, so that glucose entering the blood is cleared before it can accumulate.

Insulin doesn't clear all the glucose as it enters the bloodstream, however. Some of it does accumulate, leading to a spike in blood glucose. This usually doesn't exceed 130 mg/dL in a truly healthy person, and even if it approaches that level it's only briefly. However, diabetics have reduced insulin signaling, and eating a typical meal can cause their glucose to exceed 300 mg/dL due to reduced insulin action and/or insulin secretion. In affluent nations, this is typically due to type II diabetes, which begins as insulin resistance, a condition in which insulin is actually higher than normal but cells fail to respond to it.  The next step is the failure of insulin-secreting beta cells, which is what generally precipitates actual diabetes.

The precursor to diabetes is called glucose intolerance, or pre-diabetes. In someone with glucose intolerance, blood glucose after a typical meal will exceed that of a healthy person, but will not reach the diabetic range (a common definition of diabetes is 200 mg/dL or higher, 2 hours after ingesting 75g of glucose). Glucose tolerance refers to a person's ability to control blood glucose when challenged with dietary glucose, and can be used in some contexts as a useful predictor of diabetes risk and general metabolic health. Doctors use the oral glucose tolerance test (OGTT), which involves drinking 60-100g glucose and measuring blood glucose after one or two hours, to determine glucose tolerance.

Why do we care about glucose tolerance in non-industrial cultures?

One of the problems with modern medical research is that so many people in our culture are metabolically sick that it can be difficult to know if what we consider "normal" is really normal or healthy in the broader sense. Non-industrial cultures allow us to examine what the human metabolism is like in the absence of metabolic disease. I admit this rests on certain assumptions, particularly that these people aren't sick themselves. I don't think all non-industrial cultures are necessarily healthy, but I'm going to stick with those that research has shown have an exceptionally low prevalence of diabetes (by Western standards) and other "diseases of civilization" for the purposes of this post.

Here's the question I really want to answer in this post: do healthy non-industrial cultures with a very high carbohydrate intake have an excellent glucose tolerance, such that their blood glucose doesn't rise to a high level, or are they simply resistant to the damaging effects of high blood glucose?

The data

I'm going to start with an extreme example. In the 1960s, when it was fashionable to study non-industrial cultures, researchers investigated the diet and health of a culture in Tukisenta, in the highlands of Papua New Guinea. The eat practically nothing but sweet potatoes, and their typical daily fare is 94.6 percent carbohydrate. Whether or not you believe that exact number, their diet was clearly extraordinarily high in carbohydrate. They administered 100g OGTTs and measured blood glucose at one hour, which is a very stringent OGTT. They compared the results to those obtained in the 1965 Tecumseh study (US) obtained by the same method. Here's what they found (1):
Compared to Americans, in Tukisenta they had an extraordinary glucose tolerance at all ages. At one hour, their blood glucose was scarcely above normal fasting values, and glucose tolerance only decreased modestly with age. In contrast, in Americans over 50 years old, the average one-hour value was around 180 mg/dL!

Now let's take a look at the African Bantu in the Lobaye region of the Central African Republic. The Bantu are a large ethnic group who primarily subsist on a diverse array of starchy foods including grains, beans, plantains and root crops. One hour after a 100g OGTT, their blood glucose was 113 mg/dL, compared to 139 mg/dL in American controls (2). Those numbers are comparable to what investigators found in Tukisenta, and indicate an excellent glucose tolerance in the Bantu.

In South America, different investigators studied a group of native Americans in central Brazil that subsist primarily on cassava (a starchy root crop) and freshwater fish. Average blood glucose one hour after a 100g OGTT was 94 mg/dl, and only 2 out of 106 people tested had a reading over 160 mg/dL (both were older women) (Western Diseases: Their Emergence and Prevention, p. 149). Again, that indicates a phenomenal glucose tolerance by Western standards.

I have to conclude that high-carbohydrate non-industrial cultures probably don't experience damaging high blood glucose levels, because their glucose tolerance is up to the task of shuttling a huge amount of glucose out of the bloodstream before that happens.

Not so fast...

Now let's turn our attention to another study that may throw a wrench in the gears. A while back, I found a paper containing OGTT data for the !Kung San (also called the Bushmen), a hunter-gatherer group living in the Kalahari desert of Africa. I reported in an earlier post that they had a good glucose tolerance. When I revisited the paper recently, I realized I had misread it and in fact, their glucose tolerance was actually pretty poor.

Investigators administered a 50g OGTT, half what the other studies used. At one hour, the San had blood glucose readings of 169 mg/dL, compared to 142 mg/dL in Caucasian controls (3)! I suspect a 100g OGTT would have put them close to the diabetic range.

Wait a minute, these guys are hunter-gatherers living the ancestral lifestyle; aren't they supposed to be super healthy?? First of all, like many hunter-gatherer groups the San are very small people: the men in this study were only 46 kg (101 lbs).  The smaller you are, the more a given amount of carbohydrate will raise your blood glucose.  Also, while I was mulling this over, I recalled a discussion where non-diabetic people were discussing their 'diabetic' OGTT values while on a low-carbohydrate diet. Apparently, carbohydrate refeeding for a few days generally reverses this and allows a normal OGTT in most people. It turns out this effect has been known for the better part of a century.

So what were the San eating? The study was conducted in October of 1970. The San diet changes seasonally, however their main staple food is the mongongo nut, which is mostly fat and which is available year-round (according to The !Kung San: Men, Women and Work in a Foraging Society). Their carbohydrate intake is generally low by Western standards, and at times of the year it is very low. This varies by the availability of other foods, but they generally don't seem to relish the fibrous starchy root crops that are available in the area, as they mostly eat them when other food is scarce. Jean-Louis Tu has posted a nice analysis of the San diet on BeyondVeg (4). Here's a photo of a San man collecting mongongo nuts from The !Kung San: Men, Women and Work in a Foraging Society:

What did the authors of the OGTT study have to say about their diet? Acknowledging that prior carbohydrate intake may have played a role in the OGTT results of the San, they made the following remark:
a retrospective dietary history (M. J. Konner, personal communication, 1971) indicated that the [San], in fact, consumed fairly large amounts of carbohydrate-rich vegetable food during the week before testing.
However, the dietary history was not provided, nor has it been published, so we have no way to assess the statement's accuracy or what was meant by "fairly large amounts of carbohydrate-rich vegetable food." Given the fact that the San diet typically ranges from moderately low to very low in carbohydrate, I suspect they were not getting much carbohydrate as a percentage of calories. Looking at the nutritional value of the starchy root foods they typically eat in appendix D of The !Kung San: Men, Women and Work in a Foraging Society, they are fibrous and most contain a low concentration of starch compared to a potato for example. The investigators may have been misled by the volume of these foods eaten, not realizing that they are not as rich in carbohydrate as the starchy root crops they are more familiar with.

You can draw your own conclusions, but I think the high OGTT result of the San probably reflect a low habitual carbohydrate intake, and not pre-diabetes. I have a very hard time believing that this culture wasn't able to handle the moderate amount of carbohydrate in their diet effectively, as observers have never described diabetic complications among them.

Putting it all together

This brings me to my hypothesis. I think a healthy human body is extraordinarily flexible in its ability to adapt to a very broad range of carbohydrate intakes, and adjusts glucose tolerance accordingly to maintain carbohydrate handling in a healthy range. In the context of a healthy diet and lifestyle (from birth), I suspect that nearly anyone can adjust to a very high carbohydrate intake without getting dangerous blood glucose spikes. A low carbohydrate intake leads to impaired glucose handling and better fat handling, as one would expect. This can show up as impaired glucose tolerance or even 'diabetes' on an OGTT, but that does not necessarily reflect a pathological state in my opinion.

Every person is different based on lifestyle, diet, personal history and genetics. Not everyone in affluent nations has a good glucose tolerance, and some people will never be able to handle starch effectively under any circumstances. The best way to know how your body reacts to carbohydrate is to test your own post-meal blood glucose using a glucose meter. They are inexpensive and work well. For the most informative result, eat a relatively consistent amount of carbohydrate for a week to allow your body to adapt, then take a glucose measurement 1 and 2 hours after a meal. If you don't eat much carbohydrate, eating a potato might make you think you're diabetic, whereas after a week of adaptation you may find that a large potato does not spike your blood glucose beyond the healthy range.

Exercise is a powerful tool for combating glucose intolerance, as it increases the muscles' demand for glucose, causing them to transport it out of the blood greedily after a meal. Any exercise that depletes muscle glycogen should be effective.

* Assuming a typical carbohydrate intake. Chris Kresser recently argued, based on several studies, that true normal fasting glucose for a person eating a typical amount of carbohydrate is below 83 mg/dL. Low-carbohydrate eating may raise this number, but that doesn't necessarily indicate a pathological change. High-carbohydrate cultures such as the Kitavans, Aymara and New Guineans tend to have fasting values in the low 60s to low 70s. I suspect that a very high carbohydrate intake generally lowers fasting glucose in healthy people. That seems to be the case so far for Chris Voigt, on his diet of 20 potatoes a day. Stay tuned for an interview with Mr. Voigt in early December.

Tuesday, November 16, 2010

Impressions from the Wise Traditions Conference

I spent last weekend at the Weston A. Price Foundation Wise Traditions conference in King of Prussia, PA. Here are some highlights:

Spending time with several people in the diet-health community who I’ve been wanting to meet in person, including Chris Masterjohn, Melissa McEwen and John Durant. John and Melissa are the public face of the New York city paleo movement. The four of us spent most of the weekend together tossing around ideas and making merry. I’ve been corresponding with Chris quite a bit lately and we’ve been thinking through some important diet-health questions together. He is brimming with good ideas. I also got to meet Sally Fallon Morell, the founder and president of the WAPF.

Attending talks. The highlight was Chris Masterjohn’s talk “Heart Disease and Molecular Degeneration: the New Paradigm”, in which he described his compelling theory on oxidative damage and cardiovascular disease, among other things. You can read some of his earlier ideas on the subject here. Another talk I really enjoyed was by Anore Jones, who lived with an isolated Inuit group in Alaska for 23 years and ate a mostly traditional hunter-gatherer diet. The food and preparation techniques they used were really interesting, including various techniques for extracting fats and preserving meats, berries and greens by fermentation. Jones has published books on the subject that I suspect would be very interesting, including Nauriat Niginaqtuat, Plants that We Eat, and Iqaluich Niginaqtuat, Fish that We Eat. The latter is freely available on the web here.

I attended a speech by Joel Salatin, the prolific Virginia farmer, writer and agricultural innovator, which was fun. I enjoyed Sally Fallon Morell’s talk on US school lunches and the politics surrounding them. I also attended a talk on food politics by Judith McGeary, a farmer, attorney and and activist, in which she described the reasons to oppose or modify senate bill 510. The gist is that it will be disproportionately hard on small farmers who are already disfavored by current regulations, making high quality food more difficult to obtain, more expensive or even illegal. It’s designed to improve food safety by targeting sources of food-borne pathogens, but how much are we going to have to cripple national food quality and farmer livelihood to achieve this, and will it even be effective? I don’t remember which speaker said this quote, and I’m paraphrasing, but it stuck with me: “I just want to be able to eat the same food my grandmother ate.” In 2010, that’s already difficult to achieve. Will it be impossible in 2030?

Giving my own talk. I thought it went well, although attendance was not as high as I had hoped. The talk was titled “Kakana Dina: Diet and Health in the Pacific Islands”, and in it I examined the relationship between diet and health in Pacific island cultures with different diets and at various stages of modernization. I’ve covered some of this material on my blog, in my posts on Kitava, Tokelau and sweet potato eating cultures in New Guinea, but other material was new and I went into greater detail on food habits and preparation methods. I also dug up a number of historical photos dating back as far as the 1870s.

The food. All the meat was pasture-raised, organic and locally sourced if possible. There was raw pasture-raised cheese, milk and butter. There was wild-caught fish. There were many fermented foods, including sauerkraut, kombucha and sourdough bread. I was really impressed that they were able to put this together for an entire conference.

The vendors. There was an assortment of wholesome and traditional foods, particularly fermented foods, quality dairy and pastured meats. There was an entire farmer’s market on-site on Saturday, with a number of Mennonite vendors selling traditional foods. I bought a bottle of beet kvass, a traditional Russian drink used for flavor and medicine, which was much better than the beet kvass I’ve made myself in the past. Beets are a remarkable food, in part due to their high nitrate content—beet juice has been shown to reduce high blood pressure substantially, possibly by increasing the important signaling molecule nitric oxide. I got to meet Sandeep Agarwal and his family, owners of the company Pure Indian Foods, which domestically produces top-quality pasture-fed ghee (Indian-style clarified butter). They now make tasty spiced ghee in addition to the plain flavor. Sandeep and family donated ghee for the big dinner on Saturday, which was used to cook delicious wild-caught salmon steaks donated by Vital Choice.

There were some elements of the conference that were not to my taste. But overall I’m glad I was able to go, meet some interesting people, give my talk and learn a thing or two.

Monday, November 15, 2010

Your mind as an anabolic steroid

The figure below, taken from Wilmore et al. (2007), is based on a classic 1972 study conducted by Ariel and Saville. The study demonstrated the existence of what is referred to in exercise physiology as the “placebo effect on muscular strength gains”. The study had two stages. In the first stage, fifteen male university athletes completed a 7-week strength training program. Gains in strength occurred during this period, but were generally small as these were trained athletes.

In the second stage the same participants completed a 4-week strength training program, very much like the previous one (in the first stage). The difference was that some of them took placebos they believed to be anabolic steroids. Significantly greater gains in strength occurred during this second stage for those individuals, even though this stage was shorter in duration (4 weeks). The participants in this classic study increased their strength gains due to one main reason. They strongly believed it would happen.

Again, these were trained athletes; see the maximum weights lifted on the left, which are not in pounds but kilograms. For trained athletes, gains in strength are usually associated with gains in muscle mass. The gains may not look like much, and seem to be mostly in movements involving big muscle groups. Still, if you look carefully, you will notice that the bench press gain is of around 10-15 kg. This is a gain of 22-33 lbs, in a little less than one month!

This classic study has several implications. One is that if someone tells you that a useless supplement will lead to gains from strength training, and you believe that, maybe the gains will indeed happen. This study also provides indirect evidence that “psyching yourself up” for each strength training session may indeed be very useful, as many serious bodybuilders do. It is also reasonable to infer from this study that if you believe that you will not achieve gains from strength training, that belief may become reality.

As a side note, androgenic-anabolic steroids, better known as “anabolic steroids” or simply “steroids”, are synthetic derivatives of the hormone testosterone. Testosterone is present in males and females, but it is usually referred to as a male hormone because it is found in much higher concentrations in males than females.

Steroids have many negative side effects, particularly when taken in large quantities and for long periods of time. They tend to work only when taken in doses above a certain threshold (Wilmore et al., 2007); results below that threshold may actually be placebo effects. The effective thresholds for steroids tend to be high enough to lead to negative health side effects for most people. Still, they are used by bodybuilders as an effective aid to muscle gain, because they do lead to significant muscle gain in high doses. Adding to the negative side effects, steroids do not usually prevent fat gain.


Ariel, G., & Saville, W. (1972). Anabolic steroids: The physiological effects of placebos. Medicine and Science in Sports and Exercise, 4(2), 124-126.

Wilmore, J.H., Costill, D.L., & Kenney, W.L. (2007). Physiology of sport and exercise. Champaign, IL: Human Kinetics.

Tuesday, November 9, 2010

The Twinkie Diet for Fat Loss

The Experiment

I've received several e-mails from readers about a recent experiment by nutrition professor Mark Haub at Kansas State university (thanks to Josh and others). He ate a calorie-restricted diet in which 2/3 of his calories came from junk food: Twinkies, Hostess and Little Debbie cakes, Dorito corn chips and sweetened cereals (1). On this calorie-restricted junk food diet (800 calorie/day deficit), he lost 27 pounds in two months.

Therefore, junk food doesn't cause fat gain and the only thing that determines body fatness is how much you eat and exercise. Right?


Let's start with a few things most people can agree on. If you don't eat any food at all, you will lose fat mass. If you voluntarily force-feed yourself with a large excess of food, you will gain fat mass, whether the excess comes from carbohydrate or fat (2). So calories obviously have something to do with fat mass.

But of course, the situation is much more subtle in real life. Since a pound of body fat contains roughly 3,500 calories, eating an excess of 80 calories per day (1 piece of toast) should lead to a weight gain of 8 lbs of fat per year. Conversely, if you're distracted and forget to eat your toast, you should lose 8 lbs of fat per year, which would eventually be dangerous for a lean person. That's why we all record every crumb of food we eat, determine its exact calorie content, and match that intake precisely with our energy expenditure to maintain a stable weight.

Oh wait, we don't do that? Then how do so many people maintain a stable weight over years and decades? And how do wild animals maintain a stable body fat percentage (except when preparing for hibernation) even in the face of food surpluses? How do lab rats and mice fed a whole food diet maintain a stable body fat percentage in the face of literally unlimited food, when they're in a small cage with practically nothing to do but eat?

The answer is that the body isn't stupid. Over hundreds of millions of years, we've evolved sophisticated systems that maintain "energy homeostasis". In other words, these systems act to regulate fat mass and keep it within the optimal range. The evolutionary pressures operating here are obvious: too little fat mass, and an organism will be susceptible to starvation; too much, and an organism will be less agile and less efficient at locomotion and reproduction. Energy homeostasis is such a basic part of survival that even the simplest organisms regulate it.

Not only is it clear that we have an energy homeostasis system, we even know a thing or two about how it works. Early studies showed that lesioning a part of the brain called the ventromedial hypothalamus causes massive obesity (3; this is also true in humans, when a disruption results from cancer). Investigators also discovered several genetic mutations in rats and mice that result in massive obesity*. Decades-long research eventually demonstrated that these models have something in common: they all interfere with an energy homeostasis circuit that passes information about fat mass to the hypothalamus via the hormone leptin.

The leptin system is a classic negative feedback loop: the more fat mass accumulates, the more leptin is produced. The more leptin is produced, the more the hypothalamus activates programs to reduce hunger and increase energy expenditure, which continues until fat mass is back in the optimal range. Conversely, low fat mass and low leptin lead to increased hunger and energy conservation by this same pathway**.

So if genetic mutants can become massively obese, I guess that argues against the idea that voluntary food intake and energy expenditure are the only determinants of fat mass. But a skeptic might point out that these are extreme cases, and such mutations are so rare in humans that the analogy is irrelevant.

Let's dig deeper. There are many studies in which rodents are made obese using industrial high-fat diets made from refined ingredients. The rats eat more calories (at least in the beginning), and gain fat rapidly. No big surprise there. But what may come as a surprise to the calorie counters is that rodents on these diets gain body fat even if their calorie intake is matched precisely to lean rodents eating a whole food diet (4, 5, 6). In fact, they sometimes gain almost as much fat as rodents who are allowed to eat all the industrial food they want. This has been demonstrated repeatedly.

How is this possible? The answer is that the calorie-matched rats reduce their energy expenditure to a greater degree than those that are allowed free access to food. The most logical explanation for this behavior is that the "set point" of the energy homeostasis system has changed. The industrial diet causes the rodents' bodies to "want" to accumulate more fat, therefore they will accomplish that by any means necessary, whether it means eating more, or if that's not possible, expending less energy. This shows that a poor diet can, in principle, dysregulate the system that controls energy homeostasis.

Well, then why did Dr. Haub's diet allow him to lose weight? The body can only maintain body composition in the face of a calorie deficit up to a certain point. After that, it has no choice but to lower fat mass. It will do so reluctantly, at the same time increasing hunger, and reducing lean mass***, muscular strength and energy dedicated to tissue repair and immune function. However, I hope everyone can agree that a sufficient calorie deficit can lead to fat loss regardless of what kind of food is eaten. Dr. Haub's 800 calorie deficit qualifies. I think only a very small percentage of people are capable of maintaining that kind of calorie deficit for more than a few months, because it is mentally and physically difficult to fight against what the hypothalamus has decided is in your best interest.

My hypothesis is that, in many people, industrial food and an unnatural lifestyle lead to gradual fat gain by dysregulating the energy homeostasis system. This "breaks" the system that's designed to automatically keep our fat mass in the optimal range by regulating energy intake, energy expenditure and the relative partitioning of energy resources between lean and fat tissue. This system is not under our conscious control, and it has nothing to do with willpower.

I suspect that if you put a group of children on this junk food diet for many years, and compared them to a group of children on a healthy diet, the junk food group would end up fatter as adults. This would be true if neither group paid any attention to calories, and perhaps even if calorie intake were identical in the two groups (as in the rodent example). The result of Dr. Haub's experiment does not contradict that hypothesis.

So do calories matter? Yes, but in a healthy person, all the math is done automatically by the hypothalamus and energy balance requires no conscious effort. In 2010, many people have already accumulated excess fat mass. How that may be sustainably lost is another question entirely, and a more challenging one in my opinion. As they say, an ounce of prevention is worth a pound of cure. There are many possible strategies, with varying degrees of efficacy that depend highly on individual differences, but I think overall the question is still open. I discussed some of my thoughts in a recent series on body fat regulation (7, 8, 9, 10, 11).

* ob/ob and db/db mice. Zucker and Koletsky rats. Equivalent mutations in humans also result in obesity.

** Via an increase in muscular efficiency and perhaps a decrease in basal metabolism. Thyroid hormone activity drops.

*** Loss of muscle, bone and connective tissue can be compensated for by strength training during calorie restriction. Presumed loss of other non-adipose tissues (liver, kidney, brain, etc.) is probably not affected by strength training.

Monday, November 8, 2010

High-heat cooking will AGE you, if you eat food deep-fried with industrial vegetable oils

As I said before on this blog, I am yet to be convinced that grilled meat is truly unhealthy in the absence of leaky gut problems. I am referring here to high heat cooking-induced Maillard reactions (browning) and the resulting advanced glycation endproducts (AGEs). Whenever you cook a food in high heat, to the point of browning it, you generate a Maillard reaction. Searing and roasting meat usually leads to that.

Elevated levels of serum AGEs presumably accelerate the aging process in humans. This is supported by research with uncontrolled diabetics, who seem to have elevated levels of serum AGEs. In fact, a widely used measure in the treatment of diabetes, the HbA1c (or percentage of glycated hemoglobin), is actually a measure of endogenous AGE formation. (Endogenous = generated by our own bodies.)

Still, evidence that a person with an uncompromised gut can cause serum levels of AGEs to go up significantly by eating AGEs is weak, and evidence that any related serum AGE increases lead the average person to develop health problems is pretty much nonexistent. The human body can handle AGEs, as long as their concentration is not too high. We cannot forget that a healthy HbA1c in humans is about 5 percent; meaning that AGEs are created and dealt with by our bodies. A healthy HbA1c in humans is not 0 percent.

Thanks again to Justin for sending me the full text version of the Birlouez-Aragon et al. (2010) article, which is partially reviewed here. See this post and the comments under it for some background on this discussion. The article is unequivocally titled: “A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases.”

This article is recent, and has already been cited by news agencies and bloggers as providing “definitive” evidence that high-heat cooking is bad for one’s health. Interestingly, quite a few of those citations are in connection with high-heat cooking of meat, which is not even the focus of the article.

In fact, the Birlouez-Aragon et al. (2010) article provides no evidence that high-heat cooking of meat leads to AGEing in humans. If anything, the article points at the use of industrial vegetable oils for cooking as the main problem. And we know already that industrial vegetable oils are not healthy, whether you cook with them or drink them cold by the tablespoon.

But there are a number of good things about this article. For example, the authors summarize past research on AGEs. They focus on MRPs, which are “Maillard reaction products”. One of the summary statements supports what I have said on this blog before:

"The few human intervention trials […] that reported on health effects of dietary MRPs have all focused on patients with diabetes or renal failure."

That is, there is no evidence from human studies that dietary AGEs cause health problems outside the context of preexisting conditions that themselves seem to be associated with endogenous AGE production. To that I would add that gut permeability may also be a problem, as in celiacs ingesting large amounts of AGEs.

As you can see from the quote below, the authors decided to focus their investigation on a particular type of AGE, namely CML or carboxymethyllysine.

"...we decided to specifically quantify CML, as a well-accepted MRP indicator ..."

As I noted in my comments under this post (the oven roasted pork tenderloin post), one particular type of diet seems to lead to high serum CML levels – a vegetarian diet.

So let us see what the authors studied:

"... we conducted a randomized, crossover, intervention trial to clarify whether a habitual diet containing high-heat-treated foods, such as deep-fried potatoes, cookies, brown crusted bread, or fried meat, could promote risk factors of type 2 diabetes or cardiovascular diseases in healthy people."

Well, “deep-fried potatoes” is a red flag, don’t you think? They don’t say what oil was used for deep-frying, but I bet it was not coconut or olive oil. Cheap industrial vegetable oils (corn, safflower etc.) are the ones normally used (and re-used) for deep-frying. This is in part because these oils are cheap, and in part because they have high “smoke points” (the temperature at which the oil begins to generate smoke).

Let us see what else the authors say about the dietary conditions they compared:

"The STD was prepared by using conventional techniques such as grilling, frying, and roasting and contained industrial food known to be highly cooked, such as extruded corn flakes, coffee, dry cookies, and well-baked bread with brown crust. In contrast, the STMD comprised some raw food and foods that were cooked with steam techniques only. In addition, convenience products were chosen according to the minimal process applied (ie, steamed corn flakes, tea, sponge cakes, and mildly baked bread) ..."

The STD diet was the one with high-heat preparation of foods; in the STMD diet the foods were all steam-cooked at relatively low temperatures. Clearly these diets were mostly of plant-based foods, and of the unhealthy kind!

The following quote, from the results, pretty much tells us that the high omega-6 content of industrial oils used for deep frying was likely to be a major confounder, if not the main culprit:

"... substantial differences in the plasma fatty acid profile with higher plasma concentrations of long-chain omega-3 fatty acids […] and lower concentrations of omega-6 fatty acids […] were analyzed in the STMD group compared with in the STD group."

That is, the high-heat cooking group had higher plasma concentrations of omega-6 fats, which is what you would expect from a group consuming a large amount of industrial vegetable oils. One single tablespoon per day is already a large amount; these folks were probably consuming more than that.

Perhaps a better title for this study would have been: “A diet based on foods deep-fried in industrial vegetable oils promotes risk factors for diabetes mellitus and cardiovascular diseases.”

This study doesn’t even get close to indicting charred meat as a major source of serum AGEs. But it is not an exception among studies that many claim to do so.


H Birlouez-Aragon, I., Saavedra, G., Tessier, F.J., Galinier, A., Ait-Ameur, L., Lacoste, F., Niamba, C.-N., Alt, N., Somoza, V., & Lecerf, J.-M. (2010). A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases. The American Journal of Clinical Nutrition, 91(5), 1220-1226.

Friday, November 5, 2010

Observations from France

I recently got back from a trip to the UK and France visiting family and friends. It was great to see everyone, eat great food and even do some unexpected foraging (chestnuts, mushrooms, walnuts, blackberries). French people are in better general health than most industrialized nations. The obesity, diabetes and heart disease rates are all considerably lower than in the US, although still much higher than in non-industrial cultures. Here are a few of my observations about French food:

  1. The French diet generally contains a lot of fat, mostly from traditional animal sources such as dairy and pork fat. Industrial seed oils have crept into the diet over the course of the 20th century, although not to the same degree as in most affluent nations. People seem to think that eating a lot of fat is unhealthy, particularly the younger generation, but they do it anyway. I had dinner with my family at a traditional restaurant in Lyon (a "bouchon Lyonnais" called Stepharo) last week. Before we ordered, they immediately brought out crispy fried chunks of pork skin and fat (I'm not claiming this is healthy!). The entree was a salad: a bed of lettuce piled high with chicken livers, herring, and "pig's feet". The pigs feet were essentially gobs of pork fat. It was a very good meal that I'll continue describing later in the post. I think it's worth pointing out that Lyon is in Southern France. Is this the "Mediterranean diet"?
  2. French people eat organs. Yes, they never got the memo that muscle meat is the only edible tissue. A typical butcher or even grocery store will have liver, tripe, kidney and blood sausage on full display next to the meat. If you want to make a French person angry, try selling them a chicken or a rabbit without the liver, gizzard and heart. The main course at Stepharo was a large "andouilette", or tripe sausage, baked in mustard sauce. This was a typical traditional restaurant, not a hangout for gastronauts.
  3. French people fiercely defend the quality of their food. Have you heard of the abbreviation AOC? It stands for "Appellation d’Origine Contrôlée", or controlled designation of origin. A familiar example is Champagne, which has the AOC label. You can't call your sparkling wine Champagne unless it comes from the region Champagne. However, that's only half the story. AOC also designates a specific, traditional production method, in this case called the "méthode champenoise." The AOC label can apply to a variety of food products, including wine, butter, cheese, honey, mustard and seafood, and is a guarantee of quality and tradition. 44 cheeses currently have the AOC designation, and these are commonly available in markets and grocery stores throughout the country (1). These are not fancy products that only the wealthy can afford-- many of them are quality foods that are accessible to nearly everyone. AOC defines many aspects of cheese production, often requiring a minimum amount of pasture time and specifying livestock breeds. The US has a few products that are regulated in a similar fashion, such as Bourbon whiskey, but generally we are far behind in assuring food quality and transparency.
  4. French people cook. There is less outsourcing of food processing in France, for several reasons. One reason is that restaurants are generally expensive. That trend is changing however.
I don't think the French diet is optimal by any means. They eat a lot of white flour, some sugar, seed oils and other processed foods. But I do think the French diet has many good qualities, and it certainly poses a number of problems for the mainstream concept of healthy food. Hence the "French paradox."

Monday, November 1, 2010

Amino acids in skeletal muscle: Are protein supplements as good as advertised?

When protein-rich foods, like meat, are ingested they are first broken down into peptides through digestion. As digestion continues, peptides are broken down into amino acids, which then enter circulation, becoming part of the blood plasma. They are then either incorporated into various tissues, such as skeletal muscle, or used for other purposes (e.g., oxidation and glucose generation). The table below shows the amino acid composition of blood plasma and skeletal muscle. It was taken from Brooks et al. (2005), and published originally in a classic 1974 article by Bergström and colleagues. Essential amino acids, shown at the bottom of the table, are those that have to be consumed through the diet. The human body cannot synthesize them. (Tyrosine is essential in children; in adults tryptophan is essential.)

The data is from 18 young and healthy individuals (16 males and 2 females) after an overnight fast. The gradient is a measure that contrasts the concentration of an amino acid in muscle against its concentration in blood plasma. Amino acids are transported into muscle cells by amino acid transporters, such as the vesicular glutamate transporter 1 (VGLUT1). Transporters exist because without them a substance’s gradient higher or lower than 1 would induce diffusion through cell membranes; that is, without transporters anything would enter or leave cells.

Research suggests that muscle uptake of amino acids is positively correlated with the concentration of the amino acids in plasma (as well as the level of activity of transporters) and that this effect is negatively moderated by the gradient. This is especially true after strength training, when protein synthesis is greatly enhanced. In other words, if the plasma concentration of an amino acid such as alanine is high, muscle uptake will be increased (with the proper stimulus; e.g., strength training). But if a lot of alanine is already present in muscle cells when compared to plasma (which is normally the case, since alanine’s 7.3 gradient is relatively high), more plasma alanine will be needed to increase muscle uptake.

The amino acid makeup of skeletal muscle is a product of evolutionary forces, which largely operated on our Paleolithic ancestors. Those ancestors obtained their protein primarily from meat, eggs, vegetables, fruits, and nuts. Vegetables and fruits today are generally poor sources of protein; that was probably the case in the Paleolithic as well. Also, only when very young our Paleolithic ancestors obtained their protein from human milk. It is very unlikely that they drank the milk of other animals. Still, many people today possess genetic adaptations that enable them to consume milk (and dairy products in general) effectively due to a more recent (Neolithic) ancestral heritage. A food-related trait can evolve very fast – e.g., in a few hundred years.

One implication of all of this is that protein supplements in general may not be better sources of amino acids than natural protein-rich foods, such as meat or eggs. Supplements may provide more of certain amino acids than others sources, but given the amino acid makeup of skeletal muscle, a supplemental overload of a particular amino acid is unlikely to be particularly healthy. That overload may induce an unnatural increase in amino acid oxidation, or an abnormal generation of glucose through gluconeogenesis. Depending on one’s overall diet, those may in turn lead to elevated blood glucose levels and/or a caloric surplus. The final outcome may be body fat gain.

Another implication is that man-made foods that claim to be high in protein, and that are thus advertised as muscle growth supplements, may actually be poor sources of those amino acids whose concentration in muscle are highest. (You need to check the label for the amino acid composition, and trust the manufacturer.) Moreover, if they are sources of nonessential amino acids, they may overload your body if you consume a balanced diet. Interestingly, nonessential amino acids are synthesized from carbon sources. A good source of carbon is glucose.

Among the essential amino acids are a group called branched-chain amino acids (BCAA) – leucine, isoleucine, and valine. Much is made of these amino acids, but their concentration in muscle in adults is not that high. That is, they do not contribute significantly as building blocks to protein synthesis in skeletal muscle. What makes BCAAs somewhat unique is that they are highly ketogenic, and somewhat glucogenic (via gluconeogenesis). They also lead to insulin spikes. Ingestion of BCAAs increases the blood concentration of two of the three human ketone bodies (acetone and acetoacetate). Ketosis is both protein and glycogen sparing (but gluconeogenesis is not), which is among the reasons why ketosis is significantly induced by exercise (blood ketones concentration is much more elevated after exercise than after a 20 h fast). This is probably why some exercise physiologists and personal trainers recommend consumption of BCAAs immediately prior to or during anaerobic exercise.

Why do carnivores often consume prey animals whole? (Consumption of eggs is not the same, but similar, because an egg is the starting point for the development of a whole animal.) Carnivores consume prey animals whole arguably because prey animals have those tissues (muscle, organ etc. tissues) that carnivores also have, in roughly the same amounts. Prey animals that are herbivores do all the work of converting their own prey (plants) to tissues that they share with carnivores. Carnivores benefit from that work, paying back herbivores by placing selective pressures on them that are health-promoting at the population level. (Carnivores usually target those prey animals that show signs of weakness or disease.)

Supplements would be truly natural if they provided nutrients that mimicked eating an animal whole. Most supplements do not get even close to doing that; and this includes protein supplements.


Brooks, G.A., Fahey, T.D., & Baldwin, K.M. (2005). Exercise physiology: Human bioenergetics and its applications. Boston, MA: McGraw-Hill.