The Body Fat Setpoint

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

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

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

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

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

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

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

OK, so why do we care?

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

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

This raises two questions:

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

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


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

Tropical Plant Fats: Palm Oil

A Fatal Case of Nutritionism

The concept of 'nutritionism' was developed by Dr. Gyorgy Scrinis and popularized by the food writer Michael Pollan. It states that the health value of a food can be guessed by the sum of the nutrients it contains. Pollan argues, I think rightfully, that nutritionism is a reductionist philosophy that assumes we know more about food composition and the human body than we actually do. You can find varying degrees of this philosophy in most mainstream discussions of diet and health*.

One conspicuous way nutritionism manifests is in the idea that saturated fat is harmful. Any fat rich in saturated fatty acids is typically assumed to be unhealthy, regardless of its other constituents. There is also apparently no need to directly test that assumption, or even to look through the literature to see if the assumption has already been tested. In this manner, 'saturated' tropical plant fats such as palm oil and coconut oil have been labeled unhealthy, despite essentially no direct evidence that they're harmful. As we'll see, there is actually quite a bit of evidence, both indirect and direct, that their unrefined forms are not harmful and perhaps even beneficial.

Palm Oil and Heart Disease

Long-time readers may recall a post I wrote a while back titled Ischemic Heart Attacks: Disease of Civilization (1). I described a study from 1964 in which investigators looked for signs of heart attacks in thousands of consecutive autopsies in the US and Africa, among other places. They found virtually none in hearts from Nigeria and Uganda (3 non-fatal among more than 4,500 hearts), while Americans of the same age had very high rates (up to 1/3 of hearts).

What do they eat in Nigeria? Typical Nigerian food involves home-processed grains, starchy root vegetables, beans, fruit, vegetables, peanuts, red palm oil, and a bit of dairy, fish and meat**. The oil palm Elaeis guineensis originated in West Africa and remains one of the main dietary fats throughout the region.

To extract the oil, palm fruit are steamed, and the oily flesh is removed and pressed. It's similar to olive oil in that it is extracted gently from an oil-rich fruit, rather than harshly from an oil-poor seed (e.g., corn or soy oil). The oil that results is deep red and is perhaps the most nutrient-rich fat on the planet. The red color comes from carotenes, but red palm oil also contains a large amount of vitamin E (mostly tocotrienols), vitamin K1, coenzyme Q10 and assorted other fat-soluble constituents. This adds up to a very high concentration of fat-soluble antioxidants, which are needed to protect the fat from rancidity in hot and sunny West Africa. Some of these make it into the body when it's ingested, where they appear to protect the body's own fats from oxidation.

Mainstream nutrition authorities state that palm oil should be avoided due to the fact that it's approximately half saturated. This is actually one of the main reasons palm oil was replaced by hydrogenated seed oils in the processed food industry. Saturated fat raises blood cholesterol, which increases the risk of heart disease. Doesn't it? Let's see what the studies have to say.

Most of the studies were done using refined palm oil, unfortunately. Besides only being relevant to processed foods, this method also introduces a new variable because palm oil can be refined and oxidized to varying degrees. However, a few studies were done with red palm oil, and one even compared it to refined palm oil. Dr. Suzanna Scholtz and colleagues put 59 volunteers on diets predominating in sunflower oil, refined palm oil or red palm oil for 4 weeks. LDL cholesterol was not different between the sunflower oil and red palm oil groups, however the red palm oil group saw a significant increase in HDL. LDL and HDL both increased in the refined palm oil group relative to the sunflower oil group (2).

Although the evidence is conflicting, most studies have not been able to replicate the finding that refined palm oil increases LDL relative to less saturated oils (3, 4). This is consistent with studies in a variety of species showing that saturated fat generally doesn't raise LDL compared to monounsaturated fat in the long term, unless a large amount of purified cholesterol is added to the diet (5).

Investigators have also explored the ability of palm oil to promote atherosclerosis, or hardening and thickening of the arteries, in animals. Not only does palm oil not promote atherosclerosis relative to monounsaturated fats (e.g., olive oil), but in its unrefined state it actually protects against atherosclerosis (6, 7). A study in humans hinted at a possible explanation: compared to a monounsaturated oil***, palm oil greatly reduced oxidized LDL (8). As a matter of fact, I've never seen a dietary intervention reduce oxLDL to that degree (69%). oxLDL is a major risk factor for cardiovascular disease, and a much better predictor of risk than the typically measured LDL cholesterol (9). The paper didn't state whether or not the palm oil was refined. I suspect it was lightly refined, but still rich in vitamin E and CoQ10.

As I discussed in my recent interview with Jimmy Moore, atherosclerosis is only one factor in heart attack risk (10). Several other factors are also major determinants of risk: clotting tendency, plaque stability, and susceptibility to arrhythmia. Another factor that I haven't discussed is how resistant the heart muscle is to hypoxia, or loss of oxygen. If the coronary arteries are temporarily blocked-- a frequent occurrence in modern people-- the heart muscle can be damaged. Dietary factors determine the degree of damage that results. For example, in rodents, nitrites derived from green vegetables protect the heart from hypoxia damage (11). It turns out that red palm oil is also protective (12, 13). Red palm oil also protects against high blood pressure in rats, an effect attributed to its ability to reduce oxidative stress (14, 15).

Together, the evidence suggests that red palm oil does not contribute to heart disease risk, and in fact is likely to be protective. The benefits of red palm oil probably come mostly from its minor constituents, i.e. the substances besides its fatty acids. Several studies have shown that a red palm oil extract called palmvitee lowers serum lipids in humans (16, 17). The minor constituents are precisely what are removed during the refining process.

Palm Oil and the Immune System

Red palm oil also has beneficial effects on the immune system in rodents. It protects against bacterial infection when compared with soybean oil (18). It also protects against certain cancers, compared to other oils (19, 20). This may be in part due to its lower content of omega-6 linoleic acid (roughly 10%), and minor constituents.

The Verdict

Yet again, nutritionism has gotten itself into trouble by underestimating the biological complexity of a whole food. Rather than being harmful to human health, red palm oil, an ancient and delicious food, is likely to be protective. It's also one of the cheapest oils available worldwide, due to the oil palm's high productivity. It has a good shelf life and does not require refrigeration. Its strong, savory flavor goes well in stews, particularly meat stews. It isn't available in most grocery stores, but you can find it on the internet. Make sure not to confuse it with refined palm oil or palm kernel oil.


* The approach that Pollan and I favor is a simpler, more empirical one: eat foods that have successfully sustained healthy cultures.

** Some Nigerians are also pastoralists that subsist primarily on dairy.

*** High oleic sunflower oil, from a type of sunflower bred to be high in monounsaturated fat and low in linoleic acid. I think it's probably among the least harmful refined oils. I use it sometimes to make mayonnaise. It's often available in grocery stores, just check the label.

Gluten-Free January Survey Data, Part II: Health Effects of a Gluten-Free Diet

GFJ participants chose between three diet styles: a simple gluten-free diet; a "paleo light" diet diet that eliminated sugar and industrial seed (vegetable) oils in addition to gluten; and a "paleo full monty" diet that only included categories of food that would have been available to our pre-agricultural ancestors. The data in this post represent the simple gluten-free diet group, and do not represent the other two, which I'll analyze separately.

To get the data I'll be presenting below, first I excluded participants who stated on the survey that they did not adhere to the diet. Next, I excluded participants who were gluten-free before January, because they would presumably not have experienced a change from continuing to avoid gluten. That left us with 53 participants.

For each of these graphs, the vertical axis represents the number of participants in each category. They won't necessarily add up to 53, for several reasons. The most common reason is that for the questions asking about changes in health conditions, I didn't include responses from people who didn't have the condition in question at baseline because there was nothing to change.

Question #1: What is your overall opinion of the effect of gluten free January on you?

Participants had a very positive experience with the gluten-free diet. Not one person reported a negative overall experience.

Question #2: Did you note a weight change at the end of gluten free January?

And here are the data for people who described themselves as overweight at baseline:

Two-thirds of people who were overweight at baseline lost weight, and only one person out of 37 gained weight. That is striking. A number of people didn't weigh themselves, which is why the numbers only add up to 37.

Question #3: Before January 2011, did you have a problem with intestinal transit (frequent constipation or diarrhea)? If so, did your symptoms change during the month of January?


Responses are heavily weighted toward improvement, although there were a few instances where transit worsened. Transit problems are one of the most common manifestations of gluten sensitivity.

Question #4: Before January 2011, did you have frequent digestive discomfort (pain, bloating, etc.)? If so, did your symptoms change during the month of January?


Digestive discomfort was common, and the gluten-free diet improved it in nearly everyone who had it at baseline. I find this really impressive.

Question #5: Before January 2011, did you have acid reflux? If so, did your symptoms change during the month of January?

Acid reflux responded well to a gluten-free diet.

Question #6: Before January 2011, did you have a problem with tiredness/lethargy? If so, did your symptoms change during the month of January?
Lethargy was common and generally improved in people who avoided gluten. This doesn't surprise me at all. The recent controlled gluten study in irritable bowel syndrome patients found that lethargy was the most reliable consequence of eating gluten that they measured (1, 2). That has also been my personal experience.

Question #7: Before January 2011, did you have a problem with anxiety? If so, did your symptoms change during the month of January?

Anxiety tended to improve in most participants who started with it.

Question #8: Before January 2011, did you have a problem with an autoimmune or inflammatory condition? If so, did your symptoms change during the month of January?

Autoimmune and inflammatory conditions tended to improve in the gluten-free group, although one person experienced a worsening of symptoms.

Question #9: If you ate gluten again or did a gluten challenge after gluten free January, what was the effect?

Just under half of participants experienced moderate or significant negative symptoms when they re-introduced gluten at the end of the month. Two people felt better after re-introducing gluten.


Conclusion

I find these results striking. Participants overwhelmingly improved in every health category we measured. Although the data may have been somewhat biased due to the 53% response rate, it's indisputable that a large number of participants, probably the majority, benefited from avoiding gluten for a month. At some point, we're going to compile some of the comments people left in the survey, which were overwhelmingly positive. Here's a typical comment in response to the question " In your own words, how would you describe your January 2011 experience" (used with permission):

Amazing! I would recommend the experiment to anyone. I felt completely more alert, and less bloated. When I ate some gluten at the close of the experiment, I felt gross, bloated, and lethargic.

I think it's worth mentioning that some participants also eliminated other starches, particularly refined starches. Judging by the comments, the diet was probably lower in carbohydrate for a number of participants. We may try to assess that next year.

Gluten-Free January Survey Data, Part I: Demographics and Limitations

Thanks to Matt Lentzner for organizing Gluten-Free January, and everyone who participated and completed the survey, we have a nice data set illustrating what happens when a group of people stop eating gluten for a month. Janine Jagger, Matt and I have been busy analyzing the data, and I'm ready to begin sharing our findings.

GFJ had over 500 participants, 527 of which received the survey and 279 of which completed the survey at the end of the month. Of those who received the survey, 53 percent completed it. I think these are respectable numbers for a survey of this nature, and it reflects the conscientious nature of the people who participated in GFJ.

Demographics

Although respondents were primarily from the United States, I'm happy to say that the data represent 18 different nationalities:

Respondents represented a diversity of ages, the largest group being 30-39 years old, with similar numbers in the 20-29 and 40-49 year groups.
Respondents were just under 2/3 women.

Respondents represented a variety of weights, but the sample was biased toward lean people, in comparison with the general population. There were not many obese participants.
Overall, I was pleased to see that the demographics were quite diverse, particularly in the age and gender categories.

Limitations

There are a few caveats to keep in mind when interpreting the survey results:

1. GFJ participants do not represent a random cross-section of the population at large. They represent primarily health-conscious individuals who were motivated enough to make a substantial dietary change. In addition, many of the people who participated probably did so because they already suspected they had a problem with gluten.
   
2. The survey response rate was 53%. Although I think that's a reasonable number considering the circumstances, it leaves open the possibility that survey responders differ from non-responders. It's conceivable that participants with better adherence and better outcomes were more likely to complete the survey than those who did not adhere to the diet or had neutral or unfavorable outcomes, despite our efforts to encourage everyone to complete the survey regardless of adherence or outcome. So the results could be biased toward positive outcomes, meaning that we will need to see a strong effect for it to be believable.
   
3. This was a non-blinded diet trial without a control group. There's no way to know how much of the effect was due to avoiding gluten per se, how much was due to overall changes in diet patterns, and how much was a placebo effect.
   

With that in mind, what can we take from the survey data? I feel that we can use it to answer the following question: "what is likely to happen when a motivated, health-conscious person decides to avoid gluten for a month?" And I think we can also use it to generate (but not test) hypotheses about the effects of eating gluten on the general population.

Magnesium and Vitamin D Metabolism

Ted Hutchinson posted a link in the comments section of my last post, pointing to a page on the Vitamin D Council's website where Dr. John Cannell discusses cofactors required for proper vitamin D metabolism. It's actually the site's home page, highlighting how important he feels this matter is. In this case, 'cofactor' simply means another nutrient that's required for the efficient production and use of vitamin D. They include:

• Magnesium
• Zinc
• Vitamin K2
• Vitamin A
• Boron

And probably others we aren't yet aware of. On another page, Dr. Cannell links to two papers that review the critical interaction between magnesium status and vitamin D metabolism (1, 2). Here's a quote from the abstract of the second paper:

Magnesium... is essential for the normal function of the parathyroid glands, metabolism of vitamin D and adequate sensitivity of target tissues to [parathyroid hormone] and active vitamin D metabolites. Magnesium deficit is usually associated with hypoparathyroidism, low production of active vitamin D metabolites, in particular 1,25(OH)2 vitamin D3 and resistance to PTH and vitamin D. On the contrary, magnesium excess, similar to calcium, inhibits PTH secretion. Bone metabolism is impaired under positive as well as under negative magnesium balance.

Magnesium status is critical for normal vitamin D metabolism, insulin sensitivity, and overall health. Supplemental magnesium blocks atherosclerosis in multiple animal models (3, 4). Most Americans don't get enough magnesium (5).

The bottom line is that no nutrient acts in a vacuum. The effect of every part of one's diet and lifestyle is dependent on every other part. I often talk about single nutrients on this blog, but my core philosophy is that a proper diet focuses on Real Food, not nutrients. Tinkering with nutritional status using supplements is potentially problematic. Despite what some people might tell you, our understanding of nutrition and human health is currently rather crude-- so it's best to respect the accumulated wisdom of cultures that don't get the diseases we're trying to avoid.

The Diabetes Epidemic

The CDC just released its latest estimate of diabetes prevalence in the US (1):

Diabetes affects 8.3 percent of Americans of all ages, and 11.3 percent of adults aged 20 and older, according to the National Diabetes Fact Sheet for 2011. About 27 percent of those with diabetes—7 million Americans—do not know they have the disease. Prediabetes affects 35 percent of adults aged 20 and older.

Wow-- this is a massive problem. The prevalence of diabetes has been increasing over time, due to more people developing the disorder, improvements in diabetes care leading to longer survival time, and changes in the way diabetes is diagnosed. Here's a graph I put together based on CDC data, showing the trend of diabetes prevalence (percent) from 1980 to 2008 in different age categories (2):

These data are self-reported, and do not correct for differences in diagnosis methods, so they should be viewed with caution-- but they still serve to illustrate the trend. There was an increase in diabetes incidence that began in the early 1990s. More than 90 percent of cases are type 2 diabetics. Disturbingly, the trend does not show any signs of slowing.

The diabetes epidemic has followed on the heels of the obesity epidemic with 10-20 years of lag time. Excess body fat is the number one risk factor for diabetes*. As far as I can tell, type 2 diabetes is caused by insulin resistance, which is probably due to energy intake exceeding energy needs (overnutrition), causing a state of cellular insulin resistance as a defense mechanism to protect against the damaging effects of too much glucose and fatty acids (3). In addition, type 2 diabetes requires a predisposition that prevents the pancreatic beta cells from keeping up with the greatly increased insulin needs of an insulin resistant person**. Both factors are required, and not all insulin resistant people will develop diabetes as some people's beta cells are able to compensate by hypersecreting insulin.

Why does energy intake exceed energy needs in modern America and in most affluent countries? Why has the typical person's calorie intake increased by 250 calories per day since 1970 (4)? I believe it's because the fat mass "setpoint" has been increased, typically but not always by industrial food. I've been developing some new thoughts on this lately, and potentially new solutions, which I'll reveal when they're ready.


* In other words, it's the best predictor of future diabetes risk.

** Most of the common gene variants (of known function) linked with type 2 diabetes are thought to impact beta cell function (5).

Flu Season is Here

I've noticed everyone around me getting sick lately (I seem to have become mostly immune to colds and the flu in the last couple of years), so I took a look at Google Flu Trends. Lo and behold, the United States is currently near peak flu incidence for the 2010-2011 season. Here's a graph from Flu Trends. This year's trend is in dark blue:


Flu Trends also has data for individual US states and a number of other countries.

It's time to tighten up your diet and lifestyle if you want to avoid the flu this year. Personally, I feel that eating well, managing stress effectively, and taking 2,000 IU of vitamin D3 per day in winter have helped me avoid colds and the flu.

Gluten-Free January Raffle Winners Selected!

Raffle winners have been selected and shirts are on their way. You know who you are. Thanks to everyone who participated and filled out the survey! For those who didn't, there's always next year.

Janine Jagger, Matt Lentzner and I are busy crunching the mountain of data we collected from the GFJ survey. We got 279 responses, which is remarkable for a survey of this nature.

Stay tuned for data!

Oltipraz

Oltipraz is a drug that was originally used to treat intestinal worms. It was later found to prevent a broad variety of cancers (1). This was attributed to its ability to upregulate cellular detoxification and repair mechanisms.

Researchers eventually discovered that oltipraz acts by activating Nrf2, the same transcription factor activated by ionizing radiation and polyphenols (2, 3, 4). Nrf2 activation mounts a broad cellular protective response that appears to reduce the risk of multiple health problems.

A recent paper in Diabetologia illustrates this (5). Investigators put mice on a long-term refined high-fat diet, with or without oltipraz. These carefully crafted diets are very unhealthy indeed, and when fed to rodents they rapidly induce fat gain and something that looks similar to human metabolic syndrome (insulin resistance, abdominal adiposity, blood lipid disturbances). Adding oltipraz to the diet prevented the fat gain, insulin resistance and inflammatory changes that occurred in the refined high-fat diet group.

The difference in fasting insulin was remarkable. The mice taking oltipraz had 1/7 the fasting insulin of the refined high-fat diet comparison group, and 1/3 the fasting insulin of the low-fat comparison group! Yet their glucose tolerance was normal, indicating that they were not low on insulin due to pancreatic damage. The low-fat diet they used in this study was also refined, which is why the two control groups (high-fat and low-fat) didn't diverge more in body fatness and other parameters. If they had used a group fed unrefined rodent chow as the comparator, the differences between groups would have been larger.

This shows that in addition to preventing cancer, Nrf2 activation can attenuate the metabolic damage caused by an unhealthy diet in rodents. Oltipraz illustrates the power of the cellular hormesis response. We can exploit this pathway naturally using polyphenols and other chemicals found in whole plant foods.