Hormonal reductionism is as myopic as biochemical reductionism

Biochemistry-based arguments can be very misleading. Yet, biochemistry can be extremely useful in the elucidation of diet and lifestyle effects that are suggested by well-designed studies of humans. If you start with a biochemistry-based argument though, and ignore actual studies of humans, you can easily convince someone that glycogen-depleting exercise (e.g., weight training) is unhealthy, because many health markers change for the worse after that type of exercise. But it is the damage caused by glycogen-depleting exercise that leads to health improvements, via short- and long-term compensatory adaptations ().

Biochemistry is very helpful in terms of providing “pieces for the puzzle”, but biochemical reductionism is a problem. Analogous to biochemical reductionism, and perhaps one example of it, is hormonal reductionism – trying to argue that all diet and lifestyle effects are mediated by a single hormone. A less extreme position, but still myopic, is to argue that all diet and lifestyle effects are mostly mediated by a single hormone.

One of my own “favorite” hormones is adiponectin, which I have been discussing for years in this blog (). Increased serum adiponectin has been found to be significantly associated with: decreased body fat (particularly decreased visceral fat), decreased risk of developing diabetes type 2, and decreased blood pressure. Adiponectin appears to also have anti-inflammatory and athero-protective properties.

As a side note, typically women have higher levels of serum adiponectin than men, particularly young women. Culturally we have a tendency to see young women as “delicate” and “vulnerable”. Guess what? Young women are the closest we get to “indestructible” in the human species. And there is an evolutionary reason for that, which is that fertile women have been in our evolutionary past, and still are, the bottleneck of any population. A population of 100 individuals, where 99 are men and 1 is a woman, will quickly disappear. If it is 99 women and 1 fertile man, the population will grow; but there will also be some problems due to inbreeding. Even if the guy is ugly the population will grow; without competition, he will look very cute.

Jung and colleagues measured various hormone levels in 78 obese people who had visited obesity clinics at five university hospitals (Ajou, Ulsan, Catholic, Hanyang and Yonsei) in Korea (). Those folks restricted their caloric intake to 500 calories less than their usual intake, and exercised, for 12 weeks. Below are the measured changes in tumor necrosis factor α (TNF-α, now called only TNF), interleukin-6 (IL-6), resistin, leptin, adiponectin, and interleukin-10 (IL-10).

We see from the table above that the hormonal changes were all significant (all at the P equal to or lower than 0.001 level except one, at the P lower than 0.05 level), and all indicative of health improvements. The serum concentrations of all hormones decreased, with two exceptions – adiponectin and interleukin-10, which increased. Interleukin-10 is an anti-inflammatory hormone produced by white blood cells. The most significant increase of the two was by far in adiponectin (P = .001, versus P = .041 for interleukin-10).

Now, should we try to find a way of producing synthetic adiponectin then? My guess is that doing that will not lead to very positive results in human trials; because, as you can see from the table, hormones vary in concert. At the moment, the only way to “supplement” adiponectin is to lose body fat, and that leads to concurrent changes in many other hormones (e.g., TNF decreases).

Trying to manipulate one single hormone, or build an entire health-improvement approach based on its effects, is myopic. But that is what often happens. Leptin is a relatively recent example.

One reason why biochemistry is so complex, with so many convoluted processes, is that evolution is a tinkerer that is “blind” to complexity. Traits appear at random in populations and spread if they increase reproductive success; even if they decrease survival success, by the way ().

Evolution is not an engineer, and is not even our “friend” (). To optimize our health, we need to “hack” evolution.

Refined carbohydrate-rich foods, palatability, glycemic load, and the Paleo movement

A great deal of discussion has been going on recently revolving around the so-called “carbohydrate hypothesis of obesity”. I will use the acronym CHO to refer to this hypothesis. This acronym is often used to refer to carbohydrates in nutrition research; I hope this will not cause confusion.

The CHO could be summarized as this: a person consumes foods with “easily digestible” carbohydrates, those carbohydrates raise insulin levels abnormally, the abnormally high insulin levels drive too much fat into body fat cells and keep it there, this causes hunger as not enough fat is released from fat cells for use as energy, this hunger drives the consumption of more foods with “easily digestible” carbohydrates, and so on.

It is posited as a feedback-loop process that causes serious problems over a period of years. The term “easily digestible” is within quotes for emphasis. If it is taken to mean “refined”, which is still a bit vague, there is a good amount of epidemiological evidence in support of the CHO. If it is taken to mean simply “easily digestible”, as in potatoes and rice (which is technically a refined food, but a rather benign one), there is a lot of evidence against it. Even from an unbiased (hopefully) look at county-level data in the China Study.

Another hypothesis that has been around for a long time and that has been revived recently, which we could call the “palatability hypothesis”, is a competing hypothesis. It is an interesting and intriguing hypothesis, at least at first glance. There seems to be some truth to this hypothesis. The idea here is that we have not evolved mechanisms to deal with highly palatable foods, and thus end up overeating them.  Therefore we should go in the opposite direction, and place emphasis on foods that are not very palatable to reach our optimal weight. You might think that to test this hypothesis it would be enough to find out if this diet works: “Eat something … if it tastes good, spit it out!”

But it is not so simple. To test this palatability hypothesis one could try to measure the palatability of foods, and see if it is correlated with consumption. The problem is that the formulations I have seen of the palatability hypothesis treat the palatability construct as static, when in fact it is dynamic – very dynamic. The perception of the reward associated with a specific food changes depending on a number of factors.

For example, we cannot assign a palatability score to a food without considering the particular state in which the individual who eats the food is. That state is defined by a number of factors, including physiological and psychological ones, which vary a lot across individuals and even across different points in time for the same individual. For someone who is hungry after a 20 h fast, for instance, the perceived reward associated with a food will go up significantly compared to the same person in the fed state.

Regarding the CHO, it seems very clear that refined carbohydrate-rich foods in general, particularly the highly modified ones, disrupt normal biological mechanisms that regulate hunger. Perceived food reward, or palatability, is a function of hunger. Abnormal glucose and insulin responses appear to be at the core of this phenomenon. There are undoubtedly many other factors at play as well. But, as you can see, there is a major overlap between the CHO and the palatability hypothesis. Refined carbohydrate-rich foods generally have higher palatability than natural foods in general. Humans are good engineers.

One meme that seems to be forming recently on the Internetz is that the CHO is incompatible with data from healthy isolated groups that consume a lot of carbohydrates, which are sometimes presented as alternative models of life in the Paleolithic. But in fact among influential proponents of the CHO are the intellectual founders of the Paleolithic dieting movement. Including folks who studied native diets high in carbohydrates, and found their users to be very healthy (e.g., the Kitavans). One thing that these intellectual founders did though was to clearly frame the CHO in terms of refined carbohydrate-rich foods.

Natural carbohydrate-rich foods are clearly distinguished from refined ones based on one key attribute; not the only one, but a very important one nonetheless. That attribute is their glycemic load (GL). I am using the term “natural” here as roughly synonymous with “unrefined” or “whole”. Although they are often confused, the GL is not the same as the glycemic index (GI). The GI is a measure of the effect of carbohydrate intake on blood sugar levels. Glucose is the reference; it has a GI of 100.

The GL provides a better way of predicting total blood sugar response, in terms of “area under the curve”, based on both the type and quantity of carbohydrate in a specific food. Area under the curve is ultimately what really matters; a pointed but brief spike may not have much of a metabolic effect. Insulin response is highly correlated with blood sugar response in terms of area under the curve. The GL is calculated through the following formula:

GL = (GI x the amount of available carbohydrate in grams) / 100

The GL of a food is also dynamic, but its range of variation is small enough in normoglycemic individuals so that it can be treated as a relatively static number. (Still, the reference are normoglycemic individuals.) One of the main differences between refined and natural carbohydrate-rich foods is the much higher GL of industrial carbohydrate-rich foods, and this is not affected by slight variations in GL and GI depending on an individual’s state. The table below illustrates this difference.

Looking back at the environment of our evolutionary adaptation (EEA), which was not static either, this situation becomes analogous to that of vitamin D deficiency today. A few minutes of sun exposure stimulate the production of 10,000 IU of vitamin D, whereas food fortification in the standard American diet normally provides less than 500 IU. The difference is large. So is the difference in GL of natural and refined carbohydrate-rich foods.

And what are the immediate consequences of that difference in GL values? They are abnormally elevated blood sugar and insulin levels after meals containing refined carbohydrate-rich foods. (Incidentally, the GL  happens to be relatively low for the rice preparations consumed by Asian populations who seem to do well on rice-based diets.)  Abnormal levels of other hormones, in a chronic fashion, come later, after many years consuming those foods. These hormones include adiponectin, leptin, and tumor necrosis factor. The authors of the article from which the table above was taken note that:

Within the past 20 y, substantial evidence has accumulated showing that long term consumption of high glycemic load carbohydrates can adversely affect metabolism and health. Specifically, chronic hyperglycemia and hyperinsulinemia induced by high glycemic load carbohydrates may elicit a number of hormonal and physiologic changes that promote insulin resistance. Chronic hyperinsulinemia represents the primary metabolic defect in the metabolic syndrome.

Who are the authors of this article? They are Loren Cordain, S. Boyd Eaton, Anthony Sebastian, Neil Mann, Staffan Lindeberg, Bruce A. Watkins, James H O’Keefe, and Janette Brand-Miller. The paper is titled “Origins and evolution of the Western diet: Health implications for the 21st century”. A full-text PDF is available here. For most of these authors, this article is their most widely cited publication so far, and it is piling up citations as I write. This means that not only members of the general public have been reading it, but that professional researchers have been reading it as well, and citing it in their own research publications.

In summary, the CHO and the palatability hypothesis overlap, and the overlap is not trivial. But the palatability hypothesis is more difficult to test. As Karl Popper noted, a good hypothesis is a testable hypothesis. Eating natural foods will make an enormous difference for the better in your health if you are coming from the standard American diet, and you can justify this statement based on the CHO, the palatability hypothesis, or even a few others – e.g., a nutrient density hypothesis, which would be closer to Weston Price's views. Even if you eat only plant-based natural foods, which I cannot fully recommend based on data I’ve reviewed on this blog, you will be better off.

Lipotoxicity or tired pancreas? Abnormal fat metabolism as a possible precondition for type 2 diabetes

The term “diabetes” is used to describe a wide range of diseases of glucose metabolism; diseases with a wide range of causes. The diseases include type 1 and type 2 diabetes, type 2 ketosis-prone diabetes (which I know exists thanks to Michael Barker’s blog), gestational diabetes, various MODY types, and various pancreatic disorders. The possible causes include genetic defects (or adaptations to very different past environments), autoimmune responses, exposure to environmental toxins, as well as viral and bacterial infections; in addition to obesity, and various other apparently unrelated factors, such as excessive growth hormone production.

Type 2 diabetes and the “tired pancreas” theory

Type 2 diabetes is the one most commonly associated with the metabolic syndrome, which is characterized by middle-age central obesity, and the “diseases of civilization” brought up by Neolithic inventions. Evidence is mounting that a Neolithic diet and lifestyle play a key role in the development of the metabolic syndrome. In terms of diet, major suspects are engineered foods rich in refined carbohydrates and refined sugars. In this context, one widely touted idea is that the constant insulin spikes caused by consumption of those foods lead the pancreas (figure below from Wikipedia) to get “tired” over time, losing its ability to produce insulin. The onset of insulin resistance mediates this effect.

Empirical evidence against the “tired pancreas” theory

This “tired pancreas” theory, which refers primarily to the insulin-secreting beta-cells in the pancreas, conflicts with a lot of empirical evidence. It is inconsistent with the existence of isolated semi/full hunter-gatherer groups (e.g., the Kitavans) that consume large amounts of natural (i.e., unrefined) foods rich in easily digestible carbohydrates from tubers and fruits, which cause insulin spikes. These groups are nevertheless generally free from type 2 diabetes. The “tired pancreas” theory conflicts with the existence of isolated groups in China and Japan (e.g., the Okinawans) whose diets also include a large proportion of natural foods rich in easily digestible carbohydrates, which cause insulin spikes. Yet these groups are generally free from type 2 diabetes.

Humboldt (1995), in his personal narrative of his journey to the “equinoctial regions of the new continent”, states on page 121 about the natives as a group that: "… between twenty and fifty years old, age is not indicate by wrinkling skin, white hair or body decrepitude [among natives]. When you enter a hut is hard to differentiate a father from son …" A large proportion of these natives’ diets included plenty of natural foods rich in easily digestible carbohydrates from tubers and fruits, which cause insulin spikes. Still, there was no sign of any condition that would suggest a prevalence of type 2 diabetes among them.

At this point it is important to note that the insulin spikes caused by natural carbohydrate-rich foods are much less pronounced than the ones caused by refined carbohydrate-rich foods. The reason is that there is a huge gap between the glycemic loads of natural and refined carbohydrate-rich foods, even though the glycemic indices may be quite similar in some cases. Natural carbohydrate-rich foods are not made mostly of carbohydrates. Even an Irish (or white) potato is 75 percent water.

More insulin may lead to abnormal fat metabolism in sedentary people

The more pronounced spikes may lead to abnormal fat metabolism because more body fat is force-stored than it would have been with the less pronounced spikes, and stored body fat is not released just as promptly as it should be to fuel muscle contractions and other metabolic processes. Typically this effect is a minor one on a daily basis, but adds up over time, leading to fairly unnatural patterns of fat metabolism in the long run. This is particularly true for those who lead sedentary lifestyles. As for obesity, nobody gets obese in one day. So the key problem with the more pronounced spikes may not be that the pancreas is getting “tired”, but that body fat metabolism is not normal, which in turn leads to abnormally high or low levels of important body fat-derived hormones (e.g., high levels of leptin and low levels of adiponectin).

One common characteristic of the groups mentioned above is absence of obesity, even though food is abundant and often physical activity is moderate to low. Repeat for emphasis: “… even though food is abundant and often physical activity is moderate to low”. Note that having low levels of activity is not the same as spending the whole day sitting down in a comfortable chair working on a computer. Obviously caloric intake and level of activity among these groups were/are not at the levels that would lead to obesity. How could that be possible? See this post for a possible explanation.

Excessive body fat gain, lipotoxicity, and type 2 diabetes

There are a few theories that implicate the interaction of abnormal fat metabolism with other factors (e.g., genetic factors) in the development of type 2 diabetes. Empirical evidence suggests that this is a reasonable direction of causality. One of these theories is the theory of lipotoxicity.

Several articles have discussed the theory of lipotoxicity. The article by Unger & Zhou (2001) is a widely cited one. The theory seems to be widely based on the comparative study of various genotypes found in rats. Nevertheless, there is mounting evidence suggesting that the underlying mechanisms may be similar in humans. In a nutshell, this theory proposes the following steps in the development of type 2 diabetes:

    (1) Abnormal fat mass gain leads to an abnormal increase in fat-derived hormones, of which leptin is singled out by the theory. Some people seem to be more susceptible than others in this respect, with lower triggering thresholds of fat mass gain. (What leads to exaggerated fat mass gains? The theory does not go into much detail here, but empirical evidence from other studies suggests that major culprits are refined grains and seeds, as well as refined sugars; other major culprits seem to be trans fats, and vegetable oils rich in linoleic acid.)

    (2) Resistance to fat-derived hormones sets in. Again, leptin resistance is singled out as the key here. (This is a bit simplistic. Other fat-derived hormones, like adiponectin, seem to clearly interact with leptin.) Since leptin regulates fatty acid metabolism, the theory argues, leptin resistance is hypothesized to impair fatty acid metabolism.

    (3) Impaired fat metabolism causes fatty acids to “spill over” to tissues other than fat cells, and also causes an abnormal increase in a substance called ceramide in those tissues. These include tissues in the pancreas that house beta-cells, which secrete insulin. In short, body fat should be stored in fat cells (adipocytes), not outside them.

    (4) Initially fatty acid “spill over” to beta-cells enlarges them and makes them become overactive, leading to excessive insulin production in response to carbohydrate-rich foods, and also to insulin resistance. This is the pre-diabetic phase where hypoglycemic episodes happen a few hours following the consumption of carbohydrate-rich foods. Once this stage is reached, several natural carbohydrate-rich foods also become a problem (e.g., potatoes and bananas), in addition to refined carbohydrate-rich foods.

    (5) Abnormal levels of ceramide induce beta-cell apoptosis in the pancreas. This is essentially “death by suicide” of beta cells in the pancreas. What follows is full-blown type 2 diabetes. Insulin production is impaired, leading to very elevated blood glucose levels following the consumption of carbohydrate-rich foods, even if they are unprocessed.

It is widely known that type 2 diabetics have impaired glucose metabolism. What is not so widely known is that usually they also have impaired fatty acid metabolism. For example, consumption of the same fatty meal is likely to lead to significantly more elevated triglyceride levels in type 2 diabetics than non-diabetics, after several hours. This is consistent with the notion that leptin resistance precedes type 2 diabetes, and inconsistent with the “tired pancreas” theory.

Weak and strong points of the theory of lipotoxicity

A weakness of the theory of lipotoxicity is its strong lipophobic tone; at least in the articles that I have read. See, for example, this article by Roger H. Unger in the Journal of the American Medical Association. There is ample evidence that eating a lot of the ultra-demonized saturated fat, per se, is not what makes people obese or type 2 diabetic. Yet overconsumption of trans fats and vegetable oils rich in linoleic acid does seem to be linked with obesity and type 2 diabetes. (So does the consumption of refined grains and seeds, and refined sugars.) The theory of lipotoxicity does not seem to make these distinctions.

In defense of the theory of lipotoxicity, it does not argue that there cannot be thin diabetics. Many type 1 diabetics are thin. Type 2 diabetics can also be thin, even though that is much less common. In certain individuals, the threshold of body fat gain that will precipitate lipotoxicity may be quite low. In others, the same amount of body fat gain (or more) may in fact increase their insulin sensitivity under certain circumstances – e.g., when growth hormone levels are abnormally low.

Autoimmune disorders, perhaps induced by environmental toxins, or toxins found in certain refined foods, may cause the immune system to attack the beta-cells in the pancreas. This may lead to type 1 diabetes if all beta cells are destroyed, or something that can easily be diagnosed as type 2 (or type 1.5) diabetes if only a portion of the cells are destroyed, in a way that does not involve lipotoxicity.

Nor does the theory of lipotoxicity predict that all those who become obese will develop type 2 diabetes. It only suggests that the probability will go up, particularly if other factors are present (e.g., genetic propensity). There are many people who are obese during most of their adult lives and never develop type 2 diabetes. On the other hand, some groups, like Hispanics, tend to develop type 2 diabetes more easily (often even before they reach the obese level). One only has to visit the South Texas region near the Rio Grande border to see this first hand.

What the theory proposes is a new way of understanding the development of type 2 diabetes; a way that seems to make more sense than the “tired pancreas” theory. The theory of lipitoxicity may not be entirely correct. For example, there may be other mechanisms associated with abnormal fat metabolism and consumption of Neolithic foods that cause beta-cell “suicide”, and that have nothing to do with lipotoxicity as proposed by the theory. (At least one fat-derived hormone, tumor necrosis factor-alpha, is associated with abnormal cell apoptosis when abnormally elevated. Levels of this hormone go up immediately after a meal rich in refined carbohydrates.) But the link that it proposes between obesity and type 2 diabetes seems to be right on target.

Implications and thoughts

Some implications and thoughts based on the discussion above are the following. Some are extrapolations based on the discussion in this post combined with those in other posts. At the time of this writing, there were 90 posts on this blog, in addition to many comments. See under "Labels" at the bottom-right area of this blog for a summary of topics addressed. It is hard to ignore things that were brought to light in previous posts.

    - Let us start with a big one: Avoiding natural carbohydrate-rich foods in the absence of compromised glucose metabolism is unnecessary. Those foods do not “tire” the pancreas significantly more than protein-rich foods do. While carbohydrates are not essential macronutrients, protein is. In the absence of carbohydrates, protein will be used by the body to produce glucose to supply the needs of the brain and red blood cells. Protein elicits an insulin response that is comparable to that of natural carbohydrate-rich foods on a gram-adjusted basis (but significantly lower than that of refined carbohydrate-rich foods, like doughnuts and bagels). Usually protein does not lead to a measurable glucose response because glucagon is secreted together with insulin in response to ingestion of protein, preventing hypoglycemia.

    - Abnormal fat gain should be used as a general measure of one’s likelihood of being “headed south” in terms of health. The “fitness” level for men and women shown on the table in this post seem like good targets for body fat percentage. The problem here, of course, is that this is not as easy as it sounds. Attempts at getting lean can lead to poor nutrition and/or starvation. These may make matters worse in some cases, leading to hormonal imbalances and uncontrollable hunger, which will eventually lead to obesity. Poor nutrition may also depress the immune system, making one susceptible to a viral or bacterial  infection that may end up leading to beta-cell destruction and diabetes. A better approach is to place emphasis on eating a variety of natural foods, which are nutritious and satiating, and avoiding refined ones, which are often addictive “empty calories”. Generally fat loss should be slow to be healthy and sustainable.

    - Finally, if glucose metabolism is compromised, one should avoid any foods in quantities that cause an abnormally elevated glucose or insulin response. All one needs is an inexpensive glucose meter to find out what those foods are. The following are indications of abnormally elevated glucose and insulin responses, respectively: an abnormally high glucose level 1 hour after a meal (postprandial hyperglycemia); and an abnormally low glucose level 2 to 4 hours after a meal (reactive hypoglycemia). What is abnormally high or low? Take a look at the peaks and troughs shown on the graph in this post; they should give you an idea. Some insulin resistant people using glucose meters will probably realize that they can still eat several natural carbohydrate-rich foods, but in small quantities, because those foods usually have a low glycemic load (even if their glycemic index is high).

Lucy was a vegetarian and Sapiens an omnivore. We apparently have not evolved to be pure carnivores, even though we can be if the circumstances require. But we absolutely have not evolved to eat many of the refined and industrialized foods available today, not even the ones marketed as “healthy”. Those foods do not make our pancreas “tired”. Among other things, they “mess up” fat metabolism, which may lead to type 2 diabetes through a complex process involving hormones secreted by body fat.

References

Humboldt, A.V. (1995). Personal narrative of a journey to the equinoctial regions of the new continent. New York, NY: Penguin Books.

Unger, R.H., & Zhou, Y.-T. (2001). Lipotoxicity of beta-cells in obesity and in other causes of fatty acid spillover. Diabetes, 50(1), S118-S121.

Subcutaneous versus visceral fat: How to tell the difference?

The photos below, from Wikipedia, show two patterns of abdominal fat deposition. The one on the left is predominantly of subcutaneous abdominal fat deposition. The one on the right is an example of visceral abdominal fat deposition, around internal organs, together with a significant amount of subcutaneous fat deposition as well.

Body fat is not an inert mass used only to store energy. Body fat can be seen as a “distributed organ”, as it secretes a number of hormones into the bloodstream. For example, it secretes leptin, which regulates hunger. It secretes adiponectin, which has many health-promoting properties. It also secretes tumor necrosis factor-alpha (more recently referred to as simply “tumor necrosis factor” in the medical literature), which promotes inflammation. Inflammation is necessary to repair damaged tissue and deal with pathogens, but too much of it does more harm than good.

How does one differentiate subcutaneous from visceral abdominal fat?

Subcutaneous abdominal fat shifts position more easily as one’s body moves. When one is standing, subcutaneous fat often tends to fold around the navel, creating a “mouth” shape. Subcutaneous fat is easier to hold in one’s hand, as shown on the left photo above. Because subcutaneous fat tends to “shift” more easily as one changes the position of the body, if you measure your waist circumference lying down and standing up, and the difference is large (a one-inch difference can be considered large), you probably have a significant amount of subcutaneous fat.

Waist circumference is a variable that reflects individual changes in body fat percentage fairly well. This is especially true as one becomes lean (e.g., around 14-17 percent or less of body fat for men, and 21-24 for women), because as that happens abdominal fat contributes to an increasingly higher proportion of total body fat. For people who are lean, a 1-inch reduction in waist circumference will frequently translate into a 2-3 percent reduction in body fat percentage. Having said that, waist circumference comparisons between individuals are often misleading. Waist-to-fat ratios tend to vary a lot among different individuals (like almost any trait). This means that someone with a 34-inch waist (measured at the navel) may have a lower body fat percentage than someone with a 33-inch waist.

Subcutaneous abdominal fat is hard to mobilize; that is, it is hard to burn through diet and exercise. This is why it is often called the “stubborn” abdominal fat. One reason for the difficulty in mobilizing subcutaneous abdominal fat is that the network of blood vessels is not as dense in the area where this type of fat occurs, as it is with visceral fat. Another reason, which is related to degree of vascularization, is that subcutaneous fat is farther away from the portal vein than visceral fat. As such, it has to travel a longer distance to reach the main “highway” that will take it to other tissues (e.g., muscle) for use as energy.

In terms of health, excess subcutaneous fat is not nearly as detrimental as excess visceral fat. Excess visceral fat typically happens together with excess subcutaneous fat; but not necessarily the other way around. For instance, sumo wrestlers frequently have excess subcutaneous fat, but little or no visceral fat. The more health-detrimental effect of excess visceral fat is probably related to its proximity to the portal vein, which amplifies the negative health effects of excessive pro-inflammatory hormone secretion. Those hormones reach a major transport “highway” rather quickly.

Even though excess subcutaneous body fat is more benign than excess visceral fat, excess body fat of any kind is unlikely to be health-promoting. From an evolutionary perspective, excess body fat impaired agile movement and decreased circulating adiponectin levels; the latter leading to a host of negative health effects. In modern humans, negative health effects may be much less pronounced with subcutaneous than visceral fat, but they will still occur.

Based on studies of isolated hunger-gatherers, it is reasonable to estimate “natural” body fat levels among our Stone Age ancestors, and thus optimal body fat levels in modern humans, to be around 6-13 percent in men and 14–20 percent in women.

If you think that being overweight probably protected some of our Stone Age ancestors during times of famine, here is one interesting factoid to consider. It will take over a month for a man weighing 150 lbs and with 10 percent body fat to die from starvation, and death will not be typically caused by too little body fat being left for use as a source of energy. In starvation, normally death will be caused by heart failure, as the body slowly breaks down muscle tissue (including heart muscle) to maintain blood glucose levels.

References:

Arner, P. (2005). Site differences in human subcutaneous adipose tissue metabolism in obesity. Aesthetic Plastic Surgery, 8(1), 13-17.

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

Fleck, S.J., & Kraemer, W.J. (2004). Designing resistance training programs. Champaign, IL: Human Kinetics.

Taubes, G. (2007). Good calories, bad calories: Challenging the conventional wisdom on diet, weight control, and disease. New York, NY: Alfred A. Knopf.