Lifeworld

(Note: My apologies for the sarcastic tone of this post. I am not really congratulating anybody here!)

Dr. Nick Delgado shows us in this YouTube video how to "become diabetic" in 6 hours!

I must admit that I liked the real-time microscope imaging, and wish he had shown us more of that.

But really!

After consulting with my mentor, the MIMIW, I was reminded that there is at least one post on this blog that shows how one can "become diabetic" in just over 60 minutes – that is, about 6 times faster than using the technique described by Dr. Delgado.

The technique used in the post mentioned above is called "intense exercise", which is even believed to be health-promoting! (Unlike drinking olive oil as if it was water, or eating white bread.)

The advantage of this technique is that one can "become diabetic" by doing something healthy!

Thanks Dr. Delgado, your video ranks high up there, together with this Ali G. video, as a fine example of how to bring real science to the masses.

The idea that heavy physical activity is a main trigger of heart attacks is widespread. Often endurance running and cardio-type activities are singled out. Some people refer to this as “death by running”. Others think that strength training has a higher lethal potential. We know based on the Oregon Sudden Unexpected Death Study that this is a myth.

Here is some evidence that heavy physical activity in fact has a significant protective effect. The graph below, from Brooks et al. (2005) shows the number of deaths from coronary heart disease, organized by age group, in longshoremen (dock workers). The shaded bars represent those whose level of activity at work was considered heavy. The unshaded bars represent those whose level of activity at work was considered moderate or light (essentially below the “heavy” level).


The data is based on an old and classic study of 6351 men, aged 35 to 74 years, who were followed either for 22 years, or to death, or to the age of 75. It shows a significant protective effect of heavy activity, especially after age 45. The numbers atop the unshaded bars reflect the relative risk of death from coronary heart disease in each age group. For example, in the age group 65-74, the risk among those not in the heavy activity group is 110 percent higher (2.1 times higher) than in the heavy activity group.

It should be noted that this is a cumulative effect, of years of heavy activity. Based on the description of the types of activities performed, and the calories spent, I estimate that the heavy activity group performed the equivalent of a few hours of strength training per week, plus a lot of walking and other light physical activities. The authors of the study concluded that “… repeated bursts of high energy output established a plateau of protection against coronary mortality.”

Heavy physical activity may not make you lose much weight, but has the potential to make you live longer.

Reference:

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

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.

Moderate strength training has a number of health benefits, and is viewed by many as an important component of a natural lifestyle that approximates that of our Stone Age ancestors. It increases bone density, muscle mass, and improves a number of health markers. Done properly, it may decrease body fat percentage.

Generally one would expect some muscle gain as a result of strength training. Men seem to be keen on upper-body gains, while women appear to prefer lower-body gains. Yet, many people do strength training for years, and experience little or no muscle gain.

Paradoxically, those people experience major strength gains, both men and women, especially in the first few months after they start a strength training program. However, those gains are due primarily to neural adaptations, and come without any significant gain in muscle mass. This can be frustrating, especially for men. Most men are after some noticeable muscle gain as a result of strength training. (Whether that is healthy is another story, especially as one gets to extremes.)

After the initial adaptation period, of “beginner” gains, typically no strength gains occur without muscle gains.

The culprits for the lack of anabolic response are often believed to be low levels of circulating testosterone and other hormones that seem to interact with testosterone to promote muscle growth, such as growth hormone. This leads many to resort to anabolic steroids, which are drugs that mimic the effects of androgenic hormones, such as testosterone. These drugs usually increase muscle mass, but have a number of negative short-term and long-term side effects.

There seems to be a better, less harmful, solution to the lack of anabolic response. Through my research on compensatory adaptation I often noticed that, under the right circumstances, people would overcompensate for obstacles posed to them. Strength training is a form of obstacle, which should generate overcompensation under the right circumstances. From a biological perspective, one would expect a similar phenomenon; a natural solution to the lack of anabolic response.

This solution is predicted by a theory that also explains a lack of anabolic response to strength training, and that unfortunately does not get enough attention outside the academic research literature. It is the theory of supercompensation, which is discussed in some detail in several high-quality college textbooks on strength training. (Unlike popular self-help books, these textbooks summarize peer-reviewed academic research, and also provide the references that are summarized.) One example is the excellent book by Zatsiorsky & Kraemer (2006) on the science and practice of strength training.

The figure below, from Zatsiorsky & Kraemer (2006), shows what happens during and after a strength training session. The level of preparedness could be seen as the load in the session, which is proportional to: the number of exercise sets, the weight lifted (or resistance overcame) in each set, and the number of repetitions in each set. The restitution period is essentially the recovery period, which must include plenty of rest and proper nutrition.


Note that toward the end there is a sideways S-like curve with a first stretch above the horizontal line and another below the line. The first stretch is the supercompensation stretch; a window in time (e.g., a 20-hour period). The horizontal line represents the baseline load, which can be seen as the baseline strength of the individual prior to the exercise session. This is where things get tricky. If one exercises again within the supercompensation stretch, strength and muscle gains will likely happen. (Usually noticeable upper-body muscle gain happens in men, because of higher levels of testosterone and of other hormones that seem to interact with testosterone.) Exercising outside the supercompensation time window may lead to no gain, or even to some loss, of both strength and muscle.

Timing strength training sessions correctly can over time lead to significant gains in strength and muscle (see middle graph in the figure below, also from Zatsiorsky & Kraemer, 2006). For that to happen, one has not only to regularly “hit” the supercompensation time window, but also progressively increase load. This must happen for each muscle group. Strength and muscle gains will occur up to a point, a point of saturation, after which no further gains are possible. Men who reach that point will invariably look muscular, in a more or less “natural” way depending on supplements and other factors. Some people seem to gain strength and muscle very easily; they are often called mesomorphs. Others are hard gainers, sometimes referred to as endomorphs (who tend to be fatter) and ectomorphs (who tend to be skinnier).


It is not easy to identify the ideal recovery and supercompensation periods. They vary from person to person. They also vary depending on types of exercise, numbers of sets, and numbers of repetitions. Nutrition also plays a role, and so do rest and stress. From an evolutionary perspective, it would seem to make sense to work all major muscle groups on the same day, and then do the same workout after a certain recovery period. (Our Stone Age ancestors did not do isolation exercises, such as bicep curls.) But this will probably make you look more like a strong hunter-gatherer than a modern bodybuilder.

To identify the supercompensation time window, one could employ a trial-and-error approach, by trying to repeat the same workout after different recovery times. Based on the literature, it would make sense to start at the 48-hour period (one full day of rest between sessions), and then move back and forth from there. A sign that one is hitting the supercompensation time window is becoming a little stronger at each workout, by performing more repetitions with the same weight (e.g., 10, from 8 in the previous session). If that happens, the weight should be incrementally increased in successive sessions. Most studies suggest that the best range for muscle gain is that of 6 to 12 repetitions in each set, but without enough time under tension gains will prove elusive.

The discussion above is not aimed at professional bodybuilders. There are a number of factors that can influence strength and muscle gain other than supercompensation. (Still, supercompensation seems to be a “biggie”.) Things get trickier over time with trained athletes, as returns on effort get progressively smaller. Even natural bodybuilders appear to benefit from different strategies at different levels of proficiency. For example, changing the workouts on a regular basis seems to be a good idea, and there is a science to doing that properly. See the “Interesting links” area of this web site for several more focused resources of strength training.

Reference:

Zatsiorsky, V., & Kraemer, W.J. (2006). Science and practice of strength training. Champaign, IL: Human Kinetics.

There are human traits that evolved in spite of being survival handicaps. These counterintuitive traits are often called costly traits, or Zahavian traits (in animal signaling contexts), in honor of the evolutionary biologist Amotz Zahavi (Zahavi & Zahavi, 1997). I have written a post about this type of traits, and also an academic article (Kock, 2009). The full references and links to these publications are at the end of this post.

The classic example of costly trait is the peacock’s train, which is used by males to signal health to females. (Figure below from: animals.howstuffworks.com.) The male peacock’s train (often incorrectly called “tail”) is a costly trait because it impairs the ability of a male to flee predators. It decreases a male’s survival success, even though it has a positive net effect on the male’s reproductive success (i.e., the number of offspring it generates). It is used in sexual selection; the females find big and brightly colored trains with many eye spots "sexy".


So costly traits exist in many species, including the human species, but we have not identified them all yet. The implication for human diet and lifestyle choices is that our ancestors might have evolved some habits that are bad for human survival, and moved away from others that are good for survival. And I am not only talking about survival among modern humans; I am talking about survival among our human ancestors too.

The simple reason for the existence of costly traits in humans is that evolution tends to maximize reproductive success, not survival, and that applies to all species. (Inclusive fitness theory goes a step further, placing the gene at the center of the selection process, but this is a topic for another post.) If that were not the case, rodent species, as well as other species that specialize in fast reproduction within relatively short life spans, would never have evolved.

Here is an interesting piece of news about research done at the University of Michigan. (I have met the lead researcher, Dan Kruger, a couple of times at HBES conferences. My impression is that his research is solid.) The research illustrates the evolution of costly traits, from a different angle. The researchers argue, based on the results of their investigation, that competing for a woman’s attention is generally bad for a man’s health!

Very romantic ...

References:

Kock, N. (2009). The evolution of costly traits through selection and the importance of oral speech in e-collaboration. Electronic Markets, 19(4), 221-232.

Zahavi, A. & Zahavi, A. (1997). The Handicap Principle: A missing piece of Darwin’s puzzle. Oxford, England: Oxford University Press.