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.

Body fat and disease: How much body fat can I lose in one day?

Body fat is not an inert deposit of energy. It can be seen as a distributed endocrine organ. Body fat cells, or adipocytes, secrete a number of different hormones into the bloodstream. Major hormones secreted by adipose tissue are adiponectin and leptin.

Estrogen is also secreted by body fat, which is one of the reasons why obesity is associated with infertility. (Yes, abnormally high levels of estrogen can reduce fertility in both men and women.) Moreover, body fat secretes tumor necrosis factor-alpha, a hormone that is associated with generalized inflammation and a number of diseases, including cancer, when in excess.

The reduction in circulating tumor necrosis factor-alpha and other pro-inflammatory hormones as one loses weight is one reason why non-obese people usually experience fewer illness symptoms than those who are obese in any given year, other things being equal. For example, the non-obese will have fewer illness episodes that require full rest during the flu season. In those who are obese, the inflammatory response accompanying an illness (which is necessary for recovery) will often be exaggerated.

The exaggerated inflammatory response to illness often seen in the obese is one indication that obesity in an unnatural state for humans. It is reasonable to assume that it was non-adaptive for our Paleolithic ancestors to be unable to perform daily activities because of an illness. The adaptive response would be physical discomfort, but not to the extent that one would require full rest for a few days to fully recover.

Inflammation markers such as C-reactive protein are positively correlated with body fat. As body fat increases, so does inflammation throughout the body. Lipid metabolism is negatively affected by excessive body fat, and so is glucose metabolism. Obesity is associated with leptin and insulin resistance, which are precursors of diabetes type 2.

Some body fat is necessary for survival; that is normally called essential body fat. The table below (from Wikipedia) shows various levels of body fat, including essential levels. Also shown are body fat levels found in athletes, as well as fit, “not so fit” (indicated as "Acceptable"), and obese individuals. Women normally have higher healthy levels of body fat than men.

If one is obese, losing body fat becomes a very high priority for health reasons.

There are many ways in which body fat can be measured.

When one loses body fat through fasting, the number of adipocytes is not actually reduced. It is the amount of fat stored in adipocytes that is reduced.

How much body fat can a person lose in one day?

Let us consider a man, John, whose weight is 170 lbs (77 kg), and whose body fat percentage is 30 percent. John carries around 51 lbs (23 kg) of body fat. Standing up is, for John, a form of resistance exercise. So is climbing stairs.

During a 24-hour fast, John’s basal metabolic rate is estimated at about 2,550 kcal/day. This is the number of calories John would spend doing nothing the whole day. It can vary a lot for different individuals; here it is calculated as 15 times John’s weight in lbs.

The 2,550 kcal/day is likely an overestimation for John, because the body adjusts its metabolic rate downwards during a fast, leading to fewer calories being burned.

Typically women have lower basal metabolic rates than men of equal weight.

For the sake of discussion, we expect each gram of John’s body fat to contribute about 8 kcals of energy, assuming a rate of conversion of body fat to calories of about 90 percent.

Thus during a 24-hour fast John burns about 318 g of fat, or about 0.7 lbs. In reality, the actual amount may be lower (e.g., 0.35 lbs), because of the body's own down-regulation of its basal metabolic rate during a fast. This down-regulation varies widely across different individuals, and is generally small.

Many people think that this is not much for the effort. The reality is that body fat loss is a long term game, and cannot be achieved through fasting alone; this is a discussion for another post.

It is worth noting that intermittent fasting (e.g., one 24-hour fast per week) has many other health benefits, even if no overall calorie restriction occurs. That is, intermittent fasting is associated with health benefits even if one fasts every other day, and eats twice one's normal intake on the non-fasting days.

Some of the calories being burned during John's 24-hour fast will be from glucose, mostly from John’s glycogen reserves in the liver if he is at rest. Muscle glycogen stores, which store more glucose substrate (i.e., material for production of glucose) than liver glycogen, are mobilized primarily through anaerobic exercise.

Very few muscle-derived calories end up being used through the protein and glycogen breakdown pathways in a 24-hour fast. John’s liver glycogen reserves, plus the body’s own self-regulation, will largely spare muscle tissue.

The idea that one has to eat every few hours to avoid losing muscle tissue is complete nonsense. Muscle buildup and loss happen all the time through amino acid turnover.

Net muscle gain occurs when the balance is tipped in favor of buildup, to which resistance exercise and the right hormonal balance (including elevated levels of insulin) contribute.

One of the best ways to lose muscle tissue is lack of use. If John's arm were immobilized in a cast, he would lose muscle tissue in that arm even if he ate every 30 minutes.

Longer fasts (e.g., lasting multiple days, with only water being consumed) will invariably lead to some (possibly significant) muscle breakdown, as muscle is the main store of glucose-generating substrate in the human body.

In a 24-hour fast (a relatively short fast), the body will adjust its metabolism so that most of its energy needs are met by fat and related byproducts. This includes ketones, which are produced by the liver based on dietary and body fat.

How come some people can easily lose 2 or 3 pounds of weight in one day?

Well, it is not body fat that is being lost, or muscle. It is water, which may account for as much as 75 percent of one’s body weight.

References:

Elliott, W.H., & Elliott, D.C. (2009). Biochemistry and molecular biology. New York: NY: Oxford University Press.

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

Large, V., Peroni, O., Letexier, D., Ray, H., & Beylot, M. (2004). Metabolism of lipids in human white adipocyte. Diabetes & Metabolism, 30(4), 294-309.