Niacin and its effects on growth hormone, glucagon, cortisol, blood lipids, mental disorders, and fasting glucose levels

Niacin is a very interesting vitamin. It is also known as vitamin B3, or nicotinic acid. It is an essential vitamin whose deficiency leads to a dreadful disease known as pellagra. In large doses of 1 to 3 g per day it has several effects on blood lipids, including these: it increases HDL cholesterol, decreases triglycerides, and decreases Lp(a). Given that this is essentially a reversal of the metabolic syndrome, for those who are on their way to developing it, niacin must really do something good for our body. Niacin is also a powerful antioxidant.

The lipid modification effects of niacin are so consistent across a broad spectrum of the population that some companies that commercialize niacin-based products guarantee some measure of those effects. The graphs below (click to enlarge) are from Arizona Pharmaceuticals, a company that commercializes an instant-release niacin formulation called Nialor (see: arizonapharmaceuticals.com). The graphs show the peak effects on HDL cholesterol and triglycerides at the recommended dose, which is 1.5 g per day. The company guarantees effects; not the peak effects shown, but effects that are large enough to have clinical significance.

Niacin also has been used in the treatment of various mental disorders, including schizophrenia. Its effectiveness in this domain (mental disease) is still under debate. Yet many people, including reputable mental health researchers, swear by it. Empirical research suggests beyond much doubt that niacin helps in the treatment of depression and bipolar disorder.

Abram Hoffer, a Canadian psychiatrist who died in 2009, at the age of 91, has discussed at length the many beneficial health effects of niacin. He was also a niacin user. He argued that it can even make people live longer, and be generally healthier and more active. The effect on longevity may sound far-fetched, but there is empirical data supporting this hypothesis as well. (For more, see this book.)

By the way, moderate niacin supplementation seems to increase the milk output of cows, without any effect on milk composition.

Most people dislike the sensation that is caused by niacin, the “niacin flush”. This is a temporary sensation similar to that of sunburn covering one’s full torso and face. It goes away after a few minutes. This is niacin’s main undesirable side effect at doses up to 3 g per day. Higher doses are not recommended, and can be toxic to the liver.

Nobody seems to understand very well how niacin works. This leads to some confusion. Many people think that niacin inhibits the production of VLDL, free fatty acids, and ketones; preventing the use of fat as an energy source. And it does!

So it makes you fat, right?

No, because these effects are temporary, and are followed, often after 3 to 5 hours, by a large increase in circulating growth hormone, cortisol and glucagon. These hormones are associated with (maybe they cause, maybe are caused by) a large increase in free fatty acids and ketones in circulation, but not with an increase in VLDL secretion by the liver. So ketosis is at first inhibited by niacin, and then comes in full force after a few hours.

The decreased VLDL secretion is no surprise, because VLDL is not really needed in large quantities if muscle tissues (including the heart) are being fed what they really like: free fatty acids and ketones. When VLDL particles are secreted by the liver in small numbers, they tend to be large. As they shrink in size after delivering their lipid content to muscle tissues, they become large LDL particles; too large to cross the endothelial gaps and cause plaque formation.

It is as if niacin held you back for a few hours, in terms of fat burning, and then released you with a strong push.

Since niacin does not seem to suppress the secretion of chylomicrons by the intestines, it should be taken with meals. The meals do not necessarily have to have any carbohydrates in them. If you take niacin while fasting, you may feel “funny” and somewhat weak, because of the decrease in VLDL, free fatty acids, and ketones in circulation. These, particularly the free fatty acids and ketones, are important sources of energy in the fasted state.

Given niacin’s delayed effects, it does not seem to make much sense to take slow release niacin of any kind. In fact, the form of niacin that seems to work best is the instant-release one, the one that gives you the flush. It may be a good idea to wait until 3 to 5 hours after you take it to do heavy exercise. You may feel a surge of energy 3 to 5 hours after taking it, when the delayed effects kick in.

The delayed effects of niacin on growth hormone, cortisol and glucagon are probably the reasons why people taking niacin frequently see a small increase in fasting glucose levels. This increase is usually of a few percentage points, but can be a bit higher in some people. Growth hormone, cortisol and particularly glucagon increase blood glucose levels; and the blood levels of these hormones naturally rise in the morning to get you ready for the day ahead. Niacin seems to boost that. Hence the increase in fasting blood glucose levels. This appears to be a benign effect, easily counterbalanced by niacin’s many benefits.

In spite of a possible increase in fasting glucose levels, there is no evidence that niacin increases average blood glucose levels. If it did, that would not be a good thing. In fact, it has been argued that niacin intake can be part of an effective approach to treating diabetes; Robert C. Atkins discussed this in his Vita-Nutrient Solution book.

Niacin’s effects on lipids are somewhat similar to those of low carbohydrate dieting. For example, both lead to a decrease in fasting triglycerides and an increase in HDL cholesterol. But the mechanisms by which those effects are achieved appear to be rather different.

References:

Quabbe, H.J., Trompke, M., & Luyckx, A.S. (1983). Influence of ketone body infusion on plasma growth hormone and glucagon in man. J. Clin Endocrinol Metab., 57(3):613-8.

Quabbe, H.J., Luyckx, A.S., L'age M., & Schwarz, C. (1983). Growth hormone, cortisol, and glucagon concentrations during plasma free fatty acid depression: different effects of nicotinic acid and an adenosine derivative (BM 11.189). J. Clin Endocrinol Metab., 57(2):410-4.

Schade, D.S., Woodside, W., & Eaton, R.P. (1979). The role of glucagon in the regulation of plasma lipids. Metabolism, 28(8):874-86.

Low omega-6 to omega-3 ratio: Grain-fed meats or industrial vegetable oils?

Just a little note on the use of language. Clearly there is no such a thing as grain-fed or grass-fed beef, because one does not feed beef anything. One feeds cattle grain or grass, and then the resulting beef is said to be “grain-fed” or “grass-fed”. It is a manner of speaking that facilitates discourse, which is why it is used here.

To compensate for this digression, let me show you a graph, which pretty much summarizes the "punch line" of this post. The graph below shows the omega-6 fat contents of 1 lb (454 g) of grain-fed beef and 1 tablespoon (roughly 14 g) of a typical industrial vegetable oil (safflower oil, of the high linoleic acid variety). As you can see, there is a lot more omega-6 in the much smaller amount of industrial vegetable oil. A gram-for-gram comparison would practically make the beef content bar disappear.

It has been estimated that our Paleolithic ancestors consumed a diet with an omega-6 to omega-3 ratio of about 1. While other estimates exist, the general consensus seems to be that that ratio was not much greater than 5. Western diets, in contrast, typically have omega-6 to omega-3 ratios of between 15 and 40. In some cases, the ratio is even higher.

Omega-6 fats are essential fats, meaning that they must be part of one’s diet. Fats make up about 60 percent of our brain. About 20 percent is made up of omega-6 and omega-3 fats. The primary omega-6 fat found in our brain is arachidonic acid, which is either synthesized by our body based on linoleic acid from plant foods or obtained directly from animal foods such as meat and eggs. The predominant omega-3 fat found in our brain is docosahexaenoic acid (DHA), of which certain types of fish and algae are rich sources.

Inflammation is an important process in the human body, without which wounds would never heal. Incidentally, muscle gain would not occur without inflammation either. Strength training causes muscle damage and inflammation, after which recovery leads to muscle gain. Omega-6 fats play an important role in inflammation. Generally, they are pro-inflammatory.

Too much inflammation, particularly in a chronic fashion, is believed to be very detrimental to our health. A very high omega-6 to omega-3 ratio seems to cause excessive and chronic inflammation. The reason is that omega-3 fats are generally anti-inflammatory, counteracting the pro-inflammatory action of omega-6 fats. Over time, a very high omega-6 to omega-3 ratio is believed to cause a number of Western diseases. Among them are cardiovascular complications, cancer, and various autoimmune diseases.

So, should you worry about too much omega-6 from grain-fed meats?

If you think that the answer is “yes”, consider this. Apparently the (arguably) longest-living group in the world, the non-Westernized Okinawans, consume plenty of pork. Pork is a staple of their traditional diet. It is true that the average cut will have an omega-6 to omega-3 ratio of more than 7, which is not very favorable. Pork in general, whether grain-fed or not, is relatively high in omega-6 fats. As a side note, pork is not a good source of linoleic acid (found in plants), even though it is a rich source of arachidonic acid, the omega-6 fat synthesized from linoleic acid by various animals.

It is difficult to estimate the exact amounts of omega-6 and omega-3 fats from grain-fed cuts of meat; different sources provide different estimates. Here are some reasonable estimates based on various sources, including Nutritiondata.com. A typical 100 g portion of grain-fed pork should contain about 690 mg of omega-6 fats, and 120 mg of omega-3 fats. A typical 100 g portion of grain-fed beef should have about 234 mg of omega-6 fats, and 12 mg of omega-3 fats. It does not take that much omega-3 to counterbalance the omega-6 obtained from grain-fed pork or beef, even if one eats a lot of them. Two softgels of fish oil will normally contain about 720 mg of omega-3 fats (they will also come with 280 mg of omega-6 fats). Three sardines will have over 2 g of omega-3 fats, and less than 200 mg of omega-6 fats.

Industrial vegetable oils (made from, e.g., safflower seeds, soybean, and sunflower seeds) are very, very rich sources of omega-6 fats, in the form of linoleic acid. There is a lot more omega-6 in them than in grain-fed meats. One tablespoon of safflower oil contains over 10 g of omega-6 fats, in the form of linoleic acid, and virtually zero omega-3 fats. About 2 kg (4.4 lbs) of grain-fed pork, and 5 kg (11 lbs) of grain-fed beef will give you that much omega-6; but they will also come with omega-3.

How much fish oil does one need to neutralize 10 g of pure omega-6 fats? A lot! And there is a problem. Excessive fish oil consumption may be toxic to the liver.

If you cook with industrial vegetable oils rich in linoleic acid (this excludes olive and coconut oils), or eat out a lot in restaurants that use them (the vast majority), you will probably be consuming significantly more than 10 g of omega-6 fats per day. The likely negative health effects of eating grain-fed meats pales in comparison with the likely negative health effects of this much omega-6 fats from industrial vegetable oils.

You should reduce as much as possible your consumption of industrial vegetable oils rich in linoleic acid, as well as other products that use them (e.g., margarine). Keep in mind that industrial vegetable oils are in many, many industrialized foods; even canned sardines, if they are canned with soybean oil.

It is also advisable to couple this with moderate consumption of fish rich in omega-3, such as sardines and salmon. (See this post for a sardine recipe.) Taking large doses of fish oil every day may not be such a good idea.

Should you also consume only grass-fed meat? Do it if you can. But, if you cannot, maybe you shouldn’t worry too much about it. This also applies to eggs, dairy, and other animal products.

References:

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

Ramsden, C.E., Faurot, K.R., Carrera-Bastos, P., Cordain, L., De Lorgeril, M., & Sperling (2009). Dietary fat quality and coronary heart disease prevention: A unified theory based on evolutionary, historical, global, and modern perspectives. Current Treatment Options in Cardiovascular Medicine, 11(4), 289-301.

Schmidt, M.A. (1997). Smart fats: How dietary fats and oils affect mental, physical and emotional intelligence. Berkeley, CA: North Atlantic Books.

38 g of sardines or 2 fish oil softgels? Let us look at the numbers

The bar chart below shows the fat content of 1 sardine (38 g) canned in tomato sauce, and 2 fish oil softgels of the Nature Made brand. (The sardine is about 1/3 of the content of a typical can, and the data is from Nutritiondata.com. The two softgels are listed as the “serving size” on the Nature Made bottle.) Both the sardine and softgels have some vegetable oil added; presumably to increase their vitamin E content and form a more stable oil mix. This chart is a good reminder that looking at actual numbers can be quite instructive sometimes. Even though the chart focuses on fat content, it is worth noting that the 38 g sardine also contains 8 g of high quality protein.

If your goal with the fish oil is to “neutralize” the omega-6 fat content of your diet, which is most people’s main goal, you should consider this. A rough measure of the omega-6 neutralization “power” of a food portion is, by definition, its omega-3 minus omega-6 content. For the 1 canned sardine, this difference is 596 mg; for the 2 fish oil softgels, 440 mg. The reason is that the two softgels have more omega-6 than the sardine.

In case you are wondering, the canning process does not seem to have much of an effect on the nutrient composition of the sardine. There is some research suggesting that adding vegetable oil (e.g., soy) helps preserve the omega-3 content during the canning process. There is also research suggesting that not much is lost even without any vegetable oil being added.

Fish oil softgels, when taken in moderation (e.g., two of the type discussed in this post, per day), are probably okay as “neutralizers” of omega-6 fats in the diet, and sources of a minimum amount of omega-3 fats for those who do not like seafood. For those who can consume 1 canned sardine per day, which is only 1/3 of a typical can of sardines, the sardine is not only a more effective source of omega-3, but also a good source of protein and many other nutrients.

As far as balancing dietary omega-6 fats is concerned, you are much better off reducing your consumption of foods rich in omega-6 fats in the first place. Apparently nothing beats avoiding industrial seed oils in that respect. It is also advisable to eat certain types of nuts with high omega-6 content, like walnuts, in moderation.

Both omega-6 and omega-3 fats are essential; they must be part of one’s diet. The actual minimum required amounts are fairly small, probably much lower than the officially recommended amounts. Chances are they would be met by anyone on a balanced diet of whole foods. Too much of either type of fat in synthetic or industrialized form can cause problems. A couple of instructive posts on this topic are this post by Chris Masterjohn, and this one by Chris Kresser.

Even if you don’t like canned sardines, it is not much harder to gulp down 38 g of sardines than it is to gulp down 2 fish oil softgels. You can get the fish oil for $12 per bottle with 300 softgels; or 8 cents per serving. You can get a can of sardines for 50 cents; which gives 16.6 cents per serving. The sardine is twice as expensive, but carries a lot more nutritional value.

You can also buy wild caught sardines, like I do. I also eat canned sardines. Wild caught sardines cost about $2 per lb, and are among the least expensive fish variety. They are not difficult to prepare; see this post for a recipe.

I don’t know how many sardines go into the industrial process of making 2 fish oil softgels, but I suspect that it is more than one. So it is also probably more ecologically sound to eat the sardine.

Moderate alcohol consumption’s benefits: Blood flow or hormesis?

Moderate alcohol consumption has been found again and again to be beneficial to health (, , ). Even somewhat pessimistic studies linking alcohol consumption with health suggest that 6 drinks per week is optimal (). One drink is generally defined as: a 4-ounce glass of wine, a 12-ounce bottle or can of beer, or a 1.5-ounce shot of hard liquor. The amounts of ethanol vary, with more in hard liquor: 4 ounces of wine = 10.8 g of ethanol, 12 ounces of beer = 13.2 g of ethanol, and 1.5 ounces of spirits = 15.1 g of ethanol.

Contrary to popular belief, the positive health effects of moderate alcohol consumption have little, if anything, to do with polyphenols such as resveratrol. It is in fact the ethanol content that leads to the positive effects, apparently reducing the incidence of coronary heart disease, diabetes, hypertension, congestive heart failure, stroke, dementia, Raynaud’s phenomenon, and all-cause mortality. Raynaud's phenomenon is associated with poor circulation in the extremities (e.g., toes, fingers), which in some cases can progress to gangrene.

Two main explanations for the positive health effects of moderate alcohol consumption are: (a) that it improves blood flow; and (b) that it improves liver function via hormesis. These two explanations are not mutually exclusive and may both be right. The latter explanation is based on the assumption that often a favorable biological response results from low exposures to toxins and other stressors. This is fundamentally a compensatory adaptation response ().

It is not very easy to find evidence in favor of the first explanation above – that moderate alcohol consumption improves blood flow. An old study by Fewings and colleagues is a welcome exception. The study was published in 1966 in the British Journal of Pharmacology. It is titled: “The effects of ethyl alcohol on the blood vessels of the hand and forearm in man” ().

The figure below, from the study, shows average measures for 5 people who consumed 100 ml of brandy. This is equivalent to about 2 drinks. Each set of points reflects measurements taken at 30-minute intervals. The top graph shows the variation in blood alcohol content over time in mg / 100 ml. The middle graph shows the variation in hand blood flow over time in what the authors reported to be ml / 100 ml / min. The bottom graph shows the variation in forearm blood flow over time in the same scale as hand blood flow.

Many other measures are reported by the authors of the study, including measures in response to direct intra-arterial injection of ethanol. When injected, ethanol appears to have a nonlinear effect, opposite to that of oral consumption at first. Injected ethanol seems to impair blood flow at first, and then improve it significantly after a while.

Oral ethanol intake, through drinking alcoholic beverages, is the main focus of this post.

The authors also show evidence that the improvement in blood flow maintains itself for more than 2 h, and that flow becomes impaired at very high levels of blood alcohol.

So, as we can see, moderate alcohol consumption seems to improve blood flow. Why would this enhance one’s health?

One reason is that many important chemicals flow through the blood, which is about 90 percent water. Among these chemicals are free fatty acids, glucose, vitamins, minerals and oxygen. Without these chemicals, organs cannot operate properly, and in fact their tissues may die rather quickly. For example, for normal function the brain requires 3.3 ml / min of oxygen per 100 g of brain mass.

Another reason is that impaired blood flow seems to be significantly associated with accelerated atherosclerotic plaque growth, via a phenomenon known as endothelial cell apoptosis ().

Alcohol consumption, mortality, and cardiovascular disease

The graphs below summarize key results from a study published in April of 2018 by the highly influential journal The Lancet (). The study reported having included at least 599,912 drinkers in the analysis and having recorded 40,310 deaths and 39,018 cardiovascular disease events. The authors of the study concluded that “For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week.”

The study was presented as being somewhat pessimistic: one cannot drink as much as previous data suggested. Let’s see. Two drinks of a spirit (e.g., whiskey) served “neat” (i.e., with nothing added to it) will typically add up to about 84 g; or 3 oz. If the alcohol content is 40 percent, such a double drink will contain about 33 g of alcohol. So, according to this study, you can still enjoy three double drinks of spirit per week, or six single drinks – which is almost one per day. That is not so little.

This study is consistent with most studies of the effect of alcohol consumption on health, which generally show results in terms of averages within fixed ranges of consumption. For example, they will show average mortality risks for people consuming 1, 2, 3 etc. drinks per day. These studies suggest that there is a J-curve relationship between alcohol consumption and health. That is, drinking a little is better than not drinking; and drinking a lot is worse than drinking a little.

Contrary to popular belief, the positive health effects of moderate alcohol consumption have little, if anything, to do with polyphenols such as resveratrol. Resveratrol, once believed to be the fountain of youth, is found in the skin of red grapes.

It is in fact the alcohol content that has positive effects, apparently reducing the incidence of coronary heart disease, diabetes, hypertension, congestive heart failure, stroke, dementia, Raynaud’s phenomenon, and all-cause mortality. Raynaud's phenomenon is associated with poor circulation in the extremities (e.g., toes, fingers), which in some cases can progress to gangrene.

In most studies of the effects of alcohol consumption on health, the J-curves emerge from visual inspection of the plots of averages across ranges of consumption. Rarely you find studies where nonlinear relationships are “discovered” by software tools such as WarpPLS (), with effects being adjusted accordingly.

Still, this study is indeed consistent with some past studies suggesting that the amount of alcohol intake that is optimal maybe less than most of us think ().

Baked cod and lobster

Many years ago I lost 60 lbs (27 kg) over a period of about 2-3 years, and kept it off. Often people are surprised when I show them an old picture of myself, where I am visibly obese ().

I have always felt that one of the keys to losing a significant amount of body fat without triggering body starvation responses is to eat a diet that has a high nutrient-to-calorie ratio. The baked cod and lobster dish below, with photos before and after baking, is a good example of a meal in such a diet.

This is a fairly simple meal to prepare; simple and delicious. The cost of this dish goes down significantly if you do not include the lobster. Below is a recipe. I used it to prepare the baked cod and lobster shown on the photos above.

- Cut and spread on two sheet pans about 4 tomatoes, 1 cup of onion, 1 cup of spinach, 2 lbs of cod, and 4 lobster tails (approx. 4 oz each).

- Add some butter to the mix. I recommend more butter on the lobster than on the cod.

- Preheat the oven to 350 degrees Fahrenheit.

- Add seasoning to taste. I suggest using a small amount of salt, and some chili powder, garlic powder, cayenne pepper, and herbs.

- Bake for about 30 minutes, or until the lobster is soft.

Let us say you are hungry, so you eat about one-fourth of all of this. That is one lobster tail and about a quarter of the cod dish. The nutrition content of such a meal is shown below.

So you will be getting about 86 g of protein in this one single meal. The vitamins and mineral contents listed are mostly above 100 percent of the usually recommended intake. All of this while taking in only a little over 500 calories.

It is very difficult to get fat eating like this!

Could the low testosterone problem be a mirage?

Low testosterone (a.k.a. “low T”) is caused by worn out glands no longer able to secrete enough T, right? At least this seems to be the most prevalent theory today, a theory that reminds me a lot of the “tired pancreas” theory () of diabetes. I should note that this low T problem, as it is currently presented, is one that affects almost exclusively men, particularly middle-aged men, not women. This is so even though T plays an important role in women’s health.

There are many studies that show associations between T levels and all kinds of diseases in men. But here is a problem with hormones: often several hormones vary together and in a highly correlated fashion. If you rely on statistics to reach conclusions, you must use techniques that allow you to rule out confounders; otherwise you may easily reach wrong conclusions. Examples are multivariate techniques that are sensitive to Simpson’s paradox and nonlinear algorithms; both of which are employed, by the way, by modern software tools such as WarpPLS (). Unfortunately, these are rarely, if ever, used in health-related studies.

Many low T cases may actually be caused by something other than tired T-secretion glands, perhaps a hormone (or set of hormones) that suppress T production; a T “antagonist”. What would be a good candidate? The figure below shows two graphs. It is from a study by Starks and colleagues, published in the Journal of the International Society of Sports Nutrition in 2008 (). The study itself is not directly related to the main point that this post tries to make, but the figure is.



Look at the two graphs carefully. The one on the left is of blood cortisol levels. The one on the right is of blood testosterone levels. Ignore the variation within each graph. Just compare the two graphs and you will see one interesting thing – cortisol and testosterone levels are inversely related. This is a general pattern in connection with stress-induced cortisol elevations, repeating itself over and over again, whether the source of stress is mental (e.g., negative thoughts) or physical (e.g., intense exercise).

And the relationship between cortisol and testosterone is strong. Roughly speaking, an increase in cortisol levels, from about 20 to 40 μg/dl, appears to bring testosterone levels down from about 8 to 5 ηg/ml. A level of 8 ηg/ml (the same as 800 ηg/dl) is what is normally found in young men living in urban environments. A level of 5 ηg/ml is what is normally found in older men living in urban environments.

So, testosterone levels are practically brought down to almost half of what they were before by that variation in cortisol.

Chronic stress can easily bring your cortisol levels up to 40 μg/dl and keep them there. More serious pathological conditions, such as Cushing’s disease, can lead to sustained cortisol levels that are twice as high. There are many other things that can lead to chronically elevated cortisol levels. For instance, sustained calorie restriction raises cortisol levels, with a corresponding reduction in testosterone levels. As the authors of a study () of markers of semistarvation in healthy lean men note, grimly:

“…testosterone (T) approached castrate levels …”

The study highlights a few important phenomena that occur under stress conditions: (a) cortisol levels go up, and testosterone levels go down, in a highly correlated fashion (as mentioned earlier); and (b) it is very difficult to suppress cortisol levels without addressing the source of the stress. Even with testosterone administration, cortisol levels tend to be elevated.

Isn't possible that cortisol levels go up because testosterone levels go down - reverse causality? Possible, but unlikely. Evidence that testosterone administration may reduce cortisol levels, when it is found, tends to be rather weak or inconclusive. A good example is a study by Rubinow and colleagues (). Not only were their findings based on bivariate (or unadjusted) correlations, but also on a chance probability threshold that is twice the level usually employed in statistical analyses; the level usually employed is 5 percent.

Let us now briefly shift our attention to dieting. Dieting is the main source of calorie restriction in modern urban societies; an unnatural one, I should say, because it involves going hungry in the presence of food. Different people have different responses to dieting. Some responses are more extreme, others more mild. One main factor is how much body fat you want to lose (weight loss, as a main target, is a mistake); another is how low you expect body fat to get. Many men dream about six-pack abs, which usually require single-digit body fat percentages.

The type of transformation involving going from obese to lean is not “cost-free”, as your body doesn’t know that you are dieting. The body “sees” starvation, and responds accordingly.

Your body is a little bit like a computer. It does exactly what you “tell” it to do, but often not what you want it to do. In other words, it responds in relatively predictable ways to various diet and lifestyle changes, but not in the way that most of us want. This is what I call compensatory adaptation at work (). Our body often doesn’t respond in the way we expect either, because we don’t actually know how it adapts; this is especially true for long-term adaptations.

What initially feels like a burst of energy soon turns into something a bit more unpleasant. At first the unpleasantness takes the form of psychological phenomena, which were probably the “cheapest” for our bodies to employ in our evolutionary past. Feeling irritated is not as “expensive” a response as feeling physically weak, seriously distracted, nauseated etc. if you live in an environment where you don’t have the option of going to the grocery store to find fuel, and where there are many beings around that can easily kill you.

Soon the responses take the form of more nasty body sensations. Nearly all of those who go from obese to lean will experience some form of nasty response over time. The responses may be amplified by nutrient deficiencies. Obesity would have probably only been rarely, if ever, experienced by our Paleolithic ancestors. They would have never gotten obese in the first place. Going from obese to lean is as much a Neolithic novelty as becoming obese in the first place, although much less common.

And it seems that those who have a tendency toward mental disorders (e.g., generalized anxiety, manic-depression), even if at a subclinical level under non-dieting conditions, are the ones that suffer the most when calorie restriction is sustained over long periods of time. Most reports of serious starvation experiments (e.g., Roy Walford’s Biosphere 2 experiment) suggest the surfacing of mental disorders and even some cases of psychosis.

Emily Deans has a nice post () on starvation and mental health.

But you may ask: What if my low T problem is caused by aging; you just said that older males tend to have lower T? To which I would reply: Isn’t possible that the lower T levels normally associated with aging are in many cases a byproduct of higher stress hormone levels? Take a look at the figure below, from a study of age-related cortisol secretion by Zhao and colleagues ().



As you can see in the figure, cortisol levels tend to go up with age. And, interestingly, the range of variation seems very close to that in the earlier figure in this post, although I may be making a mistake in the conversion from nmol/l to ηg/ml. As cortisol levels go up, T levels should go down in response. There are outliers. Note the male outlier at the middle-bottom part, in his early seventies. He is represented by a filled circle, which refers to a disease-free male.

Dr. Arthur De Vany claims to have high T levels in his 70s. It is possible that he is like that outlier. If you check out De Vany’s writings, you’ll see his emphasis on leading a peaceful, stress-free, life (). If money, status, material things, health issues etc. are very important for you when you are young (most of us, a trend that seems to be increasing), chances are they are going to be a major source of stress as you age.

Think about individual property accumulation, as it is practiced in modern urban environments, and how unnatural and potentially stressful it is. Many people subconsciously view their property (e.g., a nice car, a bunch of shares in a publicly-traded company) as their extended phenotype. If that property is damaged or loses value, the subconscious mental state evoked is somewhat like that in response to a piece of their body being removed. This is potentially very stressful; a stress source that doesn’t go away easily. What we have here is very different from the types of stress that our Paleolithic ancestors faced.

So, what will happen if you take testosterone supplementation to solve your low T problem? If your problem is due to high levels of cortisol and other stress hormones (including some yet to be discovered), induced by stress, and your low T treatment is long-term, your body will adapt in a compensatory way. It will “sense” that T is now high, together with high levels of stress.

Whatever form long-term compensatory adaptation may take in this scenario, somehow the combination of high T and high stress doesn’t conjure up a very nice image. What comes to mind is a borderline insane person, possibly with good body composition, and with a lot of self-confidence – someone like the protagonist of the film American Psycho.

Again, will the high T levels, obtained through supplementation, suppress cortisol? It doesn’t seem to work that way, at least not in the long term. In fact, stress hormones seem to affect other hormones a lot more than other hormones affect them. The reason is probably that stress responses were very important in our evolutionary past, which would make any mechanism that could override them nonadaptive.

Today, stress hormones, while necessary for a number of metabolic processes (e.g., in intense exercise), often work against us. For example, serious conflict in our modern world is often solved via extensive writing (through legal avenues). Violence is regulated and/or institutionalized – e.g., military, law enforcement, some combat sports. Without these, society would break down, and many of us would join the afterlife sooner and more violently than we would like (see Pinker’s take on this topic: ).

Sir, the solution to your low T problem may actually be found elsewhere, namely in stress reduction. But careful, you run the risk of becoming a nice guy.