Lifeworld

One common outcome of doing glycogen-depleting exercise (e.g., strength training, sprinting) in combination with intermittent fasting is an increase in growth hormone (GH) levels. See this post for a graph showing the acute effect on GH levels of glycogen-depleting exercise. This effect applies to both men and women, and is generally healthy, leading to improvements in mood and many health markers.

It is a bit like GH therapy, with GH being “administered” to you by your own body. Both glycogen-depleting exercise and intermittent fasting increase GH levels; apparently they have an additive effect when done together.

Still, a complaint that one sees a lot from people who have been doing glycogen-depleting exercise and intermittent fasting for a while is that their fasting blood glucose levels go up. This is particularly true for obese folks (after they lose body fat), as obesity tends to be associated with low GH levels, although it is not restricted to the obese. In fact, many people decide to stop what they were doing because they think that they are becoming insulin resistant and on their way to developing type 2 diabetes. And, surely enough, when they stop, their blood glucose levels go down.

Guess what? If your blood glucose levels are going up quite a bit in response to glycogen-depleting exercise and intermittent fasting, maybe you are one of the lucky folks who are very effective at increasing their GH levels. The blood glucose increase effect is temporary, although it can last months, and is indeed caused by insulin resistance. An HbA1c test should also show an increase in hemoglobin glycation.

Over time, however, you will very likely become more insulin sensitive. What is happening is compensatory adaptation, with different short-term and long-term responses. In the short term, your body is trying to become a more efficient fat-burning machine, and GH is involved in this adaptation. But in the short term, GH leads to insulin resistance, probably via actions on muscle and fat cells. This gradually improves in the long term, possibly through a concomitant increase in liver insulin sensitivity and glycogen storage capacity.

This is somewhat similar to the response to GH therapy.

The figure below is from Johannsson et al. (1997). It shows what happened in terms of glucose metabolism when a group of obese men were administered recombinant GH for 9 months. The participants were aged 48–66, and were given in daily doses the equivalent to what would be needed to bring their GH levels to approximately what they were at age 20. For glucose, 5 mmol is about 90 mg, 5.5 is about 99, and 6 is about 108. GDR is glucose disposal rate; a measure of how quickly glucose is cleared from the blood.


As you can see, insulin sensitivity initially goes down for the GH group, and fasting blood glucose goes up quite a lot. But after 9 months the GH group has better insulin sensitivity. Their GDR is the same as in the placebo group, but with lower circulating insulin. The folks in the GH group also have significantly less body fat, and have better health markers, than those who took the placebo.

There is such a thing as sudden-onset type 2-like diabetes, but it is very rare (see Michael’s blog). Usually type 2 diabetes “telegraphs” its arrival through gradually increasing fasting blood glucose and HbA1c. However, those normally come together with other things, notably a decrease in HDL cholesterol and an increase in fasting triglycerides. Folks who do glycogen-depleting exercise and intermittent fasting tend to see the opposite – an increase in HDL cholesterol and a decrease in triglycerides.

So, if you are doing things that have the potential to increase your GH levels, a standard lipid panel can help you try to figure out whether insulin resistance is benign or not, if it happens.

By the way, GH and cortisol levels are correlated, which is often why some associate responses to glycogen-depleting exercise and intermittent fasting with esoteric nonsense that has no basis in scientific research like “adrenal fatigue”. Cortisol levels are meant to go up and down, but they should not go up and stay up while you are sitting down.

Avoid chronic stress, and keep on doing glycogen-depleting exercise and intermittent fasting; there is overwhelming scientific evidence that these things are good for you.

Let me start this post with a warning about spirits (hard liquor). Taken on an empty stomach, they cause an acute suppression of liver glycogenesis. In other words, your liver becomes acutely insulin resistant for a while. How long? It depends on how much you drink; possibly as long as a few hours. So it is not a very good idea to consume them immediately before eating carbohydrate-rich foods, natural or not, or as part of sweet drinks. You may end up with near diabetic blood sugar levels, even if your liver is insulin sensitive under normal circumstances.

The other day I was thinking about this, and the title of this article caught my attention: Alcohol Consumption and the Risk of Type 2 Diabetes Mellitus. This article is available here in full text. In it, Kao and colleagues show us a very interesting table (Table 4), relating alcohol consumption in men and women with incidence of type 2 diabetes. I charted the data from Model 3 in that table, and here is what I got:


I used the data from Model 3 because it adjusted for a lot of things: age, race, education, family history of diabetes, body mass index, waist/hip ratio, physical activity, total energy intake, smoking history, history of hypertension, fasting serum insulin, and fasting serum glucose. Whoa! As you can see, Model 3 even adjusted for preexisting insulin resistance and impaired glucose metabolism.

So, according to the charts, the more women drink, the lower is the risk of developing type 2 diabetes, even if they drink more than 21 drinks per week. For men, the sweet spot is 7-14 drinks per week; after 21 drinks per week the risk goes up significantly.

A drink is 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.

Initially I thought that these results were due to measurement error, particularly because the study relies on questionnaires. But I did some digging and checking, and now think they are not. In fact, there are plausible explanations for them. Here is what I think, and it has to do with a fundamental difference between men and women – sex hormones.

In men, alcohol consumption, particularly in large quantities, suppresses testosterone production. And testosterone levels are inversely associated with diabetes in men. Heavy alcohol consumption also increases estrogen production in men, which is not good news either.

In women, alcohol consumption, particularly in large quantities, increases estrogen production. And estrogen levels are (you guessed it) inversely associated with diabetes in women. Unnatural suppression of testosterone levels in women is not good either, as this hormone also plays important roles in women; e.g., it influences mood and bone density.

What if we were to disregard the possible negative health effects of suppressing testosterone production in women; should women start downing 21 drinks or more per week? The answer is “no”, because alcohol consumption, particularly in large quantities, increases the risk of breast cancer in women. So, for women, alcohol consumption in moderation may also provide overall health benefits, as it does for men; but for different reasons.

Mazess & Mather (1974) is probably the most widely cited article summarizing evidence that bone mineral content in older North Alaskan Eskimos was lower (10 to 15 percent) than that of United States whites. Their finding has been widely attributed to the diet of the Eskimos, which is very high in animal protein. Here is what they say:

“The sample consisted of 217 children, 89 adults, and 107 elderly (over 50 years). Eskimo children had a lower bone mineral content than United States whites by 5 to 10% but this was consistent with their smaller body and bone size. Young Eskimo adults (20 to 39 years) of both sexes were similar to whites, but after age 40 the Eskimos of both sexes had a deficit of from 10 to 15% relative to white standards.”

Note that their findings refer strictly to Eskimos older than 40, not Eskimo children or even young adults. If a diet very high in animal protein were to cause significant bone loss, one would expect that diet to cause significant bone loss in children and young adults as well. Not only in those older than 40.

So what may be the actual reason behind this reduced bone mineral content in older Eskimos?

Let me make a small digression here. If you want to meet quite a few anthropologists who are conducting, or have conducted, field research with isolated or semi-isolated hunter-gatherers, you should consider attending the annual Human Behavior and Evolution Society (HBES) conference. I have attended this conference in the past, several times, as a presenter. That gave me the opportunity to listen to some very interesting presentations and poster sessions, and talk with many anthropologists.

Often anthropologists will tell you that, as hunter-gatherers age, they sort of “shrink”. They lose lean body mass, frequently to the point of becoming quite frail in as early as their 60s and 70s. They tend to gain body fat, but not to the point of becoming obese, with that fat replacing lean body mass yet not forming major visceral deposits. Degenerative diseases are not a big problem when you “shrink” in this way; bigger problems are  accidents (e.g., falls) and opportunistic infections. Often older hunter-gatherers have low blood pressure, no sign of diabetes or cancer, and no heart disease. Still, they frequently die younger than one would expect in the absence of degenerative diseases.

A problem normally faced by older hunter-gatherers is poor nutrition, which is both partially caused and compounded by lack of exercise. Hunter-gatherers usually perceive the Western idea of exercise as plain stupidity. If older hunter-gatherers can get youngsters in their prime to do physically demanding work for them, they typically will not do it themselves. Appetite seems to be negatively affected, leading to poor nutrition; dehydration often is a problem as well.

Now, we know from this post that animal protein consumption does not lead to bone loss. In fact, it seems to increase bone mineral content. But there is something that decreases bone mineral content, as well as muscle mass, like nothing else – lack of physical activity. And there is something that increases bone mineral content, as well as muscle mass, in a significant way – vigorous weight-bearing exercise.

Take a look at the figure below, which I already discussed on a previous post. It shows a clear pattern of benign ventricular hypertrophy in Eskimos aged 30-39. That goes down dramatically after age 40. Remember what Mazess & Mather (1974) said in their article: “… after age 40 the Eskimos of both sexes had a deficit of from 10 to 15% relative to white standards”.


Benign ventricular hypertrophy is also known as athlete's heart, because it is common among athletes, and caused by vigorous physical activity. A prevalence of ventricular hypertrophy at a relatively young age, and declining with age, would suggest benign hypertrophy. The opposite would suggest pathological hypertrophy, which is normally induced by obesity and chronic hypertension.

So there you have it. The reason older Eskimos were found to have lower bone mineral content after 40 is likely not due to their diet.  It is likely due to the same reasons why they "shrink", and also in part because they "shrink". Not only does physical activity decrease dramatically as Eskimos age, but so does lean body mass.

Obese Westerners tend to have higher bone density on average, because they frequently have to carry their own excess body weight around, which can be seen as a form of weight-bearing exercise. They pay the price by having a higher incidence of degenerative diseases, which probably end up killing them earlier, on average, than osteoporosis complications.

Reference

Mazess R.B., & Mather, W.W. (1974). Bone mineral content of North Alaskan Eskimos. American Journal of Clinical Nutrition, 27(9), 916-925.