Growth hormone may rise 300 percent with exercise: Acute increases also occur in cortisol, adrenaline, and noradrenaline

The figure below (click to enlarge) is from the outstanding book Physiology of sport and exercise, by Jack H. Wilmore, David L. Costill, and W. Larry Kenney. If you are serious about endurance or resistance exercise, or want to have a deeper understanding of exercise physiology beyond what one can get in popular exercise books, this book should be in your personal and/or institutional library. It is one of the most comprehensive textbooks on exercise physiology around. The full reference to the book is at the end of this post.

The hormonal and free fatty acid responses shown on the two graphs are to relatively intense exercise combining aerobic and anaerobic components. Something like competitive cross-country running in an area with hills would lead to that type of response. As you can see, cortisol spikes at the beginning, combining forces with adrenaline and noradrenaline (a.k.a. epinephrine and norepinephrine) to quickly increase circulating free fatty acid levels. Then free fatty acid levels are maintained elevated by adrenaline, noradrenaline, and growth hormone. As you can see from the graphs, free fatty acid levels are initially pulled up by cortisol, and then are very strongly correlated with adrenaline and noradrenaline.  Those free fatty acids feed muscle, and also lead to the production of ketones, which provide extra fuel for muscle tissue.

Growth hormone stays flat for about 40 minutes, after which it goes up steeply. At around the 90-minute mark, it reaches a level that is quite high; 300 percent higher than it was prior to the exercise session. Natural elevation of circulating growth hormone through intense exercise, intermittent fasting, and restful sleep, leads to a number of health benefits. It helps burn abdominal fat, often hours after the exercise session, and helps builds muscle (in conjunction with other hormones, such as testosterone). It appears to increase insulin sensitivity in the long run. Maybe natural elevation of circulating growth hormone is one of the “secrets” of people like Bob Delmonteque, who is probably the fittest octogenarian in the world today.

Aerobic activities normally do not elevate growth hormone levels, even though they are healthy, unless they lead to a significant degree of glycogen depletion. Glycogen is stored in the liver and muscle, with muscle storing about 5 times more than the liver (about 500 g in adults). Once those reserves go down significantly during exercise, it seems that growth hormone is recruited to ramp up fat catabolism and facilitate other metabolic processes. Walking for an hour, even if briskly, is good for fat burning, but generates only a small growth hormone elevation. Including a few all-out sprints into that walk can help significantly increase growth hormone secretion.

Having said that, it is not really clear whether growth hormone elevation is a response to glycogen depletion, or whether both happen together in response to another stimulus or related metabolic process. There are other factors that come into play as well. For example, circulating growth hormone increase is moderated by sex hormone (e.g., testosterone, estrogen) secretion, thus larger growth hormone increases in response to exercise are observed in older men than in older women. (Testosterone declines more slowly with age in men than estrogen does in women.) Also, growth hormone increase seems to be correlated with an increase in circulating ketones.

Heavy resistance exercise seems to lead to a higher growth hormone elevation per unit of time than endurance exercise. That is, an intense resistance training session lasting only 30 minutes can lead to an acute circulating growth hormone response, similar to that shown on the figure. The key seems to be reaching the point during the exercise where muscle glycogen stores are significantly depleted. Many people who weight-train achieve this regularly by combining a reasonable number of sets (e.g., 6-12), with repetitions in the muscle hypertrophy range (again, 6-12); and progressive overload, whereby resistance is increased incrementally every session.

Progressive overload is needed because glycogen reserves are themselves increased in response to training, so one has to increase resistance every session to keep up with those increases. This goes on only up to a point, a point of saturation, usually reached by elite athletes. Glycogen is the primary fuel for anaerobic exercise; fat is used as fuel in the recovery period between sets, and after the exercise is over. Glycogen is expended proportionally to the number of calories used in the anaerobic effort. Calories are expended proportionally to the total amount of weight moved around, and are also a function of the movements performed (moving a certain weight 1 feet spends less energy than moving it 3 feet). By the way, not much glycogen is depleted in a 30-minute session. The total caloric expenditure will probably be around 250 calories above the basal metabolic rate, which will require about 63 g of glycogen.

Many sensations are associated with reaching the glycogen depletion level required for an acute growth hormone response during heavy anaerobic exercise. Often light to severe nausea is experienced. Many people report a “funny” feeling, which is unmistakable to them, but very difficult to describe. In some people the “funny” feeling is followed, after even more exertion, by a progressively strong sensation of “pins and needles”, which, unlike that associated with a heart attack, comes slowly and also goes away slowly with rest. Some people feel lightheaded as well.

It seems that the optimal point is reached immediately before the above sensations become bothersome; perhaps at the onset of the “funny” feeling. My personal impression is that the level at which one experiences the “pins and needles” sensation should be avoided, because that is a point where your body is about to “force” you to stop exercising. (Note: I am not a bodybuilder; see “Interesting links” for more extensive resources on the subject.) Besides, go to that point or beyond and significant muscle catabolism may occur, because the body prioritizes glycogen reserves over muscle protein. It will break that protein down to produce glucose via gluconeogenesis to feed muscle glycogenesis.

That the body prioritizes muscle glycogen reserves over muscle protein is surprising to many, but makes evolutionary sense. In our evolutionary past, there were no selection pressures on humans to win bodybuilding tournaments. For our hominid ancestors, it was more important to have the glycogen tank at least half-full than to have some extra muscle protein. Without glycogen, the violent muscle contractions needed for a “fight or flight” response to an animal attack simply cannot happen. And large predators (e.g., a bear) would not feel intimated by big human muscles alone; it would be the human’s response using those muscles that would result in survival or death.

Overall, selection pressures probably favored functional strength combined with endurance, leading to body types similar to those of the hunter-gatherers shown on this post.

Even though the growth hormone response to exercise can be steep, the highest natural growth hormone spike seems to be the one that occurs at night, during deep sleep.

Exercising hard pays off, but only if one sleeps well.

Reference:

Wilmore, J.H., Costill, D.L., & Kenney, W.L. (2007). Physiology of sport and exercise. Champaign, IL: Human Kinetics.

Guest Commentary: Obesity Trends - There is Hope

Laura Kimberly, MSW, MBE
Director of Special Projects
Jefferson School of Population Health

Recently at JSPH, two presenters at separate events referenced the CDC’s Behavioral Risk Factor Surveillance System obesity trend maps in their presentations. These maps track obesity rates over time and create a powerful visual demonstration of the sharp increases in states’ obesity rates since the 1980’s. The numbers are startling, and the associated costs, both fiscal and social, paint a grim picture.

Much has been written recently about the challenge of addressing rising rates of obesity in the United States, and the outlook tends to be gloomy. Well-intentioned interventions may enjoy isolated, short-term success, yet behavioral change with staying power seems elusive. However, at JSPH’s Health Policy Forum on May 12th, Karen Glanz, PhD, MPH, offered a note of hope. She discussed her work, which strives to make connections between academia and the community and to measure the impact of evidence-based interventions. She began by noting that the national vision for health, articulated in the Healthy People 2020 goals, includes an emphasis on creating social and physical environments that improve health for all, and she referenced T. R. Frieden’s health impact pyramid as a helpful framework for examining population health issues.

Dr. Glanz advocates for a social ecological approach to health promotion, and she pointed to several examples of interventions which have had a positive impact in the sphere of community and health system environmental interventions, and in legislation, regulation, and enforcement. In particular, Dr. Glanz discussed the success of tobacco control initiatives and was hopeful that our experiences with tobacco may help point us in the right direction as we develop strategies to address obesity.

She ended by cautioning that there is more work to be done and reminded us that we can’t assume causal relationships and shouldn’t always rely on randomized control trials as the gold standard when we do have access to natural experiments which can offer valuable insight. In addition, we need to reach disadvantaged populations and develop more practical tools.

All-in-all a sobering and immensely sensitive topic, but an area in which we can’t afford to throw up our hands. Do you think we can develop effective strategies to address rising rates of obesity? Please share your thoughts.

Postprandial glucose levels, HbA1c, and arterial stiffness: Compared to glucose, lipids are not even on the radar screen

Postprandial glucose levels are the levels of blood glucose after meals. In Western urban environments, the main contributors to elevated postprandial glucose are foods rich in refined carbohydrates and sugars. While postprandial glucose levels may vary somewhat erratically, they are particularly elevated in the morning after breakfast. The main reason for this is that breakfast, in Western urban environments, is typically very high in refined carbohydrates and sugars.

HbA1c, or glycated hemoglobin, is a measure of average blood glucose over a period of a few months. Blood glucose glycates (i.e., sticks to) hemoglobin, a protein found in red blood cells. Red blood cells are relatively long-lived, lasting approximately 3 months. Thus HbA1c (given in percentages) is a good indicator of average blood glucose levels, if you don’t suffer from anemia or a few other blood abnormalities.

Based on HbA1c, one can then estimate his or her average blood glucose level for the previous 3 months or so before the test, using one of the following equations, depending on whether the measurement is in mg/dl or mmol/l.

Average blood glucose (mg/dl) = 28.7 × HbA1c − 46.7
Average blood glucose (mmol/l) = 1.59 × HbA1c − 2.59

Elevated blood glucose levels cause damage in the body primarily through glycation, which leads to the formation of advanced glycation endproducts (AGEs). Given this, HbA1c can be seen as a proxy for the level of damage done by elevated blood glucose levels to various body tissues. This damage occurs over time; often after many years of high blood glucose levels. It includes kidney damage, neurological damage, cardiovascular damage, and damage to the retina.

Most regular blood exams focus on fasting blood glucose as a measure of glucose metabolism status. Many medical practitioners have as a target a fasting blood glucose level of 125 mg/dl (7 mmol/l) or less, and largely disregard postprandial glucose levels or HbA1c in their management of glucose metabolism. Leiter and colleagues (2005; full reference at the end of this post) showed that this focus on fasting blood glucose is a mistake. They are not alone; many others made this point, including some very knowledgeable bloggers who focus on diabetes (see “Interesting links” section of this blog). Leiter and colleagues (2005) also provided some interesting graphs and figures, including eye-opening correlations between various variables and arterial stiffness. The figure below (click to enlarge) shows the contribution of postprandial glucose to HbA1c.

Note that the lower the HbA1c is in the figure (horizontal axis), the higher is the postprandial glucose contribution to HbA1c. And, the lower the HbA1c, the closer the individuals are to what one could consider having a perfectly normal HbA1c level (around 5 percent). That is, only for individuals whose HbA1c levels are very high, fasting blood glucose levels are relatively reliable measures of the tissue damage done be elevated blood glucose levels.

The table below (click to enlarge) shows P values associated with the impact of various variables (listed on the leftmost column) on arterial stiffness. This measure, arterial stiffness, is strongly associated with an increased risk of cardiovascular events. Look at the middle column showing P values adjusted for age and height. The lower the P value, the more a variable affects arterial stiffness. The variable with the lowest P value by far is 2-hour postprandial blood glucose; the blood glucose levels measured 2 hours after meals.

Fasting glucose levels were reported to be statistically insignificant because of the P = 0.049, in terms of their effect on arterial stiffness, but this P value is actually significant, although barely, at the 0.05 level (95 percent confidence). Interestingly, the following measures are not even on the radar screen, as far as arterial stiffness is concerned: systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, and fasting insulin levels.

What about the lipid hypothesis, and the “bad” LDL cholesterol!? This study is telling us that these are not very relevant for arterial stiffness when we control for the effect of blood glucose measures. Not even fasting insulin levels matters much! Wait, not even HDL!!! A high HDL has been definitely shown to be protective, but when we look at the relative magnitude of various effects, the story is a bit different. A high HDL’s protective effect exists, but it is dwarfed by the negative effect of high blood glucose levels, especially after meals, in the context of cardiovascular disease.

What all this points at is what we could call a postprandial glucose hypothesis: Lower your postprandial glucose levels, and live a longer, healthier life! And, by the way, if your postprandial glucose levels are under control, lipids do not matter much! Or maybe your lipids will fall into place, without any need for statin drugs, after your postprandial glucose levels are under control. One way or another, the outcome will be a positive one. That is what the data from this study is telling us.

How do you lower your postprandial glucose levels?

A good way to start is to remove foods rich in refined carbohydrates and sugars from your diet. Almost all of these are foods engineered by humans with the goal of being addictive; they usually come in boxes and brightly colored plastic wraps. They are not hard to miss. They are typically in the central aisles of supermarkets. The sooner you remove them from your diet, the better. The more completely you do this, the better.

Note that the evidence discussed in this post is in connection with blood glucose levels, not glucose metabolism per se. If you have impaired glucose metabolism (e.g., diabetes type 2), you can still avoid a lot of problems if you effectively control your blood glucose levels. You may have to be a bit more aggressive, adding low carbohydrate dieting (as in the Atkins or Optimal diets) to the removal of refined carbohydrates and sugars from your diet; the latter is in many ways similar to adopting a Paleolithic diet. You may have to take some drugs, such as Metformin (a.k.a. Glucophage). But you are certainly not doomed if you are diabetic.

Reference:

Leiter, L.A., Ceriello, A., Davidson, J.A., Hanefeld, M., Monnier, L., Owens, D.R., Tajima, N., & Tuomilehto, J. (2005). Postprandial glucose regulation: New data and new implications. Clinical Therapeutics, 27(2), S42-S56.

Oven roasted meat: Pork tenderloin

This cut of pork is the equivalent in the pig of the filet mignon in cattle. It is just as soft, and lean too. A 100 g portion of roasted pork tenderloin will have about 22 g of protein, and 6 g of fat. Most of the fat will be monounsaturated and saturated, and some polyunsaturated. The latter will contain about 450 mg of omega-6 and 15 mg of omega-3 fats in it.

The saturated fat is good for you. The omega-6-to-omega-3 ratio is not a great one, but a 100 g portion will have a small absolute amount of omega-6 fats, which can be easily offset with some omega-3 from seafood or a small amount of fish oil. Pork tenderloin is easy to find in supermarkets, and is much less expensive than filet mignon, even though it is a relatively expensive cut of meat.

Below are the before and after photos of a roasted pork tenderloin we prepared and ate recently; a simple recipe follows the photos. This type of cooking leads to a Maillard reaction, which is clear from the browning of the meat and around it on the casserole. I am not too concerned; more about this after the recipe.

Below is the simple recipe. The roasted pork pieces come off easily after the roasting is done, and almost melt in the mouth!

- Make about 10 holes on 2 lbs of pork tenderloin, and add chopped garlic pieces into each of them.
- Pour about a cup of salsa evenly over the pork tenderloin pieces.
- Cover roasting container (casserole in photos) with aluminum foil to preserve moisture.
- Preheat over to 375 degrees Fahrenheit.
- Roast the pork tenderloin for about 3 hours.

Now back to the Maillard reaction. When it happens inside the body, it is a step in the formation of advanced glycation endproducts (AGEs), which is not very good, as AGEs are believed to cause accelerated aging. However, the evidence that cooked meat is unhealthy, in the absence of leaky gut problems, is very slim. There are many hypothesized causes of the leaky gut syndrome, one of which is consumption of refined wheat products.

Our Paleolithic ancestors must have eaten charred meat on a regular basis, so it does not make much evolutionary sense to think that eating roasted meat leads to accelerated aging through the ingestion of AGEs. It is possible that eating charred meat caused health problems for our ancestors, and they threw their meat in the fire and then ate it charred anyway. Perhaps the health problems caused by charring were offset by the benefits of killing parasites living in meat with the heat of fire.

This is an open issue that needs much more research. Based on most of the research I have seen so far, eating roasted meat is not even in the same universe, in terms of the health problems that it can possibly generate, as is eating foods rich in refined carbohydrates and sugars (e.g., white bread, bagels, pasta, and non-diet sodas).

Intermittent fasting, engineered foods, leptin, and ghrelin

Engineered foods are designed by smart people, and the goal is not usually to make you healthy; the goal is to sell as many units as possible. Some engineered foods are “fortified” with the goal of making them as healthy as possible. The problem is that food engineers are competing with many millions of years of evolution, and evolution usually leads to very complex metabolic processes. Evolved mechanisms tend to be redundant, leading to the interaction of many particles, enzymes, hormones etc.

Natural foods are not designed to make you eat them nonstop. Animals do not want to be eaten (even these odd-looking birds below). Most plants do not “want” their various nutritious parts to be eaten. Fruits are exceptions, but plants do not want one single individual to eat all their fruits. That compromises seed dispersion. Multiple individual fruit eaters enhance seed dispersion. Plants "want" one individual animal to eat some of their fruits and then move on, so that other individuals can also eat.

(Source: Teamsugar.com)

It is safe to assume that doughnut manufacturers want one single individual to eat as many doughnuts as possible, and many individuals to want to do that. That takes some serious food engineering, and a lot of testing. Success will increase the manufacturers' revenues, the real bottom line for them. The medical establishment will then take care of those individuals, and prolong their miserable lives so that they can continue eating doughnuts for as long as possible. It is self-perpetuating system.

As mentioned in this previous post, to succeed in the practice of intermittent fasting, one has to stop worrying about food, and one good step in that direction is to avoid engineered foods. In this sense, intermittent fasting can be seen as a form of liberation. Doing something enjoyable and forgetting about food. Like children playing outdoors; they do not care as much about food as they do about play. Even sleeping will do; most people forget about eating when they are asleep.

Intermittent fasting as a religious and/or social activity, as in the Great Lent and Ramadan, also seems to work well. Any activity that brings people together with a common goal, especially if the goal is not to do something evil, has a lot of potential for success.

If you approach intermittent fasting as another thing to worry about, then it will be tough – one fast per week, on the same day of the week, from 7.33 pm of one day to 3.17 pm of the next day. I exaggerate a bit. Anyway, if you approach it as another obligation, another modern stressor, you will probably fail in the medium to long term. It is just commonsense. Maybe you will be able to do it for a while, but not for long enough to reap some serious benefits. A few fasts are not going to make you lose a lot of weight; the body will adapt in a compensatory way during the fast, slowing down your metabolism a bit and conserving calories. On top of that, you will feel very, very hungry. That will make you binge when you break your fast. Compensatory adaptation (a very general phenomenon) is something that our body is very good at, regardless of what we want it to do.

From a more pragmatic perspective, for most people it is easier to fast at night and in the morning. Eating a big meal right after you wake up is not a very natural activity; several hormones that promote body fat catabolism are often elevated in the morning, causing mild physiological insulin resistance.

If you have dinner at 7 pm, skip breakfast, and then have brunch the next day at 10 am, you will have fasted for 15 h. If you skip breakfast and brunch, and have lunch at noon the next day, you will have fasted for 17 h.

On the other hand, if you have breakfast at 8 am, skip lunch, and then have dinner at 6 pm, you will have fasted only for 10 h.

Leptin levels seem to go down significantly after 12 h of fasting, leading to increased body fat catabolism and leptin sensitivity. This is a good thing, since leptin resistance seems to frequently precede insulin resistance.

Many people think that skipping breakfast will make them fat, for various reasons, including that being what sumo wrestlers do to put on enormous amounts of body fat. Well, skipping breakfast probably will make people fat if, when they break the fast, they stuff themselves to the point of almost throwing up, combine plenty of easily digestible carbohydrates (e.g., multiple bowls of rice) with a lot of dietary fat, and then go to sleep. That is what sumo wrestlers normally do.

Eating fat is great, but not together with lots of easily digestible carbohydrates. Even eating a lot of fat by itself will make it difficult for you to shed enough fat to look like the hunter-gatherers in this post. But your body fat set point will be much lower if you eat a lot of fat by itself than if you eat a lot of fat with a lot of easily digestible carbohydrates.

Anyway, if people skip breakfast and eat what they normally eat at lunch, they will not gain more body fat than they would have if they had breakfast. If they do anything to boost their metabolism in the morning, they will most certainly lose body fat in a noticeable way over several weeks, as long as they have enough fat to lose. For example, they can add some light activity in the morning (such as walking), or have a metabolism-boosting drink (e.g., coffee, green tea), or both.

Our hunter-gatherer ancestors, living outdoors, probably spent most of their day performing light activities that involved little stress. Those activities increase metabolism and fat burning, while keeping stress hormone levels at low ranges. Hunger suppression was the result, making intermittent fasting fairly easy.

Again, intermittent fasting should be approached as a form of liberation. You are no longer a slave of food.

It helps staying away from engineered foods as much as possible, because, again, they are usually engineered with food addiction in mind. I am talking primarily about foods rich in refined carbohydrates and sugars. They come in boxes and plastic bags with labels describing calories and macronutrient composition, which are often wrong or misleading.

Let us say we could transport a group of archaic Homo sapiens to a modern city, and feed them white bread, bagels, doughnuts, potato chips industrially fried in vegetable oils, and the like. Would they say “Yuck, how can these people eat this?” No, they would not. It would be heaven for them; they would want nothing else for the rest of their gustatorily happy but health-wise miserable lives.

While practicing intermittent fasting, it is probably a good idea to have fixed meal times, and skipping them from time to time. The reason is the hunger hormone ghrelin, secreted by the stomach (mostly) and pancreas to stimulate hunger and possibly prepare the digestive tract for optimal or quasi-optimal absorption of food. Its secretion appears to follow the pattern of habitual meals adopted by a person.

References:

Elliott, W.H., & Elliott, D.C. (2009). Biochemistry and molecular biology. 4th Edition. New York: NY: Oxford University Press.

Fuhrman, J., & Barnard, N.D. (1995). Fasting and eating for health: A medical doctor's program for conquering disease. New York, NY: St. Martin’s Press.

On Hiatus

On hiatus until July 2010 or later. Stay tuned for more!

JSPH Inaugural Commencement

TODAY, marks the inaugural commencement for our brand new School of Population Health. That's right---Population Health. A school whose mission is to prepare leaders with global vision to develop, implement and evaluate health policies and systems that improve the health of populations and thereby enhance, the quality of life.

We strive to fulfill this mission by providing exemplary graduate training in health policy, chronic care management, health care quality and safety, AND of course today, in public health.

Our nation stands today at a population health crossroad exemplified in part, by a new law----a law that is 10 weeks old. Whatever your politics, health care delivery in our country will never be the same. We have a lot of work to do!!! We must work hard to reduce the unexplained variation in health care services.
We must reduce disparities in how care is delivered. We must improve the coordination of care. We must improve the quality and safety of the care we deliver.

AND, we must put the patient at the center of all that we do.

Our school, in the great Jefferson University tradition, exemplified by these graduates here today, is preparing a new generation of leaders to meet these challenges. Men and women from a diverse background who now have the skills to go forth and to make a world of difference.

As the inaugural Dean, I am especially proud of the accomplishments of this class, and the support that they received from our faculty and our staff.