Wednesday, February 9, 2011

Dangerous protein drinks? by Jerry Brainum

For bodybuilders looking to add muscle and strength, cortisol is a dirty word. Cortisol, a stress-induced adrenal hormone, is classified as a ‘catabolic steroid’. Catabolic refers to the breakdown or degradation of something — in this case muscle. It may also play a role in increasing body fat and through other mechanisms is linked to excess water retention.

So it’s not surprising that bodybuilders are wary of cortisol, which has led to many misconceptions about it. For example, the lower the cortisol, the higher your levels of anabolic hormones, such as growth hormone, insulin and testosterone. True enough, those three hormones have an inverse relationship with cortisol. When cortisol is elevated, they’re often on the low side. The full truth, however, is a little more complex.

One mechanism by which anabolic steroids spur muscle growth is their ability to counteract cortisol in muscle. The steroids compete with cortisol for attachment to glucocorticoid receptor sites and tend to keep the cortisol from attaching to its receptors. When that happens, the cortisol remains inactive, which tips the balance toward anabolism rather than catabolism. The net effect is that steroid users recover far more rapidly between training sessions and get increased muscle protein synthesis, which translates into gains in muscle mass and strength.

Cortisol’s release is set off by various types of stress, including exercise, but that’s where another popular misconception about cortisol and bodybuilding comes into play. While overtraining is a form of stress that usually results in a drop in anabolic hormones and a rise in cortisol, a situation that favours muscle loss, bodybuilders often don’t understand that the exercise-induced cortisol is related to exercise intensity and to how long the workout lasts.

You hear bodybuilders warning about not doing aerobics because it “increases cortisol and causes muscle loss”. In reality, you get more cortisol release with an intense weight workout than you do with aerobics. In fact, the release of cortisol during low-intensity aerobics  — based on heart rate — is negligible. Cortisol doesn’t even begin to rise with aerobic training until you pass the one-hour mark. The one exception would involve the amount of glycogen you have in your muscles and liver. If you’re following an ultralow-carb diet — less than 50 grams of carb a day — your glycogen may be on the low side. When that happens, you’ll get a more rapid release of cortisol during exercise.

One reason for that — and it’s something also usually overlooked — is that a primary function of cortisol is to provide fuel, which it does by triggering the breakdown of proteins into amino acids. The aminos are then converted in the liver to glucose. Cortisol also blocks insulin, resulting in increased blood glucose. With longer-duration exercise, cortisol even sparks the breakdown of fat for use as energy.

All that suggests that if you maintain optimal fuel stores during exercise, cortisol release will be minimised. Because the most rapidly available fuel source is carbohydrate, taking in carbs while you train is an effective way to blunt cortisol release. Studies show that getting some carbs during training works particularly well for those over 40. That’s good news, since older people release more cortisol during exercise than younger people. A drink containing no more than 8 per cent carb, sipped gradually throughout the workout, is best. Getting some carbs and protein immediately after training will also help fend off cortisol’s catabolic effects.

Cortisol: The facts

Like testosterone and estrogen, which are also steroid hormones, cortisol is produced from a base of cholesterol. It’s made in a section of the adrenal glands called the zona fasciculata of the adrenal cortex. When the body perceives stress, whether physical or mental, it’s detected in the hypothalamus (located in the brain), which has a direct connection to the nervous system.

The hypothalamus responds by secreting a hormone called corticotropin-releasing factor, which then travels to the anterior portion of the pituitary gland, where it triggers the release of adrenocorticotropic hormone in the blood. The ACTH travels to the adrenal cortex, where it sets in motion the production of cortisol.

Scientists are still squabbling about how this all happens, but we do know that only about 4 per cent of circulating cortisol is unbound, or active in body tissues.

Cortisol counts vary throughout the day, being highest early in the morning and lowest around midnight. Some studies show that training early in the morning compounds the natural exercise-induced release of cortisol.

Among the many effects of cortisol:

• As noted above, cortisol counters the activity of insulin in lowering blood glucose. Conversely, higher insulin blocks cortisol’s catabolic activity in muscle.

• Cortisol stimulates gastric acid secretion. While that would tend to make stomach ulcers worse, the main cause of ulcers isn’t stress or cortisol but a type of acid-resistant bacteria called H. pylori.

• Cortisol causes sodium retention while speeding the loss of potassium, which translates to high blood pressure, commonly associated with stress. One of the reasons that people who use high doses of anabolic steroids often retain water is that some steroids inhibit an enzyme that suppresses cortisol.

• Cortisol depresses the immune response. An excess of it dampens immune response so much that it becomes much easier to catch a bug when your cortisol is elevated — one reason overtraining is associated with more frequent illness. You can counteract exercise-induced immune suppression by taking larger amounts of the amino acid glutamine.

• Some brain researchers believe that the memory defects older people often have could be due to long-term stress, which elevates cortisol in the brain. There, cortisol selectively and gradually destroys neurons in the hippocampus, the seat of memory retention. So a big presence of cortisol considerably ages the brain, resulting in problems with memory and learning.

• Cortisol opposes the activity of anabolic hormones, including testosterone, growth hormone, insulinlike growth factor 1 — a.k.a. IGF-1 — and insulin, although, conversely, the same hormones oppose cortisol’s catabolic activity. One measure of overtraining is the ratio of testosterone to cortisol — if it tips in favour of cortisol, you’ve slipped into overtraining. Interestingly, however, one study found that cortisol actually encourages greater activity of free — that is, active — testosterone following exercise by stimulating its release from its protein binder in the blood.1 Another recent study showed that intense training increases cortisol by stimulating the enzyme that converts inactive cortisone into active cortisol.2 Yet another found that, contrary to popular belief, low-intensity exercise not only doesn’t increase cortisol but actually lowers it.3

Does having high Cortisol make you fat?

People who have Cushing’s syndrome produce excess cortisol. One symptom is excess fat in the trunk and abdomen. Others include insulin resistance, high blood pressure, increased blood fats and a greater rate of cardiovascular disease. That’s the same constellation of symptoms that comprise the metabolic syndrome.

An emerging medical hypothesis is that people who have excess body fat tend to have an overactivity of the enzyme that converts inactive cortisone into active cortisol in fat cells. Indeed, fat cells contain an abundance of the glucocorticoid receptors that interact with cortisol. Research has demonstrated that mice that had excess activity of the cortisol-activating enzyme in fat also had more body fat, along with all the symptoms of the metabolic syndrome. Conversely, mice specially bred to lack the enzyme showed protection against the metabolic syndrome, including resistance to obesity. So scientists have inferred that having higher-than-normal cortisol is the root cause of the metabolic syndrome.4 Some figure that taking drugs that inhibit the enzyme helps prevent obesity.5

The problem with the cortisol-makes-you-fat idea is that we don’t know which comes first, the obesity or the increased activity of the cortisol-activating enzyme in fat cells. Also, does stress play a role in the scenario? Many people are prone to overeat during high-stress conditions, and that may amplify the negative effects.

What we do know is that blocking the cortisol-activating enzyme in fat cells reduces the formation of new fat cells, improves insulin sensitivity, increases fat burning in the liver and fat cells and tends to redistribute fat away from the dangerous central portion of the body to more benign peripheral regions. A recent study found that the loquat, a fruit indigenous to China, contains elements that effectively block the activity of the cortisol-activating enzyme in fat cells.6

While some of the theories about cortisol are controversial, no one disputes its catabolic effects on muscle. Diseases that are characterized by high cortisol always result in muscle wasting. Cortisol is known to selectively cause atrophy, or shrinkage, of the fast-twitch, or type 2, muscle fibres, which are most amenable to muscular growth with training. In contrast, cortisol doesn’t appear to affect the slow-twitch, or type 1, muscle fibres, the so-called endurance fibres. Why that’s so isn’t known. Cortisol increases the rate of muscle breakdown while decreasing muscle-protein-synthesis reactions, and its catabolic effects are more potent in older people. Animal-based studies show that cortisol triggers increased protein breakdown in adult rats, but in aged animals it depresses protein synthesis.

Cortisol unleashes its catabolic properties in muscle in various ways. First, it inhibits the transport of amino acids into muscle, interfering with protein synthesis — the opposite of what insulin does. Cortisol also inhibits the activity of anabolic hormones involved in muscle protein synthesis, including insulin, IGF-1, testosterone and growth hormone, and it blocks the effects of amino acids in that process, particularly the potent branched-chain aminos. Research also shows that cortisol causes muscle atrophy by slowing the production of myogenin, a substance involved in muscle repair and growth.

In addition, cortisol triggers the activity of major muscle cellular breakdown systems — systems that particularly affect contractile proteins linked to added muscle growth and strength. It does that by increasing the expression of certain genes. It blocks muscle protein synthesis directly by inhibiting a muscle-protein-synthesis pathway called mTOR, and it blocks muscle amino acid uptake by depressing a substance called ATF-4 — although insulin can block that effect.

Finally, cortisol encourages the release of myostatin, a protein that blocks muscle growth. That’s thought to be one of its primary catabolic mechanisms in muscle.

Preventing cortisol-induced muscle loss

Some molecular compounds are known to affect what cortisol does in muscle. Here’s a sample, for both good and ill:

Anabolic hormones, including growth hormone, insulin-like growth hormone 1, testosterone and anabolic steroids. Using large doses of anabolic steroids, however, may bring on a cortisol rebound when steroid use ceases. That can lead to a rapid loss of muscle.

Branched-chain amino acids. As noted above, the BCAAs are the most potent amino acids when it comes to stimulating muscle protein synthesis, and leucine is the most powerful of them all at it. In fact, when cortisol tips the balance in favour of muscle breakdown, it’s mainly the BCAAs that are affected. While you might expect that supplementing with extra BCAAs would counter the catabolic effects of cortisol, cortisol in fact overrides the BCAAs and can hinder muscle protein synthesis.

Glutamine. Several studies have shown that the amino acid glutamine opposes cortisol’s catabolic activity. Hospital patients in extreme catabolic states — for example, those who have severe burns — have experienced increased muscle protein synthesis when given high doses of glutamine. Recent studies show that glutamine helps prevent the cortisol-induced release of myostatin in muscle.

Taurine. Test-tube studies show that the amino acid taurine prevents muscle cell atrophy caused by high cortisol. It remains to be seen, however, whether taurine can replicate that effect in an intact human body.

Creatine. Creatine exerts anti-catabolic effects by increasing local production of IGF-1 in muscle and also encourages muscle protein synthesis. Recent studies also show that it helps block myostatin in muscle.

Clenbuterol. Clenbuterol is a drug used to prevent asthma, but animal-based studies show that in large doses it appears to stimulate muscle growth. In muscle, -clenbuterol increases IGF-1 production and lowers myostatin, but those effects are induced only by high doses. In humans, the doses required to produce a true anticatabolic effect will also adversely affect cardiovascular function.

Magnesium. The mineral lowers serum cortisol after aerobic, but not resistance, exercise.

Omega-3 fatty acids. Found in fatty fish, they lower elevated cortisol levels caused by mental stress.

Music. Listening to what’s perceived as pleasant music can lower cortisol, while listening to music perceived as jarring produces the opposite effect.

Phosphatidylserine. PS was shown to lower cortisol by 39 per cent after training when subjects took 600 milligrams daily. It’s thought to work by blunting the release of ACTH from the pituitary gland.

Vitamin C. The antioxidant slightly lowers cortisol, as does drinking black tea.

• Caffeine. The stimulant raises cortisol counts, as does sleep deprivation.

Birth control pills. Some types increase cortisol in women who lift weights.

Driving long distances in heavy traffic increases cortisol; laughing lowers it.

Phlebodium decumanum. This fern extract was shown in a study of young men to block the increase in cortisol produced during exercise. Taking it with PS would be a great combination.

Closing in on cortisol

Finally, keep in mind that besides maintaining vital energy production, cortisol has potent anti-inflammatory effects. Cortisol-based drugs are prescribed primarily for their rapid anti-inflammatory attributes, which makes them useful for treating such diseases as asthma. Inflammation is a by-product of intense exercise, and without cortisol the pain associated with intense-exercise inflammation would be unbearable.

The major goal with cortisol is to keep it under control and in balance with the anabolic hormones so that your body favours anabolic over catabolic effects in muscle. Not having any cortisol release is not only detrimental but potentially life threatening if you’re exposed to something that causes shock. Without cortisol you’d quickly die.

1 Brownlee, K.K., et al. (2005). Relationship between circulating cortisol and testosterone: influence of physical exercise. J Sports Sci Med. 4:76-83.

2 Dovlo, A., et al. (2010). Intense physical exercise increases systemic 11 beta-hydroxysteroid dehydrogenase type 1 activity in healthy adult subjects. Eur J Appl Physiol. 108(4):681-7.

3 Hill, E.E., et al. (2008). Exercise and circulating cortisol levels: the intensity threshold effect. J Endocrinol Investig. 7:587-91.

4 Walker, B.R. (2006). Cortisol — cause and cure for the metabolic syndrome? Diabet Med. 23:1281-1288.

5 Morton, N.M. (2010). Obesity and corticosteroids: 11B-hydroxysteroid type-1 as a cause and therapuetic target in metabolic disease. Mole Cell Endocrinol. 316(2):154-164. .

6 Rollinger, J.M., et al. (2010). 11 b-hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches. Bioorg Medcin Chemistry. 18(4):1507-1515.

7 Gonzalezjurado, J.A., et al. (2008). Effects of the consumption of Phlebodium decumanum on plasma cortisol and testosterone levels in subjects participating in an exercise program. Rev Med Chil. 4:497-503.


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