Articles Written by Rehan Jalali

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CORTISOL and Muscle Breakdown

The pain in my muscles was so exaggerated it seemed surreal.  It felt almost as if Popeye had worked me over after eating five cans of spinach.  The intense aches I felt that day would bring about an epiphany that would change everything.  I had been hitting the weights mercilessly for the past six months on a schedule of five days on, one day off with sessions of lung-burning cardio squeezed in.  I was exhausted, sore and wasn’t making the gains in muscle mass that I had expected from such an intense training regimen.  I tried everything—you name it: protein, creatine, vitamins, minerals, etc.  But they only seemed to help minimally.  I took two days off every 12 days, which I thought was plenty; however, after doing some intensive research on overtraining, I realized that high cortisol levels might be my problem.  I quickly went to my physician and had him measure my cortisol levels first thing in the morning.  The verdict was in—my cortisol levels were too high.  This was not only a problem for me, but it afflicts many people across the nation.  Now, most people have heard of cortisol.  And many know it’s bad news.  But unfortunately, they don’t know the extent of damage this catabolic hormone can cause.  This muscle-wasting hormone is literally eating away at their full muscle-building potential.  Weight training enthusiasts must declare all-out war on this catabolic hormone if they have any aspirations of building muscle.  Before we attack all of your cortisol problems, some background on this intriguing subject is in order.  After all, understanding leads to solutions (or was it madness).

Cortisol is the primary glucocorticoid.  It is a natural hormone of the adrenal glands. Although cortisol’s precise actions are not completely understood, we know that it is essential for life.  Cortisol is necessary to maintain important processes in times of prolonged stress.  Most of it’s effects are not directly responsible for the initiation of metabolic or circulatory processes but it is necessary for their full response.

Diagram: Cholesterolà Pregnenoloneà Progesterone à 17-Hydroxyprogesteroneà11-Deoxycortisol à Cortisol.

Cortisol can exert it’s effects on peripheral tissue.  Once in circulation, cortisol is typically bound to a specific glucocorticoid-binding alpha2-globulin called transcortin.  About 75% of cortisol is bound to transcortin, 15-20% bound less tightly to albumin, and 5% of circulating cortisol is unbound (1).  This is an important factor to take into consideration when measuring cortisol levels.  The 24-hour urinary excretion of unmetabolized cortisol is one of the best ways to accurately gauge cortisol levels.  This helps take into account bound and free cortisol.  Exogenous cortisol has a half-life of about 70-90 minutes.  Cortisol can be converted to it’s 11-keto analogue cortisone (you know, the stuff you take when you have some bad swelling or inflammation).

 Normal renal function also requires cortisol.  When there is an absence of cortisol or cortisol is decreased, glomerular filtration rates fall and water cannot be excreted rapidly.  This can consequently lead to water retention and you’ll look just like the Michelin man.

The major catabolic effects of cortisol involve it’s facilitating the conversion of protein in muscles and connective tissue into glucose and glycogen (cortisol may increase liver glycogen). Gluconeogenesis involves both the increased degradation of protein already formed and the decreased synthesis of new protein. Cortisol can also decrease the utilization of glucose by cells by directly inhibiting glucose transport into the cells (1).  A cortisol excess can also lead to a decrease in insulin sensitivity.  Cortisol also reduces the utilization of amino acids for protein formation in muscle cells. A cortisol excess can lead to a progressive loss of protein, muscle weakness and atrophy, and loss of bone mass through increased calcium excretion and less calcium absorption. That is one of the reasons long distance runners tend to have skinny physiques.  With the amount of stress that runners place on their body’s, they have high levels of free radicals as well as cortisol.  Excess cortisol can also adversely affect tendon health.  Cortisol causes a redistribution of bodyfat to occur through an unknown mechanism.  Basically, the extremities lose fat and muscle while the trunk and face become fatter.  Some of the signs of overtraining include higher cortisol levels which may cause depression type of effects.  Cortisol excess can also lead to hypertension because it causes sodium retention (which can make you appear bloated) and potassium excretion.  In other words, excessively high cortisol levels may turn you into a girly man!  So the real challenge becomes how can cortisol levels be controlled but not inhibited completely because of cortisol’s necessary anti-inflammatory effects.  One way is to take anti-cortisol supplements in the morning upon rising and then before bed time as these are two times that cortisol levels seem to be raised.  Timed release would not be an option here because this may suppress cortisol levels over too long of an extended period.  The key is to suppress elevated levels of cortisol not decrease normal physiological levels of this hormone because as I mentioned earlier, a small amount is needed for it’s anti-inflammatory and other effects.

Another one of cortisol’s undesirable effects for athletes is that it causes insulin resistance by decreasing the rate at which insulin activates the glucose uptake system, likely because of a post-insulin receptor block (2).  Any type of stress that occurs to the body signals the nervous system to relay this to the hypothalamus.  The hypothalamus then responds by initiating the stress hormone cascade starting with CRF (corticotrophin releasing hormone) followed by ACTH (adrenocorticotropic hormone) release and finally glucocorticoid production (pretty intense huh?).  Stress to the human body can include trauma, anxiety, infections, surgery, and even resistance training and aerobics.  Recent research has shown that increased cortisol levels also increased protein breakdown by 5-20%. (3).  Even mild elevations in serum cortisol can increase plasma glucose concentration and protein catabolism within a few hours in healthy individuals (4). Cortisol increases with increasing time of intense exercise.  In overtrained individuals, cortisol levels increase while testosterone levels decrease. That is why one measure of overtraining is the testosterone: cortisol ratio.  By the way, overtraining is defined as an increase in training volume and /or intensity of exercise leading to a decrease in performance. Cortisol can increase bodyfat levels especially when it is increased dramatically in the body.  Increased cortisol levels have an adverse effect on testosterone levels.  In fact, one of the primary anti-catabolic effects of testosterone and anabolic steroids is it’s decreasing muscle cortisol metabolism (5).  That is one reason why many athletes can completely overtrain when taking anabolic steroids and still increase lean body mass and strength. 

Some research indicates that cortisol response to resistance training normalizes after about 5 weeks and that the testosterone: cortisol ratio is not adversely affected after long periods of resistance training (6).  This suggests that the body has an adaptive response. 

Cortisol can inhibit growth hormone levels by stimulating the release of somatostatin (a growth hormone antagonist).  It may also reduce IGF-1 expression (IGF-1 is one of the most anabolic agents in the body and is the substance that is responsible for most of growth hormones positive effects because GH converts into IGF-1 in the liver).

Cortisol has other hormone modifying effects.  Cortisol can directly inhibit pituitary gonadotropin and TSH (thyroid stimulating hormone) (7).  By doing so, it can make the target tissues of sex steroids and growth factors resistant to these substances.  It may also suppress an enyme known as 5’ deiodinase which converts the relatively inactive thyroid hormone T4 to the active one known as T3 or triiodothyronine.  This can decrease metabolic rate and make it harder to lose bodyfat (it’s already hard enough for people and anything making it harder definitely needs to be kicked to the curb).

There are different stages in sleep and during one stage, cortisol levels are elevated because protein is being re-cycled.  This is one reason that cortisol suppressing supplements should be taken before bed time to help minimize excess cortisol production during sleep.

Cortisol also seems to play a role in various disease states. It is found in higher than normal levels in diseases ranging from AIDS and multiple sclerosis to

Alzheimer's.  Prolonged high levels of cortisol can throw the immune

system into chaos and ravage the human body.  A growing number of researchers believe that many of the worst, and least understood, diseases will soon be identified as caused by high cortisol, and subsequently treated with cortisol-reducing drugs or supplements.

There was an anti-cortisol conference (the second one ever conducted) held in Las Vegas in 1997 and headed up by Steroidogenesis Inhibitors Inc. and Dr. Alfred T. Sapse.  This conference had many researchers involved in anti-cortisol research.  Abstracts were presented on various supplemental and drug therapies for decreasing cortisol levels especially in excessive cortisol production disorders.  In particular, there was an abstract presented by Dr.Sapse that mentioned some nutritional supplements to lower cortisol levels in the body.  These included gingko biloba, Vitamin A, Zinc, and acetyl l-carnitine (8).  Other abstracts presented there discussed the role of DHEA and it’s metabolites in helping to decrease cortisol levels (9).  Some abstracts presented looked at the progression of cortisol induced diseases. Overall, the conference was very informative and helped researchers answer many questions on cortisol and anti-cortisol therapies as well as opened the door for further anti-cortisol research.

Cortisol suppression may be an essential part in the recovery process for athletes involved in a rigorous training program.  In fact, one of the signs of overtraining syndrome is high cortisol levels.  Moderating (not completely diminishing) cortisol levels is an essential factor in allowing weight training individuals to completely recover from their exercise session and maximize results (something we would all like to do).

It may be a very good idea to get cortisol levels tested by a qualified physician (when I say qualified, I mean one that has done this sort of thing before and has been to med. school) on a regular basis.  One of the best times to test cortisol levels is first thing in the morning on an empty stomach.  This reference value or proper range for cortisol first thing in the morning should be between 4-19 mcg/dl with sample being taken from blood.  The normal range for free cortisol levels measured from urine is between 10-110 pg/ml.  There is also another way to measure cortisol through a salivary cortisol screening.  The normal range for cortisol with this test first thing in the morning is 100-300nmol/L.  These tests may not be the final say in determining high cortisol levels but it will certainly give you an idea about where your cortisol levels stand.

Here are some solid tips to help control cortisol levels:

1)      Diet – Make sure you are supplying your body with all the essential nutrients you need to prevent deficiencies and for optimal function. This includes plenty of high quality protein, complex carbohydrates, essential fatty acids, and vitamins and minerals. Try not to restrict calories continuously as some research suggests that restricting normal caloric intake by 50% can lead to a subsequent increase in cortisol levels by 38% (10).

2)       Do not overtrain – Try not to work out 3 or more days in a row without taking a day off.  Keep workouts to under an hour at the most and train efficiently and intensely.  I know this phrase has been beaten to death but LISTEN TO YOUR BODY!

3)      Take enough rest days between workouts – If you are really sore, then wait an extra day to train until your body fully recovers from your previous workout.  Remember, less may be more in this case.

4)      Relax and try not to get stressed out easily – Take an evening walk with a loved one or take a nap when you get a chance.

5)      Try to get at least 8 hours of sleep per night – Sleep is crucial to the recovery and recuperation process.

6)      Spike Insulin levels after a workout - Insulin actually interferes with cortisol and may enhance cortisol clearance from the body. Spiking insulin levels after a workout (by consuming a high glycemic index carbohydrate) may help minimize excessive cortisol levels since cortisol levels are elevated significantly post resistance training.

Supplements that may help control increased cortisol levels secondary to intense exercise

Phosphatidylserine -This phospholipid which has been known mainly for it’s cognitive effects seems to have cortisol suppressive properties.  Recent research shows that 800 mg Phosphatidylserine given in two divided oral doses helps suppress cortisol secondary to intense weight training (11).  In fact, in this same study, the individuals using PS experienced less muscle soreness as well.  Earlier research by Monteleone confirms these results.  By decreasing cortisol levels, the testosterone:cortisol ratio can increase possibly relating to anabolic effects.  PS seems to only decrease cortisol levels when they are elevated and does not seem to decrease cortisol levels below normal.  Decreasing cortisol levels or suppression of cortisol production is not desired in many instances as it may cause adverse effects such as a decrease in reaction time to wounds and healing mechanisms in the body.  There are two forms of PS available: a brain cortex derivative and a soy lecithin derivative.  The brain cortex PS has been used in most of the studies and shown to be effective. 

Acetyl-L-carnitine – This is basically the acetylated ester of L-carnitine.  This supplement may help prevent the decline in testosterone that occurs during and after an intense resistance training session.   It seems to lessen the response to stress. 

L-Glutamine  - This is the most abundant free amino acid in muscle tissue (12).  It seems to play a very important role in protein synthesis and is very important to weight training athletes.  Some research suggests that glutamine levels may be a good indicator of overtraining or overreaching (12).  In other words, athletes who were overtrained generally had low levels of glutamine along with high levels of cortisol.  One study actually showed that glutamine directly prevents the cortisol-induced degradation of muscle contractile proteins (13).  Some of it’s positive effects include enhancing protein synthesis, increasing GH levels which can counteract some of the catabolic effects of cortisol, potent cell volumizing effects which can create an anabolic environment in muscle cells, and partially determining the rate of protein turnover in the muscle.  An oral glutamine supplement can help athletes prevent some of the symptoms of overtraining.   It may also enhance glycogen synthesis through an unknown mechanism.  It also helps provide a source of fuel for the small intestine and may enhance anti-inflammatory function.   It has been shown to boost immune function.  I hope you get the point--Glutamine is a vital nutrient for weight training athletes. 

Vitamin C – This vitamin, mainly known for it’s anti-oxidant properties, may also have some anti-cortisol effects.  A study done by Stone entitled “Effects of Vitamin C on cortisol and the Testosterone: cortisol ratio” showed a decrease in cortisol levels in 17 junior elite weight lifters. This study also showed that the individuals taking Vitamin C (an extra gram a day) improved their testosterone: cortisol ratio by over 20%.  This type of decrease in cortisol can lead to increased muscle and connective tissue hypertrophy and enhanced recovery from training.  Since Vitamin C also decreases your chances of suffering from a cold or flu infection by 30% (14) and may aid in collagen synthesis, it would be wise to take some extra vitamin C when involved in an intense weight training program.

Zinc - A mineral that is an essential cofactor in over 300 enzymatic reactions in the body including testosterone synthesis and steroid hormone production.  Getting enough zinc may make the difference between making great gains and only making average gains in a weight training program.

Vitamin A – This vitamin which is often times used for healthy skin function may also minimize cortisol levels according to Dr. Sapse.  He suggested this in an abstract he presented at the 1997 conference on cortisol and anti-cortisols (8).  

Gingko Biloba – This herb is mainly used for it’s excellent cognitive effects by increasing blood flow and oxygen to the brain which can lead to greater mental focus and concentration.  It may also have additional benefits of decreasing cortisol levels according to an abstract presented at the 1997 conference on cortisol and anti-cortisols (15).  The anti-stress and neuroprotective effects of ginkgo biloba in this study were due to it’s effect on glucocorticoid biosynthesis.  The EGb 761 standardized gingko biloba extract was used in this study and many of the studies showing that it enhances cognition.

DHEA - This natural hormone of the adrenal glands that declines after the age of 30 seems to have some powerful anti-cortisol effects.  Many abstracts presented at the 1997 conference on cortisol and anti-cortisols discussed DHEA’s role in decreasing cortisol levels.  DHEA is fat soluble so it can cross the blood-brain barrier and have some effects on cognition as well.

Androstenedione – This prohormone is a direct precursor to testosterone which may explain it’s anti-cortisol effects since increases in testosterone can bunt elevated cortisol levels secondary to intense weight training.   Different metabolites of androstenedione and testosterone such as 4-androstenediol, 5-androstendiol, and nornadrostenediol may also exert some anti-cortisol effects.  However, more research needs to be done in this area to make this clear!

Androstenetriol - This steroid metabolite which is chemically known as Delta 5-androstene-3b,7b,17b,triol was shown in an abstract presented at the 1997 conference on cortisol and anti-cortisols to counteract the immunological effects of glucocorticoids (16).  This is an interesting compound that definitely needs to be looked at further. 

Conclusion

This is a subject that will be studied thoroughly in the future.  Studies investigating supplemental strategies against cortisol may help weight trainers get the most out of their workouts and help enhance the recovery and recuperation process.  Now before you think suppressing cortisol levels can make you Hercules, remember, cortisol levels are one piece to a large and complex puzzle. It takes a combination of proper training, nutrition, and supplementation to achieve your true muscle building potential.  However, getting cortisol levels checked by your doctor and implementing strategies against cortisol may be a good idea, especially during a calorie-restrictive dieting phase.  So, the next time you feel tired, sluggish or sore for an abnormally long time in your weight training program, and you don’t know why, look into cortisol levels, and you might find the answer.

References cited:

1.      Griffin J, Ojeda S. Textbook of endocrine physiology, 3^rd ed. New York: Oxford University Press, 1996.

2.      Rizza, et al., “Cortisol-induced insulin resistance in man.  Impaired suppression of glucose production and stimulation of glucose utilization due to a post receptor defect of insulin action,” J Clin Endocrinol Metab 54 (1982) : 131-138.

3.      Brillon, et al., “Effect of cortisol on energy expenditure and amino acid metabolism in humans,” Am J Physiol 268 (1995) : E501-13.

4.      Simmons, et al., “Increased proteolysis: an effect of increases in plasma cortisol within the physiological range,” J Clin Invest 73 (1984) : 412-420.

5.      Hickson, et al., “Glucocorticoid antagonism by exercise and androgenic-anabolic steroids,” Med Sci Sports Exerc 22 (1990) : 331-340. 

6.      Fry, et al., “Resistance exercise overtraining and overreaching.  Neuroendocrine responses,” Sports Med 23.2 (1997) : 106-129.

7.      Chrousos, et al., CRH, Stress and Depression: An Etiological Approach (Las Vegas, NV: Conference on Cortisol and Anti-Cortisols, 1997)

8.      Sapse, et al., Anticortisols in the Treatment of Retinitis Pigmentosa (Las Vegas, NV: Conference on Cortisol and Anti-Cortisols, 1997)

9.      Baulieu, et al., Anticortisols: Their Potential Usefulness (Las Vegas, NV: Conference on Cortisol and Anti-Cortisols, 1997)

10.  Kelley, et al., “Energy restriction and immunocompetence in overweight women,” Nutrition Research 18.2 (1998) : 159-169.

11.  Fahey, et al., Hormonal Effects of Phosphatidylserine (PS) during two weeks of intense weight training (Orlando, Fl : ACSM Conference, 1998)

12.  Rowbottom, et al., “The emerging role of glutamine as an indicator of exercise stress and overtraining,” Sports Med 21.2 (1996) : 80-97.

13.  Hickson, et al., “Glutamine prevents down regulation of myosin heavy chain synthesis and muscle atrophy from glucocorticoids,” Am J Physiol 268 (1995) : E730-E734.

14.  Anderson, et al., “Vitamin C and the common cold: A double-blind trial,” J Canadian Med Assoc 107 (1972) : 503-508.

15.  Papadopoulos, et al., Regulation of Glucocorticoid Synthesis by the Ginkgo Biloba Extract EGb 761 and isolated Ginkgolides (Las Vegas, NV: Conference on Cortisol and Anti-Cortisols, 1997)

16.  Norbiato, et al., In Vitro Immunomodulatory Effects of Delta 5-Androstene-3b,7b,17b Triol (AET) in Hypercortisolemic Patients (Las Vegas, NV: Conference on Cortisol and Anti-Cortisols, 1997)

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