Written by Dan Gwartney, M.D.
07 January 2015


How Cortisol Could Be Sabotaging Your Fat-Loss Efforts



A parade of fat-loss products promised rapid weight loss by reducing cortisol, the stress hormone associated with fat accumulation and muscle loss. Bodybuilders are more familiar with cortisol being the catabolic steroid that causes muscle loss. Cortisol activates processes in the muscle cell that lead to the breakdown of contractile protein to make amino acids available to vital organs in an environment perceived as stressful or threatening. Through the course of evolution/adaptation, stress occurred during wars, droughts, and natural disasters; grueling workouts and long sessions on the treadmill weren’t much of a concern to primitive man.

 Adrenal glands produce a number of hormones, including corticosteroids— cortisol and cortisone. These two similar-sounding hormones are co-metabolites, meaning each can be generated from or converted into the other. There is an enzyme that can turn cortisol on or off, depending upon which type it is.

 In healthy individuals, the role of cortisol in fat loss/gain is played within the fat cell. Most obese people have normal circulating cortisol levels.1 Circulating cortisol can be maintained in the normal range by avoiding hypoglycemia (low blood sugar), getting sufficient sleep, sharing healthy social relationships, and avoiding excess physical or emotional stress. Intracellular cortisol concentration is determined by the presence and activity of 11-HSD.

 It’s A Cycle

Obesity also affects 11-HSD1, with the obese having higher fat cell 11-HSD1 content and activity than lean people— two to seven times as much; this is true in both sexes.6,8,9 This effect creates a self-perpetuating condition, as being obese induces changes that promote fat storage. Additionally, inflammatory cytokines— chemical messengers associated with a number of health risks— also increase 11-HSD1.10 As with obesity, this can be self-perpetuating, as the visceral fat depot is a primary source of these harmful cytokines. Also, obese people tend to have larger individual fat cells, called hypertrophic fat cells that along with the surrounding connective tissue, overproduce inflammatory cytokines— another self-perpetuating mechanism that makes it so difficult for the morbidly obese to really make changes without intensive intervention.11

 It Could Be Caused By Intense Exercise

Intensive exercise, particularly resistance training, can increase 11-HSD1 in skeletal muscle.12 This accounts for some of the breakdown in muscle protein that happens with all exercise, but it also serves a physiologic (beneficial) role. Increasing cortisol within the muscle cell helps regulate exercise-related inflammation. However, repeated sessions of severe training, particularly of the same muscle groups, can lead to local (tissue) cortisol excess. This may explain why an elevation in circulating cortisol is not always seen in overtraining, but the (potentially intracellular cortisol-induced) loss of muscle mass and strength still occurs.

You Are Basically A Walking Biochemical Hazard

It should not surprise anyone that insulin can increase cortisol via 11-HSD1 in fat.13 It seems this effect requires the co-presence of cortisol in visceral fat and is more pronounced in hypertrophic fat cells, such as is seen in the obese.14 Table sugar (sucrose) also increases 11-HSD1, possibly due to its fructose content.2 Again, it appears that once a person exceeds a certain threshold, fat goes from being a physiologic store of energy to a pathologic source of inflammatory and harmful biochemicals. Ironically, beta-adrenergic drugs (salbutamol, possibly clenbuterol, etc.) increase 11-HSD1; seemingly, this would contradict the known fat-loss effect of such drugs.10 Consider that adrenaline is the first “fight-or-flight” hormone released during immediate threats.

Maximizing Fat-Loss Efforts

Reducing the activity of 11-HSD1 in fat cells, especially visceral fat cells, would be of great value to the general health of obese Americans. Visceral fat is the “bad fat” more strongly associated with type 2 diabetes, cardiovascular disease, liver abnormalities, and other health conditions. Combining this pathway with other fat-reducing mechanisms (diet, exercise, etc.) would help maximize the efficiency and potency of one’s fat-loss efforts. Reducing the 11-HSD1 activity in the liver would minimize the self-sabotage that occurs during insulin resistance as muscle protein is cannibalized (due to increased 11-HSD1 in the muscle) to make sugar, which perpetuates the need for more insulin. 11-HSD1 promotes the activity of fat-storing and fat-cycling enzymes, and diverts amino acid into sugar production.

 Licorice Root Extract

One source of 11-HSD inhibitors has been available on the shelves of nutrition stores for decades. Licorice root extract (not to be confused with candy licorice) contains a number of derivatives, inhibiting both types of 11-HSD. Unfortunately, licorice does not appear to contain a specific 11-HSD1 inhibitor. These derivatives, including glycyrrhetinic acid and carbenoxolone, are not tissue specific, and inhibit both 11-HSD1 and 11-HSD2.17 The downside to inhibiting 11-HSD2, which is present in the kidneys and colon, is that it leads to potassium loss in the urine and can elevate blood pressure to dangerous levels in some people.

 Another factor discouraging the use of licorice-based supplements for fat loss in male athletes is the negative effect glycyrrhetennic acid and carbenoxolone have on testosterone production. Licorice consumption and animal studies using carbenoxolone, as well as a synthetic 11-HSD1 inhibitor, is associated with lowering natural testosterone production.18 For the drug-using athlete who uses anabolic steroids, a potassium-sparing diuretic, and possibly an ACE inhibitor, this may not be an issue. However, this has never been studied— and certainly is not a recommendation.

 Drugs That Are Used To Inhibit 11-HSD1

A little-mentioned drug uncommonly used by bodybuilders is adrenocorticotropic hormone (ACTH). A pituitary hormone, much like growth hormone (GH), ACTH’s traditional role is to stimulate the adrenal glands to increase circulating cortisol production. Ironically, fat cells exposed to ACTH reduce 11-HSD1.10 GH stimulates the liver, and to a lesser degree skeletal muscle, to produce a secondary messenger called IGF-1. It is IGF-1 but not GH that inhibits 11-HSD1 in both the liver and fat cells, reducing cortisol in these tissues.19

 It has been mentioned that many of the benefits of GH treatment, or signs of GH deficiency, may be related to the concentration of tissue cortisol affected by IGF-1. Interestingly, neither GH nor IGF-1 appear to affect 11-HSD2, supporting the role GH or IGF-1 therapy may have in many conditions. Note: it may take one month or longer for the effects to be evident through blood analysis, or subjectively.