Corticosteroids and Weight Gain: Can the Association Tell Us What's Driving the Obesity Epidemic?

Corticosteroids have been shown to associate closely with weight gain in patients, irrespective of changes in diet or exercise patterns. Why might this happen? And what might the answer tell us about the root cause of obesity?

The Caloric Balance Hypothesis -- the traditional explanation for why people get fat -- gives us the idea that "calories count." People gain weight by eating too much and exercising too little.

If corticosteroids cause weight gain, they must do so first by stimulating appetite and/or by slowing "calorie burning" somehow. This would establish a positive caloric balance, which would drive the accumulation of fat in the fat cells.

The Lipophilia Hypothesis tells us that hormonally-driven changes to our fat tissue drive obesity and overweight. A positive caloric balance does not cause obesity -- it results from it. So if corticosteroids cause weight gain, they must do so first by deranging fat tissue metabolism. For instance, they might cause excessive secretion of insulin or changes in insulin sensitivity. This would lead to a deposition of excess fat, which would in turn drive us to establish a positive energy balance.

So both hypotheses make different predictions. But what does the evidence say?

Let's consider some ideas gathered from cursory internet searches about the relationship among corticosteroids, insulin, and weight gain.

1. Here is an article from the Department of Physiology, School Of Medicine from the University of California, San Francisco: "Feast and famine: critical role of glucocorticoids with insulin and daily energy flow."[1]

The authors conclude that: "there are marked interactions between glucocorticoids and insulin on most aspects of metabolism."

They also write: "corticosteroids interact with insulin on food intaken by decomposition, and corticosteroids also increase insulin secretion."

So these drugs stimulate insulin. These drugs also cause weight gain. Both observations are in line with our alternative hypothesis's predictions.

Is this a fluke piece of research? Or can we find other articles that support similar conclusions?

2. Here is more confirmatory evidence from The Journal of Clinical Oncology -- an article written in 1993 entitled: "Body composition changes in patients who gain weight while receiving megestrol acetate."[2]

The authors state that:

"Randomized placebo controlled clinical trials have now established that megestrol acetate [a corticosteroid] causes appetite stimulation and weight gain... there is positive available data to delineate the substance of this increased weight."

As a result, the authors conclude that "the vast majority of the gained weight was clearly from an increase in adipose tissue."

Read that again. The gained weight resulted from excess fat tissue accumulation, not from excessive appetite! How can defenders of Caloric Balance reconcile this?

3. Here is another randomly selected article from The Journal of American Academy of Dermatology entitled: "Super potent topical corticosteroid use associated with adrenal suppression: Clinical considerations."[3]

Since adrenaline is a catabolic hormone while insulin is an anabolic hormone; the suppression of adrenaline would tend to theoretically aid in anabolism. In other words, even if we don't dig deeper into this article, we can see that it implies that these drugs do impact the hormonal/metabolic ensemble, just as Lipophilia predicts.

4. Here is another curious article: "Medication associated with weight gain."[4]

The authors conclude that "clinically significant weight gain is associated with some commonly prescribed medications."

Again, this begs the question. Why? If calories are alone responsible for why we accumulate weight, why are we talking about medications at all?

Even this sliver of essentially randomly selected articles on the topic yields up data and arguments which seem to be very much in line with the Lipophilia Hypothesis and very troublesome for the Caloric Balance Hypothesis.

Weight gain on these medications presents a paradox that the prevailing wisdom cannot untangle. Unless advocates of the idea that "calories count" can somehow explain away the clinically significant weight gain on these medications within the framework of their idea, good scientists have no choice but to throw out this hypothesis.

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1. Dallman MF, Strack AM, Akana SF, Bradbury MJ, Hanson ES, Scribner KA, Smith M. "Feast and famine: critical role of glucocorticoids with insulin and daily energy flow." Front Neuroendocrinol. 1993 Oct;14(4):303-47.

2. CL Loprinzi, DJ Schaid, AM Dose, NL Burnham and MD Jensen. "Body composition changes in patients who gain weight while receiving megestrol acetate." Journal of Clinical Oncology, Vol 11, 152-154, Copyright © 1993 by American Society of Clinical Oncology.

3. E.Gilbertson, M.Spellman, D.Piacquadio, M.Mulford. "Super potent topical corticosteroid use associated with adrenal suppression: Clinical considerations." Journal of the American Academy of Dermatology, Volume 38, Issue 2, Pages 318-321.

4. Margaret Malone, PhD FCCP. "Medication associated with weight gain." The Annals of Pharmacotherapy: Vol. 39, No. 7, pp. 1204-1208. DOI 10.1345/aph.1E434.

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