Alpha Blockers and Weight Gain

If patients on alpha blockers gain or lose weight on their medications independent of their caloric intake or general level of activity, what might this tell us about the root cause of overweight and obesity -- and about the obesity epidemic?

The Caloric Balance Hypothesis says that, for a medication to make us gain weight, it must first drive us to eat more calories or burn off fewer calories, and this positive caloric balance then makes us accumulate fat in the fat tissue.

The Lipophilia Hypothesis says that an establishment of a positive caloric balance is a consequence and not a cause of the weight gain. The real cause is the hormonal derangement of the fat tissue itself.

So can we find evidence to test these hypotheses? In particular:

1. Do alpha blockers lead to weight changes independent of factors related to diet and exercise?

2. Can these medications impact the body's hormonal/metabolic ensemble? For instance, can they change insulin sensitivity or otherwise change the ways in which fat tissue metabolism operates?

As to the first point, a rough and not-at-all-comprehensive internet search about alpha adrenergic blockers yields some surprisingly strong support for the Lipophilia conjecture.

1. Consider this article from the December 1998 Journal of Cardiovascular Pharmacology: "Long-term alpha adrenergic blockade attenuates diet-induced dyslipidemia and hyperinsulinemia in the rat."[1]

Now, this article talks about rats, not human beings. But it does suggest that these medications can affect insulin levels.

2. Here's another article that discusses "The effect of the alpha adrenergic blocker, Doxazosin, on endothelial function and insulin action."[2]

3. And here's another article that discusses: "The regulation of plasma insulin level by alpha 2 adrenergic receptors."[3]

4. And here's another yet article on "Insulin inhibition of alpha adrenergic actions in the liver."[4]

Now obviously, our references are relatively arbitrary. But even without delving into the science, the fact that alpha blockers can effect both changes in weight and changes in insulin levels seems to suggest that our alternative hypothesis holds up.

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References


1. Fajardo N, Deshaies Y. "Long-term alpha adrenergic blockade attenuates diet-induced dyslipidemia and hyperinsulinemia in the rat." J Cardiovasc Pharmacol. 1998 Dec;32(6):913-9.

2. C.Hamish Courtneya, David R McCancea, A.Brew Atkinsona, Jonathan Bassettb, Cieran N Ennisa, Brian Sheridana, Patrick M Bella. "The effect of the alpha adrenergic blocker, Doxazosin, on endothelial function and insulin action." Metabolism Clinical and Experimental; Volume 52, Issue 9, Pages 1147-1152 (September 2003).

3. Nakadate T, Nakaki T, Muraki T, Kato R. "The regulation of plasma insulin level by alpha 2 adrenergic receptors." Eur J Pharmacol. 1980 Aug 8;65(4):421-4.

4. J P Dehaye, B P Hughes, P F Blackmore, and J H Exton. Insulin inhibition of alpha-adrenergic actions in liver. Biochem J. 1981 March 15; 194(3): 949–956.

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