Antihistamine Weight Gain May Give Us Clues about the Fundamental Causes of Human Obesity

Antihistamine weight gain is a well-documented phenomenon. But what causes it?

Mainstream dietitians admonish that "a calorie is a calorie is a calorie." In other words, we gain weight by overeating and/or being inactive. This idea, the Caloric Balance Hypothesis, underlies practically all of our received wisdom about weight control. It tells us that antihistamines can only cause fat accumulation if the drugs somehow can drive us to eat more or to slow down our metabolisms.

Lipophilia, our alternative hypothesis, posits a very different explanation for antihistamine weight gain. It tells us that medications that change the constitution of our fat tissue must do so at a physiological level. Thus, we might expect that antihistamines impact insulin levels or impact the ability of cells to process insulin, for instance. The drugs don't directly change our behaviors; they change the constitution of our fat tissue.

Okay, so we have two theories. Let's take a look at some evidence from a cursory Google search for potentially relevant scientific articles about antihistamine weight gain.

1. Here is one interesting article. We can only see its title (without logging in), but the title itself is very interesting: "Chemical genetic identification of the histamine H1 receptor as a stimulator of insulin induced adipogenesis."[1]

"Insulin induced adipogenesis" is a fancy way of saying "fat tissue created by insulin." If you're talking about a particular histamine receptor being able to stimulate insulin induced fat creation, that would seem to support Lipophilia. Of course, without the rest of the article, it is kind of useless to speculate further.

2. Here's another interesting article about antihistamine weight gain: "Effects of antihistamines in adult asthma: a meta analysis of clinical trials."[2]

Studies conducted to determine the relationship between antihistamines and asthma yielded up the following:

"Side effects [of anti-histamines]... include[d] weight gain."

3. Here is another paper from Psychopharmacology in 1974: "The effect of cyproheptadine on hunger, calorie intake and body weight in man."[3]

The abstract tells us that:

"The weight gain potential of... treatment with the antihistamine and antiserotonergic compound of cyproheptadine... 4 mg three times daily was compared to placebo and a double blind crossover trial in sixteen... otherwise normal volunteers who wanted to gain weight. The subjects gained significantly more weight on cyproheptadine than on placebo. There was also a corresponding relative increase in subjective hunger ratings and food intake during the period on active drug."

Maybe the antihistamines induced appetite or led these people to be more drowsy and lethargic. Thus, they overate and/or under exercised, and that's why the weight gain occurred. But it is equally plausible to argue that the drugs somehow changed fat metabolism, which in turn drove the subjects to establish a positive caloric balance.

Given that this survey of the research is cursory, and that more compelling evidence linking antihistamines to changes in factors like glucose, insulin, and so forth seem likely to exist -- once again, it seems like our preferred hypothesis should be -- must be -- Lipophilia.

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1. Y. Kawazoe, S. Tanaka, M. Uesugi. "Chemical genetic identification of the histamine H1 receptor as a stimulator of insulin induced adipogenesis." Chemistry & Biology, Volume 11, Issue 7, Pages 907-913.

2. E Van Ganse, L Kaufman, MP Derde, JC Yernault, L Delaunois, and W Vincken. "Effects of antihistamines in adult asthma: a meta analysis of clinical trials." Eur Respir J 1997; 10: 2216-2224 Copyright © ERS Journals Ltd 1997.

3. T. Silverstone1 and D. Schuyler. "The effect of cyproheptadine on hunger, calorie intake and body weight in man." Psychopharmacology Springer Berlin / Heidelberg Issue Volume 40, Number 4 / December, 1975.

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