Anticonvulsants and Changes in Body Fat: What the Weight Gain Might Tell Us about the Fundamental Cause of Obesity

Anticonvulsants have long been linked to weight gain. Most of us assume that calories ultimately control how many pounds we put on. We think that when we overeat or under exercise, our bodies accumulate fat. But from the perspective of this theory -- also known as the Caloric Balance Hypothesis -- the phenomenon of weight gain on anticonvulsant drugs makes little sense, unless you're willing to make the case that these drugs stimulate patients to over-consume calories and/or under exercise.

The alternative theory, the Lipophilia Hypothesis, implies that changes in weight due to medications must result from changes that occur on the hormonal/metabolic level. The drugs change the constitution of the fat tissue itself.

So let's look at two things:

First, let's examine evidence that anticonvulsants do indeed cause weight gain.

Next, let's check out some science articles to see whether we can find evidence that anticonvulsants change insulin levels.

1. Let's start with this article: "Safety of available agents used to treat bipolar disorder: focus on weight gain."[1]

"Weight gain has been recognized as a common and adverse effect of valproic acid (VPA) that leads to discontinuation in some patients but its incidence and correlates have rarely been studied."

Valproic acid is an anticonvulsant, so what these authors say seems to validate the theory that these drugs do cause weight gain. They conclude that:

"A weight gain of more than 4 kilograms in 70% of the VPA group was observed... from the structured patient interviews, patients with no personal history of weight problems experienced the greatest initial weight increase."

2. Here's another article that seems again to support Lipophilia's predictions: "Effects of sodium valproate in 100 children with special reference to weight."[2]

"Excessive weight gain occurred in a patient who was taking sodium valproate and phenytoin."

The authors conducted a retrospective analysis on 100 different children who had epilepsy and who had been treated with this anticonvulsant. In terms of side effects: "the commonest was increased weight gain, which occurred in 44 cases"

3. Here is yet another article on "Drug induced weight gain."[3] The authors write:

"Drug induced weight gain is a serious side effect of many commonly used drugs leading to noncompliance with therapy and the exacerbation of comorbid conditions related to obesity."

They also state that:

"Antidepressants... and some serotonin reuptake inhibitors... also may promote appreciable weight gain that cannot be explained solely by improvement in depressive symptoms."

4. "Effect of antiepileptic drugs on plasma lipids, lipoprotein A, and liver enzymes."[4]

This paper, from the Journal of Child Neurology, focuses on how anticonvulsants can affect factors such as HDL and cholesterol. The authors conclude that:

"Antiepileptic drugs significantly increase the level of lipoprotein a, which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters."

In other words, these drugs seem to be able to have effects that are strikingly similar to the effects that carbohydrates can have on lipid profiles.

5) And here's another study: "Body weight gain and anticonvulsants: a comparative review."[5]

The authors begin:

"Body weight gain is a common and frequent undesirable effect associated with the use of anticonvulsant drugs. This has been observed for many years..."

The authors discuss how this weight gain seems to be associated with risk for type 2 diabetes, heart disease, polycystic ovary syndrome, and other diseases. In other words, drug therapy does not just predispose for obesity but also for other diseases of civilization. Again, this supports Lipophilia. The authors suggest that:

"Lower blood glucose levels may result from a competition between the binding of the drug and long chain fatty acids. An increased availability of the latter stimulates insulin production and lowers the serum glucose levels."

The authors also discussed how patients demonstrated "increase[d] appetite for carbohydrates and reduced energy expenditure."

We're not talking about calories, folks. We're talking about the stuff that's going on at the level of our physiology.

Once again, even from this cursory research, we seem practically compelled to reject the Caloric Balance Hypothesis explanation out of hand and embrace some version of the alternative hypothesis, Lipophilia.

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1. NEMEROFF Charles B. "Safety of available agents used to treat bipolar disorder: focus on weight gain." The Journal of clinical psychiatry 2003, vol. 64, no5, pp. 532-539.

2. J Egger and E M Brett. "Effects of sodium valproate in 100 children with special reference to weight." Br Med J (Clin Res Ed). 1981 August 29; 283(6291): 577–581.

3. Ness-Abramof, R., Apovian, C.M. Drug-induced Weight Gain Drugs Today 2005, 41(8): 547 ISSN 1699-3993 Copyright 2005 Prous Science.

4. Fatma Mujgan Sonmez, MD. "Effect of antiepileptic drugs on plasma lipids, lipoprotein A, and liver enzymes." Journal of Child Neurology, Vol. 21, No. 1, 70-74 (2006).

5. Jallon P, Picard F. Bodyweight gain and anticonvulsants: a comparative review. Drug Saf. 2001;24(13):969-78.

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