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Locaserin: The Serotonin Way To Get Skinny

Posted Jul 12 2012 9:58am
The FDA's recent approval of Locaserin as a weight loss medication puts serotonin back in the spotlight as a major player in controlling appetite. Clearly reducing calorie consumption is the most common way to lose weight, but this is hard to do when you can't stop polishing off the ice cream after dinner. Gratefully the neurotransmitter serotonin is better than will power because it makes the dieter feel full, even when the stomach is still somewhat empty.

Serotonin is known as a mood regulator, and many drugs that treat mood disorders increase serotonin activity. But serotonin has another critical function in the brain: it produces a sensation of satiety or satisfaction after eating, and the specific sites or receptors in the brain involved in turning off the appetite differ from those regulating mood.

The newly approved diet drug Locaserin enhances serotonin's interaction with these satiety sites, turning up the volume, as it were, so that the dieter stops eating even if there is food on your plate. The feeling is somewhat similar to no longer wanting to drink any water when our body has had enough. We may have been gulping water a minute earlier but when the thirst goes, drinking more may even feel aversive. People who feel satiated can figuratively and literally walk away from the food they were eating seconds before.

The body's signal to halt water intake is natural; we don't have to use will power to stop ourselves. And the body's signal to stop eating is also natural. Indeed, serotonin is nature's way of controlling our food intake. But of course just as someone can continue drinking beer long after the thirst is gone, many of us continue eating long after our brain is telling us to stop. (This is why we eat dessert after announcing that we can't eat another bite.)

Locaserin will make it harder, but not impossible, to continue eating after feeling full. This is probably why the results of a two year trial with the drug showed a significant but relatively small reduction in weight loss after the first treatment year, and no further weight loss after two years among those still taking the medication. 1

Locaserin does not work by itself; like antidepressants, it works by making serotonin more effective. But what if the dietary recommendations cause too little serotonin to be made? Would the drug eventually become less effective? Diets that limit or avoid carbohydrate consumption, such as the popular high protein-low carbohydrate diets of the last decade, might actually impair the potency of the weight loss drug because of low levels of serotonin.

It's important to note that serotonin is made only when non-fruit carbohydrates are eaten with little or no protein. Protein prevents the uptake into the brain of the amino acid tryptophan, the building block of serotonin. Increasing one's serotonin production naturally is as easy as eating 25-30 g of non-fruit carbohydrate, with little, if any, fat and protein, approximately one half hour before mealtime. I assume that the subjects in the Locaserin clinical trials followed conventional weight loss diets, so presumably enough carbohydrate was eaten to provide the brain with serotonin. However, if diets are recommended that prevent serotonin from being made, this weight loss drug may decrease its efficacy.

I had two other concerns pop out after reading about the clinical trials: why wasn't weight lost during the second year? All the subjects still had a considerable amount of weight to lose, but progress was halted. And those who were switched without their knowledge from the drug to placebo during the second year gained back all their weight. Why?

It's important to note that all weight loss pharmaceuticals, Locaserin is not the magic weight loss pill. It won't eliminate one's personal triggers to overeat, i.e. exhaustion, stress, overwork, financial concerns, bad marriages or loneliness. But by giving the dieter control over food intake, perhaps he or she can now focus on what caused the overeating and develop strategies to resolve those problems so the weight will not be regained.

1 Smith, BM Weissman NJ Anderson CM et al Multicenter, Placebo Controlled Trial of Lorcaserin for Weight Management. NEJ of Med. 2010:363:245-256
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