Wednesday, August 31, 2005

New Study Concludes that Nicotine Increases Appetite: The Dangers of Extrapolation from Mice to Humans

According to a press release issued by its authors, a new study to be published in the journal Psychopharmacology shows that nicotine increases appetite, rather than to decrease it as previously thought.

The study apparently found that mice exposed to nicotine were more likely to respond for food, even for weeks after their last nicotine exposure. The authors conclude that smoking may actually increase weight in smokers and that these findings may help discourage people from taking up smoking because of weight concerns.

According to the press release: "A new study by Yale researchers shows that prior nicotine exposure in mice can increase their motivation to respond work for food, weeks after their last exposure to nicotine, a finding that runs counter to the popular belief that nicotine exposure curbs appetite. ... Although acute nicotine can act as an appetite suppressant, these data are the first to suggest that repeated exposure to nicotine has the opposite effect, that nicotine increases motivation for food for weeks following exposure to the drug. ... This research suggests that when young people take up smoking to regulate their weight, this may be counterproductive in addition to being harmful to their health. ... the research might help discourage people from starting to smoke to regulate their weight."

The Rest of the Story

This story I think really demonstrates the dangers of making too much of pure science and laboratory research and of a perspective that would put greater reliance on what happens in an animal laboratory than in the actual human world.

There is abundant human experience as well as clinical research to document that smoking has a significant, and often profound effect on appetite suppression. And because of that effect, along with other factors (such as smoking's effect on the body's metabolism and level of stimulation), smoking has been well-documented to be associated with weight loss or weight suppression.

While the magnitude of weight gain associated with smoking cessation has perhaps been overstated, it does amount, on a population level, to an average of about 4 pounds per smoker. So there seems to be little question, based on human experience and clinical studies, that smoking is associated with appetite and weight suppression.

In fact, the Surgeon General has concluded that 80% of smokers will gain weight after quitting (although, again, the magnitude of the weight gain is small). And the mechanism for this weight gain is also clear: "Increases in food intake and decreases in resting energy expenditure are largely responsible for postcessation weight gain."

The fact that mice in a cage that were exposed to nicotine were more likely to press a lever to obtain food is hardly evidence that the overwhelming experience of smokers through the years has been wrong and that we should change our thinking to believe that nicotine actually increases appetite rather than decreases it.

But that appears to be precisely what the press release is concluding.

The press release states that this research "suggests that when young people take up smoking to regulate their weight, this may be counterproductive." Thus, it is actually suggesting to the press covering this story that based on this one study in mice, we should abandon just about everything we know based on years of human experience (and based on clinical studies involving no fewer than 20,000 human subjects).

Had the release simply reported the finding and made note of the fact that the finding is unexpected based on current beliefs, that would have been fine. The problem here is that the release goes way beyond the conclusion that should be made from this research, and makes a sweeping assertion that suggests throwing out existing belief based on real-life human experience and replacing it with a contrary finding based on the behavior of some mice.

I treated many smokers in my career as a physician, and there is no question based on my experience that in general, smoking is an appetite suppressant and that it does appear to be associated with at least some degree of weight suppression. I will certainly continue to believe what my experience and existing clinical research shows rather than abandoning that because of the behavior of some mice in a cage.

While one could argue that there would be nothing wrong with suggesting to people that smoking actually will increase weight - on the grounds that if it helps prevent smoking then it will be good for the public's health - there are two major problems with that.

First, it raises the question of ethics. Is it appropriate to send false messages for good purposes?

Second, and possibly more significantly, if public health advice ends up being contrary to popular experience, then public health authorities are quickly going to lose credibility. If public health officials, based on this research and its associated press release, actually begin to counsel people not to smoke because they may gain weight, but this ends up flying in the face of people's actual experience (or their observations in other people), then public health's credibility will suffer. This is precisely the type of thing that could lead to an eventual erosion of the credibility, and thus impact, of public health messages.

The rest of the story suggests that too much reliance on what happens in an animal lab rather than in the real human world can result in a loss of perspective that results in inappropriate conclusions, but more importantly: inappropriate messages being sent to the public.

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