The Food Issue The Calorie-Restriction Experiment By JON GERTNER The New York Times October 11, 2009
AS AMERICANS become fatter and fatter - a study published in July revealed that obesity rates increased in 23 states last year and declined in none - a select group of men and women under the watchful care of medical professionals have spent the past few years becoming thinner and thinner. There are 132 of them, located in and around Boston, St. Louis and Baton Rouge, La. All are enrolled in a large clinical trial that is financed by the National Institutes of Health and known as Calerie, which stands for Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy. A few years ago, researchers at Washington University in St. Louis, Tufts in Boston and the Pennington Biomedical Research Center in Baton Rouge began recruiting subjects to examine what happens to people who reduce their daily calories by 25 percent for two years. Admissions are rolling, so not all recruits begin and end at the same time. A few of the early participants, in fact, have just completed their two-year stint. The final recruits began their regimens last month. In late summer, in St. Louis and Boston, I met with nearly two dozen subjects in the study. At the Washington University medical complex, Doug Hansen was reclining on his hospital bed one afternoon when I walked in to say hello. Hansen, who is 45 and had been in the Calerie study for six months, seemed the picture of good health: tan, tall, friendly, energetic. Maybe a little thin. "Let me pull up some chairs," he said, and he jumped out of bed. He was dressed in jeans that struck me as noticeably baggy. His T-shirt hung loosely on his frame. After checking in 24 hours earlier, Hansen told me, he went through a battery of tests, which were required of participants at the half-year mark. Some of these were cognitive: interviews and questionnaires, administered by a behavioral researcher, that evaluated his memory and perceptions. Others were mildly invasive. His blood was drawn repeatedly, and his bone-mineral density was measured by scanning equipment that utilized low-levels of radiation. Early that morning, his resting-metabolic rate was calculated by medical technicians who asked him to remain motionless on his bed for 45 minutes as they put a ventilated plastic tent over his head and measured his respiratory output. Also that morning, Hansen swallowed a pink capsule that was slowly passing through his digestive tract. As we spoke, the pill was measuring his core internal temperature and transmitting the information via radio signal to a small, boxlike receiver strapped to his belt. "I've got to wear it until 5 p.m.," he said. Then he shrugged. "It's really not a big deal." At the start, the recruits taking part in what is called calorie restriction were told they would likely see their weight decrease by around 15 percent during the first year. (A smaller number of recruits were put in a control group and instructed to continue their normal eating habits for two years.) After their weight drop, they would plateau at a "weight stability" level. This was Hansen's experience, as well as that of most of the Calerie subjects I met. After six months in the study, Hansen told me, he dropped to 168 pounds from 198, or near his plateau. A curious aspect of the Calerie project, though, is that it is not meant to study weight loss or if one type of diet is better than another. Instead, Calerie is investigating how (and if) a spartan diet affects the aging process and its associated diseases. To the Calerie researchers, these are quite distinct. The aging process, which researchers sometimes call "primary" or "intrinsic" aging, refers to the damage that ordinarily accumulates in our cells as we grow older, a natural condition that seems to have limited the maximal lifespan of humans to 120 years. Diseases that accompany the aging process - often called "secondary aging" - are those afflictions increasingly prevalent in the elderly, like cancer, diabetes and cardiovascular disease. There seems little doubt that calorie restriction can have significant effects on secondary aging. A recent spate of papers in some of the world's leading medical journals demonstrate that in small studies, human subjects following such diets experience astounding drops in cardiovascular risk factors; a forthcoming review on cancer risks in animals with such diets, moreover, suggests a stark correlation - fewer calories mean fewer tumors. This explains why the stakes for Calerie are high. Essentially, the study asks whether calorie restriction allows people to grow older in better health - with less disease, fewer drugs and shorter hospital stays - through a method that neither medicine nor scientific technology have yet come close to approximating. Meanwhile, the experiment aims to shed some light on the more complex and still-unsettled question of whether calorie restriction affects primary aging, and thus longevity, in humans. Going back more than a half century to an experiment at Cornell University in the mid-1930s, calorie restriction has been shown again and again to extend the lives of mice, rats and other animals. An ongoing experiment at the University of Wisconsin on rhesus monkeys, which began in 1989, portends similar results: compared with normal-weight primates on a regular calorie regimen, the monkeys on restricted diets are healthier and more vigorous and seem destined (at least at the moment) for a longer life. A clinical trial that follows human subjects through their entire lives, much as the primate study in Wisconsin does, would be impossible. For one thing, it would be ethically problematic to restrict calories in children (though with animals, the earlier that calorie restriction begins, the longer they live). For another, we already live a long time now, thanks to advances in medicine, surgery and public health, so "if you wanted to do longitudinal studies in humans, it would take 125 years," Eric Ravussin, who leads the team doing the Calerie experiment at Pennington in Baton Rouge, told me. Thus the researchers in the two-year study are instead looking at changes in what they call biomarkers. A decline in Doug Hansen's core internal temperature, for instance, would suggest a slowdown in his primary aging process (data from a respected study on aging shows individuals with lower temperatures generally live longer). Other characteristics related to secondary aging are just as important. As Hansen curtails his calories for the next 18 months, doctors and medical technicians will measure, among other variables, inflammation, insulin levels and blood pressure. Reductions in any of these things would indicate a lessened vulnerability to heart disease and diabetes. Another problem humans present is their susceptibility to temptation. Primates and mice are kept in cages and eat what they are fed; none have ever had to choose to forswear a spring roll or a cupcake. The medical literature on calorie restriction sometimes cites an experiment conducted in Minnesota in the 1940s to study the effects of starvation, especially with the war-torn populations of Europe in mind. The men - all lean to begin with, all volunteers (they were conscientious objectors to World War II) - were subjected to about a 40 percent decrease in caloric consumption. The state of near starvation led a few of the subjects to the threshold of insanity. They became irritable and depressed; some began to lie and cheat; at least one engaged in acts of self-mutilation. Some of the potential insights of the Calerie study, therefore, are psychological as much as physiological. If ordinary Americans want to cut their energy intake by a more modest 25 percent - whether to slow down the aging process or seek a pharmaceutical-free way to reduce the risks of, say, cardiovascular disease - can they actually do it? The feasibility of long-term food reduction has never been adequately investigated. "Here there are really three things we want to know," Susan Roberts, a professor of nutrition and psychiatry who is in charge of the Calerie team at Tufts, told me. "The first is, can we really implement human caloric restriction? The second is, can we really implement it in a way that doesn't neglect the biology? People can't walk around hungry, so is hunger a necessary part of the biology of calorie restriction? The third is, are there unacceptable side effects that you wouldn't pick up in animals that you would pick up in humans?" Roberts went on to say: "And if we found that caloric restriction was healthy and everyone can do it? The goal of the trial is to see if this is ready for prime time." ... http://www.nytimes.com/2009/10/11/magazine/11Calories-t.html *********************************** * POST TO MEDIANEWS@ETSKYWARN.NET * *********************************** Medianews mailing list Medianews@etskywarn.net http://lists.etskywarn.net/mailman/listinfo/medianews
