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Today in Mice

October 1, 2008

Calorie-Restricted Diets Only Work for Rodents

A diet that is low in calories but highly nutritious may not be as effective in extending the lifespan of humans as it is in rodents


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OK, fine, we admit it: From time to time, despite the best intentions of this blog, the genetic similarities between mice and men don’t quite go far enough.

According to a new study from the Washington University School of Medicine in St. Louis, a diet that is low in calories but highly nutritious may not be as effective in extending the lifespan of humans as it is in rodents. In an article published online in the journal Aging Cell, scientists reveal a discrepancy between humans and animals on calorie restriction.

Previous research had shown that laboratory animals given 30 to 50 percent less food can live as much as 50 percent longer. In part because of those widely publicized findings, calorie restriction diets had become popular among people hoping to lengthen their lives. But the new research suggests that calorie restriction is only effective if people also pay close attention to their protein intake.

In most of the animal models of longevity, a liver-produced protein called IGF-1 (insulin-like growth factor-1) is linked to extended lifespans; in calorie-restricted animals, levels of circulating IGF-1 decline between 30 and 40 percent.

“We looked at IGF-1 in humans doing calorie restriction,” said first author Luigi Fontana, assistant professor of medicine at Washington University and a researcher at the Istituto Superiore di Sanità in Rome, Italy. “For years, we have been following a cohort of people from the CR Society who have been on long-term calorie restriction. We found no difference in IGF-1 levels between people on calorie restriction and those who are not.”

Calorie Restriction Society members call themselves CRONies (Calorie Restriction with Optimal Nutrition), and had been on a calorie-restriction diet for an average of seven years when Fontana took his measurements. But their IGF-1 levels were the same as sedentary people who ate a standard, Western diet.

In another study, called the CALERIE study (Comprehensive Assessment of the Long term Effects of Reducing Intake of Energy), Fontana and colleagues randomly divided 48 people into three groups: Eighteen slashed their caloric intake by 25 percent for one year. Another 18 started exercising to increase their energy use by 25 percent for a year. A third group of 10 people didn’t change anything. At the end of the year, investigators found no reductions of IGF-1 levels in the group on calorie restriction.

“That was puzzling because it was the first time we hadn’t seen agreement between mice and rats on calorie restriction and humans on calorie restriction,” Fontana said. “But we know there are two major influences on IGF-1 levels: calorie intake and protein intake. So we decided to look at the influence of protein.”

Fontana’s team had also been following another quintessential group for testing over several years: a population of strict vegans, who tended to eat less protein than the CRONies from the CR Society. He compared IGF-1 levels between the two groups and found that the vegans had significantly less circulating IGF-1, even if they weighed more and had more body fat than CRONies. This led Fontana to conclude that protein in the diet seemed to correspond with the lower levels of IGF-1, because the strict vegans got about 10 percent of their total calories from protein, whereas those on calorie restriction tended to get about 23 or 24 percent of calories from protein.

Fontana then asked a group of CRONies to eat less protein for a few weeks — not an easy task for folks on calorie-restricted diets. “But six of them agreed to lower their protein intake,” Fontana said, “and after three weeks their circulating IGF-1 declined dramatically.”

Fontana admits his evidence is preliminary, but the findings suggest that when people adjust their diets to improve health and lengthen life, they should control not only calories and fat but also keep an eye on protein. Traditionally, Fontana pointed out, nutritionists have not worried about people eating too much protein, but these findings suggest that they should.

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