Calorie restriction, a diet that is low in calories and high in nutrition, may not be as effective at extending life in people as it is in rodents, according to School of Medicine scientists.
Previous research had shown that laboratory animals given 30 percent to 50 percent less food can live up to 50 percent longer. Because of those findings, some people have adopted calorie restriction in the hope that they can lengthen their lives. But the new research suggests the diet may not have the desired effect unless people on calorie restriction also pay attention to their protein intake.
In an article published online in September in Aging Cell, investigators point to a discrepancy between humans and animals on calorie restriction. In the majority of the animal models of longevity, extended lifespan involves pathways related to a growth factor called IGF-1 (insulin-like growth factor-1), which is produced primarily in the liver. Production is stimulated by growth hormone and can be reduced by fasting or by insensitivity to growth hormone. In calorie-restricted animals, levels of circulating IGF-1 decline between 30 percent and 40 percent.
"We looked at IGF-1 in humans doing calorie restriction," said first author Luigi Fontana, M.D., Ph.D., assistant professor of medicine at WUSTL and an investigator at the Istituto Superiore di Sanita in Rome, Italy. "We found no difference in IGF-1 levels between people on calorie restriction and those who are not."
The CR Society members, who call themselves CRONies (Calorie Restriction with Optimal Nutrition), had been on a calorie-restriction diet for an average of seven years when Fontana did the measurements, but their IGF-1 levels were virtually identical to sedentary people who ate a standard Western diet.
Because calorie restriction is linked to extraordinary increases in maximal lifespan in rats and mice, Fontana and colleagues at WUSTL, including principal investigator John O. Holloszy, M.D., professor of medicine, have been involved in a scientific study that compares calorie restriction to exercise and measures many biological factors linked to longevity and health.
Called the CALERIE study (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy), the project randomly divided 48 people into three groups: Eighteen cut their caloric intake by 25 percent for one year, another 18 started exercising to increase their energy expenditure by 25 percent for a year, and 10 people didn't change anything.
At the end of that year, the investigators measured IGF-1 levels in all three groups. Again they found no reductions 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 had a ready-made study group — a population of strict vegans his team has followed for several years. They tend to eat less protein than the CRONies, so he compared IGF-1 levels between the two groups.
"The vegans had significantly less circulating IGF-1, even if they were heavier and had more body fat than CRONies," he said. "Protein in the diet seemed to correlate with the lower levels of IGF-1. The strict vegans took in 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."
The investigators wanted to take one more look at the relationship between dietary protein and IGF-1, so Fontana asked a group of CRONies to eat less protein for a few weeks, which can be difficult because those on calorie restriction have to do a lot of calculating to ensure they take in very few calories and still get adequate nutrition.
"But six of them agreed to lower their protein intake," Fontana said, "and after three weeks their circulating IGF-1 declined dramatically."
Previous research from Fontana's group had found that a diet lower in protein might protect against some cancers. These more recent findings suggest lowering protein also might be important to longevity. 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.
Fontana isn't proposing radical low-protein diets but is suggesting the current recommended daily allowance (RDA) for protein, which is 0.82 grams of protein per kilogram of body weight, or about 56 grams of protein for an average adult man and 46 grams for an average adult woman. Most people, including CRONies, consume much more protein than the RDA recommendation.
"If our research is on the right track, maybe humans don't need to be so calorie restricted," he said. "Limiting protein intake to .7 or .8 grams per kilogram per day might be more effective. This is just a hypothesis."