The study, led by John O. Holloszy, M.D., professor of medicine, will appear in the April 27 issue of the Proceedings of the National Academy of Sciences. It will appear in the online edition of the journal the week of April 19. The first author is Luigi Fontana, M.D., Ph.D., research instructor in medicine.
"It's very clear from these findings that calorie restriction has a powerful, protective effect against diseases associated with aging," Holloszy says. "We don't know how long each individual actually will end up living, but they certainly have a much longer life expectancy than average because they're most likely not going to die from a heart attack, stroke or diabetes."
Research on mice and rats has shown that stringent and consistent calorie restriction increases the animals' maximum lifespan by about 30 percent and protects them against cancer. This study is the first to examine individuals who have been on calorie restriction diets for a long period of time.
The researchers recruited participants through a national organization called the Caloric Restriction Optimal Nutrition Society. By eating small amounts of nutrient-dense foods, members of this group try to consume between 10 and 25 percent fewer calories than the average American while still attempting to maintain proper nutrition. The 18 individuals who participated in the study had voluntarily been following this very low-calorie diet for three to 15 years. This group was compared with 18 age- and gender-matched individuals who ate a typical Western diet.
Holloszy's team found the two groups not only differed in the number of calories consumed, but also in the composition of their diets. Individuals in the calorie restriction group ate between about 1,100 and 1,950 calories per day depending on height, weight and gender, and these calories consisted of about 26 percent protein, 28 percent fat and 46 percent complex carbohydrates. In contrast, the comparison group consumed between about 1,975 and 3,550 calories per day, with only 18 percent of their calories from protein, 32 percent from fat and 50 percent from carbohydrates, including refined, processed starches.
Atherosclerosis -- clogged arteries that can lead to a heart attack or stroke -- already is the leading cause of death in the Western world, and the problem is continuing to grow. So Holloszy's team specifically focused on the risk factors for this condition. They measured multiple indications of early or impending atherosclerosis, including blood pressure and levels of several biological markers in the blood, including cholesterol and triglycerides. They also measured the levels of glucose and insulin in the blood to gauge diabetes risk, another major health concern in the American population.
People in the calorie restriction group had total and low-density lipoprotein -- known as LDL or "bad" cholesterol -- levels comparable to the lowest 10 percent of the population in their respective age groups. Their high-density lipoprotein -- known as HDL or "good" cholesterol -- levels were in the 85 to 90 percentile for middle-aged men. That finding was a surprise because HDL levels typically decrease when individuals follow low-fat diets to lose weight.
Triglyceride levels -- which, when elevated, can lead to atherosclerosis -- were even more impressive in the calorie restriction group: They were lower than more than 95 percent of Americans in their twenties, despite the fact that the study participants' ages ranged from 35 to 82.
In contrast, cholesterol and triglyceride levels in the comparison group were in the 50th percentile for average middle-aged Americans. Moreover, 12 of the individuals in the calorie restriction group provided medical records from before and during the diet. Their cholesterol and triglyceride scores also were close to the 50th percentile for middle-aged Americans before the diet, and levels fell the most dramatically during their first year of calorie restriction.
Blood pressure scores in the restricted group also were equivalent to those of much younger individuals. The average blood pressure in the normal diet group was about 130/80, which is standard for the typical American. In comparison, the calorie restriction group's average was about 100/60, akin to the blood pressure of an average 10-year-old. Fasting glucose and insulin -- both markers of the risk of developing diabetes -- also were significantly lower in the calorie restriction group, with insulin concentrations as much as 65 percent lower.
All other risk factors measured also were significantly better in the calorie restriction group. They included body mass index, body fat mass, C-reactive protein and the thickness of the carotid artery, the main blood vessel that runs from the heart to the brain.
"These effects are all pretty dramatic," Fontana says. "For the first time, we've shown that calorie restriction is feasible and has a tremendous affect on the risk for atherosclerosis and diabetes."
The team currently is conducting a controlled, prospective study comparing calorie restriction to the average American diet. They ultimately hope to follow these individuals for a longer period of time to assess the long-term effects of calorie restriction on biological markers of aging.
Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proceedings of the National Academy of Sciences, April 27, 2004.
Funding from the National Institutes of Health supported this research.
The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Proceedings of the National Academy of Sciences