Drastically cutting calories lowers some risk factors for age-related diseases​​

Two-year study finds no changes in metabolic markers linked to longevity

The​ largest study to date of sustained calorie reduction in adults shows that it does not produce all of the metabolic effects associated with longevity that have been found in animal studies. Severely cutting calorie intake, however, did appear to lower the risk of cardiovascular disease and make people more sensitive to insulin.

The study is published in the September 2015 issue of the Journal of Gerontology: Medical Sciences.

Over two years, the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial followed 218 young and middle-aged healthy men and women who were of normal weight or just slightly overweight. The study was designed to see what would happen to resting metabolic rate and body temperature if people were to cut daily calorie intake by 25 percent. Body temperature decreases and resting metabolic rate drops in laboratory animals on calorie-restriction diets — changes thought to be potential contributors to increased lifespan.

John O. Holloszy, MD, and colleagues found that calorie restriction does not produce all of the metabolic effects associated with longevity that have been found in animal studies. (Credit: Robert Boston)

But human subjects didn’t experience those changes, according to John O. Holloszy, MD, principal investigator of the study at Washington University School of Medicine in St. Louis.

“People in the study lost weight with calorie restriction,” Holloszy said. “But we didn’t see the same changes that we see in animals. That could mean that calorie restriction doesn’t work the same way in people as it does in animals, or it could mean that other changes linked to calorie restriction are the ones affecting longevity. Whatever those beneficial changes are, we’d like to identify them and see whether there’s some way to help people get those benefits without having to cut calorie intake so dramatically.”

Calorie restriction helped people in the study lose weight but not the 15.5 percent weight loss that had been expected. Those who practiced calorie restriction lost an average of 10 percent of their body weight in the first year of the study and maintained that weight during the study’s second year. Although that average fell short of the study’s target, it was still the largest sustained weight loss reported in a study of people who were not obese.

One reason for the less than expected weight loss may have been that most participants were not able to lower their calorie intake as much as expected. Originally, the plan was for study subjects to lower the number of calories they were consuming by 25 percent, but participants cut calories by about half of that amount, averaging a reduction of about 12 percent.​​​​​​​​​​​​​

“Lowering calorie intake by 25 percent is very difficult to sustain,” Holloszy explained. “In addition, we may not have seen the same metabolic effects in people that we see in animals because the people in the study were not calorie restricted for the first several decades of life. In animal studies, we begin calorie restriction when the animals are very young, so that may be a factor.”

Although the researchers did not see the effects they had expected, calorie restriction significantly lowered several predictors of cardiovascular disease when compared with such predictors in subjects who did not reduce calorie intake. Blood pressure decreased 4 percent. Total cholesterol fell 6 percent. Levels of HDL cholesterol — the “good” cholesterol —rose, and C-reactive protein, a marker of inflammation, dropped by 47 percent.

The calorie-restriction group also had decreased insulin resistance, and a marker of thyroid hormone activity called T3 decreased by more than 20 percent. Some studies have found that lower thyroid activity may be associated with longer life span.

“As we continue to try to unlock the mechanisms that make calorie-restricted animals live longer, we are certain that eating smaller portions of healthier food is a good idea for all of us,” Holloszy said. “But cutting intake by 25 percent is very difficult for most people.”

There were no adverse effects on mood related to calorie restriction. However, a few participants developed transient anemia, and some had greater than expected decreases in bone density, reinforcing the importance of clinical monitoring during calorie restriction.

“Calorie-restriction intervention did not produce significant effects on the pre-specified primary metabolic endpoints, but it did modify several risk factors for age-related diseases,” said Richard J. Hodes, MD, director of the National Institute on Aging, which helped fund the study. “However, we need to learn much more about the health consequences of this type of intervention in healthy people before considering dietary recommendations. In the meantime, we do know that exercise and maintaining a healthy weight and diet can contribute to healthy aging.”

Other clinical sites were at the Pennington Biomedical Research Institute of Louisiana State University in Baton Rouge and Tufts University in Boston. The study’s coordinating center was at Duke University in Durham, North Carolina.

Funding for this research comes from the National Institute Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, and National Institutes of Health (NIH) Cooperative Agreements, grant numbers U01 AG022132, U01 AG020478, U01 AG020487 and U01 AG020480.
Ravussin, E., et al. A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. Journal of Gerontology: Medical Sciences, September 2015.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff 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 sixth 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.
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