A high-protein diet during middle age was associated with higher mortality in a new study. In adults over 65, however, a high-protein diet was linked to lower mortality.

Calorie restriction increases longevity in many animals. It’s not known, however, if restriction works by lowering calorie intake or by reducing the intake of protein or other nutrients. A team led by Dr. Valter Longo at the University of Southern California set out to explore the link between dietary protein and mortality. The study was funded in part by NIH’sNational Institute on Aging (NIA).

The researchers analyzed information on more than 6,800 U.S. adults, ages 50 and over, from the Third National Health and Nutrition Examination Survey (NHANES III), a periodic health and nutritional survey of the U.S. population. The researchers linked the survey data with National Death Index data, which provides the timing and causes of death. Results were published on March 4, 2014, in Cell Metabolism.

Participants were categorized into 3 groups based on the percent of self-reported calorie intake that came from protein: high (20% or more), moderate (10-19%), or low (less than 10%). They were further split into 2 age categories: 50 to 65, and 66 and older.

Adults in the 50 to 65 group who reported a high protein intake had a 75% increase in overall mortality and were 4 times more likely to die from cancer during the following 18 years than those in the low protein group. The moderate-protein diet was associated with a 3-fold increase in cancer mortality compared to the low-protein diet.

These associations—which were adjusted for numerous factors including smoking, waist circumference, and chronic conditions—weren’t altered when the percentage of calories from fat or carbohydrate were considered. However, the associations were only found when the proteins were derived from animal, rather than plant, sources.

Conversely, in participants ages 65 and older, those who consumed high amounts of protein had a 28% lower risk of dying from any cause and a 60% lower risk of dying from cancer. These associations weren’t influenced by whether the protein was derived from animal or plant sources.

A high-protein diet was also associated with a 5-fold increase in diabetes mortality across all ages. One limitation of the study, the researchers note, is that the participants’ protein intake was based on a single 24-hour dietary recall. The study also didn’t examine the effects of specific types of plant- or animal-derived proteins, such as beef or fish.

Mouse studies confirmed the effects of high protein intake. Mice fed a higher protein diet had increased progression of breast and melanoma tumors than those fed a lower protein diet. The low-protein diet, however, had detrimental effects in very old mice. The link between diet and longevity appeared to be moderated by a pathway involving insulin-like growth factor 1 (IGF-1).

“The research shows that a low-protein diet in middle age is useful for preventing cancer and overall mortality, through a process that involves regulating IGF-1 and possibly insulin levels,” says co-author Dr. Eileen Crimmins. “However, we also propose that at older ages, it may be important to avoid a low-protein diet to allow the maintenance of healthy weight and protection from frailty.”

—by Carol Torgan, Ph.D.