July 13, 2015

Health Effects of a Diet that Mimics Fasting

At a Glance

  • Periodic cycles of a low-calorie diet that mimicked fasting improved metabolic, immune, and other functions in mice.
  • Preliminary findings in people fed a similar diet for 5 days a month showed some beneficial health effects.
  • More work will be needed to confirm the benefits and determine the mechanisms of the approach.
Knife and fork with a glass of water. Animal studies show that dietary restriction can have many health benefits, but how best to apply such diets in people is still under study.NastjaPungracic\iStock\Thinkstock

Dietary restriction has been shown in a variety of animal models to have many health benefits. Fasting, in which food isn’t consumed (but water is), represents the extreme form of restriction. Previous studies in animals and people suggested that periodic cycles of fasting may improve certain metabolic and immune functions. Fasting for 2 or more days, however, is difficult for many people, and can have adverse health effects.

A team led by Dr. Valter Longo at the University of Southern California studied diets designed to mimic the beneficial effects of fasting while minimizing the risks and difficulty associated with complete food restriction. The research was funded in part by NIH’s National Institute on Aging (NIA). Results were published in Cell Metabolism on July 7, 2015.

The team first tested cycles of prolonged fasting in yeast, a single-celled organism. Yeast that were switched back and forth from a nutrient-rich environment to water for several cycles had a longer lifespan and were better able to survive toxin exposure—a marker of increased stress resistance—than yeast not exposed to periodic starvation.

The team next tested a very low-calorie, low-protein diet in mice. The diet was designed to mimic some of the beneficial effects of fasting, including improving markers of longevity and metabolism. Middle-aged mice (16 months old) were fed the diet for 4 consecutive days, followed by 10 days of unlimited access to food. The mice overate during these phases so that their overall calorie intake was similar to mice continuously fed a regular diet.

Mice fed the diet twice a month for several months had various metabolic changes, including lower blood glucose and insulin levels, than mice fed a control diet. These metabolic markers all returned to normal levels during periods of re-feeding. Mice fed the diet had less fat around their organs (known as deep or visceral fat) at 28 months of age. They also had greater bone density at old age and increased nerve cell development in the brain. At the end of life, mice on the diet had fewer tumors and skin lesions than control mice.

The team next conducted a pilot study in a small group of people. Nineteen healthy adults consumed a proprietary plant-based diet that provided between 34% and 54% of the normal caloric intake with at least 9–10% protein, 34–47% carbohydrate, and 44–56% fat. Participants consumed the diet 5 days a month for 3 months (3 cycles), resuming their normal diet at the end of each diet period. A control group of 19 adults ate a normal diet.

People on the diet had improvements in blood glucose and decreased body weight compared to the control group. Those with initially elevated C-reactive protein levels (a marker of heart disease risk) had lower levels, while those with normal levels had no change. Reports of side effects were low and included fatigue, weakness, and headache.

“Strict fasting is hard for people to stick to, and it can also be dangerous, so we developed a complex diet that triggers the same effects in the body,” Longo says. “It’s not a typical diet because it isn't something you need to stay on.”

More research will be needed to determine the long-term impact of the diet on human health and provide information on when and how such a diet might be applied.

—by Carol Torgan, Ph.D.

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References: A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD. Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012. Epub 2015 Jun 18. PMID: 26094889.

Funding: NIH’s National Institute on Aging (NIA) and National Center for Research Resources (NCRR); Bakewell Foundation; V Foundation for Cancer Research; USC Norris Cancer Center; and USC Edna Jones chair fund.