Calorie restriction has been shown to have beneficial effects on health in organisms from yeast to humans, yet following a regimen of extreme fasting is psychologically difficult, and its advantages for humans are controversial. In a study published June 18 in Cell Metabolism, researchers discovered that feeding mice a calorie-restricted diet that mimics fasting for just eight days a month promoted regeneration in multiple systems and extended longevity.

Then they monitored the health of a diverse group of nineteen people adhering to a similar five-day low-calorie/low-protein diet once per month for three months. The investigators found that the diet, meant to mimic fasting and be medically supervised, had a positive impact on health and aging-related risk factors. Larger randomized clinical trials will be needed to support the results.

Previous work by Valter Longo -- who has joint appointments at the USC Davis School of Gerontology and the USC Dornsife College of Letters, Arts and Science -- and his colleagues revealed that fasting can increase cells' resistance to stressors by reducing levels of certain proteins and molecules with roles in growth and aging. In their attempt to develop a dietary intervention that induces these same effects while minimizing risks such as malnutrition and avoiding the burden of complete food restriction, the team designed a diet that's low in protein, low in carbohydrates, and high in healthy fats.

When mice were fed this Fasting Mimicking Diet (FMD) starting at middle age for only four days, twice per month, stem cell numbers increased considerably and various cell types -- such as bone, muscle, liver, brain, and immune cells -- were regenerated. Many of these regenerative effects had not been demonstrated in previous chronic or short-term dietary restriction studies. The animals also experienced better health and a prolonged lifespan, with benefits including reduced inflammatory diseases and cancer, improved learning and memory, and retarded bone loss, without a decrease in muscle mass.

Given these promising results in mice, the investigators conducted a pilot randomized clinical trial with nineteen individuals who adhered to the FMD and eighteen controls who continued to consume their normal diet. The FMD lasted five days every month for three months and provided between 34 percent and 54 percent of the normal caloric intake with a composition of 11 percent to 14 percent proteins, 42 percent to 43 percent carbohydrates, and 44 percent to 46 percent fat. By the end of the study, participants receiving the FMD intervention had decreased risk factors associated with aging, diabetes, heart disease, and cancer compared to the control group.

'This is arguably the first non-chronic pre-clinically and clinically tested anti-aging and healthspan-promoting intervention shown to work and to be very feasible as a doctor or dietitian-supervised intervention,' says Longo, who is director of the USC Longevity Institute. 'The FMD intervention will now undergo the rigorous process needed for FDA approval, which will first require confirmation and additional tests in 60 to 70 participants, followed by a trial with 500-1,000 participants.'

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The National Institutes of Health, the National Institutes on Aging, and the Bakewell Foundation funded this research. The University of Southern California has licensed intellectual property to L-Nutra that is under study in this research. As part of this license agreement, the University has the potential to receive royalty payments from L-Nutra, for which Dr. Longo serves as a scientific advisor.

Cell Metabolism, Brandhorst and Choi et al. 'A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan.'