Fasting-like diet lowers risk factors for disease, reduces biological age in humans

Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat in humans, resulting in a lower biological age, according to a new USC Leonard Davis School of Gerontology-led study.

The study, which appears in Nature Communications on Feb. 20, adds to the body of evidence supporting the beneficial effects of the fasting-mimicking diet (FMD).

The FMD is a five-day diet high in unsaturated fats and low in overall calories, protein, and carbohydrates and is designed to mimic the effects of a water-only fast while still providing necessary nutrients and making it much easier for people to complete the fast. The diet was developed by the laboratory of USC Leonard Davis School Professor Valter Longo, the senior author of the new study.

“This is the first study to show that a food-based intervention that does not require chronic dietary or other lifestyle changes can make people biologically younger, based on both changes in risk factors for aging and disease and on a validated method developed by the Levine group to assess biological age,” Longo said.

Previous research led by Longo has indicated that brief, periodic FMD cycles are associated with a range of beneficial effects. They can:

• Promote stem cell regeneration
• Lessen chemotherapy side effects
• Reduce the signs of dementia in mice

In addition, the FMD cycles can lower the risk factors for cancer, diabetes, heart disease and other age-related diseases in humans.

The Longo lab also had previously shown that one or two cycles of the FMD for five days a month increased the healthspan and lifespan of mice on either a normal or Western diet, but the effects of the FMD on aging and biological age, liver fat, and immune system aging in humans were unknown until now.

Lower disease risks & more youthful cells

The study analyzed the diet’s effects in two clinical trial populations, each with men and women between the ages of 18 and 70. Patients who were randomized to the fasting-mimicking diet underwent 3-4 monthly cycles, adhering to the FMD for 5 days, then ate a normal diet for 25 days.

The FMD is comprised of plant-based soups, energy bars, energy drinks, chip snacks, and tea portioned out for 5 days as well as a supplement providing high levels of minerals, vitamins, and essential fatty acids. Patients in the control groups were instructed to eat either a normal or Mediterranean-style diet.

An analysis of blood samples from trial participants showed that patients in the FMD group had lower diabetes risk factors, including less insulin resistance and lower HbA1c results. Magnetic resonance imaging also revealed a decrease in abdominal fat as well as fat within the liver, improvements associated with a reduced risk of metabolic syndrome. In addition, the FMD cycles appeared to increase the lymphoid-to-myeloid ratio – an indicator of a more youthful immune system.

Further statistical analysis of the results from both clinical studies showed that FMD participants had reduced their biological age – a measure of how well one’s cells and tissues are functioning, as opposed to chronological age – by 2.5 years on average.

“This study shows for the first time evidence for biological age reduction from two different clinical trials, accompanied by evidence of rejuvenation of metabolic and immune function,” Longo said.

The study, conducted by first authors Sebastian Brandhorst, USC Leonard Davis research associate professor, and Morgan E. Levine, founding principal investigator of Altos Labs and USC Leonard Davis PhD alumna, lends more support to the FMD’s potential as a short-term periodic, achievable dietary intervention that can help people lessen their disease risk and improve their health without extensive lifestyle changes, Longo said.

“Although many doctors are already recommending the FMD in the United States and Europe, these findings should encourage many more healthcare professionals to recommend FMD cycles to patients with higher than desired levels of disease risk factors as well as to the general population that may be interested in increased function and younger age,” Longo said.

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About the study

Along with Longo, Brandhorst and Levine, the study’s coauthors include Min Wei, Mahshid Shelechi, Todd E. Morgan, Eileen Crimmins and Pinchas Cohen of the USC Leonard Davis School; Krishna S. Nayak of the USC Viterbi School of Engineering; and Tanya Dorff and Kurt Hong of the Keck School of Medicine of USC.

Funding was provided by the USC Edna Jones chair fund to Longo, in addition to NIH/NIA 4R00AG052604-02 to Levine, NIH/NIA 1R01AG060110-01 to Levine and Crimmins, and the Yale PEPPER Center P30AG021342 to Levine. Longo is the founder of and has an ownership interest in L-Nutra; the company’s food products are used in studies of the fasting-mimicking diet. Longo’s interest in L-Nutra was disclosed and managed per USC’s conflict-of-interest policies. USC has an ownership interest in L-Nutra and the potential to receive royalty payments from L-Nutra. USC’s financial interest in the company has been disclosed and managed under USC’s institutional conflict-of-interest policies.