Fasting mimicking diets for regeneration, age-related disease

Curing disease is not the key to living longer, said Valter Longo, PhD, professor at the University of Southern California Leonard Davis School of Gerontology, at the 2019 Integrative Healthcare Symposium in New York City.

Looking at patients who have lived a long time and their lifestyles draws oversimplified conclusions, he said. Aging, and aging well, is a complex process and is dependent on several factors, Longo said.

It’s important to start with genetics because this tells us a lot about longevity, he said. Yeast, for example, is considered the most potent pro-aging agent. If you starve a yeast colony, it lives ten times longer.

Similar research in flies found a single genetic mutation resulted in a fly living twice as long. In mice, growth hormone receptor (GHRD) and IGF-1 deficient mice never developed disease, and had record longevity of nearly 50 percent longer than control mice. With calorie restriction, they can live even longer, about twice as long.

“This is remarkable that a combination of genetics and calorie restriction can result in a longer life,” said Longo. “What’s even more remarkable is the mice make it through this long life with no diseases.”

But how does this happen? When looking at humans who were GHRD and IGF-1 deficient who ate a poor diet and did not exercise at all, even if relatives had higher rates of cancer, GHRD subjects did not. Obesity is also higher in the GHRD population, but a low number develop diabetes.

“Humans with this single mutation in GHRD are protected from disease,” Longo said. “It can be explained by this one mutation, and reinforced in mice who have the same phenotype, that cancer is reduced in this very long lifespan.”

Since current medical capabilities don’t offer direct influence on genetics, Longo says he and his team have been interested in food, specifically how they can use food to regulate genes that regulate aging that regulate disease.

This research started with calorie restriction. Using monkeys, researchers found those that were calories restricted had reduced mortality from major disease but did not live much longer. Calorie restricted monkeys did not experience diabetes, while 60 percent of the control animals on a normal diet did, and tumors and cardiovascular diseases were reduced by 50 percent.

“Calorie restriction has benefits,” said Longo, “but the trade-off is there are some major problems that counterbalance the positive effects.

In the first human calorie restriction study, which includes eight people who lived in a biosphere, the results were consistent with the monkey study, Longo said. Calorie restriction led to lower systolic blood pressure, fasting glucose, cholesterol, and disease. However, subjects became so undernourished they were considered anorexic.

“Calorie restriction has never been applied to humans because it can be dangerous,” Longo said.

This led Longo to look at how to achieve the effects of calorie restriction without the potential health problems, to potentially use starvation intervention periodically for brief periods. Thus, the fasting mimicking diet (FMD). 

• Low calorie
• Low sugar
• Low protein
• High unsaturated fats

An FMD is as effective as water-only fasting in altering genetic markers such as IGF-1, IGF-BP1, glucose, and ketone bodies. The purpose is to regulate IGF-1 and ketone bodies I the same way starvation would.

If you take a middle-aged mouse and give them an FMD, where they follow an FMD for eight days a month and eat normally the rest of the month, there are a number of effects. Even mice that overeat during their non-FMD periods still see results, Longo said. The FMD activates blood stem cells, resulting in regeneration and rejuvenation of the immune system.

Specifically in cancer prevention, FMD cycles reduce and delay cancer. When combined with conventional chemotherapy, cancer-free survival goes up dramatically, 60 percent in mice.

“We believe fasting protects [non-cancerous] cells and is very powerful in protecting cells from chemotherapy,” said Longo.

[FMD] sensitizes cancer cells as well, Longo said. While targeted therapy and immunotherapy is great, cancer evolves rapidly. Immunotherapy can fail because cancer can adapt to get around the targeted therapy. An FMD alone can cause tumor growth to accelerate. When used together, a combination of chemotherapy and FMD can create what Longo calls “death by confusion,” and cancer is reduced or eliminated.

Longo has conduced a number of clinical trials, which have consistently found that patients who fast two days before and one day after chemotherapy are protected form side effects and show no decrease in quality of life, whereas a normal diet led to significant decline in quality of life.

Four new trials will be published in the next few months, Longo said, all of which are very positive in support of these findings. Further, the concept of incorporating FMD to treatment protocols can be applied to other chronic age-related diseases, such as diabetes and autoimmune disease, and is proven more effective than a continuous ketogenic diet, Longo said.

“The idea is combining targeted therapies with dietary interventions, so when cancer adapts, change is made impossible by extreme conditions caused by FMD,” said Longo. “This prevents disease of age.”