Short, food-based fasting activates body’s clean-up system while improving weight and blood sugar, marking milestone for longevity science.
For decades, scientists have known that the body has an internal “clean-up” team that repairs damage at the cellular level. What they have not been able to show – until now – is whether a specific diet can reliably switch that system on in humans.
A newly published pilot clinical trial suggests it can. Researchers report that a five-day Fasting Mimicking Diet (FMD) not only improved markers of metabolic health, such as weight and blood sugar, but also increased activity in autophagy, the body’s natural process of breaking down and recycling worn-out cell parts [1].
Autophagy’s importance to human health was recognized in physiology and medicine. Yet most evidence linking diet and autophagy has come from animal studies or laboratory models. This trial marks the first time autophagic activity has been directly measured in people undergoing a dietary intervention.
Autophagy means “self-eating,” but the idea is less alarming than it sounds. Think of it as spring cleaning for your cells. When food is scarce, the body shifts into repair mode, clearing out damaged components and recycling them for energy and renewal.
The process exists across almost all forms of life, from yeast to humans. Evolutionarily, it helped organisms survive periods of famine. Today, scientists see it as a key mechanism tied to metabolic health, immune function and the biology of aging.
The challenge has always been how to activate this system safely, without asking people to undergo extreme or prolonged fasting.
The randomized controlled study was led by researchers at Cedars-Sinai Medical Center and UT Health San Antonio, in collaboration with the longevity-focused nutri-tech company L-Nutra, Inc.
Thirty healthy adults were assigned to one of three groups: a five-day Prolon FMD, a second FMD formulation or a normal diet.
Blood samples were collected before, during and after the intervention. In participants following the Prolon program, researchers observed a measurable increase in what they call “autophagic flux,” a measure of how actively cells clear and recycle internal waste.
At the same time, both FMD groups showed improvements in practical, easy-to-understand markers of health. Participants lost weight, had lower fasting blood glucose, improved insulin sensitivity and higher ketone levels – changes often associated with better metabolic flexibility.
“This is among the first studies that have evaluated the dynamic process of autophagy in humans during a medical nutrition program,” said Dr Sara Espinoza, Director of the Center for Translational Geroscience at Cedars-Sinai and principal investigator of the study.
“It opens an exciting avenue for how short, periodic fasting-mimicking nutrition could be used to intervene in support of healthy aging and metabolic health,” she added.
Unlike water-only fasting, the FMD provides carefully designed nutrition that supplies essential nutrients while triggering many of the same biological responses as fasting. This distinction matters. Extreme fasting can carry risks, particularly for older adults or those with underlying conditions. A food-based approach may offer a safer, more accessible alternative.
Previous studies have already linked FMDs to improvements in cardiometabolic risk factors and reductions in biological age markers. This new trial adds another piece to the puzzle by connecting the diet directly to the body’s internal recycling system.
“After decades of preclinical data, we finally demonstrated in humans the vital connection between fasting-mimicking nutrition with autophagy – one of the most sought-after goals in longevity science,” said Dr William Hsu, Chief Medical Officer at L-Nutra.
“It’s a major step toward understanding how nutrition technology can modulate the biology of aging,” he noted.
Of course, the findings are preliminary; the study was small, and researchers are clear that larger trials are needed to confirm and expand on the results. Still, the implications are difficult to ignore. If periodic, short-term dietary interventions can safely activate the body’s own repair mechanisms, they could reshape how we think about prevention, aging and long-term health.
For now, the study offers something rare in nutrition science: direct human evidence that what and when we eat can influence some of the deepest biological processes tied to aging.
[1] https://link.springer.com/article/10.1007/s11357-025-02035-4
