First-Ever Human Trial Finds Fasting Mimicking Diet Enhances Autophagy While Improving Metabolic Health

LOS ANGELES, Dec. 16, 2025 /PRNewswire/ -- In a groundbreaking first for nutrition science, researchers have published pilot clinical trial data showing that the 5-day Fasting Mimicking Diet (FMD) was associated with increased activity of the body's natural cellular clean-up process -  autophagy - alongside significant improvements in key metabolic health indicators. Autophagy's fundamental importance to human biology was recognized with the 2016 Nobel Prize in Physiology or Medicine, underscoring how central this "cellular clean-up" system is to health and the adaptive mechanisms that have made human survival possible.

The randomized controlled trial, led by scientists at Cedars-Sinai Medical Center and UT Health San Antonio in collaboration with L-Nutra, Inc., is the first to directly measure autophagic flux in humans undergoing a dietary intervention. Autophagy - the body's natural process of breaking down and recycling damaged components - plays a central role in cellular repair, energy balance, immune defense, and resilience against premature aging. This self-renewal mechanism exists from yeast all the way to humans because our biology was shaped by regular periods of little or no food; in the face of adversity and famine, autophagy helped life not only survive but emerge stronger by identifying and repairing old, worn-out cellular components - a process many scientists describe as a true "miracle of life."

By leveraging this built-in survival mechanism through controlled, periodic fasting-mimicking nutrition, researchers can begin to harness the benefits of autophagy for disease remission and longevity while avoiding many of the harms and risks of extreme, prolonged fasting. This biologic backdrop set the stage for the current trial, which asked whether this ancient repair process could be safely and measurably activated in humans using a nutrition-based intervention.

Thirty healthy adults were randomized to receive one of two 5-day FMD formulations (Prolon or FMD2) or to continue their normal diet. Blood samples collected before, during, and after the intervention revealed that participants in the Prolon arm demonstrated a measurable increase in autophagy flux, which reflects an enhanced rate and efficiency of the cellular clean-up activity. Both FMD groups also experienced significant improvements in weight, fasting glucose, insulin sensitivity, and ketone levels compared to control.

"This is among the first studies that have evaluated the dynamic process of autophagy in humans during a medical nutrition program," said Sara Espinoza, MD, Director of the Center for Translational Geroscience, Cedars-Sinai Medical, 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."

The FMD is an evidence-based, interventional nutrition designed to deliver essential nutrients while triggering many of the same physiological effects as a water-only fast. Previous research has shown FMD's potential to reduce biological age scores, support metabolic balance, and improve a range of cardiometabolic risk factors. This new study builds on that body of evidence by directly linking the program to markers of the body's cellular recycling systems. Because dysregulated autophagy and impaired cellular clean-up are tightly linked to cellular aging - a root cause that drives premature aging - the ability to safely stimulate this pathway with nutrition may offer a powerful new tool to support healthy aging and promote healthy aging.

"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." Ultimately, the hope is that by periodically activating this ancient "survival and renewal" program through fasting-mimicking nutrition, we can help the body repair itself from within - improving metabolic health today while influencing long-term health trajectories.

The trial was registered on GeroScience and was funded by L-Nutra, Inc. The company did not participate in data collection, analysis, or interpretation. Full results are now available here.

About L-Nutra
L-Nutra is the leader in longevity and nutrition science, pioneering innovations that unlock the technology in nutrition to support healthy aging, combat age-related conditions, and transform lives. In collaboration with 18 global research institutions, L-Nutra has conducted more than 47 clinical trials and holds over 130 patents. Its flagship consumer brand, Prolon®, offers clinically tested fasting-mimicking nutrition programs, while its medical division, L-Nutra Health, delivers health concern-specific nutrition protocols.

For more information, visit www.l-nutra.com.

SOURCE L-Nutra Inc.