Human clinical trial discovers Fasting Mimicking Diet improved autophagy

Researchers have recently published pilot clinical trial data from a five-day Fasting Mimicking Diet (FMD) that was connected with autophagy, which is the increased activity of the body’s natural cellular clean-up process.¹ Additionally, there were improvements seen in key metabolic health indicators.

Scientists from Cedars-Sinai Medical Center (Los Angeles, California) and UT Health San Antonio (San Antonio, Texas), worked together with L-Nutra, Inc., on the randomized controlled trial that measured the autophagic flux in humans that are 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,” the press release mentioned.¹ “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.”

The clinical trial consisted of thirty healthy adults who were then randomized to be given one of two five-day FMD formulations (which were Prolon or FMD2) or continued their normal diet.^1,2 Participants had blood samples collected before the trial began, during, and after the trial which showed that participants that were in the Prolan arm “demonstrated a measurable increase in autophagy flux, which reflects an enhanced rate and efficiency of the cellular clean-up activity.”¹ According to the data, both FMD groups saw improvements involving insulin sensitivity, fasting glucose, weight, and ketone levels when compared to the control group.

“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.¹ “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 press release explains that 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.”¹

“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.¹ “It's a major step toward understanding how nutrition technology can modulate the biology of aging.”

According to the press release, the clinical trial was the trial was registered on GeroScience and was funded by L-Nutra, Inc.¹ “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 press release mentioned.¹

References

1. First-ever human trial finds fasting mimicking diet enhances autophagy while improving Metabolic Health https://www.prnewswire.com/news-releases/first-ever-human-trial-finds-fasting-mimicking-diet-enhances-autophagy-while-improving-metabolic-health-302643077.html (accessed Dec 19, 2025).
2. Espinoza, S.E., Park, S., Connolly, G. et al. Effect of fasting-mimicking diet on markers of autophagy and metabolic health in human subjects. GeroScience (2025). https://doi.org/10.1007/s11357-025-02035-4