For the first time, scientists have shown that Prolon’s Fasting Mimicking Diet (FMD) can directly trigger autophagy in humans—a breakthrough in longevity science.

Autophagy (from the Greek for “self-eating”) is the body’s natural cellular clean-up system. Think of it as a recycling program for cells: clearing away damaged parts, recycling what can be saved, and creating room for renewal. This process is linked to healthier metabolism, stronger immunity, and protection against age-related decline, among many other benefits. The trick is that autophagy typically requires 72 hours of water-only fasting to switch on, which is a difficult, potentially unsafe practice for most people. The FMD was designed to solve this problem, providing carefully calibrated plant-based meals that keep the body in a fasting state while still allowing people to eat. Animal trials have consistently demonstrated that the FMD triggers autophagy, and decades of research in humans has shown metabolic shifts that suggest (ital) that autophagy has occurred.

Now, researchers have measured direct signs of autophagy in human participants following the Prolon FMD, confirming that the program doesn’t just create the conditions for autophagy; it activates it.

The study: methodology 

Led by scientists at Cedars-Sinai Medical Center and UT Health San Antonio, in collaboration with L-Nutra, this was the first human study to directly measure signs of autophagy during the FMD. Thirty healthy adults between the ages of 25 and 65 took part, and notably, the majority represented groups often overlooked in longevity research: approximately 80% were female and about 80% identified as Hispanic/Latino. Participants were randomized into three groups:

• Group 1: Used Prolon (original FMD formula)
  
  

• Group 2: Used “FMD2,” a modified version with less starch, designed to better manage glucose)
  
  

• Group 3: Control group (normal diet, no changes)
  
  

Over five days, blood samples were collected at baseline, mid-fast (day four), end of fast (day six), and two days later (day eight). Researchers measured both metabolic health markers and molecular signs of autophagy in immune cells. The testing methods relied on molecular assays, advanced lab tests typically reserved for pharmaceutical research. These tests allowed scientists to track autophagic flux, the full cycle of how cells form and break down tiny “recycling sacs” called autophagosomes. By watching this process directly, researchers were able to confirm that the FMD truly activates autophagy in humans. 

The results

What the researchers found was striking: participants following the FMD showed clear molecular signs of autophagy, confirming that the body’s cellular clean-up systems had switched on. This leap from strong suggestion to direct proof shows that Prolon can activate autophagy in humans, and beyond short-term changes in weight or metabolic health, points to deeper rejuvenative processes that may influence how the body ages over time.

“After decades of preclinical data, we finally have human evidence connecting fasting-mimicking nutrition with autophagy—one of the most sought-after goals in longevity science,” says 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.”

• Weight loss and improvements in metabolic health
  Both FMD groups experienced significant improvements compared to the control group:
  
  

• • Weight loss: Average of 1.7 kg (≈3.75 lbs) in 5 days
    
    

  • Blood sugar: Fasting glucose decreased by 12–14 mg/dL
    
    

  • Insulin sensitivity: Lower insulin levels and HOMA-IR scores, indicating reduced insulin resistance
    
    These findings confirm earlier research showing that Prolon supports healthy metabolic markers and weight loss.
    
    

• First direct evidence of autophagy in humans
  For the first time, researchers were able to measure changes in autophagy markers in human participants undergoing the FMD.

• • In the Prolon group, signs of increased cellular clean-up activity appeared by day six, consistent with the body’s autophagy systems becoming more active.
    
    

  • In the FMD2 group, similar shifts were seen, with some changes peaking after the fast had ended, suggesting autophagy continued into the post-fast phase.
    
    

What this means for health and longevity 

Autophagy, long studied in cell biology, has in recent decades emerged as a cornerstone of longevity science—a recognition cemented by the 2016 Nobel Prize. However, what makes this discovery so important is that autophagy isn’t just about cleaning up proteins inside a cell; it’s about maintaining the integrity and resilience of the whole body. In other words, the ability to safely and predictably activate autophagy through a short, nutrition-based program like the FMD doesn’t just open the door to better weight care and metabolic health; it points toward a practical way for people to access one of the body’s most powerful longevity mechanisms that could influence everything from daily vitality to long-term healthspan.

“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.”

While more trials are needed to confirm and expand upon these findings, the results mark a turning point: for the first time, scientists point to direct human evidence that the FMD can directly trigger autophagy in humans—directly supporting our mission to help people live better, for longer. Read the full study here.

*The trial was registered on ClinicalTrials.gov (NCT06115551) and funded by L-Nutra, Inc. Importantly, the company did not participate in data collection, analysis, or interpretation — ensuring the independence of the findings.