Fasting-mimicking diet and cell “self-cleaning” in humans

Can a fasting-mimicking diet activate cellular self-cleaning and improve metabolic health? This article explores a clinical trial in healthy adults examining how a fasting-mimicking diet affects blood sugar, insulin and autophagy, the cell’s internal recycling system linked to aging and disease.

Study Overview

This pilot randomized clinical trial investigated the effects of a fasting-mimicking diet (FMD) on metabolic health and autophagic activity in healthy adults.

  • 30 healthy adults were randomized to two versions of an FMD (ProLon or FMD2) or a normal-diet control for 8 days, with 5 days on the low-calorie FMD and then re-feeding (Espinoza et al., 2025).
  • The FMD was plant-based, low-calorie, low-protein, low-sugar and high in unsaturated fats, designed to mimic water-only fasting while still providing nutrients (Espinoza et al., 2025).

What they measured and found

  • Metabolic markers: body weight, fasting glucose, insulin, IGF-1, ketone bodies (β-hydroxybutyrate), and insulin resistance (HOMA-IR) (Espinoza et al., 2025).
  • Autophagy: “autophagicflux”in blood immune cells, using LC3B-II/LC3B-I protein ratios with and without chloroquine treatment (Espinoza et al., 2025)

Compared with controls after 6 days:

  • FMD groups lost weight and had lower fasting glucose, insulin, HOMA-IR, and higher ketones (all statistically significant) (Espinoza et al., 2025).
  • One formulation (ProLon) showed a pattern consistent with increased autophagic flux persisting even 2 days after re-feeding (Espinoza et al., 2025).

Big picture

The article presents early human evidence that a short, periodic fasting-mimicking diet can improve metabolic markers and may enhance autophagy, suggesting a potential non-drug strategy to influence aging-related pathways and healthspan.

References

Read the study
Espinza, S., Park, S., Connolly, G., Qi, W., Zhang, N., Sembla, M., Li, Y., Lauzon, M., Salmon, A., Hsu, W., Wei, M., & Musi, N. (2025). Ef ect of fasting-mimicking diet on markers of auto-Nagy and metabolic health in human subjects.. GeroScience. 

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