Metformin as an Accessible Caloric Restriction Mimetic in Helminth-Endemic Populations: Cancer Prevention and Adjuvant Treatment Rationale

Background. The fmd/caloric restriction hypothesis paper (https://doi.org/10.5281/zenodo.20402676) proposed fasting-mimicking diet (FMD) cycles as an adjunct in parasite-associated cancers, based on the 2025 Nature Metabolism finding that dietary restriction reprograms exhausted CD8+ T cells via ketolysis. A practical limitation of FMD in helminth-endemic regions is nutritional vulnerability: many patients in Thailand, sub-Saharan Africa, and Okinawa cannot safely tolerate a 30–50% caloric restriction over 5-day cycles. Methods (Review scope). Narrative synthesis of mechanistic and epidemiological evidence for metformin as a caloric restriction mimetic, drawing on PubMed-indexed cohort studies, meta-analyses, and in vivo experimental data on metformin's anti-cancer and anti-parasitic effects, identified by systematic web search (June 2026). Results. Metformin — a biguanide on the WHO Essential Medicines List, costing approximately USD 0.03 per day, and already prescribed to millions in helminth-endemic regions for Type 2 diabetes — achieves mTOR suppression, AMPK activation, and downstream anti-proliferative effects through an overlapping molecular pathway. A 2024 paper in...