Metformin and Exercise-Linked Metabolite Lac‑Phe in Prostate Cancer Patients

Metformin treatment was observed to increase circulating N-lactoyl-phenylalanine (Lac-Phe) in men with prostate cancer, with blood levels similar to those reported after strenuous exercise.

Investigators at the Sylvester Comprehensive Cancer Center at the University of Miami linked this blood-based change to a molecular signal previously connected to high metabolic demand during physical activity.

Elevations were measurable in blood samples even when participants were not exercising at the time of collection. Lac-Phe elevation persisted after hormone-based therapy began.

Tumor-response context used prostate-specific antigen (PSA) as a standard monitoring marker, with higher Lac-Phe levels reported as not correlating with PSA changes in the cohort discussed. This disconnect is presented as a distinction between a circulating metabolic signal and a PSA-based assessment of anti-tumor response to metformin.

Metformin is associated with increased GDF-15, while Lac-Phe in this study was described as more closely tied to weight-change signals. The authors further describe that Lac-Phe and GDF-15 did not rise together, which they interpret as consistent with more than one pathway contributing to weight-related effects.