A recent study published in EMBO Molecular Medicine reports that metformin, a drug commonly used to treat diabetes, significantly increases levels of N-lactoyl-phenylalanine (Lac-Phe) in prostate cancer patients, according to an Apr. 7 announcement. The study found that this effect was observed regardless of disease stage or treatment regimen and that the rise in Lac-Phe with metformin use was similar to levels seen after strenuous exercise.
The findings are important because excess weight is closely linked with worse outcomes for cancer patients and can reduce the effectiveness of treatments. Weight management during hormone-based therapy is especially challenging for men with prostate cancer. Researchers suggest that increasing Lac-Phe through metformin could support better weight control during such therapies.
The research involved non-diabetic, overweight or obese men with hormone-sensitive prostate cancer who participated in the BIMET-1 trial. Patients were divided into groups receiving either bicalutamide alone or a combination of bicalutamide and metformin, as well as a phase involving only metformin treatment. The team also expanded their analysis to include additional men with various stages of prostate cancer, some already using metformin for metabolic issues.
Using advanced laboratory techniques to measure metabolites in blood samples, scientists confirmed that those treated with metformin had consistently higher levels of Lac-Phe compared to those who did not receive the drug. Notably, these elevated Lac-Phe concentrations matched those typically observed after intense physical activity. In addition to increased Lac-Phe, researchers measured growth differentiation factor 15 (GDF15), another marker associated with appetite suppression and weight loss following metformin use.
Most patients on metformin maintained or lost weight over six months while undergoing anti-androgen therapy—an outcome not seen among controls—though the link between rising Lac-Phe and favorable weight trends was not conclusive enough to establish causation.
The study highlights N-lactoyl-phenylalanine as a potential mediator of some metabolic benefits from both exercise and medication like metformin for people living with prostate cancer. Larger studies are needed to confirm whether targeting this pathway could improve long-term outcomes or offer an alternative strategy for individuals unable to engage in regular physical activity.
