Metformin Mimics Exercise Benefits in Prostate Cancer Patients by Boosting Key Exercise Molecule Production
Researchers reported April 6, 2026, in EMBO Molecular Medicine that metformin increased levels of the exercise-related molecule N-lactoyl-phenylalanine (Lac-Phe) in prostate cancer patients across all disease stages. The drug boosted Lac-Phe to amounts comparable to those seen after intense exercise, potentially mimicking exercise benefits in patients unable to engage in physical activity, according to the study.
The study found that metformin consistently raised levels of N-lactoyl-phenylalanine (Lac-Phe), a molecule linked to exercise, in prostate cancer patients regardless of disease stage, according to research published April 6, 2026, in EMBO Molecular Medicine.
In a clinical trial subgroup, patients treated with metformin showed significant increases in Lac-Phe, reaching concentrations comparable to those observed in healthy individuals after intense physical activity, the report said.
Lac-Phe is an exercise-induced metabolite associated with weight loss and appetite suppression, researchers said. It has been identified in healthy people and athletes, including ultramarathon runners, and is released during physical activity to mimic some metabolic benefits of exercise. Previous observations noted elevated Lac-Phe levels in diabetes patients treated with metformin, but this study is among the first to demonstrate similar effects in prostate cancer patients who may be unable to exercise due to treatment-related limitations.
The exploratory study included prostate cancer patients across various stages who were treated with metformin. Researchers compared Lac-Phe levels in patients taking the drug to those not receiving metformin, finding consistent increases regardless of cancer stage or body weight. The clinical trial subgroup showed statistically significant rises in Lac-Phe following metformin administration, and these effects persisted regardless of other treatments the patients were undergoing, according to lead author Gigen Mammoser. The findings were fact-checked by Jill Seladi-Schulman, Ph.D., and reported on April 10, 2026.
Metformin’s ability to elevate Lac-Phe to levels comparable to strenuous exercise suggests it may mimic one key metabolic effect of physical activity, officials said. This could help manage treatment-related weight gain and support metabolic health in prostate cancer patients who are unable to participate in regular exercise. While metformin does not replace all the benefits of physical activity, the drug’s impact on Lac-Phe production may contribute to improved appetite control and weight management during cancer treatment, sources confirmed.
Beyond its effects on Lac-Phe, metformin has several mechanisms of action relevant to prostate cancer, according to prior research cited in the study. It inhibits the mTOR pathway, which reduces protein synthesis and tumor cell growth by targeting proteins such as 4E-BP1 and p70S6K1. Metformin also affects the Krebs cycle, altering lipid synthesis and beta-oxidation, processes that are important in prostate cancer metabolism. Additionally, the drug inhibits fatty acid synthase, an enzyme upregulated in cancer cells to promote fatty acid production.
Metformin activates AMP-activated protein kinase (AMPK) through AICAR-like effects, inducing metabolic stress in cancer cells, and targets the PI3K pathway, a major driver of prostate cancer growth alongside the androgen receptor. These mechanisms contribute to metformin’s ability to inhibit cancer cell proliferation and affect epithelial-mesenchymal transition (EMT) markers, which influence tumor invasion and metastasis, according to the study.
Clinical trials have demonstrated broader metabolic benefits of metformin in prostate cancer patients. One randomized trial showed that combining metformin with a low glycemic index diet and exercise led to reductions in abdominal girth, weight, body mass index, and systolic blood pressure in patients undergoing androgen deprivation therapy (ADT). However, that trial did not find differences in biochemical markers of insulin resistance. The drug’s influence on EMT expression via AMPK activation has also been observed in various cancers, including prostate cancer.
The study’s authors noted that metformin, a commonly prescribed diabetes medication, offers potential advantages for prostate cancer patients who cannot engage in physical activity due to treatment side effects or other limitations. By increasing Lac-Phe levels, metformin may help regulate appetite and control weight during cancer therapy, findings that build on previous observations in diabetes and exercise research.
The research was conducted with prostate cancer patients from multiple stages and treatment backgrounds, ensuring that the findings on Lac-Phe elevation were consistent across a diverse population. This consistency supports the potential use of metformin as part of metabolic management in prostate cancer care, according to the April 6, 2026, publication in EMBO Molecular Medicine.
Future studies may further explore the clinical implications of metformin-induced Lac-Phe increases and whether these metabolic effects translate into improved patient outcomes, including cancer progression and quality of life. The current findings provide a foundation for investigating metformin’s role in mimicking exercise benefits in populations unable to engage in physical activity.
