Comment on "Impact of Intermittent Fasting with a Ketogenic Diet on AMPK Levels in Breast Cancer Patients Receiving Chemotherapy".

Abstract

The recent study by Lughmani et al. demonstrated that a 30-day regimen of 23:1 intermittent fasting combined with a ketogenic diet significantly elevated serum AMPK levels and reduced CA 15-3 in breast cancer patients undergoing chemotherapy. While these findings highlight the potential of metabolic interventions to modulate key signaling pathways, important questions remain regarding clinical translation and patient heterogeneity. First, the impact of fasting and ketogenic strategies on chemotherapy-related toxicity, treatment tolerability, and quality of life was not evaluated; integrating standardized toxicity grading (e.g., CTCAE v5.0), patient-reported outcome measures, and chemotherapy dose intensity metrics could determine whether AMPK activation confers meaningful protective benefits. Second, breast cancer subtypes exhibit distinct metabolic dependencies and AMPK pathway alterations; prespecifying subgroup analyses by receptor status and correlating intratumoral AMPK activity with molecular subtype would inform personalized dietary adjuncts. Addressing these dimensions will be pivotal for validating intermittent fasting plus ketogenic diets as safe, tailored adjuncts to standard chemotherapy.