CANCER AND METABOLISM: EVALUATING THE IMPACT OF KETOGENIC AND CALORIE-RESTRICTED DIETS

Abstract

Cancer cells exhibit distinct metabolic adaptations characterized by enhanced glycolysis and altered mitochondrial function, known as the Warburg effect. These metabolic reprogramming mechanisms support rapid proliferation and survival under stress, distinguishing tumor cells from normal counterparts. Emerging evidence highlights dietary interventions, particularly ketogenic diets (KD) and calorie restriction (CR), as promising adjuncts to cancer therapy by exploiting these metabolic vulnerabilities. The ketogenic diet induces systemic ketosis and reduces glucose availability, forcing cancer cells—often deficient in ketolytic capacity—into energetic crisis while sparing normal cells capable of utilizing ketones. Similarly, calorie restriction diminishes circulating insulin and IGF-1 levels, suppresses the PI3K/Akt/mTOR pathway, and reduces angiogenesis, collectively impeding tumor growth. Both interventions demonstrate synergistic effects with chemotherapy, radiotherapy, and immunotherapy, enhancing treatment efficacy and reducing side effects. Mechanistic insights reveal modulation of oxidative stress, histone deacetylase inhibition, and improved immune surveillance. However, patient adherence, potential nutrient deficiencies, and immune suppression under prolonged restriction remain challenges. Preclinical and limited clinical data affirm the therapeutic promise of these dietary strategies, underscoring the need for standardized protocols, biomarker-guided patient selection, and large-scale clinical trials. Dietary modulation of cancer metabolism offers a low-toxicity, personalized approach that complements existing oncologic therapies and represents a frontier in metabolic oncology.