Background/Objectives: Lung cancer (LC) remains the leading cause of cancer-related death worldwide, despite advances in systemic and targeted therapies. A mechanism of survival of tumor cells is metabolic reprogramming, characterized by increased glucose uptake, aerobic glycolysis, and alterations in mitochondrial function. These adaptations seem to support tumor growth, immune evasion, and therapeutic resistance. In parallel, supportive care and specifically nutritional interventions have become essential components of modern oncology. The interplay between metabolic reprogramming and targeted nutritional strategies represents a promising area of investigation that bridges tumor biology with supportive care, aiming to enhance both therapeutic efficacy and patient quality of life. Methods: This narrative review explores the biological and pathophysiological rationale for the ketogenic diet (KD) as a possible complementary intervention in LC management and summarizes the published preclinical and clinical data supporting this rationale. Results: We discuss key aspects of tumor metabolism, including the Warburg effect, glucose dependency, oxidative stress regulation, fatty acid metabolism, lactate cycling and tumor microenvironment interactions, with particular emphasis on how carbohydrate restriction and ketosis may exacerbate mitochondrial dysfunction in cancer cells and modulate inflammatory pathways. Furthermore, we summarize available preclinical and clinical evidence evaluating the KD in oncology and, more specifically, in LC, focusing on feasibility, safety, metabolic effects, and potential synergy with chemotherapy, radiotherapy, and immunotherapy. Conclusions: While preclinical models suggest enhanced treatment efficacy, clinical data remain limited and heterogeneous, with patient adherence representing a major challenge. Further well-designed longitudinal studies are required to clarify the therapeutic role of the ketogenic diet in lung cancer.
Eleftheriadou et al. (Fri,) studied this question.