Antioxidant Food Supplementation in Cancer: Lessons from Clinical Trials and Insights from Preclinical Studies

Food antioxidant supplementation has been widely proposed for cancer prevention and adjuvant therapy due to the pleiotropic role of antioxidants. Herein, particular attention is given to recent clinical trials based on the use of dietary supplements in cancer patients, both as monotherapy and in combination with standard treatments, exploring both their potential benefits and risks. This review focuses on the efficacy of the most important food antioxidants, highlighting how their action may change depending on different factors such as cancer type, dose, timing of administration and antioxidant status of the patient. The results of clinical trials are often contradictory, and the clinical benefit of dietary antioxidants appears more consistent in patients with a baseline antioxidant deficiency. Furthermore, by analyzing the mechanisms underlying the contradictory clinical evidence and critically addressing the issues related to the methodologies used in preclinical models, this review could be helpful in guiding the personalized use of antioxidant supplementation in cancer patients.