The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.

Supplements are widely perceived as safe and beneficial; yet in oncology, this assumption is questionable. Clinical trials over the past few decades have often produced disappointing results, raising a critical question: are these agents used correctly, or could they inadvertently cause harm? This review examines supplements frequently used in cancer care-such as oral vitamin C, berberine, N-acetylcysteine, vitamin D, vitamin E, melatonin, polyphenols, alpha-lipoic acid, selenium, and coenzyme Q10-which can act as tumor suppressors or promoters depending on dose, route, and disease stage. We examine their dual antioxidant and pro-oxidant properties, revealing that therapeutic outcomes are shaped not only by the molecule itself, but also by bioavailability, dosing thresholds, and the tumor redox environment. Building on these insights, we propose that four factors may be considered to guide clinical use: ensure that anticancer effects are not overshadowed by antioxidant activity, achieve sufficient bioavailability, confirm pro-oxidant concentrations where possible, and prioritize supplements that target the respiration-supported non-OxPhos pathways. By framing supplements as context-dependent redox modulators rather than universally beneficial agents, this review provides a mechanistically grounded framework for informing future research and safer, more effective integrative oncology strategies.