Protective Effects of Micronutrient Supplements, Phytochemicals and Phytochemical-Rich Beverages and Foods Against DNA Damage in Humans: A Systematic Review of Randomized Controlled Trials and Prospective Studies

Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative dis-eases, and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage. The objectives of this review are to: 1) assemble and systematically analyze high-level evidence for the effect of supplementation with micronutrients and phytochemicals on baseline levels of DNA damage in humans, and 2) use this knowledge to identify which of these essential micronutrients or nonessential phytochemicals promote DNA integrity in vivo in humans. We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal inter-vention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design. In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score >= 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor beta-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B12, and zinc) and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium, and zinc). Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving the maintenance of genome integrity.