Vitamins C, E, and β-Carotene and Risk of Type 2 Diabetes: A Systematic Review and Meta-Analysis

A systematic review and meta-analysis was conducted to assess the relationship between the common dietary antioxidants vitamin C, E, and beta-carotene and type 2 diabetes (T2D) and related traits. MEDLINE, Embase, and Cochrane Library were searched for relevant publications up until May 2023. Studies were eligible if they had a cohort, case-control, or randomized controlled trial (RCT) design and examined dietary intake, supplementation, or circulating levels of these antioxidants as exposure, and insulin resistance, beta cell function, or T2D incidence as outcomes. Summary relative risks (RR) or mean differences (MD) with 95% confidence intervals (CIs) were estimated using random-effects models. The certainty of evidence was assessed with GRADE. Among 6,190 screened records, 25 prospective observational studies and 15 RCTs were eligible. Inverse associations were found between dietary and circulating antioxidants and T2D (observational studies). The lowest risk was at intakes up to 70 mg/day of vitamin C (RR: 0.76; CI 0.61, 0.95), 12 mg/day of vitamin E (RR: 0.72; CI 0.61, 0.86), and 4 mg/day of beta-carotene (RR: 0.78; CI 0.65, 0.94). Supplementation with vitamin E (RR: 1.01; CI 0.93, 1.10) or beta-carotene (RR: 0.98; CI 0.90, 1.07) did not have a protective effect on T2D (RCTs), and data on vitamin C supplementation was limited. Regarding insulin resistance, higher dietary vitamin C (RR: 0.85; CI 0.74, 0.98) and vitamin E supplementation (MD: -0.35; CI -0.65, -0.06) were associated with a reduced risk. The certainty of evidence was high for the associations between T2D and dietary vitamin E and beta-carotene, and low to moderate for other associations. In conclusion, moderate intakes of vitamins C, E, and beta-carotene may lower the risk of T2D by reducing insulin resistance. Lack of protection with supplementation in RCTs suggests that adequate rather than high intakes may play a role in T2D prevention. PROSPERO(CRD42022343482)