Dietary intake and circulating levels of vitamins, antioxidants, and fatty acids in relation to coronary heart disease risk: a systematic review and dose–response meta-analysis

Abstract

Background Associations between vitamin, antioxidant, and fatty acid exposure and coronary heart disease (CHD) risk remain uncertain, and dose–response relationships are poorly defined. This study aimed to evaluate the overall and dose–response associations between dietary and circulating vitamin, antioxidant, and fatty acid levels and CHD risk from observational evidence. Methods PubMed, Web of Science, Embase, and the Cochrane Library were searched for studies published up to February 2, 2026 (PROSPERO: CRD420261380823). Eligible observational studies (case–control, cohort, cross-sectional) reporting associations between vitamin, antioxidant, or fatty acid levels and CHD risk were included. A total of 27 studies were analyzed. Categorical (highest vs. lowest) and dose–response analyses were performed, estimating pooled odds ratios (ORs), relative risks (RRs), and hazard ratios (HRs). Results Twenty-seven observational studies were included. In categorical analyses, higher circulating 25(OH)D (pooled HR = 0.79, 95% CI = 0.74–0.85; I2 = 1.4%, τ2 = 0.0000) and carotenoids (pooled OR = 0.64, 95% CI = 0.46–0.91; I2 = 0.0%, τ2 = 0.0000) were inversely associated with CHD risk. In analyses per 1-SD increase in circulating fatty acid levels, linoleic acid was inversely associated with CHD risk (pooled OR = 0.69, 95% CI = 0.57–0.84; I2 = 0.0%, τ2 = 0.0000), whereas palmitic acid (pooled OR = 1.52, 95% CI = 1.23–1.89; I2 = 0.0%, τ2 = 0.0000) and dihomo-γ-linolenic acid (DGLA; pooled OR = 1.26, 95% CI = 1.05–1.52; I2 = 0.0%, τ2 = 0.0000) were positively associated with CHD risk. Several other exposure-specific estimates and most dose–response analyses were supported by only one or two studies and should therefore be interpreted cautiously. Conclusion In observational studies, selected dietary and circulating vitamin, antioxidant, and fatty acid exposures were associated with CHD risk. These associations do not establish causality or justify specific supplementation recommendations, and findings based on sparse data require confirmation in additional prospective studies.