Causal effect of kimchi intake on HDL-cholesterol levels in middle aged Korean men: a two-sample Mendelian randomization analysis.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) helps remove excess cholesterol, and low levels are a key metabolic risk factor for cardiovascular disease. Although several studies have investigated the association between kimchi consumption and HDL-C levels, these observational findings are often limited by confounding factors and reverse causality. OBJECTIVE: We aimed to assess the causal association between kimchi intake and the reduced HDL-C using Mendelian randomization (MR), with analyses stratified by sex. METHODS: We conducted this study using participants from two cohorts of the Korean Genome and Epidemiology Study (KoGES): the Health Examinees (HEXA) cohort (n = 53,060) and the Ansan/Ansung cohort (n = 4,907). Kimchi intake was assessed via a semi-quantitative food frequency questionnaire, estimating total daily consumption (g/day) of various kimchi types including baechu (cabbage) kimchi, kkakdugi/mu-kimchi, nabak-kimchi/dongchimi, and other varieties. Single nucleotide polymorphisms (SNPs) associated with kimchi consumption were identified via genome-wide association studies (GWAS), adjusting for covariates and applying a significance threshold of p < 5 × 10⁻⁵ and linkage disequilibrium cutoff (r² < 0.001). A total of 86 SNPs in men and 82 in women were selected as instrumental variables (IVs) for MR analysis. The MR analysis was conducted using inverse-variance weighted (IVW), MR-Egger, weighted median, and MR-PRESSO methods. Sensitivity analyses included heterogeneity testing, leave-one-out analysis, and funnel plot inspection. RESULTS: In men, a significant causal relationship between higher kimchi consumption and lower odds of reduced HDL-C was identified by both the IVW (OR = 0.997, 95% CI = 0.996-0.999, p < 0.05) and MR-PRESSO (OR = 0.998, 95% CI = 0.996-0.999, p < 0.05) analyses, with no evidence of heterogeneity or horizontal pleiotropy. No significant associations were observed in women. CONCLUSION: This study provides evidence for a causal effect of kimchi consumption in preventing decreases in HDL-C levels among middle-aged Korean men. These findings support kimchi as a sex-specific dietary intervention for cardiovascular health.