A Causal and Inverse Relationship between Plant-Based Diet Intake and in a Two-Sample Mendelian Randomization Study

A plant-based diet (PBD) has been reported to be linked to metabolic syndrome (MetS) risk in observational studies, but not in causal association studies. We aimed to examine the hypothesis that high PBD exhibited a causal and inverse association with MetS and its components using two-sample Mendelian randomization (MR). PBD was clustered according to food intake, which was assessed by semi-quantitative food frequency questionnaires using a principal component analysis. The instrumental variables were generated using the genome-wide association study (GWAS) of a High-PBD group (≥67th percentiles) after adjusting for the covariates related to MetS, with a significance level of p < 5 × 10^-5 and linkage disequilibrium (r² < 0.001), in a city hospital-based cohort (n = 58,701). The causal association of the PBD intake with MetS risk was examined with a two-sample MR approach in the rural plus Ansan/Ansung cohorts (n = 13,598). The High-PBD group showed higher energy, fat, protein, cholesterol, fiber, sodium, calcium, vitamin C and D, and flavonoid intake than the Low-PBD group. The High-PBD group showed a lower risk of MetS, waist circumference, hyperglycemia, hypo-HDL-cholesterolemia, and hypertriglyceridemia using an inverse-variance weighted method (p < 0.05). Low-PBD intake significantly elevated only waist circumference in weighted-median analysis (p < 0.05). No heterogeneity, horizontal pleiotropy, or single genetic variant influenced the causal relationship. In conclusion, low PBD appeared to be causally positively related to MetS risk and its components, but not hypertension. Therefore, Korean-style PBD may be beneficial for decreasing MetS risk in Asian adults.