Dietary one‑carbon nutrients and genetic risk in Parkinson disease: a prospective cohort study

BACKGROUND: Several studies have investigated the effects of dietary one-carbon metabolism (OCM) nutrients, such as methionine, folate, vitamin B6, and vitamin B12, on Parkinson disease (PD). However, current evidence remains insufficient to definitively establish a link between OCM intake, PD incidence, and genetic risk. METHODS: Among 202 171 individuals aged 37 to 73 in the UK Biobank, we assessed dietary OCM nutrient intake via repeated 24‑hour recalls, determined PD incidence via validated International Classification of Diseases, 10th Revision (ICD‑10) codes, and quantified genetic risk with polygenic risk scores. Employing Cox proportional hazards models supplemented by sensitivity analyses, we evaluated the associations and potential interactions among OCM nutrient intake, genetic risk, and PD incidence. RESULTS: Over a median 12.27-year follow-up of 202 171 participants, 1037 incident PD cases occurred. In multivariable-adjusted Cox models, compared with participants in the lowest quartile, those in the highest quartile of methionine, vitamin B6, folate, and vitamin B12 had a lower risk of PD (hazard ratio [HR] [95% confidence interval (CI)] = 0.83 [0.69-1.00], 0.75 [0.62-0.90], 0.71 [0.59-0.85], and 0.79 [0.65-0.94]). Genetically stratified analyses showed folate inversely associated with PD risk in the low-risk group (HR [95% CI] = 0.65 [0.48-0.88]) (p for interaction = .48); vitamin B12 linked to lower risk in the high-risk group (HR [95% CI] = 0.78 [0.63-0.99]) (p for interaction = .83); and vitamin B6 inversely associated across both strata (high-risk HR [95% CI] = 0.77 [0.62-0.97]; low-risk HR [95% CI] = 0.59 [0.44-0.80]) (p for interaction = .08). CONCLUSIONS: Higher OCM nutrient intake might be inversely associated with PD risk. However, evidence regarding the independent contributions of dietary and genetic factors remains inconclusive.