Are micronutrient levels and supplements causally associated with the risk of Alzheimer's disease? A two-sample Mendelian randomization analysis

The potential of micronutrients, including vitamins and minerals, to prevent Alzheimer's disease (AD) has attracted much attention. However, the causal associations between micronutrient levels or supplements and AD risk remain unclear. We performed a two-sample Mendelian randomization (2SMR) analysis to evaluate the causal associations between micronutrient levels and supplements and AD risk. A total of 60 genome-wide association studies (GWAS) related to five types of vitamins (vitamins A, B, C, D, and E) and seven types of minerals (magnesium, calcium, iron, copper, zinc, selenium, and phosphorus) were included. For vitamins, using the data source provided by two GWAS, the analysis of 2SMR indicated that the vitamin D level was causally associated with a decreased risk of AD (IVW, OR: 0.474, 95%CI: 0.269-0.834, P-value = 0.010; OR: 0.857, 95%CI: 0.748-0.982, P-value = 0.027), while no effect of vitamin D supplement was observed. Currently, available data do not support the causal associations between the other four types of vitamins/supplements and AD risk. As for minerals, the copper level acted as a causal protective factor for AD risk (IVW, OR: 0.865, 95%CI: 0.751-0.998, P-value = 0.046). In conclusion, the present analysis indicated that among the vitamins and minerals, vitamin D and copper levels exhibited negative causal associations with AD risk, which may help in better use of micronutrients to prevent AD and require further verification by further studies.