Are micronutrient levels and supplements causally associated with the risk of Alzheimer's disease? A two-sample Mendelian randomization analysis
Lei Meng1,2, Zhe Wang1,2, Yu-Cheng Ming1,2
1Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People's Republic of China. shen@sdut.edu.cn.
Abstract:
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.
Insights
Higher vitamin D and copper levels may reduce Alzheimer's disease (AD) risk. This Mendelian randomization study found these micronutrients causally linked to decreased AD risk, suggesting potential preventative roles.
Area of Science:
- Neuroscience
- Nutritional Science
- Genetics
Background:
- Alzheimer's disease (AD) prevention is a significant public health concern.
- The role of micronutrients (vitamins and minerals) in AD etiology is under investigation.
- Causal links between micronutrient status and AD risk require robust evidence.
Purpose of the Study:
- To investigate the causal associations between genetically predicted levels of various vitamins and minerals and Alzheimer's disease risk.
- To differentiate between the effects of nutrient levels and supplement intake on AD risk.
Main Methods:
- A two-sample Mendelian randomization (2SMR) analysis was employed.
- Data from 60 genome-wide association studies (GWAS) for five vitamins and seven minerals were utilized.
- Instrumental variables were derived from genetic variants associated with nutrient levels.
Main Results:
- Elevated vitamin D levels showed a significant causal association with reduced Alzheimer's disease risk (ORs < 1, P < 0.05).
- Higher copper levels were also causally associated with a decreased risk of Alzheimer's disease (OR: 0.865, P = 0.046).
- No significant causal associations were found for vitamin D supplements or other tested vitamins and minerals.
Conclusions:
- Vitamin D and copper levels, but not their supplementation, appear to be causally protective against Alzheimer's disease.
- These findings suggest that maintaining adequate levels of vitamin D and copper may contribute to AD prevention strategies.
- Further research is warranted to confirm these causal relationships and explore underlying mechanisms.
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