Causal Effects of Circulating Micronutrients on Cognitive Function: Evidence From a Mendelian Randomization Study

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Abstract
Background: Cognitive impairment is a growing concern worldwide, driven by an aging population. Emerging evidence suggests that micronutrients may play critical roles in maintaining cognitive health and preventing neurodegeneration. However, the causal relationships between specific micronutrients and cognitive function remain unclear.Methods: This study employed a two‐sample Mendelian randomization (MR) approach to investigate the causal effects of 16 circulating micronutrients on cognitive function. Genetic variants associated with micronutrient levels were used as instrumental variables (IVs), and cognitive outcomes, including reaction time, cognitive performance, prospective memory, and fluid intelligence, were assessed using publicly available genome‐wide association study (GWAS) datasets. Sensitivity analyses were conducted to evaluate heterogeneity, pleiotropy, and robustness of the findings.Results: MR analysis revealed potential positive effects of β‐carotene and phosphorus on reaction time, reflecting faster cognitive responses. Vitamin E was positively associated with cognitive performance, while vitamin B6 had a negative effect. Selenium was positively correlated with fluid intelligence, whereas elevated vitamin A1 levels were associated with reduced fluid intelligence. No significant associations were observed for other micronutrients across the cognitive domains assessed.Conclusion: This study highlights the roles of specific micronutrients, like β‐carotene, phosphorus, selenium, and vitamin E, in cognitive health, while excessive vitamin A1 and B6 may be harmful, warranting further investigation.

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