Abstract
INTRODUCTION: Depression represents a significant global health burden, ranking as one of the leading causes of disability worldwide, and nutrition plays a key role in mental health. Vitamin A, essential for immune and neurological function, has shown conflicting associations with depression. Magnesium, essential for neurotransmission and neuroprotection, is associated with a reduced risk of depression. Importantly, magnesium is required for the activation of enzymes involved in vitamin A metabolism, suggesting a potential interaction between these nutrients in depression. However, this interaction remains poorly understood. This study investigates how magnesium intake modifies the relationship between vitamin A and depression, with the aim of elucidating their combined effects and informing personalized dietary strategies for depression prevention. RESEARCH DESIGN AND METHODS: Data for this study were extracted from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2016, involving a total of 60,936 participants. The final analysis included 25,277 adults aged ≥20 years (Female: 12,581, Male:12,696), excluding pregnant women, individuals under 20, and those with incomplete data. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), supplemented by self-reporting questionnaires. Dietary intake was assessed via a recall interview at the mobile examination center (MEC). Dietary vitamin A intake, treated as a continuous variable, was categorized based on the median intake value. Stratified analyses were conducted based on sex and magnesium intake levels (Female: low: <310 mg/day; high: ≥310 mg/day; Male: low: <400 mg/day; high: ≥400 mg/day). RESULTS: Our cross-sectional study showed that in women with low magnesium intake, higher vitamin A intake was associated with a reduced risk of depression (OR: 0.83, 95% CI: 0.76-0.92, p < 0.001), whereas no significant association was observed in the high magnesium group. Men did not show such an interaction. There was also a significant interaction between vitamin A levels and magnesium intake in reducing the incidence of depression (p-value for interaction = 0.145). CONCLUSION: Our study suggests that a sex-specific interaction between dietary magnesium and vitamin A in modulating depression risk. This interaction highlights the potential role of combined nutritional interventions in depression management. Further randomized controlled trials are warranted to confirm these findings.