Abstract
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Objectives: To prospectively evaluate the association of dietary flavonoid intake with both incident depression risk and brain structural changes.
Design: Prospective cohort study.
Setting: UK Biobank.
Participants: The study included 114 848 non-depressed individuals (with ≥ 2 eligible 24-h dietary recalls) to analyse incident depression risk; a subgroup of 2120 was analysed for brain structural changes.
Exposures: Flavonoid exposure was assessed via total intake, subclass intake, and the Flavodiet Score derived from the Top 10 flavonoid-rich foods.
Main outcome measures: Incident depression, ascertained from inpatient and death register data, and alterations in cortical grey matter volumes and white matter integrity.
Results: During a median follow-up of 10.5 years, 2965 incident depression cases were identified. After adjusting for demographic, major lifestyle, and clinical factors, the hazard ratios (HRs) and 95% confidence intervals (CIs) for total flavonoid intake, across successive quintiles comparing to the lowest, were 0.89 (0.80, 1.00), 0.93 (0.83, 1.04), 0.94 (0.84, 1.05), and 0.84 (0.75, 0.95), respectively (P trend = 0.030). Corresponding HRs (95% CIs) for the Flavodiet Score were 0.88 (0.78, 0.98), 0.94 (0.84, 1.05), 0.90 (0.80, 1.01), and 0.77 (0.68, 0.87), respectively (P trend < 0.001). No significant interactions were found between total flavonoid intake and potential effect modifiers. Regarding flavonoid subclasses, intakes of anthocyanins and flavanones were linearly associated with lower depression risk, with HRs per SD (95% CIs) being 0.91 (0.88, 0.94) and 0.94 (0.90, 0.97). Among the biochemical indices, physical measures, and chronic disease histories examined, the Creatinine-to-Cystatin C ratio exhibited the largest mediating effect on the association between total flavonoid intake and depression, accounting for 14.4%. Concerning brain structural changes, higher flavonoid intake was associated with smaller atrophy in left Caudal anterior cingulate, left Supramarginal, right Caudal middle frontal, and right Precentral, and a smaller increase in mean diffusivity in the left Anterior Thalamic Radiation tract (all P < 0.05).
Conclusions: Our study supported the beneficial contribution of dietary flavonoid consumption, particularly anthocyanins and flavanones, to depression prevention, alongside evidence for the protection of total flavonoid intake against adverse brain structural changes. Further mechanistic studies and clinical trials are warranted for translating these results into public health policy.
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