Exploring the Impact of Flavonoids on Symptoms of Depression: A Systematic Review and Meta-Analysis

Antioxidants
Q1
Oct 2021
Citations:36
Influential Citations:0
Systematic Reviews / Meta-Analyses
86
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Methods
46 studies (1999–2021): 36 clinical trials (31 randomized controlled trials) and 10 observational cohorts. Clinical trials averaged 67.4 randomized participants; durations ranged from 5 days to 2 years (most around 8 weeks). Observational cohorts averaged 9,426 participants; ages 18–92; both genders; various health conditions with depressive symptoms; 16 studies involved perimenopausal, menopausal, or postmenopausal women. Depression outcomes assessed with GDS, CES-D, BDI, HAM-D.
Intervention
Flavonoid supplementation across subclasses (isoflavones, flavonols, flavan-3-ols, flavones, anthocyanins, proanthocyanidins). Administered via tablets/capsules, liquids, or powders; durations ranged from 5 days to 2 years; dosages varied and are not specified here.
Results
Flavonoids significantly reduce depressive symptoms in adults with depressive symptoms across diverse health conditions. Pooled results from 36 clinical trials (n=2,788) show a mean difference in depression scores of −1.65 (95% CI −2.54 to −0.77; p<0.01). Sensitivity analysis removing outliers yielded a still-significant reduction (−0.69; 95% CI −1.13 to −0.25; p<0.01) with heterogeneity reduced (I2 from 92% to 35%). Subgroups with significant effects include isoflavones, flavonols, and flavan-3-ols; effects observed in both controlled and uncontrolled trials, and in double-blind studies. Observational studies suggest higher flavonoid intake associates with lower depressive symptoms in some contexts. Evidence is preliminary and not specific to major depressive disorder; well-powered, long-term trials with standardized intake assessment are needed to define optimal dosages and populations; potential for depression prevention if confirmed.
Limitations
High heterogeneity (I2 ≈ 92%), varied flavonoid subclasses, doses, durations and sources; many trials small/underpowered; depressive symptoms measured rather than diagnosed MDD; inconsistent blinding and compliance reporting; dietary intake assessment not standardized; possible confounding dietary factors; observational studies varied in quality; generalizability limited.

Abstract

Recent evidence suggests that diet modifies key biological factors associated with the development of depression. It has been suggested that this could be due to the high flavonoid content commonly found in many plant foods, beverages and dietary sup...