The prevalence of anxiety and depression has increased worldwide, especially in the wake of the COVID-19 pandemic. “Therefore, identifying specific interventions that improve depressive status is critical for public health policy,” wrote Huan Wang, MD, of First Hospital of Jilin University, Changchun, China, and colleagues.
Recent evidence suggests that modifiable lifestyle factors, including nutrition, may have a positive impact on symptoms of anxiety and depression, and observational studies have shown that antioxidant supplements affect depressive status, but data from randomized, controlled trials are limited by small sample sizes, they wrote.
In a study published in the Journal of Affective Disorders, the researchers conducted a meta-analysis of 52 studies with a total of 4,049 patients. Of these, 2,004 received antioxidant supplements and 2,045 received a placebo supplement or no supplements. The median treatment duration was 11 weeks; treatment durations ranged from 2 weeks to 2 years. All 52 studies addressed the effect of antioxidants on depressive status, and 21 studies also assessed anxiety status. The studies used a range of depression scales, including the Beck Depression Inventory, the Edinburgh Postnatal Depression Scale, Montgomery-Asberg Depression Rating Scale, Hamilton Depression Rating Scale, Center for Epidemiologic Studies–Depression, and Hospital Anxiety and Depression Scale.
Overall, the meta-analysis revealed a statistically significant improvement in depressive status associated with antioxidant supplement use (standardized mean difference, 0.60; P < .00001). When broken down by supplement, significant positive effects appeared for magnesium (SMD = 0.16; P = .03), zinc (SMD = 0.59; P = .01), selenium (SMD = 0.33; P = .009), CoQ10 (SMD = 0.97; P = .05), tea and coffee (SMD = 1.15; P = .001) and crocin (MD = 6.04; P < .00001).
As a secondary outcome, antioxidant supplementation had a significantly positive effect on anxiety (SMD = 0.40; P < .00001).
The mechanism of action for the effect of antioxidants remains unclear, the researchers wrote in their discussion, but, “Depriving or boosting the supply of food components with antioxidant capabilities might worsen or lessen oxidative stress,” they said.
The researchers attempted a subgroup analysis across countries, and found that, while antioxidant supplementation improved depressive status in populations from Iran, China, and Italy, “no significant improvement was found in the United States, Australia, Italy and other countries.” The reasons for this difference might be related to fewer studies from these countries, or “the improvement brought about by antioxidants might be particularly pronounced in people with significant depression and higher depression scores,” they wrote. “Studies have shown that Asian countries have fewer psychiatrists and more expensive treatments,” they added.
The findings were limited by several factors including the inability to include all types of antioxidant supplements, the range of depression rating scales, and insufficient subgroup analysis of the range of populations from the included studies, the researchers noted.
“Additional data from large clinical trials are needed to confirm the efficacy and safety of antioxidant supplements in improving depressive status,” they said. However, the results suggest that antioxidants may play a role as an adjunct treatment to conventional antidepressants, they concluded.
The study was funded by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.