Zinc in depression: From development to treatment: A comparative/ dose response meta-analysis of observational studies and randomized controlled trials.

BACKGROUND: A previous meta-analysis suggested that zinc status may be linked to depression status. However, it remains unclear whether zinc status can predict the risk of depression development, or whether the monotherapy of zinc is superior to the combination of zinc supplementation and antidepressant medications in the treatment of depression. Therefore, this meta-analysis aimed to clarify the impact of zinc status and supplementation on depression development and status across all available evidence. METHODS: PubMed, EMBASE, Scopus, and ISI web of science were searched, up to 14 May 2020, for relevant publications. Pooled relative risks (RRs) with 95% confidence intervals (CI) in observational studies, and mean and standard deviation (SD) for the change in depression score in RCTs were calculated using a random-effects model. RESULTS: The meta-analysis of RCTs indicated that zinc supplementation significantly lowered depressive symptom scores of depressed patients [weighted mean difference (WMD = -4.15 point; 95% CI: -6.56, -1.75 point; P < 0.01)], and the improvement in depression status occurred only when zinc supplementation was prescribed as a monotherapy. The cohort studies showed that the highest level of zinc intake was associated with a 28% reduced risk of depression (RR: 0.66; 95% CI: 0.50, 0.82; I2 = 13.90). Dose-response analyses revealed a significant non-linear effect of baseline mood status on depression score. CONCLUSION: Current evidence from observational studies and RCT's supports the potential benefits zinc to reduce the risk of, and alleviate, depression. However, further trials are needed to confirm the beneficial effect of zinc as a monotherapy versus adjunctive therapies.

The effect of vitamin C supplementation on mood status in adults: a systematic review and meta-analysis of randomized controlled clinical trials.

OBJECTIVE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to clarify the effect of vitamin C supplementation on mood in both depressed and non-depressed populations. METHODS: A systematic search of PubMed, EMBASE, ISI web of science and Scopus databases was conducted, from inception to 1 March 2020. Random-effects meta-analyses were used to estimate the effect size (as Hedge's g) of vitamin C supplementation on depressive symptoms. RESULTS: Finding from 10 trials with 836 participants revealed no significant improvement in mood status in overall analysis (n = 10, Hedge's g = 0.09; 95% confidence interval: -0.15 to 0.33; P = 0.465). However, subgroup analysis showed beneficial effects of vitamin C supplementation in patients who were not prescribed antidepressants (subclinical depressed) (n = 5, Hedge's g: -0.18; 95% CI: -0.35, -0.01, P = 0.041; I2 = 0.00%,). CONCLUSIONS: Although no significant effect on mood status was observed in overall population, this meta-analysis tentatively suggests that vitamin C may produce mood-elevating effects in patients with subclinical depression. Further research is recommended to reach a firm conclusion. PROTOCOL REGISTRATION: The study protocol was registered in the international prospective register of systematic reviews database (http://www.crd.york.ac.uk/PROSPERO, registration no: CRD42018086677).

Effects of zinc, vitamin D, and their co-supplementation on mood, serum cortisol, and brain-derived neurotrophic factor in patients with obesity and mild to moderate depressive symptoms: A phase II, 12-wk, 2 × 2 factorial design, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: The aim of this study was to investigate the effects of zinc, vitamin D, and their co-supplementation versus placebo on changes in the Beck Depression Inventory II (BDI-II) score, serum cortisol level, and brain-derived neurotrophic factor (BDNF) in obese/overweight patients with depressive symptoms. METHOD: This 2 × 2 factorial, double-blind, randomized, placebo-controlled trial with obese/overweight patients with depressive symptoms was conducted in the Endocrinology and Metabolism Research Center (EMRC), Vali-Asr, Emam Khomeini Hospital between July 2016 and February 2017. The intervention period was 12 wk. There were 140 randomized participants who were obese or overweight (mean ± SD, 38.35± 6.70 y of age; mean ± SD body mass index, 30.1 ± 3.78 kg/m2) with BDI ≥ 10. Participants were randomly assigned to one of four groups in a 1:1:1:1 ratio: 2000 IU/d vitamin D + zinc placebo; 30 mg/d zinc gluconate + vitamin D placebo; 2000 IU/d vitamin D + 30 mg/d zinc gluconate; or vitamin D placebo + zinc placebo for 12 wk. RESULTS: We analyzed 125 participants, and a significant decrease in BDI-II was found among those who received zinc, vitamin D, or joint zinc-vitamin D supplements compared with the placebo group (P < 0.001). Zinc was significantly more effective than vitamin D on decreasing the depression score. Supplementation with zinc, vitamin D, or a combination of the two had no significant effects on serum cortisol (P = 0.974) or BDNF (P = 0.076). Fifteen patients discontinued participation owing to pregnancy (n = 1), severe anemia (n = 1), and unspecified unwillingness to continue (n = 13). CONCLUSION: Supplementation with zinc, vitamin D, or in combination for 12 wk yielded significant beneficial effects on the BDI-II score in obese or overweight patients with BDI-II ≥10.