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

•Significant decreases were seen in the Beck Depression Inventory score among those who received zinc, vitamin D, or a combination of zinc and vitamin D supplements.•Zinc had a more significant effect than vitamin D on the depression score.•Supplementation with zinc, vitamin D, and a combination of the two had no significant effects on serum cortisol or brain-derived neurotrophic factor. 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. 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. 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). 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.