Table 1.

Salient features of vitamin D supplementation trials

Author, year, place	Type of study/sampling	Sample size and characteristics	Intervention details	Main findings	Special remarks (if any)
Jorde et al., 2008 Norway[40]	Randomized controlled trial	441 subjects aged 21-70 years	Trial of 20,000 or 40,000 IU vitamin D per week versus placebo for 1 year	In the two groups given vitamin D, but not in the placebo group, there was a significant improvement in BDI scores after 1 year	Subjects with serum 25(OH)D levels <40 nmol/L scored significantly higher on the BDI total and the BDI subscale than those with levels >40 nmol/L
Kjærgaard et al., 2012 Norway[41]	Randomized controlled trial	357 subjects aged 30-75 years with serum 25(OH)D levels below 55 nmol/l (n=243), those with serum 25(OH)D levels above 70 nmol/l (n=114) served as nested controls	Participants with low 25(OH)D levels were randomised to either placebo or 40 000 IU vitamin D(3) per week for 6 months	In the intervention study, no significant effect of high-dose vitamin D was found on depressive symptom scores when compared with placebo	Participants with low 25(OH)D levels at baseline were more depressed than participants with high 25(OH)D levels
Yalamanchili and Gallagher, 2012 United States[42]	Randomized controlled trial (secondary data)	489 community dwelling elderly post-menopausal women aged 65-77 years	Three interventions: Hormonal therapy (conjugated equine estrogens with or without medroxyprogesterone acetate), calcitriol or combination therapy (HT plus calcitriol) and matching placebos for 3 years	There was no effect of hormone therapy, calcitriol or hormone therapy with calcitriol on depression	In post-menopausal women, there was no effect of hormone therapy and calcitriol either individually or in combination with depression.
Khoraminiya et al., 2013 Iran[43]	Randomized controlled trial	42 outpatients aged 18-65 years with a diagnosis of MDD without psychotic features	Daily oral 1,500 IU of vitamin D3 plus 20 mg fluoxetine or placebo plus 20 mg fluoxetine for 8 weeks	Depression severity decreased significantly in the intervention group compared to controls.	Combination therapy was superior to fluoxetine alone in controlling mood symptoms from the fourth week of treatment
Mozaffari-Khosravi et al., 2013 Iran[44]	Randomized controlled trial	120 subjects aged 20-60 years with depressive symptoms and vitamin D deficiency	Two single intramuscular injections equivalent to 300,000 IU (G300) and 150,000 IU (G150) of vitamin D were compared with a no treatment group (NTG) for 3 months	Significant improvement on Beck depression inventory scores was noted between G300 and NTG, but not between G150 and NTG groups	Correction of vitamin D deficiency also improved the depression state
Sepehrmanesh et al., 2016 Iran[45]	Randomized controlled trial	40 patients aged 18-65 years with a diagnosis of MDD	Single capsule of 50,000 IU vitamin D per week (n=20) or placebo (n=20) for 8 weeks	A trend towards a greater decrease in the BDI was observed in the vitamin D group but not the placebo group	No statistically significant differences were observed
Wang et al., 2016 China[46]	Randomized controlled trial	726 dialysis patients with depression	52-week treatment of oral 50,000 IU per week of vitamin D3 versus a placebo control group	Depressive symptoms and BDI scores were not significantly improved in the test group versus the control group	Authors found a beneficial effect on the subtype of vascular depression
Choukri et al., 2018 New Zealand[47]	Randomized controlled trial	152 healthy young adult women aged 18-40 years	50, 000 IU of oral vitamin D3 or placebo once per month for 6 months	No benefits were noted in the intervention group with regard to depressive or anxiety outcomes over controls
Jorde and Kubiak, 2018 Norway[48]	Randomized controlled trial	408 healthy adult subjects aged 40 and above	Vitamin D 100,000 IU as a bolus dose (capsule) followed by 20,000 IU per week versus placebo for 4 months	BDI scores did not differ significantly between the vitamin D and placebo group
Dumville et al., 2006 United Kingdom[50]	Randomized controlled trial	2117 women aged 70 years or more	Daily oral supplementation of 800 IU if vitamin D plus information sheet on increasing calcium in diet versus only information sheet in controls	No significant differences were observed between the two groups on subjective psychological wellbeing scores
Vieth et al., 2004 Canada[51]	Randomized controlled trial (two sequential partly overlapping studies)	Study 1: 64 outpatients with 25(OH)D <61 nmol/L) Study 2: 117 patients with serum 25(OH)D <51 nmol/L	Study 1: low dose supplementation (600 IU/day) versus high dose supplementation (4,000 IU/day) of vitamin D versus no supplementation for 2-6 months Study 2: Only supplementation arms were compared	In Study 1, wellbeing score improved more for the 100 mcg/day group than for the lower-dosed group. In Study 2, wellbeing scores improved with both doses of vitamin D	High dose supplementation was superior to low dose supplementation in subjects with average higher levels of serum vitamin D
Vaziri et al., 2016 Iran[56]	Randomized controlled trial	169 pregnant women aged 18 years or older with gestational age of 26-28 weeks and EPDS score of 0-13	Intervention group received 2,000 IU vitamin D3 daily from 26 to 28 weeks of gestation until childbirth Control group received two placebo pills composed of starch daily for same period	Intervention group had greater reduction in depression scores than control group at 38-40 weeks of gestation and at 4 and 8 weeks after birth	Supplementation of vitamin D3 daily during late pregnancy was effective in decreasing perinatal depression levels
Föcker et al., 2018 Germany[63]	Randomized controlled trial (protocol only)	200 inpatient children and adolescents (aged 11-18.9 years) with vitamin D deficiency and BDI score >13	Intervention group will receive 2,640 I.E. vitamin D3 daily for 28 days along with TAU while placebo group will receive only TAU. After 28 days, both groups receive 1,000 I.E vitamin D daily for next 11 months	Awaited	Tests the hypothesis that delaying vitamin D supplementation in placebo group will impact improvement of depression scores
Azzam et al., 2015 Egypt[62]	Randomized controlled trial	21 children with ASD aged 2-12 years	Intervention group received daily oral dose of 2,000 IU vitamin D3 versus no supplementation in placebo group (6-month study)	No significant differences between groups on ASD outcome scores	Limitation was that baseline 25(OH)D levels were lower in intervention group and levels did not rise following supplementation

BDI: Beck depression inventory; MDD: Major depressive disorder; EPDS: Edinburg postnatal depression scale; TAU: Treatment as usual; ASD: Autism spectrum disorder