The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta‐analysis of randomized controlled trials

Figures & data

Table 1. Results of statistical syntheses.

	No. of RCTs (references)	Patients/control (n)	Effect sizes (95 % CI)	Effect size p-value	Heterogeneity I^2 (%)
Groups by all participants	41 (Amini et al. 2022; Kaviani et al. 2020; Sikaroudi et al. 2020; Yosaee et al. 2020; Zheng et al. 2019; Arvold et al. 2009; Alavi et al. 2019; Bertone-Johnson et al. 2012; Choukri et al. 2018; Dabbaghmanesh et al. 2019; de Koning et al. 2019; Dean et al. 2011; Fazelian et al. 2019; Frandsen et al. 2014; Ghaderi et al. 2017; 2020; Hansen et al. 2019; Jalali-Chimeh et al. 2019; Jorde et al. 2008; Jorde and Kubiak 2018; Khoraminya et al. 2013; Kjaergaard et al. 2012; Lansdowne and Provost 1998; Mason et al. 2016; Mousa et al. 2018; Omidian et al. 2019; Rolf et al. 2017; Rouhi et al. 2018; Sanders et al. 2011; Sharifi et al. 2019; Vaziri et al. 2016; Wang et al. 2016; Wepner et al. 2014; Yalamanchili and Gallagher 2012; 2018; Zhang et al. 2018; Okereke et al. 2020; Vellekkatt et al. 2020; Abiri, Sarbakhsh, and Vafa 2021; Bagheri et al. 2022; Rajabi‐Naeeni et al. 2021)	26,885/ 26,350	−0.317 (−0.405, −0.230)	0.000	88.16
Subgroup analyses
Study population
Patients with diagnosed major depressive disorder	7 (Kaviani et al. 2020; Alavi et al. 2019; Hansen et al. 2019; Khoraminya et al. 2013; Wang et al. 2016; Zhang et al. 2018; Vellekkatt et al. 2020)	578/588	−0.729 (−1.100, −0.358)	0.000	82.34
Healthy participants	12 (Bertone-Johnson et al. 2012; Choukri et al. 2018; Dean et al. 2011; Frandsen et al. 2014; Jorde and Kubiak 2018; Kjaergaard et al. 2012; Lansdowne and Provost 1998; Mason et al. 2016; Mousa et al. 2018; Yalamanchili and Gallagher 2012; 2018; Okereke et al. 2020)	23,888/ 23,512	0.043 (0.025, 0.061)	0.000	0
Participants with antenatal/postnatal depressive symptoms	4 (Dabbaghmanesh et al. 2019; Rouhi et al. 2018; Vaziri et al. 2016; Amini et al. 2022)	205/202	−0.930 (−1.229, −0.632)	0.000	44.63
Participants with seasonal affective syndrome symptoms	3 (Frandsen et al. 2014; Lansdowne and Provost 1998; Kjaergaard et al. 2012)	172/152	−0.443 (−0.982, 0.096)	0.107	77.27
Participants without clinically relevant depressive symptoms (<cutoff values of scales)	15 (Sikaroudi et al. 2020; Zheng et al. 2019; Choukri et al. 2018; Dabbaghmanesh et al. 2019; Dean et al. 2011; Frandsen et al. 2014; Jorde et al. 2008; Jorde and Kubiak 2018; Kjaergaard et al. 2012; Mousa et al. 2018; Rolf et al. 2017; Sharifi et al. 2019; Yalamanchili and Gallagher 2012; 2018; Okereke et al. 2020)	6,258/ 5,808	−0.157 (−0.284, −0.030)	0.015	77.87
Participants with clinically relevant depressive symptoms (≥cutoff values of scales)	21 (Amini et al. 2022; Kaviani et al. 2020; Yosaee et al. 2020; Alavi et al. 2019; de Koning et al. 2019; Fazelian et al. 2019; Ghaderi et al. 2017; 2020; Hansen et al. 2019; Jalali-Chimeh et al. 2019; Khoraminya et al. 2013; Omidian et al. 2019; Rouhi et al. 2018; Vaziri et al. 2016; Wang et al. 2016; Wepner et al. 2014; Zhang et al. 2018; Vellekkatt et al. 2020; Abiri, Sarbakhsh, and Vafa 2021; Bagheri et al. 2022; Rajabi‐Naeeni et al. 2021)	1,132/ 1,135	−0.604 (−0.802, −0.406)	0.000	78.42
No antidepressant usage outside study protocol allowed	17 (Amini et al. 2022; Kaviani et al. 2020; Sikaroudi et al. 2020; Yosaee et al. 2020; Choukri et al. 2018; de Koning et al. 2019; Fazelian et al. 2019; Jalali-Chimeh et al. 2019; Jorde et al. 2008; Khoraminya et al. 2013; Kjaergaard et al. 2012; Mousa et al. 2018; Omidian et al. 2019; Rouhi et al. 2018; Wang et al. 2016; Okereke et al. 2020; Abiri, Sarbakhsh, and Vafa 2021)	5,880/ 5,766	−0.461 (−0.673, −0.250)	0.000	91.27
Antidepressant usage outside study protocol allowed	14 (Zheng et al. 2019; Alavi et al. 2019; Bertone-Johnson et al. 2012; Ghaderi et al. 2017; 2020; Hansen et al. 2019; Jorde and Kubiak 2018; Mason et al. 2016; Sanders et al. 2011; Wepner et al. 2014; Yalamanchili and Gallagher 2012; 2018; Zhang et al. 2018; Vellekkatt et al. 2020)	20,552/ 20,157	−0.162 (−0.286, −0.039)	0.010	82.47
Female participants only	14 (Amini et al. 2022; Bertone-Johnson et al. 2012; Choukri et al. 2018; Dabbaghmanesh et al. 2019; Fazelian et al. 2019; Jalali-Chimeh et al. 2019; Mason et al. 2016; Rouhi et al. 2018; Sanders et al. 2011; Vaziri et al. 2016; Yalamanchili and Gallagher 2012; 2018; Abiri, Sarbakhsh, and Vafa 2021; Rajabi‐Naeeni et al. 2021)	20,317/ 19,922	−0.372 (−0.540, −0.204)	0.000	90.88
Baseline serum vitamin D level
≤50 nmol/L	20 (Arvold et al. 2009; Amini et al. 2022; Sikaroudi et al. 2020; Zheng et al. 2019; Dabbaghmanesh et al. 2019; de Koning et al. 2019; Ghaderi et al. 2017; 2020; Hansen et al. 2019; Jalali-Chimeh et al. 2019; Jorde and Kubiak 2018; Kjaergaard et al. 2012; Mousa et al. 2018; Omidian et al. 2019; Sanders et al. 2011; Vaziri et al. 2016; Wepner et al. 2014; Yalamanchili and Gallagher 2018; Vellekkatt et al. 2020; Abiri, Sarbakhsh, and Vafa 2021)	2,524/ 2,384	−0.380 (−0.561, −0.198)	0.000	85.02
>50 nmol/L	19 (Kaviani et al. 2020; Yosaee et al. 2020; Alavi et al. 2019; Bertone-Johnson et al. 2012; Choukri et al. 2018; Dean et al. 2011; Fazelian et al. 2019; Frandsen et al. 2014; Jorde et al. 2008; Khoraminya et al. 2013; Mason et al. 2016; Rolf et al. 2017; Sharifi et al. 2019; Wang et al. 2016; Yalamanchili and Gallagher 2012; Zhang et al. 2018; Okereke et al. 2020; Bagheri et al. 2022; Rajabi‐Naeeni et al. 2021)	24,292/ 23,911	−0.236 (−0.342, −0.131)	0.000	88.01
No calcium co-supplementation	37 (Arvold et al. 2009; Kaviani et al. 2020; Sikaroudi et al. 2020; Yosaee et al. 2020; Zheng et al. 2019; Alavi et al. 2019; Choukri et al. 2018; Dabbaghmanesh et al. 2019; Dean et al. 2011; Fazelian et al. 2019; Frandsen et al. 2014; Ghaderi et al. 2017; 2020; Hansen et al. 2019; Jalali-Chimeh et al. 2019; Jorde and Kubiak 2018; Khoraminya et al. 2013; Kjaergaard et al. 2012; Lansdowne and Provost 1998; Mason et al. 2016; Mousa et al. 2018; Omidian et al. 2019; Rolf et al. 2017; Rouhi et al. 2018; Sanders et al. 2011; Sharifi et al. 2019; Vaziri et al. 2016; Wang et al. 2016; Wepner et al. 2014; Yalamanchili and Gallagher 2012; Zhang et al. 2018; Okereke et al. 2020; Vellekkatt et al. 2020; Amini et al. 2022; Abiri, Sarbakhsh, and Vafa 2021; Rajabi‐Naeeni et al. 2021; Bagheri et al. 2022)	8,068/7,867	−0.391 (−0.513, −0.268)	0.000	87.25
Calcium co-supplementation	5 (Bertone-Johnson et al. 2012; de Koning et al. 2019; Jorde et al. 2008; Yalamanchili and Gallagher 2018; Amini et al. 2022)	18,817/ 18,483	−0.102 (−0.315, 0.111)	0.346	84.18
Only studies adopting BDI or BDI-II	17 (Kaviani et al. 2020; Yosaee et al. 2020; Dean et al. 2011; Ghaderi et al. 2017; 2020; Jalali-Chimeh et al. 2019; Jorde et al. 2008; Jorde and Kubiak 2018; Mousa et al. 2018; Omidian et al. 2019; Sharifi et al. 2019; Wang et al. 2016; Zhang et al. 2018; Abiri, Sarbakhsh, and Vafa 2021; Bagheri et al. 2022; Kjaergaard et al. 2012; Khoraminya et al. 2013)	1,482/ 1,336	−0.461 (−0.629, −0.292)	0.000	75.70
Different vitamin D dosages
Dose per intervention day ≤2,000 IU	14 (Yosaee et al. 2020; Zheng et al. 2019; Bertone-Johnson et al. 2012; Choukri et al. 2018; Dabbaghmanesh et al. 2019; de Koning et al. 2019; Khoraminya et al. 2013; Lansdowne and Provost 1998; Mason et al. 2016; Rouhi et al. 2018; Sanders et al. 2011; Vaziri et al. 2016; Okereke et al. 2020; Yalamanchili and Gallagher 2018)	24,849/ 24,593	−0.183 (−0.286, −0.079)	0.000	87.68
Dose per intervention day >2,000 IU	26 (Arvold et al. 2009; Amini et al. 2022; Kaviani et al. 2020; Sikaroudi et al. 2020; Alavi et al. 2019; Dean et al. 2011; Fazelian et al. 2019; Frandsen et al. 2014; Ghaderi et al. 2017; 2020; Hansen et al. 2019; Jalali-Chimeh et al. 2019; R. Jorde et al. 2008; Jorde and Kubiak 2018; Kjaergaard et al. 2012; Mousa et al. 2018; Omidian et al. 2019; Rolf et al. 2017; Sharifi et al. 2019; Wang et al. 2016; Zhang et al. 2018; Vellekkatt et al. 2020; Abiri, Sarbakhsh, and Vafa 2021; Bagheri et al. 2022; Rajabi‐Naeeni et al. 2021; Yalamanchili and Gallagher 2018)	1,767/1,616	−0.407 (−0.556, −0.259)	0.000	75.83
Dose per intervention day ≤4,000 IU	29 (Amini et al. 2022; Kaviani et al. 2020; Yosaee et al. 2020; Zheng et al. 2019; Bertone-Johnson et al. 2012; Choukri et al. 2018; Dabbaghmanesh et al. 2019; de Koning et al. 2019; Fazelian et al. 2019; Frandsen et al. 2014; Ghaderi et al. 2017; 2020; Hansen et al. 2019; Jorde and Kubiak 2018; Khoraminya et al. 2013; Lansdowne and Provost 1998; Mason et al. 2016; Mousa et al. 2018; Omidian et al. 2019; Rouhi et al. 2018; Sanders et al. 2011; Sharifi et al. 2019; Vaziri et al. 2016; Wepner et al. 2014; Okereke et al. 2020; Vellekkatt et al. 2020; Bagheri et al. 2022; Rajabi‐Naeeni et al. 2021; Yalamanchili and Gallagher 2018)	25,502/ 25,233	−0.279 (−0.371, −0.189)	0.000	85.38
Dose per intervention day >4,000 IU	11 (Arvold et al. 2009; Sikaroudi et al. 2020; Alavi et al. 2019; Dean et al. 2011; Jalali-Chimeh et al. 2019; Kjaergaard et al. 2012; Rolf et al. 2017; Wang et al. 2016; Zhang et al. 2018; Abiri, Sarbakhsh, and Vafa 2021; Yalamanchili and Gallagher 2018)	1,081/883	−0.392 (−0.605, −0.180)	0.000	78.44
Treatment duration
<12 weeks	14 (Arvold et al. 2009; Amini et al. 2022; Kaviani et al. 2020; Sikaroudi et al. 2020; Alavi et al. 2019; Dean et al. 2011; Jalali-Chimeh et al. 2019; Khoraminya et al. 2013; Lansdowne and Provost 1998; Sharifi et al. 2019; Zhang et al. 2018; Vellekkatt et al. 2020; Abiri, Sarbakhsh, and Vafa 2021; Rajabi‐Naeeni et al. 2021)	543/536	−0.659 (−0.955, −0.364)	0.000	81.18
≥12 weeks	27 (Yosaee et al. 2020; Zheng et al. 2019; Bertone-Johnson et al. 2012; Choukri et al. 2018; Dabbaghmanesh et al. 2019; de Koning et al. 2019; Fazelian et al. 2019; Frandsen et al. 2014; Ghaderi et al. 2017; 2020; Hansen et al. 2019; Jorde et al. 2008; Jorde and Kubiak 2018; Kjaergaard et al. 2012; Mason et al. 2016; Mousa et al. 2018; Omidian et al. 2019; Rolf et al. 2017; Rouhi et al. 2018; Sanders et al. 2011; Vaziri et al. 2016; Wang et al. 2016; Wepner et al. 2014; Yalamanchili and Gallagher 2012; 2018; Okereke et al. 2020)	26,342/ 25,814	−0.205 (−0.291, −0.119)	0.000	86.37
Population mean age
≤65 years	34 (Arvold et al. 2009; Amini et al. 2022; Kaviani et al. 2020; Sikaroudi et al. 2020; Yosaee et al. 2020; Zheng et al. 2019; Choukri et al. 2018; Dabbaghmanesh et al. 2019; Dean et al. 2011; Fazelian et al. 2019; Frandsen et al. 2014; Ghaderi et al. 2017; 2020; Hansen et al. 2019; Jalali-Chimeh et al. 2019; Jorde et al. 2008; Jorde and Kubiak 2018; Khoraminya et al. 2013; Kjaergaard et al. 2012; Lansdowne and Provost 1998; Mason et al. 2016; Mousa et al. 2018; Omidian et al. 2019; Rolf et al. 2017; Rouhi et al. 2018; Sharifi et al. 2019; Vaziri et al. 2016; Wang et al. 2016; Wepner et al. 2014; Zhang et al. 2018; Vellekkatt et al. 2020; Abiri, Sarbakhsh, and Vafa 2021; Bagheri et al. 2022; Rajabi‐Naeeni et al. 2021)	2,409/ 2,230	−0.421 (−0.552, −0.289)	0.000	77.13
>65 years	6 (Alavi et al. 2019; de Koning et al. 2019; Sanders et al. 2011; Yalamanchili and Gallagher 2012; 2018; Okereke et al. 2020)	6,300/ 6,014	−0.030 (−0.155, 0.095)	0.636	77.56
Risk of bias
Only studies with RoB 2 result Low overall risk of bias	5 (Choukri et al. 2018; de Koning et al. 2019; Jorde and Kubiak 2018; Okereke et al. 2020; Rajabi‐Naeeni et al. 2021)	4,974/ 5,007	0.037 (−0.002, 0.077)	0.061	0
Only studies with RoB 2 result Some concerns	21 (Amini et al. 2022; Sikaroudi et al. 2020; Zheng et al. 2019; Alavi et al. 2019; Fazelian et al. 2019; Ghaderi et al. 2017; 2020; Jalali-Chimeh et al. 2019; Khoraminya et al. 2013; Kjaergaard et al. 2012; Lansdowne and Provost 1998; Mason et al. 2016; Mousa et al. 2018; Sanders et al. 2011; Sharifi et al. 2019; Wang et al. 2016; Yalamanchili and Gallagher 2012; 2018; Zhang et al. 2018; Vellekkatt et al. 2020; Abiri, Sarbakhsh, and Vafa 2021)	2,910/ 2,515	−0.430 (−0.601, −0.259)	0.000	86.30
Only studies with RoB 2 result High overall risk of bias	15 (Kaviani et al. 2020; Yosaee et al. 2020; Arvold et al. 2009; Bertone-Johnson et al. 2012; Dabbaghmanesh et al. 2019; Dean et al. 2011; Frandsen et al. 2014; Hansen et al. 2019; Jorde et al. 2008; Omidian et al. 2019; Rolf et al. 2017; Rouhi et al. 2018; Vaziri et al. 2016; Wepner et al. 2014; Bagheri et al. 2022)	19,001/ 18,828	−0.366 (−0.595, −0.137)	0.002	88.89

Abbreviations: RCT = Randomized Controlled Trial; CI = Confidence Interval; IU = international unit; RoB 2 = Cochrane risk-of-bias tool for randomized trials version 2

Figure 1. Effect size estimates for each study.

Vitamin D supplementation providing a moderate treatment effect on depressive symptoms (Hedges’ g= −0.317, 95% CI −0.405 to −0.230, p < 0.001, I²= 88.16%).

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Availability of data, code and other materials

The data, code and other materials that support the findings of this review study are available from the corresponding author, TM, upon reasonable request.