J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Perspective

Volume 15, September 2021, pages 13-20

The use of vitamin D in depression

**Table 1.** Observational evidence of a relationship between vitamin D and depression
Associations between hypovitaminosis D and depression in adults (Anglin et al., 2013; Ju et al., 2013)
Reduced risk of developing depression in people with higher serum 25(OH)D levels (Jääskeläinen et al., 2015)
Association of depression with vitamin D deficiency in older adults (Okereke and Singh, 2016)
Association of low baseline levels of 25(OH)D3 with increased depression scores at 3-year and 6-year follow-up in elderly adults (Milaneschi et al., 2010)
Association of depression with vitamin D deficiency in young people (Kerr et al., 2015; Polak et al., 2014)
Association of depression with vitamin D deficiency in individuals with heart failure and cancer (Björkhem-Bergman and Bergman, 2016; Johansson et al., 2016)
Association between vitamin D status and antenatal and postpartum depression (Aghajafari et al., 2018)
Caveat: Correlation between low vitamin D levels and depressive symptoms is not necessarily indicative of a causal role of hypovitaminosis D in depression due to potential confounders (age, dietary intake, physical exercise, time spent outdoors etc.)

Table 1. Observational evidence of a relationship between vitamin D and depression

Associations between hypovitaminosis D and depression in adults (Anglin et al., 2013; Ju et al., 2013)

Reduced risk of developing depression in people with higher serum 25(OH)D levels (Jääskeläinen et al., 2015)

Association of depression with vitamin D deficiency in older adults (Okereke and Singh, 2016)

Association of low baseline levels of 25(OH)D3 with increased depression scores at 3-year and 6-year follow-up in elderly adults (Milaneschi et al., 2010)

Association of depression with vitamin D deficiency in young people (Kerr et al., 2015; Polak et al., 2014)

Association of depression with vitamin D deficiency in individuals with heart failure and cancer (Björkhem-Bergman and Bergman, 2016; Johansson et al., 2016)

Association between vitamin D status and antenatal and postpartum depression (Aghajafari et al., 2018)

Caveat: Correlation between low vitamin D levels and depressive symptoms is not necessarily indicative of a causal role of hypovitaminosis D in depression due to potential confounders (age, dietary intake, physical exercise, time spent outdoors etc.)

**Table 2.** Interventional evidence of a relationship between vitamin D and depression
No significant meta-analytical effect on depression following vitamin D supplementation (Li et al., 2014; Lázaro Tomé et al., 2021)
No overall meta-analytical effect of vitamin D supplementation on depressive symptoms, but moderate, statistically significant effect in people with clinically significant depressive symptoms or depressive disorder (Shaffer et al., 2014)
No significant improvement of depression following vitamin D supplementation in a meta-analysis of studies with individuals with low depression levels and sufficient vitamin D levels at baseline (Gowda et al., 2015)
Significant worsening of depression following vitamin D supplementation in a meta-analysis of “biologically flawed” studies (e.g. vitamin D deficiency not established at baseline and/or vitamin D dose administered insufficient to produce normal vitamin D levels) (Spedding, 2014)
Significant improvement of depression following vitamin D supplementation in a meta-analysis of studies without biological flaws (Spedding, 2014)
Favorable findings following vitamin D supplementation (≥800 I.U. daily) in studies demonstrating a change in vitamin levels (Spedding, 2014)
Dose dependency of effects of importance of vitamin D supplementation (Mozaffari-Khosravi et al., 2013)
Summary: Insufficient evidence in support of therapeutic efficacy of vitamin D supplementation in depression

Table 2. Interventional evidence of a relationship between vitamin D and depression

No significant meta-analytical effect on depression following vitamin D supplementation (Li et al., 2014; Lázaro Tomé et al., 2021)

No overall meta-analytical effect of vitamin D supplementation on depressive symptoms, but moderate, statistically significant effect in people with clinically significant depressive symptoms or depressive disorder (Shaffer et al., 2014)

No significant improvement of depression following vitamin D supplementation in a meta-analysis of studies with individuals with low depression levels and sufficient vitamin D levels at baseline (Gowda et al., 2015)

Significant worsening of depression following vitamin D supplementation in a meta-analysis of “biologically flawed” studies (e.g. vitamin D deficiency not established at baseline and/or vitamin D dose administered insufficient to produce normal vitamin D levels) (Spedding, 2014)

Significant improvement of depression following vitamin D supplementation in a meta-analysis of studies without biological flaws (Spedding, 2014)

Favorable findings following vitamin D supplementation (≥800 I.U. daily) in studies demonstrating a change in vitamin levels (Spedding, 2014)

Dose dependency of effects of importance of vitamin D supplementation (Mozaffari-Khosravi et al., 2013)

Summary: Insufficient evidence in support of therapeutic efficacy of vitamin D supplementation in depression

**Table 3.** Problems and future directions regarding vitamin D and depression
Unclear causality of correlations between vitamin D status and depressive symptoms
Intervention trials needed in people who are both depressed and deficient in vitamin D
Assessment of depression level and vitamin D status both at trial baseline and follow-up
Investigations needed regarding vitamin D effects in different types of depressive disorders (major depressive disorder, seasonal affective disorder, bipolar disorder, antenatal and postpartum depression, premenstrual dysphoric disorder)
Optimal dosage, duration and mode of delivery of vitamin D supplementation
Summary: Large-scale, randomized controlled trials of vitamin D in people with well-defined diagnoses of depression needed

Table 3. Problems and future directions regarding vitamin D and depression

Unclear causality of correlations between vitamin D status and depressive symptoms

Intervention trials needed in people who are both depressed and deficient in vitamin D

Assessment of depression level and vitamin D status both at trial baseline and follow-up

Investigations needed regarding vitamin D effects in different types of depressive disorders (major depressive disorder, seasonal affective disorder, bipolar disorder, antenatal and postpartum depression, premenstrual dysphoric disorder)

Optimal dosage, duration and mode of delivery of vitamin D supplementation

Summary: Large-scale, randomized controlled trials of vitamin D in people with well-defined diagnoses of depression needed