Depression is a significant burden for healthcare systems and economies worldwide. It not only affects adults but also children and adolescents. Efforts to significantly improve depression outcomes have failed thus far, suggesting that unknown factors might influence risk, pathogenesis and persistence of depressive disorders (1).

Evidence indicates that lifestyle factors such as diet quality might influence the risk of depression and mental health issues in general (2–5). Nutritional components such as vitamin D may play an important role in mental health. The observed relationship between vitamin D deficiency and depression originates from seasonal affective disorder studies. This phenomenon describes rhythmic decreases of mood during the same season each year, generally during autumn and winter months, when the days are shorter and there is less sunlight (6).

Low serum 25-hydroxy vitamin D3  levels (25(OH)D₃) levels are associated with depressed mood in population-based epidemiological and clinical studies and sub-optimal vitamin D levels may precipitate mental disorders (7–9). Currently, optimal vitamin D levels are defined as they relate to bone health outcomes. Optimal vitamin D levels in mental health are still under discussion (10–13).

Apart from environmental factors (eating pattern, sunlight-exposure) the risk of vitamin D insufficiency is also influenced by genetic factors (8,14).

There are an estimated one billion people worldwide suffering from vitamin D deficiency or insufficiency (15).

Traditional Understanding

Vitamin D levels are predominantly known for playing a role in bone disorders such as rickets, osteomalacia  and osteoporosis (6).

Depression is traditionally thought to relate to neurotransmitter imbalances in the brain (monoamine hypothesis of depression) and is treated primarily through antidepressants targeted at the monoamine neurotransmitters (i.e. serotonin, norepinephrine and dopamine) (16). This theory of depression is being revised as new evidence comes to light, such as the role of genetics in depression. However, treatment options for depression remain limited and in a large number of cases, ineffectual (17,18).

Latest Research

Vitamin D association with depression

There are many recent studies and reviews regarding the relationship between vitamin D and depression. Evidence to-date provides conflicting results, although the majority of studies indicate an association between vitamin D deficiency and depression (19–24).

A 2014 review concluded that low vitamin D is most likely a marker of ill health, including depression, rather than a cause of it (34). Other studies indicate that vitamin D deficiency may represent an underlying biological vulnerability for depressive disorder (9). An adequate vitamin D status might have a preventive role against recurrent depressive symptoms, especially among individuals with poor diet quality (38).

Study results are difficult to interpret as the findings may simply reflect the altered behaviour of depressed individuals (i.e. less outdoor activity) (6). There are also limitations in comparing studies due to different definitions of deficiency and differences in measures of depression.

• Findings from Australia and Denmark do not support an association between serum vitamin D levels and mental health status in young women, or young overweight adults (25–27). However, cross-sectional studies  from across the globe have found an association between low vitamin D serum levels and risk of depression (28–33)
• There is a strong association between low serum vitamin D levels and higher negative and depressive symptoms in psychotic disorders (35)
• Individuals with depression have lower levels of vitamin D compared to those with other psychiatric disorders (36)
• Low vitamin D levels in individuals with major depressive episodes are associated with an increased risk of cognitive impairment. However, vitamin D deficiency is neither necessary nor sufficient to cause major depression (37)
• In rheumatoid arthritis, low vitamin D levels and disease duration are associated with depression (39)
• Results are inconsistent with regards to depression in type 2 diabetes mellitus (T2DM). No association is found in older individuals with T2DM (40), although a significant association is found in a large T2DM Chinese population (41)

Vitamin D supplementation in depression

Studies have found a benefit of vitamin D supplementation for symptoms of depression, strengthening the plausibility of a causal relationship (15,23,42,43). However, efficacy in clinical trials has produced conflicting results (8,22,23,27,44). This may be due to study design limitations including (45):

• Inadequate sample size
• Comparison of results across studies with different age, geographic locations, ethnic ranges and baseline vitamin D levels of subjects
• Different definitions of deficiency and a lack of biomarkers
• Differences in the confounding variables adjusted for and compared
• Varying dosages, duration of treatment and methods of administration
• Differences in outcome assessment and differences in depression measures used

The majority of studies report on vitamin D supplementation compared to placebo. There is a recent focus on the role of vitamin D supplementation in conjunction with antidepressant treatment (45).

Recent data shows vitamin D supplementation is beneficial in the management of depression under certain circumstances:

• When vitamin D levels are raised by supplementation (25)
• With longer duration of supplementation (42)
• In moderate and severe clinical depression, but may not be beneficial in mild depression (24)
• In women with polycystic ovary syndrome (PCOS) when used in conjunction with omega-3 (46)
• In depression associated with chronic liver disease, where serum vitamin D levels are low (47)
• In bipolar disorder where serum vitamin D levels are low (48). However, another trial found that high dose vitamin D supplementation in bipolar disorder did not reduce depression symptoms, or remediate vitamin D deficiency (49)
• In individuals with mild to moderate ulcerative colitis who do not have baseline vitamin D deficiency (50)
• In adolescent girls with moderate vitamin D deficiency (51)
• In young women with severe vitamin D deficiency and clinically significant depression, treatment via safe sun exposure is effective in remediating vitamin D deficiency and improving depressive symptoms (52)
• In major depressive disorders using either vitamin D supplementation alone, or in combination with fluoxetine (53,54)

Depression in the elderly

Age-related changes affect vitamin D metabolism and increase the requirement for vitamin D (55).

• Several studies have found an association between low vitamin D status and increased likelihood of depression in older individuals, although vitamin D as a cause of depression is not yet established (19,56–58)
• Observational data suggest that vitamin D deficiency is a risk factor for late-life depression. However, the role of supplementation for the prevention or management of depression is still uncertain (32)
• A large population-based study found that vitamin D deficiency is not an independent risk factor for depression but co-occurs with late-life depression (59)

Postnatal and perinatal depression

• Most high-quality studies suggest that lower serum vitamin D levels may be associated with perinatal and postpartum depression. It is not known whether the vitamin D impact is via the function of hypothalamic-pituitary-adrenal (HPA) axis, the levels of oestradiol, serotonin, pro-inflammatory cytokines, and/or other mechanisms involved in postpartum depression (60–64)
• In women at risk for depression, low vitamin D levels in early pregnancy are associated with higher depressive symptom scores in early and late pregnancy, but not with postpartum depression (65)
• Daily vitamin D₃ during late pregnancy effectively decreases perinatal depression levels (66)