Can vitamin D cure depression?

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Vitamin D is the “sunshine vitamin”,[1] and sunshine is implicated in mood. So it makes sense that researchers have intently explored vitamin D supplementation for depression. But depression is complex, and the mechanisms at work are not well-understood. However, careful analysis of the trials testing the effects of vitamin D on depression and mood-related pathways will help provide some insight into whether, or if, vitamin D may be helpful for depression in different contexts or populations.

Two reviews of observational studies and intervention trials reached the same conclusions: When parsing the observational data, both reviews found a correlation between depression and low levels of vitamin D (≤20 ng/mL). When parsing the trial data, both reviews found benefits from supplementation, but also assessed some of the included studies as having low methodological quality and high risk of bias.[2][3]

Those two reviews were published in 2017 and 2016, so shortly after a 2015 meta-analysis of randomized controlled trials (RCTs) reported finding no significant reduction in depression after vitamin D supplementation. Its authors, however, mentioned that “most of the studies focused on individuals with low levels of depression and sufficient serum vitamin D at baseline”.[4] In other words, they didn’t rule out the possibility that in people with higher levels of depression or lower levels of vitamin D, supplementation might be more effective.

This hypothesis lines up with the conclusions of a 2014 meta-analysis, which found that, if one considered only the studies whose subjects had low levels of vitamin D at baseline (≤20 ng/mL) and were then given enough vitamin D to achieve sufficiency over the course of the trial, then supplemental vitamin D was about as effective as antidepressant medication.[5] However, this meta-analysis did not account for publication bias.

A 2018 meta-analysis focused on major depression and found a moderate benefit from vitamin D. However, it stresses the low number of qualifying studies (four trials) and, like the 2017 and 2016 reviews, deplores the low methodological quality of some of the studies.[6]

Finally, let’s mention a 2016 RCT that found that pregnant women who took a daily dose of 2,000 IU of vitamin D3during late pregnancy had lower scores on a postpartum depression screening scale than those who did not supplement.[7] However, this study only addressed postpartum depression in healthy women with a low-to-moderate pre-partum risk of depression; it may not have wider applicability, and further research is needed.

Vitamin D insufficiency (≤20 ng/mL) has been associated with depression. If your depression is severe, you are more likely to benefit from correcting an insufficiency. If your levels of vitamin D are sufficient, however, then whether your depression is severe or not, supplementation isn’t likely to help. (Due to the poor overall methodological quality of the studies, those conclusions are at best preliminary.)

Vitamin D receptors can be found pretty much everywhere in the human body, so the ways in which vitamin D might affect your mood are innumerable. One of those mechanisms could be hormonal, since vitamin D helps regulate testosterone levels,[8][9] and since low testosterone can impair the mood of both men[10][11][12][13] and women.[14]

We should remember, however, that correlation is not causation. As stated above, the observational data suggests a correlation between depression and low levels of vitamin D, but that doesn’t mean that low levels of vitamin D cause the depression. It might be that depressed people go outside less, thus getting less sunlight, thus producing less vitamin D: the depression would then be the cause of the low vitamin D levels, rather than its consequence.

Even if depression is a consequence, not a cause, it doesn’t mean that low levels of vitamin D aren’t also a consequence. People who go outside less get less sunlight, but also probably less exercise — and we know that exercise benefits mood,[15] both directly and by promoting better sleep.

And of course, a consequence can have more than one cause. For instance, a decrease in vitamin D production during the winter months is a possible factor in seasonal affective disorder (SAD),[16] but so is a decrease in illumination,[17] since one meta-analysis[18] and a more recent RCT[19] found that light therapy (using visible light, free of the UVB rays that allow your skin to produce vitamin D) can improve SAD symptoms, often as much as can pharmaceuticals. It should be noted, however, that a few trials with small sample sizes make for rather weak evidence, especially since the meta-analysis didn’t account for publication bias.

The findings on vitamin D are less consistent. One study found an association between depression and seasonal changes in vitamin D,[20] but another study found no effect of supplemental vitamin D on SAD.[21] And compounding the uncertainty, the researchers of both studies stressed that potential confounders were numerous.

To summarize:

  • Low levels of vitamin D have been associated with depression, but it doesn’t follow that low levels of vitamin D are the cause of the depression. They’re probably one of the factors at play in seasonal depression, but so is the decrease in illumination.
  • If your vitamin D levels are not low, supplementation isn’t likely to benefit your mood. If they are low, supplementation is more likely to help if you suffer from major depression.
  • If you suspect your vitamin D levels are low, you can have them assessed through a 25-hydroxyvitamin D blood test. Assessing your vitamin D levels twice in a year — in midsummer and midwinter, when there is the most and least sunlight — is an efficient way of estimating what your levels are around the year.
References
1.^Nair R, Maseeh AVitamin D: The "sunshine" vitaminJ Pharmacol Pharmacother.(2012 Apr)
2.^Parker GB, Brotchie H, Graham RKVitamin D and depressionJ Affect Disord.(2017 Jan 15)
3.^Allan GM, Cranston L, Lindblad A, McCormack J, Kolber MR, Garrison S, Korownyk CVitamin D: A Narrative Review Examining the Evidence for Ten BeliefsJ Gen Intern Med.(2016 Jul)
4.^Gowda U, Mutowo MP, Smith BJ, Wluka AE, Renzaho AMVitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trialsNutrition.(2015 Mar)
7.^Vaziri F, Nasiri S, Tavana Z, Dabbaghmanesh MH, Sharif F, Jafari PA randomized controlled trial of vitamin D supplementation on perinatal depression: in Iranian pregnant mothersBMC Pregnancy Childbirth.(2016 Aug 20)
8.^Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J, Obermayer-Pietsch B, Wehr E, Zittermann AEffect of vitamin D supplementation on testosterone levels in menHorm Metab Res.(2011 Mar)
9.^Wehr E, Pilz S, Boehm BO, März W, Obermayer-Pietsch BAssociation of vitamin D status with serum androgen levels in menClin Endocrinol (Oxf).(2010 Aug)
10.^Rodgers S, Grosse Holtforth M, Hengartner MP, Müller M, Aleksandrowicz AA, Rössler W, Ajdacic-Gross VSerum testosterone levels and symptom-based depression subtypes in menFront Psychiatry.(2015 May 4)
11.^Johnson JM, Nachtigall LB, Stern TAThe effect of testosterone levels on mood in men: a reviewPsychosomatics.(2013 Nov-Dec)
12.^Bassil N, Alkaade S, Morley JEThe benefits and risks of testosterone replacement therapy: a reviewTher Clin Risk Manag.(2009 Jun)
13.^Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor MTestosterone and depression: systematic review and meta-analysisJ Psychiatr Pract.(2009 Jul)
14.^Davis SR, Wahlin-Jacobsen STestosterone in women--the clinical significanceLancet Diabetes Endocrinol.(2015 Dec)
15.^Sharma A, Madaan V, Petty FDExercise for mental healthPrim Care Companion J Clin Psychiatry.(2006)
18.^Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM, Suppes T, Wisner KL, Nemeroff CBThe efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidenceAm J Psychiatry.(2005 Apr)
20.^Kerr DC, Zava DT, Piper WT, Saturn SR, Frei B, Gombart AFAssociations between vitamin D levels and depressive symptoms in healthy young adult womenPsychiatry Res.(2015 May 30)