Vitamin D Supplementation Does Not Prevent Depression

Vitamin D is an essential nutrient that is obtained from dietary sources, such as salmon, eggs, cod liver oil and fortified milk, and from exposure to the sun (ultraviolet radiation) — though sun exposure alone is typically insufficient for this purpose and increases skin cancer risk.

Public Citizen’s Health Research Group has previously written about vitamin D’s role in bone health (reducing fracture risks).[1] Here, potential relevance of vitamin D to prevent depression is discussed. Specifically, we review a recent double-blinded, placebo-controlled randomized trial that considered whether vitamin D supplementation prevents depression in relatively healthy adults.

Why vitamin D?[2]

The potential link between vitamin D and depression comes in part from the now long-standing though controversial observation that symptoms of depression may be triggered or exacerbated by certain seasons, especially in times of increased cold and darkness.

It has further been shown that the brain contains many cells that specifically bind to vitamin D, particularly in areas associated with depression.

Study examining vitamin D supplementation to prevent depression[3]

A study published in the Aug. 4, 2020, issue of the Journal of the American Medical Association (JAMA) randomly assigned over 18,350 American adults age 50 or older (49% female) to treatment with oral vitamin D supplementation (2,000 international units [IU] per day of cholecalciferol) or placebo. Subjects were enrolled from 2011 to 2014 and participated in the trial for at least three years with a median participation of 5 years.

The study excluded patients with a history of cancer, cardiovascular disease or kidney failure; those already taking more than 800 IU of vitamin D per day; those receiving active treatment for depression or with marked depression symptoms in the past 2 years; or those with other recent (past 1 year) major psychiatric, neurologic or substance-use disorders (including alcohol-use disorder). Accordingly, the study population was relatively healthy and free of exposure to vitamin D supplements when they began the trial.

There were two primary outcomes for this trial, both based on annual self-reports from the study subjects. The first outcome was the occurrence of a formal clinical depression diagnosis or treatment (counseling, medication or both) event. The second outcome was the score achieved on the 8-item Patient Health Questionnaire depression scale (PHQ-8). The maximum PHQ-8 score possible is 24, and higher scores correspond to more symptoms of depression. Because of the exclusion criteria, mean scores for the study population at the time of initial enrollment in the trial were low (less than 2 points).

By the conclusion of the trial, the incidence of formal depression events and changes in PHQ-8 scores did not differ between the vitamin D and placebo groups. Specifically, there were 13 formal depression events for every 1,000 person-years in the vitamin D group and 13 in the placebo group over the course of the trial. The average change in PHQ-8 score from year to year was also indistinguishable between groups (the mean difference was 0.01 points). Additionally, no differences between the two groups were observed in the incidence of first-time clinical depression (for those with no history of such illness) or recurrent clinical depression (for those with a history of such illness).

One notable aspect of this trial was that it was designed specifically to achieve a racially and ethnically diverse subject population in part because darker-skinned persons are known to have a heightened risk of vitamin D deficiency. The study thus ultimately included over 3,400 Black subjects (19% of those enrolled). Subgroup analyses found that vitamin D supplementation had no effect on depression risk in Black subjects, a finding that was essentially the same as that seen for other racial groups, including non-Hispanic White subjects.

Vitamin D screening

A separate systematic review published in the April 13, 2021, issue of JAMA provided an updated assessment for the U.S. Preventive Services Task Force (USPSTF) regarding the benefits and risks of vitamin D screening for adults.[4] (The finding of a low vitamin D level on screening often triggers a physician to recommend vitamin D supplementation.)

Based on the scientific literature available through November 2020, the USPSTF concluded that there was insufficient evidence to assess the balance of benefits and potential harms of screening for vitamin D deficiency in community-dwelling (not institutionalized), nonpregnant adults with no signs of such deficiency, such as bone pain or muscle weakness.[5] The USPSTF therefore made no recommendation for or against vitamin D screening in such adults.

Moreover, the USPSTF-commissioned review found no evidence that treatment with vitamin D in those with deficiency of the vitamin, absent any signs or symptoms of such deficiency, reduces the risk of death or of various symptoms or diseases, including depression.[6]

The USPSTF found no studies that directly evaluated the harms of screening for vitamin D deficiency. Potential harms of vitamin D supplementation in individuals found to be deficient in the vitamin, particularly if excessive amounts of the vitamin are ingested, include gastrointestinal symptoms (such as nausea and vomiting), fatigue, muscle weakness, falls and kidney stones.

What You Can Do

If you are aged 19 to 70, you should aim to get 600 IU of dietary vitamin D daily (the approximate amount of vitamin D found in 2 to 3 egg yolks, 7 ounces of salmon or 5 cups of vitamin D-fortified milk). If you are aged 71 or older you should consume 800 IU of vitamin D per day.[7]

If you are a community-dwelling, nonpregnant adult without any symptoms of vitamin D deficiency or other major illnesses, you should not take further vitamin supplements to prevent or treat depression or symptoms related to that disease.
 

References

[1] Vitamin D and calcium dietary supplements: Do they prevent bone fractures? Worst Pills, Best Pills News. August 2020. https://www.worstpills.org/newsletters/view/1349. Accessed October 7, 2021.

[2] Kaviani M, Nikooyeh B, Zand H, et al. Effects of vitamin D supplementation on depression and some involved neurotransmitters. J Affect Disord. 2020 May 15;269:28-35.

[3] Okereke OI, Reynolds CF 3rd, Mischoulon D, et al. Effect of long-term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: a randomized clinical trial. JAMA. 2020;324(5):471-480.

[4] Kahwati LC, LeBlanc E, Weber RP, et al. Screening for vitamin D deficiency in adults: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;325(14):1443-1463.

[5] U.S. Preventative Services Task Force. Screening for vitamin D deficiency in adults. U.S. Preventative Services Task Force recommendation statement. JAMA. 2021;325(14):1436-1442.

[6] Kahwati LC, LeBlanc E, Weber RP, et al. Screening for vitamin D deficiency in adults: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;325(14):1443-1463.

[7] Office of Dietary Supplements. National Institutes of Health. Vitamin D: Fact sheet for consumers. Updated: March 22, 2021. https://ods.od.nih.gov/factsheets/VitaminD-Consumer/. Accessed October 7, 2021.