Tools for Practice

#116 Vitamin D and Low Mood: The easy perky pill.

Can Vitamin D improve or prevent low mood or depression?

The present evidence does not support prescribing (or testing) Vitamin D in the treatment or prevention of low mood or depressionMost randomized controlled trials (RCTs) found no effect and the few that found small benefits are at very high risk of bias. 

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Vitamin D vs. placebo (or nothing):1-10 
  • Ten RCTs examined patients with normal mood [example: 4-7 on Beck Depression Inventory (BDI)1,2,4 and ≤15% depressed].1-9   
    • RCTs included 44-2263 patients, lasted five days to three years, and gave 400 IU/day to 40,000 IU/week of Vitamin D. 
    • Despite multiple outcomes in nine studies, only two showed any impact: 
      • Statistically but not clinically significant 1-1.5 point change on a 63-point BDI scale.1  
      • Statistically significant seven-point change (out of 40) in “positive” mood parameters, no change in “negative” mood parameters.8   
        • Limitation: Smallest and shortest study, 44 people for five days. 
    • Vitamin D had no benefit in prevention of depression.5,9  
  • Two RCTs examined depressed patients:6,10 
    • Iranian three month trial of 120 patients given single intramuscular dose of 300,000 IU or 150,000 IU or nothing.10   
    • Mean improvement in BDI was 9.3, 6.8, and 2.1. 
      • 300,000 IU statistically superior to nothing.  
    • Subgroup of 57 depressed patients in 489 person RCT.6 
      • No difference between Vitamin D and placebo for recovery. 
  • Observational studies have shown an association between low Vitamin D levels and a higher risk of depression or low mood.11  
    • This research is at very high risk of bias and cannot show causation.  
  • Dosing RCT of 600 IU/day vs. 4000 IU/day found no difference in mood.12 
  • Most RCTs included above have multiple flaws and high risk of bias, including poor randomization, lack of blinding, no description of patient characteristics, non-intention to treat analysis, large loss to follow-up, etc.1-10   
    • In general, RCTs with better design (examples2,4found no effect, while the only RCTs finding benefits were at the highest risk of bias (examples8,10).  

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  • Alma Bencivenga MD
  • G. Michael Allan MD CCFP

1. Jorde R, Sneve M, Figenschau Y, et al. J Intern Med. 2008; 264(6):599-609.

2. Dean AJ, Bellgrove MA, Hall T, et al. PLoS One. 2011; 6(11):e25966.

3. Sanders KM, Stuart AL, Williamson EJ, et al. Br J Psychiatry. 2011; 198(5):357-64.

4. Kjærgaard M, Waterloo K, Wang CE, et al. Br J Psychiatry. 2012; 201(5):360-8.

5. Bertone-Johnson ER, Powers SI, Spangler L, et al. Am J Epidemiol. 2012; 176(1):1-13.

6. Yalamanchili V, Gallagher JC. Menopause. 2012; 19(6):697-703.

7. Harris S, Dawson-Hughes B. Psychiatry Res. 1993; 49(1):77-87.

8. Lansdowne AT, Provost SC. Psychopharmacology (Berl). 1998; 135(4):319-23.

9. Dumville JC, Miles JN, Porthouse J, et al. J Nutr Health Aging. 2006; 10(2):151-3.

10. Mozaffari-Khosravi H, Nabizade L, Yassini-Ardakani SM, et al. J Clin Psychopharmacol. 2013; 33(3):378-85.

11. Anglin RE, Samaan Z, Walter SD, et al. Br J Psychiatry. 2013; 202:100-7.

12. Vieth R, Kimball S, Hu A, et al. Nutr J. 2004; 3:8.

Authors have no conflicts to disclose.