Article Text


Annual high-dose vitamin D supplementation does not affect mental well-being in older women
  1. Lisa Burback,
  2. Glen B Baker,
  3. Serdar M Dursun
  1. Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada

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Does a single annual vitamin D supplement have a beneficial effect on mental well-being, and are higher serum vitamin D levels associated with better mental well-being?


2317 women aged 70 or older with an identified risk factor for hip fracture (ie, maternal hip fracture, self-reported ‘faller’, fracture since age 50 and/or high risk of low vitamin D and osteoporosis. A group of 150 participants was selected for a substudy looking at the relationship between serum 25-hydroxyvitamin D levels and mental well-being. Exclusions: albumin-corrected calcium >2.65 mmol/l, vitamin D supplementation >400 IU/day, other bone health related parameters and inability to provide informed consent or data concerning falls/fractures.


Community setting, Melbourne, Australia; 2003–2008.


500 000 IU vitamin D3 annually during autumn/winter versus placebo. The dose was divided into 10 tablets and was taken orally on 1 day.


Mental well-being assessed using the General Mental Health Questionnaire (GHQ-12), the 12-item Short Form Health Survey (SF-12), the WHO Well-Being Index and Patient Global Impression–Improvement (PGI-I) scores. The GHQ-12 was administered to participants recruited after 2005 only and completed at baseline, 12-month postdose and 15-month postdose (GHQ-12 score ≥3 indicated the presence of psychiatric disorder). The SF-12 was completed immediately before study completion in 2008. PGI-I scale questionnaires were completed only by a randomly selected subset of the study population at predose, 1-month postdose and 3-month postdose; these participants also had serum levels of 25-hydroxyvitamin D measured at the same time points.

Patient follow-up

90% of participants completed the study (ie, did not withdraw).



Randomised controlled trial.




Double blind.

Follow-up period

3–5 years (2003–2008)

Main results

Annual high-dose vitamin D supplementation did not significantly affect mental well-being on the GHQ-12 or SF-12 (mean SF-12 physical component score: 41.4 with vitamin D vs 41.2 with placebo, p=0.66; mean SF-12 mental component score: 52.5 with vitamin D vs 52.6 with placebo, p=0.75; absolute risk of GHQ-12 score ≥3 at 15-month postdose: 17.7% with vitamin D vs 16.9% with placebo, OR 1.06, 95% CI 0.81 to 1.37). There was no evidence for interaction between treatment and use of antidepressant/antianxiety medication for either scale. Vitamin D supplementation also did not significantly affect WHO Well-Being Index (p=0.47) or PGI-I (p=0.52) scores in the substudy. Vitamin D supplementation did significantly increase mean serum 25-hydroxyvitamin D levels compared with placebo (41% increase compared with placebo, p<0.001). However, there was no evidence of an association between mean serum 25-hydroxyvitamin D levels and mental well-being at the time of sampling or for a relationship between change in serum 25-hydroxyvitamin D levels and change in mental well-being scores on either the WHO Well-Being Questionnaire or PGI-I.


Annual oral high-dose vitamin D supplementation (500 000 IU vitamin D3) does not affect mental well-being in older women although it does increase serum 25-hydroxyvitamin D levels. Biochemical serum analysis found that vitamin D status was not a predictor of mental well-being.


The study had 80% power to detect a 50% relative difference in the proportion of participants with a score of 3 or greater in the GHQ Questionnaire when 15% of the placebo group score 3 or greater (at a 0.05 level of significance).

Abstracted from

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Sanders and colleagues investigated the effectiveness of a single annual high-dose vitamin D3 (500 000 IU every autumn/winter for 3–5 consecutive years) on mental well-being in community-dwelling women aged 70 or older. Although the vitamin D-treated group had higher serum levels of 25-hydroxyvitamin D than did the placebo group 1 year after the last dose, there was no improvement in the indices of mental well-being. The authors appropriately pointed out several limitations of their study, but there is not a clear justification of the high dose of vitamin D used. A single high dose would be convenient as a public health intervention but is not physiological. As indicated by the authors, this dose actually increases falls and fractures (which could increase risk for developing future psychiatric disorders).

Extracting mental well-being data from such a study is more complex than investigating falls or fractures. There are known neurochemical actions of vitamin D that are potentially neuroprotective, but much is still unknown about its possible mechanisms in mental health, including optimum levels for neuronal health and whether serum levels of vitamin D or its metabolites correlate with brain concentrations.

It is possible that vitamin D’s effectiveness may be age dependent, with lifelong normal vitamin D levels playing a developmental or preventive role in psychiatric disorders. Three to five years of supplementation later in life may not be adequate. One rarely considered aspect of natural ‘sunshine-derived vitamin D’ is the outside activity which may accompany getting that natural source. Thus future studies on artificial vitamin D supplementation should consider inclusion of an arm of increased activity.

The current study provides some useful clinical information with regard to treatment of women in this age group with high-dose vitamin D but also demonstrates difficulties in designing and interpreting studies on vitamin D. These and other problems determining the health benefits of vitamin D have been highlighted in a recent review.1


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  • Sources of funding Australian National Health and Medical Research Council, and the Government Department of Health and Ageing.


  • Competing interests None.

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