Effect of monthly high-dose vitamin D on mental health in older adults: secondary analysis of a RCT

Authors: GUGGER, ALENKA - University Of Zurich; MARZEL, ALEX - University Of Zurich; ORAV, ENDEL - Harvard University; WILLETT, WALTER - Harvard University; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; THEILER, ROBERT - University Of Zurich; FREYSTATTER, GREGORY - University Of Zurich; EGLI, ANDREAS - University Of Zurich; BISCHOFF-FERRARI, HEIKE - University Of Zurich

Submitted to: Journal of the American Geriatrics Society
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/20/2018
Publication Date: 2/1/2019
Citation: Gugger, A., Marzel, A., Orav, E.J., Willett, W.C., Dawson-Hughes, B., Theiler, R., Freystatter, G., Egli, A., Bischoff-Ferrari, H.A. 2019. Effect of monthly high-dose vitamin D on mental health in older adults: Secondary analysis of a RCT. Journal of the American Geriatrics Society. 67(6):1211-1217. https://doi.org/10.1111/jgs.15808.
DOI: https://doi.org/10.1111/jgs.15808

Interpretive Summary: Vitamin D may be important for good mental health and well-being. In several observational studies, higher circulating levels of 25-hydroxyvitamin D (25(OH)D) were associated with better mental health scores. This study was done to determine the effect of vitamin D supplementation on mental health in pre-frail older adults. A total of 200 community-dwelling adults 70 years and older were randomized to receive 24 000 IU vitamin D3 (considered standard of care), 60 000 IU vitamin D3, or 24 000 IU vitamin D3 plus 300 micrograms of 25(OH)D per month for one year. Mental health was assessed by widely used assessment tools including components of the SF-36 Mental Health subscale and the Geriatric Depression Scale. Over time, none of these measures differed significantly among the three treatment groups. However, in the group as a whole, participants achieving the highest 25(OH)D levels at 12 months (levels in the range of 44.7-98.9 ng/mL) had the greatest improvements in both assessment scales. For mental health, this study suggests no benefit of higher monthly doses of vitamin D3 compared with the standard monthly dose of 24 000 IU; but, irrespective of vitamin D treatment dose, achieving higher 25(OH)D levels may provide a small benefit to mental health. Further study is required to confirm this.

Technical Abstract: OBJECTIVES: To test the effect of monthly high-dose vitamin D supplementation on mental health in pre-frail older adults. DESIGN: Ancillary study of a 1-year double-blind randomized clinical trial conducted in Zurich, Switzerland. SETTING AND PARTICIPANTS: A total of 200 community-dwelling adults 70 years and older with a prior fall event in the last year. Participants were randomized to receive 24 000 IU vitamin D3 (considered standard of care), 60 000 IU vitamin D3, or 24 000 IU vitamin D3 plus 300 micrograms calcifediol per month. MEASURES: The primary end point was the Mental Component Summary (MCS) of the SF-36. Secondary end points were the SF-36 Mental Health (MH) subscale and the Geriatric Depression Scale (GDS-15). RESULTS: Participants' mean age was 78 years (67% women), and 58% were vitamin D deficient (<20ng/mL). Over time, primary and secondary end points did not differ significantly among the three treatment groups or in subgroups by vitamin D status at baseline. Given the lack of a true placebo group, we explored in a predefined observational analysis the change in mental health scales by achieved 25(OH)D levels at 12 months. After adjusting for confounders, participants achieving the highest 25(OH)D quartile (Q) at 12 months (44.7-98.9 ng/mL) had the greatest improvements in MCS (Q4=0.79 vs Q1=-2.9; p=.03) and MH scales (Q4=2.54 vs Q1=-3.07; p=.03); these associations were strongest among participants who were vitamin D deficient at baseline. No association was found for GDS (p=.89). CONCLUSIONS: For mental health, our study suggests no benefit of higher monthly doses of vitamin D3 compared with the standard monthly dose of 24 000IU. However, irrespective of vitamin D treatment dose, achieving higher 25(OH)D levels at 12-month follow-up was associated with a small, clinically uncertain but statistically significant improvement in mental health scores.