Effect of Monthly High‐Dose Vitamin D on Mental Health in Older Adults: Secondary Analysis of a RCT

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 μg 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 (<20 ng/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 24 000 IU. 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.

Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases—An Umbrella Review

“…Regarding dosage, a recent RCT [162] tested whether 50 µg per day (2000 IU) is more effective than 20 µg (800 IU) vitamin D 3 for improving cognitive performance among relatively healthy adults aged ≥60 years (31% 25(OH)D < 50 nmol/l (20 ng/mL)), but found comparable results in both groups over a 24-month treatment period and no significant improvement in either group. Similarly, another recent RCT found that supplementing older adults with a history of falling (58% 25(OH)D < 50 nmol/l (20 ng/mL)) with 600 µg (24,000 IU) vitamin D 3 , 1500 µg (60,000 IU) vitamin D 3 or a combination of 600 µg (24,000 IU) vitamin D 3 with calcifediol once per month also led neither to different effects in mental health within one year, nor to any significant improvement [163]. Participants achieving the highest serum 25(OH)D levels (112.5-247.5 nmol/l (45-99 ng/mL)), however, had a "small, clinically uncertain but statistically significant improvement in mental health scores", irrespective of the supplement dose.…”

Low Vitamin D Levels and Risk of Incident Delirium in 351,000 Older UK Biobank Participants

“…Supporting a causal role for vitamin D in mental health is a 2019 randomized clinical trial of vitamin D supplementation for 1 year in 200 older (aged ≥70 years) adults who experienced a fall in the previous year; there were significant improvements in mental health (the Mental Component Summary of the Short Form Health Survey 36‐item patient health survey) in the groups achieving the highest vitamin D levels at 12 months 37 and strongest in those who were deficient at baseline.…”

Association between serum vitamin D and depressive symptoms in apparently healthy male adults undergoing routine health check-ups at a single centre

“…low vitamin D and increased PTH levels increase inflammation, which is a risk factor for depression) (41) . Fourth, although no beneficial effect of higher monthly doses of vitamin D compared with the standard monthly dose is known (43) , several studies have evaluated the effects of vitamin D supplementation on depression (44,45) . Finally, although these studies did not support a causal effect on any of the disease outcomes, multiple Mendelian randomisation studies have investigated the putative causal association of vitamin D on multiple health outcomes, especially in preventing or controlling depression and major depressive disorder (46,47) .…”