BackgroundA large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed a systematic quantitative review on characteristics of randomized clinical trials (RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D supplementation.Methods and findingsWe identified systematic reviews (SR) reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes. For each outcome, we summarized the results from available SRs and scrutinized included RCTs for a number of predefined characteristics. We identified 54 SRs including data from 210 RCTs. Most MAs as well as the individual RCTs reported null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases. Beneficial effects of vitamin D supplementation was reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have primarily been performed to determine skeletal outcomes, whereas non-skeletal effects have been assessed as secondary outcomes. Only one-third of the RCTs had low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level below 50 nmol/L was only present in less than half of the analyses.ConclusionsPublished RCTs have mostly been performed in populations without low 25OHD levels. The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels.

Total thyroidectomy causes postsurgical hypothyroidism (HypoT). Besides HypoT, as a complication patients may also develop hypoparathyroidism (HypoPT). The aim of this study was to assess quality of life (QoL), muscle function, and postural stability in patients with postsurgical hypothyroidism and hypoparathyroidism (HypoTþPT) as compared to patients with postsurgical HypoT and healthy controls. Age-and gender-matched patients on treatment for HypoTþPT and HypoT were recruited from our outpatient clinic. Matched healthy controls were recruited from the general background population. Compared with controls, HypoT was associated with a significantly lower mental summary score, whereas patients with HypoTþPT had a significantly lower physical summary score (Short Form 36 Health Survey questionnaire version 2). Moreover, the physical component score was significantly lower in patients with HypoTþPT compared with HypoT. WHO-5 well-being index was significantly lower in both groups of patients compared with controls, but did not differ between groups of patients. Compared with controls, muscle strength and maximal force production was significantly reduced in HypoTþPT, but not in HypoT. In HypoTþPT, the time spent on the Timed Up & Go test and the Repeated Chair Stands test were significantly longer than in the HypoT group and the control group. Postsurgical HypoTþPT is associated with a more severe impairment of QoL, in particular regarding physical functioning, than HypoT. HypoTþPT patients are also hampered by impaired muscle function. Studies on how to improve well-being and muscle function in HypoTþPT patients are warranted.

Vitamin D insufficiency and hyperparathyroidism have been associated with reduced muscle strength, physical performance, postural stability, well-being, and quality of life. In a double-blinded, randomized placebo-controlled trial, we aimed to investigate effects of vitamin D3 supplementation on above-mentioned outcomes in healthy community-dwelling postmenopausal women with plasma levels of 25-hydroxyvitamin D (25(OH)D) below < 50 nmol/l and high parathyroid hormone (PTH) levels. Participants (N = 81) were 1:1 treated with vitamin D3, 70 µg (2800 IU)/day or identical placebo for three months during wintertime (56°N). Vitamin D3 supplementation increased levels of 25(OH)D and 1,25(OH)D by 230% (95% CI 189 to 272)%, p < 0.001 and 58% (190 to 271%), p < 0.001, respectively, and reduced PTH by 17% (- 23 to - 11%), p < 0.001. Compared with placebo, vitamin D3 significantly reduced maximal handgrip strength by 9% (- 15 to - 3%; p < 0.01) and knee flexion strength by 13% (- 24 to - 2%; p = 0.02) and increased the time spent on performing the Timed Up and Go test by 4.4%; (0.1-8.6%; p < 0.05). Levels of physical activity, total lean body mass, appendicular lean mass index, postural stability, well-being, and quality of life did not change in response to treatment. Compared with placebo, a daily supplement with a relatively high dose of vitamin D3 had no beneficial effects on any outcomes. In some measures of muscle strength and physical performance, we even saw a small unfavorable effect. Our data call for caution on use of relatively high daily doses of vitamin D3 in the treatment of vitamin D insufficiency.

No abstract