Background: Vitamin D deficiency is associated with sleep disorders and poor sleep quality. Whether vitamin D supplementation (VDS) helps resolve these problems remains unclear. Objective: To systematically review the effect of VDS on sleep quantity, quality, and disorders, and perform a meta-analysis of available data. Methods: The reporting of this review followed the PRISMA statement. VDS human interventions studies that reported on sleep quality, quantity, or disorders were included. Medline, CINAHL, EMBASE, PsycInfo, the Cochrane Library, Clinicaltrials.gov, and the ICTRP were searched, in addition to the references of the included articles and previous relevant reviews, without language or time restrictions. Included studies were critically appraised, findings were narratively synthesized, and a meta-analysis was conducted. Furthermore, the overall certainty of the evidence was assessed. Results: A total of 19 studies were included (13 randomized controlled trials (RCTs), 1 opportunistic addition to an RCT, 4 pre–post studies, and 1 pre–post study analyzed as a case series); 3 RCTs were meta-analyses. The risk of bias was generally low. Pre–post studies showed a significant improvement in sleep quality with VDS. Similarly, the results of the meta-analysis revealed a statistically significant decrease in the Pittsburgh Sleep Quality Index with VDS compared with placebo (mean difference, −2.33 (95% CI, −3.09, −1.57); p < 0.001; I² = 0%), with a moderate certainty of evidence. The results regarding the effect of VDS on sleep-related impairment, difficulty, and disorders, as well as sleepiness and restless legs syndrome, were not unanimous. Conclusions: VDS is promising in improving sleep quality; however, its effect on sleep quantity and disorders needs to be further investigated.

The status of vitamin D is determined mainly by its formation in skin by the photochemical action of solar UVB light (wavelength 290–320 nm) on the precursor 7-dehydrocholesterol. Because of seasonal variation in intensity of solar UV light, vitamin D status falls in winter and rises in summer. It has been presumed that there is no functional store of vitamin D. Thus, to avoid deficiency, a nutritional supply would be required in winter. However, there is now evidence that the main circulating metabolite of vitamin D, 25-hydroxyvitamin D, accumulates in skeletal muscle cells, which provide a functional store during the winter months. The mechanism is mediated by muscle cell uptake of circulating vitamin D–binding protein (DBP) through a megalin-cubilin membrane transport process. DBP then binds to cytoplasmic actin to provide an array of high-affinity binding sites for 25-hydroxyvitamin D [25(OH)D]. The repeated passage of 25(OH)D into and out of muscle cells would account for its long residence time in blood.

Vitamin D, unlike the micronutrients, vitamins A, E, and K, is largely obtained not from food, but by the action of solar ultraviolet (UV) light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Since no defined storage organ or tissue has been found for vitamin D, it has been assumed that an adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D), which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into the blood. This uptake and release of 25(OH)D by muscle accounts for the very long half-life of this metabolite in the circulation. Since 25(OH)D concentration in the blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain an adequate vitamin D status in winter.

Evidence of synergic health effects of co-supplementation with vitamin D and probiotics is emerging. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement, scientific databases and the grey literature were searched, and a narrative review and risk of bias assessment were conducted. Seven randomized controlled trials were included, which had low risk of bias. Six studies were double-blind, and once single-blind, extended over 6–12 weeks, and included 50–105 participants. Conditions explored included schizophrenia, gestational diabetes, type 2 diabetes and coronary heart disease, polycystic ovarian syndrome, osteopenia, irritable bowel syndrome (IBS), and infantile colic. Supplementation frequency was daily or bi-monthly, with mainly vitamin D3, and Lactobacillus, Bifidobacterium, and Streptococcus. Comparators were placebo, vitamin D, lower vitamin D dose, and probiotics and lower vitamin D dose. The co-supplementation yielded greater health benefits than its comparators did in all studies except in one assessing IBS. Beneficial effects included decreased disease severity, improved mental health, metabolic parameters, mainly insulin sensitivity, dyslipidemia, inflammation, and antioxidative capacity, and lower use of healthcare. Co-supplementation of vitamin D and probiotics generated greater health benefits than its comparators did. More studies in other diseases and various populations are needed to confirm these findings and to elucidate the optimal form, composition, and frequency of this co-supplementation.

Background: Metabolic syndrome (MetS) increases the risk of cardiovascular disease, with atherogenic dyslipidemia being a major contributing factor. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to assess whether vitamin D supplementation (VDS) alleviates dyslipidemia in adults with MetS. Scientific databases (PUBMED, MEDLINE, CINAHL, EMBASE, Cochrane Library, ClinicalTrials.gov, International Clinical Trials Registry Platform) and the gray literature were searched for randomized controlled trials of VDS, reporting on blood lipids. A narrative review, meta-analyses, sensitivity analyses, and appraisal of the risk of bias and overall quality of evidence produced were conducted. Results: Seven studies were included, and four were meta-analyzed. The risk of bias was generally low, and the final quality of evidence was low or very low. VDS, whether in high or low dose, significantly increased endline vitamin D blood levels; did not affect total, low-density, high-density cholesterol levels, and novel lipid-related biomarkers; yet, significantly increased triglycerides (TG) levels compared with placebo (MD: 30.67 (95%CI: 4.89–56.45) mg/dL; p = 0.02 for low-dose VDS; and MD: 27.33 (95%CI: 2.06–52.59) mg/dL; p = 0.03 for high-dose VDS). Pertaining heterogeneity was high (I² = 86%; and I² = 51%, respectively), and some included studies had significantly higher baseline TG in the intervention arm. The sensitivity analyses revealed robust results. Conclusion: VDS seems not to affect blood lipids in adults with MetS.

Suboptimal vitamin D status is associated with elevated blood pressure (BP) in children and adolescents. Whether vitamin D supplementation reduces BP remains unclear. To systematically review whether vitamin D supplementation reduces BP in children and adolescents, we conducted a literature review according to the PRISMA statement. We included vitamin-D supplementation human interventions studies that reported on BP as an outcome. We searched PUBMED, MEDLINE, CINAHL, EMBASE, the Cochrane Library, and the clinical trials website. We also hand searched the references of the included articles and previous reviews of vitamin D therapy. No language or time restrictions were applied. We extracted data on population characteristics, baseline and endline vitamin D and BP values, and assessed the risk of bias of the included studies. We performed a narrative review of the findings, conducted a meta-analysis when possible, and performed sensitivity analyses to test the robustness of our results. We assessed the overall quality of the evidence produced in the meta-analysis. We included eight studies in our review and five studies in the meta-analysis, none of which included hypertensive only participants. The risk of bias was variable. In non-randomized studies, no effect of vitamin D supplementation was seen on systolic BP (SBP) (mean difference: 0.39 (95% confidence interval (CI): −0.9; 1.68) mmHg; p = 0.55; I² = 0%). Only a significant decrease in diastolic BP (DBP) (mean difference: −1.87 (95% CI: −3.02; −0.72) mmHg; p = 0.001; I² = 0%) was noted. Both analyses had a low quality of evidence. In randomized controlled trials (RCTs), no effect was noted on SBP (mean difference: −2.04 (95% CI: −5.12; 1.04) mmHg; p = 0.19; I² = 71%) nor DBP (mean difference: 0.01 (95% CI: −1.09; 1.12) mmHg; p = 0.98; I² = 0%). The final quality of evidence ranged between low and moderate. Sensitivity analyses did not affect the results. Vitamin D supplementation was found to be ineffective in lowering SBP and DBP in children and adolescents.