Vitamin D supplementation and risk of stroke: A meta-analysis of randomized controlled trials

Abstract

BackgroundPrevious observational studies have supported the hypothesis that vitamin D supplementation protects against stroke. However, several current intervention studies contradict this observation. Therefore, we conducted a meta-analysis to investigate further the association between vitamin D supplementation and the risk of stroke.MethodsThis meta-analysis was conducted in accordance with the PRISMA statement and included all the randomized controlled trials (RCTs) that analyzed the relationship between vitamin D supplementation and the risk of stroke. A literature search strategy was established, and the following Medical Search Terms (MeSH) were used: “vitamin D,” “Calcitriol,” “Calcifediol,” “Cholecalciferol,” “25-Hydroxyvitamin D 2,” “ergocalciferols,” “stroke,” and stroke-derived terms. We searched for articles published before January 2022 in several databases, namely, PubMed, Web of Science, EMBASE, and The Cochrane Library. We also reviewed references included in relevant published meta-analyses and searched the http://www.ClinicalTrials.gov website for additional RCTs. The Q test and I2 were utilized to assess the degree of heterogeneity among the studies. Review Manager 5.3 and STATA16.0 software programs were used to assess the literature quality and perform statistical analyses.ResultsIn total, twenty-four RCTs (86,202 participants) were included. There was no statistical heterogeneity among the RCTs (I2 = 0.0%, P = 0.94) included in this meta-analysis. We determined that vitamin D supplementation was not associated with a reduced risk of stroke compared with the placebo (RR = 1.02, 95% CI: 0.93–1.13, P = 0.65). In total, 10 studies only included women, and 14 studies included women and men among the 24 RCTs. Therefore, we performed a subgroup analysis based on sex. After the subgroup analysis, the effect remained statistically insignificant (mixed-sex group: RR = 1.06, 95% CI: 0.93–1.22, P = 0.37, women group: RR = 0.98, 95% CI: 0.86–1.13, P = 0.80). The results were generally comparable, based on age, body mass index (BMI), follow-up period, baseline 25-hydroxyvitamin D (25(OH)D) levels, the designated endpoint, latitude, vitamin D dosage, type of vitamin D administered, and an absence or presence of concurrent calcium supplementation (P > 0.05).ConclusionOur study revealed that additional vitamin D supplementation did not reduce the risk of stroke. Therefore, additional RCTs of similar design should not be encouraged to assess any association between vitamin D supplementation and reduced stroke risk.

Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials

“…Despite biological evidence and support from observational studies, recent metaanalyses and systematic reviews [112][113][114][115][116] of RCTs that have assessed the effect of vitamin D supplementation reported that it was not associated with a reduction in the risk of ACM, CVM, MI, stroke, HF, or MACE. A meta-analysis from the US Preventive Services Task Force (USPSTF) [117] included 77 fair-or good-quality RCTs and reported that vitamin D treatment did not affect mortality or CVD incidence.…”

A systematic review and meta‐analysis of the linkage between low vitamin D and the risk as well as the prognosis of stroke

“…Kaul and Manikinda (2021) demonstrated that VD level could work in the risk of stroke, while it could not be regarded as a risk factor for stroke. Fu et al.’s (2022) research indicated that no reduction in stroke risk was observed through supplementary vitamin D intake. Many factors can lead to differences in the effectiveness of supplementing the same dose of vitamin D, such as gender, underlying diseases, and duration of exposure to sunlight (Kennel et al., 2010).…”

Vitamin D and Atherosclerosis: Unraveling the Impact on Macrophage Function

“…[ 78 ] However, this association was not corroborated by a separate meta‐analysis encompassing 24 RCTs with 86 202 participants, which found no significant protective effect of vitamin D supplementation against stroke risk. [ 79 ]…”