Effects of vitamin D₂ or D₃ supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double‐blind placebo‐controlled trial

Abstract

AimsTo investigate the effect of short‐term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes.MethodsIn a double‐blind placebo‐controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non‐diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100 000 IU vitamin D2 (ergocalciferol) or 100 000 IU vitamin D3 (cholecalciferol), orally administered monthly for 4 months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4 months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C‐reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation.ResultsThe mean [standard deviation (s.d.)] 25‐hydroxyvitamin D [25(OH)D]2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D2 group, and the mean (s.d.) 25(OH)D3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D3 group. There was no effect of vitamin D supplementation on HbA1c: D2 versus placebo: −0.05% [95% confidence interval (CI) −0.11, 0.02] or −0.51 mmol/mol (95% CI −1.16, 0.14; p = 0.13); D3 versus placebo: 0.02% (95% CI −0.04, 0.08) or 0.19 mmol/mol (95% CI −0.46, 0.83; p = 0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo: −0.68 m/s (95% CI −1.31, −0.05); D3 versus placebo −0.73 m/s (95% CI −1.42, −0.03)]. No important safety issues were identified.ConclusionsShort‐term supplementation with vitamin D2 or D3 had no effect on HbA1c. The modest reduction in PWV with both D2 and D3 relative to placebo suggests that vitamin D supplementation has a beneficial effect on arterial stiffness.

Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta‐Analysis

“…A total of 31 trials, involving 2751 participants, were eligible for inclusion in the review . Of these, 29 trials (2641 participants) had data suitable for inclusion in the trial‐level meta‐analyses; IPD were obtained from 24 trials (2051 participants).…”

“… Data from Forouhi et al contain comparisons of D3 vs placebo and D2 vs placebo. Only D3 analysis was included in “All” category for PWV analyses. …”

“…If a level of 75 nmol/L is regarded as optimum as has been suggested from observational studies, 54 doses at the upper end of the range included in this analysis are required to reach this level. 40,55,56 Metaregression of vitamin D dose versus treatment effect suggested that higher doses of vitamin D were associated with a slightly greater treatment effect for FMD, but not for PWV or AIx. We found no evidence that daily dosing was more efficacious than intermittent dosing, despite previous work that has suggested that daily dosing provides more-consistent tissue exposure to the parent compound, facilitating uptake and autocrine activation, 57 and evidence that daily dosing may be more efficacious in some conditions (eg, respiratory disease).…”

Associations of 25-hydroxyvitamin D with markers of inflammation, insulin resistance and obesity in black and white community-dwelling adults

“…Most studies lasted approximately 3 months, often during winter months, and only a few were 6 months to a year or more in duration. In order to appreciate any role vitamin D may have in insulin resistance, inflammation, and obesity, it is possible that vitamin D supplementation should focus on vitamin D deficient individuals with chronic disease conditions particularly amenable to vitamin D replacement, such as diabetes [23]. Interestingly, adjusting for physical activity did not affect the magnitude or strength of the associations of 25(OH)D with insulin resistance, inflammation and obesity, suggesting that the associations described herein do not merely reflect healthier lifestyle but may instead represent direct biological links between lower 25(OH)D and poor metabolic health.…”

Vitamin D: the tricky hormone

“…A positive association was found in several disorders such as systemic lupus erythematosus (SLE) and its activity (2); chronic obstructive pulmonary disease (COPD) (3); inflammatory bowel disease (IBD) (4); systemic sclerosis; endocrine disorders; cancer; immune; cardiovascular and other chronic diseases (1,5); despite the presence of numerous positive observational studies, causation studies are lacking. A few good-quality randomized controlled studies on vitamin D supplementation in diverse disease endpoints show a modest effect on blood pressure, glycemic control, cancer, and immune response (5,6).…”