**Background:** Observational studies have linked low serum 25(OH)D concentrations with increased cardiometabolic disease risk, including endothelial dysfunction, inflammation, insulin resistance, hypertension, dyslipidaemia, and arterial stiffness. However, randomised controlled trials evaluating vitamin D supplementation for cardiometabolic outcomes have yielded inconsistent results. This pilot RCT aimed to investigate the effect of daily oral vitamin D₃ supplementation on vascular function and a comprehensive panel of cardiometabolic disease risk markers in vitamin D-insufficient overweight and obese adult males.
**Methods:** Fifty-five healthy males aged 18–65 years with BMI ≥ 24.9 kg/m² and plasma 25(OH)D < 75 nmol/L were recruited from November 2014 to May 2015 and October 2015 to January 2016 to minimise UVB exposure. Participants were randomly assigned to receive 125 µg/day (5000 IU/day) vitamin D₃ or placebo for 8 weeks in a double-blind, placebo-controlled design. The primary outcome was arterial stiffness assessed by pulse wave velocity (PWV). Secondary outcomes included brachial and aortic augmentation indices, central systolic blood pressure, brachial pulse pressure, peripheral blood pressure, heart rate, mean arterial pressure, and biomarkers including plasma 25(OH)D, parathyroid hormone, lipids (total cholesterol, LDL-C, HDL-C, non-HDL-C, triglycerides), high-sensitivity C-reactive protein, sE-selectin, renin, angiotensin II, glucose, insulin, HOMA-IR, and 8-isoprostane. Measurements were taken at baseline, week 4, and week 8. Dietary intake was assessed via 3-day food diaries at baseline and week 8. Mixed model repeated measures ANOVA and Mann–Whitney U tests were used for statistical analysis.
**Key Results:** Compliance was 90% in the vitamin D group and 87% in the placebo group. No adverse events were reported. Baseline characteristics were similar between groups except for slightly higher plasma glucose in the vitamin D group (5.23 ± 1.45 vs. 4.75 ± 0.82 mmol/L, p = 0.025). At baseline, 22.2%, 35.2%, and 64.8% of participants had plasma 25(OH)D concentrations <25, <30, and <50 nmol/L, respectively. Vitamin D₃ supplementation significantly increased plasma 25(OH)D from 38.5 ± 16.0 nmol/L at baseline to 62.5 ± 19.5 nmol/L at week 4 and 72.5 ± 15.8 nmol/L at week 8 (p < 0.001), while placebo group concentrations remained stable (44.0 ± 19.5 to 38.8 ± 18.0 nmol/L). Only 45.8% (11/24) of participants in the vitamin D group achieved 25(OH)D > 75 nmol/L after 8 weeks. The intervention had no significant effect on the primary outcome of PWV (p = 0.423) or on most secondary outcomes including SBP (p = 0.099), DBP (p = 0.522), MAP (p = 0.413), aortic AIx (p = 0.705), brachial AIx (p = 0.940), lipids, hs-CRP, sE-selectin, renin, angiotensin II, insulin, glucose, HOMA-IR, or 8-isoprostane. However, brachial pulse pressure significantly decreased in the vitamin D group compared to placebo (mean change −2.9 ± 3.4 mmHg, p = 0.027). A post-hoc power calculation estimated a required sample size of 1140 participants per group to detect a significant effect on PWV.
**Clinical Implications:** This pilot RCT found that 8 weeks of high-dose vitamin D₃ supplementation (125 µg/day) significantly improved vitamin D status and reduced brachial pulse pressure but did not affect arterial stiffness or most other cardiometabolic risk markers in overweight/obese adult males. The modest pulse pressure reduction may reflect changes in peripheral rather than central arterial function. The lack of effect on other outcomes may be attributable to the relatively short intervention duration, insufficient dose to achieve optimal 25(OH)D concentrations (>75 nmol/L) in most participants, the healthy normotensive and non-diabetic baseline status of participants, and potential confounding by adiposity-related vitamin D sequestration and VDR genotype polymorphisms. The authors acknowledge the pilot nature of the study and the risk of type 1 error given multiple outcome comparisons. These findings suggest that vitamin D supplementation alone is unlikely to produce broad cardiometabolic benefits in the short term, and larger-scale trials over longer durations with adequate power are needed to determine whether specific subgroups (e.g., those with hypertension, insulin resistance, or more severe vitamin D deficiency) might derive greater benefit.