Effect of vitamin D₃ supplementation on cardiometabolic disease risk among overweight/obese adult males in the UK: A pilot randomised controlled trial

Abstract

Background: Observational studies suggest links between reduced serum 25(OH)D concentration and increased cardiometabolic disease risk. However, these studies provide limited evidence of causation, with few conclusive randomised controlled trials (RCT) having been carried out to date. This RCT investigated the effect of vitamin D 3 supplementation on vascular function and cardiometabolic disease risk markers, in 55 healthy males aged 18-65 years with plasma 25(OH)D concentration <75 mol L -1 and body mass index ≥24.9 kg m -2 . Methods: Participants were assigned to consume 125 µg day -1 (5000 IU day -1 ) vitamin D 3 or placebo for 8 weeks. Blood samples and vascular function measures were obtained at baseline, as well as at weeks 4 and 8. The primary outcome was arterial stiffness, an indicator of cardiovascular disease (CVD) risk, assessed by pulse wave velocity. Biomarkers of CVD risk, insulin resistance and endothelial function were measured using an enzyme-linked immunosorbent assay. Results: Daily oral intake of 125 µg supplemental vitamin D 3 led to a significant improvement in plasma 25(OH)D concentrations over the 8-week intervention in the vitamin D group compared to the change in the placebo group (p ˂ 0.001). In the vitamin D group, the baseline mean ± SD 25(OH)D concentration was 38.4 ± 15.9 and this increased to 72.8 ± 16.1 nmol L -1 after 8 weeks of supplementation. The intervention had no effect on arterial stiffness, as measured by pulse wave velocity, although vitamin D 3 supplementation did lead to a decrease in mean ± SD brachial pulse pressure from baseline to 8 weeks of −2.9 ± 3.4 mmHg (p = 0.027) in the vitamin D group compared to the same period in the placebo group. The intervention had no effect on the remaining cardiometabolic parameters. Conclusions: Overall, treatment significantly improved brachial pulse pressure but no other cardiometabolic disease risk markers. To follow on from this pilot RCT, future large-scale clinical trials over longer durations may offer further insights.

Vitamin D Supplementation Has No Impact on Cardiorespiratory Fitness, but Improves Inflammatory Status in Vitamin D Deficient Young Men Engaged in Resistance Training

“…In our participants, the 12-week RT and supplementation period had no impact on fasting serum glucose or insulin levels or HOMA-IR. This finding is consistent with the data from other researchers [22,86] who evaluated the possible combined effect of Vit-D supplementation and RT on insulin resistance.…”

Serum vitamin D and cardiometabolic risk factors in the UK population

“…37 In addition, trials are often powered on noncardiometabolic outcomes. 18,35 Even meta-analyses of randomised controlled trials within this scope have limitations due to bias in the selection of participants and comparability of study groups and a limited selection of CVD-related outcomes. 20,33,38,39 Only one study found a significant effect with a 16% (0.22 mmol/L) decrease in serum triglycerides in those given vitamin D compared to the placebo group but an 8% (0.28 mmol/L) increase in serum LDL.…”

“…These include significant heterogeneity of study design–related factors (such as vitamin D status at baseline, vitamin D doses and form of supplement given, therapy duration, skeletal outcomes), as well as individual differences in absorption and metabolism, genetic differences in the vitamin D receptor as well as biases due to different diseases and several potentially confounding factors including age, body fat, medications, diet and physical activity 37 . In addition, trials are often powered on non‐cardiometabolic outcomes 18,35 . Even meta‐analyses of randomised controlled trials within this scope have limitations due to bias in the selection of participants and comparability of study groups and a limited selection of CVD‐related outcomes 20,33,38,39 .…”

“…10,12,15,16 That failure is thought to be related to the faulty designs of the studies, which included mainly participants with vitamin D sufficiency at low CVD risk. 5,17,18 According to a recent study from the UK Biobank, the prevalence of vitamin D deficiency in the UK population ranges between 12% and 53% depending on ethnicity. 19 Despite this there have been no nationally representative assessments on the possible relationship between serum 25(OH)D concentrations and cardiometabolic risk factors in the UK population.…”

“…Data from observational studies report that a low vitamin D status is associated with a 40% increased risk of CVD, 11 but such a strong association is not supported by current evidence from clinical trials 10,12,15,16 . That failure is thought to be related to the faulty designs of the studies, which included mainly participants with vitamin D sufficiency at low CVD risk 5,17,18 . According to a recent study from the UK Biobank, the prevalence of vitamin D deficiency in the UK population ranges between 12% and 53% depending on ethnicity 19 .…”