Vitamin D Supplementation and Endothelial Function in Vitamin D Deficient HIV-Infected Patients: A Randomized Placebo-Controlled Trial

Abstract

Background Studies suggest that vitamin D deficiency is a risk factor for cardiovascular disease and diabetes. Vitamin D deficiency is prevalent in HIV patients but the effect of vitamin D supplementation on cardiovascular risk in this population is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial among 45 HIV-infected adults in Cleveland (OH, USA) on stable antiretroviral therapy with durable virological suppression and a baseline serum 25-hydroxyvitamin D level of ≤20 ng/ml. Participants were randomized 2:1 to vitamin D3 4,000 IU daily or placebo for 12 weeks. The primary outcome was a change in flow-mediated brachial artery dilation (FMD). Results Baseline demographics were similar except for age (vitamin D versus placebo, mean ±SD 47 ±8 versus 40 ±10 years; P=0.009). Both groups had reduced FMD at baseline (median values 2.9% [IQR 1.6–4.8] for vitamin D versus 2.5% [IQR 1.7–6.4] for placebo; P=0.819). Despite an increase in the concentration of serum 25-hydroxyvitamin D from baseline to 12 weeks (5.0 ng/ml [IQR −0.9–7.4] versus −1.9 ng/ml [IQR −4.0–0.1] for vitamin D versus placebo, respectively; P=0.003), there was no difference in FMD change (0.55% [IQR −1.05–2.13] versus 0.29% [IQR −1.61–1.77]; P=0.748). Vitamin D supplementation was associated with a decrease in total and non-high-density lipoprotein cholesterol, and an increase in indices of insulin resistance. Conclusions Among HIV-infected individuals with vitamin D deficiency, supplementation with 4,000 IU vitamin D3 daily for 12 weeks modestly improved vitamin D status and cholesterol but worsened insulin resistance without change in endothelial function. The mechanisms of resistance to standard doses of vitamin D and the complex role of vitamin D in glucose metabolism in this population require further investigation.

Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review

“…One study included in this review recruited HIV patients [40] who were undertaking stable antiretroviral therapy. There could be increased catabolism of vitamin D in this study, as increased intake of the antiretroviral drug Efavirenz (EFV), has been reported by Childs et al, [68] …”

“…Four studies [40][41][42][43], recruited participants with other diseases such as cystic fibrosis, human immunodeficiency virus (HIV), polycystic ovary syndrome and non-alcoholic fatty liver disease. Amongst these studies, one study [41], performed in cystic fibrosis patients, found significant reduction in an inflammatory marker, TNF-α (mean ± SD) 55.67 ± 8.18 pg/ml -27.62 ± 5.82 pg/ml, P < 0.01) ( Table 1).…”

Review of randomized controlled trials of nutritional supplementation in people living with HIV

“…In contrast, most of the studies after the initiation of ART used single nutrients such as zinc, selenium, calcium and vitamin D, which have been recognized to be deficient after initiation of ART. 39,67,[88][89][90]102,105,106 The report from Isanaka et al 87 suggests that supplementation with multivitamin at the RDA level is still safe in coadministration with ART, but high doses of vitamins should be avoided. Another study assessed the effect of vitamin supplements on HIV shedding in breast milk in HIV-infected lactating women.…”

“…[88][89][90] Arpadi et al 88 randomized 56 children living with HIV and receiving ART into 100,000 IU of vitamin D every 2 months and 1 g of calcium daily or placebo during 1 year; the investigators concluded that the intervention did not significantly affect viral control or HIV disease progression, but serum vitamin D significantly increased in those supplemented.…”

“…Longenecker et al 89 investigated the effects of supplementation with vitamin D on the endothelial function in PLWH. The study was an RCT that included 45 HIV patients on ART therapy.…”