The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D‐deficient HIV‐1‐infected patients

Abstract

ObjectiveThe aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, bone mineral density (BMD), body fat distribution and insulin sensitivity in vitamin D-deficient HIV-1-infected patients. MethodsTwenty vitamin D-deficient HIV-1-infected patients were prospectively treated with 2000 IU cholecalciferol/day for 14 weeks, whereafter treatment was continued with half this dosage until 48 weeks. BMD, body fat distribution, 1,25-dihydroxy vitamin D 3 (1,25(OH) 2 D 3 ), fasting glucose, insulin, adiponectin, leptin, interleukin (IL)-6 and tumour necrosis factor (TNF)-a were measured at baseline, and at 24 and 48 weeks. Parathyroid hormone (PTH), 25-hydroxy vitamin D 3 [25(OH)D 3 ], cholesterol and triglycerides were measured at baseline, and at 12, 24 and 48 weeks. ResultsAfter 24 weeks, cholecalciferol supplementation significantly increased 25(OH)D 3 and 1,25(OH) 2 D 3 levels and decreased PTH and insulin sensitivity. After 48 weeks, however, only 25(OH)D 3 levels remained significantly different from baseline, while the other parameter levels returned to baseline, suggesting a dose-response effect. Cholecalciferol had no effect on BMD, adipokines and triglycerides. ConclusionsThe effect of cholecalciferol treatment in this cohort appears to be dose dependent. Cholecalciferol dosages of !2000 IU are necessary to achieve 1,25(OH) 2 D 3 levels that significantly decrease PTH, but also negatively affect insulin sensitivity. The results of this hypothesis-driven explorative study need to be confirmed in larger clinical trials.Keywords: bone mineral density, cholecalciferol supplementation, HIV/AIDS, insulin sensitivity, vitamin D deficiency Vitamin D is mainly known for its function in regulation of calcium homeostasis and maintenance of bone mineralization. Serum 25(OH)D 3 levels are the best indicator of vitamin D status [3]. The optimal 25(OH)D 3 level needed for maintenance of adequate bone mineral density (BMD) is unknown. A significant positive association between 25(OH)D 3 levels and BMD has been observed in both Another emerging problem associated with the widespread use of HAART is the lipodystrophy syndrome, which is characterized by altered fat distribution (central fat accumulation and peripheral fat loss) and metabolic alterations (dyslipidaemia, insulin resistance and diabetes mellitus). The vitamin D receptor (VDR) has also been found on adipocytes, suggesting a role for vitamin D in fat metabolism [7]. Indeed, it was demonstrated in vitro that 1,25-dihydroxy vitamin D 3 [1,25(OH) 2 D 3 ] inhibits adipocyte differentiation through, among other effects, inhibition of peroxisome proliferator-activated receptor-g (PPAR-g) [7][8][9]. However, 1,25(OH) 2 D 3 can elicit a nongenomic action on adipocytes in vitro, resulting in increased intracellular calcium levels and corresponding stimulation of adipogenesis and inhibition of lipolysis [10].A number of genetic polymorphisms in the VDR gene and low 25(OH)D 3 levels have been associated with insulin resistance and wi...

Per oral substitution with 300000 IU vitamin D (Cholecalciferol) reduces bone turnover markers in HIV-infected patients

“…It is suggested that 25OH-vitamin D levels should even be supplemented to >75 nmol/L [31]. Even if the results of studies regarding fractures rate in HIV-patients yielded conflicting results and the effect of cholecalciferol is uncertain [32-36], we actually suggest cholecalciferol supplementation. We observed a decrease in bone resorption as well as bone formation markers 3 month after supplementation.…”

Bone, fracture and frailty

“…Supplementation with cholecalciferol requires at least 2000 IU/day for 14 days followed by 1000 IU/day thereafter to normalize vitamin D levels. Despite this supplementation there was no effect on BMD at 48 weeks in a small pilot study [38].…”

Vitamin D and Calcium Abnormalities in the HIV-Infected Population

“…The authors attributed this finding to the low prevalence of osteopenia and osteoporosis at baseline among their participants. 178 Similarly, Mondy and colleagues, 179 in a cohort of 31 participants originally enrolled in an RCT powered to detect lumbar spine BMD change with the use of alendronate, showed that among subjects randomized to receive only calcium 1 g/day plus vitamin D 400 IU daily, lumbar spine BMD increased by 1.3% at 48 weeks compared with baseline (vs 5.2% in the alendronate group). This change, however, was not statistically significant.…”

“…A smaller prospective study in the Netherlands also failed to demonstrate benefit of vitamin D supplementation on insulin resistance and inflammatory markers (ie, IL-6, TNF-a) after 48 weeks. 178 In an RCT involving 52 mostly virologically suppressed vertically infected youths aged 8 to 26 years with 25-OHD less than 30 ng/mL, Giacomet and colleagues 188 showed that 12-month supplementation with cholecalciferol 100,000 IU every 3 months for 4 doses resulted in an anti-inflammatory T-cell phenotype (ie, decrease in Th17:Treg ratio) at 3 months. This effect was no longer seen at 12 months.…”