Effect of Vitamin D Supplementation on Obesity‐Induced Insulin Resistance: A Double‐Blind, Randomized, Placebo‐Controlled Trial

Abstract

ObjectiveThe aim was to investigate whether vitamin D supplementation, combined with a hypocaloric diet, could have an independent effect on insulin sensitivity in subjects with both overweight and hypovitaminosis D. Changes from baseline in anthropometric parameters, body composition, glucose tolerance, and insulin secretion were considered as secondary outcomes.MethodsEighteen volunteers who were nondiabetic and vitamin D deficient and had BMI > 25 kg/m2 were randomized (1:1) in a double‐blind manner to a hypocaloric diet + either oral cholecalciferol at 25,000 IU/wk or placebo for 3 months. Hyperinsulinemic‐euglycemic clamp to measure insulin sensitivity was performed at baseline and after intervention.ResultsBody weight in both groups decreased significantly (−7.5% in the vitamin D group and −10% in the placebo group; P < 0.05 for both), with no between‐group differences. Serum 25‐hydroxyvitamin D levels in the vitamin D group increased considerably (from 36.7 ± 13.2 nmol/L to 74.8 ± 18.7 nmol/L; P < 0.001). Insulin sensitivity in the vitamin D group improved (from 4.6 ± 2.0 to 6.9 ± 3.3 mg·kg−1·min−1; P < 0.001), whereas no changes were observed in the placebo group (from 4.9 ± 1.1 to 5.1 ± 0.3 mg·kg−1·min−1; P = 0.84).ConclusionsCholecalciferol supplementation, combined with a weight loss program, significantly improves insulin sensitivity in healthy subjects with obesity and might represent a personalized approach for insulin‐resistant subjects with obesity.

Insulin-sensitizing effects of vitamin D repletion mediated by adipocyte vitamin D receptor: Studies in humans and mice

“…Prospective studies also revealed beneficial effects of vitamin D supplementation on insulin sensitivity [ 87 , 88 ], including a meta-analysis of prospective cohort studies [ 17 , 89 , 90 ]. Intriguingly, prospective studies comparing euglycemic-hyperinsulinemic clamps at baseline and after 12 and 24 weeks of vitamin D supplementation noted improved insulin sensitivity in obese insulin-resistant subjects [ 91 , 92 ] but not in T2D subjects [ 74 ], suggesting that the established metabolic defects of T2D are not easily reversed by vitamin D repletion.…”

The Complex Context of the Involvement of Vitamin D Deficiency in Obesity

“…Obesity is abnormal or excessive fat accumulation and is associated with a number of metabolic disorders, such as insulin resistance, hyperinsulinemia, cancer, diabetes, dyslipidemia and cardiovascular disorders. Obesity is well known as having a high degree of morbidity and mortality [1][2][3].…”

Vitamin D in insulin sensitivity and obesity

“…In a Central-European population, it has been suggested that genetic variability in the VDR region (including FokI and ApaI polymorphisms) may be an important factor influencing anthropometric characteristics associated with obesity including BMI, Fat Mass and body fat distribution (85). Furthermore, a study in Poland showed that the BsmI variant may be associated with BMI in men (86), but not in women (87). However, larger genome wide studies in UK (men and women) (88) and Chinese women (89) indicate that VDR genetic variants are unlikely a major determinant of obesity related phenotype such as BMI, waist circumference (WC), and waist-to-hip ratio (WHR).…”

“…In addition to lifestyle intervention, weightreducing surgery using gastric bypass only resulted in a temporal elevation of serum 25(OH) D 3 levels, which decreased again one month after surgery (85). Furthermore, two systematic reviews and one meta-analysis concluded that weight loss interventions showed only marginal changes in serum 25(OH)D 3 following significant weight and body fat loss (86,87). Thus, the above studies provide inconsistent evidence on the relation between AT mass and the circulating levels of serum 25(OH)D 3 .…”

“…Several studies also indicate beneficial effects on metabolic health by combining vitamin D supplementation and other modes of intervention such as lifestyleinduced weight loss (i.e. diet and exercise) (87)(88)(89). Therefore, further studies with more personalized (sub-group, i.e.…”