Vitamin D and Vascular Health in Children

Our primary objective is to determine, in obese and overweight children aged 10 to 18 years with vitamin D deficiency (defined as serum 25-hydroxyvitamin D <20 ng/mL), the efficacy of enhanced vitamin D3 supplementation in improving vascular endothelial function, arterial stiffness, insulin sensitivity, and metabolic syndrome risk status; and to assess whether these effects are dose-dependent. As a secondary objective, we will examine the vitamin D supplementation-induced effect on adipokines and inflammatory markers relevant to CVD risk. In a double-masked, controlled trial, we will randomize 252 eligible children to receive either 600 IU (conventional supplementation), or 1000 IU or 2000 IU (enhanced supplementation) of vitamin D3 daily for 6 months.

In terms of reporting of results, the following pre-specified outcomes are included in the primary manuscript (PubMed PMID:31950134 -- see Reference section for citation details)

• Waist Circumference
• Serum High Density Lipoprotein (HDL) Cholesterol
• Serum Triglycerides
• Inflammatory markers (Plasma TNF-alpha, high-sensitivity C-reactive protein, and IL-6)
• Adiopkines (Plasma Leptin and Adiponectin)

Plasma nitric oxide metabolites were not measured.

Inclusion criteria

• Eligible subjects will be 10 to 18 years of age;
• obese or overweight (BMI ≥85th %tile);
• otherwise healthy, and
• have a serum 25(OH)D concentration <20 ng/mL

Children taking multivitamins should be able to hold off their multivitamins during the course of the study.

Exclusion criteria

Children will be excluded if they

• (a) have hepatic or renal disease, metabolic rickets, malabsorptive disorders, primary hyperparathyroidism, hyperthyroidism, or other chronic disorders that could affect vitamin D metabolism;
• (b) are receiving treatment with anticonvulsants, systemic glucocorticoids, pharmacologic doses of vitamin D (≥1000 IU of vitamin D2 or D3 daily), antihypertensives, vasoactive drugs, antilipidemics, metformin, antipsychotics, or other oral insulin regulators;
• (c) have cholelithiasis or urolithiasis;
• (d) have type 1 or type 2 diabetes; or
• (e) have a condition or underlying abnormality that could compromise the safety of the subject.

Post-menarchial girls with a positive pregnancy test at randomization, or subjects found during the screening phase to have hypercalcemia (serum calcium >10.8 mg/dL) or significant fasting hyperglycemia (fasting blood glucose ≥ 125 mg/dL) will also be excluded.