Effects of Body Weight on Vitamin D Metabolism and Response

Researchers published study results that demonstrated an association between higher baseline BMI and a diminished response to vitamin D supplementation in JAMA Network Open.

The study authors conducted a post hoc analysis using data collected in the Vitamin D and Omega-3 Trial (VITAL). VITAL is a completed randomized, double-blind, placebo-controlled 2 x 2 (vitamin D₃ [cholecalciferol], 2000 IU/d and marine ω-3 fatty acids, 1 g/d, respectively) factorial trial for the primary prevention of cancer and cardiovascular disease. VITAL was conducted between July 1, 2010, and November 10, 2018. This post hoc analysis was carried out between August 1, 2021, and November 9, 2021.

Of the 25,871 VITAL participants, researchers of the post hoc analysis included a total of 16,515 participants who had contributed baseline blood samples, of which 8371 were women (80.7%) and 12,420 self-reported as non-Hispanic White (76.9%). Of the total participants, 2742 provided a 2-year follow-up blood sample. Participants included in the analysis were men 50 years or older and women 55 years or older (mean SD 67.7 years) who did not have cancer or cardiovascular disease at baseline. A total of 6688 (40.05%) of these participants were classified as overweight and 4457 (27%) were classified as obese.

After receiving placebo for 3 months, participants were randomly assigned to 5-year age groups and 1 of 4 treatment combinations. Treatment variables included vitamin D (2000 IU/d) supplementation associated with clinical and novel vitamin D–related biomarkers by BMI category.

The authors stratified baseline and demographic characteristics and health status according to the following BMI categories:

• Underweight, less than 18.5;
• Standard weight, 18.5-24.9;
• Overweight, 25.-29.9;
• Obesity class I, 30.-34.9;
• Obesity class II, 35 and above.

Outcome measures were total 25-hydroxyvitamin D (25-OHD), 25-OHD3, free vitamin D (FVD), bioavailable vitamin D (BioD), vitamin D–binding protein (VDBP), albumin, intact parathyroid hormone (PTH), and calcium levels.

At baseline, total 25-OHD adjusted mean levels were incrementally lower at higher BMI categories (P <.001 for linear trend):

• Underweight, 32.3 (SE=0.7) ng/mL;
• Standard weight, 32.3 (0.1) ng/mL;
• Overweight, 30.5 (0.1) ng/mL;
• Obesity class I, 29 (0.2) ng/mL;
• Obesity class II, 28 (0.2) ng/mL.

Baseline 25-OHD3, FVD, BioD, VDBP, albumin, and calcium levels were lower in patients with higher BMI, while PTH levels were higher (P <.001).

Random assignment to vitamin D supplementation groups was associated with increases in total 25-OHD, 25-OHD3, FVD, and BioD compared with placebo measures at the 2-year follow-up; increases were significantly lower for participants with higher BMIs (P <.001). Supplementation did not significantly influence VDBP, albumin, PTH, or calcium changes.

The authors noted several study limitations, including that residual confounding could explain some differences based on baseline BMI. Other consideration include the possibility that obesity-related factors or pill adherence account for some BMI-related variations.

The researchers’ findings suggest that BMI may modify individual responses to vitamin D supplementation. The results may partially account for reduced health outcomes among individuals with higher BMIs. The authors concluded, “Sequestering of vitamin D and its metabolites from the circulation into adipose tissue may contribute to lower serum concentrations and may at least, in part, explain the reduced effectiveness of supplementation previously reported for cancer end points among VITAL participants with obesity. Obesity-related pathophysiologic factors, such as impaired vitamin D receptor sensitivity, are not ruled out and further mechanistic research is warranted. The effective dose to achieve optimal circulating and bioactive concentrations required for prevention of cancer and diabetes or other benefits may therefore be higher among patients with excess adiposity, and nutri-kinetics will elucidate this further.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.