Adults with overweight, obesity may have decreased response to vitamin D supplements
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The effect of vitamin D supplementation on total 25-hydroxyvitamin D levels may be blunted for adults with a higher BMI, according to a post hoc analysis of data from the VITAL trial.
As Healio previously reported, adults in the VITAL trial who received omega-3 or vitamin D supplements did not have a lower rate of major cardiovascular events or invasive cancers compared with placebo at 5 years of follow-up. However, subgroup analysis found the risk for cancer was lower for adults who took supplements and had a BMI of less than 25 kg/m2 compared with placebo. In a new study published in JAMA Network Open, researchers found the response to vitamin D supplementation among VITAL participants also varied based on BMI.
“The analysis of the original VITAL data found that vitamin D supplementation correlated with positive effects on several health outcomes, but only among people with a BMI under 25 kg/m2,” Deirdre K. Tobias, ScD, an associate epidemiologist in the division of preventive medicine, department of medicine at Brigham and Women’s Hospital, said in a press release. “There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated BMI.”
Researchers obtained data from 16,515 VITAL participants who had blood samples available before randomization (mean age, 67.7 years; 50.7% women; 76.9% white; 15.1% Black). Of the cohort, 2,742 had blood samples available from a 2-year follow-up. BMI was derived from self-reported height and weight in a baseline questionnaire. Total 25-(OH)D, 25-(OH)D3, free vitamin D and bioavailable vitamin D were collected.
At baseline, mean total 25-(OH)D levels were 32.3 ng/mL for adults with underweight or normal weight. Levels declined gradually with BMI to 30.5 ng/mL for those with overweight, 29 ng/mL for adults with class I obesity and 28 ng/mL for those with class II obesity (P < .001).
Among those with blood samples available at 2-year follow-up, the serum 25-(OH)D levels increased 11.9 ng/mL in the supplementation group. Increases were also observed for 25-(OH)D3, free vitamin D and bioavailable vitamin D in the supplement group.
Changes in vitamin D biomarkers were lower among adults with a higher baseline BMI. For total 25-(OH)D, the mean increase for adults receiving supplementation was 13.5 ng/mL for those with a BMI of less than 25 kg/m2, 12.7 ng/mL for adults with a BMI of 25 kg/m2 to 29.9 kg/m2, 10.5 ng/mL for those with a BMI of 30 kg/m2 to 34.9 kg/m2 and 10 ng/mL for adults with a BMI of 35 kg/m2 or higher. Similar findings were observed when 964 Clinical and Translational Science Center participants were stratified by baseline waist circumference, with less of a total 25-(OH)D change observed among adults with a higher waist circumference.
“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 endpoints among VITAL participants with obesity,” the researchers wrote. “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 nutria-kinetics will elucidate this further.”
Reference:
- Study suggests vitamin D benefits and metabolism may depend on body weight. Available at www.eurekalert.org/news-releases/976605. Published Jan. 17, 2023. Accessed Jan. 17, 2023.
Perspective
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This subgroup analysis of the VITAL trial confirmed an inverse association between obesity and vitamin D status in a large, diverse population of healthy U.S. individuals with normal or near-normal vitamin D levels, independently of other known socioeconomic and racial factors that affect vitamin D status. Furthermore, this analysis showed that 2000 IU per day of vitamin D3 raised 25-(OH)D levels and biomarkers of vitamin D metabolism, but with a blunted effect of higher BMI, though these differences were modest.
Interestingly, vitamin D supplementation did not influence vitamin D binding protein, albumin, parathyroid hormone or calcium levels, and there was no association with BMI categories, which may reflect the normal vitamin D status of the population examined, as suggested by the authors. This also suggests that changes in 25(OH)D and free vitamin D within the normal range may not have physiological relevance in calcium homeostasis, though this does not exclude effects on other tissues.
Therefore, this study lays the groundwork for further studies in the vitamin D-deficient population to evaluate the influence of BMI on biomarkers of vitamin D metabolism after supplementation and determine whether these are better predictors of clinical response in interventional trials.
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