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Weight may be linked to a modified response to vitamin D supplementation, according to a post-hoc analysis of the .

While supplementation with vitamin D 2,000 IU/day was associated with an increase in serum total 25-hydroxyvitamin D (25-OHD) levels compared with placebo at 2-year follow-up, increases were significantly lower with higher body mass index (BMI; P<0.001), reported Deirdre K. Tobias, ScD, of Brigham and Women's Hospital in Boston, and colleagues in .

Based on data from over 16,000 participants, those with a BMI of 35 or higher had the lowest total 25-OHD levels before randomization (P<0.001 for linear trend):

• Underweight: 32.3 ng/mL
• Normal weight: 32.3 ng/mL
• Overweight: 30.5 ng/mL
• Obesity class I: 29.0 ng/mL
• Obesity class II: 28.0 ng/mL

Among the 2,742 participants with repeated blood samples at 2 years, multivariable-adjusted mean total 25-OHD levels were 44 mg/mL for those with a BMI under 25 who received vitamin D supplementation compared with 41.2 ng/mL for those in the 25-29.9 BMI range, and 39.4 ng/mL and 37.9 ng/mL, respectively, for those with class I and II obesity.

This pattern held true for 25-OHD3 (43.8 ng/mL for BMI <25 vs 37.6 for BMI 35+), free vitamin D (10.20 pg/mL vs 7.04 pg/mL, respectively), and bioavailable vitamin D (3.8 ng/mL vs 2.7 ng/mL).

"Increases in vitamin D availability and bioactivity achieved with supplementation may be modestly or moderately diminished with excess adiposity," Tobias and team wrote. "These trends were also observed among the subgroup of participants with low vitamin D levels at baseline, suggesting that, even when insufficient for vitamin D, obesity may still blunt the response to supplementation."

This may be due to, at least in part, the "sequestering" of circulating vitamin D and its metabolites into adipose tissue, which may dampen the effectiveness of supplementation, they suggested.

That being said, vitamin D supplementation did not significantly move the needle when it came to vitamin D binding protein, albumin, or calcium levels at 2 years, regardless of BMI. Moreover, parathyroid hormone levels followed the exact opposite pattern -- higher baseline levels at higher BMIs.

In an , Katherine Bachmann, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, noted that the study "provide[d] novel evidence that responses to vitamin D supplementation may be attenuated in individuals with overweight and obesity," adding that this may explain some of the different outcomes seen in VITAL.

"This blunted response may also play a role in the diminished benefit of observed in individuals with overweight and obesity from the original VITAL," Bachmann wrote. "Interestingly, the reduction in cancer incidence did not appear to be affected by other plausible predictors, including the presence of baseline vitamin D insufficiency."

The VITAL study was a randomized, double-blind, placebo-controlled trial for the primary prevention of cancer and cardiovascular disease, which was conducted from July 2010 to November 2018. The current analysis included a subset of 16,515 VITAL participants who provided a blood sample at baseline and a subset of 2,742 participants with a repeated sample at 2-year follow-up.

Mean age was 67.7, 50.7% were women, and 76.9% were white. Participants with overweight (40.5%) or obesity (27.0%) were, on average, younger and more likely to self-report Black race and ethnicity, a lower household annual income, and a lower achieved educational level compared with participants with normal body weight. Participants with obesity were less likely to be physically active or report alcohol intake, but smoking status was similar across BMI levels.

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