Benefits of Vitamin D Supplementation Could Depend on Body Mass Index, Study Finds

JoAnn Manson, MD, MPH

An analysis of the landmark VITAL trial is reigniting the debate over the benefits, or lack thereof, seen with vitamin D supplementation—suggesting the determining factor of whether or not a patient will see benefit hinges on their body mass index (BMI).

Results of the analysis, which stratified patients according to baseline BMI, suggest a blunted response was observed for those with overweight or obesity Among patients in the Vitamin D and Omega-3 Trial (VITAL).

“This study sheds light on why we’re seeing 30-40 percent reductions in cancer deaths, autoimmune diseases, and other outcomes with vitamin D supplementation among those with lower BMIs but minimal benefit in those with higher BMIs, suggesting it may be possible to achieve benefits across the population with more personalized dosing of vitamin D,” said senior investigator JoAnn E. Manson, MD, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and principal investigator of VITAL, in a statement from Brigham and Women’s Hospital. “These nuances make it clear that there’s more to the vitamin D story.”

In regard to its impact on overall health, few items, outside of coffee and caffeine, have garnered the level of public interest or been studied as exhaustively as vitamin D. With the majority of these studies plagued by flawed design, confounding, or other issues, the VITAL trial was born to provide a more definitive answer to the questions surrounding vitamin D supplementation. Designed with the specific intent of assessing the effects of daily high-dose vitamin D for the prevention of cancer and cardiovascular disease, the trial enrolled 25,871 adults who were randomized and followed for a mean of 5.3 years.

Results of the trial demonstrated daily vitamin D supplementation failed to provide a significant reduction in risk of cancer, cardiovascular disease, or stroke among the study cohort. However, investigators observed a statistical correlation between BMI and cancer incidence, cancer mortality, and autoimmune disease incidence. The current study was designed as a posthoc analysis of the VITAL trial to test the investigators' hypothesis that obesity would modify vitamin D metabolism and response to supplementation. Limiting their analyses to those with a baseline vitamin D analysis, investigators identified a cohort of 16,155 patients for inclusion in their analysis.

The study cohort had a mean age of 67.7 (SD, 7.0) years, 50.7% were women, and 76.9% were non-Hispanic White. Of note, 2742 of the 16,155 patients included in the investigators’ analyses had a follow-up blood sample taken after 2 years. Investigators pointed out those with baseline overweight or overweight (40.5%) or obesity (27.0%) were typically younger and more likely to self-report Black race and ethnicity, have a lower household annual income, and have a lower achieved educational level than their counterparts with normal body weight.

Prior to undergoing randomization, levels of serum total 25-OHD levels were incrementally lower at higher BMI categories. The adjusted means for each BMI category are highlighted below (P <.001 for linear trend).

• Underweight: 32.3 (SE, 0.7) ng/mL
• Normal Weight: 32.3 (SE, 0.1) ng/mL
• Overweight: 30.5 (SE, 0.1) ng/mL
• Obesity Class I: 29.0 (SE, 0.2) ng/mL
• Obesity Class II: 28.0 (SE, 0.2) ng/mL

Further analysis indicated baseline levels of 25-OHD3, FVD, BioD, VDBP, albumin, and calcium levels were lower with higher BMI categories. In contrast, PTH level appeared to increase as BMI categories increased (all P <.001 for linear trend).

When assessing the effects of randomization, results demonstrated randomization to daily vitamin D supplementation was associated with increases in 25-OHD, 25-OHD3, FVD, and BioD levels compared with placebo at 2 years. However, investigators pointed out increases were significantly over at higher BMI categories. Additionally, no substantial change in VDBP, albumin, PTH, or calcium levels was observed as a result of vitamin D supplementation.

“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,” said lead investigator Deirdre K. Tobias, ScD, an associate epidemiologist in Brigham’s Division of Preventive Medicine, in the aforementioned statement. “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.”

This study, “Association of Body Weight With Response to Vitamin D Supplementation and Metabolism,” was published in JAMA Network Open.