Vitamin D is an essential macronutrient that is involved in several biological processes. Vitamin D production takes place endogenously as vitamin D3 (cholecalciferol) or is obtained from the diet or supplements as vitamin D2 (ergocalciferol) or vitamin D3. The role of vitamin D in preventing osteomalacia and rickets has already been established. In addition, recent research suggests that 25-hydroxyvitamin D (25-OHD) levels might also be important for the progression and incidence of cardiovascular disease and cancer. However, meta-analyses of randomized clinical trials, such as the large-scale Vitamin D and Omega-3 Trial (VITAL), on supplementation of vitamin D have not reported any beneficial effect on cardiovascular disease and cancer.
Prespecified secondary analyses in VITAL reported that supplementation with vitamin D resulted in a 22% lower incidence of autoimmune disease, 42% lower cancer mortality, and 24% lower cancer incidence for participants with normal body weight. However, similar results were not observed for participants with obesity. Additionally, meta-analyses of vitamin D supplementation and risk of type 2 diabetes also reported a similar modifying association with body mass index (BMI).
Excess body weight and obesity have been observed to be associated with lower 25-OHD blood levels along with higher vitamin D deficiency and insufficiency. One previous study reported that obesity could lead to low serum 25-OHD levels. In addition, it has been suggested that a low response to vitamin D supplementation in obesity might be due to the sequestration of vitamin D in adipose tissue. Previous studies have also indicated that obesity might be able to suppress hepatic enzyme 25-hydroxylation of vitamin D to 25-OHD, thus reducing its bioactivity. However, it is still unclear whether the reduced response of 25-OHD levels with supplementation for overweight individuals also impacts other biomarkers of vitamin D supplementation.
A new study in the journal JAMA Network Open aimed to determine whether BMI is capable of modifying vitamin D metabolism as well as response to supplementation.
Study: Association of Body Weight With Response to Vitamin D Supplementation and Metabolism. Image Credit: Iryna Imago / Shutterstock
About the study
The study involved recruiting men who were 50 years of age and above and women who were 55 years of age and above between 1st August 2021 and 9th November 2021. The participants also had to be free of cardiovascular disease and cancer at baseline. The participants were given either an active or placebo study pill while being double-blinded and followed up for 2 years. Information regarding their ethnicity, income, age and education level was also collected. Blood samples were collected from the participants through phlebotomy centers, in-home visits, or mail-based kits at both baseline and follow-up.
Information on body weight and height was collected from the participants using a self-reported questionnaire at baseline. Quantifying the total 25-OHD3 and 25-OHD took place using liquid chromatography-tandem mass spectrometry. Measurement of free vitamin D (FVD) levels took place using polyclonal VDBD and enzyme-linked immunoassay, while intact parathyroid hormone (PTH) and albumin levels took place using a chemiluminescent-based assay. Quantification of serum calcium levels took place using spectroscopy. BioD was determined, which was the circulating 25-OHD not bound to VDBP. Finally, a secondary analysis based on the World Health Organization waist circumference (WC) for obesity was carried out.
Study findings
The results indicated that a total of 16,515 participants were included in the study out of which 8,144 were men and 8371 were women. The mean age of the participants was reported to be 67.7 years. 283 participants were reported to be Asian or Pacific Islander, race and ethnicity, 12,420 non-Hispanic White, 589 non-Black Hispanic, 129 Native American or Alaska Native, 2445 as Black, and 333 were unknown or identified as other. Overweight participants were reported to be younger, belong to Black ethnicity and race, had a lower achieved educational level, and had a lower household annual income. Moreover, obese participants were reported to be less likely to intake alcohol as well as being physically active.
The mean (SD) serum 25-OHD level prior to the use of study pills was reported to be 30.6 (9.5) ng/mL. Total 25-OHD levels were observed to be lower for participants with higher BMI. Additionally, lower levels of vitamin D–binding protein (VDBP), calcium, albumin, 25-OHD3, BioD, and FVD were observed with higher BMI at baseline. However, higher PTH levels were observed with higher BMI. An increase in mean serum 25-OHD level of 11.9 (8.6) ng/mL was observed among participants with vitamin D supplementation at 2 years, along with an increase in BioD, FVD, 25-OHD3, and 25-OHD levels. Moreover, the increases in biomarkers were observed to be lower for participants with higher BMI at baseline.
Furthermore, an increase in total 25-OHD3, 25-OHD, BioD, and FVD levels were observed with supplementation that was reduced at the higher WC-derived obesity categories. However, no changes in calcium, PTH, albumin, or VDBP levels were observed for this subset, with no WC category difference.
Therefore, the current study demonstrates that vitamin D supplementation can increase the total 25-OHD levels along with markers of vitamin D status. However, BMI can modify the result of supplementation, where people with higher BMI show reduced response. Thus, the effective dose to prevent cancer, diabetes, and other health conditions must be higher among obese people and requires further research.
Limitations
The study has certain limitations. First, differences in post-randomization factors associated with BMI might introduce bias. Second, the study involved heterogeneity regarding the BMI category.
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