Vitamin D is an essential macronutrient involved in many biological processes. Vitamin D is produced endogenously as vitamin D3 (cholecalciferol) or obtained from the diet or supplementation as vitamin D2 (ergocalciferol) or vitamin D3. The role of vitamin D in the prevention of osteomalacia and rickets has already been established. In addition, recent research indicates that levels of 25-hydroxyvitamin D (25-OHD) may also be important for the development 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 vitamin d supplementation have not reported any beneficial effect on cardiovascular disease and cancer.
Preselected secondary analyzes in VITAL reported that vitamin D supplementation resulted in a 22% lower incidence of autoimmune disease, a 42% lower incidence of cancer mortality, and a 24% lower incidence of cancer for normal-weight participants. However, similar results were not seen for obese participants. In addition, meta-analyses of vitamin D supplementation and risk of type 2 diabetes also reported a similar modification association with body mass index (BMI).
It has been observed that increased body weight and obesity are associated with lower levels of 25-OHD in the blood along with higher vitamin D deficiency and insufficiency. One previous study reported that obesity can lead to lower levels of 25-OHD in the blood. In addition, it has been suggested that the reduced response to vitamin D supplementation in obesity may be due to sequestration of vitamin D in adipose tissue. Previous studies also indicated that obesity may be able to suppress the liver’s 25-hydroxy-vitamin D enzyme to 25-OHD, thus reducing its bioactivity. However, it remains unclear whether the reduced response of 25-OHD levels with supplementation to overweight individuals also affects other biomarkers of vitamin D supplementation.
A new study in the journal JAMA Network is open It aims to determine whether bmi is able to modulate vitamin d metabolism as well as response to supplementation.
The study involved men aged 50 and over and women aged 55 and over between August 1, 2021 and November 9, 2021. Participants also had to be free of cardiovascular disease and cancer at baseline. Participants were given either an active study pill or a placebo while they were double-blind and followed up for two years. Information regarding their race, income, age, and education level was also collected. Blood samples were collected from participants through phlebotomy centers, home visits, or mail collections at both baseline and follow-up.
Information on body weight and height was collected from participants using a self-reported questionnaire at baseline. Total 25-OHD3 and 25-OHD were determined using tandem liquid chromatography-mass spectrometry. Free vitamin D (FVD) levels were measured using a polyclonal VDBD and enzyme-linked immunosorbent assay, while parathyroid hormone (PTH) and intact albumin levels were performed using a radiochemi- cal assay. Quantitative measurement of serum calcium levels was performed using spectroscopy. BioD was determined, which was circulating 25-OHD not associated with VDBP. Finally, a secondary analysis was performed based on the World Health Organization (WC) waist circumference for obesity.
The results indicated that a total of 16,515 participants were included in the study, of which 8,144 were men and 8,371 were women. The mean age of the participants was reported to be 67.7 years. Participants reported 283 Asian or Pacific Islander, race and ethnicity, 12,420 non-Hispanic white, 589 non-Hispanic black, 129 Native American or Alaska Native, 2,445 black, and 333 non-Hispanic. known or identified as others. Overweight participants were reported to be younger, black and biracial, have a lower level of education, and have lower annual household income. Furthermore, it was reported that obese participants were less likely to consume alcohol as well as be physically active.
The mean (SD) serum level of 25-OHD before use of study pills was reported to be 30.6 (9.5) ng/mL. Lower total 25-OHD levels were observed for participants with a higher BMI. In addition, decreased levels of vitamin D-binding protein (VDBP), calcium, albumin, 25-OHD3, BioD, and FVD were observed with a higher BMI at baseline. However, higher thyroid hormone levels are observed with higher BMI. An increase in the mean serum 25-OHD level of 11.9 (8.6) ng/mL was observed among participants who took vitamin D supplements at 2 years of age, along with increases in BioD, FVD, 25-OHD3 and 25-OHD levels. Furthermore, it was noted that increases in vital signs were lower for participants with a higher BMI at baseline.
Moreover, an increase in total 25-OHD3, 25-OHD, BioD, and FVD levels with reduced supplementation was observed in higher WC-derived obesity classes. However, no changes in calcium, PTH, albumin, or VDBP levels were observed for this subgroup, with no WC class difference.
Therefore, the current study demonstrates that vitamin D supplementation can increase total 25-OHD levels along with markers of vitamin D status. However, BMI can modify the outcome of supplementation, with people with a higher BMI showing a lower response. Thus, the effective dose for preventing cancer, diabetes, and other health conditions should be higher among obese people and requires more research.
The study has certain limitations. First, differences in post-randomization factors associated with BMI may lead to bias. Second, the study included heterogeneity regarding BMI category.