The vitamin D paradox in Black Americans: a systems-based approach to investigating clinical practice, research, and public health - expert panel meeting report

Abstract

The Office of Dietary Supplements, the National Institute on Minority Health and Health Disparities, the National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases, all components of the U.S. National Institutes of Health, co-sponsored an expert panel meeting to discuss the vitamin D paradox in Black Americans. The paradox is that despite markedly low (or "deficient") measures of vitamin D status in Black Americans, the incidence of falls, fractures, or osteopenia are significantly lower compared to White American counterparts with similar vitamin D status. Six panelists were invited to engage in guided discussions on the state of the science with respect to key knowledge gaps impacting vitamin D status and bone health. They were also asked to reflect on best approaches for advancing the science. A central theme throughout the discussions was that there may be many factors that impact Vitamin D levels in Black Americans and understanding these factors may be key to understanding mechanisms for improving bone health in all populations. Data presented showed that although adiposity, skin pigmentation, vitamin D binding protein polymorphisms, and genetics all contributed to differences in 25(OH)D levels in Black vs. White Americans, no one factor alone could fully explain the vitamin D paradox in Black Americans. However, the panelists did agree that the paradox is significant and warrants further investigation. There was consensus that Black Americans gained no skeletal benefits from high doses of vitamin D supplementation, and that high levels of the biomarker of vitamin D status, serum 25-hydroxyvitamin D or 25(OH)D, in this population are almost certain to result in adverse effects. Some panelists proposed that additional studies are needed so that the Institute of Medicine (IOM) can better define the safe upper limits of vitamin D intake in this and other subpopulations. Others suggested a need for better, more generalizable biomarkers of bone health to advance the science.

Keywords: Black vs. White Americans; Bone health; Dietary reference intakes; Paradox; Vitamin D.

Fig. 1

Vitamin D Pathways: An Overview (source: Nutrients 2016, 8, 319) [6]. The conversion of vitamin D to the active metabolite, 1,25(OH)₂D, is shown. The pathway starts with the exposure of vitamin D from dietary sources or via cutaneous synthesis following UVB radiation. Vitamin D is bound to VDBP and transported to the liver where it is converted to 25(OH)D, the current biomarker for vitamin D status. PTH enhances 1-alpha hydroxylase in the kidneys which is responsible for the conversion of the inactive metabolite, 25(OH)D, to the active metabolite, 1,25(OH)₂D. The entire pathway is tightly regulated via catabolic and feedback loop processes as shown

Fig. 2

Comparison of percent bias of 25(OH)D Assays [7]. Comparison of % bias of Method Mean of 25(OH)D assays from NIST-assigned target values for DEQAS samples from 2012 to 2014 and 2015-2017. The error bars are ± SD of the % bias (n = 36). Adapted from C.Q. Burdette et al., J. AOAC Int., 100 (5), 1277-1287 (2017)

Fig. 3

Differences in skeletal and muscle mass with aging in Black and White women (source: Am J Physiol Endocrinol Metab, 2000, 278(6), E1153-1157) [8]. Change with age in total body potassium (TBK) in black and white women, adjusted to mean height and weight for each race. For blacks, TBK = 0.11057 − 0.00016409 × Age (P < 0.0424). For whites, TBK = 0.11841 − 0.00047214 × Age (P < 0.0001). b) Total body calcium (TBCa) plotted against age in black and white women by use of a quadratic model, adjusted to mean height for each race. For blacks, TBCa = 0.70415 + 0.0065622 × Age − 0.00010433 × Age2 (P < 0.0001). For whites, TBCa = 0.66308 + 0.0065622 × Age − 0.00010433 × Age2 (P < 0.0001)