Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research.

The field of vitamin D public health research has a pressing need to define sensitive and specific predictors of vitamin D status that can be used to determine whether an individual or population has a supply of vitamin D that is sufficient to meet requirements. The aim of this review is to highlight the considerations needed when evaluating evidence of the relations between vitamin D biomarkers and functional or health outcomes across the life cycle. It draws attention to the importance of distinguishing between biomarkers of supply, function, and outcome and of considering the many factors that could influence interpretation, such as life stage, ethnicity, body mass index, liver and kidney function, and dietary calcium and phosphorus intake. The vitamin D biomarkers that have shown the most utility to date are the plasma concentration of 25-hydroxyvitamin D (supply), the plasma concentration of parathyroid hormone (function), and the presence or absence of rickets (outcome). However, a single biomarker of vitamin D status or threshold value is unlikely to be valid in all situations. The field therefore needs research to refine existing biomarkers or establish new indicators that take the many factors into account and to identify useful functional biomarkers of vitamin D status for infants, children, women of reproductive age, and specific ethnic groups. However, evidence using the biomarkers currently available shows that frank vitamin D deficiency is a major public health problem in many parts of the world that requires urgent attention.Am J Clin Nutr 2008;88(suppl):500S-6S.

Context:There is uncertainty over the equivalence of vitamins D2 and D3 to maintain plasma 25-hydroxyvitamin D (25(OH)D).Objective:The objective of the study was to compare the plasma half-lives of 25(OH)D2 and 25(OH)D3 in two distinct populations with different dietary calcium intake and 25(OH)D status.Participants:Healthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study.Interventions:The intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated-25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days.Main Outcome Measures:25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured.Results:25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3 half-life [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2 half-life: regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half-life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d; P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration × country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2 half-lives compared with other combined genotypes (P = .007) after correction for country.Conclusions:25(OH)D2 half-life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate vitamin D metabolism and vitamin D expenditure and aid in the assessment of vitamin D requirements.

Context:Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD.Objectives:Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD.Design:This study used a cross-sectional design.Setting:The general community in the United States, United Kingdom, and The Gambia were included in this study.Participants:Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included.Exposures:Total 25OHD concentration, race, and DBP (GC) genotype exposures were included.Outcome Measures:Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures.Results:Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80–0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites.Conclusions:Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population.