Vitamin D metabolites in captivity? Should we measure free or total 25(OH)D to assess vitamin D status?

Bikle, Daniel D.; Bouillon, Roger; Thadhani, Ravi; Schoenmakers, Inez

doi:10.1016/j.jsbmb.2017.01.007

Cited by 145 publications

(146 citation statements)

References 106 publications

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“…This assay is dependent on the quality of the antibody used to bind the free 25(OH)D. The antibody in the current assay does not recognize 25(OH)D 2 as well as 25(OH)D 3 (77% of the 25(OH) D 3 value) so underestimates the free 25(OH)D 2, . However, under most situations where the predominant vitamin D metabolite is 25(OH)D 3 , the data compare quite well to those obtained from similar populations using the centrifugal ultrafiltration assay [40 61]. …”

Section: Assays and Methods For Assessing Free Vitamin D Metabolite Lsupporting

confidence: 75%

“…The lower affinity site, corresponding to albumin, was found to have a Ka for 1,25(OH) 2 D of 5.4 × 10 4 M -1 and for 25(OH)D of 6 × 10 5 M -1 [30 31]. Although differences in the affinity constants for the different DBP alleles have been reported [24], results from other laboratories have not confirmed these differences [40]. …”

Section: Assays and Methods For Assessing Free Vitamin D Metabolite Lmentioning

confidence: 99%

“…Black and Asian populations are more likely to carry the Gc1f form and the Gc2 form is rare, while Whites more frequently exhibit the Gc1s and the Gc2 form. Gc1f has been stated to have the highest affinity and Gc2 the lowest affinity for vitamin D and its metabolites [24], but these differences among alleles have not been found by others [40]. In the absence of disease or pregnancy, DBP levels are relatively constant over time in adults [49].…”

Section: Assays and Methods For Assessing Free Vitamin D Metabolite Lmentioning

confidence: 99%

“…Clinical studies have investigated relationships between calculated and directly measured free or bioavailable 25(OH)D and parathyroid hormone levels (iPTH), bone density, calcium and calcium absorption, inflammatory measures, and the disease states of cirrhosis, nephrotic syndrome, primary hyperparathyroidism, pregnancy, and in relationship to estrogens and birth control pills or race [40]. Results from investigations of calculated free 25(OH)D and directly measured free 25(OH)D have not been in complete agreement primarily due to the challenges and differences in DBP assays, total 25(OH)D assays, uncertainty regarding DBP association constants, use of static equations as discussed above, and likely genetic racial admixtures affecting DBP allele distributions in contrast to self-identified race.…”

Section: Clinical Applicationsmentioning

confidence: 99%

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Bikle

Malmstroem

Schwartz

2017

Endocrinology and Metabolism Clinics of North America

113

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Synopsis The free hormone hypothesis postulates that only the non bound fraction (the free fraction) of hormones that otherwise circulate in blood bound to their carrier proteins is able to enter cells and exert their biologic effects. For the vitamin D metabolites less than 1% (0.4% for 1,25(OH)2D and 0.03% for 25(OH)D) is free, with over 99% bound to the vitamin D binding protein (DBP) and albumin (approximately 85% and 15%, respectively). Assays to measure the free vitamin D metabolite levels have been developed, and initial studies indicated their value in subjects with altered DBP levels. With the recent development of an ELISA to directly measure free 25(OH)D, the question becomes whether it is better to use the free 25(OH)D measurement instead of the total 25(OH)D measurement to determine vitamin D status. This review will discuss the development of these assays, the initial results, and their potential role in assessing vitamin D status in a variety of clinical conditions.

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Section: Assays and Methods For Assessing Free Vitamin D Metabolite Lsupporting

confidence: 75%

Section: Assays and Methods For Assessing Free Vitamin D Metabolite Lmentioning

confidence: 99%

Section: Assays and Methods For Assessing Free Vitamin D Metabolite Lmentioning

confidence: 99%

Section: Clinical Applicationsmentioning

confidence: 99%

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Current Controversies

Bikle

Malmstroem

Schwartz

2017

Endocrinology and Metabolism Clinics of North America

113

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“…There are few data in the literature on the bioavailability of vitamin D bound to albumin; therefore, the expression "vitamin D bioavailability" is used for the 25-hydroxyvitamin D form not bound to VDBP. 12 When reaching target tissues, 25-hydroxyvitamin D is converted by the enzyme 1α-hydroxylase into 1α,25-dihydroxyvitamin D, which is the metabolically active form of the vitamin.…”

Section: Physiology and Mechanism Of Actionmentioning

confidence: 99%

Vitamin D Deficiency and Cardiovascular Diseases

Jorge

Cordeiro

Rosa

et al. 2018

International Journal of Cardiovascular Sciences

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Vitamin D is considered a steroid hormone with a broad spectrum of action in the human body. Its action arises from the binding of its active metabolite (1α,25-dihydroxyvitamin D) to its receptor (VDR), which is present throughout the body, including vascular smooth muscle cells and cardiomyocytes. Initially, vitamin D deficiency was related only to changes in the musculoskeletal system, but in recent years, researchers have demonstrated its relationship with several pathologies related to other systems, such as cardiovascular diseases. The objective of this study is to review vitamin D's pathophysiology, describe its relationship with cardiovascular diseases based on the most recent publications, and highlight the results of vitamin supplementation in the prevention of such pathologies.

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The USPSTF 2021 Recommendations on Screening for Asymptomatic Vitamin D Deficiency in Adults

Burnett-Bowie

Cappola

2021

JAMA

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Interest in the relationship between vitamin D and health has increased over the past decade, with concurrent increases in the number of 25-hydroxyvitamin D (25[OH]D) assays performed and in the use of vitamin D supplements. 1,2 In 2011, the National Academy of Medicine determined that a 25(OH)D level less than 20 ng/mL (49.9 nmol/L) was consistent with deficiency and that there was no evidence for different 25(OH)D thresholds for different health conditions. 3 This recommendation resulted in vigorous debate within the medical and scientific community regarding the merits of screening for vitamin D deficiency and the goal 25(OH)D levels in healthy persons as well as those with certain chronic conditions. 4 In the 2014 National Health and Nutrition Examination Survey (NHANES), an estimated 25% of the US population was vitamin D deficient, with 5% of individuals 1 year or older with 25(OH)D levels less than 12 ng/mL and 18% with 25(OH)D levels between 12 and 19 ng/mL. 5 In this issue of JAMA, the US Preventive Services Task Force (USPSTF) presents an updated recommendation-insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults (an I statement)-based on a commissioned updated comprehensive evidence review. 6,7 The USPSTF last made a recommendation regarding screening for asymptomatic vitamin D deficiency in 2014. 8 Additionally, the USPSTF has published separate recommendations on the use of vitamin D supplementation for the prevention of falls or fractures and for the prevention of cardiovascular disease. 9-11 Importantly, the current recommendations for screening for vitamin D deficiency in community-dwelling, nonpregnant, asymptomatic adults do not apply to individuals who are hospitalized or institutionalized or to those who have underlying conditions (eg, osteoporosis, osteomalacia, malabsorption, or chronic kidney disease) or take medications that increase the risk of vitamin D deficiency. In addition, the USPSTF did not review emerging evidence on COVID-19 and vitamin D, although a recent randomized clinical trial suggested that a single dose of vitamin D did not reduce hospital length of stay in 240 adults with moderate to severe COVID-19. 12 The current USPSTF report does not include studies directly evaluating the benefits or harms of screening for vitamin D deficiency because none were identified. However, the evidence review did identify and evaluate 26 randomized clinical trials and 1 nested case-control study that reported data on the effectiveness of treatment of vitamin D deficiency (10 new studies and 17 studies from the 2014 USPSTF report) and 36 placebo-controlled studies reporting adverse events and harms from treatment with vitamin D (17 new studies and 19 studies

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Vitamin D metabolites in captivity? Should we measure free or total 25(OH)D to assess vitamin D status?

Cited by 145 publications

References 106 publications

Current Controversies

Current Controversies

Vitamin D Deficiency and Cardiovascular Diseases

The USPSTF 2021 Recommendations on Screening for Asymptomatic Vitamin D Deficiency in Adults

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