Vitamin D: marker, measurand &amp; measurement

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Abstract

The measurement of vitamin D metabolites aids in assessing vitamin D status and in diagnosing disorders of calcium homeostasis. Most laboratories measure total 25-hydroxyvitamin D (25(OH)D), while others have taken the extra effort to measure 25(OH)D ₂ and 25(OH)D ₃ separately and additional metabolites such as 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D. The aim of this review is to provide an updated overview of the main markers of vitamin D metabolism, define the intended measurands, and discuss the advantages and disadvantages of the two most widely used assays, automated assays and liquid chromatography–tandem mass spectrometry (LC-MS/MS). Whether using the easy and fast automated assays or the more complex LC-MS/MS, one should know the pitfalls of the used technique in order to interpret the measurements. In conclusion, automated assays are unable to accurately measure 25(OH)D in all patient groups, including persons using D ₂. In these cases, an LC-MS/MS method, when appropriately developed and standardized, produces a more reliable measurement.

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Most cited references 47

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Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

Michael F Holick, Neil C Binkley, Heike A Bischoff-Ferrari … (2011)

The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

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Vitamin D deficiency 2.0: an update on the current status worldwide.

Karin Amrein, Mario Scherkl, Magdalena Hoffmann … (2020)

Vitamin D testing and the use of vitamin D supplements have increased substantially in recent years. Currently, the role of vitamin D supplementation, and the optimal vitamin D dose and status, is a subject of debate, because large interventional studies have been unable to show a clear benefit (in mostly vitamin D replete populations). This may be attributed to limitations in trial design, as most studies did not meet the basic requirements of a nutrient intervention study, including vitamin D-replete populations, too small sample sizes, and inconsistent intervention methods regarding dose and metabolites. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] < 50 nmol/L or 20 ng/ml) is associated with unfavorable skeletal outcomes, including fractures and bone loss. A 25(OH)D level of >50 nmol/L or 20 ng/ml is, therefore, the primary treatment goal, although some data suggest a benefit for a higher threshold. Severe vitamin D deficiency with a 25(OH)D concentration below <30 nmol/L (or 12 ng/ml) dramatically increases the risk of excess mortality, infections, and many other diseases, and should be avoided whenever possible. The data on a benefit for mortality and prevention of infections, at least in severely deficient individuals, appear convincing. Vitamin D is clearly not a panacea, and is most likely efficient only in deficiency. Given its rare side effects and its relatively wide safety margin, it may be an important, inexpensive, and safe adjuvant therapy for many diseases, but future large and well-designed studies should evaluate this further. A worldwide public health intervention that includes vitamin D supplementation in certain risk groups, and systematic vitamin D food fortification to avoid severe vitamin D deficiency, would appear to be important. In this narrative review, the current international literature on vitamin D deficiency, its relevance, and therapeutic options is discussed.

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Vitamin D status: measurement, interpretation, and clinical application.

Michael F Holick (2009)

Vitamin D, the sunshine vitamin, is now recognized not only for its importance in promoting bone health in children and adults but also for other health benefits, including reducing the risk of chronic diseases such as autoimmune diseases, common cancer, and cardiovascular disease. Vitamin D made in the skin or ingested in the diet is biologically inert and requires 2 successive hydroxylations first in the liver on carbon 25 to form 25-hydroxyvitamin D [25(OH)D], and then in the kidney for a hydroxylation on carbon 1 to form the biologically active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. With the identification of 25(OH)D and 1,25(OH)(2)D, methods were developed to measure these metabolites in the circulation. Serum 25(OH)D is the barometer for vitamin D status. Serum 1,25(OH)(2)D provides no information about vitamin D status and is often normal or even increased as the result of secondary hyperparathyroidism associated with vitamin D deficiency. Most experts agree that 25(OH)D of 30 ng/mL to take full advantage of all the health benefits that vitamin D provides.

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Author and article information

Journal

Journal ID (nlm-ta): Endocr Connect

Journal ID (iso-abbrev): Endocr Connect

Journal ID (hwp): EC

Title: Endocrine Connections

Publisher: Bioscientifica Ltd (Bristol )

ISSN (Electronic): 2049-3614

Publication date (Electronic): 23 January 2023

Publication date (Electronic preprint): 23 January 2023

Publication date Collection: 01 April 2023

Volume: 12

Issue: 4

Electronic Location Identifier: e220269

Affiliations

[1 ]Atalmedial Diagnostics Centre , Spaarne Gasthuis, Haarlem, The Netherlands

[2 ]Department of Clinical Chemistry , Hematology and Immunology, Noordwest Ziekenhuis, Alkmaar, The Netherlands

[3 ]Department of Clinical Chemistry , University of Liège, CHU de Liège, Liège, Belgium

[4 ]Amsterdam UMC location Vrije Universiteit Amsterdam , Department of Clinical Chemistry, Endocrine Laboratory, Boelelaan, Amsterdam, The Netherlands

[5 ]Amsterdam Gastroenterology , Endocrinology & Metabolism, Amsterdam, The Netherlands

[6 ]Amsterdam UMC location University of Amsterdam , Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands

[7 ]Amsterdam Reproduction & Development Research Institute , Amsterdam, The Netherlands

Author notes

Correspondence should be addressed to A C Heijboer: a.heijboer@ 123456amsterdamumc.nl

Author information

Annemieke C Heijboer http://orcid.org/0000-0002-6712-9955

Article

Publisher ID: EC-22-0269

DOI: 10.1530/EC-22-0269

PMC ID: 10083657

PubMed ID: 36688810

SO-VID: 42fa5970-ce09-41b4-aebf-a70ea242a566

License:

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

History

Date received : 06 November 2022

Date accepted : 23 January 2023

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