Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Mar 14;16(6):839.
doi: 10.3390/nu16060839.

Classification of Vitamin D Status Based on Vitamin D Metabolism: A Randomized Controlled Trial in Hypertensive Patients

Sieglinde Zelzer  1 , Andreas Meinitzer  1 , Dietmar Enko  1   2 , Martin H Keppel  1 , Markus Herrmann  1 , Verena Theiler-Schwetz  3 , Christian Trummer  3 , Lisa Schmitt  3 , Andreas Tomaschitz  4 , Patrick Sadoghi  5 , Jutta Dierkes  6 , Pawel Pludowski  7 , Armin Zittermann  8 , Winfried März  1   9   10 , Stefan Pilz  3
Affiliations
Randomized Controlled Trial

Classification of Vitamin D Status Based on Vitamin D Metabolism: A Randomized Controlled Trial in Hypertensive Patients

Sieglinde Zelzer et al. Nutrients. .

Abstract

Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of "functional vitamin D deficiency", i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs.

Keywords: 24,25-dihydroxyvitamin D; RCT; classification; deficiency; supplementation; vitamin D; vitamin D metabolite ratio.

PubMed Disclaimer

Conflict of interest statement

Winfried März was employed by the company SYNLAB Academy, Synlab Holding Deutschland GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
This figure shows that 25(OH)D is “activated” by 1α-hydroxylase to calcitriol, whereas 24-hydroxylase converts 25(OH)D to 24,25(OH)2D as the first step in vitamin D catabolism. We hypothesize that the catabolism by 24-hydroxylase is reduced in individuals with high vitamin D requirements, e.g., in those with functional vitamin D deficiency.
See this image and copyright information in PMC

References

    1. Bouillon R. Comparative analysis of nutritional guidelines for vitamin D. Nat. Rev. Endocrinol. 2017;13:466–479. doi: 10.1038/nrendo.2017.31. - DOI - PubMed
    1. Buttriss J.L., Lanham-New S.A., Steenson S., Levy L., Swan G.E., Darling A.L., Cashman K.D., Allen R.E., Durrant L.R., Smith C.P., et al. Implementation strategies for improving vitamin D status and increasing vitamin D intake in the UK: Current controversies and future perspectives: Proceedings of the 2nd Rank Prize Funds Forum on vitamin D. Br. J. Nutr. 2022;127:1567–1587. doi: 10.1017/S0007114521002555. - DOI - PMC - PubMed
    1. Pludowski P., Takacs I., Boyanov M., Belaya Z., Diaconu C.C., Mokhort T., Zherdova N., Rasa I., Payer J., Pilz S. Clinical Practice in the Prevention, Diagnosis and Treatment of Vitamin D Deficiency: A Central and Eastern European Expert Consensus Statement. Nutrients. 2022;14:1483. doi: 10.3390/nu14071483. - DOI - PMC - PubMed
    1. Holick M.F. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev. Endocr. Metab. Disord. 2017;18:153–165. doi: 10.1007/s11154-017-9424-1. - DOI - PubMed
    1. Ross A.C., Manson J.E., Abrams S.A., Aloia J.F., Brannon P.M., Clinton S.K., Durazo-Arvizu R.A., Gallagher J.C., Gallo R.L., Jones G., et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: What clinicians need to know. J. Clin. Endocrinol. Metab. 2011;96:53–58. doi: 10.1210/jc.2010-2704. - DOI - PMC - PubMed

Publication types