Reference values for free 25-hydroxy-vitamin D based on established total 25-hydroxy-vitamin D reference values. Issue 210 (June 2021)

• Record Type: Journal Article
• Authors: Zeng, Shufei; Chu, Chang; Doebis, Cornelia; von Baehr, Volker; Hocher, Berthold
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 210(2021)
• Publication Date: 2021-06
• Subjects: Free 25-hydroxyvitamin D -- Total 25-hydroxyvitamin D -- Recommendations -- Vitamin D; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2021.105877
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Free but not total 25(OH) vitamin D passes the lipophilic cell membrane and interacts with the nuclear vitamin D receptor. As of today, there are no established guidelines based on clinical studies for the clinical use of free 25(OH) vitamin D. By correlating free and total 25(OH) vitamin D messurements in 5060 patients and considering established international guidelines for total 25(OH) vitamin D, we established reference values for free 25(OH) vitamin D suitable for clinical use. Abstract: Measurements of total 25-hydroxyvitamin D (t25(OH)D) are currently primarily used to assess the vitamin D status. The lipophilic cell membrane can only be passed by the un-bound form of 25-hydroxyvitamin D: free 25-hydroxyvitamin D (f25(OH)D). It is thought that f25(OH)D does reflect its biological actions better than t25(OH)D. However, as of today, there are no established guidelines for the clinical use of f25(OH)D. We analysed 5060 patients with simultaneous measurements of free and total 25(OH). Linear regression was used to study the relationship between free 25(OH)D and total 25(OH)D. We reviewed and used the established t25(OH)D reference values and determined the slope of the relationship between them to calculate reference values for f25(OH)D. F25(OH)D and t25(OH)D showed a strong positive linear (r = 0.8395, p < 0.0001) correlation. The slope of the relationship was 0.2833 ± 0.00257. The recommended threshold level of f25(OH)D is 8.499 pg/mL, corresponding to a target concentration for t25(OH)D of at least 30 ng/mL considered as sufficient in most of the international vitamin D guidelines. The upper limit for vitamin D is less clear in the guidelines. Most experts favour an upper limit for t25(OH)D of 100 ng/mL. This is equivalent to 28.330 pg/mL f25OHD. We established based on international guidelines for t25(OH)D reference values for f25(OH)D that are urgently needed for clinical use of f25(OH)D. However, clinical studies with f25(OH)D to confirm our suggestions are needed but will take time.