Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Hannah TM Contreras - Wellesley College/ MIT
Co-Author(s): Albert Shieh, Department of Medicine, University of California, Los Angeles; Christina Ma, David Geffen School of Medicine; Rene F. Chun, Department of Orthopaedic Surgery, University of California, Los Angeles; Sten Witzel, Department of Orthopaedic Surgery, University of California, Los Angeles; Jonas Wittwer-Schegg, DSM Nutritional Products; Leon Swinkels, Future Diagnostics; Tonnie Huijs, Future Diagnostics; Martin Hewison, Institute of Metabolism and Systems Research, The University of Birmingham; John S. Adams, Department of Medicine, University of California, Los Angeles
Statement of the Problem/Background:
Vitamin D deficiency (25-hydroxyvitamin D [25D] <20 ng/ml) disproportionately affects non-Caucasian individuals. Controversy persists over: 1) how to best restore low 25D levels; and 2) how to best define vitamin D status (total [protein-bound + free] vs. free 25D). Research Question/Hypothesis: The research was designed to: 1) compare the effects of D3 vs. 25D3 on circulating levels of total and free 25D in a multi-ethnic cohort of healthy adults; and 2) determine if change in total or free 25D is more strongly associated with change in PTH, a marker of vitamin D bioactivity. Research Design/Methods Used in the Investigation: Study participants were randomized in blocks of four, stratified by race/ethnicity, to either D3 (60 mcg [2,400 IU]/day) or 25D3 (20 mcg/day) for 16 weeks. Expected D3 and 25D3 content was confirmed by liquid chromatography-mass spectrometry (LC/MS/MS) (Heartland Assays). Serum measurements included total 25D; free 25D; total 1,25-dihydroxyvitamin D (1,25D); calcium; and intact parathyroid hormone (PTH). Results/Summary of the Investigation: Baseline total (16.2 + 3.7 vs. 17.0 + 2.5 ng/ml, p=0.4) and free (4.2 + 0.8 vs. 4.7 + 1.0 pg/ml, p=0.2) 25D were similar between D3 and 25D3 groups. Increases in total (+25.5 ng/ml vs. +13.8 ng/ml, p=0.001) and free (+6.6 pg/ml vs. +3.5 pg/ml, p=0.03) 25D were greater with 25D3 than D3. By 4 weeks, 87.5% of 25D3 participants had total 25D levels >30 ng/ml, compared to 23.1% of D3 participants (p=0.001). These trends were true regardless of race/ethnicity. Longitudinal change in PTH was similarly associated with both total (p=0.01) and free 25D (p=0.04).
Interpretation/Conclusion of Investigation:
25D3 increased total and free 25D levels were more rapidly and robustly associated with change than D3, regardless of ethnicity. Free 25D mirrored but was not more strongly associated with change in PTH than total 25D.
Funder Acknowledgement(s): 1) NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR000124; 2) National Institute of Arthritis and Musculoskeletal and Skin Diseases awards R01AR063910 and P50 AR063020; and 3) UCLA Specialty Training and Advanced Research (STAR) Program.
Faculty Advisor: John S. Adams, firstname.lastname@example.org
Role: Data input and analysis