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Effects of High-Dose Vitamin D2 Versus D3 on Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance.
J Clin Endocrinol Metab. 2016 08; 101(8):3070-8.JC

Abstract

CONTEXT

Controversy persists over: 1) how best to restore low serum 25-hydroxyvitamin D (25D) levels (vitamin D2 [D2] vs vitamin D3 [D3]); 2) how best to define vitamin D status (total [protein-bound + free] vs free 25D); and 3) how best to assess the bioactivity of free 25D.

OBJECTIVE

To assess: 1) the effects of D2 vs D3 on serum total and free 25D; and 2) whether change in intact PTH (iPTH) is more strongly associated with change in total vs free 25D.

DESIGN

Participants previously enrolled in a D2 vs D3 trial were matched for age, body mass index, and race/ethnicity. Participants received 50 000 IU of D2 or D3 twice weekly for 5 weeks, followed by a 5-week equilibration period. Biochemical assessment was performed at baseline and at 10 weeks.

SETTING AND PARTICIPANTS

Thirty-eight adults (19 D2 and 19 D3) ≥18 years of age with baseline 25D levels <30 ng/mL were recruited from an academic ambulatory osteoporosis clinic.

OUTCOME MEASURES

Serum measures were total 25D, free 25D (directly measured), 1,25-dihydroxyvitamin D, calcium, and iPTH. Urine measure was fasting calcium:creatinine ratio.

RESULTS

Baseline total (22.2 ± 3.3 vs 23.3 ± 7.2 ng/mL; P = .5) and free (5.4 ± 0.8 vs 5.3 ± 1.7 pg/mL; P = .8) 25D levels were similar between D2 and D3 groups. Increases in total (+27.6 vs +12.2 ng/mL; P = .001) and free (+3.6 vs +6.2 pg/mL; P = .02) 25D levels were greater with D3 vs D2. Percentage change in iPTH was significantly associated with change in free (but not total) 25D, without and with adjustment for supplementation regimen, change in 1,25-dihydroxyvitamin D, and change in calcium.

CONCLUSIONS

D3 increased total and free 25D levels to a greater extent than D2. Free 25D may be superior to total 25D as a marker of vitamin D bioactivity.

Authors+Show Affiliations

Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.Department of Medicine, Division of Geriatrics (A.S.), and Department of Orthopaedic Surgery (R.F.C., S.W., B.M., B.R., J.S.A.), University of California, Los Angeles, Los Angeles, California 90095; David Geffen School of Medicine (C.M.), Los Angeles, California 90095; Future Diagnostics (L.S., T.H.), 6603 BN Wijchen, The Netherlands; Esoterix, Inc. (S.P., B.H.), Austin, Texas 78744; and Institute of Metabolism and Systems Research (M.H.), The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

27192696

Citation

Shieh, Albert, et al. "Effects of High-Dose Vitamin D2 Versus D3 On Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance." The Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 8, 2016, pp. 3070-8.
Shieh A, Chun RF, Ma C, et al. Effects of High-Dose Vitamin D2 Versus D3 on Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance. J Clin Endocrinol Metab. 2016;101(8):3070-8.
Shieh, A., Chun, R. F., Ma, C., Witzel, S., Meyer, B., Rafison, B., Swinkels, L., Huijs, T., Pepkowitz, S., Holmquist, B., Hewison, M., & Adams, J. S. (2016). Effects of High-Dose Vitamin D2 Versus D3 on Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance. The Journal of Clinical Endocrinology and Metabolism, 101(8), 3070-8. https://doi.org/10.1210/jc.2016-1871
Shieh A, et al. Effects of High-Dose Vitamin D2 Versus D3 On Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance. J Clin Endocrinol Metab. 2016;101(8):3070-8. PubMed PMID: 27192696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of High-Dose Vitamin D2 Versus D3 on Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance. AU - Shieh,Albert, AU - Chun,Rene F, AU - Ma,Christina, AU - Witzel,Sten, AU - Meyer,Briana, AU - Rafison,Brandon, AU - Swinkels,Leon, AU - Huijs,Tonnie, AU - Pepkowitz,Sam, AU - Holmquist,Brett, AU - Hewison,Martin, AU - Adams,John S, Y1 - 2016/05/18/ PY - 2016/5/19/entrez PY - 2016/5/19/pubmed PY - 2017/6/27/medline SP - 3070 EP - 8 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 101 IS - 8 N2 - CONTEXT: Controversy persists over: 1) how best to restore low serum 25-hydroxyvitamin D (25D) levels (vitamin D2 [D2] vs vitamin D3 [D3]); 2) how best to define vitamin D status (total [protein-bound + free] vs free 25D); and 3) how best to assess the bioactivity of free 25D. OBJECTIVE: To assess: 1) the effects of D2 vs D3 on serum total and free 25D; and 2) whether change in intact PTH (iPTH) is more strongly associated with change in total vs free 25D. DESIGN: Participants previously enrolled in a D2 vs D3 trial were matched for age, body mass index, and race/ethnicity. Participants received 50 000 IU of D2 or D3 twice weekly for 5 weeks, followed by a 5-week equilibration period. Biochemical assessment was performed at baseline and at 10 weeks. SETTING AND PARTICIPANTS: Thirty-eight adults (19 D2 and 19 D3) ≥18 years of age with baseline 25D levels <30 ng/mL were recruited from an academic ambulatory osteoporosis clinic. OUTCOME MEASURES: Serum measures were total 25D, free 25D (directly measured), 1,25-dihydroxyvitamin D, calcium, and iPTH. Urine measure was fasting calcium:creatinine ratio. RESULTS: Baseline total (22.2 ± 3.3 vs 23.3 ± 7.2 ng/mL; P = .5) and free (5.4 ± 0.8 vs 5.3 ± 1.7 pg/mL; P = .8) 25D levels were similar between D2 and D3 groups. Increases in total (+27.6 vs +12.2 ng/mL; P = .001) and free (+3.6 vs +6.2 pg/mL; P = .02) 25D levels were greater with D3 vs D2. Percentage change in iPTH was significantly associated with change in free (but not total) 25D, without and with adjustment for supplementation regimen, change in 1,25-dihydroxyvitamin D, and change in calcium. CONCLUSIONS: D3 increased total and free 25D levels to a greater extent than D2. Free 25D may be superior to total 25D as a marker of vitamin D bioactivity. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/27192696/Effects_of_High_Dose_Vitamin_D2_Versus_D3_on_Total_and_Free_25_Hydroxyvitamin_D_and_Markers_of_Calcium_Balance_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2016-1871 DB - PRIME DP - Unbound Medicine ER -