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Can vitamin D metabolite measurements facilitate a “treat-to-target” paradigm to guide vitamin D supplementation?

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Abstract

Summary

Substantial variability exists in the serum 25(OH)D increase observed in response to vitamin D supplementation. Measurement of circulating cholecalciferol and 24,25(OH)2D, as indicators of vitamin D absorption and degradation, respectively, account for approximately half of the variation in serum 25(OH)D observed following supplementation.

Introduction

Vitamin D supplementation produces a variable response in serum 25(OH)D. This variability likely reflects, in part, differences in vitamin D absorption and/or degradation. Despite this variation in response, virtually all expert recommendations endorse a fixed vitamin D supplementation dose, an approach also used in most prospective studies. Such utilization of a single vitamin D dose does not assure attaining any pre-specified target 25(OH)D level, thereby compromising clinical care and prospective supplementation trials. This study begins addressing this weakness by exploring the feasibility of vitamin D metabolite measurements to predict serum 25(OH)D level attained following supplementation.

Methods

Ninety-one community-dwelling postmenopausal women with baseline 25(OH)D of 10–30 ng/mL received oral vitamin D3, 2300 or 2500 IU, daily for 4–6 months. Serum 25(OH)D, cholecalciferol (D3), and 24,25(OH)2D were measured before and at the end of supplementation to determine if metabolite concentrations allow prediction of the 25(OH)D level attained.

Results

From baseline and follow-up data, we derived a multiple linear regression model predicting posttreatment 25(OH)D as follows: final 25(OH)D = 8.3 + (1.05*initial 25(OH)D) − (7.7*initial 24,25(OH)2D) + (0.53*final D3) + (4.2*final 24,25(OH)2D). This model has an adjusted R 2 = 0.55, thus accounting for approximately half of the observed variance in the final 25(OH)D level.

Conclusions

The contributions of circulating cholecalciferol and 24,25(OH)2D to this predictive model can be considered as indicators of intestinal absorption and clearance, respectively. This paradigm requires further study; it may allow efficient “treat-to-25(OH)D-target” strategies useful in optimizing prospective studies and clinical practice.

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References

  1. Aloia JF, Patel M, DiMaano R, Li-Ng M, Talwar SA, Mikhail M, Pllack S, Yeh JK (2008) Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr 87:1952–1958

    CAS  PubMed  Google Scholar 

  2. Binkley N, Gemar D, Engelke J, Gangnon R, Ramamurthy R, Krueger D, Drezner MK (2011) Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab 96:981–988

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Aguirre Castaneda R, Nader N, Weaver A, Singh R, Kumar S (2012) Response to vitamin D3 supplementation in obese and non-obese Caucasian adolescents. Horm Res Paediatr 78:226–231

    Article  CAS  PubMed  Google Scholar 

  4. Hollis BW (2005) Detection of vitamin D and its major metabolites. In: Feldman D, Pike JW, Glorieus FH (eds) Vitamin D, 2nd edn. Elsevier, Burlington, pp 931–950

    Chapter  Google Scholar 

  5. Thompson GR, Lewis B, Booth CC (1966) Absorption of vitamin D3-3H in control subjects and patients with intestinal malabsorption. J Clin Invest 45:94–101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Leichtmann GA, Bengoa JM, Bolt MJG, Sitrin MD (1991) Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in pathients with both Crohn’s disease and intestinal resection. Am J Clin Nutr 54:548–552

    CAS  PubMed  Google Scholar 

  7. Sitrin MD, Bengoa JM (1987) Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in chronic cholestatic liveer disease. Am J Clin Nutr 46:1011–1015

    CAS  PubMed  Google Scholar 

  8. Davies M, Mawer EB, Krawitt EL (1980) Comparative absorption of vitamin D3 and 25-hydroxyvitamin D3 in intestinal disease. Gut 21:287–292

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Wagner D, Hanwell HE, Schnabl K, Yazdanpanah M, Kimball S, Fu L, Sidhom G, Rousseau D, Cole DEC, Vieth R (2011) The ratio of serum 24, 25-dihydroxyvitamin D3 to serum 25-hydroxyvitamin D3 is predictive of 25-hydroxyvitamin D3 response to vitamin D3 supplementation. J Steroid Biochem Mol Biol 126:72–77

    Article  CAS  PubMed  Google Scholar 

  10. de Boer IH, Sachs MC, Chonchol M, et al. (2014) Estimated GFR and circulating 24,25-dihydroxyvitamin D concentration: a participant-level analysis of 5 cohort studies and clinical trials. Am J Kidney Dis

  11. de la Hunty A, Wallace AM, Gibson S, Viljakainen H, Lamberg-Allardt C, Ashwell M (2010) UK foods standards agency workship consensus report: the choice of method for measuring 25-hydroxyvitamin D to estimate vitamin D status for the UK National Diet and Nutrition Survey. Br J Nutr 104:612–619

    Article  PubMed  Google Scholar 

  12. Cipriani C, Romagnoli E, Pepe J, Russo S, Carlucci L, Piemonte S, Nieddu L, McMahon DJ, Singh R, Minisola S (2013) Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis. J Clin Endocrinol Metab 98:2709–2715

    Article  CAS  PubMed  Google Scholar 

  13. Thacher TD, Fischer PR, Obadofin MO, Levine MA, Singh RJ, Pettifor JM (2010) Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets. J Bone Miner Res 25:1988–1995

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Burild A, Frandsen HL, Jakobsen J. (2014) Simultaneous quantification of vitamin D, 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in human serum by LC-MS/MS. Scand J Clin Lab Invest

  15. Kaufmann M, Gallagher C, Peacock M, et al. (2014) Clinical utility of simultaneous quantitation of 25-hydroxyvitamin D & 24,25-dihydroxyvitamin D by LC-MS/MS involving derivatization with DMEQ-TAD. J Clin Endocrinol Metab jc20134388

  16. Heaney RP (2012) Vitamin D—baseline status and effective dose. N Engl J Med 367:77–78

    Article  CAS  PubMed  Google Scholar 

  17. Talwar SA, Aloia JF, Pollack S, Yeh JK (2007) Dose response to vitamin D supplementation among postmenopausal African American women. Am J Clin Nutr 86:1657–1662

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Heaney RP (2012) Vitamin D—baseline status and effective dose. N Engl J Med 367:77–78

    Article  CAS  PubMed  Google Scholar 

  19. Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B et al (2013) Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES. J Clin Endocrinol Metab 98:3001–3009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Stolzenberg-Solomon RZ, Jacobs EJ, Arslan AA et al (2010) Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: cohort consortium vitamin D pooling project of rarer cancers. Am J Epidemiol 172:81–93

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Osteoporosis Clinical Research Program, University of Wisconsin, 2870 University Avenue, Suite 100, Madison, WI, 53705, USA

    N. Binkley, D. Krueger & M. K. Drezner

  2. Creighton University, Omaha, NE, USA

    J. Lappe

  3. Mayo Clinic, Rochester, MN, USA

    R. J. Singh & S. Khosla

  4. Clement J Zablocki VAMC, Milwaukee, WI, USA

    R. D. Blank

  5. Medical College of Wisconsin, Milwaukee, WI, USA

    R. D. Blank

Authors
  1. N. Binkley
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  2. J. Lappe
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  3. R. J. Singh
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  4. S. Khosla
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  5. D. Krueger
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  6. M. K. Drezner
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  7. R. D. Blank
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Correspondence to N. Binkley.

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Binkley, N., Lappe, J., Singh, R.J. et al. Can vitamin D metabolite measurements facilitate a “treat-to-target” paradigm to guide vitamin D supplementation?. Osteoporos Int 26, 1655–1660 (2015). https://doi.org/10.1007/s00198-014-3010-0

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  • DOI: https://doi.org/10.1007/s00198-014-3010-0

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