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Serrano Díaz, N. ., Guío Mahecha, E. ., González, A. ., Plata Paredes, L. ., Quintero Lesmes, D. C. ., & Becerra Bayona, S. . (2017). Cuantificación de vitamina D: de la investigación a la práctica clínica. Biosalud, 16(1), 67–79. https://doi.org/10.17151/biosa.2017.16.1.8
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Las formas biológicamente activas de la vitamina D se han convertido en elementos de gran relevancia en la práctica clínica y la investigación, por lo tanto, su análisis se ha incrementado en años recientes. La vitamina D tiene un papel esencial en la regulación del metabolismo del calcio y fósforo; adicionalmente, esta vitamina es considerada un posible factor preventivo para diversas enfermedades crónicas como la diabetes mellitus tipo 2, algunos tipos de cáncer, cardiovasculares, autoinmunes, enfermedad pulmonar obstructiva crónica y la pre-eclampsia. Debido al posible papel en estas enfermedades y a los pocos estudios comparativos que se han realizado entre éstas y los niveles de vitamina D, los investigadores y clínicos están interesados en usar técnicas confiables y específicas que permitan determinar las concentraciones de vitamina D en el plasma. Sin embargo, no se ha establecido cuál es el mejor biomarcador que refleja la suficiencia de vitamina D y su función, ni tampoco cuál es la mejor técnica para su adecuada cuantificación. El objetivo de esta revisión es describir brevemente el metabolismo de la vitamina D y los retos que existen para su adecuada cuantificación con fines de investigación traslacional.
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1. Plum LA, DeLuca HF. Vitamin D, disease and therapeutic opportunities. Nat Rev Drug Discov. 2010; 9(12):941-955.
2. Albahrani AA, Greaves RF. Fat-soluble vitamins: clinical indications and current challenges for chromatographic measurement. ClinBiochem Rev. 2016; 37(1):27-47.
3. Roth J, Bonner-Weir S, Norman AW, Orci L. Immunocytochemistry of vitamin D-dependent calcium binding protein in chick pancreas: exclusive localization. Endocrinology. 1982; 110(6):2216-2218.
4. Norman AW, Deluca HF. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J ClinNutr. 2008; 88(2):491S-499S.
5. Sullivan SS, Rosen CJ, Halteman WA, Chen TC, Holick MF. Adolescent girls in Maine are at risk for vitamin D insufficiency. J Am Diet Assoc. 2005; 105(6):971-974.
6. Rathish N, Arun M. Vitamin D: the “sunshine” vitamin. J PharmacolPharmacother. 2012; 3(2):118-126.
7. McGreevy C, Williams D. New insights about vitamin D and cardiovascular disease: a narrative review. Ann Intern Med. 2011; 155(12):820-826.
8. Fleischer AB Jr, Fleischer SE. Solar radiation and the incidence and mortality of leading invasive cancers in the United States. Dermatoendocrinol. 2016; 8(1):e1162366.
9. Solidoro P, Bellocchia M, Facchini F. The immunobiological and clinical role of vitamin D in obstructive lung diseases. Minerva Med. 2016; 107(3 Suppl 1):12-19.
10. Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson Hughes B, Eisman JA, et al. IOF Committee of Scientific Advisors (CSA) Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009; 20(11):1807-1820.
11. Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int. 2012; 23(2):675-686.
12. Black LJ, Anderson D, Clarke MW, Ponsonby AL, Lucas RM. Analytical bias in the measurement of serum 25-hydroxyvitamin D concentrations impairs assessment of vitamin D status in clinical and research settings. PLoS One. 2015; 10(8):e0135478.
13. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, 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 ClinEndocrinolMetab. 2011; 96(1):53–58.
14. Amiot-Carlin MJ. Digestion and absorption of lipophilic food micronutrients. In: McClements DJ, Decker EA, editors. Designing functional foods: measuring and controlling food structure breakdown and nutrient absorption. Boca Raton, FL, USA: CRC Press; 2009.
15. Mostafa WZ, Hegazy RA. Vitamin D and the skin: focus on a complex relationship: a review. J Adv Res. 2015; 6(6):793-804.
16. Schuster I. Cytochromes P450 are essential players in the vitamin D signaling system. BiochimBiophysActa. 2010; 1814(1):186-199.
17. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014; 21(3):319-329.
18. White JH. Regulation of intracrine production of 1,25-dihydroxyvitamin D and its role in innate immune defense against infection. Arch BiochemBiophys. 2012; 523(1):58-63.
19. Cândido FG, Bressan J.Vitamin D: link between osteoporosis, obesity, and diabetes? Int J Mol Sci. 2014; 15(4):6569-6591.
20. Panda DK, Miao D, Bolivar I, Li J, Huo R, Hendy GN, et al. Inactivation of the 25-hydroxyvitamin D 1alphahydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis. J Biol Chem. 2004; 279(16):16754-16766.
21. Seamans KM, Cashman KD. Existing and potentially novel functional markers of vitamin D status: a systematic review. Am J ClinNutr. 2009; 89(6):1997S–2008S.
22. Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it? J Am AcadDermatol. 2006; 54(2):301-317.
23. van Driel M, van Leeuwen JP. Vitamin D endocrine system and osteoblasts. Bonekey Rep. 2014; 3:493.
24. Bosworth CR, Levin G, Robinson-Cohen C, Hoofnagle AN, Ruzinski J, Young B, et al. The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease. Kidney Int. 2012; 82(6):693–700.
25. Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol. 2009; 19(2):73-78.
26. Wacker M, Holick MF.Vitamin D - effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013; 5(1):111-148.
27. Zerwekh JE. Blood biomarkers of vitamin D status. Am J ClinNutr. 2008; 87(4):1087S-1091S.
28. Hollis BW. The determination of circulating 25-hydroxyvitamin D: no easy task. J ClinEndocrinolMetab. 2004; 89(7):3149–3151.
29. Guo T, Taylor RL, Singh RJ, Soldin SJ. Simultaneous determination of 12 steroids by isotope dilution liquid chromatography-photospray ionization tandem mass spectrometry. ClinChimActa. 2006; 372(1-2):76–82.
30. Wallace AM, Gibson S, de la Hunty A, Lamberg-Allardt C, Ashwell M. Measurement of 25-hydroxyvitamin D in the clinical laboratory: current procedures, performance characteristics and limitations. Steroids. 2010 Jul; 75(7):477-488.
31. de la Hunty A, Wallace AM, Gibson S, Viljakainen H, Lamberg-Allardt C, Ashwell M. UK Food standards agency workshop 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. 2010; 104(4):612-619.
32. Carter GD, Jones JC. Use of a common standard improves the performance of liquid chromatographytandem mass spectrometry methods for serum 25-hydroxyvitamin-D. Anal ClinBiochem. 2009; 46(Pt 1):79–81.
33. Aronov PA, Hall LM, Dettmer K, Stephensen CB, Hammock BD. Metabolic profiling of major vitamin D metabolites using Diels–Alder derivatization and ultra-performance liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem. 2008; 391(5):1917-1930.
34. Ding S, Schoenmakers I, Jones K, Koulman A, Prentice A, Volmer DA. Quantitative determination of vitamin D metabolites in plasma using UHPLC-MS/MS. Anal Bioanal Chem. 2010; 398(2):779-789.
35. Fang H, Yu S, Cheng Q, Cheng X, Han J, Qin X, et al. Determination of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3in human serum using liquidchromatography with tandem mass spectrometry. J Chromatogr B AnalytTechnol Biomed Life Sci. 2016; 1027:19-26.
36. Wang Z, Senn T, Kalhorn T, Zheng XE, Zheng S, Davis CL, et al. Simultaneous measurement of plasma vitamin D3 metabolites including 4β,25-dihydroxyvitamin D(3) using liquid chromatographytandem mass spectrometry. Anal Biochem. 2011; 418(1):126-133.
37. van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res ClinEndocrinolMetab. 2011; 25(4):671–680
38. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Endocrine, evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J ClinEndocrinolMetab. 2011; 96(7):1911–1930.
39. Cashman KD, Dowling KG, Škrabáková Z, Gonzalez-Gross M, Valtueña J, De Henauw S, et al. Vitamin D deficiency in Europe: pandemic? Am J ClinNutr. 2016 Apr; 103(4):1033-1044.
40. Last J. A dictionary of epidemiology. 4th ed. Oxford (United Kingdom): Oxford University Press; 2001.
41. Hilger J, Friedel A, Herr R, Rausch T, Roos F, Wahl DA, et al. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2014; 14; 111(1):23-45.
42. Bouillon R, Van Schoor NM, Gielen E, Boonen S, Mathieu C, Vanderschueren D, et al. Optimal vitamin D status: a critical analysis on the basis of evidence-based medicine. J ClinEndocrinolMetab. 2013; 98(8):E1283-1304.
43. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JPA. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. ross 2014; 348:g2035.
44. Lamberg-Allardt C, Brustad M, Meyer HE, Steingrimsdottir L. Vitamin D - a systematic literature review for the 5th edition of the Nordic Nutrition Recommendations. Food NutrRes. 2013; 57:22671.
45. Health Council of the Netherlands. Evaluation of dietary reference values for vitamin D. 46The Hague: Health Council of the Netherlands, 2012; publication no. 2012/15E.
46. Murphy SP, Poos MI. Dietary reference intakes: summary of applications in dietary assessment. Public Health Nutr. 2002; 6A:843-849.
47. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J ClinNutr. 2007; 85(1):6-18.
48. Kaptein S, Risselada AJ, Boerma EC, Egbers PH, Nieboer P. Life-threatening complications of vitamin D intoxication due to over-the-counter supplements. ClinToxicol (Phila). 2010; 48(5):460-462.
49. Lowe H, Cusano NE, Binkley N, Blaner WS, Bilezikian JP. Vitamin D toxicity due to a commonly available “over the counter” remedy from the Dominican Republic. J ClinEndocrinolMetab. 2011; 96(2):291-295.
50. The DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68500 patients from seven major vitamin D fracture trials in US and Europe. BMJ. 2010; 340:b5463.
51. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014; 2(1):76-89.
52. Schottker B, Jorde R, Peasey A, Thorand B, Jansen EH, Groot L, et al. Vitamin D and mortality: metaanalysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014; 348:g3656.
2. Albahrani AA, Greaves RF. Fat-soluble vitamins: clinical indications and current challenges for chromatographic measurement. ClinBiochem Rev. 2016; 37(1):27-47.
3. Roth J, Bonner-Weir S, Norman AW, Orci L. Immunocytochemistry of vitamin D-dependent calcium binding protein in chick pancreas: exclusive localization. Endocrinology. 1982; 110(6):2216-2218.
4. Norman AW, Deluca HF. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J ClinNutr. 2008; 88(2):491S-499S.
5. Sullivan SS, Rosen CJ, Halteman WA, Chen TC, Holick MF. Adolescent girls in Maine are at risk for vitamin D insufficiency. J Am Diet Assoc. 2005; 105(6):971-974.
6. Rathish N, Arun M. Vitamin D: the “sunshine” vitamin. J PharmacolPharmacother. 2012; 3(2):118-126.
7. McGreevy C, Williams D. New insights about vitamin D and cardiovascular disease: a narrative review. Ann Intern Med. 2011; 155(12):820-826.
8. Fleischer AB Jr, Fleischer SE. Solar radiation and the incidence and mortality of leading invasive cancers in the United States. Dermatoendocrinol. 2016; 8(1):e1162366.
9. Solidoro P, Bellocchia M, Facchini F. The immunobiological and clinical role of vitamin D in obstructive lung diseases. Minerva Med. 2016; 107(3 Suppl 1):12-19.
10. Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson Hughes B, Eisman JA, et al. IOF Committee of Scientific Advisors (CSA) Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009; 20(11):1807-1820.
11. Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int. 2012; 23(2):675-686.
12. Black LJ, Anderson D, Clarke MW, Ponsonby AL, Lucas RM. Analytical bias in the measurement of serum 25-hydroxyvitamin D concentrations impairs assessment of vitamin D status in clinical and research settings. PLoS One. 2015; 10(8):e0135478.
13. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, 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 ClinEndocrinolMetab. 2011; 96(1):53–58.
14. Amiot-Carlin MJ. Digestion and absorption of lipophilic food micronutrients. In: McClements DJ, Decker EA, editors. Designing functional foods: measuring and controlling food structure breakdown and nutrient absorption. Boca Raton, FL, USA: CRC Press; 2009.
15. Mostafa WZ, Hegazy RA. Vitamin D and the skin: focus on a complex relationship: a review. J Adv Res. 2015; 6(6):793-804.
16. Schuster I. Cytochromes P450 are essential players in the vitamin D signaling system. BiochimBiophysActa. 2010; 1814(1):186-199.
17. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014; 21(3):319-329.
18. White JH. Regulation of intracrine production of 1,25-dihydroxyvitamin D and its role in innate immune defense against infection. Arch BiochemBiophys. 2012; 523(1):58-63.
19. Cândido FG, Bressan J.Vitamin D: link between osteoporosis, obesity, and diabetes? Int J Mol Sci. 2014; 15(4):6569-6591.
20. Panda DK, Miao D, Bolivar I, Li J, Huo R, Hendy GN, et al. Inactivation of the 25-hydroxyvitamin D 1alphahydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis. J Biol Chem. 2004; 279(16):16754-16766.
21. Seamans KM, Cashman KD. Existing and potentially novel functional markers of vitamin D status: a systematic review. Am J ClinNutr. 2009; 89(6):1997S–2008S.
22. Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it? J Am AcadDermatol. 2006; 54(2):301-317.
23. van Driel M, van Leeuwen JP. Vitamin D endocrine system and osteoblasts. Bonekey Rep. 2014; 3:493.
24. Bosworth CR, Levin G, Robinson-Cohen C, Hoofnagle AN, Ruzinski J, Young B, et al. The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease. Kidney Int. 2012; 82(6):693–700.
25. Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol. 2009; 19(2):73-78.
26. Wacker M, Holick MF.Vitamin D - effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013; 5(1):111-148.
27. Zerwekh JE. Blood biomarkers of vitamin D status. Am J ClinNutr. 2008; 87(4):1087S-1091S.
28. Hollis BW. The determination of circulating 25-hydroxyvitamin D: no easy task. J ClinEndocrinolMetab. 2004; 89(7):3149–3151.
29. Guo T, Taylor RL, Singh RJ, Soldin SJ. Simultaneous determination of 12 steroids by isotope dilution liquid chromatography-photospray ionization tandem mass spectrometry. ClinChimActa. 2006; 372(1-2):76–82.
30. Wallace AM, Gibson S, de la Hunty A, Lamberg-Allardt C, Ashwell M. Measurement of 25-hydroxyvitamin D in the clinical laboratory: current procedures, performance characteristics and limitations. Steroids. 2010 Jul; 75(7):477-488.
31. de la Hunty A, Wallace AM, Gibson S, Viljakainen H, Lamberg-Allardt C, Ashwell M. UK Food standards agency workshop 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. 2010; 104(4):612-619.
32. Carter GD, Jones JC. Use of a common standard improves the performance of liquid chromatographytandem mass spectrometry methods for serum 25-hydroxyvitamin-D. Anal ClinBiochem. 2009; 46(Pt 1):79–81.
33. Aronov PA, Hall LM, Dettmer K, Stephensen CB, Hammock BD. Metabolic profiling of major vitamin D metabolites using Diels–Alder derivatization and ultra-performance liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem. 2008; 391(5):1917-1930.
34. Ding S, Schoenmakers I, Jones K, Koulman A, Prentice A, Volmer DA. Quantitative determination of vitamin D metabolites in plasma using UHPLC-MS/MS. Anal Bioanal Chem. 2010; 398(2):779-789.
35. Fang H, Yu S, Cheng Q, Cheng X, Han J, Qin X, et al. Determination of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3in human serum using liquidchromatography with tandem mass spectrometry. J Chromatogr B AnalytTechnol Biomed Life Sci. 2016; 1027:19-26.
36. Wang Z, Senn T, Kalhorn T, Zheng XE, Zheng S, Davis CL, et al. Simultaneous measurement of plasma vitamin D3 metabolites including 4β,25-dihydroxyvitamin D(3) using liquid chromatographytandem mass spectrometry. Anal Biochem. 2011; 418(1):126-133.
37. van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res ClinEndocrinolMetab. 2011; 25(4):671–680
38. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Endocrine, evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J ClinEndocrinolMetab. 2011; 96(7):1911–1930.
39. Cashman KD, Dowling KG, Škrabáková Z, Gonzalez-Gross M, Valtueña J, De Henauw S, et al. Vitamin D deficiency in Europe: pandemic? Am J ClinNutr. 2016 Apr; 103(4):1033-1044.
40. Last J. A dictionary of epidemiology. 4th ed. Oxford (United Kingdom): Oxford University Press; 2001.
41. Hilger J, Friedel A, Herr R, Rausch T, Roos F, Wahl DA, et al. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2014; 14; 111(1):23-45.
42. Bouillon R, Van Schoor NM, Gielen E, Boonen S, Mathieu C, Vanderschueren D, et al. Optimal vitamin D status: a critical analysis on the basis of evidence-based medicine. J ClinEndocrinolMetab. 2013; 98(8):E1283-1304.
43. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JPA. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. ross 2014; 348:g2035.
44. Lamberg-Allardt C, Brustad M, Meyer HE, Steingrimsdottir L. Vitamin D - a systematic literature review for the 5th edition of the Nordic Nutrition Recommendations. Food NutrRes. 2013; 57:22671.
45. Health Council of the Netherlands. Evaluation of dietary reference values for vitamin D. 46The Hague: Health Council of the Netherlands, 2012; publication no. 2012/15E.
46. Murphy SP, Poos MI. Dietary reference intakes: summary of applications in dietary assessment. Public Health Nutr. 2002; 6A:843-849.
47. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J ClinNutr. 2007; 85(1):6-18.
48. Kaptein S, Risselada AJ, Boerma EC, Egbers PH, Nieboer P. Life-threatening complications of vitamin D intoxication due to over-the-counter supplements. ClinToxicol (Phila). 2010; 48(5):460-462.
49. Lowe H, Cusano NE, Binkley N, Blaner WS, Bilezikian JP. Vitamin D toxicity due to a commonly available “over the counter” remedy from the Dominican Republic. J ClinEndocrinolMetab. 2011; 96(2):291-295.
50. The DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68500 patients from seven major vitamin D fracture trials in US and Europe. BMJ. 2010; 340:b5463.
51. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014; 2(1):76-89.
52. Schottker B, Jorde R, Peasey A, Thorand B, Jansen EH, Groot L, et al. Vitamin D and mortality: metaanalysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014; 348:g3656.
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