Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study

Karin Amrein, Harald Sourij, Gerit Wagner, Alexander Holl, Thomas R Pieber, Karl Heinz Smolle, Tatjana Stojakovic, Christian Schnedl, Harald Dobnig, Karin Amrein, Harald Sourij, Gerit Wagner, Alexander Holl, Thomas R Pieber, Karl Heinz Smolle, Tatjana Stojakovic, Christian Schnedl, Harald Dobnig

Abstract

Introduction: Vitamin D deficiency is encountered frequently in critically ill patients and might be harmful. Current nutrition guidelines recommend very low vitamin D doses. The objective of this trial was to evaluate the safety and efficacy of a single oral high-dose vitamin D3 supplementation in an intensive care setting over a one-week observation period.

Methods: This was a randomized, double-blind, placebo-controlled pilot study in a medical ICU at a tertiary care university center in Graz, Austria. Twenty-five patients (mean age 62 ± 16 yrs) with vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) ≤ 20 ng/ml] and an expected stay in the ICU >48 hours were included and randomly received either 540,000 IU (corresponding to 13.5 mg) of cholecalciferol (VITD) dissolved in 45 ml herbal oil or matched placebo (PBO) orally or via feeding tube.

Results: The mean serum 25(OH)D increase in the intervention group was 25 ng/ml (range 1-47 ng/ml). The highest 25(OH)D level reached was 64 ng/ml, while two patients showed a small (7 ng/ml) or no response (1 ng/ml). Hypercalcemia or hypercalciuria did not occur in any patient. From day 0 to day 7, total serum calcium levels increased by 0.10 (PBO) and 0.15 mmol/L (VITD; P < 0.05 for both), while ionized calcium levels increased by 0.11 (PBO) and 0.05 mmol/L (VITD; P < 0.05 for both). Parathyroid hormone levels decreased by 19 and 28 pg/ml (PBO and VITD, ns) over the seven days, while 1,25(OH)D showed a transient significant increase in the VITD group only.

Conclusions: This pilot study shows that a single oral ultra-high dose of cholecalciferol corrects vitamin D deficiency within 2 days in most patients without causing adverse effects like hypercalcemia or hypercalciuria. Further research is needed to confirm our results and establish whether vitamin D supplementation can affect the clinical outcome of vitamin D deficient critically ill patients. EUDRACT NUMBER: 2009-012080-34 GERMAN CLINICAL TRIALS REGISTER (DRKS): DRKS00000750.

Figures

Figure 1
Figure 1
Mean 25-hydroxyvitamin D levels (±SEM) after a single enteral dose of 540,000 IU vitamin D3 or placebo in vitamin D deficient patients at a medical ICU. The numbers given below the study days refer to the number of patients per group.

References

    1. Carlstedt F, Lind L, Rastad J, Stjernstrom H, Wide L, Ljunghall S. Parathyroid hormone and ionized calcium levels are related to the severity of illness and survival in critically ill patients. Eur J Clin Invest. 1998;28:898–903. doi: 10.1046/j.1365-2362.1998.00391.x.
    1. Forsythe RM, Wessel CB, Billiar TR, Angus DC, Rosengart MR. Parenteral calcium for intensive care unit patients. Cochrane Database Syst Rev. 2008;8:CD006163.
    1. Hastbacka J, Pettila V. Prevalence and predictive value of ionized hypocalcemia among critically ill patients. Acta Anaesthesiol Scand. 2003;47:1264–1269. doi: 10.1046/j.1399-6576.2003.00236.x.
    1. Lee P, Milliken S, Center JR. Hypocalcaemic cardiac failure post BMT secondary to unrecognized vitamin D deficiency. Bone Marrow Transplant. 2008;42:363–364. doi: 10.1038/bmt.2008.178.
    1. Lee P, Samaras K, Glanville AR, Center JR. Transplant recipients on the edge of the hypocalcemia abyss. J Heart Lung Transplant. 2009;28:93–95. doi: 10.1016/j.healun.2008.09.010.
    1. Lee P, Eisman JA, Center JR. Vitamin D deficiency in critically ill patients. N Engl J Med. 2009;360:1912–1914. doi: 10.1056/NEJMc0809996.
    1. Van den Berghe G, Van Roosbroeck D, Vanhove P, Wouters PJ, De Pourcq L, Bouillon R. Bone turnover in prolonged critical illness: effect of vitamin D. J Clin Endocrinol Metab. 2003;88:4623–4632. doi: 10.1210/jc.2003-030358.
    1. Lucidarme O, Messai E, Mazzoni T, Arcade M, du Cheyron D. Incidence and risk factors of vitamin D deficiency in critically ill patients: results from a prospective observational study. Intensive Care Med. 2010.
    1. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, Tangpricha V. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med. 2009;7:28. doi: 10.1186/1479-5876-7-28.
    1. Krishnan A, Ochola J, Mundy J, Jones M, Kruger P, Duncan E, Venkatesh B. Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients. Crit Care. 2009;14:R216. doi: 10.1186/cc9341.
    1. Louw JA, Werbeck A, Louw ME, Kotze TJ, Cooper R, Labadarios D. Blood vitamin concentrations during the acute-phase response. Crit Care Med. 1992;20:934–941. doi: 10.1097/00003246-199207000-00007.
    1. Vasilaki AT, Leivaditi D, Talwar D, Kinsella J, Duncan A, O'Reilly DS, McMillan DC. Assessment of vitamin E status in patients with systemic inflammatory response syndrome: plasma, plasma corrected for lipids or red blood cell measurements? Clin Chim Acta. 2009;409:41–45. doi: 10.1016/j.cca.2009.08.008.
    1. Galloway P, McMillan DC, Sattar N. Effect of the inflammatory response on trace element and vitamin status. Ann Clin Biochem. 2000;37:289–297. doi: 10.1258/0004563001899429.
    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281. doi: 10.1056/NEJMra070553.
    1. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. pp. 1340–1349.
    1. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay M. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–776. doi: 10.1210/er.2008-0004.
    1. Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney Int. 2010;78:140–145. doi: 10.1038/ki.2010.17.
    1. Lee P, Nair P, Eisman JA, Center JR. Vitamin D deficiency in the intensive care unit: an invisible accomplice to morbidity and mortality? Intensive Care Med. 2009;35:2028–2032. doi: 10.1007/s00134-009-1642-x.
    1. Kelly DG. Guidelines and available products for parenteral vitamins and trace elements. JPEN J Parenter Enteral Nutr. 2002;26:S34–36. doi: 10.1177/014860710202600510.
    1. Kreymann KG, Berger MM, Deutz NE, Hiesmayr M, Jolliet P, Kazandjiev G, Nitenberg G, van den Berghe G, Wernerman J, Ebner C, Hartl W, Heymann C, Spies C. ESPEN Guidelines on Enteral Nutrition: intensive care. Clin Nutr. 2006;25:210–223. doi: 10.1016/j.clnu.2006.01.021.
    1. Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, Griffiths R, Kreyman G, Leverve X, Pichard C. Espen. ESPEN Guidelines on Parenteral Nutrition: intensive care. Clin Nutr. 2009;28:387–400. doi: 10.1016/j.clnu.2009.04.024.
    1. Vieth R. Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr. 2006;136:1117–1122.
    1. Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IRL. High-dose oral vitamin D3 supplementation in the elderly. Osteoporos Int. 2009;20:1407–1415. doi: 10.1007/s00198-008-0814-9.
    1. von Restorff C, Bischoff-Ferrari HA, Theiler R. High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency. Bone. 2009;45:747–749. doi: 10.1016/j.bone.2009.06.012.
    1. Mata-Granados JM, Vargas-Vasserot J, Ferreiro-Vera C, Luque de Castro MD, Pavon RG, Quesada Gomez JM. Evaluation of vitamin D endocrine system (VDES) status and response to treatment of patients in intensive care units (ICUs) using an on-line SPE-LC-MS/MS method. J Steroid Biochem Mol Biol. 2010.
    1. Whyte MP, Haddad JG Jr, Walters DD, Stamp TC. Vitamin D bioavailability: serum 25-hydroxyvitamin D levels in man after oral, subcutaneous, intramuscular, and intravenous vitamin D administration. J Clin Endocrinol Metab. 1979;48:906–911. doi: 10.1210/jcem-48-6-906.
    1. Lawson DE, Sedrani SH, Douglas J. Interrelationships in rats of tissue pools of cholecalciferol and 25-hydroxycholecalciferol formed in u.v. light. Biochem J. 1986;233:535–540.
    1. Witham MD, Crighton LJ, Gillespie ND, Struthers AD, McMurdo ME. The effects of vitamin D supplementation on physical function and quality of life in older patients with heart failure: a randomized controlled trial. Circ Heart Fail. 2010;3:195–201. doi: 10.1161/CIRCHEARTFAILURE.109.907899.

Source: PubMed

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