Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun 4;6(6):CD008482.
doi: 10.1002/14651858.CD008482.pub6.

Vitamin K supplementation for cystic fibrosis

Vanitha A Jagannath  1 , Vidhu Thaker  2 , Anne B Chang  3 , Amy I Price  4
Affiliations

Vitamin K supplementation for cystic fibrosis

Vanitha A Jagannath et al. Cochrane Database Syst Rev. .

Abstract

Background: Malabsorption and deficiency of fat-soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an important role in both blood coagulation and bone formation, hence the role of supplementation of vitamin K in this category needs to be reviewed. This is an updated version of the review.

Objectives: To assess the effects of vitamin K supplementation in people with cystic fibrosis and to investigate the hypotheses that vitamin K will decrease deficiency-related coagulopathy, increase bone mineral density, decrease risk of fractures and improve quality of life in people with CF. Also to determine the optimal dose and route of administration of vitamin K for people with CF (for both routine and therapeutic use).

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 12 August 2019.

Selection criteria: Randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in patients with cystic fibrosis.

Data collection and analysis: Two authors independently screened papers, extracted trial details and assessed their risk of bias. The quality of the evidence was assessed using the GRADE criteria.

Main results: Three trials (total 70 participants, aged 8 to 46 years) assessed as having a moderate risk of bias were included. One trial compared vitamin K to placebo, a second to no supplementation and the third compared two doses of vitamin K. No trial in either comparison reported our primary outcomes of coagulation and quality of life or the secondary outcomes of nutritional parameters and adverse events. Vitamin K versus control Two trials compared vitamin K to control, but data were not available for analysis. One 12-month trial (n = 38) compared 10 mg vitamin K daily or placebo in a parallel design and one trial (n = 18) was of cross-over design with no washout period and compared 5 mg vitamin K/week for four-weeks to no supplementation for four-weeks. Only the 12-month trial reported on the primary outcome of bone formation; we are very uncertain whether vitamin K supplementation has any effect on bone mineral density at the femoral hip or lumbar spine (very low-quality evidence). Both trials reported an increase in serum vitamin K levels and a decrease in undercarboxylated osteocalcin levels. The cross-over trial also reported that levels of proteins induced by vitamin K absence (PIVKA) showed a decrease and a return to normal following supplementation, but due to the very low-quality evidence we are not certain that this is due to the intervention. High-dose versus low-dose vitamin K One parallel trial (n = 14) compared 1 mg vitamin K/day to 5 mg vitamin K/day for four weeks. The trial did report that there did not appear to be any difference in serum undercarboxylated osteocalcin or vitamin K levels (very low-quality evidence). While the trial reported that serum vitamin K levels improved with supplementation, there was no difference between the high-dose and low-dose groups.

Authors' conclusions: There is very low-quality evidence of any effect of vitamin K in people with cystic fibrosis. While there is no evidence of harm, until better evidence is available the ongoing recommendations by national CF guidelines should be followed.

PubMed Disclaimer

Conflict of interest statement

Anne Chang declares she has received multiple grants from the National Health and Medical Research Council (Australia), but none of these relate to the subject matter of this review.

The remaining authors declare no financial conflicts of interest and that they do not have any associations with any parties who may have vested interests in the results of this review.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: 1 mg versus 5 mg oral vitamin k, Outcome 1: Serum % uncarboxylated osteocalcin
1.2
1.2. Analysis
Comparison 1: 1 mg versus 5 mg oral vitamin k, Outcome 2: Serum vitamin k levels
See this image and copyright information in PMC

Update of

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Beker 1997 {published data only}
    1. Beker LT, Ahrens RA, Fink RJ, O'Brien ME, Davidson KW, Sokoll LJ, et al. Effect of vitamin K1 supplementation on vitamin K status in cystic fibrosis patients. Journal of Pediatric Gastroenterology and Nutrition 1997;24(5):512-7. [CFGD REGISTER: GN61b] [PMID: ] - PubMed
    1. Beker LT, Ahrens RA, Fink RJ, Sadowski JA, Davidson KW, Sokoll LJ, et al. Abnormal Vitamin K status in cystic fibrosis patients. Pediatric Pulmonology 1994;18 Suppl 10:358. [CFGD REGISTER: GN61a] - PubMed
Drury 2008 {published and unpublished data}
    1. Drury D, Grey VL, Ferland G, Gundberg C, Lands LC. Efficacy of high dose phylloquinone in correcting vitamin K deficiency in cystic fibrosis. Journal of Cystic Fibrosis 2008;7(5):457-9. [CFGD REGISTER: GN131] [PMID: ] - PubMed
Kuitert 2010 {published and unpublished data}
    1. EUCTR2006-000945-20-GB. To investigate the effect of vitamin K supplementation on markers of bone turnover and bone density in adolescents and adults with cystic fibrosis - Vitamin K supplementation in Cystic Fibrosis. www.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2006-000945-20-GB (first received 18 September 2006). [CENTRAL: CN-01814462] [CFGD REGISTER: CO47b]
    1. ISRCTN14200211. Investigating the effect of vitamin K supplementation on markers of bone turnover and bone density in adolescents and adults with cystic fibrosis. www.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN14200211 (first received 09 May 2008). [CENTRAL: CN-01816363] [CFGD REGISTER: CO47c]
    1. Powell M, Kuitert L. Effect of vitamin K supplementation over one year on bone health in adolescents and adults with cystic fibrosis. Pediatric Pulmonology 2010;45(S33):421. [ABSTRACT NO: 556] [CFGD REGISTER: CO47]

References to studies excluded from this review

Cornelissen 1992 {published data only}
    1. Cornelissen EA, Lieburg AF, Motohara K, Oostrom CG. Vitamin K status in cystic fibrosis. Acta Paediatrica 1992;81(9):658-61. [PMID: ] - PubMed
Grey 2008 {published data only}
    1. Grey V, Atkinson S, Drury D, Casey L, Ferland G, Gundberg C, et al. Prevalence of low bone mass and deficiencies of vitamins D and K in pediatric patients with cystic fibrosis from 3 Canadian centers. Pediatrics 2008;122(5):1014-20. [PMID: ] - PubMed
Mosler 2003 {published data only}
    1. Mosler K, Kries R, Vermeer C, Saupe J, Schmitz T, Schuster A. Assessment of vitamin K deficiency in CF--how much sophistication is useful? Journal of Cystic Fibrosis 2003;2(2):91-6. [PMID: ] - PubMed
Nicolaidou 2006 {published data only}
    1. Nicolaidou P, Stavrinadis I, Loukou I, Papadopoulou A, Georgouli H, Douros K, et al. The effect of vitamin K supplementation on biochemical markers of bone formation in children and adolescents with cystic fibrosis. European Journal of Pediatrics 2006;165(8):540-5. [PMID: ] - PubMed
Wilson 2001 {published data only}
    1. Wilson DC, Rashid M, Durie PR, Tsang A, Kalnins D, Andrew M, et al. Treatment of vitamin K deficiency in cystic fibrosis: Effectiveness of a daily fat-soluble vitamin combination. Journal of Pediatrics 2001;138(6):851-5. [PMID: ] - PubMed

References to studies awaiting assessment

van Hoorn 2003 {published data only}
    1. Hoorn JH, Hendriks JJ, Vermeer C, Forget PP. Vitamin K supplementation in cystic fibrosis. Archives of Disease in Childhood 2003;88(11):974-5. [CFGD REGISTER: GN104] [PMID: ] - PMC - PubMed
van Hoorn 2008 {published data only}
    1. Hoorn JH, Schurgers JJ, Vermeer C, Escher HC, Hendriks HJ. The effect of vitamin K supplementation on bone status in children with cystic fibrosis. Pediatric Pulmonology 2008;43(S31):421. [CFGD REGISTER: GN130]

Additional references

Belle 1991
    1. Belle M, Hanss M, Guillaumont M, Leclercq M, Guinet R. Des-gamma-carboxyprothrombin detection by immunoblotting after polyacrylamide gelaffinoelectrophoresis in human plasmas. Electrophoresis 1991;12(4):294-7. [PMID: ] - PubMed
Belle 1995
    1. Belle M, Brebant R, Guinet R, Leclercq M. Production of a new monoclonal antibody specific to human des-gamma-carboxyprothrombin in the presence of calcium ions. Application to the development of a sensitive ELISA-test. Journal of Immunoassay 1995;16(2):213-29. [PMID: ] - PubMed
Bobadilla 2002
    1. Bobadilla JL, Macek M Jr, Fine JP, Farrell PM. Cystic fibrosis: a worldwide analysis of CFTR mutations-correlation with incidence data and application to screening. Human Mutation 2002;19(6):575-606. - PubMed
Borowitz 2002
    1. Borowitz D, Baker RD, Stallings V. Consensus report on nutrition for paediatric patients with cystic fibrosis. Journal of Pediatric Gastroenterology & Nutrition 2002;35:246-59. - PubMed
Conway 2005
    1. Conway SP, Wolfe SP, Brownlee KG, White H, Oldroyd B, Truscott JG, et al. Vitamin K status among children with cystic fibrosis and its relationship to bone mineral density and bone turnover. Pediatrics 2005;115(5):1325-31. - PubMed
Cystic Fibrosis Trust 2002
    1. Cystic Fibrosis Trust Nutrition Working Group. Nutritional management of cystic fibrosis. London: Cystic Fibrosis Trust 2002.
Cystic Fibrosis Trust 2007
    1. UK CF Trust. Bone Mineralisation in Cystic Fibrosis.Report of the UK Cystic Fibrosis Trust Bone Mineralisation Working Group. www.cftrust.org.uk/aboutcf/publications/consensusdoc/Bone-Mineral-Bookle... February 2007.
Davis 2006
    1. Davis PB. Cystic fibrosis since 1938. American Journal of Respiratory and Critical Care Medicine 2006;173(5):475-82. [PMID: ] - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JP, Altman DG. Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JP, Green S (editors). Cochrane Handbook of Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org . [REFWORKS: ID: 1335]
Dodge 2006
    1. Dodge JA, Turck D. Cystic fibrosis: nutritional consequences and management. Best Practice & Research. Clinical Gastroenterology 2006;20(3):531-46. - PubMed
Dougherty 2010
    1. Dougherty KA, Schall JI, Stallings VA. Suboptimal vitamin K status despite supplementation in children and young adults with cystic fibrosis. American Journal of Clinical Nutrition 2010;92(3):660-7. [PMID: ] - PMC - PubMed
Durie 1994
    1. Durie PR. Vitamin K and the management of patients with cystic fibrosis. CMAJ 1994;151(7):933-6. [PMID: ] - PMC - PubMed
Fuchs 1998
    1. Fuchs JR, Langer JC. Long-term outcome after neonatal meconium obstruction. Pediatrics 1998;101(4):E7. [PMID: ] - PubMed
Gee 2000
    1. Gee L, Abbott J, Conway SP, Etherington C, Webb AK. Development of a disease specific health related quality of life measure for adults and adolescents with cystic fibrosis. Thorax 2000;55(11):946-54. [PMID: ] - PMC - PubMed
Goss 2004
    1. Goss CH, Rosenfeld M. Update on Cystic Fibrosis Epidemiology. Current Opinion in Pulmonary Medicine 2004;10(6):510-4. [PMID: ] - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60. - PMC - PubMed
Higgins 2011
    1. Higgins JP, Altman DG. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S (editors). Cochrane Handbook of Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Klimova 2017
    1. Klimova B, Kuca K, Novotny M, Maresova P. Cystic fibrosis revisited - a review study. Medicinal Chemistry (Shariqah (United Arab Emirates)) 2017;13(2):102-9. [PMID: ] - PubMed
Krzyzanowska 2010
    1. Krzyzanowska P, Lisowska A, Skorupa W, Pogorzelski A, Kaminska B, Cichy W, et al. Vitamin K deficiency in patients with CF despite supplementation [Niedobor witaminy K u chorych na mukowiscydoze pomimo stosowanej suplementacji]. Medycyna Wieku Rozwojowego 2010;14(1):68-72. [PMID: ] - PubMed
Krzyzanowska 2015
    1. Krzyzanowska P, Pogorzelski A, Skorupa W, Moczko J, Grebowiec P, Walkowiak J. Exogenous and endogenous determinants of vitamin K status in cystic fibrosis. Scientific Reports 2015;5:12000. [DOI: 10.1038/srep12000] [PMID: ] - DOI - PMC - PubMed
Krzyzanowska 2018
    1. Krzyzanowska P, Drzymala-Czyz S, Rohovyk N, Bober L, Moczkco J, Rachel M, et al. Prevalence of vitamin K deficiency and associated factors in non-supplemented cystic fibrosis patients [Prevalencia de deficiencia de vitamina K y factores asociados en pacientes con fibrosis quistica sin aporte suplementario.]. Archivos argentinos de pediatria 2018;116(1):e19-25. [PMID: ] - PubMed
Morgan 1999
    1. Morgan WJ, Butler SM, Johnson CA, Colin AA, FitzSimmons SC, Geller DE, et al. Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada. Pediatric Pulmonology 1999;28(4):231-41. - PubMed
Okano 2005
    1. Okano T. Vitamin D, K and bone mineral density. Clinical Calcium 2005;15(9):1489-94. [PMID: ] - PubMed
Olsen 1994
    1. Olson RE. Vitamin K. In: Shils ME, Olson JA, Shike M, editors(s). Modern Nutrition in Health and Disease. 8th edition. Baltimore: Williams and Wilkins, 1994:343-58.
Quittner 2000
    1. Quittner AL, Sweeny S, Watrous M, Munzenberger P, Bearss K, Gibson NA, et al. Translation and linguistic validation of a disease-specific quality of life measure for cystic fibrosis. Journal of Pediatric Psychology 2000;25(6):403-14. - PubMed
Ramsey 1992
    1. Ramsey BW, Farrell PM, Pencharz P, and the Consensus Committee. Nutritional assessment and management in cystic fibrosis: a consensus report. American Journal of Clinical Nutrition 1992;55(1):108-16. - PubMed
Rashid 1999
    1. Rashid M, Durie P, Andrew M, Kalnins D, Shin J, Corey M, et al. Prevalence of vitamin K deficiency in cystic fibrosis. American Journal of Clinical Nutrition 1999;70(3):378–82. - PubMed
Ratjen 2003
    1. Ratjen F, Döring G. Cystic fibrosis. Lancet 2003;361(9358):681-9. - PubMed
RevMan 2014 [Computer program]
    1. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Schünemann 2017a
    1. Schünemann HJ, Oxman AD, Higgins JP, Vist GE, Glasziou P, Akl E, et al, on behalf of the Cochrane GRADEing Methods Group and the Cochrane Statistical Methods Group. Chapter 11: Completing ‘Summary of findings’ tables and grading the confidence in or quality of the evidence. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017). The Cochrane Collaboration, 2017. Available from www.training.cochrane.org/handbook.
Schünemann 2017b
    1. Schünemann HJ, Oxman AD, Vist GE, Higgins JP, Deeks JJ, Glasziou P, et al, on behalf of the Cochrane GRADEing Methods Group and the Cochrane Statistical Methods Group. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017). The Cochrane Collaboration, 2017. Available from www.training.cochrane.org/handbook.
Shearer 1995
    1. Shearer MJ. Vitamin K. Lancet 1995;345(8944):229-34. [PMID: ] - PubMed
Sinaasappel 2002
    1. Sinaasappel M, Stern M, Littlewood J, Wolfe S, Steinkamp G, Heijerman HG, et al. Nutrition in patients with cystic fibrosis: a European Consensus. Journal of Cystic Fibrosis 2002;1(2):51-75. [PMID: ] - PubMed
Staab 2004
    1. Staab D. Cystic fibrosis - therapeutic challenge in cystic fibrosis children. European Journal of Endocrinology / European Federation of Endocrine Societies 2004;151 Suppl 1:S77-80. [PMID: ] - PubMed
Sterne 2011
    1. Sterne JA, Egger M, Moher D, on behalf of the Cochrane Bias Methods Group. Chapter 10: Addressing reporting biases. In: Higgins JP, Green S (editors). Cochrane Handbook of Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Uotila 1990
    1. Uotila L. The metabolic functions and mechanism of action of vitamin K. Scandinavian Journal of Clinical and Laboratory Investigation 1990;201 Suppl:109-17. [PMID: ] - PubMed
Verghese 2003
    1. Verghese T, Beverley D. Vitamin K deficient bleeding in cystic fibrosis. Archives of Disease in Childhood 2003;88(6):553. [PMID: ] - PMC - PubMed
Wagener 2003
    1. Wagener JS, Headley AA. Cystic fibrosis: current trends in respiratory care. Respiratory Care 2003;48(3):234-45. - PubMed
Wang 2004
    1. Wang LY, Bates CJ, Yan L, Harrington DJ, Shearer MJ, Prentice A. Determination of phylloquinone (vitamin K1) in plasma and serum by HPLC with fluorescence detection. Clinica Chimica Acta 2004;347(1-2):199-207. [PMID: ] - PubMed

References to other published versions of this review

Jagannath 2010
    1. Jagannath VA, Fedorowicz Z, Thaker V, Chang AB, Al-Harthy N. Vitamin K supplementation for cystic fibrosis. Cochrane Database of Systematic Reviews 2010, Issue 4. [DOI: 10.1002/14651858.CD008482] - DOI
Jagannath 2011
    1. Jagannath VA, Fedorowicz Z, Thaker V, Chang AB. Vitamin K supplementation for cystic fibrosis. Cochrane Database of Systematic Reviews 2011, Issue 1. [DOI: 10.1002/14651858.CD008482.pub2] - DOI - PubMed
Jagannath 2013
    1. Jagannath VA, Fedorowicz Z, Thaker V, Chang AB. Vitamin K supplementation for cystic fibrosis. Cochrane Database of Systematic Reviews 2013, Issue 4. [DOI: 10.1002/14651858.CD008482.pub3] - DOI - PubMed
Jagannath 2015
    1. Jagannath VA, Fedorowicz Z, Thaker V, Chang AB. Vitamin K supplementation for cystic fibrosis. Cochrane Database of Systematic Reviews 2015, Issue 1. [DOI: 10.1002/14651858.CD008482.pub4] - DOI - PMC - PubMed
Jagannath 2017
    1. Jagannath VA, Thaker V, Chang AB, Price AI. Vitamin K supplementation for cystic fibrosis. Cochrane Database of Systematic Reviews 2017, Issue 8. [DOI: 10.1002/14651858.CD008482.pub5] - DOI - PMC - PubMed

Publication types

MeSH terms