Vitamin K Status Based on K1, MK-4, MK-7, and Undercarboxylated Prothrombin Levels in Adolescent and Adult Patients with Cystic Fibrosis: A Cross-Sectional Study
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
- Shearer, M.J.; Fu, X.; Booth, S.L. Vitamin K nutrition, metabolism, and requirements: Current concepts and future research. Adv. Nutr. 2012, 3, 182–195. [Google Scholar] [CrossRef]
- Hatziparasides, G.; Loukou, I.; Moustaki, M.; Douros, K. Vitamin K and cystic fibrosis: A gordian knot that deserves our attention. Respir. Med. 2019, 155, 36–42. [Google Scholar] [CrossRef] [PubMed]
- Sokol, R.J.; Durie, P.R. Recommendations for management of liver and biliary tract disease in cystic fibrosis. Cystic Fibrosis Foundation Hepatobiliary Disease Consensus Group. J. Pediatr. Gastroenterol. Nutr. 1999, 28, S1–S13. [Google Scholar] [CrossRef] [PubMed]
- Kapple, M.; Espach, C.; Schweiger-Kabesch, A.; Lang, T.; Hartl, D.; Hector, A.; Glasmacher, C.; Griese, M. Ursodeoxycholic acid therapy in cystic fibrosis liver disease-a retrospective long-term follow-up case-control study. Aliment. Pharmacol. Ther. 2012, 36, 266–273. [Google Scholar] [CrossRef] [PubMed]
- Bertolaso, C.; Groleau, V.; Schall, J.I.; Maqbool, A.; Mascarenhas, M.; Latham, N.E.; Dougherty, K.A.; Stallings, V.A. Fat-soluble vitamins in cystic fibrosis and pancreatic insufficiency: Efficacy of a nutrition intervention. J. Pediatr. Gastroenterol. Nutr. 2014, 58, 443–448. [Google Scholar] [CrossRef] [PubMed]
- Turck, D.; Braegger, C.P.; Colombo, C.; Declercq, D.; Morton, A.; Pancheva, R.; Robberecht, E.; Stern, M.; Strandvik, B.; Wolfe, S.; et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin. Nutr. 2016, 35, 557–577. [Google Scholar] [CrossRef] [PubMed]
- Krzyżanowska, P.; Pogorzelski, A.; Skorupa, W.; Moczko, J.; Grebowiec, P.; Walkowiak, J. Exogenous and endogenous determinants of vitamin K status in cystic fibrosis. Sci. Rep. 2015, 5, srep12000. [Google Scholar] [CrossRef] [PubMed]
- Shea, M.K.; Booth, S.L. Concepts and Controversies in Evaluating Vitamin K Status in Population-Based Studies. Nutrients 2016, 8, 8. [Google Scholar] [CrossRef] [PubMed]
- Mosler, K.; von Kries, R.; Vermeer, C.; Saupe, J.; Schmitz, T.; Schuster, A. Assessment of vitamin K deficiency in CF—How much sophistication is useful? J. Cyst. Fibros. 2003, 2, 91–96. [Google Scholar] [CrossRef]
- Choonara, I.A.; Winn, M.J.; Park, B.K. Plasma vitamin K1 concentrations in cystic fibrosis. Arch. Dis. Child. 1989, 64, 732–734. [Google Scholar] [CrossRef]
- Cornelissen, E.A.; van Lieburg, A.F.; Motohara, K.; van Oostrom, C.G. Vitamin K status in cystic fibrosis. Acta Paediatr. 1992, 81, 658–661. [Google Scholar] [CrossRef] [PubMed]
- Beker, L.T.; Ahrens, R.A.; Fink, R.J.; O’Brien, M.E.; Davidson, K.W.; Sokoll, L.J.; Sadowski, J.A. Effect of vitamin K1 supplementation on vitamin K status in cystic fibrosis patients. J. Pediatr. Gastroenterol. Nutr. 1997, 24, 512–517. [Google Scholar] [CrossRef] [PubMed]
- Conway, S.P.; Wolfe, S.P.; Brownlee, K.G.; White, H.; Oldroyd, B.; Truscott, J.G.; Harvey, J.M.; Shearer, M.J. Vitamin K status among children with cystic fibrosis and its relationship to bone mineral density and bone turnover. Pediatrics 2005, 115, 1325–1331. [Google Scholar] [CrossRef] [PubMed]
- Nicolaidou, P.; Stavrinadis, I.; Loukou, I.; Papadopoulou, A.; Georgouli, H.; Douros, K.; Priftis, K.N.; Gourgiotis, D.; Matsinos, Y.G.; Doudounakis, S. The effect of vitamin K supplementation on biochemical markers of bone formation in children and adolescents with cystic fibrosis. Eur. J. Pediatr. 2006, 165, 540–545. [Google Scholar] [CrossRef] [PubMed]
- Drury, D.; Grey, V.L.; Ferland, G.; Gundberg, C.; Lands, L.C. Efficacy of high dose phylloquinone in correcting vitamin K deficiency in cystic fibrosis. J. Cyst. Fibros. 2008, 7, 457–459. [Google Scholar] [CrossRef] [PubMed]
- Siwamogsatham, O.; Dong, W.; Binongo, J.N.; Chowdhury, R.; Alvarez, J.A.; Feinman, S.J.; Enders, J.; Tangpricha, V. Relationship Between Fat-Soluble Vitamin Supplementation and Blood Concentrations in Adolescent and Adult Patients With Cystic Fibrosis. Nutr. Clin. Pract. 2014, 29, 491–497. [Google Scholar] [CrossRef] [PubMed]
- Konieczna, L.; Kaźmierska, K.; Roszkowska, A.; Szlagatys-Sidorkiewicz, A.; Bączek, T. The LC-MS method for the simultaneous analysis of selected fat-soluble vitamins and their metabolites in serum samples obtained from pediatric patients with cystic fibrosis. J. Pharm. Biomed. Anal. 2016, 124, 374–381. [Google Scholar] [CrossRef] [PubMed]
- Bergeron, C.; Potter, K.J.; Boudreau, V.; Ouliass, B.; Bonhoure, A.; Lacombe, J.; Mailhot, M.; Lavoie, A.; Ferron, M.; Ferland, G.; et al. Low vitamin K status in adults with cystic fibrosis is associated with reduced body mass index, insulin secretion, and increased pseudomonal colonization. Appl. Physiol. Nutr. Metab. 2023, 48, 321–330. [Google Scholar] [CrossRef] [PubMed]
- Hirota, Y.; Tsugawa, N.; Nakagawa, K.; Suhara, Y.; Tanaka, K.; Uchino, Y.; Takeuchi, A.; Sawada, N.; Kamao, M.; Wada, A.; et al. Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. J. Biol. Chem. 2013, 288, 33071–33080. [Google Scholar] [CrossRef] [PubMed]
- Castellani, C.; Southern, K.W.; Brownlee, K.; Roelse, J.D.; Duff, A.; Farrell, M.; Mehta, A.; Munck, A.; Pollitt, R.; Sermet-Gaudelus, I.; et al. European best practice guidelines for cystic fibrosis neonatal screening. J. Cyst. Fibros. 2009, 8, 153–173. [Google Scholar] [CrossRef] [PubMed]
- Farrell, P.M.; White, T.B.; Ren, C.L.; Hempstead, S.E.; Accurso, F.; Derichs, N.; Howenstine, M.; McColley, S.A.; Rock, M.; Rosenfeld, M.; et al. Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation. J. Pediatr. 2017, 181S, S4–S15. [Google Scholar] [CrossRef] [PubMed]
- Walkowiak, J. Faecal elastase-1: Clinical value in the assessment of exocrine pancreatic function in children. Eur. J. Pediatr. 2000, 159, 869–870. [Google Scholar] [CrossRef]
- Walkowiak, J. Assessment of maldigestion in cystic fibrosis. J. Pediatr. 2004, 145, 285–287. [Google Scholar] [CrossRef] [PubMed]
- Dunovska, K.; Klapkova, E.; Sopko, B.; Cepova, J.; Prusa, R. LC-MS/MS quantitative analysis of phylloquinone, menaquinone-4 and menaquinone-7 in the human serum of a healthy population. PeerJ 2019, 7, e7695. [Google Scholar] [CrossRef] [PubMed]
- von Elm, E.; Altman, D.G.; Egger, M.; Pocock, S.J.; Gøtzsche, P.C.; Vandenbroucke, J.P. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies. J. Clin. Epidemiol. 2008, 61, 344–349. [Google Scholar] [CrossRef]
- Krzyżanowska, P.; Drzymała-Czyż, S.; Pogorzelski, A.; Duś-Żuchowska, M.; Skorupa, W.; Bober, L.; Sapiejka, E.; Oralewska, B.; Rohovyk, N.; Moczko, J.; et al. Vitamin K status in cystic fibrosis patients with liver cirrhosis. Dig. Liver Dis. 2017, 49, 672–675. [Google Scholar] [CrossRef]
- Mahdinia, E.; Demirci, A.; Berenjian, A. Production and application of menaquinone-7 (vitamin K2): A new perspective. World J. Microbiol. Biotechnol. 2017, 33, 2. [Google Scholar] [CrossRef] [PubMed]
- Jadhav, N.; Ajgaonkar, S.; Saha, P.; Gurav, P.; Pandey, A.; Basudkar, V.; Gada, Y.; Panda, S.; Jadhav, S.; Mehta, D.; et al. Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities. Front. Pharmacol. 2022, 13, 896920. [Google Scholar] [CrossRef] [PubMed]
- Forli, L.; Bollerslev, J.; Simonsen, S.; Isaksen, G.A.; Kvamsdal, K.E.; Godang, K.; Gadeholt, G.; Pripp, A.H.; Bjortuft, O. Dietary vitamin K2 supplement improves bone status after lung and heart transplantation. Transplantation 2010, 89, 458–464. [Google Scholar] [CrossRef]
- Rønn, S.H.; Harsløf, T.; Pedersen, S.B.; Langdahl, B.L. Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. Eur. J. Endocrinol. 2016, 175, 541–549. [Google Scholar] [CrossRef]
- Zhang, Y.; Liu, Z.; Duan, L.; Ji, Y.; Yang, S.; Zhang, Y.; Li, H.; Wang, Y.; Wang, P.; Chen, J.; et al. Effect of Low-Dose Vitamin K2 Supplementation on Bone Mineral Density in Middle-Aged and Elderly Chinese: A Randomized Controlled Study. Calcif. Tissue Int. 2020, 106, 476–485. [Google Scholar] [CrossRef] [PubMed]
- Caluwé, R.; Vandecasteele, S.; Van Vlem, B.; Vermeer, C.; De Vriese, A.S. Vitamin K2 supplementation in haemodialysis patients: A randomized dose-finding study. Nephrol. Dial. Transplant. 2014, 29, 1385–1390. [Google Scholar] [CrossRef] [PubMed]
- Knapen, M.H.; Braam, L.A.; Drummen, N.E.; Bekers, O.; Hoeks, A.P.; Vermeer, C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb. Haemost. 2015, 113, 1135–1144. [Google Scholar] [CrossRef] [PubMed]
- Eelderink, C.; Kremer, D.; Riphagen, I.J.; Knobbe, T.J.; Schurgers, L.J.; Pasch, A.; Mulder, D.J.; Corpeleijn, E.; Navis, G.; Bakker, S.J.L.; et al. Effect of vitamin K supplementation on serum calcification propensity and arterial stiffness in vitamin K-deficient kidney transplant recipients: A double-blind, randomized, placebo-controlled clinical trial. Am. J. Transplant. 2023, 23, 520–530. [Google Scholar] [CrossRef] [PubMed]
- Abdel-Rahman, M.S.; Alkady, E.A.; Ahmed, S. Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: A clinical study. J. Pharmacol. 2015, 761, 273–278. [Google Scholar] [CrossRef] [PubMed]
- Ozaki, I.; Zhang, H.; Mizuta, T.; Ide, Y.; Eguchi, Y.; Yasutake, T.; Sakamaki, T.; Pestell, R.G.; Yamamoto, K. Menatetrenone, a vitamin K2 analogue, inhibits hepatocellular carcinoma cell growth by suppressing cyclin D1 expression through inhibition of nuclear factor kappaB activation. Clin. Cancer Res. 2007, 13, 2236–2245. [Google Scholar] [CrossRef] [PubMed]
- Xia, J.; Matsuhashi, S.; Hamajima, H.; Iwane, S.; Takahashi, H.; Eguchi, Y.; Mizuta, T.; Fujimoto, K.; Kuroda, S.; Ozaki, I. The role of PKC isoforms in the inhibition of NF-kappaB activation by vitamin K2 in human hepatocellular carcinoma cells. J. Nutr. Biochem. 2012, 23, 1668–1675. [Google Scholar] [CrossRef] [PubMed]
- Sibayama-Imazu, T.; Fujisawa, Y.; Masuda, Y.; Aiuchi, T.; Nakajo, S.; Itabe, H.; Nakaya, K. Induction of apoptosis in PA-1 ovarian cancer cells by vitamin K2 is associated with an increase in the level of TR3/Nur77 and its accumulation in mitochondria and nuclei. J. Cancer Res. Clin. Oncol. 2008, 134, 803–812. [Google Scholar] [CrossRef] [PubMed]
- Showalter, S.L.; Wang, Z.; Costantino, C.L.; Witkiewicz, A.K.; Yeo, C.J.; Brody, J.R.; Carr, B.I. Naturally occurring K vitamins inhibit pancreatic cancer cell survival through a caspase-dependent pathway. J. Gastroenterol. Hepatol. 2010, 25, 738–744. [Google Scholar] [CrossRef] [PubMed]
- Enomoto, M.; Tsuchida, A.; Miyazawa, K.; Yokoyama, T.; Kawakita, H.; Tokita, H.; Naito, M.; Itoh, M.; Ohyashiki, K.; Aoki, T. Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines. Int. J. Mol. Med. 2007, 20, 801–808. [Google Scholar] [CrossRef] [PubMed]
- Miyazawa, K.; Yaguchi, M.; Funato, K.; Gotoh, A.; Kawanishi, Y.; Nishizawa, Y.; You, A.; Ohyashiki, K. Apoptosis/differentiation-inducing effects of vitamin K2 on HL-60 cells: Dichotomous nature of vitamin K2 in leukemia cells. Leukemia 2001, 15, 1111–1117. [Google Scholar] [CrossRef] [PubMed]
- Hadipour, E.; Tayarani-Najaran, Z.; Fereidoni, M. Vitamin K2 Protects PC12 Cells against Aβ (1-42) and H2O2-Induced Apoptosis via P38 MAP Kinase Pathway. Nutr. Neurosci. 2020, 23, 343–352. [Google Scholar] [CrossRef]
- Rahimi Sakak, F.; Moslehi, N.; Niroomand, M.; Mirmiran, P. Glycemic control improvement in individuals with type 2 diabetes with vitamin K2 supplementation: A randomized controlled trial. Eur. J. Nutr. 2021, 60, 2495–2506. [Google Scholar] [CrossRef] [PubMed]
- Pan, M.H.; Maresz, K.; Lee, P.S.; Wu, J.C.; Ho, C.T.; Popko, J.; Mehta, D.S.; Stohs, S.J.; Badmaev, V. Inhibition of TNF-α, IL-1α, and IL-1β by Pretreatment of Human Monocyte Derived Macrophages with Menaquinone-7 and Cell Activation with TLR Agonists In Vitro. J. Med. Food 2016, 19, 663–669. [Google Scholar] [CrossRef] [PubMed]
- Mehta, D.S.; Dound, Y.A.; Jadhav, S.S.; Bhave, A.A.; Devale, M.; Vaidya, A.D.B. A Novel Potential Role of Vitamin K2-7 in Relieving Peripheral Neuropathy. J. Pharmacol. Pharmacother. 2018, 9, 180–185. [Google Scholar] [CrossRef]
- Conway, S.P. Vitamin K in cystic fibrosis. J. R. Soc. Med. 2004, 97, 48–51. [Google Scholar] [PubMed]
- Maqbool, A.; Stallings, V.A. Update on fat-soluble vitamins cystic fibrosis. Curr. Opin. Pulm. Med. 2008, 14, 574–581. [Google Scholar] [CrossRef] [PubMed]
- Borowitz, D.; Baker, R.D.; Stallings, V. Consensus report on nutrition for paediatric patients with cystic fibrosis. J. Pediatr. Gastroenterol. Nutr. 2002, 35, 246–259. [Google Scholar] [CrossRef] [PubMed]
- Sinaasappel, M.; Stern, M.; Littlewood, J.; Wolfe, S.; Steinkamp, G.; Heijerman, H.G.; Robberecht, E.; Döring, G. Nutrition in patients with cystic fibrosis: A European Consensus. J. Cyst. Fibros. 2002, 1, 51–75. [Google Scholar] [CrossRef]
- Jagannath, V.A.; Thaker, V.; Chang, A.B.; Price, A.I. Vitamin K supplementation for cystic fibrosis. Cochrane Database Syst. Rev. 2020, 6, CD008482. [Google Scholar] [CrossRef] [PubMed]
- Rashid, M.; Durie, P.; Andrew, M.; Kalnins, D.; Shin, J.; Corey, M.; Tullis, E.; Pencharz, P.B. Prevalence of vitamin K deficiency in cystic fibrosis. Am. J. Clin. Nutr. 1999, 70, 378–382. [Google Scholar] [CrossRef] [PubMed]
- van Hoorn, J.H.; Hendriks, J.J.; Vermeer, C.; Forget, P.P. Vitamin K supplementation in cystic fibrosis. Arch. Dis. Child. 2003, 88, 974–975. [Google Scholar] [CrossRef] [PubMed]
- Thijssen, H.H.; Vervoort, L.M.; Schurgers, L.J.; Shearer, M.J. Menadione is a metabolite of oral vitamin K. Br. J. Nutr. 2006, 95, 260–266. [Google Scholar] [CrossRef] [PubMed]
- Okano, T.; Shimomura, Y.; Yamane, M.; Suhara, Y.; Kamao, M.; Sugiura, M.; Nakagawa, K. Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: Two possible routes for menaquinone-4 accumulation in cerebra of mice. J. Biol. Chem. 2008, 283, 11270–11279. [Google Scholar] [CrossRef] [PubMed]
- Shearer, M.J.; Okano, T. Key Pathways and Regulators of Vitamin K Function and Intermediary Metabolism. Annu. Rev. Nutr. 2018, 38, 127–151. [Google Scholar] [CrossRef] [PubMed]
- Fewtrell, M.S.; Benden, C.; Williams, J.E.; Chomtho, S.; Ginty, F.; Nigdikar, S.V.; Jaffe, A. Undercarboxylated osteocalcin and bone mass in 8-12 year old children with cystic fibrosis. J. Cyst. Fibros. 2008, 7, 307–312. [Google Scholar] [CrossRef] [PubMed]
- Dougherty, K.A.; Schall, J.I.; Stallings, V.A. Suboptimal vitamin K status despite supplementation in children and young adults with cystic fibrosis. Am. J. Clin. Nutr. 2010, 92, 660–667. [Google Scholar] [CrossRef]
- Krzyżanowska, P.; Drzymala-Czyż, S.; Rohovyk, N.; Bober, L.; Moczko, J.; Rachel, M.; Walkowiak, J. Prevalence of vitamin K deficiency and associated factors in non-supplemented cystic fibrosis patients. Arch. Argent. Pediatr. 2018, 116, e19–e25. [Google Scholar] [CrossRef] [PubMed]
- Hergenroeder, G.E.; Faino, A.; Bridges, G.; Bartlett, L.E.; Cogen, J.D.; Green, N.; McNamara, S.; Nichols, D.P.; Ramos, K.J. The impact of elexacaftor/tezacaftor/ivacaftor on fat-soluble vitamin levels in people with cystic fibrosis. J. Cyst. Fibros. 2023, 22, 1048–1053. [Google Scholar] [CrossRef] [PubMed]
- Petersen, M.C.; Begnel, L.; Wallendorf, M.; Litvin, M. Effect of elexacaftor-tezacaftor-ivacaftor on body weight and metabolic parameters in adults with cystic fibrosis. J. Cyst. Fibros. 2022, 21, 265–271. [Google Scholar] [CrossRef]
Clinical Parameters Median (1st–3rd Quartile) | CF Group (N = 63) | Control Group (N = 61) | p | |
---|---|---|---|---|
Gender | Female | 40 (63.5%) | 41 (67.2%) | 0.6634 |
Male | 23 (36.5%) | 20 (32.8%) | ||
Age [years] | 23.1 (19.4−29.4) | 22.5 (21.4−23.4) | 0.4656 | |
Body weight [kg] | 59.0 (51.5−66.5) | 60.0 (55.0−68.5) | 0.1844 | |
Body height [cm] | 168 (161−174) | 168 (163−176) | 0.5402 | |
BMI [kg/m2] | 20.9 (19.7−22.2) | 21.6 (20.4−22.7) | 0.0829 |
Median (1st–3rd Quartile) | CF all (N = 63) | CF with K1 Supplementation (N = 37) | CF with K1 and MK-7 Supplementation (N = 19) | CF without Any Supplementation (N = 7) | Healthy Adults (N = 61) | p |
---|---|---|---|---|---|---|
K1 [ng/mL] | 0.315 (0.169−0.532) | 0.407 (0.225–0.573) | 0.270 (0.145–0.396) | 0.093 (0.066–0.298) | 0.274 (0.203–0.387) | 0.3526 a 0.0453 b |
MK-4 [ng/mL] | 0.778 (0.589−1.086) | 0.782 (0.600–1.163) | 0.748 (0.587–1.029) | 0.671 (0.533–0.840) | 0.349 (0.256–0.469) | <0.0001 a 0.4219 b |
MK-7 [ng/mL] | 0.150 (0.094–0.259) | 0.140 ** (0.095–0.188) | 0.259 *,** (0.178–0.464) | 0.093 * (0.068–0.137) | 0.231 (0.191–0.315) | 0.0007 a 0.0063 b |
PIVKA-II [ng/mL] | 1.78 (0.86−3.25) | 1.16 (0.73–2.18) | 2.47 (1.38–3.67) | 3.37 (2.07–3.97) | 1.63 (0.74–2.64) | 0.5671 a 0.0606 b |
Vitamin K1 [mg/kg/day] | 0.03 (0.01–0.06) | 0.06 (0.03–0.08) | 0.01 (0.01–0.02) | - | - | <0.0001 c |
MK-7 [µg/kg/day] | 0 (0–1.57) | - | 2.08 (1.74–3.03) | - | - | - |
Mean ± SD | CF with K1 Supplementation (N = 37) | CF with K1 and MK-7 Supplementation (N = 19) | Cohen’s D index |
---|---|---|---|
K1 [ng/mL] | 0.986 ± 1.769 | 0.556 ± 1.009 | 0.299 |
MK-4 [ng/mL] | 0.901 ± 0.450 | 0.899 ± 0.525 | 0.004 |
MK-7 [ng/mL] | 0.294 ± 0.805 | 0.464 ± 0.497 | 0.254 |
CF with K1 Supplementation (N = 37) | CF without any Supplementation (N = 7) | Cohen’s D index | |
K1 [ng/mL] | 0.986 ± 1.769 | 0.245 ± 0.293 | 0.584 |
MK-4 [ng/mL] | 0.901 ± 0.450 | 0.636 ± 0.257 | 1.711 |
MK-7 [ng/mL] | 0.294 ± 0.805 | 0.115 ± 0.095 | 0.312 |
CF with K1 and MK-7 Supplementation (N = 19) | CF without any Supplementation (N = 7) | Cohen’s D index | |
K1 [ng/mL] | 0.556 ± 1.009 | 0.245 ± 0.293 | 0.419 |
MK-4 [ng/mL] | 0.899 ± 0.525 | 0.636 ± 0.257 | 0.636 |
MK-7 [ng/mL] | 0.464 ± 0.497 | 0.115 ± 0.095 | 0.975 |
Clinical Parameters | Study Subgroups | K1 [ng/mL] | MK-4 [ng/mL] | MK-7 [ng/mL] | |||
---|---|---|---|---|---|---|---|
Rho | p | rho | p | rho | p | ||
Age [years] | I | 0.1241 | 0.3325 | 0.0988 | 0.4411 | −0.0678 | 0.5976 |
II | 0.2160 | 0.1991 | 0.2067 | 0.2198 | 0.1123 | 0.5082 | |
III | −0.0650 | 0.7916 | −0.1027 | 0.6756 | −0.0720 | 0.7696 | |
Body weight [kg] | I | −0.2556 | 0.0431 | −0.0664 | 0.6053 | −0.1632 | 0.2013 |
II | −0.1293 | 0.4458 | −0.2276 | 0.1756 | −0.2004 | 0.2344 | |
III | −0.3038 | 0.2061 | 0.2283 | 0.3472 | −0.1466 | 0.5492 | |
Body height [cm] | I | −0.1677 | 0.1890 | 0.0179 | 0.8896 | −0.0576 | 0.6537 |
II | −0.0084 | 0.9605 | −0.0970 | 0.5679 | −0.0714 | 0.6742 | |
III | −0.3008 | 0.2108 | 0.2348 | 0.3332 | 0.0897 | 0.7149 | |
BMI [kg/m2] | I | −0.2007 | 0.1147 | −0.0896 | 0.4850 | −0.2240 | 0.0776 |
II | −0.1011 | 0.5515 | −0.2382 | 0.1558 | −0.2344 | 0.1627 | |
III | −0.1140 | 0.6420 | 0.1228 | 0.6165 | −0.2754 | 0.2537 | |
FEV1 [s] | I | 0.0075 | 0.9538 | 0.1099 | 0.3950 | −0.0401 | 0.7571 |
II | 0.0302 | 0.8590 | 0.0977 | 0.5650 | −0.1945 | 0.2487 | |
III | 0.0279 | 0.9125 | 0.0386 | 0.8752 | −0.1203 | 0.6238 | |
Vitamin K1 dose [mg/kg/day] | II | 0.3788 | 0.0208 | 0.2619 | 0.1174 | 0.1203 | 0.4781 |
III | −0.0053 | 0.9829 | −0.0754 | 0.7589 | −0.0579 | 0.8139 | |
MK-7 dose [µg/kg/day] | III | 0.1580 | 0.5184 | 0.0570 | 0.8166 | 0.1071 | 0.6626 |
PIVKA-II [ng/mL] | I | −0.0877 | 0.4943 | 0.0383 | 0.7658 | −0.1018 | 0.4274 |
II | −0.0598 | 0.7248 | 0,0149 | 0.9301 | −0.1494 | 0.3776 | |
III | 0.2982 | 0.2149 | 0.1614 | 0.5092 | 0.0351 | 0.8866 |
Clinical Parameters Median (1st–3rd Quartile) | K1 [ng/mL] | |||
---|---|---|---|---|
0.115 (0.069–0.166) (N = 21) | 0.763 (0.545–1.571) (N = 21) | p | ||
Age [years] | 22.1 (20.8–26.0) | 23.8 (20.4–31.5) | 0.5629 | |
BMI [kg/m2] | 21.4 (20.4–22.0) | 20.6 (19.1–21.6) | 0.0919 | |
FEV1 [s] | 59.8 (45.4–79.0) | 64.0 (55.0–85.1) | 0.7444 | |
Vitamin K1 dose [mg/kg/day] | 0.023 (0.008–0.054) | 0.058 (0.020–0.081) | 0.0414 | |
PIVKA-II [ng/mL] | 1.97 (0.95–3.37) | 1.41 (0.82–3.46) | 0.8999 | |
Gender [%] | Female | 14 (66.7) | 12 (57.1) | 0.3757 |
Male | 7 (33.3) | 9 (42.9) | ||
CFLD [%] | Yes | 11 (52.4) | 10 (47.6) | 0.5000 |
No | 10 (47.6) | 11 (52.4) | ||
Diabetes [%] | Yes | 2 (9.5) | 6 (28.6) | 0.1190 |
No | 19 (90.5) | 15 (71.4) | ||
Ps. aeruginosa colonization [%] | Yes | 13 (61.9) | 14 (66.7) | 0.5000 |
No | 8 (38.1) | 7 (33.3) | ||
CFTR gene mutations [%] | F508del/F508del | 13 (61.9) | 7 (33.3) | 0.0607 |
F508/other or other/other | 8 (38.1) | 14 (66.7) | ||
Supplementation of vitamin MK-7 [%] | Yes | 7 (33.3) | 4 (19.0) | 0.2420 |
No | 14 (66.7) | 17 (81.0) |
Clinical Parameters Median (1st–3rd Quartile) | MK-4 [ng/mL] | MK-7 [ng/mL] | |||||
---|---|---|---|---|---|---|---|
0.459 (0.327–0.585) (N = 21) | 1.306 (1.104–1.594) (N = 21) | p | 0.084 (0.070–0.093) (N = 21) | 0.386 (0.259–0.506) (N = 21) | p | ||
Age [years] | 22.1 (18.9–23.8) | 26.1 (18.7–31.5) | 0.4504 | 23.4 (21.9–29.3) | 21.3 (18.7–26.8) | 0.1218 | |
BMI [kg/m2] | 21.4 (20.4–22.0) | 20.5 (18.8–22.3) | 0.1743 | 21.3 (20.3–22.4) | 20.3 (18.5–22.0) | 0.0663 | |
FEV1 [s] | 71.0 (53.7–80.5) | 71.0 (56.0–85.1) | 0.6294 | 64.0 (45.4–79.0) | 65.6 (57.0–76.0) | 0.6765 | |
Vitamin K1 dose [mg/kg/day] | 0.043 (0.009–0.061) | 0.054 (0.018–0.081) | 0.2224 | 0.043 (0.007–0.074) | 0.016 (0.010–0.030) | 0.5044 | |
PIVKA-II [ng/mL] | 1.34 (0.61–2.19) | 1.41 (0.74–3.14) | 0.6689 | 2.61 (0.90–4.08) | 1.78 (0.82–3.46) | 0.3786 | |
Gender [%] | Female | 15 (71.4) | 14 (66.7) | 0.5000 | 13 (61.9) | 13 (61.9) | 0.6243 |
Male | 6 (28.6) | 7 (33.3) | 8 (38.1) | 8 (38.1) | |||
CFLD [%] | Yes | 13 (61.9) | 7 (33.3) | 0.0607 | 7 (33.3) | 9 (42.9) | 0.3757 |
No | 8 (38.1) | 14 (66.7) | 14 (66.7) | 12 (57.1) | |||
Diabetes [%] | Yes | 2 (9.5) | 4 (19.0) | 0.3314 | 1 (4.8) | 3 (14.3) | 0.3030 |
No | 19 (90.5) | 17 (81.0) | 20 (95.2) | 18 (85.7) | |||
Ps. aeruginosa colonization [%] | Yes | 15 (71.4) | 12 (57.1) | 0.2602 | 13 (61.9) | 12 (57.1) | 0.5000 |
No | 6 (28.6) | 9 (42.9) | 8 (38.1) | 9 (42.9) | |||
CFTR gene mutations [%] | F508del/F508del | 12 (57.1) | 7 (33.3) | 0.1073 | 10 (47.6) | 11 (52.4) | 0.5000 |
F508/other or other/other | 9 (42.9) | 14 (66.7) | 11 (52.4) | 10 (47.6) | |||
Supplementation of vitamin MK-7 [%] | Yes | 6 (28.6) | 6 (28.6) | 0.6331 | 4 (19.0) | 12 (57.1) | 0.0123 |
No | 15 (71.4) | 15 (71.4) | 17 (81.0) | 9 (42.9) |
r | β | SE | t | p | |
---|---|---|---|---|---|
Age [years] | −0.0002 | −0.0043 | 0.1291 | −0.0328 | 0.9740 |
BMI [kg/m2] | −0.0280 | −0.1911 | 0.1267 | −1.5078 | 0.1369 |
FEV1 [s] | −0.0014 | −0.0976 | 0.1296 | −0.7533 | 0.4546 |
Vitamin K1 dose [mg/kg/day] | −1.6735 | −0.2193 | 0.1260 | −1.7411 | 0.0868 |
Vitamin MK-7 dose [µg/kg/day] | 0.1237 | 0.4623 | 0.1145 | 4.0387 | 0.0002 |
Gender a | 0.0231 | 0.0708 | 0.1288 | 0.5500 | 0.5843 |
CFLD b | −0.0317 | −0.1007 | 0.1284 | −0.7839 | 0.4362 |
Diabetes c | 0.0356 | 0.0865 | 0.1286 | 0.6728 | 0.5037 |
Pseudomonas aeruginosa colonization | −0.0406 | −0.1247 | 0.1281 | −0.9738 | 0.3340 |
Clinical Parameters | MK-7 [ng/mL] |
---|---|
p model | 0.0005 |
R2 for model | 0.2266 |
Adjusted R2 for model | 0.2004 |
Vitamin K1 dose [mg/kg/day] | 0.326196 {−0.116650 ± 0.117823} 1 |
Vitamin MK-7 dose [µg/kg/day] | 0.000491 {0.434790 ± 0.117823} |
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Krzyżanowska-Jankowska, P.; Nowak, J.; Karaźniewicz-Łada, M.; Jamka, M.; Klapkova, E.; Kurek, S.; Drzymała-Czyż, S.; Lisowska, A.; Wojsyk-Banaszak, I.; Skorupa, W.; et al. Vitamin K Status Based on K1, MK-4, MK-7, and Undercarboxylated Prothrombin Levels in Adolescent and Adult Patients with Cystic Fibrosis: A Cross-Sectional Study. Nutrients 2024, 16, 1337. https://doi.org/10.3390/nu16091337
Krzyżanowska-Jankowska P, Nowak J, Karaźniewicz-Łada M, Jamka M, Klapkova E, Kurek S, Drzymała-Czyż S, Lisowska A, Wojsyk-Banaszak I, Skorupa W, et al. Vitamin K Status Based on K1, MK-4, MK-7, and Undercarboxylated Prothrombin Levels in Adolescent and Adult Patients with Cystic Fibrosis: A Cross-Sectional Study. Nutrients. 2024; 16(9):1337. https://doi.org/10.3390/nu16091337
Chicago/Turabian StyleKrzyżanowska-Jankowska, Patrycja, Jan Nowak, Marta Karaźniewicz-Łada, Małgorzata Jamka, Eva Klapkova, Szymon Kurek, Sławomira Drzymała-Czyż, Aleksandra Lisowska, Irena Wojsyk-Banaszak, Wojciech Skorupa, and et al. 2024. "Vitamin K Status Based on K1, MK-4, MK-7, and Undercarboxylated Prothrombin Levels in Adolescent and Adult Patients with Cystic Fibrosis: A Cross-Sectional Study" Nutrients 16, no. 9: 1337. https://doi.org/10.3390/nu16091337
APA StyleKrzyżanowska-Jankowska, P., Nowak, J., Karaźniewicz-Łada, M., Jamka, M., Klapkova, E., Kurek, S., Drzymała-Czyż, S., Lisowska, A., Wojsyk-Banaszak, I., Skorupa, W., Szydłowski, J., Prusa, R., & Walkowiak, J. (2024). Vitamin K Status Based on K1, MK-4, MK-7, and Undercarboxylated Prothrombin Levels in Adolescent and Adult Patients with Cystic Fibrosis: A Cross-Sectional Study. Nutrients, 16(9), 1337. https://doi.org/10.3390/nu16091337