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Original Communication

Vitamin K1 Supplementation Did Not Alter Inflammatory Markers and Clinical Status in Patients with Rheumatoid Arthritis

Published Online:https://doi.org/10.1024/0300-9831/a000276

Abstract.Background: Rheumatoid arthritis (RA) is an inflammatory disorder in which the disease severity might be decreased by anti-inflammatory agents. There are several lines of evidence which support anti-inflammatory effects of vitamin K. The aim of this study was to examine whether vitamin K is a useful strategy for reducing inflammation in RA subjects. Materials and methods: In this double-blind placebo controlled trial, 58 patients with definitive RA were randomly allocated into two groups to receive vitamin K1 as phylloquinone [10 mg/day] or placebo pills for 8 weeks. Clinical status using disease activity score-28 (DAS-28) and serum concentrations of some inflammatory markers (IL-6, hs-CRP, TNFα) were assessed at baseline and at the end of intervention. Results: There were no significant differences between the two groups regarding any of the baseline characteristics. In the vitamin K1 group, a 27 % decrease in serum levels of IL-6 (P = 0.006) and a 13 % decrease in DAS-28 (P = 0.041) were observed. However, after adjusting for relevant confounders, i. e.; duration of RA, intake of folic acid supplements, energy intake, weight and baseline values of each variable, by comparing the two groups, we found no significant reduction in these markers. Conclusion: Vitamin K1 supplementation at 10 mg/day for 8 weeks had no significant effects on blood biomarkers of inflammation and disease severity of patients with rheumatoid arthritis compared with the placebo group.

Literature

  • Scott, D., Wolfe, F. and Huizinga, T. (2010) The Lancet Seminar: Rheumatoid arthritis. Lancet 376, 1094–1108. First citation in articleCrossrefGoogle Scholar

  • Smith, H., Smith, A. and Seidner, P. (2011) Painful rheumatoid arthritis. Pain Physician 14, E427–458. First citation in articleGoogle Scholar

  • Monjamed, Z. and Razavian, F. (2005) Effect of disease symptoms on quality of life in patients with rheumatoid arthritis who were admitted to Tehran university of medical sciences hospitals in 2005. Qom. Uni. Med. Sci. J. 1, 27–35 [in Persian]. First citation in articleGoogle Scholar

  • Amani, R., Shooyooee, R., Seraj, M. and Haghighizadeh, M. (2009) Dietary intake of antioxidants and dietary factors affecting rheumatoid arthritis in women. J. Iran Med. Univ. 62, 39–46. First citation in articleGoogle Scholar

  • Bae, S., Kim, S. and Sung, M. (2003) Inadequate antioxidant nutrient intake and altered plasma antioxidant status of rheumatoid arthritis patients. J. Am. Coll. Nutr. 22, 311–315. First citation in articleCrossrefGoogle Scholar

  • Fionula, M., Brennan, B. and Iain, B. (2008) Evidence that cytokines play a role in rheumatoid arthritis. J. Clin. Invest. 118, 3537–3545. First citation in articleCrossrefGoogle Scholar

  • Liao, K., Alfredsson, L. and Karlson, E. (2009) Environmental influences on risk for rheumatoid arthritis. Curr. Opin. Rheumatol. 21, 279–283. First citation in articleCrossrefGoogle Scholar

  • Mobini, M. (2009) Probable risk factors of rheumatoid arthritis, a case control study. J. Mazand. Med. Sci. 20, 38–44. First citation in articleGoogle Scholar

  • Ohsaki, Y., Shirakawa, H., Hiwatashi, K., Furukawa, Y., Mizutani, T. and Komai, M. (2006) Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat. Biosci. Biotechnol. Biochem. 70, 926–932. First citation in articleCrossrefGoogle Scholar

  • Okamato, H. (2008) Vitamin K and rheumatoid arthritis. IUBMB Life. 60, 355–361. First citation in articleCrossrefGoogle Scholar

  • Ohsaki, Y., Shirakawa, H., Miura, A., Giriwono, P., Sato, S., Ohashi, A., Iribe, M., Goto, T. and Komai, M. (2010) Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor κB through the repression of IKKα/β phosphorylation. J. Nutr. Biochem. 21:1120–1126. First citation in articleCrossrefGoogle Scholar

  • Shea, M., Booth, S., Massaro, J., Jacques, P., D‘Agostino, R. S., Dawson-Hughes, B., Ordovas, J. M., O‘Donnell, C. J., Kathiresan, S., Keaney, J. F. Jr et al. (2008) Vitamin K and Vitamin D Status: Associations with Inflammatory Markers in the Framingham Offspring Study. Am. J. Epidemiol. 167, 313–320. First citation in articleGoogle Scholar

  • Kawamura, F., Nakanishi, M. and Hirashima, N. (2010) Effects of menadion, a reactive oxygen generator, on leukotreine secretion from RBL-2H3 cells. Biol. Pharm. Bull. 33, 881–885. First citation in articleGoogle Scholar

  • Van Summeren, M., Vermeer, C., Engelbert, R., Schurgers, L., Takken, T., Fischer, K. and Kuis, W. (2008) Extremes in vitamin K status of bone are related to bone ultrasound properties in children with juvenile idiopathic arthritis. Clin. Exp. Rheumatol. 26, 484–491. First citation in articleGoogle Scholar

  • Neogi, T., Booth, S., Zhang, Y., Jacques, P., Terkeltaub, R., Aliabadi, P. and Felson, D. T. (2006) Low vitamin K status is associated with osteoarthritis in the hand and knee. Arthritis Rheum. 54, 1255–1261. First citation in articleCrossrefGoogle Scholar

  • Okamoto, H., Shidara, K., Hoshi, D. and Kamatani, N. (2007) Anti-arthritis effects of vitamin K(2) (menaquinone-4) – a new potential therapeutic strategy for rheumatoid arthritis. FEBS J. 274, 4588–4594. First citation in articleCrossrefGoogle Scholar

  • Kameda, T., Miyazawa, K., Mori, Y., Yuasa, T., Shiokawa, M., Nakamaru, Y., Mano, H., Hakeda, Y., Kameda, A. and Kumegawa, M. (1996) Vitamin K2 inhibits osteoclastic bone resorption by inducing osteoclast apoptosis. Biochem. Biophys. Res. Commun. 220, 515–519. First citation in articleGoogle Scholar

  • Ginaldi, L., Di Benedetto, M. and De Martinis, M. (2005) Osteoporosis, inflammation and ageing. Immun. Aging 2, 14. First citation in articleGoogle Scholar

  • Baschant, U., Lane, N. E. and Tuckermann, J. (2012) The multiple facets of glucocorticoid action in rheumatoid arthritis. Nat: Rev: Rheumatol. 8; 645–655: First citation in articleCrossrefGoogle Scholar

  • Shea, M., Dallal, G., Dawson-Hughes, B., Ordovas, .J, O‘Donnell, C., Gundberg, C., Peterson, J. W. and Booth, S. L. (2008) Vitamin K, circulating cytokines, and bone mineral density in older men and women. Am. J. Clin. Nutr. 88, 356–363. First citation in articleCrossrefGoogle Scholar

  • Kristensen, M., Kudsk, J., and Bügel, S. (2008) Six weeks phylloquinone supplementation produces undesirable effects on blood lipids with no changes in inflammatory and fibrinolytic markers in postmenopausal women. Eur. J. Nutr. 47, 375–379. First citation in articleCrossrefGoogle Scholar

  • Juanola-Falgarona, M., Salas-Salvadó, J., Estruch, R., Portillo, M., Casas, R., Miranda, J., Martínez-González, M. A. and Bulló, M. (2013) Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk. Cardiovasc. Diabetol. 12, 7. First citation in articleCrossrefGoogle Scholar

  • Wells, G., Becker, J., Teng, J., Dougados, M., Schiff, M., Smolen, J., Aletaha, D. and van Riel, P. L. (2009) Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann. Rheum. Dis. 68, 954–960. First citation in articleCrossrefGoogle Scholar

  • Ebina, K., Shi, K., Hirao, M., Kaneshiro, S., Morimoto, T., Koizumi, K., Yoshikawa, H. and Hashimoto, J. (2013) Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis. Mod. Rheumatol. 23, 1001–1007. First citation in articleGoogle Scholar

  • Braam, L., Knapen, M., Geusens, P., Brouns, F. and Vermeer, C. (2003) Factors affecting bone loss in female endurance athletes: A two-year follow-up study. Am. J. Sports Med. 31, 889–895. First citation in articleCrossrefGoogle Scholar

  • Craciun, A., Wolf, J., Knapen, M., Brouns, F. and Vermeer, C. (1998) Improved bone metabolism in female elite athletes after vitamin K supplementation. Int. J. Sports Med. 19, 479–484. First citation in articleCrossrefGoogle Scholar

  • Gallagher, M. The nutrients and their metabolism. In: Krause’s food and nutrition therapy. (Mahan, L.K, Escott-Stump, S, eds.) Ed. 12, pp. 80–18, Elsevier Health Sciences, St. Louis, MO, USA. First citation in articleGoogle Scholar

  • AsghariJafarabadi, M. and Mohammadi, S. (2013) Statistical series: Summarizing and displaying data. J. Diabetes Lipid Dis. 12, 83–100. First citation in articleGoogle Scholar

  • AsghariJafarabadi, M. and Mohammadi, S. (2013) Statistical series: Introduction to statistical inference (point estimation, confidence interval and hypothesis testing. J. Diabetes Lipid Dis.;12, 173–192. First citation in articleGoogle Scholar

  • AsghariJafarabadi, M. and Mohammadi, S. (2013) Statistical series: Tests for comparing of means. J. Diabetes Lipid Dis. 12, 83–100. First citation in articleGoogle Scholar

  • Kolahi, S., Pourghassem Gargari, B., Mesgari Abbasi, M., Asghari Jafarabadi, M. and Ghamarzad Shishavan, N. (2015) Effects of phylloquinone supplementation on lipid profile in women with rheumatoid arthritis: a double blind placebo controlled study. Nutr. Res. Pract. 9, 186–191. First citation in articleCrossrefGoogle Scholar

  • Tanaka, S., Nishiumi, S., Nishida, M., Mizushina, Y., Kobayashi, K., Masuda, A., Fujita, T., Morita, Y., Mizuno, S., Kutsumi, H., et al. (2010) Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-KB activation. Clin. Exp. Immunol. 160, 283–292. First citation in articleGoogle Scholar

  • Lamson, D. and Plaza, S. (2003) The anticancer effects of vitamin K. Altern. Med. Rev. 8, 303–318. First citation in articleGoogle Scholar

  • Pitsillides, A., Blake, S., Glynn, L., Bitensky, L. and Chayen, J. (1990) Amelioration by menadione of the experimental chronic immune arthritis in the rabbit. Cell Biochem. Funct. 8. 221–226. First citation in articleCrossrefGoogle Scholar

  • Pitsillides, A., Blake S., Glynn, L., Frost, G., Bitensky, L. and Chayen, J. (1991) The effect of menadione epoxide on the experimental immune arthritis in the rabbit. Int. J. Exp. Pathol. 72, 301–309. First citation in articleGoogle Scholar