Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients

Richard F. Macko, Steven J. Kittner, Frederick M. Ivey, Anne Epstein, Mary J. Sparks, J. Richard Hebel, Constance C. Johnson, Robert J. Wityk, Per M. Ueland, Helga Refsum

Research output: Contribution to journalArticle

Abstract

Hyperhomocystinemia linked to B-vitamin deficiency is prevalent and associated with increased risk for stroke. While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B6 (100 mg), and B12 (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23% in plasma TM (P <.005) and 27% in fasting tHcy levels (P <.0001) and a paradoxical 30% rise in vWF antigen levels (P <.05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20% to 28% decline in plasma t-PA activity after methionine load (n = 49, P <.02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalJournal of Stroke and Cerebrovascular Diseases
Volume11
Issue number1
DOIs
StatePublished - 2002

Fingerprint

Homocysteine
Fibrinolysis
Vitamins
Tissue Plasminogen Activator
Vitamin B Complex
Stroke
Thrombomodulin
Wounds and Injuries
Methionine
Plasminogen Inactivators
Antigens
Fasting
Vitamin B Deficiency
Therapeutics
Vascular System Injuries
Plasminogen Activator Inhibitor 1
Folic Acid
Blood Vessels

Keywords

  • Fibrinolysis
  • Homocysteine
  • Methionine load
  • Stroke
  • Thrombomodulin
  • Vitamin therapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Health Professions(all)

Cite this

Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients. / Macko, Richard F.; Kittner, Steven J.; Ivey, Frederick M.; Epstein, Anne; Sparks, Mary J.; Hebel, J. Richard; Johnson, Constance C.; Wityk, Robert J.; Ueland, Per M.; Refsum, Helga.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 11, No. 1, 2002, p. 1-8.

Research output: Contribution to journalArticle

Macko, RF, Kittner, SJ, Ivey, FM, Epstein, A, Sparks, MJ, Hebel, JR, Johnson, CC, Wityk, RJ, Ueland, PM & Refsum, H 2002, 'Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients', Journal of Stroke and Cerebrovascular Diseases, vol. 11, no. 1, pp. 1-8. https://doi.org/10.1053/jscd.2002.123968
Macko, Richard F. ; Kittner, Steven J. ; Ivey, Frederick M. ; Epstein, Anne ; Sparks, Mary J. ; Hebel, J. Richard ; Johnson, Constance C. ; Wityk, Robert J. ; Ueland, Per M. ; Refsum, Helga. / Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients. In: Journal of Stroke and Cerebrovascular Diseases. 2002 ; Vol. 11, No. 1. pp. 1-8.
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abstract = "Hyperhomocystinemia linked to B-vitamin deficiency is prevalent and associated with increased risk for stroke. While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B6 (100 mg), and B12 (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23{\%} in plasma TM (P <.005) and 27{\%} in fasting tHcy levels (P <.0001) and a paradoxical 30{\%} rise in vWF antigen levels (P <.05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20{\%} to 28{\%} decline in plasma t-PA activity after methionine load (n = 49, P <.02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke.",
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