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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5520-5521. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tsamaloukas, A. G. Search for Related Content PubMed Articles by Tsamaloukas, A. G. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CORRESPONDENCE Vitamins and Thrombosis (VITRO) study—homocysteine lowering with B vitamins To the editor: Den Heijer et al1 present their randomized, placebo-controlled, double-blind trial for homocysteine lowering with B vitamins as a measure for secondary prevention of deep vein thrombosis and pulmonary embolism. Of the 8 water-soluble B vitamins, they used folic acid (5 mg), cyanocobalmin (0.4 mg), and pyridoxine (50 mg). In the context of the known genotype-phenotype relation between the MTHFR (OMIM [Online Inheritance in Man] *607093), the homocysteine level, and thrombophilia (OMIM #188050), there remain some problems and questions. What is the share of patients homozygous for the MTHFR C677T genotype? This genetic variant renders this enzyme thermolabile and affects its noncovalent binding of its prosthetic group FAD.2–5 Vitamin B2, or riboflavin, is the biosynthetic precursor of FMN or FAD, the coenzymes or prosthetic groups of diverse oxidoreductases. If there is a link between folate and riboflavin mediated by the MTHFR6–9 as a flavoprotein, what effect or benefit for the cohort of patients in that study could an additional riboflavin supplementation to the aforementioned vitamin B cocktail have? In most of the published studies for lowering homocysteine with B vitamins, riboflavin supplementation is neglected. What are the scientific rationales for choosing the mentioned doses of the 3 vitamins used? Following Ames et al's proposal4 of high-dose vitamin therapy, it may be an underdosing. The MTHFR C677T is an FAD-responsive mutant,2,3 and this should guide future trials for homocysteine lowering by vitamin supplementation with at least folic acid, riboflavin, pyridoxin, and cyanocobalamin in proper dosing. Authorship Correspondence: A. G. Tsamaloukas, Schulstrasse 16-18, D-40721 Hilden, Germany; e-mail: tsamaloukas{at}oxphos.de. Conflict-of-interest disclosure: The author declares no competing financial interests. Antonis Georg Tsamaloukas References den Heijer M, Willems HP, Blom HJ, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial. Blood 2007; 109:139–144.[Abstract/Free Full Text] Scott JM. Genetic diversity and disease: opportunities and challenge. Proc Natl Acad Sci U S A 2001; 98:14754–14756.[Free Full Text] Yamada K, Chen Z, Rozen R, Matthews RG. Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Proc Natl Acad Sci U S A 2001; 98:14853–14858.[Abstract/Free Full Text] Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. Am J Clin Nutr 2002; 75:616–658.[Abstract/Free Full Text] Sibani S, Leclerc D, Weisberg IS, et al. Characterization of mutations in severe methylenetetrahydrofolate reductase deficiency reveals an FAD-responsive mutation. Hum Mutat 2003; 21:509–520.[CrossRef][Medline] [Order article via Infotrieve] Rozen R. Genetic modulation of homocysteinemia. Semin Thromb Hemost 2000; 26:255–261.[CrossRef][Medline] [Order article via Infotrieve] McKinley MC, McNulty H, McPartlin J, Strain JJ, Scott JM. Effect of riboflavin supplementation on plasma homocysteine in elderly people with low riboflavin status. Eur J Clin Nutr 2002; 56:850–856.[CrossRef][Medline] [Order article via Infotrieve] Rozen R. Methylenetetrahydrofolate reductase: a link between folate and riboflavin? Am J Clin Nutr 2002; 76:301–302.[Free Full Text] McNulty H, Dowey LE, RC, Strain JJ, et al. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C T polymorphism. Circulation 2006; 113:74–80.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Response: Homocysteine lowering and recurrent venous thrombosis: the VITRO trial Martin den Heijer, Henk J. Blom, Frits R. Rosendaal, and Gerard M. J. Bos Blood 2007 109: 5521-5522. [Full Text] [PDF] Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial Martin den Heijer, Huub P. J. Willems, Henk J. Blom, Wim B. J. Gerrits, Marco Cattaneo, Sabine Eichinger, Frits R. Rosendaal, and Gerard M. J. Bos Blood 2007 109: 139-144. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tsamaloukas, A. G. Search for Related Content PubMed Articles by Tsamaloukas, A. G. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?

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