Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism

Clinical Chemistry and Laboratory Medicine

Volumn 51, Issue 8, 2013, Pages 1643-1650

  Smith, Desirée E C ^a   Hornstra, Jacqueline M ^a   Kok, Robert M ^a   Blom, Henk J ^a,b   Smulders, Yvo M ^a,b  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b VU UNIVERSITY AMSTERDAM   (Netherlands)

Author keywords

cardiovascular disease; folate; homocysteine; intracellular concentrations; S adenosylmethionine

Indexed keywords

5 METHYLTETRAHYDROFOLIC ACID; 5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); CYSTATHIONINE; FOLIC ACID; HOMOCYSTEINE; METHIONINE; PLACEBO; S ADENOSYLHOMOCYSTEINE; S ADENOSYLMETHIONINE;

ADULT; AMINO ACID BLOOD LEVEL; ARTICLE; CARBON METABOLISM; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; FEMALE; HUMAN; HUMAN EXPERIMENT; IN VITRO STUDY; LIQUID CHROMATOGRAPHY; LYMPHOBLAST; MALE; NORMAL HUMAN; ONE CARBON METABOLISM; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SUPPLEMENTATION; TANDEM MASS SPECTROMETRY;

ADULT; CARBON; DIETARY SUPPLEMENTS; DOUBLE-BLIND METHOD; FEMALE; FOLIC ACID; HOMOCYSTEINE; HUMANS; LEUKOCYTES, MONONUCLEAR; MALE; MIDDLE AGED; REFERENCE VALUES; YOUNG ADULT;

EID: 84882971137     PISSN: 14346621     EISSN: 14374331     Source Type: Journal    
DOI: 10.1515/cclm-2012-0694     Document Type: Article

References (28)

1. Homocysteine and risk of ischemic heart disease and stroke: A meta-Analysis. J Am Med Assoc 2002;288:2015-22
2. McCully KS. Vascular pathology of homocysteinemia: Implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969;56:111-28
3. Shaw GM, Schaffer D, Velie EM, Morland K, Harris JA. Periconceptional vitamin use, dietary folate, and the occurrence of neural tube defects. Epidemiology 1995;6:219-26
4. Clarke R, Halsey J, Bennett D, Lewington S. Homocysteine and vascular disease: Review of published results of the homocysteine-lowering trials. J Inherit Metab Dis 2011;34: 83-91
5. Smulders YM, Blom HJ. The homocysteine controversy. J Inherit Metab Dis 2011;34:93-9
6. Finkelstein JD. The metabolism of homocysteine: Pathways and regulation. Eur J Pediatr 1998;157:S40-4
7. Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990;1:228-37 (Pubitemid 20199381)
8. Kerins DM, Koury MJ, Capdevila A, Rana S, Wagner C. Plasma S-Adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine. Am J Clin Nutr 2001;74:723-9 (Pubitemid 33101791)
9. Green TJ, Skeaff CM, McMahon JA, Venn BJ, Williams SM, Devlin AM, et al. Homocysteine-lowering vitamins do not lower plasma S-Adenosylhomocysteine in older people with elevated homocysteine concentrations. Br J Nutr 2010;103:1629-34
10. Becker A, Smulders YM, Teerlink T, Struys EA, de MK, Kostense PJ, et al. S-Adenosylhomocysteine and the ratio of S-Adenosylmethionine to S-Adenosylhomocysteine are not related to folate, cobalamin and vitamin B6 concentrations. Eur J Clin Invest 2003;33:17-25 (Pubitemid 36051287)
11. Caudill MA, Wang JC, Melnyk S, Pogribny IP, Jernigan S, Collins MD, et al. Intracellular S-Adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyldeficient cystathionine beta-synthase heterozygous mice. J Nutr 2001;131:2811-8 (Pubitemid 33063107)
12. Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ. Increase in plasma homocysteine associated with parallel increases in plasma S-Adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem 2000;275:29318-23 (Pubitemid 32043802)
13. Huang Y, Lu ZY, Brown KS, Whitehead AS, Blair IA. Quantification of intracellular homocysteine by stable isotope dilution liquid chromatography/tandem mass spectrometry. Biomed Chromatogr 2007;21:107-12 (Pubitemid 46164999)
14. Deguchi T, Barchas J. Inhibition of transmethylations of biogenic amines by S-Adenosylhomocysteine. Enhancement of transmethylation by adenosylhomocysteinase. J Biol Chem 1971;246:3175-81
15. Struys EA, Jansen EE, de Meer K, Jakobs C. Determination of S-Adenosylmethionine and S-Adenosylhomocysteine in plasma and cerebrospinal fluid by stable-isotope dilution tandem mass spectrometry. Clin Chem 2000;46:1650-6
16. Smith DE, Kok RM, Teerlink T, Jakobs C, Smulders YM. Quantitative determination of erythrocyte folate vitamer distribution by liquid chromatography-Tandem mass spectrometry. Clin Chem Lab Med 2006;44:450-9
17. Kok RM, Smith DE, Barto R, Spijkerman AM, Teerlink T, Gellekink HJ, et al. Global DNA methylation measured by liquid chromatography-Tandem mass spectrometry: Analytical technique, reference values and determinants in healthy subjects. Clin Chem Lab Med 2007;45:903-11 (Pubitemid 47041882)
18. Steed MM, Tyagi SC. Mechanisms of cardiovascular remodeling in hyperhomocysteinemia. Antioxid Redox Signal 2011;15:1927-43
19. Ashfield-Watt PA, Moat SJ, Doshi SN, McDowell IF. Folate, homocysteine, endothelial function and cardiovascular disease. What is the link? Biomed Pharmacother 2001;55: 425-33 (Pubitemid 32913566)
20. Medina M, Urdiales JL, Mores-Sanchez MI. Roles of homocysteine in cell metabolism: Old and new functions. Eur J Biochem 2001;268:3871-82 (Pubitemid 32878521)
21. Melnyk S, Pogribna M, Pogribny IP, Yi P, James SJ. Measurement of plasma and intracellular S-Adenosylmethionine and S-Adenosylhomocysteine utilizing coulometric electrochemical detection: Alterations with plasma homocysteine and pyridoxal 5-phosphate concentrations. Clin Chem 2000;46:265-72 (Pubitemid 30104251)
22. Antoniades C, Shirodaria C, Leeson P, Baarholm OA, Van-Assche T, Cunnington C, et al. MTHFR 677 C > T Polymorphism reveals functional importance for 5-methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state and endothelial function in human atherosclerosis. Circulation 2009;119:2507-15
23. Stead LM, Brosnan ME, Brosnan JT. Characterization of homocysteine metabolism in the rat liver. Biochem J 2000;350:685-92
24. Jung AY, Smulders Y, Verhoef P, Kok FJ, Blom H, Kok RM, et al. No effect of folic acid supplementation on global DNA methylation in men and women with moderately elevated homocysteine. PLoS One 2011;6:e24976
25. Finkelstein JD. Metabolic regulatory properties of S-Adenosylmethionine and S-Adenosylhomocysteine. Clin Chem Lab Med 2007;45:1694-9 (Pubitemid 350232969)
26. Stam F, Smulders YM, van Guldener C, Jakobs C, Stehouwer CD, de Meer K. Folic acid treatment increases homocysteine remethylation and methionine transmethylation in healthy subjects. Clin Sci (Lond) 2005;108:449-56 (Pubitemid 40685675)
27. Ross J, Green J, Baugh CM, MacKenzie RE, Matthews RG. Studies on the polyglutamate specificity of methylenetetrahydrofolate dehydrogenase from pig liver. Biochemistry 1984;23:1796-801 (Pubitemid 14139818)
28. van der Molen EF, Hiipakka MJ, van Lith-Zanders H, Boers GH, van den Heuvel LP, Monnens LA, et al. Homocysteine metabolism in endothelial cells of a patient homozygous for cystathionine beta-synthase (CS) deficiency. Thromb Haemost 1997;78:827-33 (Pubitemid 27365579)