The effect of homocysteine reduction by B-vitamin supplementation on inflammatory markers
-
Anita C.T.M. Peeters
Abstract
Background: Hyperhomocysteinemia has been associated with vascular disease in many epidemiological studies. However, the pathophysiology is unclear. It is postulated that increased levels of homocysteine induce an inflammatory response in endothelial cells, mediated by pro-inflammatory cytokines and chemokines. The aim of this study was to investigate whether plasma concentrations of interleukin-6, interleukin-8, C-reactive protein, and monocyte chemoattractant protein-1 are increased with higher plasma homocysteine concentrations and whether decreasing homocysteine by vitamin supplementation decreases the concentration of these markers.
Methods: Plasma homocysteine, interleukin-6, interleukin-8, C-reactive protein, and monocyte chemoattractant protein-1 concentrations were measured in 230 volunteers before and after 8 weeks of multivitamin supplementation (folic acid, B6, and B12).
Results: At baseline, plasma homocysteine concentration was weakly associated with interleukin-8, but not with interleukin-6, C-reactive protein or monocyte chemoattractant protein-1. Vitamin supplementation resulted in a significant decrease in homocysteine concentration, but no effect on interleukin-6, interleukin-8, C-reactive protein or monocyte chemoattractant protein-1 was observed.
Conclusions: At baseline homocysteine was only weakly correlated with interleukin-8, but not with interleukin-6, C-reactive protein or monocyte chemoattractant protein-1. Vitamin supplementation affected homocysteine concentration, but not cytokine levels. The hypothesis that hyperhomocysteinemia increases arteriosclerotic or thrombotic risk through vascular inflammation was not supported by this study.
Clin Chem Lab Med 2007;45:54–8.
References
1. Homocysteine studies collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. J Am Med Assoc 2002;288:2015–22.10.1001/jama.288.16.2015Search in Google Scholar
2. Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost2005;3:292–9.10.1111/j.1538-7836.2005.01141.xSearch in Google Scholar
3. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Br Med J2002;325:1202.10.1136/bmj.325.7374.1202Search in Google Scholar
4. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med1998;338:1042–50.10.1056/NEJM199804093381507Search in Google Scholar
5. Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol2003;42:1149–60.10.1016/S0735-1097(03)00994-XSearch in Google Scholar
6. Van Aken BE, Jansen J, van Deventer SJ, Reitsma PH. Elevated levels of homocysteine increase IL-6 production in monocytic Mono Mac 6 cells. Blood Coagul Fibrinolysis2000;2:159–64.10.1097/00001721-200011020-00007Search in Google Scholar
7. Poddar R, Sivasubramanian N, DiBello PM, Robinson K, Jacobsen DW. Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells. Circulation2001;103:2717–23.10.1161/01.CIR.103.22.2717Search in Google Scholar PubMed
8. Zeng XK, Remick DG, Wang X. Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood. Acta Pharmacol Sin2004;25:1419–25.10.1161/01.RES.0000087642.01082.E4Search in Google Scholar PubMed
9. Ridker PM, Brown NJ, Vaughan DE, Harrison DG, Mehta JL. Established and emerging plasma biomarkers in the prediction of first atherothrombotic events. Circulation2004;109(Suppl V):6–19.10.1161/01.CIR.0000133444.17867.56Search in Google Scholar PubMed
10. Fruchart JC, Nierman MC, Stroes ES, Kastelein JJ, Duriez P. New risk factors for atherosclerosis and patient risk assessment. Circulation2004;109(Suppl II):15–9.10.1161/01.CIR.0000131513.33892.5bSearch in Google Scholar PubMed
11. Den Heijer M, Brouwer IA, Bos GM, Blom HJ, van der Put NM, Spaans AP, et al. Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol1998;18:356–61.10.1161/01.ATV.18.3.356Search in Google Scholar
12. Peeters AC, van der Molen EF, Blom HJ, den Heijer M. The effect of homocysteine reduction by B-vitamin supplementation on markers of endothelial dysfunction. Thromb Haemost2004;92:1086–91.10.1160/TH04-05-0284Search in Google Scholar PubMed
13. Klerk M, Verhoef P, Verbruggen B, Schouten EG, Blom HJ, Bos GM, et al. Effect of homocysteine reduction by B-vitamin supplementation on markers of clotting activation. Thromb Haemost2002;88:230–5.10.1055/s-0037-1613192Search in Google Scholar
14. Fiskerstrand T, Refsum H, Kvalheim G, Ueland PM. Homocysteine and other thiols in plasma and urine: automated determination and sample stability. Clin Chem1993;39:263–71.10.1093/clinchem/39.2.263Search in Google Scholar
15. Te Poele-Pothoff MT, van den Berg M, Franken DG, Boers GH, Jacobs C, de Kroon IF, et al. Three different methods for the determination of total homocysteine in plasma. Ann Clin Biochem1995;32:218–20.10.1177/000456329503200218Search in Google Scholar PubMed
16. Wolbink GJ, Brouwer MC, Buysmann S, ten Berge IJ, Hack CE. CRP-mediated activation of complement in vivo: assessment by measuring circulating complement-C-reactive protein complexes. J Immunol1996;157:473–9.10.4049/jimmunol.157.1.473Search in Google Scholar
17. Holven KB, Aukrust P, Torbjørn H, Ose L, Nenseter MS. Folic acid treatment reduces chemokine release from peripheral blood mononuclear cells in hyperhomocysteinemic subjects. Arterioscler Thromb Vasc Biol2002;22:699–703.10.1161/01.ATV.0000013288.35930.90Search in Google Scholar PubMed
18. Holven KB, Aukrust P, Retterstol K, Hagve TA, Morkrid L, Ose L, et al. Increased levels of C-reactive protein and interleukin-6 in hyperhomocysteinemic subjects. Scand J Clin Lab Invest2006;66:45–54.10.1080/00335510500429821Search in Google Scholar PubMed
19. Gori AM, Corsi AM, Fedi S, Gazzini A, Sofi F, Bartali B, et al. A proinflammatory state is associated with hyper-homocysteinemia in the elderly. Am J Clin Nutr2005;82:335–41.10.1093/ajcn/82.2.335Search in Google Scholar
20. Dusitanond P, Eikelboom JW, Hankey GJ, Thom J, Gilmore G, Loh K, et al. Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke. Stroke2005;36:144–6.10.1161/01.STR.0000150494.91762.70Search in Google Scholar PubMed
21. Spoelstra-de Man AM, Brouwer CB, Terheggen F, Bollen JM, Stehouwer CD, Smulders YM. No effect of folic acid on markers of endothelial dysfunction or inflammation in patients with type 2 diabetes mellitus and mild hyper-homocysteinaemia. Neth J Med2004;62:246–53.Search in Google Scholar
22. Klerk M, Durga JG, Schouten EG, Kluft C, Kok FJ, Verhoef P. No effect of folic acid markers on haemostasis markers and C-reactive protein in older adults. Thromb Haemost2005;94:96–100.10.1160/TH04-08-0524Search in Google Scholar
23. Church TS, Earnest CP, Wood KA, Kampert JB. Reduction of C-reactive protein levels through use of a multivitamin. Am J Med2003;115:702–7.10.1016/j.amjmed.2003.08.024Search in Google Scholar PubMed
24. Vermeulen EG, Rauwerda JA, van den Berg M, de Jong SC, Schalkwijk C, Twisk JW, et al. Homocysteine-lowering treatment with folic acid plus vitamin B6 lowers urinary albumin excretion but not plasma markers of endothelial function or C-reactive protein: further analysis of secondary end-points of a randomized clinical trial. Eur J Clin Invest2003;33:209–15.10.1046/j.1365-2362.2003.01135.xSearch in Google Scholar PubMed
25. Lentz SR, Sobey CG, Piegors DJ, Bhopatkar MY, Faraci FM, Malinow MR, et al. Vascular dysfunction in monkeys with diet-induced hyperhomocyst(e)inemia. J Clin Invest1996;98:24–9.10.1172/JCI118771Search in Google Scholar PubMed PubMed Central
26. Chambers JC, Ueland PM, Obeid OA, Wrigley J, Refsum H, Kooner JS. Improved vascular endothelial function after oral B vitamins – an effect mediated through reduced concentrations of free plasma homocysteine. Circulation2000;102:2479–83.10.1161/01.CIR.102.20.2479Search in Google Scholar
27. Signorello MG, Pascale R, Leoncini G. Effect of homocysteine on arachidonic acid release in human platelets. Eur J Clin Invest2002;32:279–84.10.1046/j.1365-2362.2002.00971.xSearch in Google Scholar PubMed
28. Leoncini G, Pascale R, Signorello MG. Effects of homocysteine on L-arginine transport and nitric oxide formation in human platelets. Eur J Clin Invest2003;33:713–9.10.1046/j.1365-2362.2003.01203.xSearch in Google Scholar PubMed
29. Riba R, Nicolaou A, Troxler M, Homer-Vaniasinkam S, Naseem KM. Altered platelet reactivity in peripheral vascular disease complicated with elevated plasma homocysteine levels. Atherosclerosis2004;175:69–75.10.1016/j.atherosclerosis.2004.02.008Search in Google Scholar PubMed
30. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med2006;354:1578–88.10.1056/NEJMoa055227Search in Google Scholar PubMed
31. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med2006;354:1567–77.10.1056/NEJMoa060900Search in Google Scholar PubMed
©2007 by Walter de Gruyter Berlin New York
Articles in the same Issue
- CCLM: Bringing advances in laboratory medicine to the “New World”
- Diagnostic approach to inherited bleeding disorders
- Linking laboratory and medication data: new opportunities for pharmacoepidemiological research
- Association between polymorphisms of ACE, B2AR, ANP and ENOS and cardiovascular diseases: a community-based study in the Matsu area
- Anti-thyroid-stimulating hormone receptor antibodies determined by second-generation assay
- Serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) in pancreatic cancer patients
- Surrogate markers of insulin resistance in assessing individuals with new categories “prehypertension” and “prediabetes”
- Evaluation of pre-analytical, demographic, behavioural and metabolic variables on fibrinolysis and haemostasis activation markers utilised to assess hypercoagulability
- Hyperhomocysteinaemia and immune activation in patients with cancer
- The effect of homocysteine reduction by B-vitamin supplementation on inflammatory markers
- Lipid peroxidation in Down syndrome caused by regular trisomy 21, trisomy 21 by Robertsonian translocation and mosaic trisomy 21
- Pregnancy-associated plasma protein A in dialysis patients
- L-Cysteine supplementation prevents exercise-induced alterations in human erythrocyte membrane acetylcholinesterase and Na+,K+-ATPase activities
- Assessment of homocysteine, neopterin and nitric oxide levels in Behcet's disease
- Increased adenosine deaminase in hydatidiform mole
- Classification tree analysis for the discrimination of pleural exudates and transudates
- External quality assessment of hemoglobin A2 measurement: data from an Italian pilot study with fresh whole blood samples and commercial HPLC systems
- Comparison of four commercial quantitative HIV-1 assays for viral load monitoring in clinical daily routine
- Interchangeability of measurements of CA 19-9 in serum with four frequently used assays: an update
- Analytical validation of the new version of the Liaison N-Tact PTH assay
- Validation of an automated sensitive immunoassay for quantitation of cytokines in the sputum of cystic fibrosis patients
- Strong interference of hemoglobin concentration on CSF total protein measurement using the trichloroacetic acid precipitation method
- Correction of patient results for Beckman Coulter LX-20 assays affected by interference due to hemoglobin, bilirubin or lipids: a practical approach
- Acquiring a measurement system within the framework of standard ISO 15189
- Six Sigma and laboratory consultation
- ESR or LSRB, that is the question!
- Reply to the Letter written by Hardeman
- Natriuretic peptides. The hormones of the heart
Articles in the same Issue
- CCLM: Bringing advances in laboratory medicine to the “New World”
- Diagnostic approach to inherited bleeding disorders
- Linking laboratory and medication data: new opportunities for pharmacoepidemiological research
- Association between polymorphisms of ACE, B2AR, ANP and ENOS and cardiovascular diseases: a community-based study in the Matsu area
- Anti-thyroid-stimulating hormone receptor antibodies determined by second-generation assay
- Serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) in pancreatic cancer patients
- Surrogate markers of insulin resistance in assessing individuals with new categories “prehypertension” and “prediabetes”
- Evaluation of pre-analytical, demographic, behavioural and metabolic variables on fibrinolysis and haemostasis activation markers utilised to assess hypercoagulability
- Hyperhomocysteinaemia and immune activation in patients with cancer
- The effect of homocysteine reduction by B-vitamin supplementation on inflammatory markers
- Lipid peroxidation in Down syndrome caused by regular trisomy 21, trisomy 21 by Robertsonian translocation and mosaic trisomy 21
- Pregnancy-associated plasma protein A in dialysis patients
- L-Cysteine supplementation prevents exercise-induced alterations in human erythrocyte membrane acetylcholinesterase and Na+,K+-ATPase activities
- Assessment of homocysteine, neopterin and nitric oxide levels in Behcet's disease
- Increased adenosine deaminase in hydatidiform mole
- Classification tree analysis for the discrimination of pleural exudates and transudates
- External quality assessment of hemoglobin A2 measurement: data from an Italian pilot study with fresh whole blood samples and commercial HPLC systems
- Comparison of four commercial quantitative HIV-1 assays for viral load monitoring in clinical daily routine
- Interchangeability of measurements of CA 19-9 in serum with four frequently used assays: an update
- Analytical validation of the new version of the Liaison N-Tact PTH assay
- Validation of an automated sensitive immunoassay for quantitation of cytokines in the sputum of cystic fibrosis patients
- Strong interference of hemoglobin concentration on CSF total protein measurement using the trichloroacetic acid precipitation method
- Correction of patient results for Beckman Coulter LX-20 assays affected by interference due to hemoglobin, bilirubin or lipids: a practical approach
- Acquiring a measurement system within the framework of standard ISO 15189
- Six Sigma and laboratory consultation
- ESR or LSRB, that is the question!
- Reply to the Letter written by Hardeman
- Natriuretic peptides. The hormones of the heart
