Jeetendra Kumar Gupta



Hyperhomocysteinemia (Hhcy) is a pathological condition characterized by abnormally large levels of homocysteine in blood. Homocysteine (Hcy) is a highly reactive sulphur-containing amino acid derived from methionine, an essential amino acid. Excess homocysteine produced in the body is excreted out of the tightly regulated cell environment into the blood. It is the role of the liver and kidney to remove excess Hcy from the blood. Hyperhomocysteinemia increases the generation of ROS by activating NADPH oxidase, downregulates the endothelial nitric oxide synthase (eNOS) and thus reduces the bioavailability of nitric oxide (NO). Moreover, it increases the production of proinflammatory cytokines like tumor necrosis factor-α (TNF-α) by activating nuclear factor-kappa B (NF-κB). Hyperhomocysteinemia is caused by the excess deficiencies of the vitamins like pyridoxine (B6), folic acid (B9), or B12 and is considered as an independent risk factor for various cardiovascular diseases like endothelial dysfunction, vascular inflammation, atherosclerosis, hypertension, cardiac hypertrophy and heart failure. 

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McCully K. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969;56:111-28

Thomas G Guilliams. Homocysteine: A Risk Factor Worth Treating. The Standard. 2004;6(1):1-7

Paul Ganguly, Sreyoshi Fatima Alam. Role of homocysteine in the development of cardiovascular disease. Nutrition Journal. 2015;14(6):1

Boushey C, et al. A Quantitative Assessment of Plasma Homocysteine as a Risk Factor for Vascular Disease. Probable Benefits of Increasing Folic Acid Intakes. JAMA. 1995;274:1049-57

Van Guldener C, Stehouwer CD. Homocysteine-lowering treatment: an overview. Expert Opinion on Pharmacotherapy. 2001;2(9):1449-1460.

Reddy N, et al. Prevalence of risk factors for Coronary Atherosclerosis in a Cross-sectional Population of Andhra Pradesh. Indian Heart J. 2002; 54:697-701.

Vollset S et al. Plasma total homocysteine and Cardiovascular mortality. Am J Clin Nutrition. 2001;74:130-6.

Sandesh P Kamdi, Prashant Palkar. Prevelance of hyperhomocysteinemia in healthy Indian doctors. Bioinformation. 2013;9(4):193-194.

D.Mohanty, S Sukumar et al. Hyperhomocysteinemia in healthy Asian Indians. American Journal of Hematology. 2003;72:150-154.

Allon N Friedman, Andrew G Bostom, Andrew S Levey. The Kidney and Homocysteine Metabolism. J Am Soc Nephrol. 2001;12:2181-2189.

Kimura H, Gejyo F, Suzuki S, Miyazaki R: The C677T methylenetetrahydrofolate reductase gene mutation in hemodialysis patients. J Am Soc Nephrol. 2000;11: 885–893.

Silbernagl S. The renal handling of amino acids and oligopeptides. Physiol Rev. 1988;68: 911–1007.

Lars Brattstorm and David E L Wilcken. Homocysteine and cardiovascular disease: cause or effect. AM J Clin Nutri. 2000;72:315-23.

Gupta JK and Qureshi Shaiba Sana. Potential Benefits of Methylcobalamin: A Review. Austin Journal of Pharmacology and Therapeutics. 2015;3(3):1-3.

Pisciotta L, et al. Serum Homocysteine, Methylenetetrahydrofolate Reductase Gene Polymorphism and Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia, Atherosclerosis. ISSN Journal. 2005;179:333-8

Ramakrishnan S, Sulochna KN, Lakshmi S. Biochemistry of Homocysteine in Health and Disease. Indian Journal of Biochemistry & Biophysics. 2006;43:275-283

Jakubowski H. An Overview of Homocysteine Metabolism. Springer-verlag Wien. 2013;7-18.

Alan L Miller, Gregory S Kelly. Methionine and Homocysteine Metabolism and the Nutritional Prevention of Certain Birth defects and Complication of Pregnancy. Alternative Medicine Review.1996;1(4):221-223.

Selhub J. Homocysteine Metabolism. Annual Review of Nutrition. 1999;19:217-246.

Lehmann M, Gottfries CG. Vitamin B12-B6-folate treatment improves blood-brain barrier function in patients with hyperhomocysteinaemia and mild cognitive impairment. Dement Geriatr Cogn Disord. 2003; 16(3):145-50.

Bostom A, et al. Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial. Ann Intern Med. 1997; 127:1089-92

Attilakos A, Papakonstantinou E, Schulpis K, Voudris K. Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy. Epilepsy Res. 2006;71:229–232.

Auer J, Eber B. Homocysteine and Risk of Cardiovascular Disease. J Clin Basic Cardiol 2001; 4:261-4.

Herrmann W. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview. Clin Chem Lab Med. 2001; 39(8):666-74.

Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002;325(7374):1202.

Vollset SE, Refsum H et al. Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study. Am J Clin Nutr. 2001; 74(1):130-6.

Welch G, Loscalzo J. Homocysteine and Atherothrombosis. NEJM. 1998; 338:1042-50.

Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci. 2003;26:137–146.

Vermeer S, et al. Homocysteine, silent brain infarcts and white matter lesions. The Rotterdam Scan study Annals Neurol. 2002; 51:385-9.

Eliza Oprea, Mihai Berteanu et al. Homocysteine and vitamin therapy in stroke prevention and treatment: a review. ABP Journal. 2010;57(4):467-477.

Carluccio MA, Massaro M et al. Homocysteine induces VCAM-1 gene expression through NF-κB and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants. Am J Physiol-Heart Journal. 2007;293:2344-2354.

Nadja Plazar and Mihaela Jurdana. Hyperhomocysteinemia and the role of B vitamins in cancer. Radiol Oncol. 2010; 44(2): 79-85.

Fassbender K, Orell M, Hennerici M. Plasma Homocysteine Concentrations in Cerebrovascular Disease. Stroke. 1999;30:2224-38.

Sun CF, Haven TR, Wu TL, Tsao KC. Serum total homocysteine increases with the rapid proliferation rate of tumor cells and decline upon cell death: a potential new tumor marker. Clin Chim Acta. 2002; 321: 55-62.

Rickles FR, Levine M, Edwards RL. Hemostatic alteration in cancer patients. Cancer Metastasis Rev. 1992;11:237-48.

Welch G, Loscalzo J. Homocysteine and Atherothrombosis. NEJM. 1998;338:1042-50.

Hoogeveen E, et al. Hyperhomocysteinemia increases Risk of Death especially in Type 2 Diabetes: 5 year follow up of the Hoorn Study. Circulation. 2000;101:1506-11.

Buysschaert M, et al. Hyperhomocysteinemia and Type 2 Diabetes. Diabetes Care. 2000;23:1816-22.

Muhammed Khalid Shaikh, Bikha Ram Devrajani, Amjad Shaikh, Syed Zulfiquar Ali Shah, Samina Shaikh and Dolat Singh. Plasma Homocysteine Level in Patients with Diabetes mellitus. World Applied Sciences Journal. 2012;16(9):1269-1273.

Meigs, J.B., P.F. Jacques and J. Selhub. Fasting Plasma Homocysteine Levels in the Insulin Resistance Syndrome. Diabetes Care. 2001; 24:1403-10.

Arroliga AC et al. Association between hyperhomocysteinemia and primary pulmonary hypertension. Respir Med. 2003; 97(7):825-9.

Rodrigo R, Passalacqua W, Araya J, Orellana M, Rivera G. Implications of oxidative stress and homocysteine in the pathophysiology of essential hypertension . J Cardiovasc Pharmacol. 2003; 42(4):453-61.

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Innovare Journal of Medical Sciences
Vol 4 Issue 2 2016 ( April - May) Page: 11-14

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Jeetendra Kumar Gupta
GLA University


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