SpringerLink
Log in

Metabolic Role of Hyperhomocysteinemia in the Etiology of Chronic Diseases

  • Chapter
  • First Online:
Nutritional Management and Metabolic Aspects of Hyperhomocysteinemia

Abstract

The significance of elevated blood homocysteine (Hcy) in clinical practice is a serious subject for researchers and is considered as a marker of certain diseases [1]. Hcy, is a sulfur containing, non-proteinogenic amino acid required for the growth of cells and tissues [2, 3]. It is produced exclusively from methionine (Met), an essential amino acid obtained from diet [4]. Hcy is normally present in human plasma at lower concentrations. The normal range is reported to be 5–15 micromol/L [5]. The level could be affected by health-related behaviours, including diet, excessive coffee intake, alcohol consumption, cigarette smoking, and sedentary lifestyle [6, 7]. Total plasma Hcy could be in the form of free Hcy, protein-bound Hcy, oxidized forms of Hcy, and Hcy-thiolactone [3]. This is used as a predictive risk factor for stroke progression, cardiovascular disorders, test for vitamin B12 deficiency, and screening for inborn errors of Met metabolism. An increase of Hcy is referred to as hyperhomocysteinemia (HHcy) which is a sensitive marker of folate and vitamin B 12 deficiency and is associated with an increased risk of cardiovascular disease (CVD), pregnancy complications, cognitive impairment, stoke, and other diseases [8–10]. Plasma levels between 15 and 30 micromol/L are referred as mild HHcy, whereas levels between 31 and 100 micromol/L are moderate HHcy and levels above 100 micromol/L are described as severe HHcy [11]. There are also other studies which report that HHcy are associated with atherosclerosis, thrombosis, birth defects, osteoporosis, diabetes, and renal disease [2]. It is also reported to be highly prevalent in chronic kidney disease (CKD) patients. There are several risk factors that could lead to HHcy- the main cause being insufficient intake of vitamin B group especially folic acid (B9), pyridoxine (B6), or B12 (cyanocobalamin), and several polymorphisms involved in methionine (Met) metabolism [9]. This could also lead to high excretion of Hcy (oxidized Hcy) in urine (homocystinuria) [12]. The relation between HHcy and morphological changes in the organs are extremely important to improve the diagnostic methods and to develop effective treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
EUR 29.95
Price includes VAT (Germany)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
EUR 85.59
Price includes VAT (Germany)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
EUR 106.99
Price includes VAT (Germany)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
EUR 106.99
Price includes VAT (Germany)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Djurovic Z, Mutavdzin S, Drobnjakovic M, Djurovic M, Cvrkota I, Jovanovic V (2018) Relationship between malignant brain tumors and values of homocysteine, folic acid and vitamin B12. Ser J Exp Clin Res 2018:1–6

    Google Scholar 

  2. El-Gharib M (2018) Hyperhomocysteinemia and polycystic ovary syndrome. Reprod Med Int 1:1–3

    Google Scholar 

  3. Škovierová H, Vidomanová E, Mahmood S, Sopková J, Drgová A, Cervenová T, Halašová E, Lehotský J (2016) The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int J Mol Sci 17:1–18

    Google Scholar 

  4. Cardoso IL (2018) Hyperhomocysteinemia: how does it affect the development of cardiovascular disease? Int Arch Cardiovasc Dis 2:1–12

    Google Scholar 

  5. Yakub M, Iqbal MP, Iqbal R (2010) Dietary patterns are associated with hyperhomocysteinemia in an urban Pakistani population. J Nutr 140:1261–1266

    Article  CAS  PubMed  Google Scholar 

  6. Ansari R, Mahta A, Mallack E, Luo JJ (2014) Hyperhomocysteinemia and neurologic disorders: a review. J Clin Neurol 10:281–288

    Article  PubMed  PubMed Central  Google Scholar 

  7. Dinavahi R, Falkner B (2004) Relationship of homocysteine with cardiovascular disease and blood pressure. J Clin Hypertens 6:494–500

    Article  CAS  Google Scholar 

  8. Pinzon RT, Sanyasi RDLR, Pramudita EA (2020) The proportion hyperhomocysteinemia in chronic kidney disease patients. Asian J Med Sci 11:14–17

    Article  Google Scholar 

  9. AL-Haially FFH, Mahood RAH (2019) Effects of hyperhomocysteinemia, vitamin B12, vitamin B6 and troponine-I on patients with myocardial infarction in Baghdad city, Iraq. Biosci Res 16:830–833

    Google Scholar 

  10. Moon HW, Whang DH, Ko YJ, Joo SY, Yun YM, Hur M, Kim JQ (2011) Reference interval and determinants of the serum homocysteine level in a Korean population. J Clin Lab Anal 25:317–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hillenbrand R, Hillenbrand A, Liewald F, Zimmermann J (2008) Hyperhomocysteinemia and recurrent carotid stenosis. BMC Cardiovasc Disord 8:1–6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Vargas CR, Sitta A, Wajner M (2018) The role of hyperhomocysteinemia in disease. J Inborn Errors Metab Screen 6:1–2

    Article  CAS  Google Scholar 

  13. Wijekoon EP, Brosnan ME, Brosnan JT (2006) Homocysteine metabolism. In: Cheema SK (ed) Biochemistry of atherosclerosis. Springer, New York, pp 329–357

    Chapter  Google Scholar 

  14. Phipps MS, Cronin CA (2020) Management of acute ischemic stroke. BMJ 368:1–15

    Google Scholar 

  15. Saadah MA, Thakre MC, Saadah LM (2006) Homocystinemia and stroke in vegetarians. Neurosciences 2006(11):107–111

    Google Scholar 

  16. Torphy JM, Burke AE, Glass RM (2010) Hemorrhagic stroke. JAMA 303:2312

    Article  Google Scholar 

  17. Kristensen B, Malm J, Nilsson TK, Hultdin J, Carlberg B, Dahlen G, Olsson T (1999) Hyperhomocysteinemia and hypofibrinolysis in young adults with ischemic stroke. Stroke 30:974–980

    Article  CAS  PubMed  Google Scholar 

  18. Luo Y, ** H, Guo ZN, Zhang P, Zhang LY, Chen J, Yu Y, Wang Y, Liu J, He QY, Sun X, Yang Y (2019) Effect of hyperhomocysteinemia on clinical outcome and hemorrhagic transformation after thrombolysis in ischemic stroke patients. Front Neurol 10:1–8

    Article  Google Scholar 

  19. Kelly PJ, Barron M, Furie KL (2002) Hyperhomocysteinemia, MTHFR 677C→T polymorphism, and stroke. Stroke 33:1452–1453

    Article  CAS  PubMed  Google Scholar 

  20. Davì G, Minno GD, Coppola A, Andria G, Cerbone AM, Madonna P, Antonella T, Falco A, Marchesani P, Ciabattoni G, Patrono C (2001) Oxidative stress and platelet activation in homozygous homocystinuria. Circulation 104:1124–1128

    Article  PubMed  Google Scholar 

  21. Essouma M, Noubiap JJN (2015) Therapeutic potential of folic acid supplementation for cardiovascular disease prevention through homocysteine lowering and blockade in rheumatoid arthritis patients. Biomark Res 3:1–11

    Article  Google Scholar 

  22. Annerbo S, Wahlund LO, Lokk J (2006) The significance of thyroid-stimulating hormone and homocysteine in the development of Alzheimer’s disease in mild cognitive impairment: a 6-year follow-up study. Am J Alzheimers Dis Other Dement 21:182–188

    Article  Google Scholar 

  23. Janelidze M, Botchorishvili N (2018) Mild cognitive impairment. Alzheimer’s disease. Intech Open, pp 91–107

    Google Scholar 

  24. Kim HJ, Sohn IW, Kim YS, Jun JB (2020) The different relationship between homocysteine and uric acid levels with respect to the MTHFR C677T polymorphism according to gender in patients with cognitive impairment. Nutrients 12:1–13

    CAS  Google Scholar 

  25. Price BR, Wilcock DM, Weekman EM (2018) Hyperhomocysteinemia as a risk factor for vascular contributions to cognitive impairment and dementia. Front Aging Neurosci 10:1–12

    Article  CAS  Google Scholar 

  26. Schneider JA, Bennett DA (2010) Where vascular meets neurodegenerative disease. Stroke 41:1–6

    Article  Google Scholar 

  27. Vemuri P, Knopman DS (2016) The role of cerebrovascular disease when there is concomitant Alzheimer disease. Biochim Biophys Acta 1862:952–956

    Article  CAS  PubMed  Google Scholar 

  28. Miller JW, Green R, Mungas DM, Reed BR, Jagust WJ (2002) Homocysteine, vitamin B6, and vascular disease in AD patients. Neurology 58:1471–1475

    Article  CAS  PubMed  Google Scholar 

  29. Clarke R, Harrison G, Richards S, Vital Trial Collaborative Group (2003) Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. J Intern Med 254:67–75

    Article  CAS  PubMed  Google Scholar 

  30. Rasic-Markovic A, Stanojlovic O, Hrncic D, Krstic D, Colovic M, Susic V, Radosavljevic T, Djuric D (2009) The activity of erythrocyte and brain NaC/KC and Mg2C-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration. Mol Cell Biochem 327:39–45

    Article  CAS  PubMed  Google Scholar 

  31. Moustafa AA, Hewedi DH, Eissa AM, Myers CE, Sadek HA (2012) The relationship between associative learning, transfer generalization, and homocysteine levels in mild cognitive impairment. PLoS One 7:1–11

    Article  CAS  Google Scholar 

  32. Blasko I, Jellinger K, Kemmler G, Krampla W, Jungwirth S, Wichart I, Tragl KH, Fischer P (2008) Conversion from cognitive health to mild cognitive impairment and Alzheimer’s disease: prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine. Neurobiol Aging 29:1–11

    Article  CAS  PubMed  Google Scholar 

  33. Kado DM, Karlamangla AS, Huang MH, Troen A, Rowe JW, Selhub J, Seeman TE (2005) Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. Am J Med 118:161–167

    Article  CAS  PubMed  Google Scholar 

  34. Ford AH, Flicker L, Alfonso H, Thomas J, Clarnette R, Martins R, Almeida OP (2010) Vitamins B12, B6, and folic acid for cognition in older men. Neurology 75:1540–1547

    Article  CAS  PubMed  Google Scholar 

  35. Reitz C, Tang MX, Miller J, Green R, Luchsinger JA (2009) Plasma homocysteine and risk of mild cognitive impairment. Dement Geriatr Cogn Disord 27:11–17

    Article  CAS  PubMed  Google Scholar 

  36. Lakshmaiah P, Saisree BH, Sai CS, Deepthi L, Sridevi B (2019) A short review on scales for outcomes in Parkinson’s disease. J Emerg Technol Innov Res 6:180–187

    Google Scholar 

  37. Vallelunga A, Pegoraro V, Pilleri M, Biundo R, Iuliis AD, Marchetti M, Facchini S, Dojot PF, Antonini A (2013) The MTHFR C677T polymorphism modifies age at onset in Parkinson’s disease. Neurol Sci 35:73–77

    Article  PubMed  Google Scholar 

  38. Lee HJ, Song IU, Kim YD, Cho HJ, Chung SW, Yang YS (2012) Is there the preventive effect of COMT-inhibitor on Parkinson’s disease associated with dementia? Dement Neurocogn Disord 11:136–140

    Article  Google Scholar 

  39. Chen H, Zhang SM, Schwarzschild MA, Hernán MA, Logroscino G, Willett WC, Ascherio A (2004) Folate intake and risk of Parkinson’s disease. Am J Epidemiol 160:368–375

    Article  PubMed  Google Scholar 

  40. Zhang S, Shi CH, Mao C, Song B, Hou H, Wu J, Liu X, Luo H, Sun S, Xu Y (2015) Plasma homocysteine, vitamin B12 and folate levels in multiple system atrophy: a case-control study. PLoS One 10:1–7

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  42. Christine CW, Auinger P, Joslin A, Yelpaala Y, Green R (2018) Vitamin B12 and homocysteine levels predict different outcomes in early Parkinson’s disease. Mov Disord 33:762–770

    Article  CAS  PubMed  Google Scholar 

  43. Ibrahimagic OC, Smajlovic D, Dostovic Z, Pasic Z, Kunic S, Iljazovic A, Salihovic DS (2016) Hyperhomocysteinemia and its treatment in patients with Parkinson’s disease. Mater Socio Med 28:303–306

    Article  Google Scholar 

  44. McCann H, Stevens C, Cartwright H, Halliday G (2014) α-Synucleinopathy phenotypes. Parkinsonism Relat Disord 20:S62–S67

    Article  PubMed  Google Scholar 

  45. Bhosale UA, Yegnanarayan R, Agrawal A, Patil A (2019) Efficacy study of folic acid supplementation on homocysteine levels in adolescent epileptics taking antiepileptic drugs: a single blind randomized controlled clinical trial. Ann Neurosci 26:50–54

    Article  PubMed  Google Scholar 

  46. Mahdavi A, Alavi Naeini A, Najafi M, Ghazvini M, Meracy M (2019) Vitamin B12 and folate status in patients with epilepsy under levetiracetam monotherapy. Int J Prev Med 10:1–5

    Google Scholar 

  47. Varshney KK, Gupta JK, Mujwar S (2019) Homocysteine induced neurological dysfunctions: a link to neurodegenerative disorders. Int J Med Res Health Sci 8:135–146

    Google Scholar 

  48. Shaheen HA, ElGawhary S, Neazeye M, Makhlof H, ElShafay S (2006) Epilepsy, hyperhomocysteinemia and mutant methylenetetrahydrofolate reductase gene. Egypt J Neurol Psychiatry Neurosurg 43:495–505

    Google Scholar 

  49. Attilakos A, Paschalidou M, Garoufi A, Tsirouda M, Papadopoulou A, Karalexi M, Dinopoulos A (2019) Short-term and long-term effects of levetiracetam monotherapy on homocysteine metabolism in children with epilepsy: a prospective study. J Clin Neurol 15:149–151

    Article  PubMed  PubMed Central  Google Scholar 

  50. Gorgone G, Caccamo D, Pisani LR, Curro M, Parisi G, Oteri G, Lentile R, Rossini PM (2009) Hyperhomocysteinemia in patients with epilepsy: does it play a role in the pathogenesis of brain atrophy? A preliminary report. Epilepsia 50:33–36

    Article  CAS  PubMed  Google Scholar 

  51. Azad MAK, Huang P, Liu G, Ren W, Teklebrh T, Yan W, Zhou X, Yin Y (2018) Hyperhomocysteinemia and cardiovascular disease in animal model. Amino Acids 50:3–9

    Article  CAS  PubMed  Google Scholar 

  52. Mieres JH (2006) Review of the American Heart Association’s guidelines for cardiovascular disease prevention in women. Heart 92:iii10–iii13

    Article  PubMed  PubMed Central  Google Scholar 

  53. Poppas A (2020) Cardiovascular disease a focus on women’s health. JACC Case Rep 2:168–170

    Article  PubMed  PubMed Central  Google Scholar 

  54. McCully KS (1969) Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 56(1):111–128

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Choy PC, Mymin D, Zhu Q, Dakshinamurti K, Karmin O (2000) Atherosclerosis risk factors: the possible role of homocysteine. Mol Cell Biochem 207:143–148

    Article  CAS  PubMed  Google Scholar 

  56. Manolescu BN, Oprea E, Farcasanu IC, Berteanu M, Cercasov C (2010) Homocysteine and vitamin therapy in stroke prevention and treatment: a review. Acta Biochim Pol 57:467–477

    Article  CAS  PubMed  Google Scholar 

  57. He L, Zeng H, Li F, Feng J, Liu S, Liu J, Yu J, Mao J, Hong T, Chen AF, Wang X, Wang G (2010) Homocysteine impairs coronary artery endothelial function by inhibiting tetrahydrobiopterin in patients with hyperhomocysteinemia. Am J Physiol Endocrinol Metab 299:E1061–E1065

    Article  CAS  PubMed  Google Scholar 

  58. Antoniades C, Shirodaria C, Leeson P, Baarholm OA, Van-Assche T, Cunnington C, Pillai R, Ratnatunga C, Tousoulis D, Stefanadis C, Refsum H, Channon KM (2009) 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 119:2507–2515

    Article  CAS  PubMed  Google Scholar 

  59. Kim BJ, Seo M, Huh JK, Kwon CH, Kim JT, Sung KC, Kim BS, Kang JH (2011) Associations of plasma homocysteine levels with arterial stiffness in prehypertensive individuals. Clin Exp Hypertens 33:411–417

    Article  CAS  PubMed  Google Scholar 

  60. Wu N, Sarna LK, Siow YL, Karmin O (2011) Regulation of hepatic cholesterol biosynthesis by berberine during hyperhomocysteneimia. Am J Phys Regul Integr Comp Phys 300:R635–R643

    CAS  Google Scholar 

  61. Wijekoon EP, Brosnan ME, Brosnan JT (2007) Homocysteine metabolism in diabetes. Biochem Soc Trans 35:1175–1179

    Article  CAS  PubMed  Google Scholar 

  62. Chen S, Dong Z, Zhao Y, Sai N, Wang X, Liu H, Huang G, Zhang X (2017) Homocysteine induces mitochondrial dysfunction involving the crosstalk between oxidative stress and mitochondrial pSTAT3 in rat ischemic brain. Sci Rep 7:1–12

    CAS  Google Scholar 

  63. Zhang XM, Zhao YQ, Yan H, Liu H, Huang GW (2017) Inhibitory effect of homocysteine on rat neural stem cell growth in vitro is associated with reduced protein levels and enzymatic activities of aconitase and respiratory complex III. J Bioenerg Biomembr 49:131–138

    Article  CAS  PubMed  Google Scholar 

  64. Watanabe M, Osada J, Aratani Y, Kluckman K, Reddick R, Malinow MR, Maeda N (1995) Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci 92:1585–1589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Dayal S, Bottiglieri T, Arning E, Maeda N, Malinow MR, Sigmund CD, Heistad DD, Faraci FM (2001) Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice. Circ Res 88:1203–1209

    Article  CAS  PubMed  Google Scholar 

  66. Schwahn BC, Laryea MD, Chen Z, Melnyk S, Pogribny I, Garrow T, James SJ, Rozen R (2004) Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency. Biochem J 382:831–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Virdis A, Iglarz M, Neves M, Amiri F, Touyz R, Rozen R, Schiffrin E (2003) Effect of hyperhomocystinemia and hypertension on endothelial function in methylenetetrahydrofolate reductase-deficient mice. Arterioscler Thromb Vasc Biol 23:1352–1357

    Article  CAS  PubMed  Google Scholar 

  68. Ambrosi P, Rolland PH, Bodard H, Barlatier A, Charpiot P, Guisgand G, Friggi A, Ghiringhelli O, Habib G, Bouvenot G, Garcon D, Luccioni R (1999) Effects of folate supplementation in hyperhomocysteinemic pigs. J Am Coll Cardiol 34:274–279

    Article  CAS  PubMed  Google Scholar 

  69. Lang D, Kredan MB, Moat SJ, Hussain SA, Powell CA, Bellamy MF, Powers HJ, Lewis MJ (2000) Homocysteine-induced inhibition of endothelium-dependent relaxation in rabbit aorta: role for superoxide anions. Arterioscler Thromb Vasc Biol 20:422–427

    Article  CAS  PubMed  Google Scholar 

  70. Turrini E, Ferruzzi L, Fimognari C (2015) Potential effects of pomegranate polyphenols in cancer prevention and therapy. Oxidative Med Cell Longev 2015:938475

    Article  Google Scholar 

  71. Sestili P, Fimognari C (2015) Cytotoxic and antitumor activity of sulforaphane: the role of reactive oxygen species. Biomed Res Int 2015:1–9

    Article  CAS  Google Scholar 

  72. Thun MJ, DeLancey JO, Center MM, Jemal A, Ward EM (2010) The global burden of cancer: priorities for prevention. Carcinogenesis 31:100–110

    Article  CAS  PubMed  Google Scholar 

  73. Marrett LD, De P, Airia P, Dryer D (2008) Cancer in Canada in 2008. CMAJ 179:1163–1170

    Article  PubMed  PubMed Central  Google Scholar 

  74. Schouten LJ, Straatman H, Kiemeney LALM, Verbeek ALM (1994) Cancer incidence: life table risk versus cumulative risk. J Epidemiol Community Health 48:596–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Callahan MA, Sexton K (2007) If cumulative risk assessment is the answer, what is the question? Environ Health Prospect 115(5):799–806

    Article  CAS  Google Scholar 

  76. Ames BN, Gold LS (1998) The causes and prevention of cancer: the role of environment. Biotherapy 11:205–220

    Article  CAS  PubMed  Google Scholar 

  77. Mwaka AD, Orach CG, Were EM, Lyratzopoulos G, Wabinga H, Roland M (2015) Awareness of cervical cancer risk factors and symptoms: cross-sectional community survey in post-conflict northern Uganda. Health Expect 19(4):854–867

    Article  PubMed  PubMed Central  Google Scholar 

  78. Plazar N, Jurdana M (2010) Hyperhomocysteinemia and the role of B vitamins in cancer. Radiol Oncol 44:79–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Shiao SPK, FAAN RN, Yu CH (2016) Meta-prediction of MTHFR gene polymorphism mutations and associated risk for colorectal cancer. Biol Res Nurs 18:357–369

    Article  CAS  PubMed  Google Scholar 

  80. Keshteli AH, Baracos VE, Madsen K (2015) Hyperhomocysteinemia as a potential contributor of colorectal cancer development in inflammatory bowel diseases: a review. World J Gastroenterol 21:1081–1090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Phelip J, Ducros V, Faucheron JL, Flourie B (2008) Association of hyperhomocysteinemia and folate deficiency with colon tumors in patients with inflammatory bowel disease. Inflamm Bowel Dis 14:242–248

    Article  PubMed  Google Scholar 

  82. Chiang FF, Wang HM, Lan YC, Yang MH (2013) High homocysteine is associated with increased risk of colorectal cancer independently of oxidative stress and antioxidant capacities. Clin Nutr 33:1054–1060

    Article  PubMed  CAS  Google Scholar 

  83. Lim YJ, Kim JH, Park SK, Son HJ, Kim JJ, Kim YH (2012) Hyperhomocysteinemia is a risk factor for colorectal adenoma in women. J Clin Biochem Nutr 51:132–135

    Article  PubMed  PubMed Central  Google Scholar 

  84. Kim YI (2006) Folate: a magic bullet or a double-edged sword for colorectal cancer prevention? Gut 55:1387–1389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Hekim N, Ergen A, Yaylim I, Yilmaz H, Zeybek U, Ozturk O, Isbir T (2005) No association between methylenetetrahydrofolate reductase C677T polymorphism and breast cancer. Cell Biochem Funct 25:115–117

    Article  Google Scholar 

  86. Al-Awadi F, Yang M, Tan Y, Han Q, Li S, Hoffman RM (2008) Human tumor growth in nude mice is associated with decreased plasma cysteine and homocysteine. Anticancer Res 28:2541–2544

    CAS  PubMed  Google Scholar 

  87. Murr C, Fuith LC, Widner B, Wirleitner B, Baier-Bitterlich G, Fuchs D (1999) Increased neopterin concentrations in patients with cancer: indicator of oxidative stress? Anticancer Res 19:1721–1728

    CAS  PubMed  Google Scholar 

  88. Battistelli S, Vittoria A, Stefanoni M, Bing C, Roviello F (2006) Total plasma homocysteine and methylenetetrahydrofolate reductase C677T polymorphism in patients with colorectal carcinoma. World J Gastroenterol 12:6128–6132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Miller JW, Beresford S, Neuhouser ML, Cheng TYD, Song X, Brown EC, Zheng Y, Rodriguez BL, Green R, Ulrich CM (2013) Homocysteine, cysteine, and risk of incident colorectal cancer in the Women’s Health Initiative observational cohort. Am J Clin Nutr 97:827–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Food Technology, Saintgits College of Engineering, Kerala, India

    Sithara Suresh

  2. Food Science and Nutrition Department, CAMS, Sultan Qaboos University, Muscat, Oman

    Mostafa I. Waly

Authors
  1. Sithara Suresh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mostafa I. Waly
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Food Science and Nutrition, Sultan Qaboos University, Alkhod, Oman

    Mostafa I. Waly

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Suresh, S., Waly, M.I. (2021). Metabolic Role of Hyperhomocysteinemia in the Etiology of Chronic Diseases. In: Waly, M.I. (eds) Nutritional Management and Metabolic Aspects of Hyperhomocysteinemia. Springer, Cham. https://doi.org/10.1007/978-3-030-57839-8_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-57839-8_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-57838-1

  • Online ISBN: 978-3-030-57839-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation