Abstract
Dietary proteins metabolism involves the production of homocysteine which result from methionine as a sulfur-containing amino acid. Elevated levels of plasma homocysteine are associated with high risk of cardiovascular diseases. However, Previous studies indicate that plasma homocysteine can be used as a tumor marker and can be considered as a risk factor for cancer. The levels of homocysteine in the plasma is highly controlled by diet and several strategies were suggested for lowering plasma homocysteine. In this chapter, homocysteine biosynthesis and metabolism were explained. Diseases associated with hyperhomocysteinemia were discussed with special emphasis on cancer. Various natural products and dietary interventions were evaluated for their anticancer effects through lowering plasma homocysteine. This chapter will provide a solid ground for researchers to understand the link between hyperhomocysteinemia and cancer and the possible role of diet and natural product in lowering plasma homocysteine.
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References
Mcdonald L, Bary C, Field C, Love F, Davies B (1964) Homocystinuria, thrombosis, and the blood-platelets. Lancet 1:745–746
Sharma GS, Kumar T, Dar TA, Singh LR (2015) Protein N-homocysteinylation: from cellular toxicity to neurodegeneration. Biochim Biophys Acta 1850:2239–2245
Azzini E, Ruggeri S, Polito A (2020) Homocysteine: its possible emerging role in at-risk population groups. Int J Mol Sci 21(4):1421
Hasan T, Arora R, Bansal AK, Bhattacharya R, Sharma GS, Singh LR (2019) Disturbed homocysteine metabolism is associated with cancer. Exp Mol Med 51(2):1–13
Wu LL, Wu JT (2002) Hyperhomocysteinemia is a risk factor for cancer and a new potential tumor marker. Clin Chim Acta 322:21–28
Kumar A et al (2017) The metabolism and significance of homocysteine in nutrition and health. Nutr Metab 14(1):78
Selhub J (1999) Homocysteine metabolism. Annu Rev Nutr 19(1):217–246
Škovierová H et al (2016) The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int J Mol Sci 17(10):1733
Mudd SH, Cantoni G (1958) Activation of methionine for transmethylation III. The methionine-activating enzyme of bakers’ yeast. J Biol Chem 231(1):481–492
McCully KS (2001) The biomedical significance of homocysteine. J Sci Explor 15(1):5–20
Blom HJ, Smulders Y (2011) Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis 34(1):75–81
Cantoni G, Chiang P (1980) Natural sulfur compounds, in novel biochemical and structural aspects. Plenum Publishing Co, New York, pp 67–80
Mandaviya PR, Stolk L, Heil SG (2014) Homocysteine and DNA methylation: a review of animal and human literature. Mol Genet Metab 113(4):243–252
Esse R et al (2013) Protein arginine methylation is more prone to inhibition by S-adenosylhomocysteine than DNA methylation in vascular endothelial cells. PLoS One 8(2):e55483
Jung M, Pfeifer GP (2015) Aging and DNA methylation. BMC Biol 13(1):7
Champe PC, Harvey RA, Ferrier DR (2005) Biochemistry. Lippincott Williams & Wilkins, Philadelphia
Li YN et al (1996) Cloning, mapping and RNA analysis of the human methionine synthase gene. Hum Mol Genet 5(12):1851–1858
Castro R et al (2006) Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: an overview. J Inherit Metab Dis 29(1):3–20
Pajares MA, Pérez-Sala D (2006) Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? Cell Mol Life Sci 63(23):2792–2803
Teng Y-W, Cerdena I, Zeisel SH (2012) Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake. J Nutr 142(11):1964–1967
Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta Gen Subj 1830(5):3143–3153
Vitvitsky V et al (2003) Redox regulation of homocysteine-dependent glutathione synthesis. Redox Rep 8(1):57–63
Chiku T et al (2009) H2S biogenesis by human cystathionine γ-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia. J Biol Chem 284(17):11601–11612
Yang Q, He G-W (2019) Imbalance of homocysteine and H2S: significance, mechanisms, and therapeutic promise in vascular injury. Oxidative Med Cell Longev 2019:7629673
Barroso M, Handy DE, Castro R (2017) The link between hyperhomocysteinemia and hypomethylation: implications for cardiovascular disease. J Inborn Errors Metab Screen 5:2326409817698994
Sunden SL et al (1997) Betaine–homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Arch Biochem Biophys 345(1):171–174
Maron BA, Loscalzo J (2009) The treatment of hyperhomocysteinemia. Annu Rev Med 60:39–54
Feligioni M et al (2019) Hyperhomocysteinemia as a risk factor and potential nutraceutical target for certain pathologies. Front Nutr 6:49
Jakubowski H (2002) Homocysteine is a protein amino acid in humans implications for homocysteine-linked disease. J Biol Chem 277(34):30425–30428
Manolescu BN et al (2010) Homocysteine and vitamin therapy in stroke prevention and treatment: a review. Acta Biochim Pol 57(4):467–477
Kim J et al (2018) Causes of hyperhomocysteinemia and its pathological significance. Arch Pharm Res 41(4):372–383
Fowler B (2005) Homocystein – an independent risk factor for cardiovascular and thrombotic diseases. Ther Umsch Revue Ther 62(9):641–646
Asfar S, Safar H (2007) Homocysteine levels and peripheral arterial occlusive disease: a prospective cohort study and review of the literature. J Cardiovasc Surg 48(5):601
Wierzbicki AS (2007) Homocysteine and cardiovascular disease: a review of the evidence. Diab Vasc Dis Res 4(2):143–149
Morris AA et al (2017) Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis 40(1):49–74
Dutta S et al (2005) Cystathionine β-synthase T833C/844INS68 polymorphism: a family-based study on mentally retarded children. Behav Brain Funct 1(1):25
Kruger WD et al (2000) Polymorphisms in the CBS gene associated with decreased risk of coronary artery disease and increased responsiveness to total homocysteine lowering by folic acid. Mol Genet Metab 70(1):53–60
Yakub M et al (2012) Polymorphisms in MTHFR, MS and CBS genes and homocysteine levels in a Pakistani population. PLoS One 7(3):e33222
Fischer JD, Holliday GL, Thornton JM (2010) The CoFactor database: organic cofactors in enzyme catalysis. Bioinformatics 26(19):2496–2497
Miller JW et al (1994) Vitamin B− 6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats. Am J Clin Nutr 59(5):1033–1039
Markišić M, Pavlović AM, Pavlović DM (2017) The impact of homocysteine, vitamin b12, and vitamin d levels on functional outcome after first-ever ischaemic stroke. Biomed Res Int 2017:5489057
Miller AL (2003) The methionine-homocysteine cycle and its effects on cognitive diseases. (Homocysteine & cognitive). Altern Med Rev 8(1):7–20
Guney T, Yikilmaz AS, Dilek I (2016) Epidemiology of vitamin B12 deficiency. Epidemiol Commun Non-Commun Dis Attrib Lifestyle Nat Humankind 2016:103
Brown MJ, Beier K (2018) Vitamin B6 deficiency (pyridoxine). In: StatPearls [Internet]. StatPearls Publishing
Collaboration, H.L.T (1998) Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ 316(7135):894–898
De Bree A et al (2004) Evidence for a protective (synergistic?) effect of B-vitamins and omega-3 fatty acids on cardiovascular diseases. Eur J Clin Nutr 58(5):732–744
Miodownik C et al (2007) High-dose vitamin B6 decreases homocysteine serum levels in patients with schizophrenia and schizoaffective disorders: a preliminary study. Clin Neuropharmacol 30(1):13–17
Garlick PJ (2006) Toxicity of methionine in humans. J Nutr 136(6):1722S–1725S
Chwatko G et al (2007) Mutations in methylenetetrahydrofolate reductase or cystathionine β-syntase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice. FASEB J 21(8):1707–1713
van Guldener C (2006) Why is homocysteine elevated in renal failure and what can be expected from homocysteine-lowering? Nephrol Dial Transplant 21(5):1161–1166
Van guldener C, Robinson K (2000) Homocysteine and renal disease. In: Seminars in thrombosis and hemostasis. Copyright© 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New …
Veldman B et al (2005) Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance. Diabet Med 22(3):301–305
Foundation, N.K (2018) Estimated glomerular filtration rate (eGFR) [cited 2020 May 26]. Available from: https://www.kidney.org/atoz/content/gfr
Long Y, Nie J (2016) Homocysteine in renal injury. Kidney Dis 2(2):80–87
Van Guldener C, Stam F, Stehouwer CD (2001) Homocysteine metabolism in renal failure. Kidney Int 59:S234–S237
Laidlaw SA et al (1994) Patterns of fasting plasma amino acid levels in chronic renal insufficiency: results from the feasibility phase of the Modification of Diet in Renal Disease Study. Am J Kidney Dis 23(4):504–513
Loehrer F et al (1998) Evidence for disturbed S-adenosylmethionine: S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions? Nephrol Dial Transplant 13(3):656–661
Ducloux D et al (2002) Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12. Nephrol Dial Transplant 17(5):865–870
Suliman M et al (1997) Total, free, and protein-bound sulphur amino acids in uraemic patients. Nephrol Dial Transplant 12(11):2332–2338
Yildirim I et al (2019) Serum sulphate levels in hemodialysis patients. Int J Nephrol 2019:1063514
Nakanishi T et al (2002) Association of hyperhomocysteinemia with plasma sulfate and urine sulfate excretion in patients with progressive renal disease. Am J Kidney Dis 40(5):909–915
Lien EA et al (2001) Total plasma homocysteine in hypo-and hyperthyroidism: covariations and causality. J Clin Endocrinol Metab 86(4):1846–1846
Bamashmoos SA et al (2013) Relationship between total homocysteine, total cholesterol and creatinine levels in overt hypothyroid patients. Springerplus 2(1):423
Morris MS et al (2001) Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in the third US National Health and Nutrition Examination Survey. Atherosclerosis 155(1):195–200
Mincer Dl Fau, Jialal I (2020) Hashimoto thyroiditis. BTI – StatPearls
Cicone F et al (2018) Hyperhomocysteinemia in acute iatrogenic hypothyroidism: the relevance of thyroid autoimmunity. J Endocrinol Investig 41(7):831–837
Demirbas B et al (2004) Plasma homocysteine levels in hyperthyroid patients. Endocr J 51(1):121–125
Orzechowska-Pawilojc A et al (2009) Homocysteine, folate, and cobalamin levels in hyperthyroid women before and after treatment. Endokrynol Pol 60(6):443–448
Catargi B et al (1999) Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. Thyroid 9(12):1163–1166
de Benoist B (2008) Conclusions of a WHO technical consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 29(2_Suppl 1):S238–S244
Hariz A, Bhattacharya PT (2020) Megaloblastic anemia. In: StatPearls [Internet]. StatPearls Publishing
Lowenthal EA et al (2000) Homocysteine elevation in sickle cell disease. J Am Coll Nutr 19(5):608–612
Nozari E, Ghavamzadeh S, Razazian N (2019) The effect of vitamin B12 and folic acid supplementation on serum homocysteine, anemia status and quality of life of patients with multiple sclerosis. Clin Nutr Res 8(1):36–45
Lin J et al (2010) Plasma homocysteine and cysteine and risk of breast cancer in women. Cancer Res 70(6):2397–2405
Zhang D et al (2015) Elevated homocysteine level and folate deficiency associated with increased overall risk of carcinogenesis: meta-analysis of 83 case-control studies involving 35,758 individuals. PLoS One 10(5):e0123423
Wu LL, Wu JT (2002) Hyperhomocysteinemia is a risk factor for cancer and a new potential tumor marker. Clin Chim Acta 322(1–2):21–28
Hasan T et al (2019) Disturbed homocysteine metabolism is associated with cancer. Exp Mol Med 51(2):1–13
Sun C-F et al (2002) 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 321(1–2):55–62
Desouza C et al (2002) Drugs affecting homocysteine metabolism. Drugs 62(4):605–616
Fallah S et al (2012) Influence of oral contraceptive pills on homocysteine and nitric oxide levels: as risk factors for cardiovascular disease. J Clin Lab Anal 26(2):120–123
Norouzi V et al (2011) Effect of oral contraceptive therapy on homocysteine and C-reactive protein levels in women: an observational study. Anatol J Cardiol/Anadolu Kardiyol Derg 11(8):698–702
Giovannucci E et al (1995) Alcohol, low-methionine – low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst 87:265–273
Kato I et al (1999) Serum folate, homocysteine and colorectal cancer risk in women: a nested case–control study. Br J Cancer 79:1917–1921
Ma J et al (1999) A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocyst(e)ine, and colorectal cancer risk. Cancer Epidemiol Biomark Prev 8:825–829
Bravatà V (2015) Controversial roles of methylenetetrahydrofolate reductase polymorphisms and folate in breast cancer disease. Int J Food Sci Nutr 66:43–49
Montfort WR et al (1990) Structure, multiple site binding, and segmental accommodation in thymidylate synthase on binding dUMP and an antifolate. Biochemistry 29:6964–6977
Blount BC et al (1997) Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A 94:3290–3295
Crider KS, Yang TP, Berry RJ, Bailey LB (2012) Folate and DNA methylation: a review of molecular mechanisms and the evidence for Folate’s role. Adv Nutr 3:21–38
Hall LE, Mitchell SE, O’Neill RJ (2012) Pericentric and centromeric transcription: a perfect balance required. Chromosom Res 20:535–546
Ehrlich M (2002) DNA methylation in cancer: too much, but also too little. Oncogene 21:5400–5413
Refsum H et al (2006) The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr 136:1731S–1740S
Rickles FR, Levine M, Edwards RL (1992) Hemostatic alterations in cancer patients. Cancer Metastasis Rev 11:237–248
GATT A et al (2007) Hyperhomocysteinemia in women with advanced breast cancer. Int J Lab Hematol 29:421–425
Welch GN, Loscalzo J (1998) Homocysteine and atherothrombosis. N Engl J Med 338:1042–1050
Sharma GS, Kumar T, Singh LR (2014) N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins. PLoS One 9:e116386
Lentz SR et al (1996) Vascular dysfunction in monkeys with diet-induced hyperhomocyst (e) inemia. J Clin Invest 98:24–29
FitzGerald GA (2003) Parsing an enigma: the pharmacodynamics of aspirin resistance. Lancet 361:542–544
Talib WH (2017) Consumption of garlic and lemon aqueous extracts combination reduces tumor burden by angiogenesis inhibition, apoptosis induction, and immune system modulation. Nutrition 43:89–97
Talib WH (2017) Regressions of breast carcinoma syngraft following treatment with piperine in combination with thymoquinone. Sci Pharm 85(3):27
Talib WH, Al-hadid SA, Ali MBW, Al-Yasari IH, Ali MRA (2018) Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action. Breast Cancer Target Ther 10:207
Talib WH, Al Kury LT (2018) Parthenolide inhibits tumor-promoting effects of nicotine in lung cancer by inducing P53-dependent apoptosis and inhibiting VEGF expression. Biomed Pharmacother 107:1488–1495
Al Obaydi MF, Hamed WM, Al Kury LT, Talib WH (2020) Terfezia boudieri: a desert truffle with anticancer and immunomodulatory activities. Front Nutr 7:38
Kim J et al (2018) Causes of hyperhomocysteinemia and its pathological significance. Arch Pharm Res 41(4):372–383
Craig SA (2004) Betaine in human nutrition. Am J Clin Nutr 80(3):539–549
Kumar A et al (2017) The metabolism and significance of homocysteine in nutrition and health. Nutr Metab (Lond) 14:78
Malinow MR, Bostom AG, Krauss RM (1999) Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 99(1):178–182
Robinson K et al (1998) Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. Eur COMAC Group Circ 97(5):437–443
Kang SS, Wong PW, Norusis M (1987) Homocysteinemia due to folate deficiency. Metabolism 36(5):458–462
Selhub J et al (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270(22):2693–2698
Tinelli C et al (2019) Hyperhomocysteinemia as a risk factor and potential nutraceutical target for certain pathologies. Front Nutr 6:49
Khan KM, Jialal I (2020) Folic acid (folate) deficiency. In: StatPearls. StatPearls Publishing Copyright ©, StatPearls Publishing LLC, Treasure Island
Rasmussen K et al (1996) Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation. Clin Chem 42(4):630–636
Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference, I., O.B.V. Its Panel on Folate, and Choline (1998) The national academies collection: reports funded by National Institutes of Health. In: Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B(6), folate, vitamin B(12), pantothenic acid, biotin, and dholine. National Academies Press (US) Copyright ©, National Academy of Sciences, Washington, DC
Homocysteine Lowering Trialists’ Collaboration (2005) Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 82(4):806–812
van Oort FV et al (2003) Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study. Am J Clin Nutr 77(5):1318–1323
Assanelli D et al (2004) Folic acid and vitamin E supplementation effects on homocysteinemia, endothelial function and plasma antioxidant capacity in young myocardial-infarction patients. Pharmacol Res 49(1):79–84
Mitu O et al (2020) The effect of vitamin supplementation on subclinical atherosclerosis in patients without manifest cardiovascular diseases: never-ending hope or underestimated effect? Molecules (Basel, Switz) 25(7):1717
Boushey CJ et al (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 274(13):1049–1057
den Heijer M et al (1998) Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol 18(3):356–361
Brouwer IA et al (1999) Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. J Nutr 129(6):1135–1139
Alfthan G et al (2003) Folate intake, plasma folate and homocysteine status in a random Finnish population. Eur J Clin Nutr 57(1):81–88
Brouwer IA et al (1999) Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin Nutr 69(1):99–104
Appel LJ et al (2000) Effect of dietary patterns on serum homocysteine: results of a randomized, controlled feeding study. Circulation 102(8):852–857
Riddell LJ et al (2000) Dietary strategies for lowering homocysteine concentrations. Am J Clin Nutr 71(6):1448–1454
Tucker KL et al (1996) Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study. J Nutr 126(12):3025–3031
Teixeira JA et al (2020) Prudent dietary pattern influences homocysteine level more than folate, vitamin B12, and docosahexaenoic acid: a structural equation model approach. Eur J Nutr 59(1):81–91
Pintó X et al (2005) A folate-rich diet is as effective as folic acid from supplements in decreasing plasma homocysteine concentrations. Int J Med Sci 2(2):58–63
Ray JG, Cole DE, Boss SC (2000) An Ontario-wide study of vitamin B12, serum folate, and red cell folate levels in relation to plasma homocysteine: is a preventable public health issue on the rise? Clin Biochem 33(5):337–343
Gonin JM et al (2003) Controlled trials of very high dose folic acid, vitamins B12 and B6, intravenous folinic acid and serine for treatment of hyperhomocysteinemia in ESRD. J Nephrol 16(4):522–534
Ubbink JB et al (1993) Hyperhomocysteinemia and the response to vitamin supplementation. Clin Investig 71(12):993–998
MacKenzie KE et al (2006) Folate and vitamin B6 rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus. Pediatrics 118(1):242–253
Papandreou D et al (2010) Oral supplementation of folic acid for two months reduces total serum homocysteine levels in hyperhomocysteinemic Greek children. Hippokratia 14(2):105–108
Collaboration, H.L.T (1998) Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists’ Collaboration. BMJ 316(7135):894–898
Bostom AG et al (1997) Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial. Ann Intern Med 127(12):1089–1092
Ford TC et al (2018) The effect of a high-dose vitamin B multivitamin supplement on the relationship between brain metabolism and blood biomarkers of oxidative stress: a randomized control trial. Nutrients 10(12):1860
Woodside JV et al (1998) Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial. Am J Clin Nutr 67(5):858–866
Tucker KL et al (2004) Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial. Am J Clin Nutr 79(5):805–811
Powers HJ (2003) Riboflavin (vitamin B-2) and health. Am J Clin Nutr 77(6):1352–1360
Shimakawa T et al (1997) Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults. Ann Epidemiol 7(4):285–293
Jacques PF et al (2001) Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 73(3):613–621
Hustad S et al (2000) Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin Chem 46(8 Pt 1):1065–1071
Morgan KJ, Zabik ME, Leveille GA (1981) The role of breakfast in nutrient intake of 5- to 12-year-old children. Am J Clin Nutr 34(7):1418–1427
Morgan KJ, Zabik ME (1984) The influence of ready-to-eat cereal consumption at breakfast on nutrient intakes of individuals 62 years and older. J Am Coll Nutr 3(1):27–44
Preziosi P et al (1999) Breakfast type, daily nutrient intakes and vitamin and mineral status of French children, adolescents, and adults. J Am Coll Nutr 18(2):171–178
Moat SJ et al (2003) Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR (C677T) genotype. Clin Chem 49(2):295–302
Krishnaswamy K (1971) Erythrocyte glutamic oxaloacetic transaminase activity in patients with oral lesions. Int J Vitam Nutr Res 41(2):247–252
Lakshmi AV, Bamji MS (1974) Tissue pyridoxal phosphate concentration and pyridoxaminephosphate oxidase activity in riboflavin deficiency in rats and man. Br J Nutr 32(2):249–255
McGregor DO et al (2002) Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure. Kidney Int 61(3):1040–1046
Brouwer IA, Verhoef P, Urgert R (2000) Betaine supplementation and plasma homocysteine in healthy volunteers. Arch Intern Med 160(16):2546–2547
Wilcken DE, Dudman NP, Tyrrell PA (1985) Homocystinuria due to cystathionine beta-synthase deficiency – the effects of betaine treatment in pyridoxine-responsive patients. Metabolism 34(12):1115–1121
Carmel R et al (1988) Hereditary defect of cobalamin metabolism (cblG mutation) presenting as a neurologic disorder in adulthood. N Engl J Med 318(26):1738–1741
Schwab U et al (2002) Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am J Clin Nutr 76(5):961–967
Steenge GR, Verhoef P, Katan MB (2003) Betaine supplementation lowers plasma homocysteine in healthy men and women. J Nutr 133(5):1291–1295
Melse-Boonstra A et al (2005) Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations. Am J Clin Nutr 81(6):1378–1382
Holm PI et al (2005) Betaine and folate status as cooperative determinants of plasma homocysteine in humans. Arterioscler Thromb Vasc Biol 25(2):379–385
Zeisel SH et al (2003) Concentrations of choline-containing compounds and betaine in common foods. J Nutr 133(5):1302–1307
Chiuve SE et al (2007) The association between betaine and choline intakes and the plasma concentrations of homocysteine in women. Am J Clin Nutr 86(4):1073–1081
Lee JE et al (2010) Are dietary choline and betaine intakes determinants of total homocysteine concentration? Am J Clin Nutr 91(5):1303–1310
Olthof MR et al (2005) Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr 82(1):111–117
Mahmoud AM, Ali MM (2019) Methyl donor micronutrients that modify DNA methylation and cancer outcome. Nutrients 11(3):608
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Talib, W.H., Barakat, M., Al Kury, L.T. (2021). Hyperhomocysteinemia and Cancer: The Role of Natural Products and Nutritional Interventions. In: Waly, M.I. (eds) Nutritional Management and Metabolic Aspects of Hyperhomocysteinemia. Springer, Cham. https://doi.org/10.1007/978-3-030-57839-8_2
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