Homocysteine is a sulfur-containing amino acid produced by the intracellular demethylation of the essential amino acid, methionine. Homocysteine has three metabolic functions within the human body: first, to be remethylated into methionine; second, to enter the biosynthetic pathway of cysteine; and third, to be released into the extracellular medium (blood and urine). The third metabolic function is the direct cause of elevated homocysteine concentrations in urine and plasma. Hyperhomocysteinemia (elevated levels of homocysteine) has been identified in numerous conditions and disease states including cardiovascular disease (atherosclerosis and thrombosis), pregnancy complications, psoriasis, cognitive impairment in the elderly, mental disorders, neural tube defects and birth defects.1,2 Homocysteine levels have been proven to be influenced by several factors, including: sex, age, the C677T polymorphism of the MTHFR gene and folate status.3 While men in general have higher levels of homocysteine compared to women, elevated homocysteine levels have been identified as bearing an increased risk of disease in women compared to men. In this article, several disease states and conditions will be identified whereby homocysteine levels are elevated in women.
Cardiovascular disease (CVD)
Elevated levels of circulating homocysteine correlate with an increased risk of vascular occlusion (blockage of a blood vessel). Hyperhomocysteinemia can cause inflammation of the endothelium (thin layer of cells linking the interior blood vessels). Failure to lower homocysteine levels can cause further inflammation of the arteries, veins, and capillaries causing atherosclerosis. Consequently, blood and oxygen supply to tissues is reduced, increasing the risk of CVD. Hyperhomocysteinemia correlates with higher diastolic and systolic blood pressure, causing hypertension. However, this correlation is stronger in women than in men. Women with elevated levels of homocysteine have a three-fold increased risk of CVD, whereas men have a two-fold increased risk.4
Hyperhomocysteinemia correlates with an increased risk of colorectal cancer with elevated homocysteine levels being highly prevalent in patients with inflammatory bowel diseases (IBDs), which is believed to be associated with either an increased or decreased absorption of folate and other B vitamins.5 Furthermore, it has been established that elevated homocysteine levels are a significant risk factor for colorectal adenoma in women.6 In addition, more studies are emerging linking hyperhomocysteinemia to a variety of cancers including prostate and breast, however, research is required to determine if homocysteine has any effect on the growth and proliferation of tumor cells.7
Pregnancy complications and birth defects
Homocysteine levels should decline during pregnancy, however, in some cases, levels increase. Hyperhomocysteinemia is associated with fetal neural tube defects which causes various conditions, characterized by placental vasculopathy, including preeclampsia, abruption and recurrent pregnancy loss. It has been identified that folate supplementation can reduce the risk of fetal neural tube defects by half.8 One study found that hyperhomocysteinemia was associated with a two- to three-fold increased risk of abrupyio placentae, pregnancy-induced hypertension and intrauterine growth restriction.9 Furthermore, hyperhomocysteinemia has been identified as inducing oxidative stress in pregnancy. Oxidative stress in the utero-placental tissues has been recognized in the development of severe uteroplacental disturbance, an uncommon yet serious complication of pregnancy. Moreover, oxidative stress and hyperhomocysteinemia was also observed in women with preterm birth or at risk of abortion.10
These complications in women as a direct result of hyperhomocysteinemia indicate the necessity for homocysteine testing.
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- Roles of homocysteine in cell metabolism: Old and new functions. Medina MA, Urdiales JL, Amores-Sanchez MI. Malaga: European Journal of Biochemistry, 2001, Vol. 268.
- Age and Gender Affect the Relation between Methylenetetrahydrofolate Reductase C677T Genotype and Fasting Plasma Homocysteine Concentrations in the Framingham Offspring Study Cohort. Russo GT, et al. 11, s.l. : The Journal of Nutrition, 2003, Vol. 133.
- Role of homocysteine in the development of cardiovascular disease. Ganguly P, Alam SF. 6, Riyadh, Kingdom: Nutrition Journal, 2015, Vol. 14.
- Meta-analysis of homocysteine-related factors on the risk of colorectal cancer. Shiao SPK, Lie A, Yu CH. 39, s.l.: Oncotarget, 2018, Vol. 9.
- Hyperhomocysteinemia as a potential contributor of colorectal cancer development in inflammatory bowel diseases: A review. Keshteli AH, Baracos VE, Madsen KL. 4, Alberta: World Journal of Gastroenterology, 2015, Vol. 21.
- Disturbed homocysteine metabolism is associated with cancer. Hasan T, et al. 51, s.l. : Experimental & Molecular Medicine, 2019, Vol. 21.
- Homocysteine and pregnancy. Hague, WM. 3, North Adelaide: Best Practice & Research, Clinical Obstetrics & Gynaecology, 2003, Vol. 17.
- Hyperhomocysteinemia, pregnancy complications and the timing of investigation. Steegers-Theunissen RP, et al. 2, Nijmegen: Obstetrics & Gynecology, 2004, Vol. 104.
- The influence of homocysteine and oxidative stress on pregnancy outcome. Micle O, et al. 1, s.l. : Journal of Medicine and Life, 2012, Vol. 5.