Heart, Stroke | September 27, 2014 | Author: The Super Pharmacist
Homocysteine is an alternative form of the natural amino acid (the basic components of proteins) cysteine. It plays a role in the synthesis of another amino acid, methionine, in the body. However, it cannot be used in protein synthesis, due to its structural differences to cysteine. Therefore, it has the potential to build up in the bloodstream, which may lead to a condition known as hyperhomocysteinemia. This condition is associated with an increased risk of cardiovascular and cardiocerebral (e.g. stroke) disorders.
The mechanisms by which homocysteine affects cardiovascular health are not completely clear, but is most likely related to oxidative damage caused by the molecule when left to circulate in the blood.
Elevated homocysteine levels may play a role in other conditions, such as Alzheimer's disease, via the same method. There is evidence that hyperhomocysteinemia is associated with cognitive decline and be associated with the behavioural and emotional symptoms of Alzheimer's. Increased homocysteine may also be associated with a higher risk of breast cancer.
Homocysteine is converted to methionine in the body, which is facilitated by another molecule called cyanocobalamin, also known as vitamin B12. This is dependant on another B-vitamin, folic acid (or vitamin B9).
Therefore, a deficiency of these vitamins (present in dietary sources and in supplements) may contribute to hyperhomocysteinemia.
This condition may be hereditary, due to mutations in certain genes associated with the control of methionine or folic acid metabolism.
Some studies indicate that chronic alcohol abuse may result in elevated homocysteine levels.
As outlined above, homocysteine may negatively affect cardiovascular tissues through oxidative damage.
There are a number of tests to determine the concentration of homocysteine in the blood. These include:
As homocysteine levels depend to a degree on B-vitamins, an optimal concentration of these is the main strategy to keep the concentrations of this molecule low. However, there is evidence for some other methods by which homocysteine levels may be controlled.
There is some evidence that the increased intake of B vitamins may reduce homocysteine concentrations in the body, and thus reduce the risk of conditions with which this is associated.
An analysis of 14 studies, including approximately 55,000 subjects, found that B-vitamin supplementation significantly reduced the risk of stroke. However, another analysis of 18 trials incorporating over 57,000 subjects indicated that this strategy is more effective for men in comparison with women.
It is not clear which of the three subtypes of vitamin B associated with homocysteine regulation has the greatest effect on hyperhomocysteinemia.
A review of 13 trials with over 39,000 subjects on the effects of folic acid, a B-vitamin with many other health benefits, found that it was not associated with significant homocysteine reduction alone, but that its combination with other B-vitamins yielded more positive effects.
Vitamin B deficiency is particularly prevalent in old age, and is associated with elevated homocysteine levels in this population. A study including 209 elderly outpatient clinic visitors showed that vitamin B (3mg vitamin B6, 0.5mg B12 and 0.8mg folic acid) supplementation daily for four months significantly reduced homocysteine levels.
A systematic review of 19 randomised-controlled clinical trials including over 47,000 subjects indicated that B-vitamin supplementation (B6, B9, B12 or a combination of these) was associated with the prevention of stroke, but not other types of cardiovascular disease, such as coronary heart disease.
A trial randomising over 3700 patients who had recently experienced a heart attack, to B-vitamins in different combinations or placebo, found that supplementation had no effect on the risk of recurring cardiovascular disease.
Taurine is another modified amino acid which may have homocysteine-reducing properties. A one-way trial of 22 healthy female subjects receiving 3 grams of taurine daily for four weeks showed that this treatment significantly reduced homocysteine concentrations. On the other hand, taurine failed to elicit this effect in a recent animal trial of artifically-induced hyperhomocysteinemia.
As methionine can be synthesised in the body, it follows that an intake of this amino acid from the diet may render this unnecessary and lead to increased, unconverted homocysteine in the blood. Animal-derived foods such as eggs, fish and meat tend to be rich in methionine. However, there is no scientific evidence that a reduction of dietary methionine has an effect on homocysteine levels or the risk of cardiovascular disease.
Okura T, Miyoshi K, Irita J, et al. Hyperhomocysteinemia is one of the risk factors associated with cerebrovascular stiffness in hypertensive patients, especially elderly males. Scientific reports.2014;4:5663.
Debreceni B, Debreceni L. The role of homocysteine-lowering B-vitamins in the primary prevention of cardiovascular disease. Cardiovascular therapeutics.2014;32(3):130-138.
Zheng Z, Wang J, Yi L, et al. Correlation between behavioural and psychological symptoms of Alzheimer type dementia and plasma homocysteine concentration. BioMed research international.2014;2014:383494.
Wu X, Zou T, Cao N, et al. Plasma homocysteine levels and genetic polymorphisms in folate metablism are associated with breast cancer risk in chinese women. Hereditary cancer in clinical practice.2014;12(1):2.
Gupta SK, Kotwal J, Kotwal A, Dhall A, Garg S. Role of homocysteine & MTHFR C677T gene polymorphism as risk factors for coronary artery disease in young Indians. The Indian journal of medical research.2012;135(4):506-512.
Bleich S, Carl M, Bayerlein K, et al. Evidence of increased homocysteine levels in alcoholism: the Franconian alcoholism research studies (FARS). Alcoholism, clinical and experimental research.2005;29(3):334-336.
Guilland JC, Favier A, Potier de Courcy G, Galan P, Hercberg S. [Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease?. 1. Basic data]. Pathologie-biologie.2003;51(2):101-110.
Sun Q, Jia X, Gao J, et al. Association of serum homocysteine levels with the severity and calcification of coronary atherosclerotic plaques detected by coronary CT angiography. International angiology : a journal of the International Union of Angiology.2014;33(4):316-323.
Xiao W, Bai Y, Ye P, et al. Plasma homocysteine is associated with aortic arterial stiffness but not wave reflection in Chinese hypertensive subjects. PloS one.2014;9(1):e85938.
May HT, Alharethi R, Anderson JL, et al. Homocysteine levels are associated with increased risk of congestive heart failure in patients with and without coronary artery disease. Cardiology.2007;107(3):178-184.
Hao L, Chen L, Sai X, et al. Synergistic effects of elevated homocysteine level and abnormal blood lipids on the onset of stroke. Neural regeneration research.2013;8(31):2923-2931.
Mizrahi EH, Noy S, Sela BA, Fleissig Y, Arad M, Adunsky A. Further evidence of interrelation between homocysteine and hypertension in stroke patients: a cross-sectional study. The Israel Medical Association journal : IMAJ.2003;5(11):791-794.
Zhang W, Zhang X. Correlation Between the Youth Cerebral Infarction in Different TOAST Classifications and High Homocysteine. Cell biochemistry and biophysics.2014.
Miroshnichenko, II, Platova AI, Safarova TP, Iakovleva OB. [Determination of homocysteine by tandem mass spectrometry with chemical ionization]. Biomeditsinskaia khimiia.2014;60(2):235-245.
Ji Y, Tan S, Xu Y, et al. Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: a meta-analysis. Neurology.2013;81(15):1298-1307.
Zhang C, Chi FL, Xie TH, Zhou YH. Effect of B-vitamin supplementation on stroke: a meta-analysis of randomized controlled trials. PloS one.2013;8(11):e81577.
Lee M, Hong KS, Chang SC, Saver JL. Efficacy of homocysteine-lowering therapy with folic Acid in stroke prevention: a meta-analysis. Stroke; a journal of cerebral circulation.2010;41(6):1205-1212.
Lewerin C, Nilsson-Ehle H, Matousek M, Lindstedt G, Steen B. Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial. European journal of clinical nutrition.2003;57(11):1426-1436.
Huang T, Chen Y, Yang B, Yang J, Wahlqvist ML, Li D. Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular and all-cause mortality. Clinical nutrition (Edinburgh, Scotland).2012;31(4):448-454.
Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. The New England journal of medicine.2006;354(15):1578-1588.
Ahn CS. Effect of taurine supplementation on plasma homocysteine levels of the middle-aged Korean women. Advances in experimental medicine and biology.2009;643:415-422.
Deminice R, Rosa FT, da Silva LE, Jordao AA. Taurine supplementation does not decrease homocysteine levels and liver injury induced by a choline-deficient diet. Life sciences.2014;105(1-2):43-47.