Does the chemical formula C4H9NO2S ring any bells? How about 2-amino-4-mercaptobutyric acid? This is homocysteine, a sulphur-containing amino acid formed during methionine metabolism, which is now recognised as a powerful predictor of cardiovascular disease, independent of other known risk factors. It is potentially cytotoxic and elevated blood levels have been found in patients with peripheral vascular disease, myocardial infarction, stroke and venous thromboembolism.

The link between high serum levels of homocysteine and vascular pathology was first suspected when it was found that sufferers from homocystinuria, who are unable to break down homocysteine, often died from strokes and heart attacks before reaching adulthood. The cause is advanced atherosclerosis, and there is evidence that homocysteine not only reacts with arterial epithelium, but also causes platelet aggregation, affects coagulation factors, reduces vasodilatation and interacts with low density lipoproteins. The epidemiological evidence linking high plasma homocysteine to heart disease is convincing, and this site gives details of several studies involving large numbers of patients.

Only last month research was published which suggests that elevated homocysteine levels may be a new, independent risk factor for stroke. Stable heart patients with the highest levels were found to be more than four times as likely to suffer the commonest type of stroke as those with the lowest levels. The likelihood of stroke increased as homocysteine rose, and this was true even after other risk factors were taken into account.

The long-running Framingham study has revealed that high plasma homocysteine is also associated with the future development of Alzheimer's Disease (AD) and other dementias. Levels greater than 14 mmol/litre doubled the chance of developing AD and each 5 mmol/litre elevation increased the risk by 40 percent. Again, this was independent of other factors such as age, gender and APOE genotype. To see an abstract of the original paper, click here . One mechanism which could explain this effect is the potentiation of copper neurotoxicity .

Maternal derangement of homocysteine-methionine metabolism may be responsible for certain birth defects and complications of pregnancy; this abnormality has been found in approximately 20% of cases of neural tube defects, recurrent miscarriage and placental infarcts. Animal studies suggest that decreased conversion of homocysteine to methionine could be a crucial factor in causing neural tube defects, and elevated plasma homocysteine is much more common in women who experience placental abruption or infarction than in those who have a normal pregnancy.

Measuring plasma homocysteine can be useful in certain clinical situations. For example , it indicates the extent of ischaemic myocardial damage in patients with acute cardiac syndromes, such as acute myocardial infarction and unstable angina pectoris. The level on hospital admission is also an independent predictor of long term survival in patients with these conditions.

If you have reached this far, you will be well aware that folic acid (folate), vitamin B6 and vitamin B12 are essential co-factors in homocysteine metabolism, and in many people plasma homocysteine can be lowered by an increased dietary intake of these compounds. The Linus Pauling Institute has a detailed account of the various mechanisms involved. The DASH (Dietary Approaches to Stop Hypertension ) diet, for example, not only lowers blood pressure quickly and significantly, but also reduces homocysteine levels. It is rich in fruits, vegetables and low fat dairy foods, but low in saturated fat, total fat and cholesterol, whilst including whole grains, poultry, fish, and nuts. A large scale, multi-centre trial is currently looking at whether a high-dose combination of folic acid, B6 and B12 will reduce the incidence of cardiovascular disease among renal transplant recipients, who are at high risk of developing it.

Folic acid is a water-soluble B vitamin found in green leaves, fortified grain products, peas and beans, and some other fruits and vegetables. The US National Institutes of Health site has comprehensive information about dietary requirements, as well as current issues and controversies involving folate. For a brief summary of recent research, click here . Among the topics that have been investigated are the role of folate in cancer, Crohn's Disease, atherosclerosis, chronic fatigue syndrome and Alzheimer's Disease.

Vitamin B6, or pyridoxine – also water-soluble – is essential for protein metabolism and the formation of haemoglobin. There is a three-dimensional diagram of its molecular structure here , but you will need to download a browser plug-in to view it. Deficiency of vitamin B6 not only increases the risk of cardiovascular disease and dementia, but also has an adverse impact on immune function – this is comprehensively explained here . Other information on this page includes the therapeutic use of B6 in a variety of conditions, sources of the vitamin, and its relative safety.

The present consensus is that any vitamin B12 in plant foods is unlikely to be available to humans, and the only reliable sources are meat, dairy products and eggs. For this reason, many vegan foods are fortified with B12, which is synthesised exclusively by bacteria (http://www.vegsoc.org/info/b12.html ). It is needed for the maturation of red blood cells, maintenance of the nervous system, and growth and development in children; deficiency can result in pernicious anaemia and neuropathy. Research has linked B12 deficiency with Helicobacter pylori infection, stomach surgery, neuropsychiatric abnormalities and the development of Alzheimer's Disease.

Returning to homocysteine, psychological and behavioural factors may also be important. It has been found that plasma levels in pre- and post-menopausal women can be temporarily increased by mild psychological stress. Moreover, in both men and women, high levels of hostility and anger (worse in men!) can be correlated with increased homocysteine levels, which might explain why these feelings are acknowledged to be potent risk factors for coronary heart disease. Perhaps in addition to eating a healthy diet we should try to eliminate stress and anger from our lives. Transcendental meditation? This tour was submitted by Derrick Garwood, a Freelance Medical Writer and Editor whose contact details can be found in our directory of freelancers.

If you have any comments on this article, please feel free to email Derrick or let us know.

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