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Homocysteine: Impacts of elevated levels on the body

Heart, Stroke | September 27, 2014 | Author: The Super Pharmacist

heart, Stroke

Homocysteine: Impacts of elevated levels on the body

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.

Causes of Increased Homocysteine Levels

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).

Causes of Increased Homocysteine LevelsHomocysteine may be converted back to cysteine, which involves vitamin B6 (pyridoxine). 

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.

Homocysteine and Cardiovascular Disease

As outlined above, homocysteine may negatively affect cardiovascular tissues through oxidative damage. 

  • Increased homocysteine is associated with damage to the cells that make up the linings of arteries, and  to those that form the musculature of these blood vessels (which keeps blood flowing through these).
     
  • Homocysteine may play a role in the formation of thromboses within blood vessels, which may contribute to stroke or embolism.
     
  • Increasing concentrations of the molecule is associated with the formation of cholesterol plaques within arteries, known as atherosclerosis, and with the increasing severity of existing plaques.
     
  • On a less molecular level, increased homocysteine is associated with arterial resistance (also known as 'arterial stiffness'), a marker of hypertension.
     
  • High concentrations of homocysteine has been found to have an association with an increased risk of congestive heart failure.
     
  • Homocysteinemia appears to interact with other cardiovascular risk factors to affect the probability of disease.
     
  • High homocysteine levels in conjunction with increased concentrations of fat molecules (lipids) in the blood (another risk factor for disorders such as stroke and coronary artery disease) have been found to increase the risk of stroke in comparison with increased blood lipids alone. Recurrent stroke was found to be significantly associated with elevated homocysteine and a history of hypertension in comparison with other risk factors.

Diagnostic Tools to Assess Homocysteine Levels

There are a number of tests to determine the concentration of homocysteine in the blood. These include:

  • Molecular: Laboratory and diagnostic assays, such as enzyme-linked immunosorbent assays, mass spectrometry and enzyme cycling can detect and quantify homocysteine in a sample.
  • Genetic: These detect mutations in genes, which as discussed above may be hereditary, that may lead to homocysteinemia. Diagnostic tests for specific genetic changes include polymerase chain reaction (PCR).

Treatment Strategies to Reduce Homocysteine Levels

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.

B-vitamin supplementation

Treatment Strategies to Reduce Homocysteine LevelsThere 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 supplementation

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.

Methionine restriction

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.

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