Homosysteine:

The history of homocysteine

Homocysteine was first described by Butz and du Vigneaud in 1932. Homocysteine is a sulphur-containing amino acid that is closely related to the essential amino acid methionine and to cysteine.

An association between elevated homocysteine levels and human disease was first suggested in 1962 by Carson and Neil. They had found high homocysteine concentrations in the urine of some children with mental retardation. The elevated homocysteine levels in these patients were caused by severe enzyme defects blocking the homocysteine metabolism.

This condition, homocystinuria, was later found to be associated with premature occlusive cardiovascular disease, even in childhood, and about 25% of the patients died before the age of 30 of cardiovascular events.

In 1969, McCully described the vascular pathology in these patients, including smooth muscle proliferation, progressive arterial stenosis, and haemostatic changes.

During the last 15 years it has been thoroughly documented that also moderately elevated homocysteine levels in serum or plasma is a strong and independent risk factor for occlusive arterial disease, and of venous thrombosis, and also predicts vascular and all-cause mortality. As many as 50% of patients with stroke and other atherothrombotic diseases have high homocysteine levels (over 15 µmol/L).

Plasma homocysteine is already proven to be a useful predictor of cardiovascular as well as non-cardiovascular morbidity and mortality. The next step will be to reduce the incidence of these conditions by monitoring homocysteine levels.

Why is homocysteine harmful?

The synthesis of glutathione is dependent on the trans-sulphuration of homocysteine. Glutathione is an important endogenous antioxidant. It protects many cellular components against oxidative damage and other types of injury. Glutathione also maintains alpha-tocopherol in its reduced form, either by a direct reaction or by a pathway involving ascorbate. Glutathione may also have protective vascular effects, possibly by interaction with nitric oxide.

Finally, certain forms of homocysteine itself, are proposed to have oxidative effects and to react with proteins leading to protein damage.

Why do homocysteine levels increase?

The higher the concentrations seen in the elderly may be caused by many factors such as malabsorption owing to prevalent atrophic gastritis or insufficient nutritional supply of vitamins, lower nutritional intake, a slowdown of the metabolism, reduced kidney function, and other physiological, age-related changes. Moreover, many drugs interact either by reducing the absorption of co-factors, or by increasing the catabolism of the vitamins. Certain diseases also influence the homocysteine metabolism. Nutritional and other lifestyle factors are important determinants, and may explain the observed variation between different populations.

Smoking, high alcohol intake and coffee consumption also interact by increasing the catabolism of vitamins or reducing the absorption of them. Several other lifestyle factors are also of importance for the homocysteine metabolism. Lack of physical exercise, obesity and even stress, are also associated with hyperhomocysteinaemia. The plasma levels are thus influenced by many factors.

Therefore, several factors may contribute to a patient´s hyperhomocysteinaemia, even if vitamin status, primarily of folate, vitamin B12 and B6, is a major determinant. Enzyme defects, disturbed distribution of the vitamins, which are actively transported by means of specific transport proteins and receptors, interaction with lifestyle factors, diseases and drugs, or a combination can thus impair the homocysteine metabolism with various metabolic disturbances as a consequence.

Many of the factors causing hyperhomocysteinaemia, for instance, unhealthy lifestyle factors, can be eliminated. The diagnosis of hyperhomocysteinaemia could therefore be used as an incentive for the patient to opt for a healthier lifestyle.

Homocysteine-lowering therapy

Many studies have shown that vitamin supplementation may normalise metabolite levels even when serum vitamin levels are within the normal reference range. Combination of folate with vitamin B12 and/or vitamin B6 more efficiently lowers homocysteine than folate alone.

Different doses and combinations have been used. An important meta-analysis of randomised trials was recently published by the Homocysteine Trialists’ Collaboration. The conclusion was that a supplementation with 0.5-5 mg of folic acid and about 0.5 mg of vitamin B12 would be expected to reduce homocysteine levels by about 25-30% in a typical population, or for instance from about 12 µmol/L to 8-9 µmol/L. However, for reasons earlier mentioned, the optimal combination should rather be individual than general, as many factors interact.

Some life style changes and supplements, that can help lower Homosysteine are as follows:

For more information on Homosysteine: Click Here

For more information on Homosysteine: Click Here

For more information on Homosysteine: Dr. Mercola 10/1/2000