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Condition - Homocysteine

By Jacqueline Newson BSc (Hons) Nutritional Therapy

We are constantly bombarded with media information about the dangers of cardiovascular disease, in particular the need to reduce our cholesterol levels. However, there are many other risk factors associated with heart disease, including smoking, obesity, stress and high blood pressure, to name but a few.  

Not many people are aware that elevated homocysteine levels create an additional risk that is associated with coronary heart disease (CHD), or that an increased plasma homocysteine level is a strong, independent risk factor for the development of dementia and Alzheimer’s disease. As well as this, it appears that homocysteine has an effect on bone health.

What is homocysteine?

Homocysteine is an intermediate amino acid, formed during the metabolism of methionine from methyl groups during methylation – a key biological function. Methyl groups are essential in our diet. The nervous system, kidneys, liver, immune system and heart and blood vessels are all dependent on methyl groups to function normally. Dietary sources of the methyl groups in order of importance are betaine, choline, methionine, vitamin B6 and folic acid. These can be found in a range of foods, including prawns, turkey, salmon, lamb, eggs, fish, cheese, lentils, wheat germ, peanuts, avocado, spinach and kidney beans.

So what happens during methylation?

The methyl groups combine with homocysteine in the body to form methionine. This is then turned into S-adenosylmethionine (SAMe). After SAMe has donated its methyl group, it becomes S-adenosyl homocysteine, which breaks down into the toxic amino acid homocysteine.

Sufficient methyl groups are needed to transform the homocysteine back into methionine; otherwise, the homocysteine levels rise, leaving us at higher risk of CHD and Alzheimer’s disease.

The body is not able to synthesise methyl groups and needs a diet that consistently contains enough methyl groups in order to maintain the cycle, keeping levels of SAMe up and the levels of homocysteine down. To obtain sufficient methyl groups, the diet should include the foods listed above. If these foods are not readily available, supplementation with vitamin B6, folic acid, B12 or TMG (tri-methyl glycine) reduces the concentration of homocysteine in the bloodstream. However, it should be noted that the vitamins B6, B12 and folic acid are not the best donors; betaine – also known as TMG – is the most effective.

What effect does homocysteine have on our body?

It is thought that homocysteine degrades and inhibits the formation of the three main structural components of the artery – elastin, collagen and proteoglycans. In addition, homocysteine permanently degrades lysine amino acid residues in proteins and the cysteine disulfide bridges, which, over a period of time, affects the function and structure. Overall, it can be said that homocysteine has a corrosive effect on long-living proteins, such as collagen and elastin, and on the life-long proteins, i.e. fibrillin. However, according to studies, it seems that reducing homocysteine can be useful for prevention of CHD rather than being of benefit to those with existing conditions.

How can homocysteine damage the brain?

Alzheimer’s disease accounts for more than 70% of all cases of dementia. In two case-controlled studies, a specific relation between homocysteine levels and the risk of Alzheimer’s was found, with each study finding a significant elevation of the serum homocysteine levels in people with Alzheimer’s compared to other non sufferers in the same age group. Accumulating evidence suggests that high homocysteine levels and low vitamin B status gives you an increased chance of declining memory, low mood, poor concentration, poor circulation and degeneration of the brain.

SAMe, derived from the methylation of homocysteine, is an important methyl donor for the brain, helping to activate a variety of neurotransmitters, particularly acetylcholine, which aids memory. B vitamin and SAMe deficiency always accompany raised homocysteine levels, so it appears this might contribute to the damage to the brain seen in Alzheimer’s.

In addition, some in vitro studies suggest that interaction between homocysteine and copper in the brain can cause the neuronal degeneration that is central to Alzheimer’s-type dementia. Neurodegenerative disorders, such as Alzheimer's disease, are characterised by specific patterns of neuronal cell loss or dysfunction. It appears that homocysteine levels may potentiate copper toxicity in the brain.The homocysteine is thought to promote atherosclerotic damage by interacting with copper and resulting in oxidative toxicity.

What effect does homocysteine have on bone health?

Research shows that increased fractures in the elderly are linked to elevated homocysteine levels. Although bone density is not affected by homocysteine, it seems that it affects the cross-linking between the collagen fibres and the tissues they reinforce. A study trialling homocysteine-lowering vitamins B12 and folate showed an 80% reduction in fractures, particularly those in the hip. Supplementing with these vitamins appears to counter the deleterious effects of homocysteine on collagen.

Keeping an eye on our homocysteine levels and maintaining a diet rich in methyl donors, whether through food or supplementation, seems the logical answer to ensuring we maintain healthy, hearts, minds and bones into our old age. For those with poor eating habits, dietary restrictions or compromised digestion, supplementing with a good vitamin B complex and TMG may be a useful addition to the diet. 

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