Homocysteine - the new time bomb?

Homocysteine is now one of the most active areas in medical research, with over 8,000 papers published on the subject during 2004 alone.

Interest in homocysteine has rocketed because scientists have found a link between having raised levels in the blood and over 50 potentially serious medical conditions, including coronary heart disease, stroke, osteoporosis, dementia and birth defects. People with a high homocysteine level, for example, are at least three times more likely to have a heart attack than those with a normal level and it now appears to be at least as important a risk factor for heart and circulatory problems as LDL-cholesterol.

WHAT IS HOMOCYSTEINE?

It is an amino-acid that is naturally made in the body during the breakdown of another amino acid, methionine. Usually, homocysteine is quickly pounced on by three enzymes that convert it into other harmless substances, but these enzymes need good supplies of vitamins B12, B6 and folic acid to work properly. Some people inherit versions of these enzymes that work sluggishly, or which need higher levels of vitamins than normal to function properly. Homocysteine processing also becomes less efficient as we get older – especially after the menopause in women. As a result, an estimated 10% to 15% of the population (and almost 30% of those with coronary heart disease) do not break down homocysteine as well as they should. One in 160,000 people have an extremely high level of homocysteine – high enough to increase their risk of premature heart disease by thirty-fold.

WHY IS IT SO HARMFUL?

When homocysteine builds up in the circulation, it damages the lining of artery walls so they become more narrow and inelastic. The exact way this happens is still under investigation, but it is thought that homocysteine triggers oxidation of LDL-cholesterol so it is more likely to ‘stick’ to artery walls, forming porridge-like swellings known as atheroma. It may also promote overgrowth of smooth muscle cells in the artery linings, interfere with the normal dilation and contraction of blood walls and/or activate blood- clotting factors and platelets to hasten the development of abnormal blood clots. If your homocysteine levels are persistently raised, that will lead to eventual health problems such as coronary heart disease, stroke, peripheral vascular disease, dementia and other problems – especially those linked with thrombosis and reduced blood supply.

WHAT’S A NORMAL LEVEL?

The safe, normal level of homocysteine is still uncertain. Initially, it was suggested as between 8 and 15 micromol/L. Researchers now believe it is important to maintain even tighter control as levels above 6.9 micromol/L may be harmful for long-term health. As homocysteine levels naturally rise with age, however, a level of 12 or under may still be acceptable for those aged over 60.

“Studies in people with pre-existing heart and circulatory problems suggest that taking folic acid / B12 supplements can produce clinical improvements in their condition.”

HOW DO I KNOW IF MY LEVELS ARE RAISED?

If problems such as coronary heart disease, stroke or certain developmental birth abnormalities (neural tube defects) run in your family, it is possible that a raised level of homocysteine is involved. Your doctor may be willing to measure your homocysteine levels but this is not yet routinely requested. If testing is not available on the NHS, a self-administered, pin-prick blood test is available from pharmacies. If you know you have a high homocysteine level, it is relatively easy to lower it by making dietary and lifestyle changes – much easier, in fact, than it is to correct an abnormal cholesterol balance. These changes include eating more foods rich in folate/folic acid, vitamins B6 and B12, as well as taking vitamin supplements. Even people who have inherited an abnormal homocysteine metabolism do not necessarily develop a raised homocysteine level if they maintain a relatively high intake of folic acid.

DIETARY CHANGES

To process homocysteine, it is important to eat plenty of foods that are rich in folate and vitamins B12 and B6. Unfortunately, dietary lack of these vitamins seems to be common. A survey in the US, for example, suggests that only 40% – 50% of people obtained enough folic acid from their diet to process homocysteine normally.

Folate (the natural form of folic acid) is found in green leafy vegetables, wholegrains, nuts, beans and yeast extracts. Vitamins B12 and B6 are in liver, kidney, oily fish – especially sardines – red meats and eggs. Some B6 is also present in wholegrains, soy products, bananas, nuts (especially walnuts), green leaves, avocado and yeast extract.

It is hard to obtain optimum levels from foods alone, however, especially if your enzymes need higher amounts than normal to work properly. Natural folate, for example, is not absorbed or used in the body as well as the synthetic form, folic acid, so supplements and fortified foods are usually

In a study of 350 people aged 65-75, folic acid supplements of just 400-600mcg per day were shown to produce significant lowering of homocysteine levels compared to placebo. Due to reduced absorption in the very elderly, however it was estimated they would need over 900mcg per day to avoid folate deficiency and to lower their cardiovascular risk. Adding in vitamin B12 is also important – both to lower the homocysteine level by a further 7% and to help prevent a vitamin B12 deficiency which can be masked by taking folic acid supplements.

Studies in people with pre-existing heart and circulatory problems suggest that taking folic acid/B12 supplements can produce clinical improvements in their condition. Large-scale trials are also under way to see whether lowering homocysteine levels with supplements can reduce overall cardiovascular mortality.

Exciting recent results from the Netherlands suggests that folic acid supplements (800mg daily) may help to slow the decline in memory and thinking power that often goes with age. The researchers found those using the supplements during a three-year period had memory scores as good as those of people 5.5 years younger than them, while in tests of thinking speed, they performed as well as people who were almost two years younger.

As homocysteine is thought to cause damage partly by triggering oxidation reactions in the body, it is also important to consider taking antioxidant supplements such as selenium, vitamins A, C and E, carotenoids, alpha-lipoic acid and green tea.

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