An essential building block of protein, Homocysteine is showing a dark side because of increasing indications of a likely link to heart disease. Iva Pocock reports
There's a new kid on the block when it comes to heart disease. No longer are high cholesterol, blood pressure, family history and smoking the only easily identifiable risk factors for suffering cardio-vascular disease. They have been joined by homocysteine, a protein present in all our cells, but which at high levels poses as great a risk of heart disease as smoking or high cholesterol.
Irish medical researchers have been to the forefront of international investigations into the relationship between blood homocysteine levels and heart disease and stroke, which began in the 1960s following the observation that those with a rare genetic disorder, homocystinuria, who have high homocysteine levels, tend to get cardiovascular disease in their 20s.
"This led to the homocysteine hypothesis in the late 1970s and early 1980s," explains cardiologist Dr Pat O'Callaghan. A former researcher with international homocysteine expert Professor of Cardiology Ian Graham of the Adelaide and Meath Hospital, he is now senior registrar at Britain's national heart hospital, the Royal Brompton in London. "Then people started looking at people with heart disease and discovered that their homocysteine levels were slightly elevated."
As only 50-60 per cent of cardiovascular disease is accounted for by the traditional risk factors such as smoking, high blood pressure, high cholesterol and family history, homocysteine became topical about 15 years ago.
One large survey involving 19 medical centres in nine European countries, co-ordinated by Prof Graham, showed a definite link between homocysteine and premature coronary disease. Those in the top fifth of homocysteine levels had double the risk of cardiovascular disease.
"It also showed that certain subsets, in particular smokers and people with high blood pressure, had a much higher risk of cardiovascular disease if they had high homocysteine," Dr O'Callaghan explains.
A subsequent international study which assessed all relevant research between 1966-1999 quantified the level of risk and showed that a slight decrease in blood homocysteine level decreases the risk of heart disease by 11 per cent and stroke by 19 per cent.
Genetic studies also corroborate the link between homocysteine levels and risk of heart disease, says Trinity biochemist Prof John Scott. Those who inherit two copies of the gene which causes high homocysteine levels (about 12 per cent of the population) have a significantly higher risk of coronary heart disease than those without this genetic mutation.
People born with just one of these "bad" genes have an intermediate risk.
"It's almost impossible to explain away that result unless there's a cause and effect relationship between homocysteine levels and risk of heart disease," adds Prof Scott.
So is it possible to decrease one's homocysteine levels if they are high? Yes - by simply taking folate supplements.
The relationship between homocysteine levels and the amount of folate (also called folic acid) in one's diet has been of interest to scientists such as Prof Scott and Prof Hélène McNulty of the University of Ulster for many years.
"You can't be a folate researcher without being interested in homocysteine and vice versa," says Prof McNulty.
The relationship is straightforward: if you have homocysteine levels twice the normal level they will immediately come down if you take 400 micrograms of folic acid per day. This is the same amount recommended for women in early pregnancy who want to decrease the risk of neural tube defects.
"The six million dollar question is whether lowering homocysteine with folate will lower the risk of heart disease," says Prof McNulty.
The majority of cardiologists and scientists agree there is very powerful evidence that this is the case but clinical trials which definitively demonstrate a cause and effect relationship between supplementing folic acid and reducing cardiovascular disease will not be concluded for another two years. The largest study involves 12,000 people
In the meantime, what are cardiologists and public health bodies recommending? Should we be getting our homocysteine levels checked and taking folic acid to reduce our chances of having a stroke?
No, say the cautious such as the Department of Health and the European Association of Cardiology - yes, say others such as Prof Scott and a number of European colleagues.
"We do not recommend mass screening at the moment. We suggest that patients with cardio-vascular disease or at high risk of it should have their homocysteine levels measured and if elevated treated with vitamins namely folic acid and vitamin B12."
In addition, Prof Scott, who knows his homocysteine levels are low because he takes a vitamin B supplement, feels that "those who are aware of the evidence should also have their levels measured".
Cardiologist Dr O'Callaghan agrees it looks pretty likely that B vitamins will reduce the risk of heart disease: "I have yet to come across a cardiologist who discounts it completely as there is too much strong evidence."
But he respects the fact that the medical profession wants proof: "It's fairly standard."
However he regularly puts patients on folic acid in the knowledge that it may not be helping them but with the comfort that it is not posionous. He believes the majority of cardiologists are doing likewise.
The bottom line is that Dr O'Callaghan says: "If I myself had high homocysteine I would put myself on folic acid. And if one of my family had high homocysteine I'd advice they did too."