Moderately High Homocysteine Tied To Stroke, Alzheimer’s Risk

Homocysteine is an amino acid believed to be toxic to blood vessels. Several studies have linked high blood levels of it to increased heart attack risk. This study found that homocysteine levels in patients with stroke, Alzheimer's disease or vascular dementia were consistently higher than homocysteine levels in age-matched healthy volunteers.

"Since B vitamins and foods fortified with folate can reduce homocysteine levels, this study suggests that B vitamin supplementation may be appropriate for most adults. It warrants a large placebo-controlled study of folate, and vitamins B6 and B12 in people at risk from dementia and stroke," says lead author Stephen P. McIlroy, Ph.D., a lecturer in geriatric medicine at Queen's University in Belfast, Ireland.

McIlroy and his colleagues studied 83 Alzheimer's patients (average age 77); 78 patients with dementia caused by poor blood flow to the brain, a condition called vascular dementia (average age 77); 64 stroke patients (average age 74) and 71 healthy volunteers (average age 74).

There is some disagreement among scientists about what constitutes an elevated homocysteine level. Here, researchers designated the upper quartile of homocysteine levels of the healthy volunteers – 13.3 micromoles per liter (ìmol/L) or higher – as an elevated level.

They also collected data on education, diet, blood pressure, cholesterol, and smoking history. Several of these factors are associated with the risk for Alzheimer's disease, and smoking directly affects homocysteine levels, he says. The researchers also used DNA testing to determine if any of the subjects had a variation in the gene methylenetetrahydrofolate (MTHFR), which can adversely affect folate metabolism.

After correcting for other risk factors, elevated homocysteine was associated with a 2.9 times greater risk for Alzheimer's disease than risk in volunteers with lower levels of homocysteine. The stroke risk was 5.5 times greater, and for vascular dementia, it was 4.9 times greater. These findings were not related to having the MTHFR mutated gene.

In an accompanying editorial, Amos D. Korczyn, M.D., of the department of neurology at Tel-Aviv University Medical School in Ramat-Aviv, Israel, notes that there is no ultimate proof that homocysteine causes stroke or dementia. He says that elevated homocysteine could theoretically be the result of stroke or dementia. Additionally, he notes that poor diet – which is common in old age, particularly among people with dementia – may raise homocysteine.

However, Korcyzn also says it may now be appropriate to recommend that elderly people and particularly those with higher risk of vascular disease or dementia take vitamins B12 and folate.

"Since dietary habits are so different among people, it may be appropriate to recommend 2 to 5 mg folic acid and a similar dose of vitamin B12 daily," he says. "This recommendation is based on the known safety of both vitamins, which do not have side effects even if used in excessive amounts, and their low cost." McIlroy notes that in the United States many foods, especially cereals, are fortified with folate but this is not the case in the United Kingdom. Even with the fortified foods, a daily vitamin B supplement may be warranted especially after a stroke, he says.

The American Heart Association recommends that healthy people obtain adequate nutrient intakes from foods eaten in variety and moderation, rather than from supplements.

McIlroy's co-authors are Kevin B. Dynan, M.D.; John T. Lawson, M.D.; Christopher C. Patterson, Ph.D.; and A. Peter Passmore, M.D.