Our Daily Folate

By Dick Thompson

When University of Kentucky epidemiologist David Snowdon makes an important discovery, he doesn't break the news at a scientific meeting or even in a peer-reviewed journal. First he tells the School Sisters of Notre Dame, a group of Roman Catholic nuns who have given their bodies--and, after death, their brains--to help Snowdon study the slow mental wasting known as Alzheimer's disease.

The nuns and their carefully preserved brains have proved to be an Alzheimer's research treasure. From it, Snowdon has already found that tiny strokes may be the switch that flips a mildly deteriorating brain into full-fledged dementia and, bizarrely, that the density of ideas in the writings of a 20-year-old novice may be, for reasons nobody can fathom, a predictor of Alzheimer's at age 80. But in nine years of study, Snowdon has never been able to identify anything that might prevent the disease.

Until now. Snowdon's latest discovery, which he will present at the National Institutes of Health this week but which he first revealed at congregation headquarters in Rome last fall, shows a strong relationship between the severe brain atrophy of Alzheimer's disease and low levels of the common B vitamin known as folic acid, or folate. Furthermore, nuns with the highest levels of folate suffered the lowest levels of cognitive decline. Says Charles Halsted, professor of internal medicine at the University of California at Davis: "It's pretty exciting stuff."

Indeed, anything that can prevent or even slow down Alzheimer's will have an enormous impact. Today about 4 million Americans suffer from the degenerative brain disorder, and caring for them costs some $100 billion a year. With the aging of the baby-boom generation, those numbers could triple within 40 years. Warns Bill Thies, vice president for scientific affairs at the Alzheimer's Association: "We are facing an imminent epidemic."

While Snowdon's study was small, involving only 30 individuals, the statistical relationship was unusually powerful. Moreover, it follows a similar finding made by researchers in England last year. "It's a remarkable confirmation in an entirely different population," says David Smith, director of Oxford University's Project to Investigate Memory and Ageing.

In fact, it was shortly after reading the Oxford paper that Snowdon began trolling through his database to see if he too could find a link between folate and Alzheimer's. He began with 30 brains that had been discovered in autopsy to have had the distinguishing plaques and tangles of Alzheimer's disease. Of those 30 brains, 15 had the severe atrophy of the neocortex associated with advanced dementia. Next Snowdon analyzed blood samples taken from the nuns while they were alive. He screened for 19 different components, including vitamin E and cholesterol. The only statistically significant relationship he found, how- ever, was a link between Alzheimer's and folate. Drilling deeper into the data, he found a powerful link between brains with the most advanced Alzheimer's and the lowest levels of folate.

Despite the strong evidence, Snowdon cautions, it is still possible that folate does not play a direct role in the disease. The link could be coincidental. Or it could be that the same mechanism that triggers the disease also destroys the body's ability to retain folate. But folate and the amino acid it controls, homocysteine, have already been implicated in a broad range of diseases, as well as certain neurological birth defects (see box).

To nail down the low-folate, high-homocysteine link to Alzheimer's, researchers will have to explain how it might be doing damage. They are pursuing a growing list of theories. It may be that folate bestows some protective effect directly on the cell. Or it may be that without folate to control it, homocysteine reaches levels that are toxic to neurons or to the cells that line blood vessels. This could lead to the type of ministrokes found in Snowdon's earlier studies.

Indisputable confirmation will require large-scale clinical trials. Luckily, these may not be long in coming. The National Institute on Aging has already modified a trial currently under way that looks at the influence of supplemental B vitamins, including folic acid, on heart disease in 3,000 older women. To make the Alzheimer's connection, the NIA simply added an annual test of cognitive function to the heart study to see whether the vitamins lower the rate of expected dementia in the group. Results from that study should be available within three years.

Meanwhile, how much vitamin B should you take? That's what the nuns asked too. Unfortunately, there is very little information about how such nutrients are metabolized in the elderly. Snowdon suggests that taking double the current recommended daily allowance is probably a safe precaution. But it is possible to take too much of a good thing. Excessive folic acid can be dangerous if it masks symptoms of other diseases.

So the best advice may be the same that your mother gave you--and that Sister Mary Aloysius, former dietitian at the Mankato, Minn., convent, has been giving the sisters there for the past 30 years: Eat a balanced diet, including plenty of beans and leafy green vegetables. The advice may be the same, but Mary Aloysius reports that ever since the nuns heard about Snowdon's folate findings, they have been crowding around the salad bar.