Folate and B vitamin pills failed to help keep elderly people's brains and memories sharp in the longest study yet to test this approach.
Some scientists said the study was too small to be the final word, but it was one of the best done so far and came after three very large studies produced disappointing results using the same nutrients to try to prevent heart disease.
"We'd love to have something that is simple and reproducible and cheap and effective that would reduce the amount of dementia," but proof that vitamin supplements can do this is still lacking, said Bill Thies, scientific director of the Alzheimer's Association, which had no role in the study.
The findings were published in Thursday's New England Journal of Medicine.
Folate and B vitamins lower homocysteine, a blood substance that can make arteries stiffen and clog. Many studies have observed that people with higher levels of homocysteine also have a greater risk of heart disease, Alzheimer's and other forms of dementia.
But whether lowering homocysteine can prevent these problems is unknown. In two studies of people at high risk of dementia, vitamin pills did not help, but these experiments lasted less than four months.
Researchers at the University of Otago in New Zealand tested the approach for two years in 276 healthy people 65 and older with relatively high levels of homocysteine at the outset.
Half were given daily pills containing 1,000 micrograms of folate, 500 micrograms of B-12 and 10 milligrams of B-6; the other half got dummy pills.
Homocysteine levels fell in those taking the supplements, but cognitive function, as measured by several different tests, remained the same in both groups.
Dr. Robert Clarke of the University of Oxford in England, a proponent of the theory that lowering homocysteine may help, said that because the placebo group had no decline in function, it would not have been possible to see any benefit from the vitamins.
"We cannot rule out the possibility of a benefit with long-term treatment," or that different doses might have made a difference, the researchers wrote.
Similarly, Thies theorized that people may need to take the pills even longer to benefit, or start earlier in life.
Longer and larger studies are under way.