Folate Weakly Linked to Reduced Alzheimer's Disease Risk

NEW YORK, Jan. 8 -- Folate appears associated with a lower risk of Alzheimer's disease, although the relationship is tenuous, according to an observational study here.

In the study of older, predominantly African-American and Hispanic women, a 50% reduction in the risk of Alzheimer's was found only for those consuming the highest amount of folate (488 g or more), and only after adjusting for vitamin B intake, said Jos A. Luchsinger, M.D., of Columbia University, and colleagues.

The recommended intake of folate is 400 g per day for adults, according to the NIH Office of Dietary Supplements.

Furthermore, the finding could have an explanation other than a direct effect of folate on Alzheimer's risk, the researchers reported in the January issue of Archives of Neurology.

The study also found no protective effect for B vitamins against Alzheimer's. But the authors also urged caution in interpreting this result.

"To our knowledge, ours is the first published study to associate homocysteine-related vitamins and Alzheimer's disease in a cohort that is predominantly African American and Caribbean Hispanic," the authors said.

Previous research has suggested that folate and vitamin B deficiencies may lead to elevated plasma homocysteine levels, which in turn may be a risk factor for cardiovascular disease, stroke, and Alzheimer's, they said.

The current study included 965 participants 65 or older living in northern Manhattan. Participants were given a food frequency questionnaire at baseline and followed for an average of about six years. The mean age at follow-up was nearly 75.8.

About one-third (32.6%) were African American, 45.3% were Hispanic, and 22.1% were white. The majority (70.5%) were women.

In an unadjusted analysis, those in the highest quartile of energy-adjusted folate intake (488 g or more) did not have a significantly reduced risk of Alzheimer's compared with those in the lowest quartile (293 g or less) (hazard ratio=0.7; 95% confidence interval=0.5 to 1.1; P=.13). The association remained non-significant after adjusting for factors such as sex, age, education, ethnicity, diabetes, heart disease, smoking, and stroke.

However, after adjustment and intake of B vitamins, there was a statistically significant risk reduction (HR=0.5; 95% CI=0.3 to 0.9; P=.02), the study found.

The analyses were based on total folate intake, which included both dietary intake and supplements. In separate analyses, dietary intake alone was not associated with reduced risk (HR=0.8; 95% CI=0.5 to 1.2; P=.25). Nor was supplement intake related, not even intake of high-dose supplements of 400 g or greater (HR=0.7; 95% CI=0.5 to 1.2; P not given), although the data suggested a trend toward lower risk, the authors said.

"Our results are consistent with those of studies suggesting that higher intake of folate is related to a lower risk of Alzheimer's Disease, and that intake of vitamins B₁₂ and B₆ is not related to or is not as important to the risk," the authors said.

"We found this association for total (dietary and supplement) folate intake, but not for dietary or supplement sources alone, suggesting that what is important is the total cumulative intake of folate from both sources," they said.

On the one hand, the study suggested that folate may have a protective effect against Alzheimer's that is "unmasked" after adjusting for B vitamin intake, the authors said.

On the other hand, higher folate intake may simply be a marker of a healthier diet higher in fruits and vegetables that does not have an independent association with Alzheimer's, they said.

Furthermore, the negative finding for B vitamins may simply be due to the limited accuracy of the study's single measurement of dietary intake, the authors said.

"In addition, there have been sobering examples of the lack of translation of apparent benefit in epidemiological data to clinical trials," the authors said. "Thus, the decision to increase folate intake to prevent Alzheimer's Disease should await clinical trials."