Higher Folate Intake Decreases Alzheimer’s Risk – Study

A study published in the January Archives of Neurology shows higher folate intake may decrease the risk of Alzheimer's disease, but the researchers say the results require confirmation with clinical trials.

Jose A. Luchsinger, M.D., Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University, et al., found "the risk of AD decreased with the increasing quartile of total folate intake and this association was statistically significant after adjustment for intake of vitamins B6 and B12."

The mean total folate intake was 446.0 ± 226.8 µg. The total mean intake of vitamin B12 was 12.6 + 18.8µgl, and for vitamin B6 it was 7.1 + 17.3 mg.

"There was a modest correlation of total folate intake to lower homocysteine levels and higher serum folate levels and a moderate inverse correlation of serum folate with homocysteine levels," Luchsinger et al. say.

The finding indirectly suggests a "lower homocysteine level is a potential mechanism of the association between higher folate intake and a lower AD risk," the researchers add.

"The inverse correlation between vitamin B12 and homocysteine levels was stronger than that for folate and homocysteine levels, and the association between folate intake and AD was independent of homocysteine level," the researchers say.

"We must consider whether there are mechanisms relating folate intake to AD independent of homocysteine level, which we cannot address," Luchsinger et al. say.

They also note their study conflicts with recent study findings.

A June 2006 New England Journal of Medicine study found homocysteine levels that were reduced by B vitamin supplementation did not improve cognitive performance in older people, contrary to an existing hypothesis (¹ (Also see "Vitamin B Has No Effect On Cognitive Function – NEJM Study" - Pink Sheet, 3 Jul, 2006.), p. 11).

A study in the August 2005 Alzheimer's & Dementia says "older adults whose diets include a total folate intake at or above the recommended dietary allowance are at a significantly reduced risk of developing Alzheimer's diease," (² 'The Tan Sheet' Aug. 22, 2005, In Brief).

Luchsinger et al., from 1992 through 1994 in northern Manhattan, collected data from 965 people age 65 and up. Through the course of the study, 192 developed AD.

The researchers say a "semiquantitative," 61-item food frequency questionnaire was included and "likely resulted in underestimation of nutrient intake."

However, they note 98 percent of the dietary questionnaires were obtained prior to the implementation of folate fortification in grain.

"Folate deficiency is less common now, and our results apply only to the time before folate fortification," Luchsinger et al. say. "These results may not be reproduced in more recent studies."

The researchers stress the importance of the "total cumulative intake of folate" from food and dietary supplements. They did not find the association of a lower risk of AD from food alone or dietary supplements alone.

"When only intake of high-dose supplements of folic acid (>400 µg) was considered, the association between folic acid intake and AD remained non-significant but in a direction suggesting a lower risk," Luchsinger et al. say.

In the study, 70.2 percent of the participants were women, 32.6 percent African-American, 45.3 percent Hispanic and 22.1 percent white.

An "important consideration is that the cohort in this study consists of subjects 65 years or older, with a high prevalence of vascular risk factors, and the results should be interpreted in this context," Luchsinger et al. say.

The authors conclude "low levels of serum folate, but not other vitamins, may increase the risk of AD" but "the decision to increase folate intake to prevent AD should await clinical trials."

- Rebekah Moan