OXFORD, UNITED KINGDOM. An inadequate intake of folic acid is firmly associated with an increased risk of vascular disease and, among women of childbearing age, with a significantly heightened risk of giving birth to a baby with neural tube defects. Now a team of researchers from the universities of Oxford and Bergen (Norway) report that low folate levels are associated with an increased risk of developing Alzheimer's disease (AD). Their study which spanned the period 1988 to 1996 involved 164 patients with a clinical diagnosis of AD and 108 control subjects. The AD diagnosis was confirmed by autopsy in 76 of the 164 patients who died during the study. The researchers found that AD patients had significantly lower blood levels of folic acid and vitamin B12 (cobalamin) than did controls. They also had significantly higher levels of the amino acid homocysteine. Homocysteine is a strong risk factor for vascular disease and its level has been found to be inversely proportional to the level of folic acid in the blood. Study participants with homocysteine concentrations equal to or higher than 14 micromol/liter were found to have a 4.5 fold higher risk of AD than did participants with a homocysteine level at or below 11 micromol/liter. This association held true even when corrected for age, sex, social class, cigarette smoking, and level of apolipoprotein E epsilon 4 (a known risk factor for the development of AD). Study participants with folate levels in the lower third of the overall distribution had a 3.3 fold higher risk of AD when compared to subjects in the upper third. Similarly, participants in the lower third of vitamin B12 levels had a 4.3 times higher risk of AD as compared to subjects in the upper third. The researchers also observed that disease progression was more rapid among AD patients with high initial homocysteine levels. They conclude that high homocysteine levels are an important risk factor for AD and that this risk can be significantly reduced by ensuring an adequate intake of folic acid and vitamin B12. They suggest that daily supplementation with 0.5 to 5 mg of folic acid and 0.5 mg of vitamin-B12 (cyanocobalamin) will lower the typical homocysteine levels found in Western populations by about a third. NOTE: This study was partially funded by Bristol-Myers Squibb.
Clarke, Robert, et al. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Archives of Neurology, Vol. 55, November 1998, pp. 1449-55
Diaz-Arrastia, Ramon. Hyperhomocysteinemia - A new risk factor for Alzheimer disease? Archives of Neurology, Vol. 55, November 1998, pp. 1407-08 (editorial)