In Reply: Dr Pratico notes that homocysteine levels in the study participants were generally in the normal range. He further states that homocysteine is not a risk factor for dementia unless levels rise above 15 μmol/L. Evidence from the US population, however, suggests that the association with dementia is not based on a threshold effect.1 We therefore hypothesized that reduction of homocysteine in individuals without elevated levels would be therapeutic, although our trial results refuted this idea. Pratico makes the interesting point that it is possible that reduction of normal levels could impair homocysteine-dependent metabolic processes. We found no positive or negative effect of high-dose vitamin treatment on cognition in participants in the highest baseline homocysteine quartile (mean [SD], 13.42 [2.45] μmol/L) or lowest baseline quartile (5.66 [0.86] μmol/L). Within the highest quartile, 16 of 94 participants (17%) had baseline homocysteine levels above 15 μmol/L; 14 of these were assigned to the active treatment group.
Aisen PS, Schneider LS, Sano M. High-Dose B Vitamin Supplements and Alzheimer Disease—Reply. JAMA. 2009;301(10):1020-1022. doi:10.1001/jama.2009.213