High homocysteine levels linked to brain atrophy in alcoholics

There is strong correlation between high blood plasma levels of homocysteine and reduced brain hippocampal volume in chronic alcoholics, an MRI study has shown for the first time. These findings suggest that increased plasma levels of the excitatory amino acid may be a risk factor for alcohol-induced brain atrophy, according to a professor of psychiatry at Friedrich-Alexander-University of Erlangen-Nuremberg in Erlangen, Germany.

The correlation also introduces the possibility that lowering homocysteine levels might protect alcoholics from brain damage. Homocysteine and its metabolites act as agonists at the Nmethyl-D-aspartate (NMDA) receptor. Over-stimulation of the NMDA receptor is believed to mediate neurotoxicity, leading investigators to hypothesize that alcohol-induced hyperhomocysteinemia is part of the brain damage mechanism in alcoholics. The prospective investigation used neuroimaging and blood plasma analysis to detect the influence of different variables on the hippocampal volume of chronic alcoholics . Volumetric MRI was performed on 52 chronic alcoholics with an established diagnosis of alcohol dependence according to DSM-IV criteria and on 30 healthy controls. The active drinkers were detoxified upon admission to the hospital and underwent MRT within 10 days. All patients underwent clinical diagnosis and laboratory investigations, including high-performance liquid chromatography for detection of plasma homocysteine. The investigators compared the laboratory samples and hippocampal volumes of the alcoholics and the healthy controls, and analyzed the association between hippocampal volumes in the alcoholics and independent variables such as patient gender, body mass index (BMI), and number of years drinking.

The average total hippocampal volumes and the left and right hippocampal volumes were significantly reduced in alcoholics, compared with the control group. The laboratory analyses showed that the women drinkers had significantly increased homocysteine levels and lower folate and vitamin B6 levels than the women controls.

The men drinkers also had significantly increased homocysteine levels and lower folate levels, but did not have lower levels of vitamin B6. Women drinkers had significantly lower results than did men in the study for total, right, and left hippocampal volumes, vitamin B6 levels, and lifetime drinking. Among the alcoholic patients, there were significant correlations between hippocampal volume and homocysteine, and less significant correlations between hippocampal volume and body mass index. Additionally, men with more years of alcohol drinking had smaller hippocampal volumes. Overall, patients who had greater brain atrophy were twice as likely to have high homocysteine levels as those with less at atrophy.

These results are consistent with those observed in homocysteine studies of Alzheimer’s disease patients, in which Alzheimer’s patients with elevated homocysteine levels have more rapid brain atrophy than those with lower homocysteine levels. The observed folate status of the alcoholic subjects is also significant. The reduced folate levels support the increasing body of evidence associating chronic ethanol-induced brain damage with nutritional deficiencies or withdrawal hyperexcitability. The inverse relationship between folate and plasma homocysteine levels further validates the hypothesis of homocysteine’s involvement in the brain damage mechanism. Further research is needed to determine whether lowering plasma homocysteine levels through nutritional supplementation (vitamins B6, B12, and folic acid) or other means could protect alcoholics from brain damage.