Activity of Secretory Sphingomyelinase Is Increased in Plasma of Alcohol-Dependent Patients

Background: Acid sphingomyelinase (ASM, EC 3.1.4.12) hydrolyzes sphingomyelin to ceramide and represents a major regulator of sphingolipid metabolism. Increased activity of ASM has been observed in a variety of human diseases, and a critical contribution of ASM to medical conditions was demonstrated in several mouse models. In agreement with increased ASM activity in cell lines treated with ethanol, we have recently found higher levels of ASM activity in peripheral blood cells of active drinkers. However, the influence of ethanol on secretory ASM (S-ASM) has not been investigated so far. Methods: ASM activity and routine blood parameters were determined in plasma samples of 27 patients with alcohol dependence during physical withdrawal and compared to a group of 36 healthy volunteers. Results: Compared to the control group, patients with alcohol dependence had S-ASM activity increased by about 3-fold (141 +/- 69 vs. 428 +/- 220 pmol/ml/h; p < 0.001) at the beginning of physical withdrawal. During withdrawal, S-ASM activity decreased by about 50% (p < 0.001; day 0 vs. day 7 to 10) and finally approximated nearly normal values. On the day of admission, S-ASM activity correlated positively with levels of carbohydrate-deficient transferrin (r = 0.410, p = 0.034) and high-density lipoprotein cholesterol (r = 0.440, p = 0.022) and inversely with body mass index (r = -0.509; p = 0.007), glucose (r = -0.480; p = 0.011), triglycerides (r = -0.592; p = 0.001), and large unstained cells (r = -0.526; p = 0.017). Conclusions: Activity of S-ASM is increased in alcohol-dependent patients and correlates with established biomarkers of excessive drinking. The increased S-ASM activity is implicated in alcohol-induced lipid alterations and might be relevant for the occurrence of alcohol-related disorders.