Kinetics of HDL Cholesterol and Paraoxonase Activity in Moderate Alcohol Consumers Aafje Sierksma, Martijn S. van der Gaag†, Arie van Tol, Richard W. James, and Henk F. J. Hendriks Background: The inverse association between moderate drinking and coronary heart disease mortality is well established. This study was performed to investigate the kinetics of the alcohol-induced increases in apo A-1, HDL cholesterol, and paraoxonase (PON) activity, as well as to study whether the alcohol-induced increases in PON activity differ within different PON polymorphisms, and to investigate whether moderate alcohol consumption has similar effects on the outcome measures in postmenopausal women as in middle- aged men. Methods: In a randomized, diet-controlled, crossover study, 10 middle-aged men and 9 postmenopausal women, all apparently healthy, nonsmoking, and moderate alcohol drinkers, consumed beer or no-alcohol beer (control) with evening dinner during two successive periods of 3 weeks. During the beer period, alcohol intake equaled 40 and 30 g/day for men and women, respectively. The total diet was supplied to the subjects and had essentially the same composition during these 6 weeks. Before each treatment was a 1-week washout period, in which the subjects were not allowed to drink alcoholic beverages. Results: Moderate alcohol consumption significantly increased serum apo A-I level after 5 days (3.7%, p  0.05); after 10 days, serum HDL cholesterol level was increased (6.8%, p  0.001), and after 15 days serum PON activity was increased (3.7%, p  0.05), all compared with no alcohol consumption. Gene polymorphisms did not modulate the alcohol effect on PON. Conclusions: Serum apo A-I, HDL cholesterol, and PON activity were significantly increased during 3 weeks of moderate alcohol consumption as compared with no alcohol consumption. Moreover, the results suggest that there is a sequence in induction of these parameters. After an increase in apo A-I, HDL cholesterol is increased followed by an increase in PON activity. Increased serum HDL cholesterol level and PON activity may be a mechanism of action not only in healthy middle-aged men but also in post- menopausal women, underlying the reduced coronary heart disease risk in moderate drinkers. Key Words: Moderate Alcohol Consumption, Apo A-I, HDL Cholesterol, Paraoxonase, Gender. T HE INVERSE ASSOCIATION between moderate drinking and coronary heart disease mortality is well established. Epidemiological and physiologic data are in favor of a causal relationship (van Tol and Hendriks, 2001). Three major physiologic systems have been proposed for the protective action of moderate alcohol consumption: (1) increases in HDL cholesterol levels (Hendriks et al., 1998; van der Gaag et al., 1999), with associated increases in paraoxonase (PON) activity (van der Gaag et al., 1999) and cholesterol efflux (van der Gaag et al., 2001); (2) stimula- tion of fibrinolysis (Hendriks et al., 1994) and decrease in coagulation (Dimmitt et al., 1998); (3) decrease in inflam- matory processes (Imhof et al., 2001; Koenig et al., 1999). PON is an enzyme entirely complexed to HDL and may protect against atherosclerosis by its antioxidative proper- ties (Aviram et al., 1998; Mackness et al., 1997, Mackness et al., 1998; Watson et al., 1995). In our previous study in middle-aged men, we observed an increase in serum PON activity after 3 weeks of moderate alcohol consumption as compared with water consumption, which correlated strongly with increases in HDL cholesterol and apo A-I concentration (van der Gaag et al., 1999). The aim of the present experimental study was 3-fold: (1) to investigate the kinetics of the alcohol-induced increases in apo A-I, HDL cholesterol, and PON activity; (2) to study whether the alcohol-induced increases in PON activity dif- fer within different PON polymorphisms; and (3) to inves- tigate whether moderate alcohol consumption has similar effects on the outcome measures in postmenopausal women as in middle-aged men. From the Department of Nutritional Physiology, TNO Nutrition and Food Research (AS, MSG, HFJH), Zeist, The Netherlands; University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care (AS), Utrecht, The Netherlands; Department of Biochemistry, Cardiovascular Re- search Institute COEUR (AvT), Erasmus University Rotterdam, The Neth- erlands; and Division of Endocrinology and Diabetes (RWJ), University Hospital, Geneva, Switzerland. Received for publication February 25, 2002; accepted July 6, 2002. The research described in this paper was funded by the Dutch Foundation for Alcohol Research (SAR). RWJ was supported by a grant from the Swiss National Research Foundation. Reprint requests: Reprint requests: Dr. Henk F.J. Hendriks, Department of Nutritional Physiology, TNO Nutrition and Food Research, Utrechtseweg 48, P.O. Box 360, 3700 AJ Zeist, The Netherlands; Fax: +31 30 6944928; E-mail: hendriks@voeding.tno.nl †Deceased. DOI: 10.1097/01.ALC.0000030639.57507.60 0145-6008/02/2609-1430$03.00/0 ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 26, No. 9 September 2002 1430 Alcohol Clin Exp Res, Vol 26, No 9, 2002: pp 1430–1435