Gamma-Glutamyl Transferase as a Marker of Alcohol Abuse

Excessive alcohol consumption is a major cause of health problems throughout the Western world, and the need for objective clinical tools for detecting alcohol abuse in its early phase has been widely acknowledged. Gamma-glutamyl transferase (GGT) is a liver-derived enzyme, which has long been used as a marker of excessive alcohol consumption, but the amount of drinking needed to elevate GGT levels has remained unknown. Also, it has been suggested that GGT levels may be elevated by factors such as obesity and increasing age in addition to alcohol consumption, although the magnitude of such effects have remained unclear. The relationships between alcohol consumption, obesity, age and GGT values are studied here in a large number of heavy drinkers and apparently healthy reference individuals, classified as follows: subjects reporting no alcohol consumption (abstainers), subjects reporting 1–40 grams of ethanol consumed per day (moderate drinkers) and subjects reporting 40–540 grams of ethanol consumed per day (heavy drinkers). The reference population was further classified according to body mass index (BMI) into underweight (BMI<20), normal weight (BMI 20–25), overweight (BMI 25– 30) and obese (BMI>30), and by age into those under 18 years, 18–30 years, 30–50 years, 50–70 years and over 70 years. GGT activity was markedly higher in the heavy drinkers than in the moderate drinkers (p<0.001) or abstainers (p<0.001), and the values in the moderate drinkers also exceeded those for the abstainers, although the difference was significant only for men (p<0.001). GGT activities in the moderate drinkers also showed additive effects of overweight or obesity which were not present in the abstainers, although the changes occurring as a function of increasing BMI and moderate drinking were of a lesser magnitude in the women than in the men. Consequently, the upper normal GGT limits based on normal weight abstainers (men: 53 U/l; women: 45 U/l) were markedly lower than those based on the unselected reference population (men: 68 U/l; women: 50 U/l) and the analytical sensitivity of GGT as a marker of alcohol abuse showed significant variation as a function of BMI in the reference population. The rates of false positive values varied from 2 to 26% in the subgroups from low to high BMI, respectively. GGT activities also increased with age until after 70 years, although decreasing activities were noted in males who abstained from drinking ethanol. The heavy drinkers in the age groups 18–30, 30–50 and 50–70 years showed several-fold higher mean GGT activities than the abstainers and moderate drinkers of corresponding ages, and the values for moderate drinkers also exceeded those for abstainers in all age groups among the men, whereas for the women the difference was significant only among those aged 18–30 years. The data show that serum GGT is a highly sensitive indicator of ethanol consumption, although its diagnostic value could be improved by using reference data based solely on abstainers of normal weight, or else BMI-specific reference intervals. Also, the fact that GGT activity responds to etha-