The primary role of cellular gamma glutamyltransferase (GGT) is to metabolize extracellular reduced glutathione (GSH), allowing for precursor amino acids to be assimilated and reutilized for intracellular GSH synthesis. Paradoxically, recent experimental studies indicate that cellular GGT may also be involved in the generation of reactive oxygen species in the presence of iron or other transition metals. Although the relationship between cellular GGT and serum GGT is not known and serum GGT activity has been commonly used as a marker for excessive alcohol consumption or liver diseases, our series of epidemiological studies consistently suggest that serum GGT within its normal range might be an early and sensitive enzyme related to oxidative stress. For example, serum and dietary antioxidant vitamins had inverse, dose-response relations to serum GGT level within its normal range, whereas dietary heme iron was positively related to serum GGT level. More importantly, serum GGT level within its normal range positively predicted F2-isoprostanes, an oxidative damage product of arachidonic acid, and fibrinogen and C-reactive protein, markers of inflammation, which were measured 5 or 15 years later, in dose-response manners. These findings suggest that strong associations of serum GGT with many cardiovascular risk factors and/or events might be explained by a mechanism related to oxidative stress. Even though studies on serum and/or cellular GGT is at a beginning stage, our epidemiological findings suggest that serum GGT might be useful in studying oxidative stress-related issues in both epidemiological and clinical settings.

Is serum gamma glutamyltransferase a marker of oxidative stress

Verbal report procedures, such as interviews, tests and questionnaires, have become the dominant method to obtain clinical data on alcohol abuse and its modification through treatment. The extent to which this method provides reliable and valid information for research purposes, and how its accuracy and usefulness can be enhanced, is examined. A review of methodological studies in the alcohol literature shows that although the information obtained from alcoholics and heavy drinkers tends to be reliable and valid, there can be considerable variability in accuracy, depending on the sensitivity of the information sought, the specificity of the validation criteria, the personal characteristics of the respondents and the demand characteristics of the task. It is suggested that the question of whether verbal report procedures are valid or invalid is less important than the issue of how they can be improved to the point that confidence can be placed in their findings. To facilitate this process, methodological t...

Verbal report methods in clinical research on alcoholism: response bias and its minimization.

https://www.amjmed.com/article/0002-9343(87)90061-1/pdf

Screening for alcohol abuse using the cage questionnaire

Beyond alcohol: Beverage consumption and cardiovascular mortality

Objective—To investigate the association of -glutamyltransferase (GGT) with incident CHD and stroke. GGT is a marker of alcohol intake but may also reflect oxidative stress and nonalcoholic fatty liver disease. Alanine aminotransferase (ALT) is the enzyme most closely associated with liver fat content. Methods and Results—Associations of GGT and ALT with incident CHD, stroke, and a combined outcome of CHD or stroke were examined in the British Women’s Heart and Health study (n2961), and a meta-analysis of population based studies examining these associations was performed. In pooled analyses of fully adjusted results of 10 prospective studies, a change of 1 U/L of GGT was associated with a HR1.20 (95% CI: 1.02, 1.40) for CHD; a HR1.54 (95% CI: 1.20, 2.00) for stroke; and HR1.34 (95% CI: 1.22, 1.48) for CHD or stroke. Heterogeneity was substantially decreased when 2 studies in Asian populations were excluded. In a subgroup of nondrinkers results were similar to the main analysis. Meta analyses of the only 2 studies that examined the association of ALT with incident cardiovascular events found a HR1.18 (95% CI: 0.99, 1.41) for CHD and a HR1.10 (95% CI: 0.89, 1.36) for CHD or stroke (combined). Conclusion—GGT is associated with incident vascular events independently of alcohol intake. The mechanisms underlying this association remain unclear and require future study. (Arterioscler Thromb Vasc Biol. 2007;27:2729-2735.)

Gamma-Glutamyltransferase Is Associated With Incident Vascular Events Independently of Alcohol Intake: Analysis of the British Women’s Heart and Health Study and Meta-Analysis

A panel of blood tests, purportedly markers for alcohol abuse, were examined in 543 relatively healthy alcoholics entering ambulatory rehabilitation treatment. Individual tests were too low in sensitivity: gamma-glutamyl transpeptidase was abnormally high in only 49%, then mean corpuscular volume (45%), high density lipoprotein cholesterol (HDLC) (25%), serum glutamic oxaloacetic transaminase (SGOT) (28%), and blood alcohol (21%). HDLC was of low sensitivity, generally unaffected by liver disease, and related to quantitation of recent alcohol consumed. Combining seven markers, 82% of males and 71% females had at least one abnormally high value. Histories of heavy recent drinking, positive blood alcohol levels on admission, and manifest liver disease on physical examination or by hyperbilirubinemia were associated with high sensitivities of individual and pooled markers. The biochemical markers studied can be useful to suggest alcohol abuse, especially in some populations of drivers. In other populations of alcoholics, especially with intermittent alcohol or recent abstinence, their sensitivities were so low as to discourage extensive reliance on their use. The diagnosis of alcoholism continues to depend on clinical history of alcohol-related problems, including social, familial, legal, medical, psychological, and economic.

Biochemical markers for alcoholism: sensitivity problems

The possible use of high density lipoprotein cholesterol (HDLC) as a marker of alcohol abuse was studied in 92 alcoholic patients entering an inpatient treatment program. The average HDLC levels of 68 male patients (66 +/- 23 mg/dl) and 24 female patients (83 +/- 18 mg/dl) were significantly higher than the values for the corresponding control groups of similar ages. Approximately 20% of the male patients had HDLC levels over the mean +/- 2 SD over the control groups. Following 2 wk of alcohol abstinence, the HDLC levels decreased to the control range. HDLC, as a measure of alcohol abuse, may be especially useful in combination with determination of gamma glutamyl transpeptidase (GGT), since these two tests singly or in combination were elevated in 65% of the male and 85% of the female patients.

Chronic alcohol abuse and high density lipoprotein cholesterol.

Abstinence-induced changes in plasma apolipoprotein levels of alcoholics

The major medical sequelae of opioid addiction.

Plasma lipids, including high density lipoproteins (HDL) components, were studied in 26 healthy male alcohol abusers. Age- and gender-matched controls denied the use of substances or behaviors associated with increased HDL. On admission to abstinence treatment, the alcohol abusers' total cholesterol and triglycerides were usually normal. Their HDL-cholesterol levels were high, and fell to normal within 2 weeks of sobriety. Apolipoprotein (APO) AI and AII were high initially and also became normal in 2 weeks. APO A I and II to HDL-cholesterol ratios appeared to change during abstinence, while APO AI/AII did not. APO CIII, high initially, fell during treatment, but was still high after 4 weeks of sobriety. Therefore, alcohol seems to affect several components of HDL and these HDL changes move toward normal at different rates. If alcohol is protective against some cardiovascular disease, it remains to be established whether HDL is involved and which HDL component is most important.

Paul Cushman

Papers

Biochemical markers for alcoholism: sensitivity problems

Chronic alcohol abuse and high density lipoprotein cholesterol.

Abstinence-induced changes in plasma apolipoprotein levels of alcoholics

The major medical sequelae of opioid addiction.

Alcohol: high density lipoproteins, apolipoproteins