Is serum γ-glutamyltransferase inversely associated with serum antioxidants as a marker of oxidative stress?

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Abstract

A series of studies in black and white women and men have suggested that serum γ-glutamyltransferase (GGT) within its normal range might be an early marker of oxidative stress. If serum GGT is a marker of oxidative stress, it might have important implications both clinically and epidemiologically because measurement of serum GGT is easy, reliable, and not expensive. We examined the cross-sectional association between deciles of serum GGT and concentrations of serum antioxidants among 9083 adult participants in the third U.S. National Health and Nutrition Examination Survey. After adjustment for race, sex, age, and total cholesterol, serum concentration of GGT across all deciles was inversely associated with serum concentrations of α-carotene, β-carotene, β-cryptoxanthin, zeaxanthin/lutein, lycopene, and vitamin C (p for trend <.01, respectively). Vitamin E was not associated with serum GGT. All these associations were not materially different after additional adjustment for total energy intake, body mass index, smoking status, smoking amount, alcohol intake, and exercise. These associations were similarly observed among most subgroups. In conclusion, the current and previous studies strongly suggest that serum GGT level within its normal range may be an early marker of oxidative stress.

Introduction

A series of studies [1], [2], [3] in Coronary Artery Risk Development in Young Adults (CARDIA) subjects have shown that serum γ-glutamyltransferase (GGT) within its normal range might be related to oxidative stress. In these studies, both dietary and serum antioxidants inversely predicted future serum GGT, whereas dietary heme iron positively predicted it [2], [3]. In addition, serum GGT predicted C-reactive protein, a marker of inflammation, and F2-isoprostanes, a marker of oxidative damage to arachidonic acid, measured 15 years later in dose–response assays [1].

Experimental studies [4], [5], [6], [7] have reported that cellular GGT has a central role in glutathione homeostasis by initiating the breakdown of extracellular glutathione (GSH), a critical antioxidant defense for the cell. Paradoxically, there is evidence that, under physiological conditions, GGT is directly involved in the generation of reactive oxygen species, especially in the presence of iron or other transition metals [8], [9], [10], [11].

With an increasing interest in oxidative stress, emphasis is now being placed on developing functional biomarkers of oxidative stress status, that is, biomarkers that integrate the effects of exposure to oxidants coupled with the full range of antioxidant protective mechanisms in vivo [12]. Many such biomarkers are being studied, including various measures of lipid, DNA, and protein oxidation [12]. Measurement of serum GGT is reliable, easy, and not expensive [13]. Thus, if serum GGT is a marker of oxidative stress, it might have important implications both clinically and epidemiologically.

However, to our knowledge, only the results from the CARDIA study suggest that serum GGT is a marker of oxidative stress in a human population. Therefore, we examined the association between serum antioxidants and serum GGT level among another group of subjects, namely a representative sample of the U.S. population, using the third National Health and Nutrition Examination Survey (NHANES III).

Section snippets

Materials and methods

The NHANES III was a national examination survey conducted in the United States from 1988 to 1994 by the National Center for Health Statistics of the Centers for Disease Control and Prevention. It used complex, multistage, stratified, clustered samples of civilian, noninstitutionalized populations age 2 months and older. A detailed description of survey methods and data collection procedures has been published elsewhere [14].

Results

The average age of the sample was 47.6 years. The proportions of ethnic groups were 47.3% for non-Hispanic white, 28.1% for non-Hispanic black, and 24.6% for Mexican American. There were more females (53.6%) than males (46.4%) in the sample.

After adjusting for race–ethnicity, gender, age, and serum cholesterol level, serum GGT levels across most deciles were inversely associated with serum concentrations of α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, and vitamin C (

Discussion

In this sample of the U.S. population, we documented that serum carotenoids and vitamin C concentrations are strongly and inversely associated with serum GGT levels within its normal range, but serum vitamin E concentration was not associated with serum GGT levels. These inverse associations were consistently demonstrated in most subgroups. Our parallel study in the CARDIA subjects also reported inverse associations of serum concentrations of some carotenoids and α-tocopherol with serum GGT

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