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In the remainder of this paper, we will first present in Section 2 evidence linking elevations in GGT levels to cardiovascular disease risks, heart failure, cancer, and all-cause mortalities. We suggest simple, primarily dietary lifestyle changes and targeted therapies that could lower GGT levels and improve health status across the population. We hypothesize that GGT is a marker for glutathione depletion in the liver and that elevations in GGT reflect increased exposure to organic xenobiotics that are metabolized in the liver through glutathionylation. We believe this is indicative of both increased disease risk over time at the population level and evidence of changing environmental factors, such as excessive iron intake and increased exposure to xenobiotics, and nutritionally related impairment of cell membranes that may be playing a role. Not only do we demonstrate strong potential for GGT to predict later disease risk, but we also show variations in GGT levels among different population groups (gender, ethnic, and regional) and show evidence of temporal upward trends in population level GGT values, particularly in Korea and the United States. In this paper, we review an extensive research literature on GGT as a marker for disease. to even include GGT as a marker for oxidative stress in periodontal disease.
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Other investigators have added many newly identified GGT-related diseases and conditions to a rapidly growing list that very recently was modified by Sreeram et al. This combination of factors is observed with increasing frequency in many chronic diseases. Increased levels of prooxidation can lead to downstream cell, tissue, and DNA damage caused by oxidative and nitrosative stress and the generation of deleterious reactive oxygen species or nitric oxide (ROS or NO). When GGT levels are elevated, damage to red blood cell membranes can occur causing the release of these potentially toxic transition metals, which can further result in chain, prooxidant reactions. However, elevated GGT levels, as noted by Whitfield and others, contribute to prooxidant activity, particularly in the presence of iron or copper. Although gamma-glutamyl compounds include antioxidants, inflammatory molecules, drug metabolites, and neuroreactive compounds, the major function of GGT is enabling metabolism of glutathione and glutathionylated xenobiotics. However, Whitfield had already extended that description to include elevated GGT in association with risk of coronary heart disease, type-II diabetes (T2D), and stroke. Some generalized or summary medical and scientific literature still describe GGT in those terms. We review literature both from the medical sciences and from life insurance industries demonstrating that serum GGT is a superior marker for future disease risk, when compared against multiple other known mortality risk factors.Ī comprehensive review by Whitfield in 2001 described GGT in its traditional role as a marker of liver dysfunction, bile duct conditions, and alcohol consumption. GGT is an early predictive marker for atherosclerosis, heart failure, arterial stiffness and plaque, gestational diabetes, and various liver diseases, including viral hepatitis, other infectious diseases, and several life-threatening cancers. Since the late 1970s, both GGT and incident MetS and its related disorders have risen in virtual lockstep. We observe a general upward trend in population levels of GGT over time, particularly in the US and Korea. Here, we examine the relationship of GGT to other serum markers such as serum ferritin (SF) levels, and we suggest a link to exposure to environmental and endogenous toxins, resulting in oxidative and nitrosative stress. The literature from multiple population groups worldwide consistently shows strong predictive power for GGT, even across different gender and ethnic categories. However, GGT's predictive utility applies well beyond liver disease: elevated GGT is linked to increased risk to a multitude of diseases and conditions, including cardiovascular disease, diabetes, metabolic syndrome (MetS), and all-cause mortality. Gamma-glutamyltransferase (GGT) is a well-established serum marker for alcohol-related liver disease.