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Gamma Glutamyl transferase (GGT) & antioxidant health

Gamma Glutamyltransferase or GGT is a liver enzyme that has traditionally been measured to detect liver health and function and alcohol consumption. GGT is a very sensitive measure than can change very quickly compared to other biochemical markers. In recent years, elevated GGT measurements have proved to be effective early warning signs of other health risks such as atherosclerosis, stroke, type 2 diabetes, kidney disease and cancer. Large population studies conducted in the US and around the world have identified increased risks of metabolic syndrome, including heart and cardiovascular diseases and diabetes, as well as cancer and all-cause mortality in both men and women. When GGT concentrations exceeded the lowest 25% to 35% of normal population ranges, disease risks grow in proportion to increases in GGT. People faced increased disease risk once GGT rose above the “low-normal” range for their gender. Medical researchers describe this phenomenon as a “dose-response relationship,” essentially, the higher the GGT concentration, the greater the risks of future diseases and premature mortality, even when GGT levels were still well-within "normal" laboratory ranges.

The high end of normal GGT laboratory ranges are generally 50–70 U/L for men and 40–45 U/L for women. Although GGT correlates with other risk factors, most research has demonstrated that elevated GGT, independent of other risk factors, predicts increased disease risk and mortality. Researchers have concluded this by studying large, free-living (i.e.,apparently healthy) populations from which they analyzed data covering multiple known risk factors. Years later they compared health and mortality outcomes data gathered from health, hospital and death records. After stratifying the populations into smaller groups according to similar risk factors like age, sex, body mass index, smoking, cholesterol, alcohol consumption, and diet and exercise, the researchers were able to calculate that elevated GGT, even within normal laboratory ranges, presented significant additional risks, independent of those shared by individuals with similar baseline risk and health profiles.

Scientists generally describe the mechanism behind these findings as follows: The normal biologic role of GGT is to reconstitute glutathione, the body’s master antioxidant. Glutathione (or GSH) provides natural protection against harmful oxidative stress. When GGT concentrations are above “low-normal” ranges, excess GGT can catabolize (degrade) glutathione causing critical depletion of this very important antioxidant. When glutathione is depleted, and only insufficient amounts remain to protect the body’s organs from oxidative stress, damage starts to occur. Over time, this process can lead to a vicious cycle of irreversible cell, tissue and DNA damage, and ultimately to severe impairment of vital organ function and premature death.

 

Fortunately, an inexpensive blood test can determine GGT concentration. GGT levels can be lowered through a balanced diet that includes ample portions of grains, fruits, nuts and vegetables; this bolsters the body’s natural antioxidant defenses. Several studies have shown that blood donation or phlebotomy reduces GGT and other risk markers associated with liver diseases and insulin resistance. Interestingly, moderate to high coffee consumption has been universally shown to reduce GGT. Consequently, fairly high levels of coffee plus these other healthy food choices promote glutathione production and the body's natural antioxidant defense system. On the other hand, excessive alcohol and red meat consumption have been demonstrated to increase GGT, which depletes glutathione and impairs antioxidant protection. Excessive alcohol consumption facilitates both iron absorption and increased GGT, an unhealthy combination for sure.

It might be important for some people to test GGT periodically. An Austrian study of 76,000 people followed over seven years demonstrated that not only were the initial GGT testing levels important, but also, the direction and degree of change over time modified initial risks significantly. Irrespective of the original GGT measurement, although lower initial GGT always indicated less risk than higher, individuals whose GGT concentrations increased over time were subject to heightened disease and mortality risk, while those whose GGT declined faced reduced risks. As in the studies based on one-time GGT measurements, the degree of change over time (up or down) also followed a “dose-response relationship.” An interesting common finding of almost all of the research in this area indicated the strength of these relationships, and therefore the risks, were significantly greater among men and women less than 60 or 65 years of age than they were for older people.

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