How to prepare for the «GGT» test: rules for taking it

Gamma-glutamyl transferase (GGT) is an enzyme that doctors use to assess the state of the biliary tract and liver, and also as a laboratory marker of regular alcohol consumption. Unlike the transaminases, GGT hardly reacts to training, but it is very sensitive to alcohol, certain medications and body weight. And most importantly — it changes slowly: the consequences of a «festive weekend» can show up in the test for weeks. Our editorial team explains how to prepare for a GGT test and what to consider when reading the result.

What GGT is and why it is measured

GGT is located on the membranes of the cells of many organs — the kidneys, pancreas, intestine — but it enters the blood predominantly from the liver and biliary tract. The enzyme participates in the metabolism of glutathione, one of the main intracellular antioxidants.

Most often GGT is ordered together with alkaline phosphatase in order to determine the source of its rise: if both enzymes rise, a problem with bile outflow is likely; if only alkaline phosphatase — the cause may be in the bones. GGT is also part of the standard «liver profile» together with ALT, AST and bilirubin.

For athletes GGT has another valuable property: it is practically absent from skeletal muscle. Therefore, when AST and ALT jump after a hard workout, a normal GGT hints to the doctor that the source of the enzymes is muscle, not the liver.

A large review by Whitfield (2001) showed that GGT is not only a liver marker: its level is associated with obesity, insulin resistance, oxidative stress and cardiovascular risk. That is why the interpretation of the result always takes the person's overall condition into account.

Alcohol: why preparation takes weeks

Regular alcohol consumption stimulates the synthesis of GGT in the liver — this phenomenon is called enzyme induction. Because of this, GGT has long been used as a laboratory marker of prolonged excessive alcohol consumption, although its sensitivity and specificity for this purpose are not ideal.

After giving up alcohol, induced GGT declines gradually, over several weeks. Therefore abstaining from alcohol for one evening before the test is not enough if a person consumes it regularly. To assess the real state of the liver, doctors often advise repeating the GGT after a few weeks of sobriety.

On the other hand, a single moderate alcohol intake in a healthy person who usually does not drink does not substantially raise GGT. But for the purity of the result the standard recommendation is no alcohol for at least 24–72 hours before the test, and with regular consumption — a talk with the doctor about a longer pause.

It is important to be honest with the doctor about the amount of alcohol. A normal GGT does not rule out problematic consumption, and an elevated one does not prove it: in some people who drink a lot the enzyme remains normal, while in people with obesity it is elevated without alcohol.

Medications that «rev up» the enzyme

Besides alcohol, the synthesis of GGT is stimulated by drugs that induce liver enzymes. Classic examples are the antiepileptic agents phenytoin, carbamazepine and phenobarbital. In people who take them, GGT is often elevated without liver injury.

Prescribed drugs are not discontinued on your own for the sake of a test. It is enough for the doctor to know that the patient is taking them, and he will take this effect into account. Discontinuing anticonvulsants on your own is dangerous.

Drugs and substances with a cholestatic effect raise GGT by disrupting bile outflow. These include, in particular, oral 17-alpha-alkylated anabolic steroids, for which cholestasis is a known side effect (Pope et al., 2014). Concealing their use from the doctor means risking a wrong diagnosis and missing a serious injury.

Also report dietary supplements, especially herbal formulas, «detox» agents and fat burners. Some of them have been described as a cause of drug-induced liver injury accompanied by changes in enzymes, including GGT.

Lifestyle: weight, smoking, coffee, training

GGT is closely linked to body weight: in people with abdominal obesity and non-alcoholic fatty liver disease it is often moderately elevated. Weight loss and improved insulin sensitivity are usually accompanied by a decrease in GGT, but this process takes months, not days.

In smokers GGT is on average higher than in non-smokers. Giving up a cigarette on the day of the test will not remove the chronic effect, but smoking right before the blood draw is still inadvisable.

An interesting fact: in epidemiological studies regular coffee consumption is associated with lower GGT levels. However, this is an observational association, and there is no point in drinking more coffee «for the test». In the morning before the draw it is better to make do with water.

• a usual diet without fatty dishes the evening before;
• no alcohol for at least 24–72 hours, and with regular consumption — longer;
• no smoking before the blood draw;
• training does not substantially affect GGT, but if the same test includes ALT and AST, it is better to take a pause of 2–3 days.

Rules for the draw and interpretation

GGT is drawn in the morning on an empty stomach, after 8–12 hours without food. Food intake is not the main factor for this enzyme, but lipemic serum after a fatty breakfast interferes with measurement, and the liver profile includes indicators that depend on food.

The reference intervals for GGT are higher in men than in women and differ between laboratories. The ACG guideline (Kwo et al., 2017) recommends not treating an isolated rise in GGT without other changes in liver panels as a diagnosis in itself, but rather looking for the cause with regard to alcohol, medications and body weight.

An isolated moderate rise in GGT with normal ALT, AST, bilirubin and alkaline phosphatase is most often explained by alcohol, inducer drugs or obesity. A combination of GGT and alkaline phosphatase points to cholestasis, and then the doctor orders an ultrasound of the biliary tract.

To monitor trends — for example, after quitting alcohol or during weight loss — repeat the test at one laboratory and with a sufficient interval so that the enzyme has time to change. Several tests a few days apart are of little information.

Editorial conclusions

GGT is a slow marker. It reflects habits over the last few weeks, not the last evening, so the main preparation is an honest assessment of how much alcohol you consume and informing the doctor about medications and supplements.

For athletes GGT is useful as a «filter»: a normal level with elevated AST and ALT after a workout points to a muscular rather than a hepatic source of the enzymes.

An elevated GGT is not treated on its own — the doctor determines its cause. Taking «liver» supplements on your own does not replace an evaluation.

We also recommend reading our articles on preparing for the ALT and AST and bilirubin tests, as well as the material on the effect of oral steroids on the liver.

References

1. Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38(4):263–355.
2. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18–35.
3. Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67(1):6–19.
4. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005;172(3):367–379.
5. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
6. Rifai N, Horvath AR, Wittwer CT (eds). Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. St. Louis: Elsevier; 2018.