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 bile ducts and liver, and also as a laboratory marker of regular alcohol consumption. Unlike the transaminases, GGT hardly reacts to exercise, but it is very sensitive to alcohol, some medications and body weight. And most importantly - it changes slowly: the consequences of a holiday weekend can show up in the test for weeks. The editorial team explains how to prepare for a GGT test and what to take into account 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 mainly from the liver and bile ducts. The enzyme takes part in the metabolism of glutathione, one of the main intracellular antioxidants.

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

For athletes, GGT has one more valuable property: it is practically absent from skeletal muscle. So when AST and ALT jump after a hard workout, a normal GGT tells 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. Therefore the interpretation of the result always takes into account the person's overall condition.

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. So abstaining from alcohol for a single 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 GGT after several weeks of sobriety.

On the other hand, a single moderate alcohol intake in a healthy person who usually does not drink does not significantly raise GGT. But for a clean result, the standard recommendation is no alcohol for at least 24-72 hours before the test, and with regular consumption - a conversation 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 problem drinking, and an elevated one does not prove it: in some people who drink a lot the enzyme remains normal, while in obese people it is elevated without alcohol.

Drugs that rev up the enzyme

Besides alcohol, GGT synthesis 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 damage.

Prescribed drugs are not discontinued on your own for the sake of the test. It is enough for the doctor to know that the patient is taking them, and they will take this effect into account. Discontinuing anticonvulsant drugs 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). To hide their use from the doctor means risking an incorrect diagnosis and missing serious damage.

Also report dietary supplements, especially herbal complexes, detox products 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 decline 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 it is still not worth smoking immediately before the blood draw.

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 sake of the test. In the morning before the draw it is better to make do with water.

• a normal diet without fatty dishes the evening before;
• no alcohol for at least 24-72 hours, longer with regular consumption;
• no smoking before the blood draw;
• training does not significantly affect GGT, but if the same test includes ALT and AST, it is better to take a 2-3 day break.

Rules for taking the test and interpretation

GGT is taken 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 the measurement, and the liver profile includes indicators that depend on food.

Reference intervals for GGT are higher in men than in women, and differ between laboratories. The ACG guideline (Kwo et al., 2017) recommends not assessing an isolated increase in GGT without other changes in liver tests as a diagnosis in its own right, but looking for the cause taking into account alcohol, medications and body weight.

An isolated moderate increase 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 suggests cholestasis, and then the doctor orders an ultrasound of the bile ducts.

To monitor the trend - for example, after giving up alcohol or during weight loss - repeat the test at the same laboratory and with a sufficient interval for the enzyme to have time to change. Several tests a few days apart are of little informative value.

Editorial conclusions

GGT is a slow marker. It reflects habits over the past weeks, not the past evening, so the main preparation is an honest assessment of how much alcohol you consume, and reporting your medications and supplements to the doctor.

For athletes, GGT is useful as a filter: a normal level with elevated AST and ALT after a workout points to a muscle, not a liver, source of the enzymes.

Elevated GGT is not treated on its own - the doctor determines its cause. Taking liver supplements on your own does not replace examination.

We also recommend reading our articles on preparing for ALT and AST tests and bilirubin, 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.