How to prepare for the «ALT and AST» test: rules for taking it

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the enzymes most often used to assess the state of the liver. They are ordered when taking medications, when fatty liver disease or hepatitis is suspected, and also for people who monitor their health during sports. However, transaminases are found not only in the liver: there is a lot of AST in muscles and red blood cells, and even ALT rises noticeably after strength training. Our editorial team examines how to prepare so that «liver panels» really speak about the liver.

What ALT and AST are and where they come from in the blood

Both enzymes participate in amino acid metabolism inside cells. In the blood there is normally little of them: they enter it when cells are damaged or when the permeability of their membranes increases. Therefore a rise in transaminases is a sign of «cell damage», but not necessarily of liver cells.

ALT is predominantly concentrated in the liver, so it is considered a relatively specific liver marker. AST, apart from the liver, is present in large amounts in skeletal muscle, the heart muscle, the kidneys and red blood cells. That is, a rise in AST without ALT often points to an extrahepatic source.

The clinical guideline of the American College of Gastroenterology (Kwo et al., 2017) and the British recommendations on abnormal liver panels (Newsome et al., 2018) emphasize: before looking for liver disease, one must make sure that the rise is persistent and is not explained by external causes — in particular physical exertion.

The half-life of AST in the blood is about a day, that of ALT longer, approximately two days. That is precisely why, after muscle damage, ALT can remain elevated for several days, when the person has already forgotten about the hard workout.

Training — the main trap for athletes

A telling example is the study by Pettersson and colleagues (2008). Healthy men who had not previously done strength training performed one intense training session. After this, AST and ALT rose substantially and remained elevated for at least a week, reaching levels that in the clinic could become grounds for a liver evaluation. In parallel, creatine phosphokinase (CPK) — a marker of muscle damage — rose significantly.

The strongest effect comes from unaccustomed exertion with an emphasis on the eccentric phase: the first workout after a break, a new program, downhill sections during running, competitions. In people who train regularly and steadily, the reaction is smaller but does not disappear entirely.

The editorial team's practical rule: do not perform intense strength or prolonged aerobic workouts for at least 48–72 hours before the test, and after unaccustomed or very hard exertion — wait about a week. Light activity — walking, stretching — is acceptable.

If avoiding a workout is impossible, it is useful to ask the doctor to add CPK to the test. A high CPK level together with a predominant rise in AST points to a muscular source of the enzymes and helps avoid an unnecessary search for liver disease.

Alcohol, food, medications and supplements

Alcohol directly harms liver cells. For a scheduled test it is recommended to abstain from alcohol for at least a few days, and better for a week or more, in order to assess the real state of the organ rather than the consequences of a party.

Blood for ALT and AST is drawn in the morning on an empty stomach, after 8–12 hours without food. Food intake in itself has little effect on transaminases, but fatty food makes the serum cloudy (lipemic), which can interfere with measurement, and the «liver profile» often includes other indicators sensitive to food.

Many medications can raise transaminases. Among the best known are paracetamol in high doses, statins, some antibiotics and antifungal agents. Prescribed drugs should not be discontinued on your own before the test: the doctor needs to see the result against the background of the usual treatment, but must know the full list.

Dietary supplements deserve separate mention. Liver injury has been described for concentrated green tea extracts, some herbal formulas and «fat burners». Oral 17-alpha-alkylated anabolic steroids are known for hepatotoxicity and can cause cholestasis. The intake of such substances should be reported to the doctor, even if it seems awkward.

Technical factors: hemolysis and the blood draw

Red blood cells contain a lot of AST. If part of the red blood cells is destroyed during the draw or transport (hemolysis), AST in the serum rises artificially. The causes are a thin needle, too strong a vacuum during the draw, vigorous shaking of the tube, prolonged storage of whole blood.

Modern laboratories assess the degree of hemolysis automatically and can flag the result as unreliable. If there is a note about hemolysis on the form, the test should be redone rather than an attempt made to interpret it.

• give blood in a calm state, after 10–15 minutes of rest;
• do not clench the fist repeatedly during the draw;
• choose a laboratory where the sample is centrifuged and analyzed quickly;
• perform repeat tests at the same laboratory.

Intramuscular injections can also slightly raise AST and CPK because of local damage to muscle tissue. If an injection was given the day before, this is worth telling the doctor.

How to read the result

The reference intervals for ALT and AST differ between laboratories and depend on sex. A small isolated rise (up to two or three upper limits of normal) in a person without complaints is most often first verified by a repeat test under standard conditions, as advised by the ACG and British society of gastroenterology guidelines.

The AST/ALT ratio provides a hint about the cause. A predominance of ALT is more characteristic of non-alcoholic fatty liver disease and viral hepatitis, a predominance of AST — of alcoholic injury or a muscular source (Giannini et al., 2005). But this is only a guide, not a diagnosis.

To distinguish a hepatic cause from a muscular one, CPK and gamma-glutamyl transferase (GGT) help: GGT is practically absent from muscle, so with a «muscular» rise in transaminases it remains normal.

If the rise persists on a repeat test after a pause in training and abstinence from alcohol, the doctor orders further evaluation: liver ultrasound, viral hepatitis markers, iron metabolism indicators and other tests.

Editorial conclusions

ALT and AST are useful but nonspecific markers. For people who train, the most common cause of «bad liver panels» is not the liver but the muscles after a hard workout.

The most important rules of preparation: a pause in intense training of 2–3 days (after unaccustomed exertion — up to a week), abstinence from alcohol, giving blood on an empty stomach and a full list of medications and supplements for the doctor.

With a doubtful result, it is sensible to repeat the test and add CPK and GGT, rather than immediately starting «hepatoprotectors» or other agents on your own.

We also recommend reviewing our materials on preparing for the GGT and bilirubin tests, as well as on monitoring the liver when taking sports supplements.

References

1. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18–35.
2. Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67(1):6–19.
3. Pettersson J, Hindorf U, Persson P, et al. Muscular exercise can cause highly pathological liver function tests in healthy men. Br J Clin Pharmacol. 2008;65(2):253–259.
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. Simundic AM, Bölenius K, Cadamuro J, et al. Joint EFLM-COLABIOCLI recommendation for venous blood sampling. Clin Chem Lab Med. 2018;56(12):2015–2038.