What I am working with: triglycerides · semaglutide.
I would like the mechanism, because I want to be able to reason about the cases nobody has written about.
I have tried to reason it out from first principles and got to two contradictory conclusions.
What is actually going on here, physically?
Mechanically, reference intervals for alanine aminotransferase differ between laboratories and have been revised downward over time, so the same value can be normal on one report and elevated on another.
Alanine aminotransferase is relatively liver-specific; aspartate aminotransferase is also present in muscle, heart and red cells. A raised AST with a normal ALT after heavy resistance training is usually muscle, and creatine kinase settles the question.
Stated carefully, weight loss of ten per cent or more typically reduces transaminases substantially in people whose elevation was driven by hepatic fat, which is the majority of mild elevations in this population.
Hy's law and its variants are the standard framework for identifying drug-induced liver injury in trials and are why bilirubin is measured alongside transaminases rather than instead.
Attributing an enzyme change to a compound requires a baseline, and most people asking have not got one.
Isolated mild elevation is common and usually improves with weight loss.
Analytical standards and reagents with traceable certificates. Every quantitative result you read inherits the accuracy of the standard behind it.
Shop standardsAnswering this needs the magnitude in multiples of the upper reference limit, because the thresholds that matter clinically are defined that way and not in absolute units.
Very rapid weight loss can transiently worsen liver biochemistry, which is one of several arguments against pursuing the steepest possible trajectory.
Reference upper limits around forty units per litre for ALT are conventional rather than physiological; several groups have argued for limits closer to thirty for men and twenty-five for women.
Transaminases plus bilirubin plus alkaline phosphatase, or you have not measured enough to conclude anything.
edited 28 Mar 2026 by nils_karlberg — reworded for clarity after a comment
Answer first: mild transaminase elevation is common in this population before any drug is involved, and the usual cause is hepatic steatosis rather than anything acute.
Hy's law describes the combination that matters: transaminases above three times the upper limit together with bilirubin above twice the upper limit and no cholestatic explanation. That combination is a signal; isolated mild transaminase elevation is not.
Stated carefully, creatine kinase, alkaline phosphatase and bilirubin together tell you which compartment the abnormality is in, and ordering the transaminases alone throws that information away.
Laboratory-specific reference intervals for transaminases vary enough that cross-laboratory comparison of borderline values is unreliable.
Nothing here is medical advice. An abnormal result needs somebody who can take a history and examine you.
New training, alcohol and over-the-counter products first. Then the interesting hypotheses.
Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.