Amino acids and derivatives. Hepatoprotective agent
ATC code: A16AA02 (Ademetionine)
Brand names
Transmetil, Donamet
S-adenosyl-L-methionine (SAMe) is a natural cofactor in methylation reactions and a methyl donor. In the liver it participates in phosphatidylcholine, glutathione, and polyamine synthesis. The manufacturer claims hepatoprotective, choleretic, antidepressant, and neuroprotective effects. International liver guidelines (, ) do not list ademetionine as an agent with established efficacy. For depression, 2010 rated it as a level C option, with no major confirmatory RCTs since.
Second line
For intrahepatic cholestasis of pregnancy, first-line therapy remains ursodeoxycholic acid. Recommended by 2022 and SMFM 2021. Ademetionine is mentioned in these documents as second-line therapy with limited data. Meta-analyses show improvement in biochemical markers (bilirubin, bile acids) but not in maternal or perinatal outcomes.
Used in hospital intravenously when ursodeoxycholic acid is ineffective or not tolerated.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
A 2017 Cochrane review of S-adenosyl-L-methionine in alcoholic liver disease concluded that evidence is insufficient to recommend it. 2018 and 2019 alcoholic liver disease guidelines are built on complete alcohol cessation and, in severe alcoholic hepatitis, corticosteroids (prednisolone) per Maddrey score. Ademetionine is not recommended in these documents.
Not recommended
SAMe has been studied as an adjunct in major depressive disorder in small RCTs. 2010 listed it as a level C option. Recent meta-analyses (2020) did not confirm clinically meaningful superiority over placebo in large, well-designed trials. NG222 does not include the drug.
Not recommended
— Liver 'detox' and cleansing: The idea of 'liver cleansing with Heptral' is actively promoted in retail. 'Cleansing' is not a clinical state – the liver performs its own detoxification and does not accumulate 'toxins'. Evidence-based ways to help the liver are removing the cause of damage (alcohol, hepatotoxic drugs, obesity, viral hepatitis), not 'detoxing' with drugs.
Not recommended
Heptral is often taken 'after drinking' – this practice is not internationally supported. Hangover is treated with hydration, sleep, and food. SAMe preparations in acute alcoholic hepatitis are not recommended by 2018 and 2019 – management is complete alcohol cessation and corticosteroids in severe disease.
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Contraindicated in the first and second trimesters. In the third trimester, used as a second-line option for intrahepatic cholestasis of pregnancy.
Data on breast milk penetration are limited. Not recommended without clear indications.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Ademetionine is evaluated for the following indications with varying evidence strength: Alcoholic liver disease (evidence tier D), Major depressive disorder (evidence tier D), Intrahepatic cholestasis of pregnancy (evidence tier D). See the full indication matrix with dosing and citations above on this page.
Common side effects of Ademetionine (≥ 1 in 100): Dyspepsia, Headache, dizziness, Insomnia with evening dosing, Allergic reactions. See the Safety section for uncommon and serious reactions.
FDA category C. Contraindicated in the first and second trimesters. In the third trimester, used as a second-line option for intrahepatic cholestasis of pregnancy.
Data on breast milk penetration are limited. Not recommended without clear indications.
Ademetionine is contraindicated in: Hypersensitivity to any component; Genetic disorders of the methionine cycle (homocystinuria, cystathioninuria); First and second trimesters of pregnancy; Age under 18 years. Full list in the Safety section.
'liver protection' is a marketing category. If a drug is hepatotoxic, it is discontinued. If a patient drinks alcohol, only cessation works. The idea 'keep harming the liver and Heptral compensates' has no scientific basis.