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Ademetionine

Amino acids and derivatives. Hepatoprotective agent

ATC code: A16AA02

Brand names – drugs: Transmetil, Donamet

Brand names – supplements: Nature Made SAM-e Complete, Doctor's Best SAM-eSupplements are not tested in clinical trials and are not registered as medications.

Updated · Methodology

Indications

C

Intrahepatic cholestasis of pregnancy

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.

Sources

  1. Cochrane Database Syst Rev: Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. (2020)
  2. Hepat Mon: Ursodeoxycholic Acid and S-adenosylmethionine for the Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-analysis. (2016)
  3. Am J Obstet Gynecol: Society for Maternal-Fetal Medicine Consult Series #53: Intrahepatic cholestasis of pregnancy: Replaces Consult #13, April 2011. (2021)
  4. BJOG: An International Journal of Obstetrics & Gynaecology: Intrahepatic cholestasis of pregnancy (2022)
  5. J Hepatol: EASL Clinical Practice Guidelines on the management of liver diseases in pregnancy (2023)

ICD-10: O26.6 · ICD-11: JA65.0

C

Knee osteoarthritis

Adjunct

Soeken 2002 meta-analysis (J Fam Pract) included 11 SAMe vs NSAID and placebo RCTs in knee and hip osteoarthritis: SAMe 1200 mg/day was as effective as NSAIDs (ibuprofen, naproxen, piroxicam) on pain and function scales with better gastrointestinal tolerability. AAOS 2021 does not include SAMe among the supplements it assesses; the Cochrane review 2009 (Rutjes) called the SAMe data inconclusive because of small low-quality RCTs and called for large trials. ESCEO 2019 for knee osteoarthritis lists prescription glucosamine sulfate and chondroitin sulfate, paracetamol, topical NSAIDs, then systemic NSAIDs at the lowest effective course and intra-articular hyaluronic acid. If SAMe was recommended as a substitute for NSAIDs or for severe osteoarthritis with arthroplasty indication, consider seeking a second opinion from an orthopaedic surgeon.

Sources

  1. J Fam Pract: Safety and efficacy of S-adenosylmethionine for osteoarthritis: meta-analysis (2002)
  2. AAOS: Management of osteoarthritis of the knee (non-arthroplasty) – evidence-based clinical practice guideline (2021)
  3. Cochrane Database Syst Rev: S-Adenosylmethionine for osteoarthritis of the knee or hip (2009)
  4. Semin Arthritis Rheum: An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) (2019)

ICD-10: M17 · ICD-11: FA01

C

Major depressive disorder

Adjunct

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.

Sources

  1. Cochrane Database of Systematic Reviews: S-adenosyl methionine (SAMe) for depression in adults (2016)
  2. General Hospital Psychiatry: S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis (2024)
  3. The Canadian Journal of Psychiatry: Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder (2016)
  4. Annals of General Psychiatry: S-Adenosylmethionine (SAMe) in major depressive disorder (MDD): a clinician-oriented systematic review (2020)
  5. GuiaSalud: Guía de Práctica Clínica sobre el Manejo de la Depresión en el Adulto (revisada mayo 2023) (2014)
  6. Am J Psychiatry: S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial (2010)
  7. NICE: Depression in adults: treatment and management (NG222) (2022)

ICD-10: F32.9 · ICD-11: 6A70.Z

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

D

Alcoholic liver disease

Not recommended

A 2006 Cochrane review of S-adenosyl-L-methionine in alcoholic liver disease concluded that evidence is insufficient to recommend it; the 2015 update was withdrawn. 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.

Sources

  1. Cochrane Database of Systematic Reviews: S-adenosyl-L-methionine for alcoholic liver diseases (2006)
  2. J Hepatol: EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. (2018)
  3. Hepatology: Diagnosis and Treatment of Alcohol-Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases (2020)

ICD-10: K70 · ICD-11: DB94

D

Hangover recovery

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.

Sources

  1. J Hepatol: EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. (2018)
  2. Hepatology: Diagnosis and Treatment of Alcohol‐Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases (2020)
  3. Addiction: The efficacy and tolerability of pharmacologically active interventions for alcohol-induced hangover symptomatology: a systematic review of the evidence from randomised placebo-controlled trials. (2022)

ICD-11: MG49

D

Non-alcoholic fatty liver disease

Not recommended

SAMe is heavily marketed at retail as a liver remedy. For non-alcoholic fatty liver disease (NAFLD/MASLD) and steatohepatitis there is no evidence base with histological steatohepatitis resolution or fibrosis endpoints. --EASO 2024 list 7–10 % weight loss via Mediterranean diet and physical activity first-line for MASLD; with concomitant T2DM – SGLT2i and GLP-1 RA; for confirmed steatohepatitis – resmetirom (Rezdiffra, 2024). SAMe is not in MASLD guidelines. The interventions with proven benefit in this condition are weight loss and correction of cardiometabolic risk factors, so SAMe should not replace them.

Sources

  1. J Hepatol: EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) (2024)

ICD-10: K76.0 · ICD-11: DB92

F

Anti-aging and longevity

Not recommended

SAMe in the biohacking segment is sold as an «epigenetic reverser» promising slower aging via DNA methylation support. No evidence base: no human RCTs with aging biomarker endpoints (telomeres, Horvath epigenetic clocks), all-cause or cardiovascular mortality. 2010 approved no «anti-aging» claim for SAMe. Proven mortality reduction paths are BP, glycaemic and lipid control, smoking cessation, Mediterranean diet and physical activity. If SAMe was recommended as a «longevity supplement» without diagnosed depression or cholestasis, consider seeking a second opinion.

Sources

  1. EFSA: Scientific Opinion on the substantiation of health claims related to various foods/food constituents – no anti-aging claim approved (2010)
  2. BMJ Case Rep: Possible SAMe-induced mania (2018)
  3. Prim Care Companion J Clin Psychiatry: A Case Report of a Manic Episode Triggered by S-Adenosylmethionine (SAMe) (2002)
F

Body detoxification and cleansing

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.

Sources

  1. J Hum Nutr Diet (Klein and Kiat): Detox diets for toxin elimination and weight management: a critical review of the evidence (2015)
  2. Am J Gastroenterol: Liver Cleansing Imposters: An Analysis of Popular Online Liver Supplements. (2026)
  3. J Emerg Med: Acute Liver Injury After Long-Term Herbal "Liver Cleansing" and "Sleep Aid" Supplement Use. (2021)
  4. BMJ Case Rep: Possible SAMe-induced mania (2018)
How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

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.

Safety

Contraindications

  • Hypersensitivity to any component
  • Genetic disorders of the methionine cycle (homocystinuria, cystathioninuria)
  • First and second trimesters of pregnancy
  • Age under 18 years

Serious adverse effects

  • Hypomanic episodes in patients with bipolar disorder
  • Anaphylactoid reactions with intravenous administration (rare)

Common adverse effects

  • Dyspepsia
  • Headache, dizziness
  • Insomnia with evening dosing
  • Allergic reactions

Pregnancy: can you take Ademetionine?

Contraindicated in the first and second trimesters. In the third trimester, used as a second-line option for intrahepatic cholestasis of pregnancy.

Breastfeeding: can you take Ademetionine?

Data on breast milk penetration are limited. Not recommended without clear indications.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Russian practice note

Heptral is among the top-selling hepatoprotectors in Russia. A treatment course costs tens of thousands of roubles. The drug is massively prescribed for any transaminase elevation, hepatic steatosis, or 'toxic liver damage'. In international gastroenterology, first-line therapy for most of these conditions is lifestyle modification (alcohol cessation, weight loss, diabetes control), not pharmacotherapy with hepatoprotectors.

Common myths

Myth: 'Heptral protects the liver when taking drugs and alcohol'. Fact: '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.

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Frequently asked

What is Ademetionine used for?

Ademetionine is evaluated for the following indications with varying evidence strength: Intrahepatic cholestasis of pregnancy (evidence tier C), Knee osteoarthritis (evidence tier C), Major depressive disorder (evidence tier C). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Ademetionine?

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.

Is Ademetionine safe during pregnancy?

Contraindicated in the first and second trimesters. In the third trimester, used as a second-line option for intrahepatic cholestasis of pregnancy.

Is Ademetionine compatible with breastfeeding?

Data on breast milk penetration are limited. Not recommended without clear indications.

Can you drink alcohol while taking Ademetionine?

In international gastroenterology, first-line therapy for most of these conditions is lifestyle modification (alcohol cessation, weight loss, diabetes control), not pharmacotherapy with hepatoprotectors. Myth: 'Heptral protects the liver when taking drugs and alcohol'.

Who should not take Ademetionine?

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.

Heptral protects the liver when taking drugs and alcohol

'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.

Official sources

Direct links to regulator labels. Open in a new tab.

  • GRLSLabel dated 02/24/2026

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