S-Adenosyl-Methionine (SAMe)
Ademetionine
Also known as: Zentonil · Denamarin · Donamet · Gumbaral · Isimet · MoodLift · S Amet · Samyr · Transmetil · Tunik · Samylin · Hepatosyl · S-adenosyl-L-methionine · Sadenosylmethionine · SAM-e · Sammy · methioninyl adenylate · SAMe · AdoMet · S-adenosylmethionine
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| General dosing / Liver support | 18 mg/kg (or based on weight: <5.5 kg: 90 mg; 5.5-11 kg: 180-225 mg; 11-16 kg: 225 mg; 16-29.5 kg: 450 mg; 29.5-41 kg: 675 mg; >41 kg: 900 mg) | PO | q24h (may divide q12h if giving >1 tablet) | — | 🌎 NA |
| Liver Disease (necro-inflammatory/cholestatic, vacuolar hepatopathy) | 20 mg/kg | PO | q24h | — | 🌎 NA |
| Liver disease, cognitive dysfunction, adjunctive therapy | At least 100 mg for every 10 kg or 20 mg/kg | PO | q24h | Long-term as needed | 🌍 EU |
- General dosing / Liver support: Give on an empty stomach, at least one hour before feeding.
- Liver Disease (necro-inflammatory/cholestatic, vacuolar hepatopathy): Give on an empty stomach; use a proven bioavailable product.
- Liver disease, cognitive dysfunction, adjunctive therapy: Administer on an empty stomach at least 1 hour before food. Tablets should be given whole.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| General dosing / Liver support | 18 mg/kg (or based on weight: <5.5 kg: 90 mg; 5.5-11 kg: 180-225 mg) | PO | q24h | — | 🌎 NA |
| Liver Disease (necro-inflammatory/cholestatic, feline hepatic lipidosis) | 20 mg/kg | PO | q24h | — | 🌎 NA |
| Liver disease, cognitive dysfunction, improve bile flow | 100 mg/cat or 20 mg/kg | PO | q24h | Long-term as needed | 🌍 EU |
- General dosing / Liver support: Give on an empty stomach, at least one hour before feeding.
- Liver Disease (necro-inflammatory/cholestatic, feline hepatic lipidosis): Give on an empty stomach; use a proven bioavailable product.
- Liver disease, cognitive dysfunction, improve bile flow: Administer on an empty stomach at least 1 hour before food. Tablets should be given whole.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
S-Adenosyl-Methionine (SAMe) is a naturally occurring endogenous molecule and a highly utilized veterinary nutraceutical, primarily serving as a hepatoprotectant.
Key clinical applications include:
- Liver Disease: Used as an adjunctive treatment for chronic hepatitis, hepatic lipidosis, cholangiohepatitis, and feline triad disease.
- Toxicity Management: Crucial in the treatment of acute hepatotoxin-induced liver injury, such as acetaminophen or xylitol toxicity, by replenishing depleted glutathione stores.
- Additional Uses: May benefit patients with osteoarthritis, age-related cognitive dysfunction (canine cognitive dysfunction syndrome), and those on long-term hepatotoxic medications (e.g., phenobarbital, lomustine).
Clinical Pearl: Because SAMe is highly reactive and unstable, commercial formulations use various salt forms (e.g., tosylate, butanedisulfonate) to improve stability. Bioavailability varies significantly between products, so choosing a reputable, veterinary-specific brand is highly recommended.
Mechanism of action
SAMe is synthesized from the amino acid methionine and ATP via the enzyme SAMe synthetase. In liver compromise, this enzyme's activity is a rate-limiting step, leading to systemic SAMe deficiency. Exogenous SAMe bypasses this block and participates in three major biochemical pathways:
- Transsulfuration → Generates sulfur-containing compounds → Precursor to Glutathione (GSH). Glutathione is the liver's master antioxidant, essential for ROS scavenging and cellular detoxification. Exogenous SAMe prevents GSH depletion.
- Transmethylation → Serves as a methyl donor → Essential for phospholipid synthesis (e.g., phosphatidylcholine) → Maintains cell membrane structure, fluidity, and function.
- Aminopropylation → Donates aminopropyl groups → Source of polyamines → Promotes anti-inflammatory effects, protein/DNA synthesis, and hepatocyte replication/regeneration.
Additionally, SAMe inhibits hepatocyte apoptosis secondary to alcohol or bile acid accumulation.
Safety & warnings
Contraindications
- Use with caution in pregnant animals (safety not definitively proven)
- No absolute contraindications documented
- Use with caution during pregnancy (safety not established)
Adverse effects
- Immediate post-dose vomiting
- Anorexia
- Nausea (reported in humans)
- Diarrhea (reported in humans)
- Flatulence (reported in humans)
- Diarrhoea
- Paradoxical anxiety
- Dry mouth (reported in humans)
- Headache (reported in humans)
- Sweating (reported in humans)
- Dizziness (reported in humans)
Precautions
There are no apparent absolute contraindications to the use of SAMe.
Pregnancy/Nursing: The safety of exogenous SAMe has not been definitively proven in pregnancy; use with caution. However, limited studies in laboratory animals and pregnant women with liver disease have not demonstrated ill effects. It is unknown if SAMe enters maternal milk.
Drug interactions
Theoretical risk of additive serotonergic effects (serotonin syndrome)
Theoretical risk of additive serotonergic effects
Theoretical risk of additive serotonergic effects
Theoretical risk of additive serotonergic effects
Theoretical risk of additive serotonergic effects
Theoretical risk of additive serotonergic effects
Theoretical risk of additive serotonergic effects
Additive serotonergic effects; potential for serotonin syndrome
Additive serotonergic effects; potential for serotonin syndrome
Additive serotonergic effects; potential for serotonin syndrome
Additive serotonergic effects; potential for serotonin syndrome
SAMe may increase the clearance of drugs undergoing hepatic glucuronidation
SAMe may increase the clearance of drugs undergoing hepatic glucuronidation
SAMe may increase the clearance of drugs undergoing hepatic glucuronidation
Monitoring
- Clinical signs (appetite, activity, attitude)
- Liver enzymes (ALT, AST, ALP, GGT)
- Liver biopsies (if indicated)
- Hepatic and erythrocyte glutathione levels (Note: may require 1-4 months before changes in lab values are noted)
- Liver enzyme panel (ALT, AST, ALP, GGT)
- Total bilirubin and bile acids
- Clinical signs of cognitive improvement or behavioral changes
- Signs of serotonin syndrome (agitation, tremors, hyperthermia) if used concurrently with serotonergic drugs
Pharmacokinetics
Half-life
Absorption
Oral bioavailability is highly dependent on the stabilizing salt (tosylate ~1%, 1,4-butanedisulfonate ~5%). The presence of food in the gut substantially reduces absorption. Peak levels occur 1-6 hours post-dosing with enteric-coated tablets. Chewable formulations yield similar AUC but faster peak levels.
Distribution
Enters portal circulation after absorption.
Metabolism
Primarily metabolized in the liver.
Elimination
In humans, 17% of a radiolabeled dose is recovered in urine within 48 hours; 27% in feces.
Overdose
SAMe appears to be quite safe. The LD50 in rodents exceeds 4.65 grams/kg. Toxicity studies in dogs and cats at usual prescribed dosages demonstrated no deleterious effects.
In the event of a massive overdose, mild gastrointestinal effects (nausea, vomiting, diarrhea) may be observed, but it is highly unlikely to require specific medical treatment beyond supportive care.
Available products
Formulations
- Enteric-coated tablets
- Chewable tablets
- Oral tablets: 90 mg, 100 mg, 200 mg, 225 mg, 400 mg, 425 mg
- Oral capsules: 50 mg, 100 mg, 200 mg
- Oral powder: 75 mg, 150 mg, 300 mg, 400 mg
- Nutraceutical mixtures (often combined with silybin/milk thistle)
Veterinary
- Denosyl (Nutramax): 90 mg, 225 mg, & 425 mg enteric-coated tablets; 225 mg chewable tablets
- Zentonil (Vetoquinol): 100 mg, 200 mg, and 400 mg tablets
- Denamarin (Nutramax): Combination product containing SAMe and silybin (silymarin)
- Denamarin (SAMe + Silybin)
- Zentonil Advanced
- Samylin
- Hepatosyl
Human-labeled
- Various over-the-counter nutritional supplements (tablets/capsules of varying concentrations)
- Various OTC SAMe dietary supplements (tablets and capsules)
Regulatory status
Classified as GSL (General Sale List) / nutraceutical.
Classified as GSL (General Sale List) / nutraceutical.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature. Avoid conditions of high temperature or humidity. SAMe is inherently unstable in acidic or aqueous environments; store in tightly sealed, moisture-resistant containers (keep in original blister packs until use).
Client information
Giving SAMe to Your Pet
- Timing is Everything: Administer the tablets on an empty stomach, preferably at least one hour before feeding. Food drastically decreases how much of the supplement your pet's body can absorb.
- Do Not Crush or Split: Unless you are specifically using a chewable formulation, do not crush, split, or break the enteric-coated tablets. The special coating protects the active ingredient from stomach acid so it can be absorbed in the intestines.
- Storage: Keep the tablets in their original blister packaging until right before you give them. SAMe is very sensitive to moisture and air and will degrade quickly if left out.
- Patience: It may take several weeks to months to see improvements in your pet's liver bloodwork, though you may notice improvements in their energy and appetite sooner.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.