S-Adenosylmethionine (SAMe)

S-adenosylmethionine, or SAMe, is a naturally occurring methyl donor supplied as a nutritional supplement. Its principal veterinary application is adjunctive support in selected liver disorders or oxidative hepatic injury. It is also included in combination hepatoprotective products. Evidence for clinical benefit varies by disorder and is less extensive than its biochemical rationale.

Group

Hepatic nutritional supplement

Mechanism of Action

SAMe participates in methyl-transfer reactions and supplies intermediates for transsulfuration pathways that support glutathione synthesis. Maintaining glutathione availability can improve cellular handling of reactive intermediates and oxidative stress. Methylation reactions also support phospholipid and other metabolic pathways. These biochemical roles provide a rationale for hepatic support, although the clinical effect depends on the underlying disease and formulation.

Dose Rates

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Hepatic support	20 mg/kg	PO	Every 24 h
Size-based hepatic supplement	Reference only	PO		Reported gives 90 mg for small, 225 mg for medium and 425 mg for large dogs without numeric weight boundaries.
Acetaminophen toxicity adjunct — Loading	40 mg/kg	PO	Once
Acetaminophen toxicity adjunct — Maintenance	20 mg/kg	PO	Every 24 h	Up to 7 days
Hepatic support	18 mg/kg	PO	Every 24 h	Reported Denosyl daily basis, adjusted to a suitable intact tablet. Give at least 1 hour before food; do not break the coating.

Cats

Use / stage	Dose	Route	Schedule	Instructions
Hepatic support	90 mg/animal	PO	Every 24 h	Cats up to 5 kg.
Acetaminophen toxicity adjunct — Initial	180 mg/animal	PO	Every 12 h	Up to 3 days
Acetaminophen toxicity adjunct — Maintenance	90 mg/animal	PO	Every 12 h	Up to 11 days; Follows first 3 days at the higher amount.
Hepatic support	18 mg/kg	PO	Every 24 h	Reported Denosyl daily basis, adjusted to a suitable intact tablet. Give at least 1 hour before food; do not break the coating.
Hepatic support	20 mg/kg	PO	Every 24 h	Alternative for hepatic lipidosis or other liver disease; proven bioavailable product.

Indications

Adjunctive nutritional support in selected dogs and cats with hepatic disease, with limited disease-specific clinical outcome evidence.
Adjunctive support during selected oxidative hepatotoxic injuries, including some acetaminophen-associated injury, within a complete toxicology treatment plan.
Selected support of age-associated canine cognitive dysfunction, supported by limited clinical evidence.

Interactions

Tricyclic antidepressants may increase serotonin-related toxicity; clomipramine interaction reported experimentally.

Adverse effects

Transient gastric upset.

Toxicity

Acute excess most often causes GI upset; specific veterinary overdose evidence is limited.

Preparations

Preparation	Form	Strength	Route
Denosyl 90 mg coated tablet Do not split or disrupt coating. Whole tablets only.	Tablet	90 mg / tablet	PO
Denosyl 225 mg coated tablet Do not split or disrupt coating. Whole tablets only.	Tablet	225 mg / tablet	PO
Denosyl 425 mg coated tablet Do not split or disrupt coating. Whole tablets only.	Tablet	425 mg / tablet	PO

Monitoring and Administration

Give 30-60 minutes before food. Administer water after feline tablets to promote swallowing. Do not break enteric-coated tablets; protect from moisture.

Monitor hepatic injury. Acetylcysteine is the more reliable primary acetaminophen antidote.

In dogs older than 8 years, 18 mg/kg/day was associated with improved cognitive scores in a study; route is not explicit in the supplied description and no separate calculable cognitive regimen is assigned.

Denosyl intact-tablet daily guide: up to 5.5 kg, 90 mg; 5.5-11 kg, two 90-mg tablets or one 225-mg tablet; 11-16 kg, 225 mg; 16-29.5 kg, 450 mg; 29.5-41 kg, 675 mg; above 41 kg, 900 mg. Printed boundary overlaps are not silently resolved; two 90-mg and one 225-mg alternatives are not equal mass doses.

SAMe deteriorates with moisture and acidic/aqueous exposure; keep intact coated tablets tightly sealed and dry.