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SAMe for Cats with Spontaneous Liver Disease

Bess P. Brosey, MZS, DVM, Diplomate ABVP & ACVIM

Integrative Medicine

|October 2005

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S-adenosylmethionine (SAMe) is an important hepatic metabolite that donates methyl, aminopropyl, and sulfhydryl groups (including glutathione) to metabolic precursors in hepatocytes. Studies in humans and experimental animal models have indicated that SAMe may have therapeutic value for necroinflammatory and cholestatic liver disorders. The synthesis of a stable SAMe salt in an enterically coated tablet has enabled the normally labile SAMe compound to be used therapeutically. While integration of SAMe in cell metabolism after oral administration has been proven in humans and various other animal species, there is little information about the influence of SAMe given orally in cats.

This long-term longitudinal trial (pre- and posttreatment variables compared) studied 15 healthy, adult female domestic shorthair cats. The cats were given a stable 1,4-butanedisulfonate SAMe salt in the form of a 180-mg enterically coated tablet. Mean dosage was 48 mg/kg given once daily on an empty stomach for 113 days. The following variables were examined: routine physical and clinicopathologic assessments, RBC osmotic fragility, liver function and histologic characteristics, liver concentrations of reduced glutathione and its oxidized disulfide form, protein, glycogen, DNA, glutathione concentrations in RBCs, total bile acids in serum and bile, oxidative membrane products in RBCs and liver, and SAMe concentrations.

SAMe concentrations increased significantly, with peak concentrations achieved 2 to 4 hours after dosing in 78% of the cats. Peak or cumulative plasma concentrations of SAMe did not change with long-term dosing, suggesting a lack of substantial change in enteric degradation, uptake, enterohepatic cycling, systemic metabolism, or elimination with long-term administration. The authors also noted a positive influence of SAMe on RBCs and hepatic redox status (oxidative membrane products in RBCs were reduced 21.1%, liver glutathione was increased 35%, and liver reduced glutathione-oxidized disulfide glutathione ratio was increased 69%), improved RBC resilience against osmotic challenge, bile acid-independent choleresis, and improved histologic characteristics in cats with asymptomatic nonsuppurative portal inflammation. The authors thus concluded that the form of SAMe used in the study is enterically available and suggest that it imparts biologic effects that may be useful for attenuating systemic or hepatic oxidant challenge.

COMMENTARY: The significance and potential control of oxidative injury in all species is a rapidly growing area of interest in veterinary medicine. There is growing evidence that such injury may lead to a variety of degenerative conditions such as arthritis, aging, and cancer, and that administration of antioxidants may alter the course of these processes. This particular study examined the use of SAMe in healthy cats with results that are encouraging-oral SAMe was bioavailable and produced detectable biologic responses in clinically normal cats. These baseline studies are vital to our understanding of the therapeutic application of this compound in health and disease.

The effects of S-adenosylmethionine on clinical pathology and redox potential in the red blood cell, liver, and bile of clinically normal cats. Center SA, Randolph JF, Warner KL, et al. J VET INTERN MED 19:303-314, 2005.

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