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k9cushings
05-12-2009, 01:48 AM
Excellent article about Milk Thistle by Dr. Susan G. Wynn, DVM:

http://web.archive.org/web/20110902063224/http://wendyblount.com/etvma2/milk-thistle.pdf

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Pretty much everything is metabolised by the liver, including drugs and other substances which may have a slight potential for a toxic effect on the liver. That said, many of our dogs who take drugs like Lysodren or Trilostane, for example, are also taking Milk Thistle, prescribed for each individual dog by their own Vet.

Milk Thistle is available in health food stores. There is a dosing guideline for companion animals mentioned in the article by Dr. Wynn, above, but dosing a dog with most brands of Milk Thistle involves some guesswork and extrapolation from dosages suggested for humans. That is, until now ... in the USA, Milk Thistle is now available in a Veterinary formulation called "Marin" and hopefully Marin will also be available in other countries soon.

Marin also contains Vitamin E and a small amount of zinc ... also good for the liver.

Denosyl (Veterinary formulation of Sam-e) is also believed to help "boost" liver function.

See: Causes of Chronic Hepatitis in the dog, by Robert C. Denovo, DVM, MS, Diplomate ACVIM
http://web.archive.org/web/20060918031248/http://www.vet.utk.edu/continuing_ed/05decCE/denovo.pdf


Antioxidant Drugs and S-Adenosyl-L-Methionine:

Most if not all damage to the liver, regardless of cause, is mediated by increased production of free radicals that cause oxidative damage to cell organelles. Recent studies indicate that antioxidant therapy is beneficial in some types of chronic hepatitis. For this reason, treatment with an antioxidant drugs to scavenge free radicals might be protective against oxidant injury to hepatocytes, particularly in patients with copper accumulation.

S-Adenosyl-L-Methionine (DenosylŽ)
Glutathione (GSH) is a major hepatic antioxidant and is necessary for hepatic detoxification of drugs and toxins. S-adenosly-L-methionine (SAMe) is a precursor or GSH and is important in the maintaining normal hepatocyte membrane functions and hepatocyte regenerative processes. GSH concentration is decreased in patients with both acute and chronic liver diseases. Conversion of methionine to SAMe, and subsequently to GSH, is also impaired. The effects of this may include methionine intolerance and accumulation of oxidants, thereby leading to worsening of the liver damage.

Treatment of human cirrhosis patients with oral SAMe results in increased plasma concentration of GSH, cysteine and taurine; and a decrease in plasma methionine, serum bile acids and bilirubin and ALT and GGT activities. Cholestatic disease associated with oral contraceptives, alcoholic hepatitis, and druginduced hepatotoxicity (e.g. acetaminophen, anticonvulsants) improve significantly when treated with SAMe. SAMe attenuates alkaline phosphatase induction and improves glutathione production in dogs given chronic high dose glucocorticoid therapy.
Several preparations of this neutraceutical are available over-the-counter, but potency is variable.

Denosyl SD4 (Nutramax Laboratories, Inc., Edgewood, Maryland) is recommended.

The recommended dose is 20 mg/kg/day given should be given on an empty stomach Conditions for which SAMe use should be considered include feline hepatic lipidosis, feline cholangitis and cholangiohepatitis, and in dogs with marked vacuolar hepatopathy from either glucocorticoid administration or idiopathic vacuolar hepatopathy, and in chronic active hepatitis.There are no known side effects in animals.

Vitamin E (d-alpha tocopherol) has been shown to protect the liver from copper-related oxidant damage and from oxidant damage caused by accumulation of hydrophobic bile acids that accumulate in cholestatic liver disease. Vitamin E is inexpensive and safe, and is recommended for use in dogs with any type of chronic hepatitis. The recommended dose is 50 - 400 IU/day.

Silymarin is a flavonolignan found in milk thistle which has been used as a natural remedy for hepatobiliary disease. Flavonolignans are reported to have antioxidant properties by scavenging for freeradicals that cause lipid membrane damage. Results of controlled studies in humans using milk thistle to treat patients with acute and chronic liver diseases are variable, but some evidence does indicate beneficial effects from this treatment. One study in beagles showed that dogs pre-treated with milk thistle were protected from the toxic effects of amanita mushroom poisoning, whereas placebo-treated dogs died. Limited studies and clinical experience preclude making firm recommendations regarding the use of milk thistle to treat chronic liver disease. Dosages extrapolated from human use range from 50 - 250 mg/kg/day.

Many over-the-counter products are available; potency varies. Recently, Nutramax released a new veterinary product, called MarinŽ which contains silybin, vitamin E, and zinc in a single tablet formulation. A formulation of MarinŽ for cats contains silybin and vitamin E only. Silybin is the most active component of silymarin, derived from the milk thistle.

Here are some more links:

Nutramax Labs archived webpages

Liver Function in Animals:
http://web.archive.org/web/20080312235823/http://www.nutramaxlabs.com/products/animal/liver/liver.asp

Denosyl Client Brochure:
http://web.archive.org/web/20070108021404/http://www.nutramaxlabs.com/products/animal/liver/documents/DENOSYLCLIENTBROCHURE.pdf

Denosyl Studies Booklet:
(see attached pdf below)


Marin Brochure:
http://web.archive.org/web/20070107055933/http://www.nutramaxlabs.com/products/animal/liver/documents/MarinBrochure.pdf


Nutramax Labs updated webpages

Liver Health for Pets:
http://www.nutramaxlabs.com/Vet/Products/liver-health.aspx

Denosyl:
http://www.nutramaxlabs.com/vet/products/Denosyl.aspx

Denosyl Client Brochure (updated version):
http://www.nutramaxlabs.com/downloads/Denosyl-Brochure.pdf

Marin:
http://www.nutramaxlabs.com/vet/products/Marin.aspx

Marin Client Brochure (updated version):
http://www.nutramaxlabs.com/downloads/Marin-Client-Brochure.pdf

Denamarin:
http://www.nutramaxlabs.com/vet/products/Denamarin.aspx

Denamarin Client Brochure:
http://www.nutramaxlabs.com/downloads/Denamarin-Client-Brochure.pdf


Another link about Sam-e:
http://www.veterinarypartner.com/Content.plx?P=A&S=0&C=0&A=1319

And a link about Milk Thistle and Marin, in particular:
http://www.veterinarypartner.com/Content.plx?P=A&A=1779&S=1&SourceID=52

More information about Milk Thistle here:
http://lowchensaustralia.com/health/thistle.htm

Speak to your Vet if you think that any of the above supplements may be a good thing for your dog.

If you and your Vet do decide to give your dog some supplements for liver support, remember that when starting a dog on something new (including foods, drugs or supplements) it's best to start one new thing at a time, so that in case the dog does have any side effects (even really minor, or temporary, such as soft stools when you first start giving it, for example) you would know that it's likely the "new thing" causing it.

k9cushings
05-12-2009, 01:50 AM
A Veterinary formulation of Sam-e which is also available in many countries, including the UK, is called Zentonil.

Zentonil Brochure:
http://web.archive.org/web/20070127221159/http://66.187.129.130/vetoquinol_pdfs/Zentonil.pdf

http://www.vetoquinolusa.com/pages/global_03.html

http://animalmedicines.co.uk/product.php?cat=253&page=1&productid=1095



Zentonil contains a pure, stabilised salt of S-Adenosylmethionine (SAM-e) in the tablet form.

Easy to use form of S-Adenosylmethionine (SAM-e) for cats or dogs. Unlike other forms of SAM-e supplementation, Zentonil tablets are enteric coated, to prevent SAM-e being digested by stomach acid. This ensures that the maximum amount is available for absorption from the duodenum.

Available in three strengths, for greater accuracy and ease of administration

- 30 x 100mg enteric-coated tablets

- 30 x 200mg enteric-coated tablets

- 30 x 400mg enteric-coated tablets

Importance of S-Adenosylmethione (SAM-e) for glutathione production:
S-Adenosylmethionine (or SAM-e) is a nucleotide –like molecule that is synthesised by all living cells. Derived from methionine and ATP, SAM-e initiates three major biochemical pathways: transmethylation, transsulphuration and aminopropylation. SAM-e is essential for the production of glutathione, a major liver antioxidant.

In a compromised liver:
Production of SAM-e synthetase, the enzyme that converts methionine to S-Adenosylmethionine (SAM-e), is decreased.

As a result, the supplemented methionine cannot be converted to SAM-e.

And the compromised liver is not able to produce the sufficient amount of glutathione - a vicious circle is created.

In a recent study, 51% of dogs and 82% of cats with liver problems were reported to be deficient in glutathione.*
By supplementing SAM-e, you are supporting the liver in producing glutathione and thus helping the liver to maintain its normal function.