Denamarin: Does it prevent chemotherapy-induced liver damage?

Silymarin and s-adensylmethionine (SAM-e) are plant-derived chemicals frequently used as supplements for a wide variety of applications. I’ve written about both before, evaluating the available evidence in humans and in dogs and cats (1,2,3). So far, the evidence concerning the safety and efficacy of these supplements is limited and conflicting. A recent study, however, provides a little bit more low-level support for the use of at least one combination product, known as Denamarin, containing these chemicals.

KA, Hammond GM, Irish AM, Kent MS, Guerrero TA, Rodriguez CO, Griffin DW. Prospective Randomized Clinical Trial Assessing the Efficacy of Denamarin for Prevention of CCNU-Induced Hepatopathy in Tumor-Bearing Dogs. J Vet Intern Med. 2011 Jul;25(4):838-45.

In this study, fifty dogs being treated for various cancers with the chemotherapy agent lomustine (CCNU) were randomly divided into two groups. One group was given Denamarin and the other was not. CCNU is known to frequently cause increases in liver enzymes measured in the blood. Although it is much more rarely the cause of serious liver damage, the elevations in liver enzyme levels often causes concern that can lead to delaying or discontinuing use of the drug. The goal of the study was to see if Denamrin could prevent the increase in liver enzyme levels.

In terms of this narrow criteria, the study showed a positive effect. While only 68% of the dogs on Denamarin showed liver enzyme increased, 86% of those not on the supplement had increased levels of the major enzyme of interest, alanine aminotransferase (ALT). And while these elevations reached the highest levels in 28% of the control dogs, only 7% of the dogs on Denamrin showed such very high increases in ALT.

There are a number of caveats, however, that limit the degree to which these results can support a general recommendation to use Denamarin in dogs given CCNU. The cause of liver enzyme elevations was not determined in most dogs, so it is possible that a progression of the underlying cancer, rather than the CCNU, caused the increases in some of these dogs. And only 1 of the fifty dogs actually showed clinical symptoms associated with liver damage, so it even if Denamarin prevents increased enzyme levels, this may or may not have any actual clinical benefits.

Methodologically, there are some additional caveats that must be considered in judging the significance of this study. There was no placebo group, and owners and investigators were not blinded to the treatment group. While this potential source of bias would not have directly affected ALT measurements, it could potentially have led to differences in how the dogs in the two groups were treated, which might have indirectly affected these levels. This is especially a concern since the study was funded by the manufacturer of Denamarin, and several of the authors have financial links to the company.

Overall, this study provides low-level evidence that Denamarin may have benefits in protecting against CCNU-induced liver damage in dogs with cancer. Independent replication with better controls and more comprehensive assessment of outcome would help to determine if the current results truly represent a clinically meaningful benefit from this supplement or not. However, given the low level of risk associated with this specific product, it is not unreasonable to consider using this supplement for this indication. This does not, of course, translate into support for a generalized use of Denamarin for any and all liver problems.

 

 

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3 Responses to Denamarin: Does it prevent chemotherapy-induced liver damage?

  1. Paul Puglisi says:

    I have come across a few of my customers using this product to combat elevated ALT without a formal diagnosis from their Vet. usually the Vet tells them to put the dog on it when elevated ALT levels show up and then they redraw in 4 to 6 weeks to see if ALT levels have decreased. Looking at the information on the two ingredients it doesn’t seem to show any efficacy on decreasing elevated liver enzymes at all and that most positive studies, like this one you are writing about, are for specific uses of this product, i.e. during cancer treatment to prevent elevation of ALT, and not as a general catch all to decrease liver enzymes of dogs that might have high ALT due to anything from copper retention to trauma or any other cause of elevated ALTs?

    Am I correct on that general take?

  2. skeptvet says:

    Yes, you are exactly right. The reflexive use of this supplement to “treat” an ALT elevation with no diagnosed cause makes no sense at all. Most such elevations are either due to a diagnosable disease or transient and self-limiting. Retesting at 4-6 weeks is pretty standard with mild-moderate elevations and no clinical symptoms (vomiting, inappetence, wight loss, etc), and often the number goes back down spontaneously. And if there is an identifiable cause, it is important to find and treat it directly. Denamarin may support liver function or regeneration to some extent, but it isn’t a specific treatment for any particular liver diseases, and it isn’t a substitute for appropriate diagnosis and treatment.

  3. Paul Puglisi says:

    That is what I was expecting the answer to be. So far all of my clients with elevated ALTs have actually shown really no signs of secondary symptoms and most of their Vets have taken a wait and see with most of their levels decreasing back to normal in most cases. Only one didn’t and was diagnosed with copper retention, he is a Westie so that was their first thought. So he is on a zinc supplement and we switched him to a lower copper food with a better zinc to copper ratio. He’s doing fine with close to normal levels.

    I’ve noticed that most ALT levels tend to go back to normal after an initial blood workup, in my limited experience. I’m perplexed as to why, at least most recently, I’ve been seeing more of my customers with spiked ALTs.

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