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.