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.
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?
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.
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.
My 2yo 85 lb female dog has highly elevated liver enzyme levels presumably due to liver trauma caused by being hit by a car. She also has obvious trauma to one lung and possibly other internal issues. The vet, today, one week from the incident, prescribed Denamarin in an attempt to, I suppose , support the liver as it heals. The dog is ambulatory, but understandably sore. Levels have been coming down but are still quite high. ALT (U/L) were 1534, 944, and 671 the day of, day two and day 3. Seven days out, today, 402. Denamarin administration has started today. Is this a shot in the dark or should we expect and accelerated and improved outcome? Peer reviewed literature is a bit hard to come by.
If the cause is trauma, the liver is likely to recover on its own. It’s hard to make a good case for a supplement to help it given the incredible regenerative capacity of the liver and the fact that there is no evidence supporting the use of Denamarin for this kind of problem. I doubt it will hurt, but my guess is that the liver will heal naturally and we’ll be tempted to give the credit to the supplement even though it is probably irrelevant.
My 8 yr old dachshund has elevated ALT 733. Was 233 2 weeks ago. Ultrasound showed no masses,lesions or leakage. But did show enlarged spleen liver and gallbladder filled with sludge which vet thinks may have caused the increase. Put her on ursodiol and clavacillin. She has no symptoms other than 1 day month ago did not want food or water or her fav treat. Had a lot of gas. This week had a very tiny mast cell tumor removed. Vet does not believe ALT increase is related to that. They want to do a liver biopsy which scares me and is not without risk. I would rather try denamarin first. Does that sound reasonable??
The problem with Denamrin is that even if it does what it is intended to do, it isn’t intended to actually treat any of the causes of liver problems. All it does is support the liver and potentially minimize damage from whatever is the underlying cause. If the reason for your dog’s elevated ALT is something that is going to go away on its own, then Denamarin might be useful as a supportive treatment. If there is a true underlying disease, though, the number might improve but we won’t have actually identified or treated the real problem. The challenge, of course, is that at this stage you know plenty of things that aren’t causing the problem but not what is, so whether it will get better on its own or require further testing and treatment is unpredictable.
It is not unreasonable to try supportive care and wait and see if you dog is not sick and the labwork isn’t getting worse, but you just need to understand that this is what you are doing.
where did the commonly used alternative medicine term “support” come from in medicine? I remember support hose and a support bra but in school we used the term “aids in” and finished the sentence in what the medicine aids in doing.
I see that the clinical studies are more focused on the efficacy of Denamarin while on CCNU. However, my dog is on Vincristine and Cytoxan, which are known to cause hepatotoxicity as well. My dog’s ALT were elevated (assuming it’s caused by these chemo meds and not something else). Will Denamarin be just as effective in supporting liver function and preventing further liver damage caused Vincristine and Cytoxan as it is with CCNU?
Neither of these drugs is likely to be very toxic to the liver, so not the primary suspects here. Both can have pretty serious GI effects (especially vincristine0, and an elevated ALT may be secondary to something in the GI tract rather than directly in the liver, so that could be an explanation, or it may be unrelated.
As for Denamarin, unfortunately, the evidence is pretty limited, so no one really knows when it will be helpful. In general, the mechanism. by which it is thought to be protective should be applicable to a wide variety of toxins, so there is no particular reason to think it won’t help in cases other than CCNU, but again hepatotoxicity is not usually high on the list of problems from these drugs, so it isn’t clear what we are protecting agains here. Unlikely to be harmful as far as we know, though it can reduce appetite in some dogs.
My vet gave me denamartin to give to my pup because there is a mass on her liver. She is very overweight & we have been sticking to a strict diet for the past month, but she did not lose weight. The vet wants us to only use a prescription digestive food and to give her this denamartin, in addition to 2 other meds to help her with leg pain.
Do you know why we wouldn’t just move forward with getting the mass biopsy? She is not showing any signs of cancer. Is it possible that the mass could shrink with weight loss? I’m very confused as to why we would continue with the weight loss for another month when they can see the mass with a sonogram?
I’m sorry you are dealing with this difficult situation. I can’t offer specific advice, but it sounds like you need to ask those questions of your vet. If you can’t get clear answers that make sense to you, you should also consider a second opinion, ideally with an internal medicine or oncology specialists if possible.