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  • Writer's pictureDr Matt Kopke

Is SAMe Safe?

Updated: Dec 21, 2023


SAMe, or S-adenosylmethionine, has become an increasingly popular nutritional supplement in both humans and veterinary patients over the past few decades.


In humans, its use has been marketed for conditions such as liver disease, osteoarthritis, and even mental health disorders. However, more recent studies have reported either a lack of efficacy in managing the above problems or an increased incidence of side effects associated with its use.


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In 2022, Fukumoto et al. were able to elaborate a bit further on SAMe’s shortcomings in their study on the use of SAMe in mice and human cells in laboratory cultures. They identified that instead of SAMe enhancing methylation reactions, as was thought to be the case, it actually inhibited such reactions because SAMe is broken down into adenine and methylthioadenosine. Both of these breakdown products are toxic and have been linked to problems such as liver and kidney damage and also gout. The generation of these toxic products also disrupts normal circadian rhythms, in other words, the body’s biological clock and their accumulation can include other consequences such as heart attacks, stroke, dementia, depression, migraines, autism, fertility problems, cancer, and even birth defects.


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Chronic use of SAMe supplements might bring about an increased risk of such problems or consequences as both adenine and methylthioadenosine accumulate, which enhances their toxicity.


So, that’s really a bit of a dampener when you consider that SAMe was often marketed as a supplement that promotes a positive mood. What’s currently not clear, though, is what dose is safe (if there is such a dose) and, therefore, potentially useful and when does this spill over into a range of possible toxicity.


What about the use of SAMe in dogs and cats?


There are a few studies in dogs that have looked at the potential use of SAMe supplementation with various disease conditions. Like in humans, SAMe has been proposed as a beneficial supplement for the management of various liver diseases, osteoarthritis, and cognitive dysfunction.

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In a 2008 study, SAMe was found to be both safe and effective in improving signs of age-related mental decline in dogs. A couple of years later, another study failed to support the use of SAMe as a standalone treatment for dogs with osteoarthritis.



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In terms of liver disease, Center et al. (2005) demonstrated that the administration of SAMe (at 20 mg/kg/day) was able to mitigate the pro-oxidant effects of prednisolone, however, it failed to block the development of the classic clinicopathologic and histologic features of vacuolar hepatopathy. In 2011, a study coming out of the University of California, Davis showed that the concurrent use of Denamarin (containing a stable salt of SAMe and silybin in a phosphatidylcholine complex) with CCNU (lomustine) served to minimize increased liver enzyme activity in dogs receiving such chemotherapy. Such treatment also increased the likelihood of dogs completing a prescribed CCNU course.


What does this mean for our veterinary patients and the potential applications for SAMe?


While at least some of the studies mentioned above suggest a potential positive impact that SAMe supplementation can have in the conditions mentioned, in general, there are limited studies that have looked at the use and safety of SAMe in dogs. Also, even though dosages have been recommended and often employed by some, it is important to inform pet parents that evidence for its efficacy is often lacking. And with studies such as the one conducted by Fukumoto et al., perhaps the widespread or common recommendation to use SAMe in dogs with, for instance, liver disease (apart from a potential protective/useful role with certain toxicities) should be put on hold until we have further research either supporting or contradicting its use.


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