S-adenosyl methionine – SAMe for short – is a popular dietary supplement available freely via the Internet. It is a naturally occurring methyl radical donor involved in enzymatic transmethylation reactions in humans and animals. It has been used for treating postpartum depression, cholestatic jaundice, osteoarthritis, and numerous other conditions. SAM-e has poor oral bioavailability. SAM-e has so far been thought of as safe. The most frequent adverse effects reported were gastrointestinal, such as nausea, and skin rashes.
I have been involved in two systematic reviews that produced positive evidence for the effectiveness of SAMe:
- One review found “consistent evidence that … S-adenosyl methionine was effective in the management of osteoarthritis.”
- Another review showed that for fibromyalgia “the effects of … S-adenosylmethionine … showed at least one statistically significant improved outcome compared with placebo.”
Now the safety of SAMe has been questioned by new research. A team from Manchester and Kyoto universities reported that the supplement can break down inside the body into substances that cause a wide range of medical problems, including kidney and liver damage. Their study showed that “excess S-adenosylmethionine disrupts rhythms and, rather than promoting methylation, is catabolized to adenine and methylthioadenosine, toxic methylation inhibitors.”
Jean-Michel Fustin, of Manchester University, said experiments that he and his collaborators had carried out had revealed that SAMe breaks down into adenine and methylthioadenosine in the body. These substances are known to be toxic, he added. “This discovery came out of the blue,” Fustin said last week. “When we gave the supplement to mice we expected they would become healthier. But instead we found the opposite. We found that when SAMe breaks down in the body, it produces very toxic molecules, including adenine which causes gout, kidney disease and liver disease.” Fustin added that, although their study was carried out on mice, their results were relevant for humans. “We have not yet tested the supplement on men and women but we have added it to human cells in laboratory cultures and have found it had the same effect as it had on mice.”
Their study, which was funded by the Medical Research Council and the Japanese Society for the Promotion of Science, makes it clear that the health benefits of SAMe are questionable, to say the very least, Fustin added. “It is unclear what dose of it might be safe, so there is a good chance that a safe dose will be exceeded if someone takes this supplement – if a safe dose exists at all.”