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:

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.”

2 Responses to SAMe: a dietary supplement that might not be as harmless as we had thought

  • The perfect demonstration that the scientific method is not to be compared with the ‘belief’ required by SCAM. In EBM you don’t believe in your particular view and if something like this happens are happy to change your previous view.

    If you were a SCAM practitioner faced with comparable evidence you would resort to saying they didn’t understand or talking about the side effects of another medication.

  • if a safe dose exists at all

    That’s a strange thing to say. Maybe what he means is that there may not be a dose that’s safe AND has the effects that people want from it.
    They found that SAM given to mice in doses that are analogous to the suggested doses in people, lengthens their circadian rhythm.

    To match the daily recommended intake of SAM supplements of 0.8–1.6 g/day in human, we administered SAM to mice at a concentration of 100 and 250 mg/kg of food, and monitored circadian locomotor (running wheel) activity rhythms in constant darkness for around 1 month to allow expression of endogenous rhythms. At both 100 and 250 mg/kg, SAM caused an increase in the circadian period compared to control, with a dose-dependent effect … While mice did not display any obvious differences in general condition including body weight after one month under these conditions, the fact that circadian rhythms were affected by exogenous SAM as observed in vitro indicate unsupervised SAM supplementation should be considered with caution.

    But they also suggest that SAM may be useful for some people with sleep disorders.

    While we have flagged the potential toxicity of SAM, the effects of SAM intake on locomotor activity rhythms in vivo suggest SAM could potentially be used to correct circadian misalignments caused by shiftwork or jetlag. Circadian rhythm sleep disorders such as delayed sleep phase disorder (DSPD) and advanced sleep phase disorder (ASPD) are often associated with depression. SAM may be especially efficient in the treatment of ASPD, since ASPD patients have a circadian clock that runs faster than 24 h, leading to early sleep onset and awakening. SAM may help slow the internal rhythms of ASPD patients down and facilitate their synchronization to the external day-night cycles.

    They also say that SAM interferes with cell division, so it may be useful in cancer treatment.
    It seems that SAM is pretty powerful stuff. Maybe it will become a prescription drug after more research.

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