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Mayo Clinic Health Library


Updated: 10-24-2017


S-adenosyl-L-methionine (SAMe) is a compound found naturally in the body. SAMe helps produce and regulate hormones and maintain cell membranes.

A synthetic version of SAMe is available as a dietary supplement in the U.S. In Europe, SAMe is a prescription drug.

SAMe can be taken orally, intravenously or through a muscular injection. People generally use SAMe to treat osteoarthritis, liver disease and depression. However, SAMe can also interact with antidepressant medications.


Research on SAMe use for specific conditions shows:

  • Depression. While research has shown that SAMe has a positive effect in treating depression, most studies weren't well-designed and included a small number of people.
  • Liver disease. It's not clear if SAMe is beneficial for people who have liver disease.
  • Osteoarthritis. Many studies comparing the use of SAMe with nonsteroidal anti-inflammatory drugs showed that each provided similar pain relief and improvement in joint function, but SAMe produced fewer side effects. A smaller number of studies haven't shown the same results.

Our take

Generally safe

SAMe appears to be safe and might be effective in treating osteoarthritis and depression. However, SAMe might interact with use of antidepressants. Don't use SAMe and prescription antidepressants together.

Safety and side effects

Side effects from SAMe are rare and, if they occur, usually mild.

SAMe can cause:

  • Upset stomach
  • Nausea
  • Mild insomnia
  • Dizziness
  • Irritability
  • Anxiety
  • Sweating
  • Constipation
  • Diarrhea

If you have bipolar disorder, talk to your doctor before taking SAMe. The supplement might increase anxiety and mania.

If you have a compromised immune system, consider avoiding SAMe. People who have weakened immune systems are at risk of an infection caused by a specific microorganism. SAMe boosts this microorganism's growth.


Possible interactions include:

  • Antidepressants and other drugs and supplements that increase levels of serotonin. Don't take SAMe with antidepressants. The combination could cause effects similar to a condition caused by high levels of the chemical serotonin to accumulate in your body (serotonin syndrome).
  • Antipsychotics. Be cautious when taking these drugs with SAMe. The combination could increase the risk of serotonin syndrome.
  • Amphetamines. Be cautious when taking these drugs with SAMe. The combination could increase the risk of serotonin syndrome.
  • Dextromethorphan. Taking SAMe with this cough suppressant could increase the risk of serotonin syndrome.
  • Narcotics. Taking SAMe with meperidine (Demerol) or tramadol (Ultam, ConZip) could increase the risk of serotonin syndrome.
  • St. John's wort. Be cautious when taking this supplement with SAMe. The combination could cause serotonin syndrome.