What is it?

SAMe is a chemical compound found naturally in your body. It stimulates the production of parts of cartilage, and may have antidepressant and painkilling properties. Evidence suggests that SAMe is effective in reducing functional limitations and, to a lesser extent, pain in osteoarthritis. Evidence for its effectiveness for fibromyalgia suggests that SAMe might be useful for reducing body tenderness and depressive symptoms.

  • Family: Nutritional supplement
  • Scientific name: S-adenosylmethionine

SAMe is a chemical compound made from methionine, an amino acid also found in protein-rich foods, and adenosine triphosphate (ATP), a nucleic acid and the product of some chemical reactions in your body. SAMe was discovered in 1952 and was first studied as a possible treatment for depression.

How does it work?

SAMe is found naturally in your body. It contributes to several biochemical pathways and in the building of hormones and neurotransmitters. Laboratory studies suggested that SAMe has some painkilling activity and stimulates the production of collagen and proteoglycans, which are major building blocks of cartilage. SAMe may work as an antidepressant, but we don’t yet understand how this may work.

Is it safe?

Side-effects, which are usually mild and infrequent, include:

  • nausea
  • restlessness
  • headaches
  • a dry mouth
  • stomach upsets.

Severe side-effects of anxiety and mania have also been reported in people with depression. SAMe can also increase the activity of antidepressants.

If you take anticoagulants, you should take SAMe under your doctor’s supervision because it might increase the risk of bleeding.

We don’t yet know what the best dose of SAMe is, but most studies have used daily doses of 400–1,600 mg.

SAMe trials for osteoarthritis

Review article (2002)

Eleven trials into the use of SAMe for osteoarthritis were included in this review:

The number of participants included ranged from 36–493 and the trials lasted from 10–84 days. Dosages varied:

  • Six trials used a dosage of 1,200 mg SAMe per day.
  • Three trials used 600 mg per day.
  • One used 400 mg per day.

In the final trial, the dose varied between participants.

Data from all these trials were combined and reanalysed:

  • SAMe was significantly better than a placebo and had an effect similar to that of NSAIDs in reducing functional limitations caused by osteoarthritis.
  • SAMe had an effect equivalent to that of NSAIDs in terms of pain reduction.
  • Two trials compared the effect of SAMe versus that of a placebo in reducing osteoarthritis related-pain. Both of them reported SAMe to be significant better than the placebo.
  • The combined reanalysis of the 10 trials which compared NSAID with SAMe found that participants taking SAMe were 58% less likely to experience side-effects than those treated with NSAIDs, regardless of the dose of SAMe and the length of treatment.

Trial 1

This trial, published in 2004, compared the effectiveness of SAMe to celecoxib (a COX-2 inhibitor, which is a type of NSAID) for pain control, functional improvement and reported side-effects in people with osteoarthritis. The trial lasted for 16 weeks and found that SAMe worked more slowly but was as effective as celecoxib in relieving pain and improving physical function.

Trial 2

In this trial, 134 people of Asian origin with knee osteoarthritis were randomly allocated to receive either 400 mg SAMe three times a day or nabumetone (an NSAID) for eight weeks.

  • Both groups reported improvements in pain, stiffness and function.
  • The participants’ overall assessment of disease and the physicians’ assessment of the participants’ response to therapy also reported improvement, with no differences between the groups.

SAMe trials for fibromyalgia

Three out of four published RCTs found that SAMe was effective, when compared to a placebo, in reducing the number of tender points and/or the intensity of tenderness of these points in people with fibromyagia. The three studies also found that SAMe was effective, compared to placebo, in reducing depressive symptoms.

The fourth RCT found that SAMe wasn’t significantly better than a placebo in reducing almost all disease-related symptoms; however, the number of participants who took part in these four trials was small (17–44 participants) and length of treatment was short (10 days–6 weeks).