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Osteoarthritis and SAM-E

Written by sshowalter.

Effect of SAM-E on Osteoarthritis

A substantial amount of evidence suggests that SAMe can be an effective treatment for osteoarthritis, the "wear and tear" type of arthritis that many people develop as they get older.1

Read more details about SAM-E.

Research Evidence on SAM-E

A substantial body of scientific evidence indicates that S-adenosylmethionine (SAMe) can relieve symptoms of arthritis.50 Numerous double-blind studies involving more than a thousand participants in total suggest that it is approximately as effective for this purpose as standard anti-inflammatory drugs. However, there is no meaningful evidence that SAMe slows the progression of the disease.

One of the best double-blind studies enrolled 732 patients and followed them for 4 weeks.51 Over this period, 235 of the participants received 1,200 mg of SAMe per day, while a similar number took either placebo or 750 mg daily of the standard drug naproxen. The majority of these patients had experienced moderate symptoms of osteoarthritis of either the knee or of the hip for an average of 6 years.

The results indicate that SAMe provided as much pain-relieving effect as naproxen and that both treatments were significantly better than placebo. However, differences did exist between the two treatments. Naproxen worked more quickly, producing readily apparent benefits at the 2-week follow-up, whereas the full effect of SAMe was not apparent until 4 weeks. By the end of the study, both treatments were producing the same level of benefit.

In a double-blind study that compared SAMe against the new anti-inflammatory drug Celebrex (celecoxib), once more, the drug worked faster than the supplement, but in time both were providing equal benefits.123

Evidence regarding slowing the progression of arthritis is, at present, limited to studies involving animals rather than people.52,53 Also, in many cases, studies are funded by those producing the products being tested, so it is suspected that there can be a conflict of interest.

How to Use SAM-E

The body makes all the SAMe it needs, so there is no dietary requirement. However, deficiencies in methionine, folate, or vitamin B12 can reduce SAMe levels. SAMe is not found in appreciable quantities in foods, so it must be taken as a supplement. (It may also help to consume adequate amounts of methionine, folate, and/or vit B12 to also help with maintaining adequate levels of SAMe.)

It's been suggested that the supplement trimethylglycine (TMG) might indirectly increase SAMe levels and provide similar benefits, but this effect has not been proven.

A typical full dosage of SAMe is 400 mg taken 3 to 4 times per day. If this dosage works, take it for a few weeks and then try reducing the dosage. As little as 200 mg twice daily may suffice to keep you feeling better once the full dosage has "broken through" the symptoms.

However, some people develop mild stomach distress if they start full dosages of SAMe at once. To get around this, you may need to start low and work up to the full dosage gradually.

Recently, SAMe has come on the US market at a recommended dosage of 200 mg twice daily. This dosage labeling makes SAMe appear more affordable (if you're only taking 400 mg per day, you'll spend only about a third or a fourth of what you'd pay for the proper dosage), but it is unlikely that SAMe will actually work when taken at such a low dosage.

There have been no reported deaths from overdose of SAM-e. Side effects can include headache, nausea, anxiety, insomnia, dry mouth, reduced appetite, sweating, and dizziness.

Some people develop mild stomach distress if they start full dosages of SAMe at once. To get around this, start with a lower dosage and work up to the full dosage gradually.

SAM-e should not be taken with MAOIs.


  1. di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med. 1987;83(5A):60-65.
    1. di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med. 1987;83(5A):60-65.
      1. Caruso I, Peitrogrande V. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen and placebo in the treatment of degenerative joint disease. Am J Med. 1987;83(5A):66-71.
      2. Kalbhen DA, Jansen G. Pharmacological studies on the antidegenerative effect of ademetionine in experimental osteoarthritis [in German; English abstract]. Arzneimittelforschung. 1990;40:1017-1021.
      3. Barcelo HA, Wiemeyer JC, Sagasta CL, et al. Experimental osteoarthritis and its course when treated with S-adenosyl-L-methionine (SAMe) [in Spanish; English abstract]. Rev Clin Esp. 1990;187:74-78.
  2. Najm WI, Reinsch S, Hoehler F, et al. S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. BMC Musculoskelet Disord. 2004;5:6.

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