Dietary Outcomes in Osteoarthritis Disease Management

Carol J. Henderson, PhD, RD
Department of Nutrition
Georgia State University
Atlanta, GA

S-adenosylmethionine (SAM-e) 

SAM-e is an intermediate metabolite of the essential amino acid methionine. SAM-e functions as a methyl doner in many biological reactions and is a precursor for polyamines (33). SAM-e's involvement in the process of methylation assists the body to grow and repair cells, helps maintain phospholipids in the cell membrane and helps maintain the action of several hormones and neurotransmitters that affect mood, including dopamine, serotonin, and melatonin (34). SAM-e is found in every living cell, with its greatest concentrations located in the brain and liver.

It has been hypothesized that IL-1 exposure decreases SAM-e levels in chondrocytes, and this effect is an important mediator of IL-1's suppressive impact on aggrecan and type II collagen synthesis (35). During clinical trials of SAM-e as a treatment for depression, Italian researchers noted that patients having OA reported pain relief with 30 mg BID IV SAM-e administered for 14 days (36). Subsequent double-blind trials of short duration (< 1 month) demonstrated that SAM-e provided pain relief in OA comparable to that of NSAIDs, with only nonspecific side effects (mostly gastrointestinal) and no reported toxicities (37,38). SAM-e was administered both intravenously and orally in typical amounts of 300 mg 2-3 times/day. A larger, longer-term open trial of SAM-e in 108 patients with knee, hip, and spine OA, 600 mg/day SAM-e was administered for 2 weeks followed by 400 mg/day to complete 2 years of treatment (39). Pain and stiffness improved within 1 week of treatment and continued through the 2-year trial. A meta-analysis of 7 randomized controlled trials compared SAM-e to NSAIDS or placebo for OA and did not give enough evidence for the efficacy of SAM-e in the treatment of OA (40). Due to lack of evidence, SAM-e efficacy could not be established.

Precautions and Possible Side Effects:
Folic acid also has an important role in the methylation process and reducing homocysteine, therefore, the increased intake of dietary intake of folic acid via dark leafy green vegetables or supplementation of 200 mcg/day is suggested when taking SAM-e.

Adverse effects of SAM-e are dose dependent and may include flatulence, vomiting, diarrhea, headache, and, in depressed patients, anxiety. SAM-e should not be taken concomitant with anti-depressive agents to avoid serotonin syndrome-like symptoms such as tremors, tachycardia, tachypnea, and hyperreflexia. Gastrointestinal side effects may be reduced by ingesting SAM-e with meals, reducing the dosage, or taking enteric coated tablets. There is insufficient data on possible drug interactions.

Recommendations: 
There is not sufficient long-term data to recommend the use of SAM-e in the treatment of OA. If used in patients with OA, a dose of 200 to 400 mg tid SAM-e/day can be given. SAM-e should be discontinued after 6 weeks if OA symptoms do not improve.