SAMe and joint pain relief: possible mechanism of action

[NO HYPE]

SAMe: unknown mechanism, but very effective in reducing joint-related pain

In-vitro research has demonstrated that SAMe aquires the ability to enhance chondrocyte proteoglycan synthesis and proliferation rates [1,2]. SAMe acts as a precursor to the aminopropylation pathway, which leads to the synthesis of polyamines (the polyamines spermine and spermidine have been shown to aquire both analgesic and antiinflammatory properties [3,4]). Methylthioadenosine is formed from SAMe, in the course of spermidine synthesis. Methylthioadenosine is thought to be at least somewhat responsible for the clinical results observed in treating osteoarthritis, rheumatoid arthritis and fibromyalgia with SAMe [5,6]. SAMe also appears to restore basal conditions following TNF-induced cell damage, and inhibit lipopolysaccharide-stimulated TNF, as well as NF-kB activity [7,8]. Additionally, a mere 400 mg of oral SAMe has been shown to significantly increase SAMe concentrations in synovial fluid by up to 4-fold compared with pretreatment values [9].


[1] Harmand MFet al. (1987), Effects of S-adenosylmethionine on human articular chondrocyte differentiation. An in vitro study.

[2] Barcelo HA et al. (1987), Effect of S-adenosylmethionine on experimental osteoarthritis in rabbits.

[3] Oyanagui Y. (1984), Anti-inflammatory effects of polyamines in serotonin and carrageenan paw edemata?possible mechanism to increase vascular permeability inhibitory protein level which is regulated by glucocorticoids and superoxide radical.

[4] Matthew & Lewis, Pharmacol. (Life Sci. Adv.), 9: 145- 152 (1990)

[5] C. di Padova (1987), [SAMe] in the treatment of osteoarthritis.

[6] A. Tavoni et al, (1987), Evaluation of [SAMe] in Primary Fibromyalgia.

[7] Gutierrez S. et al. SAMe restores the changes in the proliferation and in the synthesis of fibronectin and proteoglycans induced by tumour necrosis factor alpha on cultured rabbit synovial cells.

[8] Veal et al. (2003), Inhibition of lipopolysaccharide-stimulated TNF- promoter activity by S-adenosylmethionine and 5'-methylthioadenosine.

[9] Stramentinoli G. (1987), Ademethionine as a drug.

[Hypertrophik]

Good stuff man ! I was wondering if you came across the duration (how long of SAMe supplementation) in which these changes were observed.

[NO HYPE]

I was wondering if you came across the duration (how long of SAMe supplementation) in which these changes were observed.

With the understanding that this thread was created to merely evaluate SAMe's mechanism of action vs. the evaluation of SAMe's efficacy in reducing joint pain....

The following abstract indicates that positive results have been observed within the first few weeks of treatment, and that the elicited effects have continued for the entire duration of the study (i.e. 2-years in this particular instance). I must emphasize the fact that any SAMe product that an individual might be considering, should be incorporated into an enterically-coated capsule to improve bioavailability, as the positively charged sulfonium ion significantly limits the intracellular passage of the SAMe molecule.




Benno Konig M.D. doi:10.1016/0002-9343(87)90859-X
Copyright 1987 Published by Excerpta Medica Inc.
A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis

In a long-term multicenter open trial involving 10 general practitioners, the efficacy and tolerance of S-adenosylmethionine (SAMe) were studied for 24 months in 108 patients with osteoarthritis of the knee, hip, and spine. At the end of the 24-month observation period, 97 of the patients were still in the study. The patients received 600 mg of SAMe daily (equivalent to three tablets of 200 mg each) for the first two weeks and thereafter 400 mg daily (equivalent to two tablets of 200 mg each) until the end of the 24th month of treatment. Separate evaluations were made for osteoarthritis of the knee, hip, cervical spine, and dorsal/lumbar spine. The severity of the clinical symptoms (morning stiffness, pain at rest, and pain on movement) was assessed using scoring before the start of the treatment, at the end of the first and second week of treatment, and then monthly until the end of the 24-month period. SAMe administration showed good clinical effectiveness and was well tolerated. The improvement of the clinical symptoms during therapy with SAMe was already evident after the first weeks of treatment and continued up to the end of the 24th month. Non-specific side effects occurred in 20 patients, but in no case did therapy have to be discontinued. Most side effects disappeared during the course of therapy. Moreover, during the last six months of treatment, no adverse effect was recorded. Detailed laboratory tests carried out at the start and after six, 12, 18, and 24 months of treatment showed no pathologic changes. SAMe administration also improved the depressive feelings often associated with osteoarthritis.
http://www.sciencedirect.com/science...638dd29eea3da6

BMC Musculoskelet Disord. 2004 Feb 26;5:6.
S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial.

BACKGROUND: S-adenosylmethionine (SAMe) is a dietary supplement used in the management of osteoarthritis (OA) symptoms. Studies evaluating SAMe in the management of OA have been limited to Non Steroidal Anti-inflammatory Drugs (NSAIDs) for comparison. The present study compares the effectiveness of SAMe to a cyclooxygenase-2 (COX-2) inhibitor (celecoxib) for pain control, functional improvement and to decrease side effects in people with osteoarthritis of the knee. METHODS: A randomized double-blind cross-over study, comparing SAMe (1200 mg) with celecoxib (Celebrex 200 mg) for 16 weeks to reduce pain associated with OA of the knee. Sixty-one adults diagnosed with OA of the knee were enrolled and 56 completed the study. Subjects were tested for pain, functional health, mood status, isometric joint function tests, and side effects. RESULTS: On the first month of Phase 1, celecoxib showed significantly more reduction in pain than SAMe (p = 0.024). By the second month of Phase 1, there was no significant difference between both groups (p < 0.01). The duration of treatment and the interaction of duration with type of treatment were statistically significant (ps < or = 0.029). On most functional health measures both groups showed a notable improvement from baseline, however no significant difference between SAMe and celecoxib was observed. Isometric joint function tests appeared to be steadily improving over the entire study period regardless of treatment. CONCLUSION: SAMe has a slower onset of action but is as effective as celecoxib in the management of symptoms of knee osteoarthritis. Longer studies are needed to evaluate the long-term effectiveness of SAMe and the optimal dose to be used. http://www.ncbi.nlm.nih.gov/pubmed/1...gdbfrom=pubmed

[Hypertrophik]

Thanks !

[Hypertrophik]

Exploring the Mechanisms behind S-Adenosylmethionine (SAMe) in the Treatment of Osteoarthritis.

Hosea Blewett HJ.

Crit Rev Food Sci Nutr. 2008 May;48(5):458-63.


Department of Agriculture, Food & Nutritional Sciences University of Alberta, Edmonton, AB.

Osteoarthritis is a chronic joint disease characterized by pain and immobility due to a gradual loss of cartilage. Current treatments are palliative; there is no cure. With a growing interest in alternative therapies, due in part to safety issues regarding pharmacological treatments like Celebrex, safe dietary compounds that help the body regenerate cartilage tissue are of great clinical importance. The dietary supplement S-adenosylmethionine (SAMe) shows such potential. Clinical trials have shown reduced pain and stiffness while in vitro and animal studies have shown SAMe can stimulate the production of cartilage which is critical in reversing the disease process. The author examines many potential mechanisms of action including: reduction of inflammatory mediators; increasing levels of glutathione; direct or indirect signaling of cartilage synthesis or survival; maintenance of DNA methylation. Research into the mechanisms of supplemental SAMe in osteoarthritis is necessary to evaluate the clinical effectiveness and safety of this dietary supplement.

[NO HYPE]

Thanks. I found that abstract as well.

[hullcrush]

It is in my experience that SAM increases fluid production systemically, thus increasing synovial fluid production.

The mechanisms they've listed don't really affect that. Acetylcholine and estrogen may be manipulated... don't know for sure.

Overall, a great drug, just not for me. Wish it didn't up fluid production and suppress appetite.
Doesn't release cortisol like 5-htp and alter CYP like SJW. Guess I'll hold out for wellbutrin.