S-adenosylmethionine: SAM-e also called AdoMet. There were 4100 articles mentioning SAM on PubMed on 2/3/01. Methionine adenosyltransferase (MAT) is a critical cellular enzyme which catalyses the formation of S-adenosylmethionine (SAM), the principal methyl donor. In mammals, two different genes, MAT1A and MAT2A, encode liver-specific and non-liver-specific MATs, respectively. SAM level increases during T-lymphocyte activation and is required for proliferation. USC Med School. Biochem J 2001 Jan 1;353(Pt 1):163-168. It is a NH2 donor in biotin synthesis. Biotin synthase belongs to the family of AdoMet-dependent enzymes that reductively cleave AdoMet into a deoxyadenosyl radical, and it is responsible for the homolytic cleavage of C-H bonds. A first radical formed on dethiobiotin is trapped by the sulfur donor, which was found to be the iron-sulfur (Fe-S) center contained in the enzyme, and cyclization follows in a second step. Vitam Horm 2001;61:51-101. Folate is essential for efficient DNA synthesis and repair. Moreover, folate can affect cellular S-adenosylmethionine levels, which regulate DNA methylation and control gene expression. Altered homocysteine metabolism associated with peripheral arterial occlusive disease (PAOD) may lead to impairment of vital methylation reactions through accumulation of S-adenosylhomocysteine (AdoHcy) as well as through alteration of the ratio S-adenosylmethionine (AdoMet)/AdoHcy. Since the ratio of AdoMet/AdoHcy is closely linked with the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients. Atherosclerosis 2001 Jan;154(1):147-54

SAMe Protect Chicken Joints: German study found SAM injected in joints subjected to artificial damage, SAM significantly reduced the intensity of degenerative processes compared to the placebo (saline) treated joints. Arzneimittelforschung 1990 Sep;40(9):1017-21

SAMe Helps Rabbit Joints: Argentine DB study 24 rabbits with induced arthropathy Rx 12 weeks placebo or two diff dosages of SAM. Thickness and cell density of the lesioned cartilages were significantly greater in both groups treated with SAMe than the group control (p less than 0.001). Much more healing and more proteoglycans in SAM rx rabbits. Rev Clin Esp 1990 Jun;187(2):74-8

SAMe as Good as Naproxen: Zagreb DB 6 wk of 20 pt with SAM 400 BID found no difference with both groups improving on all of a wide range of measures, e.g. pain, swelling, walking: Int J Clin Pharmacol Ther Toxicol 1989 Jul;27(7):329-33

SAMe Good in Long-Term Open Study: U Mainz study of 108 pt for 24 months with 600mg/d for 3 weeks then 400mg/d. No one had to d/c meds and side-effects mild and gradually disappeared. Benefit noted in first weeks. Also less depression. : Am J Med 1987 Nov 20;83(5A):89-94

SAMe Open Trial Successful: 8 wk German Phase IV open trial of 20,640 patients with OA found 71% with good or very good results with 87% with good or very good tolerance. Am J Med 1987 Nov 20;83(5A):84-8

SAMe as Good as Ibuprofen: DB 36 pt German 4 week study 1200mg SAM vs. 1200mg ibuprofen found no difference for OA in pain, stiffness, swelling or ROM. Am J Med 1987 Nov 20;83(5A):81-3. Italian study of 150 pt for knee & hip OA for 30 day found SAM slightly better with fewer s-e. Int J Clin Pharmacol Res 1985;5(1):39-49. SAM studies in Italy at least as early as 1975.

SAMe as Good as Indomethacin: DB 36 pt German 4 wk study 1200mg SAM vs 150mg indomethacin found no diff for OA except mild nausea in some with SAM and much worse s-e with indomethacin. Am J Med 1987 Nov 20;83(5A):78-80

SAMe as Good as Piroxicam: DB 45 pt Argentine 84-day study 1200mg SAM vs 20mg piroxicam found equal tho SAM pts maintained improvement better at end of study. Pain benefited by day 28 and other parameters by day 56, e.g. AM stiffness, walking, ROM. Am J Med 1987 Nov 20;83(5A):72-7

SAMe as Good as Naproxen: 734 hip or knee OA pt, DB Italian study 1200mg SAM vs 750 naproxen found both improved equally with fewer s-e with SAM and no more than with placebo. Am J Med 1987 Nov 20;83(5A):66-71. Experimental investigations suggest that the administration of SAMe exerts analgesic and antiphlogistic activities and stimulates the synthesis of proteoglycans by articular chondrocytes with minimal or absent side effects on the gastrointestinal tract and other organs.

SAMe as Good as Celecoxib: In a 16-week, 61-patient DB cross-over study comparing SAMe (1200 mg) with celecoxib (Celebrex 200 mg) for 16 weeks for OA of the knee, celecoxib reduced pain faster in the first month, but there was no difference after that. S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. [ISRCTN36233495]. Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW. BMC Musculoskelet Disord. 2004 Feb 26;5(1):6

SAMe Increases Cartilage Signal: Univ.-Klinikum Steglitz der FU Berlin. This report deals with a prospective study of 21 patients with finger osteoarthritis treated over a period of three months with either Ademetionin (therapy group: 14/21) or without (control group: 7/21). MR-Imaging was carried out before and after treatment using spin-echo and 3D-Flash sequences. Morphological parameters and signal intensity changes of the hyaline cartilage were evaluated. The increase of the cartilage signal intensity was significant in the therapy group, this can be interpreted as an structural improvement. Also a decrease of the cartilage signal intensity with age was found. The morphological parameters showed no significant changes in the therapy and control groups. : Aktuelle Radiol 1995 Jan;5(1):36-40

SAMe Some Help in DB with Arthritis: S-adenosylmethionine (SAM), IV 400 mg for 5 days, followed by oral, 200 mg thrice daily for 23 days, vs placebo in 81 with symptomatic knee osteoarthritis. 7-day washout. patients had milder OA, the baseline characteristics of the treatment groups were well matched, and the SAM treated group showed significantly greater reduction in overall pain and rest pain (p < 0.05) than the placebo treated group. At the other site, the patients had more severe OA, randomization yielded markedly different treatment groups, and the response to treatment did not differ between groups. Onset of SAM effect was seen as early as 14 days after the start of treatment. CONCLUSION. SAM may be an effective treatment for some patients with symptomatic knee OA, and merits further study. Intravenous loading before oral maintenance therapy may be advantageous. Bradley, Indiana Univ. : J Rheumatol 1994 May;21(5):905-11

SAM-e Side-Effects: Consumers report cases of temporary memory dysfunction, diarrhea, loss of energy, migraines, heart palpitations, and not mixing well with alprazolam.