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Research on SAMe.... Darrell Miller 10/26/05

Research on SAMe....

Date: October 26, 2005 12:49 PM
Author: Darrell Miller (
Subject: Research on SAMe....

Two groups of researchers have conducted analyses of trials that utilized SAM-e for mood enhancement. One meta-analysis was published in 1994. The researchers analyzed the efficacy of SAM-e in oral or injection forms based on published trials dated between 1973 and 1992. The authors concluded that there was a significant improvement of 17 to 38% seen in trials of SAM-e compared to placebo response. They state that the efficacy of SAM-e was superior to placebo and its administration caused few side effects.5 A second review was published in 2002. The authors analyzed studies in which SAM-e doses ranged from 200 to 1600 mg daily. They also found a significant effect of SAM-e in comparison to placebo, with an evident rapid onset of effect at enhancing mood.6

Promotes Joint Comfort and Mobiliy*ty*

As a sulfur donor to connective tissue, SAM-e plays a major role in protecting the integrity of cartilage tissue. An in vitro trial assessed the actions of SAM-e in cultured human articular chondrocytes. At a concentration of 10 micrograms/ml, proteoglycan synthesis and sulfate residue incorporation in chondrocytes was shown to be 60% higher than control levels. Based on these results, it was shown that SAM-e has a positive influence on the growth and health of cartilaginous connective tissue.7

In a double-blind trial with 734 individuals with compromised joint health. SAM-e given orally at a dose of 1200 mg daily for 30 days was shown to significantly promote joint comfort compared to placebo, with a high level of tolerability and low incidence of side effects. The researchers concluded that SAM-e is a highly effective supplement for enhancing joint comfort.8

Another trial evaluated the response of individuals experiencing discomfort in the joints to a regimen of 1200 mg SAM-e for 1 week followed by 800 mg for the second week, and then 400 mg for weeks 3 through 8. This open trial of 20, 641 people showed a strong ability of SAM-e to enhance feelings of comfort within the joints. The treatment was rated as “very good” or “good” in 71% of the participants, with an additional 21% rating the treatment effect as “moderate”.9

In a long-term trial lasting 24 months, SAM-e was given to 108 participants with compromised joint function. Individuals were given 600 mg orally per day for the first two weeks followed by 400 mg daily for the remainder of the trial. Individuals experienced significant enhancements in joint comfort, with dramatic improvements noted after 2-4 weeks of treatment. Improvements continued to 6 months and beyond.10

In addition to the above studies, a review was conducted in 1987 to assess the results of SAM-e supplementation in clinical trials for enhancing joint Mobiliy*ty and function. Over 22,000 individuals had participated in the clinical trials that were the subject of this review. The author concluded from his analysis that SAM-e was shown to be highly efficacious, rivaling or surpassing the effectiveness of other treatments, and also possessing a high level of safety.11 Because of this, SAM-e may be the treatment of choice for enhancing joint function.

Supports Liver Health and Detoxification*

SAM-e supplementation can have profound benefits on liver function. These benefits center around its function as the major methyl donor in the liver, as well as its lipotropic activity. SAM-e also enhances the production of the antioxidant glutathione.

A number of trials have been conducted showing the ability of SAM-e to support liver detoxification functions and enhance liver health in individuals susceptible to toxin-induced liver compromise. SAM-e has the ability to normalize liver function by increasing the activity of enzymes needed to upregulate liver detoxification. These effects are comprehensive and rapid. Dosages used in these studies range from 600 mg to 1600 mg daily for 2 months to two years.12,13,14 In these trials, significant benefits of SAM-e supplementation were seen over placebo.


SAM-e has an excellent safety profile and is considered well-suited for long term use based on multiple clinical trials. Individuals diagnosed with manic depression should avoid SAM-e supplementation, as it may aggravate the manic phase *This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Scientific References

1. Agnoli A, Andreoli V, Casacchia M, Cerbo R. Effect of s-adenosyl-l-methionine (SAMe) upon depressive symptoms. J Psychiatr Res. 1976;13(1):43-54.

2. De Leo D. S-adenosylmethionine as an antidepressant. Curr Ther Research. 1987;41(6):865-70.

3. Kagan BL, Sultzer DL, Rosenlicht N,Gerner RH. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 1990 May;147(5):591-5.

4.Salmaggi P,Bressa GM,Nicchia G,Coniglio M,La Greca P,Le Grazie C.Doubleblind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom. 1993;59(1):34-40.

5. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: metaanalysis of clinical studies. Acta Neurol Scand Suppl. 1994;154:7-14. 6.Mischoulon D, Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr. 2002 Nov;76(5):1158S-61S.

7. Harmand MF, Vilamitjana J,Maloche E, Duphil R, Ducassou D. Effects of Sadenosylmethionine on human articular chondrocyte differentiation. An in vitro study. Am J Med. 1987 Nov 20;83(5A):48-54.

8. Caruso I, . Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med. 1987 Nov 20;83(5A):66-71.

9. Berger R, Nowak H. A new medical approach to the treatment of osteoarthritis. Report of an open phase IV study with ademetionine (Gumbaral). Am J Med. 1987 Nov 20;83(5A):84-8.

10. Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med. 1987 Nov 20;83(5A):89-94.

11. di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med. 1987 Nov 20;83(5A):60-5.

12. Frezza M, et al. S-adenosylmethionine counteracts oral contraceptive hepatotoxicity in women. Am J Med Sci. 1987; 293(4):234-238.

13. Frezza M, Surrenti C, Manzillo G, Fiaccadori F, Bortolini M, Di Padova C. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Gastroenterology. 1990 Jul;99(1):211-5.

14. Mato JM, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999 Jun;30(6):1081-9.

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