SAMe Abstracts 1

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S-Adenosyl-L-methionine (SAMe): from the bench to the bedside--molecular basis of a pleiotrophic molecule

         (Bottiglieri 2002) Download

S-Adenosyl-L-methionine (SAMe), a metabolite present in all living cells, plays a central role in cellular biochemistry as a precursor to methylation, aminopropylation, and transsulfuration pathways. As such, SAMe has been studied extensively since its chemical structure was first described in 1952. Decades of research on the biochemical and molecular roles of SAMe in cellular metabolism have provided an extensive foundation for its use in clinical studies, including those on depression, dementia, vacuolar myelopathy, liver disease, and osteoarthritis. This article provides an overview of the biochemical, molecular, and therapeutic effects of this pleiotrophic molecule.

Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies

         (Delle Chiaie, Pancheri et al. 2002) Download

BACKGROUND: S-Adenosyl-L-methionine (SAMe), a natural compound, is the most important methyl donor in the central nervous system. In several clinical trials, SAMe showed antidepressant activity. OBJECTIVE: Two multicenter studies were conducted in patients with a diagnosis of major depressive episode [baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D) >or=18] to confirm the efficacy and safety of SAMe in the treatment of major depression. In the first study (MC3), 1600 mg SAMe/d was given orally; whereas, in the second study (MC4), 400 mg SAMe/d was given intramuscularly. In both studies, the effects of SAMe were compared with those of 150 mg imipramine/d given orally in a double-blind design. DESIGN: In MC3, 143 patients received oral SAMe and 138 patients received imipramine for 6 wk. In MC4, 147 patients received SAMe intramuscularly and 148 patients received imipramine for 4 wk. In both studies the 2 main efficacy measures were the final HAM-D score and the percentage of responders to Clinical Global Impression at the endpoint. Secondary efficacy measures were the endpoint Montgomery-Asberg Depression Rating Scale scores and the percentage of responders, responders being those patients showing a decrease in HAM-D score of >or=50% from baseline. RESULTS: In both studies, the results of SAMe and imipramine treatment did not differ significantly for any efficacy measure. However, significantly fewer adverse events were observed in the patients treated with SAMe. CONCLUSIONS: The antidepressive efficacy of 1600 mg SAMe/d orally and 400 mg SAMe/d intramuscularly is comparable with that of 150 mg imipramine/d orally, but SAMe is significantly better tolerated.

The production of hydrogen sulfide is regulated by testosterone and S-adenosyl-L-methionine in mouse brain

         (Eto and Kimura 2002) Download

Hydrogen sulfide (H2S) is endogenously produced in the brain from L-cysteine by the enzyme cystathionine beta-synthase (CBS) and functions as a neuromodulator in the brain. H2S selectively enhances NMDA receptor-mediated responses and alters hippocampal long-term potentiation (LTP). The production of H2S is regulated by Ca2+/calmodulin-mediated pathways and is enhanced in response to neuronal excitation. In addition to this fast regulation, we describe here a slower form of the regulation of H2S production by testosterone and S-adenosyl-L-methionine (SAM), a CBS activator. Endogenous H2S in the mouse brain increases after birth, reaches a maximum level at 8 weeks and then decreases. Female brain contains less H2S than male brain at each age. A single administration of testosterone to female mice increases the endogenous H2S and SAM, which reach levels similar to those of male mice. In contrast, castration of male mice decreases the levels of testosterone, SAM and H2S in the brain. Administration of SAM once a day for 3 days increases the brain H2S without significantly changing the testosterone level. These observations suggest that testosterone can regulate the brain H2S level via changing the level of SAM.

         (Eto and Kimura 2005) Download

Since I could not reproduce the data that testosterone increases the levels of H2S in the female brain shown in Fig. 2 of the above paper, I would like to retract the paper.


Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence

         (Mischoulon and Fava 2002) Download

Major depression remains difficult to treat, despite the wide array of registered antidepressants available. In recent years there has been a surge in the popularity of natural or alternative medications. Despite this growing popularity, there is limited evidence for the effectiveness of many of these natural treatments. S-adenosyl-L-methionine (SAMe) is one of the better studied of the natural remedies. SAMe is a methyl donor and is involved in the synthesis of various neurotransmitters in the brain. Derived from the amino acid L-methionine through a metabolic pathway called the one-carbon cycle, SAMe has been postulated to have antidepressant properties. A small number of clinical trials with parenteral or oral SAMe have shown that, at doses of 200-1600 mg/d, SAMe is superior to placebo and is as effective as tricyclic antidepressants in alleviating depression, although some individuals may require higher doses. SAMe may have a faster onset of action than do conventional antidepressants and may potentiate the effect of tricyclic antidepressants. SAMe may also protect against the deleterious effects of Alzheimer disease. SAMe is well tolerated and relatively free of adverse effects, although some cases of mania have been reported in bipolar patients. Overall, SAMe appears to be safe and effective in the treatment of depression, but more research is needed to determine optimal doses. Head-to-head comparisons with newer antidepressants should help to clarify SAMe's place in the psychopharmacologic armamentarium.

Evidence for S-adenosyl-L-methionine (SAM-e) for the treatment of major depressive disorder

         (Papakostas 2009) Download

Despite the increasingly large array of antidepressants available to treat major depressive disorder, patients continue to experience relatively modest response and remission rates. In addition, patients may experience adverse side effects from pharmacotherapy that not only hinder treatment compliance and adherence but, in some cases, may also contribute to increased disability, patient suffering, morbidity, and mortality. In order to enhance treatment efficacy and tolerability, patients and clinicians have become increasingly interested in nonpharmaceutical supplements for treating depression. One of the best-studied of these supplements is S-adenosyl-L-methionine (SAM-e), a naturally occurring molecule present in all living cells and a major methyl group donor in the human body. Controlled trials have found SAM-e to be more efficacious than placebo and equal in efficacy to the tricyclic antidepressants for treating major depressive disorder (MDD) when administered parenterally (either intravenously or intramuscularly). Less evidence supports the use of oral SAM-e, although some trials have demonstrated its efficacy as well. In addition, there is a paucity of evidence examining whether oral forms of SAM-e can be safe, well tolerated, and efficacious when used as adjunctive treatment for antidepressant nonresponders with MDD. Although preliminary data suggest SAM-e may be useful as an adjunctive therapy to antidepressants, controlled studies are needed to confirm or refute these preliminary findings.

S-Adenosyl-L-methionine: beyond the universal methyl group donor

         (Roje 2006) Download

S-Adenosyl-l-methionine (AdoMet or SAM) is a substrate in numerous enzyme-catalyzed reactions. It not only provides methyl groups in many biological methylations, but also acts as the precursor in the biosynthesis of the polyamines spermidine and spermine, of the metal ion chelating compounds nicotianamine and phytosiderophores, and of the gaseous plant hormone ethylene. AdoMet is also the source of catalytic 5'-deoxyadenosyl radicals, produced as reaction intermediates by the superfamily of radical AdoMet enzymes. This review aims to summarize the present knowledge of catalytic roles of AdoMet in plant metabolism.


References

Bottiglieri, T. (2002). "S-Adenosyl-L-methionine (SAMe): from the bench to the bedside--molecular basis of a pleiotrophic molecule." Am J Clin Nutr 76(5): 1151S-7S. [PMID: 12418493]

Delle Chiaie, R., P. Pancheri, et al. (2002). "Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies." Am J Clin Nutr 76(5): 1172S-6S. [PMID: 12418499]

Eto, K. and H. Kimura (2002). "The production of hydrogen sulfide is regulated by testosterone and S-adenosyl-L-methionine in mouse brain." J Neurochem 83(1): 80-6. [PMID: 12358731]

Eto, K. and H. Kimura (2005). "The production of hydrogen sulfide is regulated by testosterone and S-adenosyl-L-methionine in mouse brain." J Neurochem 93(6): 1633. [PMID: 15935080]

Mischoulon, D. and M. Fava (2002). "Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence." Am J Clin Nutr 76(5): 1158S-61S. [PMID: 12420702]

Papakostas, G. I. (2009). "Evidence for S-adenosyl-L-methionine (SAM-e) for the treatment of major depressive disorder." J Clin Psychiatry 70 Suppl 5: 18-22. [PMID: 19909689]

Roje, S. (2006). "S-Adenosyl-L-methionine: beyond the universal methyl group donor." Phytochemistry 67(15): 1686-98. [PMID: 16766004]