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Research & Case History Support
S-adenosylmethionine modulates endotoxin-stimulated interleukin-10 production in monocytes.
Song, Zhenyuan; Barve, Shirish; Chen, Theresa; Hill, Daniell; McClain, Craig; Nelson, Wendy; Uriarte, Sylvia
JOURNAL NAME- FASEB Journal
VOLUME 17
NO 4-5
March 2003 2003
PP Abstract No. 714.7.
DOCUMENT TYPE- Meeting
ISSN- 0892-6638
SPONSOR- FASEB
CONFERENCE DATE- April 11-15, 2003
CONFERENCE TITLE- FASEB Meeting on Experimental Biology: Translating the Genome
LANGUAGE- ENGLISH
Interleukin-10 (IL-10) is produced by a large variety of cells including monocytes, macrophages, B and T lymphocytes, as well as natural killer (NK) cells and is an important suppressor for immunoproliferative and inflammatory responses. Decreased monocyte synthesis of IL-10 is well documented in alcoholic cirrhosis. In addition, IL-10 exerts antifibrotic effects in the liver. Intracellular deficiency of S-adenosylmethionine (AdoMet) is a hallmark of toxin-induced liver injury. Although the administration of exogenous AdoMet attenuates this injury, the mechanisms of its actions are not fully established. This study was performed to investigate the effect of exogenous AdoMet on IL-10 production in LPS-stimulated RAW 264.7 cells, a murine macrophage cell line. Our results demonstrated that exogenous AdoMet administration enhanced both protein production and gene _expression of IL-10 in RAW 264.7 cells. Ethionine, an inhibitor for methionine adenosyltransferases (MAT), inhibited LPS-stimulated IL-10 at both the protein and mRNA level. Exogenous AdoMet increased the intracellular cyclic AMP (cAMP) concentration as early as 3 hours and continued for 24 hours after AdoMet treatment, but the inhibitors for both adenyl cyclase and protein kinase A (PKA) did not significantly affect IL-10 production. From these results, we concluded that AdoMet administration might exert its anti-inflammatory and hepatoprotective effects, at least in part, by enhancing LPS stimulated IL-10 production.
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Modulation of endotoxin stimulated interleukin-6 production in monocytes and Kupffer cells by S-adenosylmethionine (SAMe)
EMB 04-51 2004512392 NDN- 012-2555-5007-6
Song, Z.; Chen, T.; Deaciuc, I. V.; Uriarte, S.; Hill, D.; Barve, S.; McClain, C. J.
JOURNAL NAME- Cytokine
28/6 (214-223)
21 DEC 2004
DOCUMENT TYPE- Journal
COPYRIGHT- Copyright 2005 Elsevier B.V., All rights reserved.
ISSN- 1043-4666
PUBLICATION YEAR- 2004
Interleukin-6 (IL-6) is a multifunctional cytokine having primarily anti-apoptotic and anti-inflammatory effects. Recent reports have documented that IL-6 plays a key role in liver regeneration. Intracellular deficiency of S-adenosylmethionine (SAMe) is a hallmark of toxin-induced liver injury. Although the administration of exogenous SAMe attenuates liver injury, its mechanisms of action are not fully understood. Here we investigated the effects of exogenous SAMe on IL-6 production in monocytes and Kupffer cells. RAW 264.7 cells, a murine monocyte cell line, and isolated rat Kupffer cells were stimulated with lipopolysaccharide (LPS) in the absence or presence of exogenous SAMe. IL-6 production was assayed by ELISA and intracellular SAMe concentrations were measured by HPLC. We have found that exogenous SAMe administration enhanced both IL-6 protein production and gene _expression in LPS-stimulated monocytes and Kupffer cells. Cycloleucine (CL), an inhibitor for extrahepatic methionine adenosyltransferases (MAT), inhibited LPS-stimulated IL-6 production. The enhancement of LPS-stimulated IL-6 production by SAMe was inhibited by ZM241385, a specific antagonist of adenosine (A<inf>2</inf>) receptor. Our results demonstrate that SAMe administration may exert its anti-inflammatory and hepatoprotective effects, at least in part, by enhancing LPS-stimulated IL-6 production. (copyright) 2004 Elsevier Ltd. All rights reserved.
S-adenosylmethionine (AdoMet) modulates endotoxin stimulated interleukin-10 production in monocytes
Song, Z.; Barve, S.; Chen, T.; Nelson, W.; Uriarte, S.; Hill, D.; McClain, C.
JOURNAL NAME- American Journal of Physiology - Gastrointestinal and Liver Physiology
284/6 47-6 (G949-G955)
DOCUMENT TYPE- Journal
COPYRIGHT- Copyright 2004 Elsevier B.V., All rights reserved.
ISSN- 0193-1857
PUBLICATION YEAR- 2003
IL-10 is produced by a large variety of cells including monocytes, macrophages, B and T lymphocytes, as well as natural killer cells and is an important suppressor for both immunoproliferative and inflammatory responses. IL-10 exerts antifibrotic effects in the liver, and decreased monocyte synthesis of IL-10 is well documented in alcoholic cirrhosis. Intracellular deficiency of S-adenosylmethionine (AdoMet) is a hallmark of toxin-induced liver injury. Although the administration of exogenous AdoMet attenuates this injury, the mechanisms of its actions are not fully established. This study was performed to investigate the effect of exogenous AdoMet on IL-10 production in LPS-stimulated RAW 264.7 cells, a murine macrophage cell line. Our results demonstrated that exogenous AdoMet administration enhanced both protein production and gene _expression of IL-10 in RAW 264.7 cells. Ethionine, an inhibitor for methionine adenosyltransferases, inhibited LPSstimulated IL-10 both at the protein and mRNA levels. Exogenous AdoMet increased the intracellular cAMP concentration as early as 3 h and continued for 24 h after AdoMet treatment; however, the inhibitors for both adenylyl cyclase and PKA did not significantly affect IL-10 production. On the basis of these results, we conclude that AdoMet administration may exert its anti-inflammatory and hepatoprotective effects, at least in part, by enhancing LPS-stimulated IL-10 production.
Placebo-controlled trials of antioxidant therapy including S-adenosylmethionine in patients with recurrent nongallstone pancreatitis
Bilton, D.; Schofield, D.; Mei, G.; Kay, P. M.; Bottiglieri, T.; Braganza, J. M.
JOURNAL NAME- Drug Investigation
8/1 (10-20)
DOCUMENT TYPE- Journal
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0114-2402
PUBLICATION YEAR- 1994
Having shown in a 20-week placebo-controlled double-blind crossover trial that 'global' antioxidant supplementation - including selenium, (beta)-carotene, vitamin C (ascorbic acid), vitamin E (tocopherol) and methionine - curbs symptoms while correcting oxidative stress in patients with recurrent nongallstone pancreatitis, we have investigated through two further trials the relative importance of methionine versus that of the other antioxidants in effecting this good outcome. 30 consecutive patients were entered into the second study in which therapeutic intervention involved only the active metabolite of methionine, S-adenosylmethionine (SAMe), 2.4g per day in divided doses. Blood analysis showed that subnormal baseline levels of selenium, (beta)-carotene and vitamins E and C were unchanged throughout and that drug treatment resulted in supranormal levels of SAMe in plasma. SAMe proved to be ineffective clinically as judged by attack rate and background pain , as well as biochemically as gauged by the percentages of oxidatively altered vitamin C and linoleic acid. The coadministration of selenium and (beta)-carotene with SAMe was tested in the third study. This was abandoned when 3 patients had a clearcut attack of pancreatitis while on subsequent 'open' treatment. Analysis of clinical and biochemical information from 14 patients who had completed the 20-week trial confirmed the inefficacy of the combination, although active treatment normalised serum selenium and (beta)-carotene concentrations while SAMe levels were again pushed into the supranormal range. The results show that SAMe on its own, or with additional selenium and (beta)-carotene, is ineffective in patients with recurrent nongallstone pancreatitis. By a process of elimination with reference to biochemical measurements during the 3 trials, and considering experimental evidence of the importance of methionine for pancreatic integrity, we cautiously suggest that an effective antioxidant prescription should include SAMe (or methionine) as well as vitamin C, with additional compounds as indicated by blood measurements.
A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis
Konig, B.
JOURNAL NAME- American Journal of Medicine
83/5 A (89-94)
DOCUMENT TYPE- Journal
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0002-9343
PUBLICATION YEAR- 1987
CODEN- AJMEA
AUTHOR ADDRESS- Institute of General Medicine, University of Mainz, Mainz
COUNTRY OF AUTHOR- Germany
PUBLICATION COUNTRY- United States
LANGUAGE- ENGLISH
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.
REGISTRY NUMBER- 29908-03-0; 485-80-3;
CAS SUBSTANCE NAME- s adenosylmethionine
S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies
EMB 88-01 1988116931 NDN- 012-1864-6239-1
Di, Padova C.
JOURNAL NAME- American Journal of Medicine
83/5 A (60-65)
DOCUMENT TYPE- Journal
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0002-9343
PUBLICATION YEAR- 1987
S-adenosylmethionine (SAMe), a physiologic compound that ranks with ATP as a pivotal molecule in biology, offers physicians an innovative approach to the treatment of osteoarthritis. 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. The results of extensive clinical trials, which have enrolled about 22,000 patients with osteoarthritis in the last five years, support the clinical effectiveness and the optimal tolerability of SAMe administration. The intensity of therapeutic activity of SAMe against osteoarthritis is similar to that exerted by nonsteroidal anti-inflammatory drugs, but its tolerability is higher. Based on these findings, SAMe is proposed as the prototype of a new class of safe drugs for the treatment of osteoarthritis.
Double blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis
Muller-Fassbender, H.
ABBREVIATED JOURNAL TITLE- Am. J. Med.
VOLUME 83
NO Nov 20 Suppl
1987
PP 81-83
A randomized double blind trial in 36 patients with osteoarthritis comparing patients receiving a daily oral dose of 1200 mg of ademetionine ( S-adenosylmethionine ) or 1200 mg ibuprofen for 4 wk is described. The clinical parameters improved to the same extent for each treatment group. Both treatments were well tolerated and no patient from either group withdrew from the study.
Double blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis
Vetter, G.
ABBREVIATED JOURNAL TITLE- Am. J. Med.
VOLUME 83
NO Nov 20 Suppl
1987
PP 78-80
A randomized double blind study comparing oral daily doses of 1200 mg ademetionine ( S-adenosylmethionine ; I) and indomethacin (150 mg) administered over a 4 wk period in 36 patients with osteoarthritis is described. Both drugs significantly improved the total score of all clinical findings as compared with pretreatment values. Two patients receiving I reported slight nausea, whereas adverse effects developed in 7 patients receiving II.
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Double blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis
Maccagno, A. Di; Giorgio, E. E.; Caston, O. L.; Sagasta, C. L.
ABBREVIATED JOURNAL TITLE- Am. J. Med.
VOLUME 83
NO Nov 20 Suppl
1987
PP 72-77
A double blind, randomized, 84-day controlled clinical trial comparing oral ademetionine ( S-adenosylmethionine ; I) (1200 mg per day) with oral piroxicam (II) (20 mg per day) in the management of unilateral knee osteoarthritis in 45 patients is described. Both drugs proved effective in inducing a significant improvement in the total pain score and other clinical parameters. Patients treated with I maintained clinical improvement achieved at the end of treatment longer than did patients receiving II.
ABSTRACTOR NAME- Victor Origoni
Ademetionine
Evaluation of S-adenosylmethionine in primary fibromyalgia: double blind crossover study
Tavoni, A.; Vitali, C.; Bombardieri, S.; Pasero, G.
ABBREVIATED JOURNAL TITLE- Am. J. Med.
VOLUME 83
NO Nov 20 Suppl
1987
PP 107-110
A double blind, placebo controlled crossover trial is described in 17 patients with primary fibromyalgia treated with intramuscular ademetionine ( S-adenosylmethionine ) (200 mg per day for 21 days). The drug caused a significant decrease in pain evaluated as the number of trigger points plus painful anatomic sites. Conversely, placebo treatment caused no significant changes in these parameters.
Double blind multicenter study of the activity of S-adenosylmethionine in hip and knee osteoarthritis
Glorioso, S.; Todesco, S.; Mazzi, A.; Marcolongo, R.; Cucinotta, D. et al
JOURNAL NAME- International Journal of Clinical Pharmacology Research
VOLUME 5
NO 1
1985
PP 39-49
21 REFERENCE
ISSN- 0251-1649
The efficacy and tolerance of oral S-adenosylmethionine (ademetionine I) were compared with ibuprofen (II) both given in a 0.4 g dose 3 times daily for 30 days to 150 patients (aged 40-75 yr) with hip and/or knee osteoarthritis. Oral I exhibited a slightly more marked activity than the reference drug in the management of the various painful manifestations of the joint disease. Minor side effects developed in 5 patients in the I group, and 16 patients in the II group and therapy did not have to be withdrawn in any case. No changes were observed in the routine laboratory tests.
Double-blind multicenter study of the activity of S-adenosyl-methionine in hip and knee osteoarthritis
Marcolongo, R.; Giordano, N.; Colombo, B.; Cherie-Ligniere, G.; Cucinotta, D. et al
JOURNAL NAME- Current Therapeutic Research (USA)
VOLUME 37
NO Jan
1985
PP 82-94
34 REFERENCE
ISSN- 0011-393X
The effectiveness and tolerance of S-adenosyl-L-methionine ( S-adenosylmethionine ; ademetionine; I) versus ibuprofen (II), both given as an oral dose of 0.4 g 3 times daily for 30 days, were compared in 150 patients, aged 40-75 yr, with hip and/or knee osteoarthritis. Therapy with I exhibited a slightly more marked activity than II in the management of the various painful manifestations of the joint disease. Minor side effects developed in 5 patients of I group, and in 16 patients taking II but no one discontinued treatment due to adverse reactions.
S-Adenosylmethionine protects against acetaminophen-induced hepatotoxicity in mice.
Song, Zhenyuan; McClain, Craig J; Chen, Theresa
JOURNAL NAME- Pharmacology
VOLUME 71
NO 4
2004 Aug
PP 199-208
DOCUMENT TYPE- Journal Article
JOURNAL CODE- 0152016
JOURNAL SUBSET- MEDJSIM
ISSN- 0031-7012
An overdose of acetaminophen (APAP) is the most frequent cause of fulminant liver failure in the
S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. .ISRCTN36233495a.
Najm, Wadie I; Reinsch, Sibylle; Hoehler, Fred; Tobis, Jerome S; Harvey, Phillip W
JOURNAL NAME- BMC Musculoskelet Disord
VOLUME 5
NO 1
2004 Feb 26
PP 6
DOCUMENT TYPE- Clinical Trial; Journal Article; Randomized Controlled Trial
JOURNAL CODE- 100968565
JOURNAL SUBSET- MEDJSIM
ISSN- 1471-2474
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.
Meta-analysis of the efficacy of adenosylmethionine and oxaceprol in the treatment of osteoarthritis
Witte, S; Lasek, R; Victor, N
JOURNAL NAME- Orthopade
VOLUME 31
NO 11
2002 Nov
PP 1058-65
DOCUMENT TYPE- Journal Article; Meta-Analysis
JOURNAL CODE- 0331266
JOURNAL SUBSET- MEDJSIM
ISSN- 0085-4530
The aim of this meta-analysis based on the literature was to gather all evidence of randomized clinical trials to assess the efficacy of adenosylmethionine (SAM) and oxaceprol in the treatment of osteoarthritis.Findings in MEDLINE and EMBASE were added to publications catalogued by the AkdA and a reference search.The meta-analysis was based mostly on pain scores but also on pain and function scores. We used the fixed effects and the random effects model.A superiority of SAM vs placebo ( n=468) could not be shown; the 95% CI of standardized difference of pain scores was (-0.89, 0.12). The comparison of SAM vs NSAIDs with seven studies ( n=850) did not show a difference: (-0.59, 0.19). This cannot be seen as proof for equivalence. A post-hoc analysis of SAM vs ibuprofen gave nearly a positive result for SAM: (-0.43, 0.02).No adequate placebo-controlled RCT was found. There was no significance for a difference between oxaceprol and NSAIDs using the four trials found (two diclofenac and two ibuprofen); the 95% CI of standardized difference of pain and function scores was (-0.19, 0.27).Since only a few trials with heterogeneous results were found which mostly have a low quality of the studies and/or publications, the results must be interpreted very carefully. The meta-analysis does not give enough evidence for the efficacy of SAM and oxaceprol for treating the symptoms of osteoarthritis, but it might be that there is a comparable effect to other NSAIDs.
S-Adenosylmethionine , cytokines, and alcoholic liver disease.
McClain, Craig J; Hill, Daniell B; Song, Zhenyuan; Chawla, Rajender; Watson, Walter H; Chen, Theresa; Barve, Shirish
JOURNAL NAME- Alcohol
VOLUME 27
NO 3
2002 Jul
PP 185-92
53 REFERENCE
DOCUMENT TYPE- Journal Article; Review; Review, Tutorial
JOURNAL CODE- 8502311
JOURNAL SUBSET- MEDJSIM
ISSN- 0741-8329
Hepatic deficiency of S-adenosylmethionine (AdoMet) is a critical acquired metabolic abnormality in alcoholic liver disease (ALD) and in many experimental models of hepatotoxicity. Subnormal AdoMet, elevated serum tumor necrosis factor (TNF), and endotoxemia (LPS) are hallmarks of ALD and experimental liver injury. AdoMet deficiency is attributed to its subnormal synthesis, but mechanisms for increased TNF are not known. AdoMet deficiency may affect the critical balance of proinflammatory (e.g., TNF) and antiinflammatory .e.g., interleukin (IL)-10a cytokines. Rats maintained on a choline-deficient diet with limited amounts of methionine (MCD diet) developed AdoMet deficiency. When challenged with LPS, rats fed MCD diet had significantly increased serum TNF levels and worse liver injury compared with findings for controls. Exogenous AdoMet attenuated liver injury and serum TNF levels. Results of in vitro studies with the use of RAW 264.7 cells demonstrated that exogenous AdoMet supplementation lowered LPS-induced TNF formation in a dose-dependent manner, and AdoMet deficiency enhanced TNF secretion and TNF gene _expression. AdoMet also dose-dependently decreased LPS-stimulated TNF production from monocytes obtained from patients with alcoholic hepatitis. Finally, AdoMet supplementation stimulated production of the antiinflammatory cytokine IL-10. Interleukin-10 plays a critical role in the modulation of TNF production, and IL-10 may inhibit hepatic fibrosis. This article will review (1) the role of AdoMet in ALD/liver injury, (2) the role of TNF/proinflammatory cytokines in ALD, (3) potential roles of AdoMet in TNF/proinflammatory cytokine regulation in ALD, and (4) conclusions and future directions.
Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis.
Soeken, Karen L; Lee, Wen-Lin; Bausell, R Barker; Agelli, Maria; Berman, Brian M
JOURNAL NAME- J Fam Pract
VOLUME 51
NO 5
2002 May
PP 425-30
36 REFERENCE
DOCUMENT TYPE- Journal Article; Meta-Analysis; Review; Review, Tutorial
JOURNAL CODE- 7502590
JOURNAL SUBSET- MEDJSAIM; MEDJSIM
ISSN- 0094-3509
OBJECTIVE: We assessed the efficacy of S-adenosylmethionine (SAMe), a dietary supplement now available in the Unites States, compared with that of placebo or nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of osteoarthritis (OA). STUDY DESIGN: This was a meta-analysis of randomized controlled trials. DATA SOURCES: We identified randomized controlled trials of SAMe versus placebo or NSAIDS for the treatment of OA through computerized database searches and reference lists. OUTCOMES MEASURED: The outcomes considered were pain , functional limitation, and adverse effects. RESULTS: Eleven studies that met the inclusion criteria were weighted on the basis of precision and were combined for each outcome variable. When compared with placebo, SAMe is more effective in reducing functional limitation in patients with OA (effect size .ESa =.31; 95% confidence interval .CIa,.099-.520), but not in reducing pain (ES =.22; 95% CI, -.247 to.693). This result, however, is based on only 2 studies. SAMe seems to be comparable with NSAIDs ( pain : ES =.12; 95% CI, -.029 to.273; functional limitation: ES =.025; 95% CI, -.127 to.176). However, those treated with SAMe were less likely to report adverse effects than those receiving NSAIDs. CONCLUSIONS: SAMe appears to be as effective as NSAIDs in reducing pain and improving functional limitation in patients with OA without the adverse effects often associated with NSAID therapies.
Interferons: Potential roles in affect
Hurlock, IV E. C.
JOURNAL NAME- Medical Hypotheses
56/5 (558-566)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0306-9877
PUBLICATION YEAR- 2001
A review of the literature on interferons was conducted and possible roles in neuropsychiatric disorders with affective disturbances are assessed. Interferons and interferon receptors are present in the limbic system where they appear to exert physiological effects pertinent to affect, most potently when levels rise during CNS infections. Interferons interact closely with cytokines and nitric oxide, signaling molecules implicated in depression Results from knock-out mice suggest a role for interferon-(gamma) in moderating fear and anxiety, while other lines of evidence point to a role in arousal and circadian rhythms. The interferon-(alpha) receptor deploys an arginine methyltransferase affecting RNA editing and splicing, which seem to be disrupted in schizophrenia and bipolar disorder. S-Adenosylmethionine (SAMe), an effective antidepressant, may owe its effects in the latter disorders in part to variations in the strength of interferon-(alpha) signaling impacting RNA processing. Antiviral effects of interferons are of interest in lieu of viral theories of affective disorders. Finally, the relative levels of interferons (gamma) and (alpha) might play important roles in neural, and glial, development, as well as the dialog between the CNS and the immune system. (copyright) 2001 Harcourt Publishers Ltd.
S-adenosylmethionine (ademetionine) in psychiatric disorders. Historical perspective and current status
Spillmann, M.; Fava, M.
JOURNAL NAME- CNS Drugs
6/6 (416-425)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 1172-7047
PUBLICATION YEAR- 1996
S-Adenosylmethionine (SAMe; ademetionine) is a naturally occurring compound that is found in virtually all living organisms. It serves as a major source of methyl groups in the brain, donating these groups to molecules such as hormones, neurotransmitters, nucleic acids, proteins and phospholipids, and is of fundamental importance in a number of intracellular metabolic pathways. The most commonly reported effect of SAMe is mood elevation in depressed patients. A few, relatively small clinical studies have shown that parenteral SAMe is superior to placebo and at least as effective as standard antidepressants, perhaps with a relatively rapid onset of action. Furthermore, the addition of SAMe to standard antidepressants may shorten the time to treatment response compared with the use of antidepressants alone. There are also additional reports suggesting the usefulness of the compound in dementia. SAMe appears to be remarkably well tolerated and free of severe adverse effects. Further studies are needed to clearly establish the role that SAMe may play in the treatment of depressive disorders and dementia.
Antidepressive latency and S-adenosylmethionine
Chinchilla, Moreno A.; Vega, Pinero M.; Cebollada, Gracia A.; Ochoa, Mangado E.
JOURNAL NAME- Anales de Psiquiatria
12/2 (67-71)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0213-0599
PUBLICATION YEAR- 1996
LANGUAGE- SPANISH
Several strategies have been carried out in order to increase the response of affective disturbances to antidepressive treatments. Among the substances with increasing potential on these treatments, the efficacy of the S-Adenosylmethionine (SAMe) has been tested in the treatment of major depressive disturbance in order to decrease the latency of the normotimic effect. In this work, we studied the response to disthymic disturbance in comparing two groups of 30 patients each; the control group was administered a selective inhibitor of serotonine recapturing (fluoxetine in a dose of 20 mg/day), while the other group, besides of being under the same antidepressive regime, was administered a SAMe dose of 100 mg/day by intramuscle infusion during the first two weeks. In the two groups, an improvement was noted with respect to efficacy, although in the group treated with fluoxetine + SAMe, it could be noted earlier with significant better results in the statistical analysis after two weeks.
Polyamines and their metabolizing enzymes in human frontal cortex and hippocampus: Preliminary measurements in affective disorders
Gilad, G. M.; Gilad, V. H.; Casanova, M. F.; Casero, Jr R. A.
JOURNAL NAME- Biological Psychiatry
38/4 (227-234)
DOCUMENT TYPE- Journal
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0006-3223
PUBLICATION YEAR- 1995
Affective disorders are associated with maladaptive response to stressful life events. Based on the observation that a transient increase in brain polyamine metabolism is a common response to stressful stimuli, our hypothesis is that a maladaptive polyamine stress response may be involved in the pathophysiology of affective disorders; Our current research efforts, therefore, concentrate on the characterization of this PA response, and on its pharmacological regulation. The present preliminary study is the first to measure the polyamines, putrescine, spermidine, and spermine, and their metabolizing enzymes, ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine/spermine N<sup>1</sup> acetyltransferase, in brain autopsy samples from people who suffered from depressive disorders or schizophrenia, or from those who committed suicide, The data of affected individuals did not reveal significant differences when compared to those of suicide cases, or to those of people with no known neurologic or psychiatric abnormalities. The following regional differences were observed: spermidine concentrations and ornithine decarboxylase activity were higher, but S-adenosylmethionine decarboxylase activity was lower in the hippocampus as compared to the frontal cortex. Preliminary studies with rat brain indicate that an increase in polyamine metabolizing enzyme activities occurs within several hours after death and persists for at least 48 hours. These observations, in turn, indicate that earlier autopsies are crucial for detection of changes in polyamine metabolism. We conclude that further studies to test the polyamine hypothesis are warranted.
The clinical potential of ademetionine ( S-adenosylmethionine ) in neurological disorders
Bottiglieri, T.; Hyland, K.; Reynolds, E. H.
JOURNAL NAME- Drugs
48/2 (137-152)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0012-6667
PUBLICATION YEAR- 1994
This review focuses on the biochemical and clinical aspects of methylation in neuropsychiatric disorders and the clinical potential of their treatment with ademetionine ( S-adenosylmethionine ; SAMe). SAMe is required in numerous transmethylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis of SAMe is intimately linked with folate and vitamin B<inf>12</inf> (cyanocobalamin) metabolism, and deficiencies of both these vitamins have been found to reduce CNS SAMe concentrations. Both folate and vitamin B<inf>12</inf> deficiency may cause similar neurological and psychiatric disturbances including depression , dementia, myelopathy and peripheral neuropathy. SAMe has a variety of pharmacological effects in the CNS, especially on monoamine neurotransmitter metabolism and receptor systems. SAMe has antidepressant properties, and preliminary studies indicate that it may improve cognitive function in patients with dementia. Treatment with methyl donors (betaine, methionine and SAMe) is associated with remyelination in patients with inborn errors of folate and C-1 (one-carbon) metabolism. These studies support a current theory that impaired methylation may occur by different mechanisms in several neurological and psychiatric disorders.
CAS SUBSTANCE NAME- s adenosylmethionine; 5 hydroxyindoleacetic acid; betaine; cyanocobalamin; levodopa; methionine; methotrexate; methyltransferase; phenytoin; protein; serotonin
S-adenosylmethionine blood levels in major depression : Changes with drug treatment
JOURNAL NAME- Acta Neurologica Scandinavica, Supplement
89/154 (15-18)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0065-1427
PUBLICATION YEAR- 1994
Introduction - The relationship between plasma levels of S-adenosylmethionine (SAMe), an endogenous methyl donor, and clinical response were studied in patients with a DSM-III-R diagnosis of major depression Material and methods - A double-blind randomized protocol comparing oral SAMe with oral desipramine, involving a total of 26 patients, was employed. Results - At the end of the 4-week trial, 62% of the patients treated with SAMe and 50% of the patients treated with desipramine had significantly improved. Regardless of the type of treatment, patients with a 50% decrease in their Hamilton Depression Scale (HAM-D) score showed a significant increase in plasma SAMe concentration. Conclusion - The significant correlation between plasma SAMe levels and the degree of clinical improvement in depressed patients regardless of the type of treatment suggests that SAMe may play an important role in regulating mood
Dothiepin vs. S-adenosylmethionine (SAMe) for the treatment of major depression in weaned alcoholics: A pilot study
EMB 94-01 1994105963 NDN- 012-2068-5033-6
Schifano, F.; Garofoli, F.
JOURNAL NAME- European Neuropsychopharmacology
3/3 (330)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0924-977X
PUBLICATION YEAR- 1993
NO-ABSTRACT
Psychological distress during puerperium: A novel therapeutic approach using S-adenosylmethionine
Cerutti, R.; Sichel, M. P.; Perin, M.; Grussu, P.; Zulian, O.
JOURNAL NAME- Current Therapeutic Research - Clinical and Experimental
53/6 (707-716)
COPYRIGHT- Copyright 2004 Elsevier B.V., Amsterdam. All rights reserved.
ISSN- 0011-393X
PUBLICATION YEAR- 1993
A study was undertaken to assess postpartum psychological distress and to evaluate a novel approach to treatment. Kellner's Symptom Questionnaire proved to be a valuable predictive tool for anxiety, depression , somatic symptoms, and hostility in 190 women during puerperium. This epidemiologic investigation was followed by a two-phase comparative clinical study. The first phase was a double-blind trial of oral S-adenosylmethionine (SAMe) 1600 mg/day versus placebo for 30 days administered to two groups of 30 patients each. Compared with the patients receiving placebo, patients receiving SAMe exhibited improved symptom questionnaire total scores and depression and anxiety scores by day 10 of treatment. Progressive improvement was observed throughout the duration of the study. The second phase of the study was an open trial comparing 40 SAMe-treated patients with the epidemiologic group of patients as controls. After 30 days of treatment, the patients receiving SAMe showed a significant improvement in both total scores and depression and anxiety items compared with the control group. We conclude that SAMe is an effective treatment for reducing or relieving the signs and symptoms of psychological distress during puerperium.
S-Adenosyl-methionine (SAMe) as antidepressant
Andreoli, V.
JOURNAL NAME- New Trends in Clinical Neuropharmacology
6/1-4 (11-18)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0393-5345
PUBLICATION YEAR- 1992
CODEN- NTCNE
AUTHOR ADDRESS- Psychiatric Department, Ospedale San Giovanni,Soave-Verona
COUNTRY OF AUTHOR- Italy
PUBLICATION COUNTRY- Italy
LANGUAGE- ENGLISH
In 1971 S-Adenosylmethionine (SAMe) entered in clinical research. The clinical trial as well as an extensive clinical practice in
Cerebrospinal fluid S-adenosylmethionine in depression and dementia: Effects of treatment with parenteral and oral S-adenosylmethionine
Bottiglieri, T.; Godfrey, P.; Flynn, T.; Carney, M. W. P.; Toone, B. K.; Reynolds, E. H.
JOURNAL NAME- Journal of Neurology Neurosurgery and Psychiatry
53/12 (1096-1098)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0022-3050
PUBLICATION YEAR- 1990
Cerebrospinal fluid (CSF) S-adenosylmethionine (SAM) levels were significantly lower in serverely depressed patients than in a neurological control group. The administration of SAM either intravenously or orally is associated with a significant rise of CSF SAM, indicating that it crosses the blood-brain barrier in humans. These observations provide a rational basis for the antidepressant effect of SAM, which has been confirmed in several countries. CSF SAM levels were low in a group of patients with Alzheimer's dementia suggesting a possible disturbance of methylation in such patients and the need for trials of SAM treatment.
S-Adenosylmethionine treatment of depression in patients with Parkinsons's disease. A double-blind, crossover study versus placebo
Carrieri, P. B.; Indaco, A.; Gentile, S.; Troisi, E.; Campanella, G.
JOURNAL NAME- Current Therapeutic Research - Clinical and Experimental
48/1 (154-160)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0011-393X
PUBLICATION YEAR- 1990
Depression is frequently observed in patients with Parkinson's disease (PD). A double-blind, crossover study versus placebo was conducted in 21 patients with PD and depression treated with S-adenosylmethionine (SAMe), an endogenous methyl donor. Duration of the study was 30 days for each arm, with a washout period of two weeks between treatments. At each evaluation, the Webster Rating Scale, the Northwestern University Disability Scale, the Hamilton Rating Scale for Depression , and the Beck Self Depression Inventory were used. SAMe was administered at a dose of 400 BID orally plus 200 mg IM daily. SAMe improved depression in patients with PD to a statistically larger extent than did placebo, although Parkinson symptoms appeared to be unchanged. Side effects were moderate and of brief duration.
Oral S-adenosylmethionine in depression : A randomized, double-blind, placebo-controlled trial
Kagan, B. L.; Sultzer, D. L.; Rosenlicht, N.; Gerner, R. H.
JOURNAL NAME- American Journal of Psychiatry
147/5 (591-595)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0002-953X
PUBLICATION YEAR- 1990
Methylation has been implicated in the etiology of psychiatric illness. Parenteral S-adenosylmethionine , a methyl group donor, has been shown to be an effective antidepressant. The authors studied the antidepressant effect of oral S-adenosylmethionine in a randomized, double-blind, placebo-controlled trial for 15 inpatients with major depression The results suggest that oral S-adenosylmethionine is a safe, effective antidepressant with few side effects and a rapid onset of action. S-Adenosylmethionine included mania in a patient with no history of mania. S-Adenosylmethionine may be useful for patients who cannot tolerate tricyclic antidepressants. These findings support a role for methylation in the pathophysiology of depression
The efficacy of S-adenosylmethionine in the treatment of depression : Controlled clinical study versus minaprine
Cerutti, P. G.; Savoini, G.; D'Avola, G.; Ronchi, G.; Gualtieri, S.; Verri, A. P.
JOURNAL NAME- Basi Razionali della Terapia
19/10 (591-595)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0393-7569
PUBLICATION YEAR- 1989
NO-ABSTRACT
S-adenosylmethionine in the treatment of depression
Vahora, S. A.; Malek-Ahmadi, P.
JOURNAL NAME- Neuroscience and Biobehavioral Reviews
12/2 (139-141)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0149-7634
PUBLICATION YEAR- 1988
NO-ABSTRACT
S-adenosylmethionine treatment of depression : A controlled clinical trial
JOURNAL NAME- American Journal of Psychiatry
145/9 (1110-1114)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0002-953X
PUBLICATION YEAR- 1988
The antidepressant properties of S-adenosylmethionine , an endogenous methyl donor, were studied in inpatients who met the DSM-III criteria for major depression Nine patients given intravenous S-adenosylmethionine and nine given low oral doses of imipramine were compared in a double-blind design for 14 days. The S-adenosylmethionine produced superior results by the end of the first week of treatment. By the end of the second week, 66% of the S-adenosylmethionine patients had a clinically significant improvement in depressive symptoms, compared to 22% of the imipramine patients. Side effects appeared to be fewer with S-adenosylmethionine than with imipramine during the last 5 days of the study.
REGISTRY NUMBER- 29908-03-0; 485-80-3¬; 113-52-0; 50-49-7;
CAS SUBSTANCE NAME- s adenosylmethionine; imipramine
S-adenosylmethionine and affective disorder
Carney, M. W. P.; Toone, B. K.; Reynolds, E. H.
JOURNAL NAME- American Journal of Medicine
83/5 A (104-106)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0002-9343
PUBLICATION YEAR- 1987
Several open and double-blind studies suggest that SAMe may have an anti-depressant effect, and further studies are indicated. SAMe may exert a beneficial effect selectively on endogenous rather than neurotic depression SAMe crosses the blood-brain barrier. SAMe is involved in several central enzyme pathways relating to transmethylation and folate and monoamine metabolism as well as in membrane function and neurotransmission. The neuropharmacology of SAMe's effect on mood and the switch mechanism has yet to be fully explored. The actions of SAMe on the dopaminergic system are as yet unclear. SAMe is a physiologic substance that is non-toxic and relatively free of severe side effects (with the exception of mania, which may be a manifestation of the basic mood disorder).
Treatment of depression in rheumatoid arthritic patients. A comparison of S-adenosylmethionine (Samyr) and placebo in a double-blind study
Caruso, I.; Fumagalli, M.; Boccassini, L.; Puttini, S. P.; Santandrea, S.; Giniselli, G.; Parma, E.
JOURNAL NAME- Clinical Trials Journal
24/4 (305-310)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0009-9325
PUBLICATION YEAR- 1987
A double-blind study to compare the efficacy and tolerability of S-adenosylmethionine (SAMe), Samyr, with that of placebo in the treatment of depression in rheumatoid arthritic (RA) patients was made. SAMe showed a significant improvement in the depression in RA patients and there was a significant difference between SAMe and placebo in all variables measured. No side-effects were reported during the treatment with SAMe, which is in agreement with earlier reports. Further controlled studies are required to define the effects of SAMe on depression
S-Adenosylmethionine as an antidepressant. A double-blind trial versus placebo
De, Leo D.
JOURNAL NAME- Current Therapeutic Research - Clinical and Experimental
41/6 (865-870)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
PUBLICATION YEAR- 1987
In this double-blind study S-adenosylmethionine (SAMe) was compared with placebo in a sample of 40 primary depressives (DSM III). SAMe 200 mg/day was administered intramuscularly for four weeks. Modifications occurring were evaluated with the Zung Self-Rating Depression Scale and with the Clinical Global Impression Scale. SAMe exerted an action superior to placebo and was well tolerated.
Open trial of S-adenosylmethionine for treatment of depression
Lipinski, J. F.; Cohen, B. M.; Frankenburg, F.; et, al.
JOURNAL NAME- American Journal of Psychiatry
141/3 (448-450)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
PUBLICATION YEAR- 1984
Nine depressed inpatients completed trials with S-adenosylmethionine Seven showed improvement or remission of their symptoms. As in European studies, no side effects were seen except the apparent induction of mania in two patients with bipolar disorder.
Methylation and mood
Reynolds, E. H.; Carney, M. W. P.; Toone, B. K.
JOURNAL NAME- Lancet
2/8396 (196-198)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
PUBLICATION YEAR- 1984
S-adenosylmethionine (SAM) has antidepressant properties. The commonest neuropsychiatric complication of severe folate deficiency is depression These independent observations (1) suggest that methylation in the nervous system may underlie the _expression of mood and related processes and may be implicated in some affective disorders; (2) suggest new biological approaches to the understanding and treatment of some affective disorders; and (3) may explain why methionine sometimes aggravates schizophrenia.
Blood levels of S-adenosylmethionine in unmedicated schizophrenic and depressive patients
Maj, M.; Zizolfi, S.;
JOURNAL NAME- Neuropsychobiology
7/4 (188-191)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
PUBLICATION YEAR- 1981
S-Adenosylmethionine blood levels have been estimated by a specific radioenzymatic method in 52 schizophrenics and 12 depressives, diagnosed and subtyped according to ICD-9 and compared with 38 normal controls. Previous reports of significantly lower levels of blood SAMe in acute schizophrenics in comparison with normal subjects could not be confirmed in this study. Indeed, acute schizophrenics showed higher mean SAMe blood levels as compared both with chronic and with normal controls. No significant difference has been found comparing both schizophrenics as a whole and depressives with normal controls. This investigation aims to bring a contribution to the recently started critical revision of transmethylation hypothesis of schizophrenia.
REGISTRY NUMBER- 29908-03-0; 485-80-3;
CAS SUBSTANCE NAME- s adenosylmethionine
Comparison between the antidepressant activity of S-adenosylmethionine (SAMe) and that of some tricyclic drugs
Miccoli, L.; Porro, V.; Bertolino, A.
JOURNAL NAME- Acta Neurologica
33/3 (243-255)
COPYRIGHT- Copyright 2004 Elsevier B.V.,
PUBLICATION YEAR- 1978
Two groups of patients with depressive syndromes according to Kielholz's classification were treated daily with intravenous doses of 200 mg SAMe and 100 mg of tricyclic antidepressants such as chloroimipramine or amitriptyline, respectively, over a period of 21 days. Therapeutic effects were observed after 7 and 21 days. SAMe has been shown to exert an anti-depressive action comparable to that of chloroimipramine and amitriptyline, yet with a remarkably more rapid effect and no significant side-effects.
SAMe and depression
Nguyen, M; Gregan, A
JOURNAL NAME- Australian Journal of Pharmacy
VOLUME 83
NO 984
2002
PP 244-247
ISSN- 0311-8002
This review discusses the use of S-adenosylmethionine (SAMe) in the treatment of depression Pharmacokinetics, mechanisms of action, precautions, adverse reactions, as well as clinical safety and efficacy are discussed.
Ademetionine
S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine.
Alpert, Jonathan E; Papakostas, George; Mischoulon, David; Worthington, John J; Petersen, Timothy; Mahal, Yasmin; Burns, Alana; Bottiglieri, Teodoro; Nierenberg, Andrew A; Fava, Maurizio
JOURNAL NAME- J Clin Psychopharmacol
VOLUME 24
NO 6
2004 Dec
PP 661-4
ISSN- 0271-0749
BACKGROUND: The purpose of this open trial was to evaluate the safety, tolerability, and efficacy of oral S-adenosyl-L-methionine as an antidepressant adjunct among partial and nonresponders to serotonin reuptake inhibitors or venlafaxine. METHOD: Thirty antidepressant-treated adult outpatients with persisting major depressive disorder received 800 to 1600 mg of S-adenosyl-L-methionine tosylate over a 6-week trial. RESULTS: Intent-to-treat analyses based on the Hamilton Depression Rating Scale revealed a response rate of 50% and a remission rate of 43% following augmentation with S-adenosyl-L-methionine. Gastrointestinal symptoms and headaches were the most common side effects. CONCLUSION: Augmentation of selective serotonin reuptake inhibitors or venlafaxine with S-adenosyl-L-methionine warrants a placebo-controlled trial in resistant depression
A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder.
Pancheri, Paolo; Scapicchio, Pierluigi; Chiaie, Roberto Delle
JOURNAL NAME- Int J Neuropsychopharmacol
VOLUME 5
NO 4
2002 Dec
PP 287-94
DOCUMENT TYPE- Clinical Trial; Journal Article; Randomized Controlled Trial
JOURNAL CODE- 9815893
JOURNAL SUBSET- MEDJSIM
ISSN- 1461-1457
S-adenosyl-L-methionine (SAMe) is a natural substance which constitutes the most important methyl donor in transmethylation reactions in the central nervous system. Several clinical trials have shown that SAMe possesses an antidepressant activity. This multicentre study was carried out to confirm both efficacy and safety of SAMe in the treatment of major depression SAMe was given intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d oral Imipramine (IMI) in patients with a diagnosis of major depressive episode, with a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of >or=18. A total of 146 patients received SAMe whereas 147 received IMI for a period of 4 wk. The two main efficacy measures were endpoint HAMD score and percentage of responders to Clinical Global Impression (CGI) at week 4. Secondary efficacy measures were the final Montgomery-Asberg Depression Rating Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of at least 50% with respect to baseline. The analysis of safety and tolerability was conducted in all treated patients. SAMe and IMI did not differ significantly on any efficacy measure, either main or secondary. Adverse events were significantly less in patients treated with SAMe compared to those treated with IMI. These data show 400 mg/d i.m. SAMe to be comparable to 150 mg/d oral IMI in terms of antidepressive efficacy, but significantly better tolerated. These findings suggest interesting perspectives for the use of SAMe in depression
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, Roberto; Pancheri, Paolo; Scapicchio, Pierluigi
JOURNAL NAME- Am J Clin Nutr
VOLUME 76
NO 5
2002 Nov
PP 1172S-6S
DOCUMENT TYPE- Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial
JOURNAL CODE- 0376027
JOURNAL SUBSET- MEDJSAIM; MEDJSIM
ISSN- 0002-9165
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=18a 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.
Effectiveness of SAMe for pain relief in osteoarthritis of the knee
Harvey, Phillip William; Hoehler, Fred; Najm, Wadie; Reinsch, Sibylle; Tobis, Jerome S.
JOURNAL NAME- FASEB Journal
VOLUME 17
NO 4-5
March 2003 2003
PP Abstract No. 205.10.
DOCUMENT TYPE- Meeting
ISSN- 0892-6638
While the medical profession commonly treats osteoarthritis (OA) of the knee with non-steroidal anti-inflammatory drugs (NSAIDs), the public often uses supplements like SAMe to reduce discomfort. The aim of this study was to assess the relative therapeutic effectiveness of SAMe ( S-adenosylmethionine ) and Celebrex in adults with OA of the knee. The study was randomized, double-blind cross-over trial, using SAMe at 600 mg b.i.d. compared to Celebrex 100 mg b.i.d., for a total of 8 weeks each, with one week of wash-out prior to each study medicine. Sixty-one adults met the inclusion criteria and were enrolled. The following outcomes were obtained after each medicine: pain measured with a VAS, activity impairment measured with an adapted Rowland-Morris Activity Scale, knee function with the 10-stand-ups procedure by Csuka & McCarthy and clinical assessment of OA with the WOMAC.)Conclusion: SAMe was as effective as Celebrex for pain control, activity improvement, knee function improvement and OA symptom reduction. Fewer adverse health-related changes were observed during SAMe ingestion compared to Celebrex.
Treatment of fibromyalgia with antidepressants: A meta-analysis
O'Malley, P. G.; Balden, E.; Tomkins, G.; Santoro, J.; Kroenke, K.; Jackson, J. L.
JOURNAL NAME- Journal of General Internal Medicine
15/9 (659-666)
DOCUMENT TYPE- Journal
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0884-8734
PUBLICATION YEAR- 2000
BACKGROUND: Fibromyalgia is a common, poorly understood musculoskeletal pain syndrome with limited therapeutic options. OBJECTIVE: To systematically review the efficacy of antidepressants in the treatment of fibromyalgia and examine whether this effect was independent of depression DESIGN: Meta-analysis of English-language, randomized, placebo-controlled trials. Studies were obtained from searching Medline, Embase, and Psyclit (1966-1999), the Cochrane Library, unpublished literature, and bibliographies. We performed independent duplicate review of each study for both inclusion and data extraction. MAIN RESULTS: Sixteen ramdomized, placebo-controlled trials were identified, of which 13 were appropriate for data extraction. There were 3 classes of antidepressants evaluated: tricyclics (9 trials), selective serotonin reuptake inhibitors (3 trials), and S-adenosylmethionine (2 trials). Overall, the quality of the studies was good (mean score 5.6, scale 0-8). The odds ratio for improvement with therapy was 4.2 (95% confidence interval 95% CI , 2.6 to 6.8). The pooled risk difference for these studies was 0.25 (95% CI, 0.16 to 0.34), which calculates to 4 (95% CI, 2.9 to 6.3) individuals needing treatment for 1 patient to experience symptom improvement. When the effect on individual symptoms was combined, antidepressant improved sleep, fatigue, pain , and well-being, but not trigger points. In the 5 studies where there was adequate assessment for an effect independent of depression , only 1 study found a correlation between symptom improvement and depression scores. Outcomes were not affected by class of agent or quality score using meta-regression. CONCLUSION: Antidepressants are efficacious in treating many of the symptoms of fibromyalgia. Patients were more than 4 times as likely to report overall improvement, and reported moderate reductions in individual symptoms, particularly pain Whether this effect is independent of depression needs further study.
Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation
Jacobsen, Danneskiold-Samsoe S. B.; Andersen, R. B.
JOURNAL NAME- Scandinavian Journal of Rheumatology
20/4 (294-302)
DOCUMENT TYPE- Journal
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0300-9742
PUBLICATION YEAR- 1991
S-adenosylmethionine is a relatively new anti-inflammatory drug with analgesic and antidepressant effects. Efficacy of 800 mg orally administered s-adenosylmethionine daily versus placebo for six weeks was investigated in 44 patients with primary fibromyalgia in double-blind settings. Tender point score, isokinetic muscle strength, disease activity, subjective symptoms (visual analog scale), mood parameters and side effects were evaluated. Improvements were seen for clinical disease activity (P = 0.04), pain experienced during the last week (P = 0.002), fatigue (P = 0.02), morning stiffness (P = 0.03) and mood evaluated by Face Scale (P = 0.006) in the actively treated group compared to placebo. The tender point score, isokinetic muscle strength, mood evaluated by Beck Depression Inventory and side effects did not differ in the two treatment groups. S-adenosylmethionine has some beneficial effects on primary fibromyalgia and could be an important option in the treatment hereof.
REGISTRY NUMBER- 29908-03-0; 485-80-3;
CAS SUBSTANCE NAME- s adenosylmethionine
Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis
Muller-Fassbender, H.
JOURNAL NAME- American Journal of Medicine
83/5 A (81-83)
DOCUMENT TYPE- Journal
COPYRIGHT- Copyright 2004 Elsevier B.V.,
ISSN- 0002-9343
PUBLICATION YEAR- 1987
Thirty-six subjects with osteoarthritis of the knee, the hip, and/or the spine were enrolled in a randomized doub