Key Compounds of SAMenhanced

The Benefits of SAM-e

1. SAM-e for Pain and Inflammation

S-adenosyl-L-methionine (SAM-e) is one of the best kept secrets in controlling pain and inflammation. SAMe is naturally occurring in our tissues and contributes a great deal in maintaining our health and longevity. It is as effective as aspirin in being an anti-inflammatory and analgesic but SAM-e does not produce harmful side effects to the gastrointestinal tract and kidneys. Since SAM-e also helps protect the cell from energy dysfunction, oral as well as intravenous treatments with SAM-e may benefit fibromyalgia, especially when taken with Coenzyme Q10 and Nutracene.

Research on SAMe for pain, inflammation and fibromyalgia

In 1983, Gualano demonstrated that SAM-e had anti-inflammatory and analgesic effects in injured laboratory animals. In addition, higher doses of this natural compound did not damage the gastrointestinal mucosa.⁽¹⁾

Several years later, Gualano showed that SAM-e could reduce edema in laboratory animals that had been given carrageenin or nystatin. SAM-e also reduced inflammation due to a bacterial infection by interfering with the pro-inflammatory functions of arachidonic acid.⁽²⁾

SAM-e has also show benefit in relieving pain symptoms of fibromyalgia. In a ten day cross-over study of SAM-e compared to a placebo, 34 patients with fibromyalgia perceived some improvement in pain at rest, pain with movement and overall well being from 600 mg of SAM-e given intravenously.⁽³⁾ SAM-e can take about one or two months to show benefit in difficult clinical conditions. Therefore this 1997 short term study indicates that clinical trials of longer duration are warranted in using SAM-e for the treatment of fibromyalgia.

(1) Gualano M, Stramentinoli G, Berti F. Anti-infammatory activity of S-adenosyl-L-methionine: interference with the eicosanoid system. Pharmacol Res Commun 1983; 15(7): 683-96.

(2) Gualano M, et al. Anti-inflammatory activity of S-adenosyl-L-methionine in animal models: possible interference with the eicosanoid system. Int J Tissue React 1985; 7(1): 41-6.

(3) Volkmann H, et al. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia. Scand J Rhematol 1997; 26(3): 206-11.

2. SAM-e can be beneficial in Osteoarthritis.

Osteoarthritis is the most prevalent form of arthritis. It affects about 21 million Americans, aged 25 and older. Osteoarthritis affects the cartilage area where bones meet to form joints. The loss of cartilage from injury, excessive use, auto-immunity, and/or nutritional deficiency results in joint pain and loss of range of motion that can eventually lead to disability.

SAMe has a reparative and protective effect with osteoarthritis and provides a safer and more effective alternative to the use of non-steroidal anti-inflammatory drugs for pain relief.

SAM-e shows benefits to Osteoarthritis

In a 1987 a randomized, double blind, placebo controlled study for patients with knee osteoarthritis, Bradley administered 400 mg of SAM-e intravenously for five days. The 81 patients were then given 200 mg three times a day for 23 days. The mild osteoarthitic group showed significantly less pain in rest and movement compared to the placebo group at one clinical facility but no differences were found at another facility where more severe cases predominated. In those who showed benefits, improvements were seen within 14 days of SAMe administration. The authors suggest that SAMe may be beneficial to some people with osteoarthritis.⁽¹⁾

Di Padova reviewed clinical trials over a five year period that enrolled about 22,000 patients with osteoarthritis. The effectiveness of SAMe was comparable to that of nonsteroidal anti-inflammatory drugs but without their side effects. ⁽²⁾

SAMe increases chrondrocyte proteoglycan and extracellular matrix production to compensate for their damage by inflammatory cytokines. SAM-e.s sulfur incorporation into proteoglycans may also protect them and compensate for cytokine induced glutathione depletion. Gutierrez suggests that SAM-e plays a compensatory and protective role in osteoarthritic damage from inflammation. ⁽³⁾

(1)   Bradley JD, et al. A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis. J Rhematol 1994; 21(5): 905-11.

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

(3) 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. British Journal of Rheumatology 1997; 37: 27-31.

(4) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health (NIH), NIH Publication No. 06-4617, website www.niams.nih.gov.

(5) S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease. Summary, Evidence Report/Technology Assessment: Number 64. AHRQ Publication No. 02-E033, August 2002. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/epcsums/samesum.htm.

3. SAM-e helps the Liver

S-adenosyl-L-methionine (SAM-e) is the liver.s best friend. It is naturally occurring in our tissues, especially in the liver and brain. SAMe provides many of the benefits that pharmaceuticals can provide to the liver but without their side effects.

When blood flow slows or stops, normal cell levels of SAM-e are diminished and then cell energy and cell function begin to falter. Supplementation with SAM-e helps maintain energy levels and cell activity. SAM-e also donates sulfur groups to the antioxidant, glutathione. Glutathione protects the liver from damage induced by infections (such as hepatitis C), toxins (such as alcohol) and inflammation (induced by pathogens, toxins or injuries). Glutathione also helps the immune cells and liver cells with detoxification.

In addition, SAM-e donates methyl groups that are important for normal gene expression and activity in DNA. When SAM-e levels are low, there is an increased risk of DNA aberrations that are a risk factor for the development of cancer. Supplementation with SAM-e has been reported to reduce tissue lesions and reduce early signs of liver cancer in laboratory animals.

SAM-e and Liver Disorders

SAM-e is depleted in liver cirrhosis and this depletion contributes to the development of liver cirrhosis. ATP is required for the enzyme, methionine adenosyltransferase to convert methionine to SAM-e. Without ATP, the enzyme reaction cannot transfer methionine to produce SAM-e and the resulting abnormal methionine metabolism becomes a characteristic of liver cirrhosis. Supplementation with SAM-e (and B complex) can help jump start the energy production again and help resume normal methionine metabolism.⁽¹⁾

In 2002, Lieber published an article on SAM-e.s role in liver disorders.(1)

Liver disease reduces energy in the cells which also reduces SAM-e and the enzyme SAMe-synthetase. This enzyme is needed for methionine utilization that helps produce the sulfur containing amino acid, cysteine, for glutathione. Glutathione is important in protecting the liver cells against pathogens, toxins and injuries. By supplementing the liver with SAMe (and B complex), energy production increases as well as SAM-e-synthetase and glutathione.^(2,3)

SAM-e helps reduce liver toxicity by supplying sulfur groups for taurine production. In a 1994 study by Angelico and associates, ten patients with cirrhosis, aged 48-65 years were given 800 mg a day of SAM-e that resulted in increases of taurine in their bile. Taurine binds with bile salts that are involved in the emulsification of fats. There was a significant increase in the bile salt taurochenodeoxycholic acid, which protects against liver toxicity. There was also a drop in glycocholic acid which inhibits the uptake of bile acid in the liver. Dr. Angelico concludes that SAMe is partially metabolized to taurine in those with liver cirrhosis to help with detoxification.⁽⁴⁾

SAM-e also helps improve blood viscosity and blood flow in cirrhosis patients. Alterations in membrane fluidity and transport in the liver cell promote the accumulation of toxins. In Turchetti.s 2000 study, 15 cirrhosis patients from alcoholic or viral causes were administered SAM-e intravenously for seven days and compared with those who were given traditional therapy. The SAMe group showed a significant reduction in blood viscosity, reduced biliary salts and reduced red cell pathology. These results support SAM-e.s role in promoting membrane fluidity and improved liver cell detoxification.⁽⁵⁾

SAM-e may be able to stop cancer at its beginning stages. Genetic changes from aberrant DNA methylation and free radical damage favors DNA damage and the risk of cancer. A decrease in SAM-e in the liver of laboratory rats is associated with reduced DNA methylation and the growth of preneoplastic cells. Supplementation with SAM-e over a six month period results in a reduced production of neoplastic nodules. SAM-e.s effects may be due in part to DNA methylation and antioxidant activity.⁽⁶⁾⁽⁷⁾

SAM-e may reduce symptoms of Hepatitis C. Hepatitis C virus causes liver disease. Current treatments with interferon alpha are beneficial in only about half of the hepatitis patients. The Hepatitis C virus inhibits methylation. In a recent cell culture study by Duong and associates, cell treatment with SAM-e and betaine was able to restore methylation, improve interferon alpha signaling and increases the anti-viral effect of interferon alfa.⁽⁸⁾

(1) Martinez-Chantar ML, et al. Importance of a deficiency in S-adenosyl-L-methioine synthesis in the pathogenesis of liver injury. American Journal of Clinical Nutrition 2002; 76(5): 1177S-82S.

(2) Lieber CS. S-adenosyl-L-Methionine: Its role in the Treatment of Liver Disorders. American Journal of Clinical Nutrition 2002; 76(5): 1183S-7S.

(3) CIC-Biogune, Role of S-adenosyl-L-methionine in liver health and injury. Hepatology 2007; 45(5): 1306-1312.

(4) Angelico M, et al. Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation with taurine in patients with liver cirrhosis. Scand J Clin Lab Invest 1994; 54(6): 459-64.

(5) Turchetti V, et al. Blood viscosity and red cell morphology in subjects suffering from cirrhosis before and after treatment with S-adenosyl-L-methionine (SAM). Clin Hemorheol Microcirc 2000; 22(3): 215-21.

(6) Pascale RM, et al. Chemoprevention of Hepatocarcinogenesis: S-adenosyl-L-methionine. Alcohol 2002; 27(3): 193-8.

(7) Simile MM. et al. Persistent chemopreventive effect of S-adenosyl-L-methionine on the development of liver putative preneoplastic lesions induced by thiobenzamide in diethylnitrosamine-initiated rats. Carcinogenesis 1996; 17(7): 1533-7.

(8) Duong FH, et al. S-adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro. Hepatology 2006; 43(4): 796-806.

4. SAM-e assists with Liver Detoxification from Alcohol

S-adenosyl-L-methionine (SAM-e) has the ability to protect cells in the liver and brain from alcohol toxicity.

When we have an alcoholic beverage, the alcohol is metabolized in the liver by an enzyme called alcohol dehydrogenase. In the process, acetaldehyde and free radicals are generated. Acetaldehyde is toxic to the liver tissue and DNA. Acetaldehyde also depletes the antioxidant glutathione that is involved in detoxification.

SAM-e helps by (1) maintaining cell energy for continued functioning, (2) providing methyl groups for DNA, RNA, proteins, hormones, etc., (3) providing sulfur groups to increase glutathione for better cell defense, and (4) reducing the risk of liver lesions that can lead to the development of cancer of the liver.

SAMe is a safe alternative for helping the liver with alcohol detoxification.

SAM-e and Alcohol Detoxification

Several mechanisms of action for SAM-e were discussed in 2001 at an NIH sponsored symposium on .The Role of S-Adenosyl-L-Methionine in the Treatment of Alcoholic Liver Disease.. Mechanisms that may be involved in SAM-e.s beneficial results include:

1.      Methionine metabolism is impaired in alcoholic liver injury and SAM-e promotes methionine metabolism.

2.      SAM-e assists in regulating liver function.

3.      SAM-e has an ameliorating effect on alcoholic liver disease in animal studies.

4.      The antioxidant glutathione is depleted in alcoholic liver disease and SAM-e increases glutathione levels.

5.      Pro-inflammatory cytokines are elevated in liver injury and SAM-e reduces these cytokines.

6.      Alcoholic liver injury can lead to liver cancer and SAM-e.s ability to promote DNA methylation may be able to reduce the risk of liver cancer.(1)

Alcohol depletes our normal levels of SAM-e in the liver. In 1994, Chawla and Jones demonstrated that SAM-e is substantially reduced in alcoholism as well as in liver hypoxia (lack of oxygen). The authors suggested that in both alcoholism and hypoxia, supplementation with SAMe may help prevent further tissue damage.(2)

The mitochondria are energy factors of the cell that produce ATP. Ethanol from alcohol interferes with mitochondrial function resulting in less ATP for the cell. Without sufficient energy, glutathione in its reduced form, called GSH, cannot be transported into the mitochondria for free radical protection. Supplementation with SAMe increases both energy production and GSH transport into the mitochondria to protect against free radical damage to the mitochondria.(3)

Alcohol is metabolized in the liver by alcohol dehydrogenase. In the process, acetaldehyde (a byproduct of cytochrome P4502E1) and free radicals are generated. Acetaldehyde is toxic to the liver tissue and DNA. It also depletes the antioxidant glutathione that is involved in detoxification. Free radicals are also produced in alcohol metabolism. Free radicals are single electrons that pull other electrons away from stable, functioning molecules, leaving a path of dysfunction. The results of both acetaldehyde and free radicals include DNA damage, increased cancer risk, nutritional and antioxidant deficiencies and a poor immune defense. SAMe increases glutathione levels which increases liver cell detoxification. (4)

(1) Purohit V et al. Role of S-adenosyl-L-methionine in the treatment of alcoholic liver disease: introduction and summary of the symposium. Alcohol 2002; 27(3): 151-4.

(2) Chawla RK, Jones DP. Abnormal metabolism of S-adenosyl-L-methionine in hypoxic rat liver. Similarities to its abnormal metabolism in alcoholic cirrhosis. Biochim Biophys Acta 1994; 1199(1): 45-51.

(3)   Fernandez-Checa JC, et al. S-Adenosyl-L-methionine and mitochondrial reduced glutathione depletion in alcoholic liver disease. Alcohol 2002; 27(3): 179-83.

(4)   McKillop IH, et al. Alcohol and liver cancer. Alcohol 2005; 35(3): 195-203.

5. SAM-e fights pollution.

SAMe supplementation has the ability to reduce lead concentrations in the blood, liver and brain.

SAM-e reduces the accumulation of lead.

Some researchers are not satisfied with SAM-e reducing just alcohol toxicity. In 1999, Flora and Seth decided to add lead to see how much SAM-e could take on. One group of mice ingested lead, a second group ingested alcohol and a third group ingested both lead and alcohol. In each group, liver and brain malondialdehyde levels increased (a symptom of increased free radicals). Supplementation with SAMe reduced the malondialdehyde levels and significantly reduced the accumulation of lead in the blood, liver and brain in both the lead alone and lead plus ethanol groups of mice.

Flora GJ et al. Beneficial effects of S-adenosyl-L-methionine on aminolevulinic acid dehydratase, glutathione, and lipid peroxidation during acute lead-ethanol administration in mice. Alcohol 1999; 18(2-3): 103-8.

6.  SAMe is beneficial to Major Depression

Over 10 million Americans suffer from depression each year. The financial loss from medical treatment and lost wages is at least 43 billion dollars annually. A safe alternative for many people is SAM-e. SAM-e supports energy production in the cell when oxygen and glucose levels are reduced or when pathogens and toxins are increased. SAM-e also increases serotonin levels in areas of the brain that are affected by depression, specifically in the frontal cortex, striatum and hippocampus. SAM-e may also stimulate dopamine activity in depressed male subjects. In an analysis of 47 studies of SAM-e used as an anti-depressant in patients, SAM-e was superior to the placebo by 17% to 38%, depending on the study. In addition, SAM-e was comparable to standard tricyclic antidepressants in reducing symptoms of major depression. SAM-e was also successful in treating resistant major depression when other medications had failed. SAM-e is a fast-acting anti-depressant. When SAM-e is administered with other antidepressants, the patients feel better sooner. SAM-e in oral doses of 400 mg . 1600mg has fewer side effects (minor and transient gastrointestinal symptoms and headaches) compared to other pharmaceutical medications. SAM-e can be a safe alternative to other antidepressants in reducing medical costs and lost wages for those with major depression. However SAM-e is not recommended for bipolar depression since it can increase the mania symptoms in certain individuals. The combination of SAM-e and Nutracene® (high potency B-complex) ensures that methionine metabolites will be processed properly.

SAM-e fights against Major Depression

In Alpert.s 2004 study, 800 to 1600 milligrams of S-adenosyl-L-methionine tosylate were given to 30 patients over a six week period for persisting major depression who had not responded to other medications. With the addition of SAM-e tosylate to their selective serotonin reuptake inhibitors or to venlafaxine, there was a 50% improvement in the Hamilton Depression Rating Scale and a reduced remission rate of 43%. ⁽¹⁾

The benefits of SAM-e are comparable to those of Imipramine. A multicenter study of 293 patients with major depression was conducted to compare SAMe with Imipramine on safety and effectiveness. 146 patients received an injection of 400 milligrams a day (comparable to an oral dose of 1600 mg) for four weeks and 147 patients received 150 milligrams a day of oral Imipramine for 4 weeks. The effectiveness of SAM-e was comparable to that of Imipramine. However, SAM-e was .significantly better tolerated.. ⁽²⁾

Phosphocreatine stores energy for the muscles, brain and heart that can be rapidly converted back to ATP. Creatine and phosphocreatine are important for energy production in the brain. In 2003, Silveri and associates used magnetic resonance techniques to study the effects of SAM-e (1600 mg daily oral dosage) in 12 subjects. Phosphocreatine levels were demonstrated on an MRI (1.5 tesla) to significantly increase over baseline levels in 12 depressed subjects after the SAM-e treatments. ATP levels were lower, indicating that (1) SAM-e helps produce creatine and (2) ATP was utilized to create phosphocreatine for energy storage. ⁽³⁾

A major group of anti-depressants called tricyclic antidpressants, work by increasing serotonin availability in the brain. SAM-e increases serotonin levels in areas associated with depression. In 1989, Otero-Losada studied SAM-e.s effects on serotonin metabolism in the rat brain. Within two hours of SAMe injection (10 mg/kg, i.p), serotonin levels increased in the striatum by 55%, the hippocampus by 82%, and the frontal cortex by 27% and reduced serotonin in the olfactory bulbs by 47%.⁽⁴⁾

Mischoulon reviewed research on SAM-e for major depression, stating that dosages of 200-1600 mg/day in most patients is comparable in effectiveness to tricyclic antidepressants. SAMe also has a faster onset of antidepressive action. Mischoulon states that SAM-e is well tolerated and relatively free of side effects. However, those with bipolar depression may experience increased symptoms of mania and are advised not to take SAM-e. ⁽⁵⁾

SAM-e has been shown to speed symptom improvement in depressive patients taking imipramine. This may be due to an interaction at serotonin 1A receptors, where short term imipramine treatment increases receptor activity in the frontal cortex and provides no immediate antidepressant benefit whereas the addition of SAM-e inhibits this upregulation and shows a faster onset of symptom improvement. ⁽⁶⁾

SAM-e.s effectiveness as an antidepressant may also be due to its role in polyamine synthesis. Polyamines are required for protein production, cell proliferation, and neural plasticity. Recently, antidepressants were demonstrated to increase neurogenesis and neural plasticity. Genedani and associates used rat models of depression to show that the polyamines, putrescine, spermidine and spermine are significantly reduced in the hippocampus and that only putrescine is reduced in the nucleus accumbens. SAM-e at an antidepressant dose for seven days, shows a return to normal or near normal levels of these polyamines. ⁽⁷⁾

In 1993, Salmaggi and associates published a double-blind, placebo-controlled study using SAM-e (1,600 mg/day) for 30 days in 80 postmenopausal depressed women. There were greater improvements that were statistically significant, in the SAM-e group compared to the placebo group. Symptom improvements were noticed by day 10 and continued for the duration of the study. The authors report that adverse effects at this dosage were mild and transient.⁽⁸⁾

Dopamine is a hormone that is involved in pleasure/reward centers in the brain. In 1990, Fava and associates demonstrated an association between SAM-e and dopamine activity in depressed 10 male and 7 female subjects. Both thyrotropin (SH) and prolactin secretions are inhibited by dopamine. In the males but not the females, there was a significant reduction in thyrotropin and prolactin suggesting that SAM-e has a stimulating effect on the dopaminergic system in men.⁽⁹⁾

Those who are interested in a clinical trial using SAM-e, entitled .Safety and Effectiveness of S-Adenosyl-l-Methionine (SAM-e) for the Treatment of Major Depression,. please review the following link: http://www.clinicaltrials.gov/ct/show/NCT00101452?order=1

References

(1)Alpert JE, et al. S-adenoxyl-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. Journal of Clinical Psychopharmacology 2004; 24(6): 661-4.

(2) Pancheri P, et al. 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. International Journal of Neuropsychopharmacology 2002; 5(4): 287-94.

(3) Silveri MM, et al. S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects. Biol Psychiatry 2003: 54(8): 833-9.

(4) Otero-Losada ME, et al. Acute changes in 5-HT metabolism after S-adenosyl-L-methionine administration. General Pharmacology 1989; 20(4): 403-6.

(5) Mischoulon D, et al. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. American Journal of Clinical Nutrition 2002; 76(5): 1158S-61S.

(6) Bellido I, et al. S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat. Neuroscience Letters 2002; 321(1-2): 110-4.

(7) Genedani S, et al. Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression. Neuroreport 2001; 12(18): 3939-42.

(8) Salmaggi P, et al. Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom 1993; 59(1): 34-40.

(9) Fava M, et al. Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant. Journal of Psychiatric Research, 1990; 24(2): 177-84.

(10) S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease. Summary, Evidence Report/Technology Assessment: Number 64. AHRQ Publication No. 02-E033, August 2002. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/epcsums/samesum.htm.

7. SAMe may be beneficial for Attention Deficit Hyperactivity Disorder

D-amphetamine and methylphenidate are frequently used for ADHD because they increase dopamine and norepinephrine levels. Because these medications have side effects, SAMe was used as an alternative because it is a methyl donor. SAM-e also promotes beta adrenergic and dopamine receptor activity. In Dr. Shekim.s preliminary study, 6 out of 8 adult patients improved with ranges from moderate to marked. Side effects were minimal and transient.

Shekim WO, et al. S-adenosyl-L-methioinie in adults with ADHD, RS: preliminary results from an open trial. Pscyhopharmacology Bulletin 1990; 26(2): 249-53.

8. SAM-e supports healthy aging.

S-adenosyl-L-methionine (SAM-e) is a naturally occurring compound in most cells and fluids. It is generally present in higher concentrations during childhood and then diminishes with aging. SAM-e has a number of benefits that support anti-aging. SAM-e increases energy production to maintain cell function despite injuries or toxic assault. It promotes liver detoxification and immune function by providing cysteine for glutathione. SAM-e protects the pyramidal neurons in the hippocampus, the area of learning and memory. SAMe increases serotonin levels and polyamines that play a role in neurogenesis and neural plasticity. SAM-e also reduces stress and anxiety that contributes to neuronal damage.

SAM-e supports healthy aging.

Aging is associated with a number of factors including altered membrane fluidity. SAM-e was previously shown to increase membrane fluidity in laboratory animals. In this study, SAM-e supplementation to Alzheimer.s patients also promoted a marked increase in membrane fluidity for better transfer of products in and out of the cell. ⁽¹⁾

SAM-e also improves function in old and deformed red blood cells. When young, old, and deformed red blood cells were incubated with SAM-e, ATP levels were increased. The levels were higher than with adenosine incubation.⁽²⁾

(1) Cohen BM, et al. S-adenosyl-L-methionine in the treatment of Alzheimer.s Disease. J Clin Psychopharmacol 1988; 8(1): 43-7.

(2) Maeda N, et al. Increase of ATP level in human erythrocytes induced by S-adenosyl-L-methionine. Biochem Pharmacol 1986; 35(4): 625-9.

Notes on taking SAM-e

1. Taking SAM-e on an empty stomach improves absorption.
2. Consult with your physician before reducing other medications.
3. SAM-e is not addictive and side effects are rare in doses of 400 to 1600 milligrams per day.
4. Four to six weeks may be required to feel the full effects of SAM-e as an antidepressant.
5. Avoid alcohol if taking -. Alcohol reduces SAM-e.s benefits.
6. Women who are pregnant or breast feeding should not take SAM-e unless prescribed by a physician.
7. SAM-e should not be abruptly discontinued.
8. SAM-e should be stored in a cool place and out of the reach of children.
9. SAM-e has the ability to stop the development of lesions that can lead to cancer. However, if tumors have already developed, the use of SAM-e may be counterproductive and is not recommended.
10. SAM-e is best taken with Nutracene® www.nutracene.com, a high quality formula that reduces homocysteine levels.
11. SAM-e may also be contraindicated for Parkinson.s disease. While some research supports its use, older studies do not support SAM-e supplementation for Parkinson.s symptoms.

Studies

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.   

.

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)   
01 JUN 2003   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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.   
.

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 United States. Increasing evidence demonstrates that oxidative stress plays an important etiologic role in APAP-induced liver injury. S-Adenosylmethionine (SAMe) is a key intermediate in the hepatic trans-sulfuration pathway and serves as a precursor for glutathione (GSH) as well as the methyl donor in most transmethylation reactions. In the present study, we investigated effects of SAMe on liver injury induced by APAP administration in male C57BL/6 mice. Two related studies were performed. In the first experiment, SAMe (1g/kg BW) was injected intraperitoneally 4 h before APAP (600 mg/kg BW) administration. In the second experiment, SAMe was injected intraperitoneally 1 h after APAP administration. Our results showed that APAP administration induced changes typical of confluent centrilobular necrosis by histological examination and a marked elevation in serum alanine aminotransferase (ALT) activity. APAP administration induced significant decreases in both hepatic and blood SAMe concentrations. In addition, APAP decreased intracellular (both cytosolic and mitochondrial) GSH concentrations along with increased lipid peroxidation in conjunction with mitochondrial dysfunction as documented by Ca2+-induced mitochondrial permeability transition. SAMe treatment (both before and after APAP) significantly attenuated the liver injury. Exogenous SAMe prevented the decrease in liver and blood SAMe concentrations. Moreover, SAMe treatment attenuated both cytosolic and mitochondrial GSH depletion as well as mitochondrial dysfunction. We conclude that SAMe at least in part protects the liver from APAP-induced injury by preventing intracellular GSH depletion and mitochondrial dysfunction.; Copyright 2004 S. Karger AG, Basel   

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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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 N¹ 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., Amsterdam. All rights reserved.   
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
Bell, K. M.; Potkin, S. G.; Carreon, D.; Plon, L.   

JOURNAL NAME- Acta Neurologica Scandinavica, Supplement   
89/154 (15-18)   
COPYRIGHT- Copyright 2004 Elsevier B.V., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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 Europe and more recently in the United States have shown that SAMe, related to depressive syndromes, is effective as tricyclic, but it has some characteristics which distinguish it from other antidepressant drugs. They are: - absence of side effects particularly at liver level; - rapid effect and therefore short period of latency between administration and therapeutic activity.   

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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
ISSN- 0149-7634   
PUBLICATION YEAR- 1988   


NO-ABSTRACT


S-adenosylmethionine treatment of depression : A controlled clinical trial   
Bell, K. M.; Plon, L.; Bunney, Jr W. E.; Potkin, S. G.   

JOURNAL NAME- American Journal of Psychiatry   
145/9 (1110-1114)   
COPYRIGHT- Copyright 2004 Elsevier B.V., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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.; Del, Vecchio M.   

JOURNAL NAME- Neuropsychobiology   
7/4 (188-191)   
COPYRIGHT- Copyright 2004 Elsevier B.V., Amsterdam. All rights reserved.   
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., Amsterdam. All rights reserved.   
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 Impres