Discount prices on pet meds!
BMC Musculoskelet Disord. 2004 Feb 26;5(1):6. : S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. [ISRCTN36233495].
Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW.
Department of Family Medicine & Geriatrics, University of California, Irvine, Medical Center, 101 City Drive, Orange, CA 92868, USA.
winajm@uci.edu

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 1: Clin Cancer Res. 2004 Feb 15;10(4):1299-305. : Clinical efficacy, tolerability, and safety of SAM486A, a novel polyamine biosynthesis inhibitor, in patients with relapsed or refractory non-Hodgkin's lymphoma: results from a phase II multicenter study.
Pless M, Belhadj K, Menssen HD, Kern W, Coiffier B, Wolf J, Herrmann R, Thiel E, Bootle D, Sklenar I, Muller C, Choi L, Porter C, Capdeville R.
University Hospital of Basel, Switzerland.
mpless@uhbs.ch

PURPOSE: SAM486A is a new inhibitor of S-adenosyl-methionine-decarboxylase, a key enzyme for polyamine biosynthesis. It is more potent than the first generation S-adenosyl-methionine-decarboxylase inhibitor methylglyoxal bis-guanylhydrazone. This Phase IIa study reports the findings of SAM486A monotherapy in patients with refractory or relapsed non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Forty-one previously treated patients with either diffuse large cell, follicular, or peripheral T-cell NHL were treated i.v. with 100 mg/m(2) SAM486A as a daily 1-h infusion for 5 days repeated every 3 weeks. Treatment was continued for a total of eight cycles or until disease progression. RESULTS: Two patients, both with large B-cell lymphoma, showed a complete response at cycle 3 that was maintained for >or=13 and >or=28 months. Five patients had a partial response, and 3 had stable disease at last follow-up. The overall response rate (complete response plus partial response) was 18.9% for evaluable patients (7 patients). Anemia was the primary hematological toxicity and observed in 7 (17.1%) patients. Five patients experienced grade 3/4 anemia. Four patients (9.8%) experienced grade 3/4 febrile neutropenia and grade 3/4 thrombocytopenia, respectively. Nonhematological toxicities were mild to moderate in intensity. The most frequent side effects were nausea (39%), vomiting (22%), diarrhea (19.5%), asthenia (17.1%), abdominal pain (14.6%), and flushing (9.8%). CONCLUSION: SAM486A has a promising clinical activity in patients with poor prognosis NHL and manageable safety profile. To further define the role of SAM486A, in the treatment of NHL, additional studies are warranted.
Curr Psychiatry Rep. 2003 Dec;5(6):460-6. R: S-adenosyl-methionine in depression: a comprehensive review of the literature.
Papakostas GI, Alpert JE, Fava M.
Depression Clinical and Research Program, Massachusetts General Hospital, 15 Parkman Street, WACC 812, Boston, MA 02114, USA.
gpapakostas@partners.org

As many as 29% to 46% of patients with major depressive disorder (MDD) show only partial or no response to an adequate course of an antidepressant. The current practice is to increase the dose, switch to another antidepressant, or to combine the initial antidepressant with an antidepressant of a different class or a non-antidepressant agent. A growing number of studies have also been directed toward exploring the potential use of augmenting traditional antidepressants with nonpharmaceutic supplements, or even using such supplements as monotherapy for depression. S-adenosyl-methionine (SAMe) is one such compound. Compared with many other nonpharmaceutic supplements, SAMe has been extensively studied, and impressive literature extending back three decades suggests the antidepressant efficacy of SAMe. In the present work, the authors summarize the literature, focusing on the potential role of SAMe and its precursors in the pathophysiology of MDD, followed by a review of studies examining the use of SAMe for the treatment of MDD. Finally, the authors propose a model that would explain the actions of SAMe in the central nervous system. J Gastroenterol Hepatol. 2002 Apr;17(4):448-55. : Treatment of alcoholic hepatitis.
Maher JJ.
Liver Center Laboratory, Department of Medicine, University of California-San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
jmaher@medsfgh.ucsf.edu
Alcoholic hepatitis is a common disease with an overall 1-year mortality of 20%. Although the classical treatment for alcoholic hepatitis is abstinence, in some individuals abstinence alone is inadequate to promote survival and recovery. This is particularly true of patients with severe alcoholic hepatitis, who are identified by jaundice, coagulopathy and neutrophilia. Within the last two decades, several agents have been examined as treatments for alcoholic hepatitis and cirrhosis. They have targeted several key processes in the pathophysiology of alcoholic liver disease, including hypermetabolism, inflammation, cytokine dysregulation and oxidant stress. The compounds that offer the greatest survival benefit to patients with severe alcoholic hepatitis are corticosteroids. Several groups have reported excellent results with corticosteroids, but positive results are not uniform, and there remains some controversy over their efficacy. Even if corticosteroids are beneficial for alcoholic hepatitis, they are not recommended for all patients at risk. Consequently, other agents are being tested that have broader applicability to individuals with contraindications to steroids. In this regard, pentoxifylline shows some promise, as does enteral feeding with medium chain triglycerides. Independent efforts are also being directed toward treatment of chronic alcoholic liver disease and alcoholic cirrhosis. Anti-oxidants have received the greatest attention; drugs such as S-adenosyl-methionine may be of benefit. This and others are under active study. Copyright 2002 Blackwell Publishing Asia Pty Ltd
DENOSYL is the dog and cat version of SAMe or S-adenosyl-L-methionine USED TO IMPROVE HEPATIC GLUTATHIONE LEVELS AND MAINTAIN AND PROTECT LIVER FUNCTIONbesides helping joints and depression. It is sold as non prescription here but as prescription in Europe where it has been used for years. For bipolar people, it can produce mania without a mood stabilizer.
Cleo's Liver Recovery with SAMe S-adenosyl-L-methionine and SAME Research
great dane dog recovered from liver poisoning with SAMe S-adenosyl-L-methionine Denosyl

Cleo is our miracle girl - she had the Lantana poisoning, then dx with os in Dec. of last year and amputation and chemo following. She bloated on Good Friday, with surgury to correct, followed by cardiac complications, and DIC (difuse intervascular [or intra - not sure] clotting). That ruled out her last chemo treatment, and most of her cancer diet. The photo was about 2 1/2 weeks after the bloat surgery. She is still going strong, as best we can tell....haven't put her through x-rays after all of that. She will be 8 years old in September (2003)

There is a veterinary approved SAMe product called Denosyl. Last summer, Cleo had her first return from near death - ate a posoinous plant called lantana (I had no idea it was posoinous - shame on me - she had been nibbling at it for years without adverse effects)- causes liver damage - she was at the vet for a week and they did not think whe would make it for a few days. They sent her home on Denosyl for the liver damage, and inside of 6 weeks she had normal liver enzymes. It it great - you may want to check their website for dosage. You cannot give it near eating time as that adversely affects its absortion. If you buy supplement grade SAMe, rather than the veterinary grade, be sure to get individually blister wrapped pills - everything I have read says that it degrades very easily in light/heat. the SAMe you buy at Walmart has no quality control standards it must meet - the Denosyl is a veterinary grade product, meaning likely better quality controls. It is made by Nutramax, the people who make Consequin. I think you can buy it on the pet med. type websites without a prescription. If you want generic SAMe, I think consumer reports did a review - if I recall correctly, some of the less expensive brands were better than some expensive ones - better purity and more SAMe. Also, that is where I saw that it is very important to select a product that is blister packed, as the stuff degrades so easily. .


nutramax labs writeup on denosyl the veterianian product

Z Gastroenterol. 2003 Apr;41(4):333-42. : [Alcoholic liver disease]
[Article in German]
Stickel F, Seitz HK, Hahn EG, Schuppan D.
Medizinische Klinik I und Poliklinik, Friedrich-Alexander-Universitat Erlangen-Nurnberg.
felix.stickel@med1.imed.uni-erlangen.de

Alcoholic liver disease is the most frequent organ damage encountered in chronic alcoholics and the annual death rate attributed to alcohol-induced end-stage liver disease exceeds that of car accidents. Alcoholic liver damage occurs mainly due to the toxicity of its first metabolite acetaldehyde, and due to interactions with numerous macro- and micronutrients. Established treatment options comprise psychotherapy aiming to achieve abstinence, nutritional therapy, management of hepatological complications, and liver transplantation in selected individuals. Since these therapeutic approaches are unsuccessful in many patients, pharmacological therapies of alcoholic liver disease are being investigated. Many drugs failed to be beneficial or have even shown toxicity. However, some agents are promising, such as S-adenosyl-L-methionine (SAMe), pentoxifylline, metadoxin, polyenylphosphatidylcholine or inhibitors of the cytochrome P450 2E1 isoenzyme. In severely ill patients with alcoholic hepatitis, drugs with anti-tumor necrosis factor alpha activity are currently investigated in clinical trials. If and how far corticosteroids are beneficial remains controversial and their use should be restricted to selected patients. Anabolic steroids used to enhance the nutritional status may lead to serious side effects while having a marginal benefit. Silymarin has not been proven efficacious in alcoholic cirrhosis and clinical trials are ongoing which aim to elucidate its therapeutic value in less advanced stages of liver disease. Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression.
The mechanism(s) of the antidepressant activity of S-adenosyl-L-methionine (SAMe) have not yet been elucidated. SAMe is essential for the synthesis of polyamines, which have a key role in protein synthesis, cell proliferation, and neuronal plasticity. On the other hand, accumulating data indicate that depression is associated with a reduction in regional brain volume and that antidepressants increase neurogenesis in defined brain regions and also influence neuronal plasticity. Here we show that in a validated rat model of depression (chronic unpredictable mild stress-induced anhedonia) there is a significant reduction of putrescine, spermidine and spermine in the hippocampus, and of only putrescine in the nucleus accumbens septi. SAMe, at a fully antidepressant dose (300 mg/kg i.m., daily for 7 days), completely restores the levels of putrescine in the nucleus accumbens, and restores in part the levels of both spermidine and spermine in the hippocampus. These results may suggest (i) a role for brain polyamines in depression and in reward processes, and (ii) that the antidepressant effect of SAMe may be due, at least in part, to a normalization of putrescine levels in the nucleus accumbens septi.
[ Stress-induced dynamic changes in mouse brain polyamines. Role in behavioral reactivity
Recent findings indicate that rapid and transient changes in polyamine metabolism, termed the polyamine-stress-response, may occur repeatedly in the brain after chronic intermittent stress. Here, we sought to examine the effects of chronic intermittent restraint stress, or of daily intraperitoneal dexamethasone injections on polyamine concentrations in the hippocampus of adult male C57BL/6 mice. Additionally, we studied the effects of alpha-difluoromethylornithine, an irreversible ornithine decarboxylase inhibitor, on stress-induced changes in polyamines and on behavioral reactivity to novelty stress measured in an open-field arena. As previously observed, following a single stress episode putrescine concentration increased transiently, but the polyamines spermidine and spermine remained unchanged. Following chronic restraint stress, putrescine concentration was increased after each daily stress episode with the largest increase observed after the 4th episode, while spermidine was increased just after the 2nd and 4th episodes and spermine only after the 4th daily episode. In contrast, all polyamine concentrations were increased after 10 injections of either dexamethasone or vehicle (0.9% NaCl). A 14-day course of alpha-difluoromethylornithine treatment resulted in a complete putrescine depletion and over 50% reduction in polyamines, and led to changes in open field activity indicative of altered emotional behavior. CONCLUSIONS: (a) while putrescine concentration increases in the hippocampus after each restraint stress episode, spermidine and spermine undergo a delayed but transient increase; (b) in contrast, chronic dexamethasone treatment may lead to a permanent increase in the concentrations of all polyamines and; (c) chronic alpha-difluoromethylornithine treatment reduces brain polyamine concentrations and modulates emotional reactivity to novelty stress. The study indicates that the brain polyamine-stress-response is a dynamic process that varies with the type, intensity and length of stressful stimuli, and implicates this response as an adaptive mechanism in the reaction to stressors.]
{ Melatonin attenuates the changes in polyamine levels induced by systemic kainate administration in rat brains
Systemically administered kainate has been demonstrated to induce neuronal damage and changes of the levels of biochemical substances related to neurotoxicity. Polyamines are thought to be important in the generation of edema and neuronal cell loss associated with various type of excitotoxicity. Melatonin exerts potent free radical scavenging, antioxidant, and neuroprotective properties. This study was designed to estimate the effect of exogenous melatonin administration on the changes of polyamine levels in rat brains after systemic administration of kainate. Kainate [10 mg/kg, intraperitoneally (i.p.)] was injected into the rats to produce excitotoxicity. Melatonin (15 mg/kg, i.p.) was administered 1 h before, immediately after, and 1 h after kainate treatment. We examined the polyamine [putrescine (PU), spermidine (SD) and spermine (SM)] levels in the cerebral cortex and hippocampus and neuronal density in the hippocampal CA1 and CA3 subsectors in brain sections. PU levels were increased 8 and 24 h after kainate treatment and the administration of melatonin attenuated these changes. Only minor changes were noted in the levels of the polyamine SD and SM after the kainate treatment. In histology, neuronal injuries in the hippocampal CA1 and CA3 subsectors were examined 3 days after kainate treatment and melatonin reduced the kainate-induced neuronal injuries. Our results show that melatonin inhibits the polyamine responses in the cerebral cortex and hippocampus following kainate-induced excitotoxicity and PU may be responsible for the protective effect of melatonin against kainate-induced excitotoxicity.}

Mov Disord 2000 Nov;15(6):1225-9 S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial.
Di Rocco A, Rogers JD, Brown R, Werner P, Bottiglieri T.
Department of Neurology, Beth Israel Medical Center-Albert Einstein College of Medicine, New York, NY 10003, USA.
We report a pilot study of S-adenosyl-methionine (SAM) in 13 depressed patients with Parkinson's disease. All patients had been previously treated with other antidepressant agents and had no significant benefit or had intolerable side effects. SAM was administered in doses of 800 to 3600 mg per day for a period of 10 weeks. Eleven patients completed the study, and 10 had at least a 50% improvement on the 17-point Hamilton Depression Scale (HDS). One patient did not improve. Two patients prematurely terminated participation in the study because of increased anxiety. One patient experienced mild nausea, and another two patients developed mild diarrhea, which resolved spontaneously. The mean HDS score before treatment was 27.09 +/- 6.04 (mean +/- standard deviation) and was 9.55 +/- 7.29 after SAM treatment (p < 0.0001). Although uncontrolled and preliminary, this study suggests that SAM is well tolerated and may be a safe and effective alternative to the antidepressant agents currently used in patients with Parkinson's disease.
1: Nutrition 1998 Jul-Aug;14(7-8):605-10 Related Articles, Books, LinkOut Immunonutrition: role of sulfur amino acids, related amino acids, and polyamines. Grimble RF, Grimble GK. Institute of Human Nutrition, University of Southampton, UK. Pro-inflammatory cytokines mediate widespread changes in protein metabolism. Amino acids released from peripheral tissues fulfill a number of functions. They act as substrate for acute phase protein and immunoglobulin synthesis and, together with polyamines, in the replication of immune cells. Demands for specific amino acids may outstrip the supply from endogenous sources. A number of strands of evidence suggest that sulphur amino acids, and amino acids that are metabolically related to them, may be required in increased amounts. Protein deficiency impairs the acute phase response. However, sulfur amino acid insufficiency compromises glutathione synthesis, to a greater extent than hepatic protein synthesis, in the presence and absence of an inflammatory stimulus. The resulting effect may be compromised antioxidant defences. Functioning of T cells is dependent on intracellular glutathione concentrations and may also be affected by sulphur amino acid insufficiency. It has been suggested that the increased N excretion, which occurs during the immune response, is a reflection of a relative imbalance in the profile of amino acids released from peripheral tissues and the requirements imposed by the synthesis of substances involved in the acute phase response. Phenylalanine, tyrosine, tryptophan serine, and cysteine are released in amounts closest to requirements. Polyamine synthesis may be important for the fidelity of the enhanced level DNA transcription and RNA translation that occurs in response to infection and during tissue repair, gut growth after surgery, and in gut barrier functions. Although synthesized de novo from ornithine, arginine and S-adenosyl methionine (SAM), substantial recycling is a key feature of polyamine metabolism. The recycling may be a reflection of the need to maintain adequate tissue SAM during periods of rapid cell growth. During an immune/inflammatory response the combination of enhanced utilization of cysteine for glutathione synthesis and cell replication may lead to depletion of cellular SAM. A relatively small addition of polyamines to the diet may improve gut-associated aspects of the hosts' antibacterial defenses.
               

               Taken for two decades by Europeans as a remedy
               for depression and arthritis, SAMe (pronounced
               "sammy," short for S-adenosylmethionine) was
               introduced in the U.S. in March of last year. Its
               supporters maintain this natural supplement can
               alleviate the symptoms of depression safely and
               more rapidly than standard antidepressants. And in
               the case of SAMe, these claims are backed by
               some convincing data. 
SAMe is a naturally occurring compound that regulates the action of key brain chemicals such as serotonin and dopamine, which may play a role in combating depression. It also generates enzymes that may help repair joints and the liver.
SAMe was discovered by Italian scientists in 1952, and much of the research on the compound and its possible benefits has been conducted in Italy and other European countries. Because it's being marketed as a supplement in the U.S., SAMe has not been subjected to the rigorous clinical testing required for FDA approval. However, it has been evaluated over the years as a treatment for depression, arthritis, and certain forms of liver disease in dozens of European trials involving thousands of patients. Approved as a prescription drug in Italy, Germany, Spain, and Russia, SAMe has been given successfully for two decades without producing any significant adverse effects, though mild digestive upset occasionally occurs.
Banishing the blues
Levels of SAMe are lower than normal in many people with depression, and a 1994 study by University of California researchers found that as the symptoms of depression eased, SAMe blood levels rose. Also in 1994, a major review in Acta Scandinavica Neurologica evaluated the results of more than a dozen clinical trials of SAMe for depression. This analysis revealed that SAMe was consistently more effective than a placebo in relieving depressive symptoms and that its efficacy was comparable to that of standard antidepressants. It appears that about 70% of depressed patients respond to SAMe, roughly the same proportion that benefit from treatment with the tricyclics or newer antidepressants such as Prozac.
Two important pluses for SAMe: It doesn't cause the side effects that have been linked to antidepressant drugs, including dry mouth, blurred vision, headache, drowsiness, insomnia, nervousness, and poor sexual function; and it typically works much more rapidly than the prescription drugs. "Most people taking SAMe see some effect within 10 days," says Baylor University's director of neuropharmacology, Teodoro Bottiglieri, Ph.D. By contrast, people often have to take standard antidepressants for several weeks--even a month or more--before the clouds of depression start to lift.
Although those with mild mood problems might well benefit from a trial of SAMe, experts caution that anyone experiencing serious depression should use the supplement only under the supervision of a physician or psychiatrist. In addition, SAMe should not be taken by anyone with manic depression (bipolar disorder), because it may intensify the manic "up" episodes.
Easing arthritis pain
There is also evidence that SAMe can foster joint health by preserving the gellike, shock-absorbing nature of cartilage, and it may even help repair damaged cartilage. That SAMe could relieve more than low spirits became apparent when some individuals who had been taking the compound for depression reported an unexpected bonus--relief from painful and often long-standing symptoms of osteoarthritis.
More than a decade ago, a large trial in Italy found that SAMe was more effective than a placebo, and as effective as the NSAID pain reliever naproxen, in relieving the pain of osteoarthritis. It also appeared to be safer, causing none of the stomach bleeding that occurs in some patients taking NSAIDs.
Protecting the Liver
Ongoing research suggests that SAMe may be effective for liver disease. SAMe is the body's major source of glutathione, sometimes dubbed the "master antioxidant," a substance that detoxifies harmful compounds and helps repair liver damage. By boosting glutathione levels, SAMe protects tissues from damage by oxygen free radicals. For example, a controlled trial in Spain (Journal of Hepatology, 6/99) found that long-term use of SAMe may delay the need for a liver transplant and improve survival rates in patients with alcohol-induced cirrhosis. Some doctors combine SAMe with the herb milk thistle for serious liver ailments; further study is needed.
Easing fibromyalgia
SAMe has also shown promise in treating fibromyalgia. A 1991 European study that compared SAMe with a placebo in 44 fibromyalgia sufferers found the supplement eased symptoms of the disorder, including pain, fatigue, and depression.
Suggested dose: SAMe is sold in 200 mg pills; it is quite costly, ranging from around $1 to $2 per pill. Take twice a day, an hour before breakfast and lunch for best absorption. Also take folic acid (800 mcg a day) and vitamin B12 (1,000 mcg a day) because SAMe will not work when levels of these vitamins are low. Depression: Start with 200 mg twice daily (400 mg a day); gradually increase, if necessary, to 800 or even 1,600 mg a day. Arthritis: 400 to 800 mg a day. Liver ailments:1,200 mg a day. Fibromyalgia: 800 mg a day.