SAMe - Medicinal Uses, Interactions, Side Effects, Dosage
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<p><strong>SAMe</strong> </p>
<p>S-adenosylmethionine is also known as ademetionine, SAM, or SAMe. The <em>"e" </em>in SAMe designates that SAM is endogenous. SAMe is a naturally occurring substance that functions as a methyl donor in methyl-transferase reactions for phospholipids, neurotransmitters, proteins, and deoxyribonucleic acid (DNA). </p>
<p><strong>Uses and Benefits:</strong></p>
<p>SAMe is mainly used for osteoarthritis and depression. It has been widely accepted in European countries, where it first became popular as a therapeutic agent in the 1980s. SAMe has also been employed to treat intrahepatic cholestasis of pregnancy, alcoholic liver cirrhosis, fibromyalgia, and migraine headaches, and for a variety of other conditions.</p>
<p><strong>Pharmacology: </strong></p>
<p>SAMe is formed by the amino acid methionine and adenosyltriphosPhate (ATP); it is not an essential nutrient in humans. Endogenously, folic acid and vitamin are required for its synthesis. SAMe may offer chondroprotective properties by enhancing synthesis of proteoglycans in articular chondrocytes. SAMe may also inhibit tumor necrosis factor-a (TNF-a) which is a pro-inflammatory cytokine that has been implicated in the patho­genesis of joint diseases and numerous other conditions. SAMe inhibits platelet aggregation <em>in vitro </em>by increasing vascular pro­duction of prostacyclin (an endogenous prostanoid with anti-ag­gregant and vasodilator effects).</p>
<p><strong>Clinical Trials: </strong></p>
<p>While SAMe has been evaluated in limited clin­ical trials for a number of uses, osteoarthritis and depression are the two primary indications that have been most studied using oral preparations. </p>
<p> Osteoarthritis-Many randomized, controlled clinical trials have been conducted evaluating the effectiveness of SAMe for osteoarthritis. These studies were all published in the 1980s, mainly in the proceedings of a SAMe osteoarthritis symposium. No new clinical trials have been published since then. All studies concluded that SAMe is effective in relieving the clinical symp­toms associated with osteoarthritis. Improvements in pain relief, morning stiffness, walking distance, and active and passive range of motion were all observed. SAMe was considered to be equal in analgesic and anti-inflammatory efficacy to common nonsteroidal ant-inflammatory drugs (NSAIDs).</p>
<p><strong>Adverse Effects:</strong></p>
<p>SAMe was generally well tolerated in the clinical trials. Side effects of the oral formulations, which were uncommon, included flatulence, nausea, vomiting, diarrhea, headache, and anxiety. A few patients developed mania and hypomania after receiving SAMe which also occurs with phar­maceutical antidepressants. </p>
<p><strong>Side Effects and Interactions:</strong> </p>
<p>No serious drug interactions have been reported for SAMe. Since SAMe may increase central serotonin levels, it is possible that it can have additive effects when combined with other drugs that inhibit serotonin reuptake. There is one case report of a "serotonin syndrome" in a patient taking SAMe and clomipramine. SAMe, however, has been combined with TCAs without any adverse consequences. Until more is known, patients should avoid combining SAMe with other antidepressants.</p>
<p> <strong>Cautions: </strong></p>
<p>SAMe should not be used in patients with a history of mania or bipolar disorder. The safety of the commercially available SAMe in pregnancy and lactation is unknown.</p>
<p> <strong>Preparations </strong><strong>& </strong><strong>Doses: </strong></p>
<p>To minimize gastrointestinal upset, oral SAMe is often initiated at 200 mg once or twice daily. For osteoarthritis, the dose may be increased every 1 or 2 weeks until a dose of 400-1600 mg daily is achieved. For depression, the typical initial dose used in the positive clinical trials was 1600 mg daily (in divided doses), or doses quickly increased up to this amount within 1 week; maintenance doses of 200 mg twice daily have been used. According to clinical trials, SAMe has an onset of action ranging from a few days to 2 weeks.</p>
<p>SAMe has poor oral absorption and undergoes extensive firstpass metabolism by the liver. Some of the clinical trials used intravenous or intramuscular routes of administration to avoid the high firstpass liver metabolism. Oral formulations are enteric coated to improve absorption. SAMe is synthesized from yeast fermentation and is not derived from human or animal sources. Large doses, such as 1600 mg/day, can be costly. </p>
<p><strong>Summary Evaluation:</strong></p>
<p>While SAMe is well tolerated and may be mildly effective in both osteoarthritis and depression, significant study design flaws in the existing literature make it difficult to evaluate this agent. atients should not expect major improvements. <em>SAMe </em>may be a useful alternative for those who do not want to use orthodox phar­maceuticals or who cannot tolerate prescribed drugs, but current clinical data regarding safety and efficacy with chronic use is preliminary and incomplete. </p>
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