Useful in the treatment of:

History: SAM was first discovered in 1953. This occurred in Italy and reports suggested that this could be used in the treatment of depression. This widely spread in Europe in the early 70s and in 1977, first became commercially available in Europe for that purpose. In the United States, SAM was not available until the spring of 1999.

Description: SAM is necessary for over 40 different biochemical reactions in the body. SAM functions as a methyl-donor molecule and so has a key function in many metabolic pathways involving transfer of methyl groups. SAM is much more effective in methyl group transfer than other methyl donors. Methylation reactions are important in detoxification processes as well as creation of brain chemicals and other components, such as anti-oxidants and components of joint tissues. These effects and the importance of SAM are far-reaching because of the central role it plays in many metabolic pathways.

Sources: SAM is normally manufactured in the body by combining essential amino acid methionine with adenosyl-triphosphate (ATP). Also required in conjunction with SAM in methylation reactions are Vitamin B-12, folic acid, Vitamin B-6 and choline.

Available forms of SAM: SAM is available in parenterally administered (IV)form or an oral form, which is a stabilized salt. SAM does cross the blood/brain barrier. Half-life, metabolism, and excretion are not well-known. There is some debate on the bio-availability of the oral preparations of SAM, however, there are numerous double-blind studies documenting the effectiveness of the oral form.

Primary uses of SAM: There are primarily five conditions where SAM has been utilized. These include depression, osteoarthritis, fibromyalgia, liver disorders and migraine headaches. There has also been noted to have severely depressed levels of SAM in patients with Alzheimers Disease and Parkinsons Disease.

Depression: The exact mechanism of action for treatment of depression is not known. SAM is important for the manufacture of certain brain chemicals such as neurotransmitters and phospholipids such as phosphatidylcholine and phosphatidylserine. Possible hypothesis of its effect deals with increasing neurotransmitters such as serotonin and norepinepherine and increasing the responsiveness of neurotransmitter receptors and in improving cell membrane function through its production of the phospholipids. There are over 40 clinical trials evaluating SAM for depression. Many of these compared SAM with placebo and/or antidepressant drugs. Most of these studies used SAM in the parenteral form, but there are at least five which compared these to the oral form. In general, it was shown SAM to be as effective as the antidepressant medication and superior to that of placebo. General dosages ranged from 1200-1600 mg. per day.

Osteoarthritis: SAM has had some impressive results in studies in the treatment of osteoarthritis. These were compared with both placebo and other prescription osteoarthritis drugs in double-blind trials. Patients demonstrated improvement in clinical symptoms and reduction in pain with SAM, similar to those of the NSAIDS, however, with higher tolerability and less side effects. SAM is important for the manufacture of cartilage components and this was shown in a double-blind study in Germany of a small number of patients using MRI imaging, increased cartilage response in patients given SAM. It is also demonstrated some mild pain relieving and anti-inflammatory effects in animal studies. SAM has also improved depression often associated with osteoarthritis. Many of these studies used orally administered SAM. General dosages in these studies for SAM ranged from 400-1200 mg. per day. Most of the comparative studies with SAM evaluated symptoms such as pain at rest, pain on motion, morning stiffness, swelling, range of motion, etc.

Fibromyalgia: Fibromyalgia is a disorder of chronic musculoskeletal pain and fatigue. Depression is often associated. Studies have been done utilizing SAM both parenterally (at a dose of 200 mg. per day) and orally (at doses ranging from 400-800 mg. per day). Patients in these studies have demonstrated improvement in numbers of trigger points, pain and fatigue, and mood.

Liver disorders: Because of its importance as a methyl-donor, SAM has been shown to be beneficial in liver disorders including cirrhosis and Gilberts syndrome and estrogen or oral contraceptive induced cholestasis. Because SAM performs an important function in the liver in inactivating estrogen, it has also been found useful in premenstrual syndrome. General dosages used ranged from 400-1200 mg. daily.

Migraine headache: Benefit in this condition reportedly occurs gradually and require long-term treatment. Reported dosages utilized range from 400-1200 mg. a day.

Adverse reactions and safety: SAM should not be utilized in individuals with bipolar depression (manic) since SAMs anti-depressant activity can aggravate the manic phase in these individuals. In general, SAM is well-tolerated and does not seem to have other significant side effects. It does not appear to cause anticholinergic side effects. There have been some reports of nausea or gastrointestinal disturbances. This generally though, can be avoided by starting dosages at 200 mg. twice daily, increasing to 400 mg. twice daily by day three, into 400 mg. three times a day by day 10 and then finally to higher doses, if needed after day 20. This is generally followed when utilized for depression because of the higher dosages utilized. In osteoarthritis, if an initial higher dose is utilized over the first three weeks, this then can be reduced to more of a maintenance level of 200 mg. twice daily. There has been a question of the relationship of SAM and homocysteine. There was a study reported in August 1997 that showed after oral administration of SAM, 400 mg., the levels of homocysteine and methionine did not change and in fact, there was a positive effect on a key co-factor in homocysteine metabolism, 5-methyltetrahydrofolate. Also, there are no drug or supplement interactions with SAM.

Contraindications: SAM is contraindicated if a history of mania or bipolar disorder is present.
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