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The Wonders of SAMe

SAMe or s-adenosyl-l-methionine has been the subject of many clinical trials in Europe and now in the United States. SAMe was discovered in Italy in 1952– not surprisingly, most of the research on SAMe has been conducted in the country of its discovery.

So what is SAMe? S-Adenosylmethionine (SAM) is an important physiological agent formed in the body by combining the essential amino acid methionine with adenosyl-triphosphate (ATP). SAM is involved in over 40 biochemical reactions in the body and it works closely with vitamins B-12 and folic acid. Normally the body manufactures all the SAM it needs from the amino acid methionine. However, a deficiency of methionine, vitamin B12, or folic acid can result in decreased SAM synthesis. In addition, tissue levels of SAM are typically low in the elderly and in patients suffering from osteoarthritis, depression, and various liver disorders. There are five principal conditions where SAMe is used: depression, osteoarthritis, fibromyalgia, liver disorders, and migraine headaches. SAM is also required in the manufacture of all sulfur-containing compounds in the human body, including glutathione and various sulfur-containing cartilage components.

  • SAMe is essential for the production of brain neurotransmitters (chemical messengers) such as dopamine, norephinephrine, epinephrine and serotonin. It enhances cell membrane fluidity and cellular communication. The beneficial effects of SAMe supplementation are far-reaching because of its central role in so many metabolic processes.

Let’s look at how same can be beneficial with depression, osteoarthritis, fibromyalgia, migranes and liver disorders.


SAMe is necessary in the manufacture of important brain compounds such as neurotransmitters and phospholipids like
phosphatidylcholine and phosphatidylserine. Supplementing the diet with SAMe in depressed patients results in increased levels of serotonin, dopamine, and phosphatidylserine. It improves binding of neurotransmitters to receptor sites, which causes increased serotonin and dopamine activity and improved brain cell membrane fluidity, all resulting in significant clinical improvement.

The antidepressive effects of folic acid (Vitamin B6) are mild compared to the effects noted in clinical trials using SAMe. Based on results from a number of clinical studies, it appears that SAMe is perhaps the most effective natural antidepressant (although a strong argument could be made for the extract of St. John’s Wort standardized to contain 0.3 percent hypericin). More recent studies using a new oral preparation at a dosage of 400 milligrams four times daily (1600 mg total) demonstrate that SAMe is just as effective orally as it is intravenously. SAMe is better tolerated and has a quicker onset of antidepressant action than tricyclic antidepressants.

In addition to generalized depression, there are two conditions associated with depression where SAMe produces significant effects: the postpartum (after pregnancy) period and drug rehabilitation. SAMe benefits in these conditions probably stem from a combination of its effects on brain chemistry and liver function.


In a double-blind study, orally administered SAMe (800 milligrams daily) was compared to a placebo for 6 weeks in 44 patients with fibromyalgia. Researchers evaluated tender point score, muscle strength, disease activity, subjective symptoms, mood parameters, and side effects. Patients given SAMe demonstrated improvements in clinical disease activity, pain experienced during the last week, fatigue, morning stiffness, and mood; however, the tender point score and muscle strength did not differ in the two treatment groups. SAMe was without side effects.

The most recent study compared SAMe to transutaneous electrical nerve stimulation (TENS)– a popular treatment for fibromyalgia– in 30 patients with fibromyalgia. Patients receiving SAMe (200 milligrams by injection and 400 milligrams orally daily) demonstrated significantly greater clinical benefits—decreased number of tender points, subjective feelings of pain and fatigue, and improved mood. TENS offered little benefit on most symptoms while SAM was deemed “effective in relieving the signs and symptoms of primary fibromyalgia.”


SAMe is beneficial in the treatment of migraine headaches. The benefits manifest gradually and require long-term treatment for therapeutic effectiveness. This is due to the ability of SAMe to enhance liver detoxification functions. The liver depends on same for regeneration, detoxification, bile production, methylation and the production of a substance called glutathione, a liver antioxidant.

This again relates to its ability in dealing with drug rehabilitation, excessive and unbalanced estrogen levels, and in conjunctions with hepatitis c treatments.

Joint and Connective tissue:

SAMe is essential for the rebuilding of connective tissue and the manufacture of cartilage components. Numerous clinical studies indicate that it can reduce pain, stiffness and inflammation. Doses range from 400mg to 1200 mg daily.

It is recommended to take SAMe on an empty stomach preferably one hour before eating. Usual doses are started at 200mg daily with a gradual increase every five days until desired effects are felt. It may take up to four weeks for some to notice the effects but most will be noticed within one week. Since SAMe is unstable at high temperatures it is recommend to be refrigerated. It is also important to use enteric-coated tablets to ensure stability, maximum adsorption and to avoid nausea and gastrointestinal disturbances. It is safe for pregnancy and lactation. There are no reported negative interactions with other medications or nutritional supplements.

SAMe is converted to homocysteine, which is known for its increasing risk of cardiovascular disease, when taken at high levels unless the cofactors of Vitamin b 6 (50mg), Vitamin b 12 (1000mcg), and folic acid (800mg) are taken with it. A good quality multiple vitamin supplement may be adequate but you need to check.

There are two forms of pharmaceutical grade same, tosylate and a newer more stable one called butanedisulfide. Due to the expense of SAMe at the current time many cannot afford to use this supplement. Be aware of companies promoting SAMe and be sure to research their sources.

As with any therapy it is important to consult with your health care practitioner when treating specific conditions.

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