S-Adenosylmethionine (SAMe) is a naturally occurring compound that is found in almost every tissue and fluid in the body, and is involved in many important processes. SAMe plays a role in the immune system, maintains cell membranes, and helps produce and break down brain chemicals, such as serotonin, melatonin, and dopamine. It works with vitamin B12 and folate (vitamin B6). Being deficient in either vitamin B12 or folate may reduce levels of SAMe in your body.

Numerous scientific studies have shown that SAMe helps relieve the pain of osteoarthritis, and other studies suggest that SAMe may help treat depression. Researchers have also examined SAMe's use in the treatment of fibromyalgia and liver disease, with more mixed results. Many of the early studies used SAMe given intravenously or as an injection; only recently have researchers been able to look at the effects of SAMe taken by mouth.

Depression

Some research suggests that SAMe is more effective than placebo in treating mild-to-moderate depression and is just as effective as antidepressant medications without the side affects (headaches, sleeplessness, and sexual dysfunction). In addition, antidepressants tend to take 6 - 8 weeks to begin working, while SAMe seems to begin much more quickly than that. Researchers aren't sure exactly how SAMe works to relieve depression, but they speculate it might increase the amount of serotonin in the brain (just as some antidepressants do).

However, many of the studies have examined injectable forms of SAMe, not an oral supplement, and the quality of the studies has varied. One well-designed study failed to find any benefit. More research is needed to determine whether SAMe works for depression. Because serious depression is a dangerous illness, you should seek help from your doctor before taking SAMe or any supplement; don't try to self-treat.

Osteoarthritis

A number of well-designed clinical trials show that SAMe may reduce pain and inflammation in the joints, and researchers think it may also promote cartilage repair, although they are not clear about how or why this works. In several short-term studies (ranging 4 - 12 weeks), SAMe supplements were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen in adults with knee, hip, or spine osteoarthritis. SAMe was as effectives as these medications in lessening morning stiffness, decreasing pain, reducing swelling, improving range of motion, and increasing walking pace. Several studies also suggest that SAMe has fewer side effects than NSAIDs. Another study compared SAMe to celecoxib (Celebrex), a type of NSAID called a COX-2 inhibitor, and found that over time SAMe was as effective as celecoxib in relieving pain.

Fibromyalgia

SAMe can be effective in reducing symptoms of fibromyalgia -- including pain, fatigue, morning stiffness, and depressed mood -- although most of these studies used an injectable form of SAMe. Among studies that did examine a dose of SAMe by mouth, some found that it was effective at reducing these symptoms, while others found no benefit.

Liver Disease

People with liver disease often cannot synthesize SAMe in their bodies, and some preliminary studies suggest that taking SAMe may help treat chronic liver disease caused by medications or alcoholism. A study of 123 men and women with alcoholic liver cirrhosis (liver failure) found that SAMe treatment for 2 years may improve survival rates and delay the need for liver transplants better than placebo. Other studies show that SAMe may help normalize levels of liver enzymes in people with liver disease. However, all these studies have been small and of short duration. Larger and longer studies are needed to confirm these findings.

Other

There is some evidence that taking the drug levodopa (L-dopa) for Parkinson’s disease may lower the levels of SAMe in the body, which may contribute to depression and increase the side effects of L-dopa. However, researchers have also found evidence that taking SAMe may make L-dopa less effective. If you have Parkinson’s disease, do not take SAMe without talking to your doctor first.

SAMe is not found in food. It is produced by the body from ATP and the amino acid methionine. (ATP serves as the major energy source for cells throughout the body).

SAMe is available in tablets. Look for enteric-coated tablets, which are more stable and may be more dependable in terms of the amount of SAMe in the pill. They should be stored in a cool, dry place, but not refrigerated. Tablets should be kept in the blister pack until you take them.

Starting with a low dose (for example, 200 mg per day) and increasing slowly helps avoid stomach upset.

It is important to note that many of the studies of SAMe have tested injectable, not oral, forms. It's not as clear how reliable or effective taking SAMe orally is.

Pediatric

SAMe should never be given to a child without your doctor’s supervision.

Adult

Recommended doses of SAMe vary depending on the health condition being treated. The following list gives information on the dosages used in studies for each condition:

• Depression: 800 - 1,600 mg of SAMe per day, in two divided doses (morning and afternoon)
• Osteoarthritis: 600 - 1,200 mg per day in two to three divided doses
• Fibromyalgia: A dosage of 400 mg two times per day for 6 weeks
• Alcoholic liver disease: 600 - 1,200 mg per day by mouth in divided doses for 6 months enhances liver function. For liver disease, a qualified health care provider should supervise administration of SAMe. This is because SAMe is administered intravenously.

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

Side effects may include dry mouth, nausea, gas, diarrhea, headache, anxiety, a feeling of elation, restlessness, and insomnia. For this reason, you should not take SAMe at night.

Large doses of SAMe may cause mania (abnormally elevated mood). Start at a low dose and gradually increase it; do not exceed recommended doses.

Pregnant and breast-feeding women should not take SAMe.

People with bipolar disorder (manic-depression) should not take SAMe since it may worsen manic episodes.

SAMe should not be combined with other antidepressants without first consulting your doctor.

People taking SAMe may want to take a multivitamin that contains folic acid and vitamins B12 and B6.

If you are being treated with any of the following medications, you should not use SAMe without first talking to your health care provider.

Taking SAMe at the same time as these drugs may increase the risk of serotonin syndrome (a potentially dangerous condition caused by having too much serotonin in your body):

• Dextromethorphan (Robitussin DM, other cough syrups)
• Meperidine (Demerol)
• Pentazocine (Talwin)
• Tramadol (Ultram)

Antidepressant medications -- SAMe may interact with antidepressant medications, increasing the potential for side effects including headache, irregular or accelerated heart rate, anxiety, and restlessness. Talk to your doctor before using SAMe if you are taking any medications for depression or anxiety.

Levodopa (L-dopa) -- SAMe may reduce the effectiveness of this medication for Parkinson’s disease.

Medications for diabetes -- SAMe may reduce levels of blood sugar and may strengthen the effect of diabetes medications, which increases the risk of hypoglycemia (low blood sugar).

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