SAMe (S-adenosylmethionine)

Health Tips / SAMe (S-adenosylmethionine)

What Is It?

SAMe (pronounced “sammy”) is short for S-adenosylmethionine, a molecule that the body continually produces to fuel numerous vital body functions. Discovered in 1952, the popularity of SAMe has soared recently with talk of its ability to ease depression as effectively as prescription antidepressants. (Proponents say SAMe also works faster than antidepressants and with virtually no side effects.)

Long prescribed by European doctors for both arthritis and depression, SAMe recently became available in the United States as an over-the-counter supplement. It is also emerging as an effective therapy for arthritis, fibromyalgia, certain liver disorders, and possibly even Alzheimer’s disease.

Health Benefits

The body manufactures SAMe from methionine, an amino acid found in protein-rich foods, and adenosine triphosphate (ATP), an energy-producing compound found in all the body’s cells. The SAMe molecule then donates a piece of itself (a methyl group) to body tissues and organs, providing a critical link in methylation, a chemical reaction that occurs billions of times a second throughout the body. In giving up a part of itself, SAMe promotes cell growth and repair.

SAMe also contributes to the formation of key compounds in the brain, including the neurotransmitter dopamine and the mood-enhancer serotonin. In addition, it helps to maintain desirable levels of glutathione, a major antioxidant that protects against cell damage from oxygen molecules called free radicals. Taken as a supplement, SAMe compensates for any deficiencies and encourages the body to run efficiently.

Specifically, SAMe may help to:

Relieve depression and stress-related blues. Several studies indicate that SAMe eases mild to moderately severe depression. A sweeping review of dozens of small clinical trials (called a “meta-analysis”) testing SAMe for depression concluded that it appears to work as well as the frequently prescribed tricyclic antidepressants (imipramine, amitriptyline, desipramine) in easing depression. Just as importantly, it works faster, often starting to improve mood within a week. This contrasts significantly with standard antidepressants, whose effects can take several weeks to become apparent. In a University of California study of 17 severely depressed adults, 62% of the participants who took SAMe for four weeks (1,600 mg daily) showed significant improvements in symptoms, compared to 50% of those who used desipramine (a conventional antidepressant). Unlike many prescription antidepressants, which often cause unpleasant side effects such as as drowsiness, dry mouth, and constipation, SAMe appears to cause few if any side effects.

Treat chronic fatigue syndrome (CFS).
Like conventional antidepressants used to treat chronic fatigue, SAMe appears to benefit CFS sufferers by countering depression. It alters the brain’s response to pain and improves the quality of badly needed sleep. As a result, both chronic fatigue syndrome and a condition with which it’s commonly confused–chronic fatigue syndrome-fibromylagia (CFS-FM)–are likely to respond to SAMe. CFS-FM, which is actually more common than CFS, appears to be a physical response to chronic stress and depression.

Lessen arthritis-related pain and inflammation. The eventual breakdown of SAMe in the body yields substances that help to keep the gel-like cartilage that cushions joints intact. In the common degenerative joint disease osteoarthritis, cartilage wears down over time. Studies in thousands of osteoarthritis sufferers have demonstrated that SAMe can be as effective at increasing joint mobility and reducing swelling and pain as such NSAIDs (nonsteroidal anti-inflammatories) as ibuprofen and aspirin. Moreover, SAMe doesn’t pose the risk of stomach bleeding or kidney damage that are serious risks with NSAIDs. It also doesn’t wear down joints, damage cartilage, or block the pain signals that could signal a worsening condition. Although it’s not exactly clear how SAMe works for arthritis, very preliminary but intriguing animal studies actually point to a role in repairing cartilage and lubricating joints, properties that may well extend to humans. Clearly more research is needed.

Control back pain. SAMe may improve back pain when taken for several weeks, a function of its ability to reduce swelling and pain. The theory is that SAMe takes part in the repair and restoration of spinal discs, cartilage, and the articulating surfaces of joints. Obviously, this takes time. So if you’re using SAMe for back pain, don’t expect the immediate symptom relief that you get with NSAIDs such as Motrin or COX-2 inhibitors such as Vioxx and Celebrex.

Reduce fibromyalgia symptoms. SAMe may minimize certain complications of this often debilitating disorder, such as muscle pain, depression, and fatigue. The 44 fibromylagia sufferers in a Danish study who took 800 mg of SAMe daily for six weeks reported some relief from morning stiffness and muscle aches. They also noted an improvement in mood. The results from other studies have been mixed, however. For example, a 1997 study to test the effectiveness of intraveneously administered SAMe for fibromylagia failed to show significant benefits. However, given that no single therapy for fibromyalgia is uniformly satisfactory, a trial of SAMe for this often puzzling condition is certainly reasonable.

Treat hepatitis and other liver disorders. By producing the extremely powerful antioxidant glutathion, which enhances the liver’s ability to clear out toxins, SAMe promotes efficient liver function. Research indicates that SAMe may benefit liver function impaired by alcohol-induced cirrhosis, drug toxicity, hepatitis, and cholestasis.

Protect against Alzheimer’s and age-related brain disorders. Preliminary research indicates that SAMe levels are very low in individuals suffering from Alzheimer’s disease. In one study of 40 elderly individuals with problems related to alertness and cognition, improvements in such areas as memory, mood, and ability to carry out everyday activities of life occured upon administration of a regimen of oral, intravenous, and intramuscular SAMe. Additional research is now underway to determine what role supplemental SAMe might play in antioxidant production and in disorders of the aging brain.
Note: SAMe has also been found to be useful for a number of other disorders. For information on these additional ailments, see our Dosage Recommendations Chart for SAMe.



Dosage Information

Special tips:

–Look for enteric-coated SAMe; it’s more readily absorbed by the body in this form and remains chemically stable for much longer (the coating protects it from exposure to air).

To avoid a toxic buildup of homocysteine molecules (which are formed when SAMe breaks down) be sure to take a high-quality vitamin B complex supplement along with SAMe. These vitamins disarm homocysteine, which in high concentrations poses the risk of various health problems including heart attack and stroke. A standard recommendation is to take 100 mg of a B complex once a day, regardless of the SAMe dose.

If you’re particularly sensitive to medications, start out with half the recommended daily dosage and work up to the full amount after a week.

For depression, arthritis, fibromylagia, and liver disorders: Take 400 mg of SAMe twice a day. If symptoms fail to improve after three weeks, try increasing your dose to 400 mg three times a day. On the other hand, if symptoms lessen with 400 mg twice a day, you can try to lower the dose to 200 mg twice a day.
Be sure to check out our Dosage Recommendations Chart, which has therapeutic dosages for specific ailments at a glance.

Guidelines for Use

SAMe is best absorbed on an empty stomach, so try to take it about one hour before or two hours after meals. If nausea or heartburn develop, take it with plenty of water.

To prevent insomnia, don’t take SAMe late in the day. Most people report a mild energy boost with the supplement.

SAMe can safely be combined with other natural antidepressants such as St. John’s wort, as well as conventional antidepressants.

Purchase SAMe from a reliable company whose quality standards you trust. If improperly handled, the raw material used to make SAMe can deteriorate rapidly, making these costly supplements weak or even inactive. Look for “pharmaceutical grade” products and opt for a more stable form called “butanedisulfonate” rather than “tosylate.”

General Interaction

Don’t take SAMe with MAO inhibitor antidepressants.
Note: For information on interactions with specific generic drugs, see our WholeHealth Chicago Drug/Nutrient Interactions Chart.

Possible Side Effects

SAMe seems to be free of significant side effects, even when taken for long periods of time.

In rare cases, daily doses of 400 mg or higher may cause mild stomach upset, dry mouth, and insomnia.

At extremely high doses, the supplement may cause diarrhea and heartburn.


If you suffer from severe depression, don’t take SAMe without consulting your doctor first. This precaution is particularly important if you have a bipolar disorder because SAMe could trigger or exacerbate mania (the “up” phase) in such cases.

If you’re taking prescription antidepressants, don’t discontinue them or reduce your dosage without consulting your doctor.

SAMe should lift depression relatively quickly. If you don’t notice a significant improvement after four weeks, see your doctor. You may need a different category of antidepressant.


Anxiety and Panic 400-800 mg twice a day on an empty stomach
Arthritis 400 mg twice a day for 14 days; then 200 mg twice a day as maintenance
Back Pain 400 mg twice a day. Must be taken on an empty stomach, one hour before or two hours after a meal.
Chronic Fatigue Syndrome 400 mg twice a day
Chronic Pain 400 mg twice a day
Depression 400-600 mg twice a day on an empty stomach (either one hour before, or two hours after a meal)
Fibromyalgia 400-600 mg twice a day
Hepatitis 400 mg twice a day
Stress 400 mg twice a day

Doctor Recommendations
David Edelberg, M.D.

One of the hottest new supplements, SAMe has garnered lots of press coverage lately because it seems to ease depression as well as prescription antidepressants do for many people.


I’d certainly apply the word natural to SAMe (S-adenosylmethionine) because it appears in every cell in the body. This complex molecule is derived from the amino acid methionine and adenosine triphosphate (ATP), an energy-producing compound found throughout the body.


Tips for choosing and taking SAMe Forms. There are two types of SAMe – tosylate and butanedisulfonate. Both work equally well. Enteric coating. Because the SAMe molecule is absorbed in the small intestine and can be destroyed by stomach acid, you’re better off with an enteric-coated tablet. The coating protects the SAMe as it passes through your stomach and it’s then released and absorbed. Between meals. Food will block the absorption of SAMe, so you need to take it on an empty stomach. Effectiveness. SAMe works fairly quickly, usually in a week or two. You may have to increase your dose a bit to get the full effect.


What I tell patients is that unless you eat during the very first hour after you open your eyes in the morning, have your first dose ready and waiting next to the bed and take it just as you awaken. Then, assuming you eat supper around 6 P.M., take your second dose around 3:00 in the afternoon. SAMe will work best if you have good amounts of B vitamins in your system; a B-complex vitamin can be taken any time of the day. Now, concerning price. What manufacturers charge can be outrageous. And you shouldn’t have to refinance your house to treat your depression. Just remember, more expensive is not necessarily better. A good SAMe supplement should simply have: A reliable manufacturer Enteric coating A usable form (tosylate or butanedisulfonate) A fresh product, with the expiration date at least a year ahead. After that, try to get the least-expensive product you can find. And prices should drop, so be willing to change brands.

Be well,
David Edelberg, MD