SAM-e News

SAM-e

- By udith Horstman

A supplement called SAM-e could be a new ally in the battle against the pain of osteoarthritis and fibromyalgia and the depression that so often accompanies chronic illness.

Until last spring, hardly anybody in this country had heard of a European supplement called S-adenosylmethionine. But when it hit the market as a natural remedy named SAM-e (pronounced "sammy") it zoomed in a matter of months from an unknown import to one of the top-selling dietary supplements in the country.

With that user-friendly nickname, you almost expect "sammy" pills to be wearing a little smiley face. And no wonder: It’s being touted as a treatment for depression and osteoarthritis (OA) pain (because of regulations, vaguely referenced on labels as "emotional well-being" and "joint health"). Studies suggest it can also help fibromyalgia symptoms and alcoholdamaged livers, and there are claims that it may help with migraine headaches and maybe even Alzheimer’s disease. And it seems to have no serious side effects and no known drug interactions.

These kinds of sweeping claims have a tendency to make doctors wary, says James McKoy, MD, chief of rheumatology at Kaiser Permanente in Honolulu, Hawaii. "Whenever something is promised to be a cure-all for so many diseases, physicians are very skeptical because so many miracle cures usually only benefit the producer and the seller," he says.

"But I think this substance has promise," he adds, and several other doctors agree.

Dr. McKoy says he has some arthritis patients using SAM-e supplements, "and they like it. SAM-e might be one of the most effective alternative supplements for osteoarthritis and fibromyalgia, and I think it is going to prove to be a great alternative for depression," he says.

People particularly like SAM-e supplements because they don’t have the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs), which can cause gastrointestinal damage; or of antidepressants, which can include sexual dysfunction, dry mouth or nausea. It takes a week or so for SAM-e to take effect, which is slower than NSAIDs but about twice as fast as most antidepressant drugs.

Also, SAM-e has shown no signs of drug interaction and so can be taken along with most, if not all, prescription drugs, according to Richard Brown, MD, a New York psychiatrist who has been using SAM-e for years in his practice.

The Science Behind Sam-E
SAM-e, unlike many dietary supplements, arrived in the marketplace with a thorough background of scientific studies and a history of use.

Doctors in Europe have been studying and using SAM-e for more than two decades as a treatment for osteoarthritis and depression. There are dozens of European studies, including controlled clinical trials that show it relieves osteoarthritis pain as well as NSAIDs; and that it works as well as tricyclic antidepressants in improving mood.

In several countries, it’s a prescription drug, says Teodoro Bottiglieri, PhD, a neuropharmacologist at the Baylor University Institute for Metabolic Diseases in Dallas. Bottiglieri, who has been studying SAM-e for some 15 years, also recently co-wrote a book on SAM-e, Stop Depression Now (Putnam Publishing Group, 1999), along with Dr. Brown.

SAM-e is a compound that occurs naturally in all living cells, and is a key player in a process called methylation that affects more than 100 complex biochemical reactions in the human body.

SAM-e helps our bodies make and regulate hormones, cell membranes and the neurotransmitters that affect mood. SAM-e also contributes to the building blocks for cartilage, and is involved in making glutathione, which the liver uses to remove poisons such as alcohol.

Our bodies usually make all the SAM-e we need. But the level of SAM-e decreases as we age, and levels are low in those who are depressed, or who have deficiencies of B vitamins or methionine, says Bottiglieri. Good diet and vitamin B supplements can help our bodies better use SAM-e, but unfortunately they are not going to do much to help people who have low levels of SAM-e, he says.

SAM-e supplements, however, can raise levels of this compound. And while scientists don’t know for certain how taking SAM-e supplements works, science has shown it relieves OA pain and some fibromyalgia symptoms, as well as depression.

The Osteoarthritis Connection
Roger Hollister, MD, a pediatric rheumatologist at Children’s Hospital in Denver and chair of the Arthritis Foundation’s Complementary Therapies Subcommittee, says "[Many European] studies have shown SAM-e does as well as several NSAIDs in terms of pain relief for osteoarthritis."

But in the sole U.S. study of SAM-e for osteoarthritis, it appeared only to work for those with mild OA. Two groups of men were given SAM-e for about a month, first in daily injections and then 600 milligrams (mg) per day in pills.

Those with milder OA showed significantly less overall pain than the group taking a placebo as early as two weeks into the study. However, a group that was made up of older men with more severe OA did not benefit from SAM-e, says John Bradley, MD, of the University of Indiana, lead author on the 1994 study.

"For milder osteoarthritis symptoms, it may be useful, but it needs more study," Dr. Bradley says.

Claims that this substance helps "regenerate cartilage" brought out the skeptic in some doctors. Still, "There are some interesting concepts about why it might do something for cartilage repair," says Roland W. Moskowitz, MD, of University Hospitals in Cleveland, Ohio. But, he adds, "It’s all theory. There’s no solid scientific evidence to show SAM-e modifies joint disease."

Fibromyalgia And Depression
Some doctors are suggesting SAM-e to their patients with fibromyalgia, because antidepressant drugs in small doses are often used to ease fibromyalgia symptoms. In standard-size doses they can also help relieve the depression that frequently accompanies chronic illness.

The antidepressant effects of SAM-e are documented in several studies. It’s being prescribed by some psychiatrists to treat depression, particularly for people who haven’t responded to other drugs, or who are reluctant to take prescription antidepressants because of side effects.

"It’s a promising drug," says Maurizio Fava, MD, lead author of a study that shows SAM-e is an effective antidepressant. Dr. Fava is director of the Clinical Depression Research Program at Massachusetts General Hospital, where he uses SAM-e to treat some of his patients.

But there are mixed results in studies of SAM-e for fibromyalgia. In one small European study of fibromyalgia and SAM-e, 200-mg daily injections reduced the number of tender points and improved mood in patients with fibromyalgia. In another, those taking 800 mg of SAM-e in pill form had less pain, fatigue and morning stiffness than patients taking placebo, but no effect on tender points. A third study showed no benefit.

There are also mixed opinions from physicians.

"I think SAM-e is even better for fibromyalgia than for osteoarthritis," says Dr. McKoy, who has several patients using it.

Dr. Brown agrees, saying he finds the supplement more effective than antidepressants for fibromyalgia, and that some of his patients get significant pain relief from taking it.

However, Don Goldenberg, MD, a fibromyalgia specialist and chief of rheumatology at Newton-Wellesley Hospital in the Boston area, says he’s not convinced SAM-e has much to offer people with fibromyalgia. His laboratory began and abandoned a study on SAM-e about eight years ago when it didn’t appear to have any benefit for fibromyalgia patients.

However, Dr. Goldenberg notes that the SAM-e product that was used in the discontinued trial could have been too old and thus not effective. He says he would like to see more studies.

The Downsides and the Bottom Line
However, there are some potential downsides to taking SAM-e. Although it has been used for 20 years, there are no controlled, long-term studies to show what effects might occur in people who take SAM-e daily for years, as they would for either osteoarthritis or fibromyalgia.

Few rheumatologists know enough about SAM-e or its research to be able to advise you. And the appropriate dosage isn’t known: Between 200 and 1,600 mg per day of SAM-e was used in studies, with the highest dosage used for depression.

SAM-e is not a cure: You have to keep taking it to get the effects, and it’s pricey for some: SAM-e costs approximately $60 to $230 per month, depending on the amount taken, and it’s not covered by insurance.

And, as with all supplements, loose regulations mean that there is no guarantee that consumers are getting active ingredients in the products they buy.

However, all agreed SAM-e appears to be safe when it is used short term. Both Bottiglieri and Dr. Brown say it can be taken with most prescription drugs, including antidepressants, under a doctor’s supervision. None of the experts interviewed thought SAM-e had any serious side effects – "except poverty," one scientist said, half-joking about the cost of the supplement.

"We really don’t have enough information to say if it’s effective or not," says Dr. Moskowitz. "But we need to keep an open mind."

Good Advice
If you decide you would like to try SAM-e for OA, fibromyalgia or depression, keep this advice in mind:

• Don’t try SAM-e without a doctor’s supervision if you are severely depressed. You must be under medical care. If you have bipolar disease (also known as manic-depression), SAM-e could cause a manic episode.
• Remember to tell your doctor you are planning to try SAM-e, especially if you are taking prescription drugs. And don’t stop any prescribed drugs without checking with your doctor: It can be harmful to stop some medications abruptly.
• Try to choose a SAM-e product that is stabilized. Look for SAM-e butanedisulfonate on the label. SAM-e loses potency easily, so it has to be carefully packaged in airtight, light-proof containers. Also, tablets should be coated to dissolve in your intestines, not your stomach, or you’ll be wasting some of that expensive substance.
• Do not take more than 1,600 mg per day of SAM-e. For OA pain, some doctors suggest starting with 800 mg per day, taken in two doses. If you see an improvement in pain or mood symptoms in two weeks, reduce the dosage to 400 mg. But if you don’t see any change, you may want to increase the dosage and try for another two weeks.
• Consider taking B vitamins – 800 mg of folic acid and 1,000 mg of B12 a day – along with SAM-e, because these vitamins are known to help your body utilize SAM-e.
• See a doctor about any side effects you experience. He may advise you to stop taking SAM-e or lower your dosage. Side effects are rare, but some people may get a temporary skin irritation or nausea. Nausea may be eased by taking SAM-e with meals.
• Keep up your regular routine of exercise, and maintain a healthy weight to ease pressure on your joints.

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