[Below is information taken from a July 1999 article in Newsweek and republished]
SAMe (known formally as S-adenosylmethionine) is not an herb or a hormone. It’s a molecule that all living cells, including our own, produce constantly. To appreciate its importance, you need to understand a process called methylation. It’s a simple transaction in which one molecule donates a four-atom appendage—a so-called methyl group—to a neighboring molecule. Both the donor and the recipient change shape in the process, and the transformations can have far-reaching effects. Methylation occurs a billion times a second throughout the body, affecting everything from fetal development to brain function. It regulates the expression of genes. It preserves the fatty membranes that insulate our cells. And it helps regulate the action of various hormones and neurotransmitters, including serotonin, melatonin, dopamine and adrenaline. As biochemist Craig Cooney observes in his new book, “Methyl Magic,” “Without methylation there could be no life as we know it.”
And without SAMe, there could be no methylation as we know it. Though various molecules can pass methyl groups to their neighbors, SAMe is the most active of all methyl donors. Our bodies make SAMe from methionine, an amino acid found in protein-rich foods, then continually recycle it. Once a SAMe molecule loses its methyl group, it breaks down to form homocysteine. Homocysteine is extremely toxic if it builds up within cells. But with the help of several B vitamins (B6, B12 and folic acid), our bodies convert homocysteine into glutathione, a valuable antioxidant, or “remethylate” it back into methionine.
SAMe and homocysteine are essentially two versions of the same molecule—one benign and one dangerous. When our cells are well stocked with B vitamins, the brisk pace of methylation keeps homocysteine levels low. But when we’re low on those vitamins, homocysteine can build up quickly, stalling the production of SAMe and causing countless health problems. High homocysteine is a major risk factor for heart attack and stroke. During pregnancy, it raises the risk of spina bifida and other birth defects. And many studies have implicated it in depression.
How, exactly, might taking extra SAMe improve a person’s mood? Researchers have identified several possibilities. Normal brain function involves the passage of chemical messengers between cells. SAMe may enhance the impact of mood-boosting messengers such as serotonin and dopamine—either by regulating their breakdown or by speeding production of the receptor molecules they latch on to. SAMe may also make existing receptors more responsive. These molecules float in the outer membranes of brain cells like swimmers treading water in a pool. If the membranes get thick and glutinous, due to age or other assaults, the receptors lose their ability to move and change in response to chemical signals. By methylating fats called phospholipids, SAMe keeps the membranes fluid and the receptors mobile.
Whatever the mechanism, there is little question that SAMe can help fight depression. Since the 1970s, researchers have published 40 clinical studies involving roughly 1,400 patients. And though the studies are small by FDA standards, the findings are remarkably consistent. In 1994 Dr. Giorgio Bressa, a psychiatrist at the University Cattolica Sacro Cuore in Rome, pooled results from a dozen controlled trials and found that “the efficacy of SAMe in treating depressive syndromes… is superior [to] that of placebo and comparable to that of standard… antidepressants.”
This isn’t the first natural substance to show promise as a mood booster. Small studies suggest that St. John’s wort can ease low-grade melancholy, but SAMe has been tested against far more serious disorders. In one of several small U.S. studies, researchers at the University of California, Irvine, gave 17 severely depressed patients a four-week course of SAMe (1,600 mg daily) or desipramine, a well-established antidepressant. The SAMe recipients enjoyed a slightly higher response rate (62 percent) than the folks on desipramine (50 percent).
Could SAMe also provide an alternative to anti-inflammatory medications? In a dozen clinical trials involving more than 22,000 patients, researchers have found SAMe as effective as pharmaceutical treatments for pain and inflammation. But unlike the NSAIDs, SAMe shows no sign of damaging the digestive tract. And instead of speeding the breakdown of cartilage, SAMe may help restore it. You’ll recall that after giving up its methyl group, SAMe becomes homocysteine, which can be broken down to form glutathione (the antioxidant) or remethylated to form methionine (the precursor to SAMe). As luck would have it, the reactions that produce glutathione also yield molecules called sulfate groups, which help generate those joint-sparing proteoglycans.
When German researchers gave 21 patients either SAMe or a placebo for three months, using MRI scans to monitor the cartilage in their hands, the SAMe recipients showed measurable improvements. That wouldn’t surprise Inge Kracke of Cologne. She was an active 48-year-old when a 1996 auto accident mangled her left knee and left her hobbling on a cane. Dr. Peter Billigmann of the University of Landau prescribed a regimen that combined SAMe (1,200 mg a day for three months) with injections of hyaluronic acid, a cartilage component. Cartilage injuries don’t normally heal, but a year later Kracke’s knee looked better on X-rays. She now plays golf three times a week.
SAMe may have other benefits as well. Studies suggest it can help normalize liver function in patients with cirrhosis, hepatitis and cholestasis (blockage of the bile ducts). SAMe has also been found to prevent or reverse liver damage caused by certain drugs. As patients hear more about this supplement, they may try treating themselves for all these conditions and others. But many of them will be disappointed—either because they expect miracles that SAMe can’t deliver, or because they take the wrong dose or form.
Experts advise taking SAMe twice a day on an empty stomach, but different people may require different amounts. Though studies suggest that 400 mg a day is an effective dose for arthritis, the daily doses used in depression trials have ranged as high as 1,600 mg. Clinicians generally start people with mood problems at 400 and ratchet up as necessary.
Unfortunately, there is no convincing evidence that SAMe can make healthy people happier or more mobile than they already are. But there are lessons here for everyone. We now know that methylation is vital to our well-being. It’s equally clear that the modern Western diet—rich in protein, light on the plant foods that supply folate—is a prescription for stalling that vital process. “SAMe works as a medication to treat certain diseases,” says Paul Frankel, a biostatistician at the City of Hope National Medical Center in Duarte, Calif. “But for most people the problem is undermethylation of homocysteine.” In other words, many of us could arm ourselves against low moods, bad joints and weak hearts simply by upping our intake of B vitamins. That may sound less exciting than taking a miracle supplement. But with luck, it could keep you from ever needing one.
DIRECTIONS: A typical adult dose of SAMe is between 800 to 1200 mg daily. You may want to start low and increase until desired effect is noted. However, if using in conjunction with prescribed medications (e.g., Prozac, Paxil, Celebrex) then reduce SAMe dose to 400 mg to 800 mg daily.
NOTE: SAMe can cause some upset stomach in some individuals, especially if taken on an empty stomach of in higher doses. If this occurs, consider reducing dose until better tolerated before increasing again and/or taking with food.
