She was making lunch for herself and a friend one Saturday this spring when an unfamiliar feeling swept over her. The 50-year-old social worker had fallen deep into depression two years earlier, and had given up on prescription antidepressants when the first one she tried left her sluggish, sexually dormant and numb to her own emotions. Then, in mid-March, she heard about a naturally occurring substance called SAMe (pronounced "Sammy"). She had been taking it for just a few days when she began setting the table that Saturday morning. A ginger-miso sauce was chilling in the fridge, and she was garnishing her finest plates with fresh anemones. Suddenly, there it was: a sense of undiluted pleasure.

This woman (who asked not to be named) has taken SAMe ever since, and her mood isn't the only thing that has changed. Until this spring she took prescription-strength anti-inflammatories for her arthritis, and still had trouble bending her knees. She's now off those drugs and feeling more nimble than she has in 20 years.

Could an over-the-counter tonic really do all this? Pills purporting to cure everything from hemorrhoids to hangnails are usually worthless and sometimes dangerous. And because SAMe has not been studied extensively in the United States, many doctors are leery. Beware, says Dr. Gilbert Ross of the American Council on Science and Health, a conservative watchdog group. Supplement dealers are once again trying to "flimflam the public into using untested remedies instead of FDA-approved pharmaceuticals."

The Food and Drug Administration has not rigorously evaluated SAMe, let alone approved it. (Federal law permits the unregulated sale of naturally occurring substances as long as marketers avoid therapeutic claims.) And the studies that researchers have conducted are not of the magnitude the FDA would require for a drug approval. But that doesn't mean SAMe is "untested." In dozens of European trials involving thousands of patients, it has performed as well as traditional treatments for arthritis and major depression. Research suggests it can also ease normally intractable liver conditions. SAMe doesn't seem to cause adverse effects, even at high doses. And doctors have prescribed it successfully for two decades in the 14 countries where it has been approved as a drug.

Until recently, few Americans had heard of the stuff. An Italian firm developed it as a pharmaceutical in the early 1970s but lacked the will or the resources to make a run at a drug approval in the United States. Then, this spring, two U.S. vitamin companies, GNC and Pharmavite, started importing large quantities of SAMe to sell as a supplement. The product took off quickly-Pharmavite's Nature Made brand now ranks 25th among the 13,000 supplements sold in grocery and drugstores-and the impact is still growing. When you consider that some 50 million Americans suffer from arthritis or depression, the implications are staggering.

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 (chart). 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."