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S-adenosylmethionine (SAMe)
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"Alternatives for recovering from depression"
 

One of the most interest supplements to come on the market place recently is the substance know as SAMe. 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 neighbouring 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 neighbours, 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 spinabifida 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).

No one has found SAMe significantly more effective than a prescription antidepressant, but it's clearly less toxic. The drugs that predate Prozac (tricyclics and MAO inhibitors) can be deadly in overdose, or in combination with other medications. Newer antidepressants, such as Prozac, Zoloft and Paxil, are less dangerous, but their known side effects range from headaches and diarrhoea to agitation, sleeplessness and sexual dysfunction. And SAMe? Studies suggest that unlike other antidepressantsthe most serious side effect is a mild stomach upset.
 
Until large studies confirm these findings, few Australian doctors will recommend SAMe to severely depressed people. "The evidence looks promising," says Harvard psychiatrist Maurizio Fava, "but it's not definitive".

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.

The first challenge is to buy full-strength SAMe. "Some companies are very reliable manufacturers," says Dr. Paul Packman of Washington University in St. Louis. "But some aren't. You can't always tell from the label on the bottle how much active ingredient is actually in it. Metagenics provide a reputable product called
Proxan which can only be purchased through a naturopathic practitioner. Enquiries can be made about this product by calling our office on 02 47349010 (Australia)

Assuming you buy full-strength SAMe, the second challenge is to use it effectively. Experts advise taking it twice a day on an empty stomach, but different people may require different amounts.

Unfortunately, there is no evidence at this point in time 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 which is 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 Centre in Duarte, California "But for most people the problem is under methylation 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.

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