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The safest and most effective antidepressant in the world is the European drug S-adenosylmethionine (SAMe). SAMe is a simple natural metabolite produced from the essential amino acid methionine and adenosine triphosphate (ATP) by an enzyme known as MAT (methionine adenosyl transferase). It is found in every cell within the body and plays an important role in critical biochemical processes. For one thing, it serves as a precursor for glutathione, Coenzyme A, cysteine, taurine, and other essential compounds.

When compared with other antidepressants, SAMe works faster and more effectively, with virtually no adverse side effects. In fact, unlike FDA-approved antidepressants that have both lethal and nonlethal side effects, SAMe produces side benefits, such as improved cognitive function, protection of liver function, and a potential slowing of the aging process. Some people take SAMe for its antiaging properties alone.

The major drawback of SAMe is that it is a difficult-to-produce natural substance with high manufacturing and packaging costs. At this time, the retail price of using SAMe to treat depression is more than the price of Prozac. The suggested dose of SAMe to treat depression ranges from 400 to 1600 mg a day. In one study, as little as 35 mg a day was used to treat depression, but most people have used 800 to 1600 mg a day.

A lack of SAMe is associated with an increase in clinical depression, and supplying the missing SAMe can relieve the problem. Used in Germany and Italy to treat osteoarthritis, SAMe also proved itself to be a powerful weapon against depression in 1973, during the first SAMe depression trial. By 1986 doctors knew that SAMe was helpful with endogenous depression caused by chemical imbalances in the brain.

SAMe gets to "where the action is," because clinical measurements have shown a significant rise in SAMe in the cerebral spinal fluid of treated patients. SAMe has been shown to be is as good as conventional antidepressant drugs, because it has been compared with tricyclic and other medications in single-and double-blind randomized trials, with doses ranging from 75 to 400 mg a day. The results, including scores on the Hamilton rating used to gauge depression, show that SAMe is as effective as tricyclic drugs.

As the clinical and scientific information on the benefits of SAMe mounted, scientists and physicians from around the world came together at an international symposium called "A New Treatment for Depression," held in Trieste, Italy, in June 1987. Here is some of the exciting information from the studies reported at the conference:

Researchers from the University of Alabama at Birmingham found that depressed patients were not making enough SAMe in their brains. After checking the red blood cells from patients suffering from depression and schizophrenia, they discovered a decreased amount of methionine adenosyl transferase (MAT), an enzyme necessary for the formation of SAMe. (It was, however, higher in people with mania.)

In a double-blind, randomized study, 14 women suffering from bipolar, unipolar, reactive or neurotic depression were given 45 mg of SAMe a day, and 5 women with reactive or neurotic depression received a placebo. Treatment ranged from 5 to 11 days. There was a "significant improvement" in the SAMe patients compared with those on the placebo.

Forty-nine people suffering from moderate to severe depression, as well as rheumatoid arthritis, were observed in a double-blind, randomized study. Over 21 days, 25 of the patients were given 200 mg of SAMe a day, and 24 received a placebo. The patients who were treated with SAMe showed larger drops in depression, as measured by the Hamilton Depression system, than the placebo group.

In a 1986 double-blind, randomized study, 32 severely depressed patients were divided into two groups. One group received 200 mg of SAMe for 14 days and the other was given a placebo.

SAMe reduced depression by 50% on the Hamilton or Beck scale, and was more effective in counteracting endogenous than neurotic depression. There were no side effects except a possible increase in agitation.

Twenty-two women and 18 men suffering from dysthymic disorder, atypical depression, or major depression were enlisted in a 1987 study of SAMe. The volunteers, with an average age of about 44, were divided into two groups of 20 each. The first group received 200 mg of SAMe for 30 days; the second, a placebo. SAMe was found to be superior to the placebo.

A 1990 study examined SAMe and the depression often associated with Parkinson's disease. Twenty-one patients participated in this double-blind, crossover study with SAMe and a placebo. The patients' depression was rated using various scales; then they were given either SAMe for a while and then the placebo, or the placebo first and then SAMe. Neither the doctors nor the patients knew who was receiving what, or when. The researchers concluded that SAMe was a useful treatment for the depression associated with Parkinson's disease (72% of the patients said they had improved), and that it had few side effects.

That's significant, when you consider that many Parkinson's patients are routinely turned into "zombies" by the side ffects of the powerful medicines they take.

These studies clearly showed that SAMe was an effective antidepressant. But how would SAMe fare when pitted against conventional antidepressant drugs with a proven track record? The results speak well for SAMe:

A 1975 study compared SAMe to imipramine, a standard medicine for depression. The double-blind, random study involved 31 patients, who ranged in age from 28 to 82, and suffered from endogenous, involutional, neurotic, and endoreactive depression. Sixteen of the volunteers were given 25 mg of SAMe 3 times a day, and the other 15 received 25 mg of imipramine 3 times a day. Researchers concluded that SAMe was just as effective as the drug, with slight differences favoring the natural substance.

Eighteen men and women ranging from 20 to 65 years old participated in a 14-day double-blind study comparin intravenous SAMe to oral imipramine. The researchers found that SAMe produced "superior results" by the end of the first week of treatment. By the end of the second week, 66% of SAMe patients enjoyed a clinically significant improvement in depressive symptoms, compared with 22% of imipramine patients. The researchers also noted that SAMe is "rapid, effective, and has few side effects."

In the opening discussion of a 1988 study on SAMe, Jerrold Rosenbaum, M.D., Associate Professor of Psychiatry at Harvard Medical School, reported that double-blind studies showed that
SAMe was "equally more effective" than tricyclic antidepressants,
including clomipramine, amitriptyline, and imipramine. Rosenbaum and colleagues also noted that SAMe produced an earlier response (3 to 7 days) and had fewer side effects.

SAMe was compared with desipramine in a 1994 study headed by a researcher from the University of California. In this 4-week, double-blind, randomized study of 26 patients, 62% given SAMe showed significant improvement, compared with only 50% given the drug. Moreover, plasma levels of SAMe rose in patients reporting a 50% or better improvement, suggesting that SAMe plays a major role in depression.

A 1994 meta analysis was performed on the SAMe studies, comparing it with placebo and standard antidepressants. The analysis, which looked at many studies already conducted on a large number of patients in a variety of conditions, found that SAMe was superior to placebo and just as good as the tricyclic medications. But because it is a naturally occurring compound, SAMe had relatively few of the side effects of standard drugs.

SAMe's benefits are numerous.

1. In addition to relieving depression,
2. it protects against aging (by maintaining cellular "energy factories" called mitochondria.)
3. Prevents DNA mutations.
4. Restores cellular membrane fluidity.
5. Guards against hepatitis and liver disease caused by toxins and drugs.
6. Protects against neuronal death caused by lack of oxygen.
7. May confer protection against heart disease.
8. Regenerates nerves and helps nerve fibers "re-shield" themselves.
9. May help in treating Alzheimer's disease.
10. Brain levels of SAMe are low in Alzheimer's patients. Restoring them to normal levels may help the problem.

Rarely does a simple herb take the media spotlight as did St. John's wort in 1997. A two-page feature article in Newsweek, countless mentions in magazines and newspapers, programs on local TV and radio, and even a positive segment on the widely watched TV show 20/20 have made this herb a household name. Patients who suffer from depression have been going to their doctors and asking, "Why didn't you tell me about this natural herb before?" And, fortunately, more doctors are starting to recommend it for depression. Stan Bazilian, MD, a psychiatrist who practices traditional medicine in Philadelphia, Pennsylvania, is one such example.

"I normally use Prozac and other pharmaceutical antidepressants. Lately, I've heard so much about St. John's wort that I decided to give it a try. I started two patients on this herb. So far both have improved. One of the patients was a 20 year-old who was previously on Prozac but got side effects on it. She couldn't get any orgasms. A couple of weeks after starting St. John's wort, many of her depressive symptoms, such as loss of interest in life, feelings of worthlessness, and lack of concentration, have been reversed. And her sex life is fine. She's now walking on air."