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Life Extension Magazine

LE Magazine June 2003

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A New Era for SAMe

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The results are officially in: S-adenosyl-methionine (SAMe) is potentially one of the safest and most effective treatments for depression, arthritis, liver disorders and a host of other diseases prevalent in advancing age.
While the United States is often at the forefront of pharmaceutical innovation, it frequently lags behind European nations in its understanding of the therapeutic impact of nutritional supplements. To sufferers of depression, joint and liver disease one such governmental lapse has been in recognizing the multiple benefits of SAMe.

After years of being touted by European physicians and researchers-as well as the Life Extension Foundation itself - the U.S. Department of Health and Human Services has completed a meticulous examination of previous research studies and clinical trials. The official proclamation is that SAMe has demonstrated proven efficacy in the treatment of several common disorders and is virtually free from side effects.1

In this article we discuss the therapeutic properties of SAMe being investigated by researchers that may lead to a new era in the treatment of age-related diseases in the U.S. We begin with a brief discussion of the history and biochemical influence of this remarkable natural compound.

SAMe is a biological compound that is found in virtually every living cell of the human body, affecting their function, stability and activity. Originally discovered by researchers in Italy in 1952 and later identified as a metabolite of the amino acid methionine, SAMe acts as a co-factor in a number of critical biochemical reactions necessary for sustaining life.2

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Typical adults produce anywhere from 6 to 8 grams of SAMe daily, with most of it being made in the liver where it works to detoxify the body of poisons such as drugs, alcohol, heavy metals, pesticides and solvents. Beyond its function in liver detoxification, SAMe is a critical component in cartilage production, an important factor in brain chemistry and a key element in methylation, one of the most crucial biochemical actions.3

Because of its widespread benefits to biological function, SAMe has recently generated a great deal of interest for its potential therapeutic properties. Indeed, numerous research studies have found that raising the level of SAMe in the body reduces the age-related biological processes that result in diseases such as depression, osteoarthritis and liver disorders.

Depression: limitations of conventional therapy

Depression is a modern-day epidemic. Worldwide, it is a leading public health problem with as many as one in six people suffering from the disorder and as many as 20% developing a case serious enough to warrant professional treatment.6

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Methylation:
A key reaction in biological function

If for no other reason, SAMe's key role in methylation makes it absolutely essential for healthy functioning. Methylation is a biochemical process whereby a methyl group (CH3) is passed from one molecule to another. Biologically, methylation acts as an "on-off" switch that activates more than a hundred different processes in the body - from producing neurotransmitters (such as serotonin), to preserving joint health, and even protecting against heart disease.4
Methylation activity declines with aging, resulting in a gradual slowdown in these processes, causing many researchers to theorize that this methylation decline contributes to the aging process itself as well as the many diseases associated with it.
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While drug therapy for depression can be effective, research has shown that as many as 30% of depressed people fail to respond favorably to even the newest pharmaceuticals available. To make matters worse, anti-depressants can provoke a host of side effects such as heart palpitation, hallucination, confusion, anxiety, in­som­nia, dis­orientation and loss of libido. In addition, many anti-depressive drugs are dangerous for patients with Parkinson's disease, heart problems, glaucoma, high blood pressure and liver problems, thereby placing them off limits to many older sufferers.7

Considering the potential for failure, usage limitations with respect to concurrent diseases, and potential side effects, anti-depressive drugs are not always a preferred course of treatment. As such, identifying alternative methods for combating depression is paramount. One of the most promising substitutes is SAMe.

Clinical studies supporting efficacy of SAMe

Research into SAMe's anti-depressant value was first cited in Italy in 1973 when scientists examining its effect on schizophrenic patients noticed that many of the test subjects were becoming less depressed. These unexpected results triggered a surge of clinical trials whose aim was to verify and understand this enigmatic result.8

Years of research followed, with an overwhelming number of studies concluding that SAMe is at least as effective at treating depression as its pharmaceutical counterparts - with some trials showing that it outperforms conventional medications. Furthermore, these studies also found that SAMe has surprisingly few side effects, works in as quickly as a few days and is remarkably well tolerated in elderly patients.9

A study performed by the Clinical Psychopharmacology Unit in Boston confirmed these findings in an open trial of 20 outpatients suffering from major depression who had not previously responded to conventional anti-depressant drugs. Impressively, upon receiving oral supplementation of SAMe, the group as a whole reported significant improvement, and seven out of 11 patients experienced a full anti-depressant response. In addition, only minimal and transient side effects resulted, further suggesting that SAMe is well tolerated.10

According to the U.S Agency for Healthcare Research and Quality's recent review of clinical trials, SAMe is associated with an improvement of approximately six points in the score of the 17-point Hamilton Rating Scale for Depression when measured at three weeks. Furthermore, this improvement rating is at least equal to the results achieved with conventional pharmacology. Hence, this degree of improvement is considered both statistically and clinically significant and is equivalent to verification of SAMe's beneficial effect on depression.1

SAMe and osteoarthritis

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How SAMe fights arthritis

In the test tube, SAMe increases the number of chondrocytes (cartilage cells) and proteoglycans (structural proteins). This suggests that SAMe treatment may reverse the underlying process of osteoarthritis by stimulating cartilage to grow.17 As discussed earlier, cartilage acts like a spongy cushion where bone meets bone at the joint. In osteoarthritis, this cushion gradually disintegrates.
Another major component of the joint is synovial fluid, a lubricant that allows for smooth motion. A pro-inflammatory cytokine called tumor necrosis factor-alpha (TNF-a) has been found in the synovial fluid of people with rheumatoid arthritis. TNF-a plays a role in bone and cartilage destruction. According to an article published in the British Journal of Rheumatology, researchers demonstrated that SAMe reverses the damage caused by TNF-a when added to cells at the same time.18

Osteoarthritis is a natural and unfortunate consequence of aging joints. It occurs when the cartilage cushion that lines the joints becomes stiff, resulting in bone overgrowth in the affected area. This overgrowth subsequently causes inflammation and progressively decreased mobility, eventually resulting in the complete loss of function and possibly disfigurement.11

Currently, researchers estimate that as many as 24.3 million Americans ages 35 to 65 suffer from some degree of osteoarthritis.12 Additionally, studies have found that the prevalence of osteoarthritis skyrockets to as much as 90% for people over 75 years of age.13 At present, the primary treatment options available through conventional medicine are limited - aspirin, steroids, COX-2 inhibitors and nonsteroidal anti-inflammatory (NSAIDs) drugs. While these medications effectively ease pain, they do not reverse the joint cartilage damage. Furthermore, NSAIDs and even the newer COX-2 inhibitors are commonly associated with serious side effects such as intestinal disorders and ulcers.14 Clearly, more effective treatment options are sorely needed.

A study published in Italy first investigated the effect of SAMe on osteoarthritis in 1975. In their open trial carried out on 90 patients with severe degenerative arthropathies, they found that 30 mg of SAMe administered intravenously twice a day for two weeks resulted in marked anti-inflammatory effects with no side effects. In a subsequent "double crossover" investigation, SAMe was next compared to the effects of intramuscular injections of the analgesic indo­methacin. The results showed that the therapeutic responses of the two were exactly alike, whereas the side effects following the indomethacin were not present after SAMe.15

A study performed at the Konig Institute of General Medicine in Germany tested the effectiveness of SAMe in 108 patients with osteoarthritis of the knee, hip and spine. During the 24-month study, patients received 600 mg of SAMe daily for the first two weeks, followed by 400 mg daily thereafter until the conclusion. According to researchers, improvement of clinical symptoms were reported after only two weeks of treatment, and continued throughout the trial. Minor, non-specific side effects such as nausea occurred in only 20 of the patients, most of which disappeared during the trial.16

Even more compelling, according to the latest report issued by the U.S. Department of Health and Human Services, SAMe has shown to be 80% more effective in relieving the pain associated with osteoarthritis when compared with placebo. Furthermore, their report also found that when compared to treatment with NSAID drugs, SAMe was at least equally effective. The significance of this finding is that NSAID drugs are know to induce serious side effects, whereas SAMe can provide identical results with no ill effects.1

Protecting the liver

The liver is the primary organ involved in removing toxic substances from the human body.19 One way the liver achieves this is to produce glutathione, a powerful antioxidant composed of three amino acids, cysteine, glutamic acid and glycine. When glutathione encounters a toxin, such as a pesticide or drug, it immediately attaches to it, making the substance become more water-soluble. Once it is in this water-soluble state, the toxin can then be excreted safely via the urine without causing any damage.20

Because of the liver's continuous battle against toxins, adequate concentrations of glutathione are crucial to survival. Damage occurs when the liver is so overwhelmed by toxins that it cannot produce enough glutathione. Part of that concentration burden falls to SAMe, which is a necessary component of glutathione's creation. Not coincidentally, the concentration of SAMe in the liver is one of the highest in the body.

The interrelationship between SAMe and glutathione production is of such critical importance to the removal of toxins and general liver health that it is considered by many researchers to be a liver super-nutrient. Nothing comes close to providing the spectrum of health benefits that SAMe provides for the liver.

Based on published clinical trials, elevating SAMe levels can have a beneficial effect on many conditions. As a preventive agent, SAMe is so powerful that it can reverse the effects of chemicals and alcohol as they occur.23 Studies also show that low SAMe levels create a toxic environment that can increase liver cancer risk.24 SAMe can prevent these conditions from occurring. In short, anyone concerned about the effects of drugs, chemicals, alcohol and aging on their liver should consider adding SAMe to the supple­mental regimen.

How Glutathione is created from SAMe

SAMe is the precursor for the sulfur amino acids cysteine and taurine, as well as the tri-peptide glutathione. SAMe is first transformed into S-adenosylhomocysteine, which is then converted into cysteine and taurine. Sulfur compounds are so important that under conditions of absolute deficiency of sulfur, there is no living material. Every cell in the body contains sulfur compounds.21

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Glutathione is the most important substance in the liver. The liver's principle function is to break down damaging substance the body encounters. These may be drugs, or the body's own products. Liver malfunction, whether caused by alcohol, viral infection or acetaminophne overdose is invariably accompanied by glutathione depletion. When glutathione is depleted, the liver simply can't work effectively.22

Continued on Page 2 of 3

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