Health Supreme by Sepp Hasslberger

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June 11, 2006

SAM-e: Methylating Agent Stops Depression, HIV

In two recent articles based on research done by Cal Crilly, methylation of the DNA is indicated as a mechanism that controls the expression of what we call "retrovirus" particles. These are parts of the human DNA that are mobile and that often have benign functions in our body processes. See AIDS - Retrovirus Expression Regulated by Methylation? and Why Retroviruses Appear in AIDS, Cancer and Autoimmune Diseases.

The retrovirus that is said to cause AIDS, HIV, is not an exception. It apparently gets expressed in greater quantities when there is a lack of DNA methylation.

A substance called S Adenosylmethionine (SAM-e) aids in the process of methylation, not only of the DNA but of proteins and cell membranes as well. SAM-e is effective for depression and while the following article concentrates on this aspect, the fact that the substance promotes methylation as a general mechanism and its promotion of glutathione production, would seem to make it useful for a whole number of different health problems, including AIDS.


Glutathione - Image credit: Molecular Expressions

"There is nothing more fundamental to human life than DNA. It’s the genetic "software" which runs the cells and contains the genetic code for every living thing. When SAM-e reacts with DNA by donating a methyl group, it allows our genes to spring into action. It’s like hitting the "on" switch on a computer; DNA methylation is the operating system of the body, helping it to regulate important processes such as cellular growth and repair, production of immune cells to fight disease, wound healing, and reproduction. The undermethylation of DNA is believed to be a causal factor in cancer, because it could hamper the body’s ability to repair damaged cells before they turn cancerous."

The article that contains the information is a chapter from a book titled Stop Depression Now: SAM-e: The Breakthrough Supplement that Works as Well as Prescription Drugs, by Richard Brown, M.D., Teodoro Bottiglieri, Ph.D.

Seeing what fundamental importance this substance has in many life processes and considering the great number of different "opportunistic illnesses" associated with AIDS, perhaps it would be time to look at this in more detail and include SAM-e in studies designed to find a cure for AIDS that also increases quality of life.

Actually, according to Medline, several studies have been done involving S Adenosylmethionine and HIV. But then - it is not one of your patentable molecules that a pharmaceutical manufacturer can convert into an insane income stream. So don't get up your hopes up too high...

- - -

The SAM-e Story: Stop Depression Now

(original found here)

The SAM-e Story

A chapter from the book Stop Depression Now, by Richard Brown, M.D., Teodoro Bottiglieri, Ph.D., and Carol Colman, published by Putnam Sons 1999.

When people start taking SAM-e for the first time, two things usually happen. Within days, their mood begins to lift and they have an increased sense of wellbeing. But that’s not all. They also report something quite unique to SAM-e. They consistently say that they actually feel more energetic and healthier. That’s quite a change from what you generally hear from a patient starting an antidepressant.

Unlike other antidepressants, SAM-e is made from substances normally found in the human body—methionine and adenosine triphosphate (or ATP). Methionine is an essential amino acid, a building block of protein. Found in high-protein foods such as meat and fish, methionine is also made in small amounts by our cells, but not in enough quantity to meet the body’s needs.

Good nutrition is key to maintaining adequate methionine levels. Here’s why. Two key B vitamins, B12 and folic acid, are required for the production of methionine. In fact, a deficiency in either one of these vitamins can result in depression and problems in mental function, especially among older people. Much of Terry’s research has centered on the role of these B vitamins in depression in general and in the production of SAM-e in particular. As we will explain later, the two are inextricably linked, and the SAM-e story cannot be told without including these vitamins.

ATP is a high-powered fuel that is produced by the cells to provide energy to run the body. It is present in almost every cell and provides the juice to run all of the body’s machinery. There is plenty of it to go around.

The product of this marriage of methionine and ATP is SAM-e, a molecule essential to many aspects of human health. But SAM-e levels are not evenly distributed among all humans. Blood levels of SAM-e are seven times higher in children than in adults. Men have slightly higher levels of SAM-e than women do, probably because a considerable amount of SAM-e is produced and consumed in muscle tissue, which is more abundant in men. Levels of SAM-e are notably lower among depressed people of any age.

SAM-e deficiencies are also common in people with neurological problems such as Alzheimer’s disease, Parkinson’s disease, and HIV complications that can lead to dementia. Terry, who, as noted in Chapter 1, did his Ph.D. on SAM-e in 1982, was one of the first scientists to study this remarkable molecule in connection with the central nervous system and, more specifically, its role in regulating mood and mental function. Recently, Terry discovered that levels of SAM-e are lower in the cerebrospinal fluid of people with neurological complications like depression due to severe vitamin B12 or folate deficiency. Low levels of SAM-e in cerebrospinal fluid, as we have seen, indicates an inadequate amount in the brain. Clearly, these are compelling reasons not to let your SAM-e levels fall below normal.

SAM-e Turns On Key Reactions

SAM-e’s key role in a process called the methylation cycle makes it absolutely essential for human health. Methylation, a term for a basic yet critical chemical reaction in the body, is the passing of what is known in chemistry as a methyl group - one carbon and three hydrogen atoms - from one molecule to another. Methylation is as vital to human life as breathing. It is an "on-off ‘switch that activates more than a hundred different processes in the body, from producing important neurotransmitters that allow brain cells to communicate, to preserving bone health, to protecting against heart disease. Methylation activity declines as we age, resulting in a slowdown of these vital activities, which many scientists suspect may contribute to the aging process as well as to the onset of many diseases. There is also compelling evidence that a slowdown in methylation or a genetic tendency to undermethylate may be a key factor in depression for many. There are different kinds of SAMe/methylation reactions that trigger biological responses throughout the body. These reactions are the "greatest hits" of metabolism. They are what make us alive. When you review the list below, you will see why SAM-e is so fundamental to life that we could not exist without it.

DNA METHYLATION. There is nothing more fundamental to human life than DNA. It’s the genetic "software" which runs the cells and contains the genetic code for every living thing. When SAM-e reacts with DNA by donating a methyl group, it allows our genes to spring into action. It’s like hitting the "on" switch on a computer; DNA methylation is the operating system of the body, helping it to regulate important processes such as cellular growth and repair, production of immune cells to fight disease, wound healing, and reproduction. The undermethylation of DNA is believed to be a causal factor in cancer, because it could hamper the body’s ability to repair damaged cells before they turn cancerous.

PROTEIN METHYLATION. Proteins form the basic structures of many key components of the human body, including muscles, tissues, organs, and even hormones. The methylation of protein is critical for cell growth and repair. Sluggish protein methylation can trigger a downward spiral that can have a devastating impact on the body and mind, leading to deterioration of key organ systems, including the heart and brain. Protein methylation undoubtedly plays a major role in the onset of depression. It is involved in the activation of receptors, special sites on cell membranes which bind with other molecules to stimulate a response-in other words, the body’s basic communication system. As discussed in the last chapter, this is especially true of the brain, where sluggish protein metabolism can pitch someone into depression. Studies show that SAMe supplementation can stimulate protein methylation, which not only boosts levels of the key neurotransmitters but increases the number of receptors.

PHOSPHOLIPID METHYLATION. Cell membranes are composed of fatlike substances called phospholipids. In order to get into the cell, substances must first pass through the cell membrane. As we age, cell membranes can become rigid, making it difficult for vital substances to move in and out. SAM-e is important for phospholipid methylation, which helps maintain the flexibility of the cell membrane, keeping it more youthful. Through methylation, SAM-e also boosts the production of phosphatidylserine, a phospholipid important for both mood and memory.

Its role in the methylation cycle places SAM-e at the heart of many lifesaving functions. But the SAM-e story doesn’t stop here. SAM-e is also essential for another critical process, called trans-sulfuration, which produces a key chemical, glutathione.

SAM-e Boosts Glutathione

Many of you have heard of antioxidants, a group of compounds produced by the body and also found in many different foods, primarily fruits, vegetables, legumes, and whole grains. Some well-known vitamins like C, E, and beta carotene are, in fact, antioxidants. As noted in Chapter 1, antioxidants protect us from damage caused by highly reactive compounds called free radicals. The human body requires oxygen for its basic chemical functioning, for metabolism, for energy. Everything we do requires energy, both conscious activities like walking and automatic body functions like our heartbeat and breathing. Oxygen is the fuel that drives energy production and makes life possible, but it leaves behind a potentially dangerous by-product - the unstable oxygen molecules called free radicals. Free radicals are fine up to a point - in fact, without them, we couldn’t live. If allowed to accumulate, however, they can cause a great deal of mischief. They can attack DNA, possibly initiating cancer. They can attack fat molecules in the blood, causing them to oxidize and form plaque, thereby clogging the arteries. They can target cells in key areas of the brain and may be a factor in brain aging.

The body has a defense system that controls free radicals, and glutathione - known as the "master antioxidant" - is at its heart. You cannot obtain glutathione through diet; it must be produced by the cells. So crucial is it to the body that living a long, healthy life requires making a constant supply. Below is a review of just a few of the lifesaving functions that glutathione performs in the body. It could not perform any of these tasks without SAM-e.

DETOXIFIES THE LIVER. There is a huge amount of glutathione in the liver, which also contains the body’s heaviest concentration of SAM-e. The liver has many crucial jobs, including the production of bile, but its most important role is the detoxification of drugs (including the tricyclic antidepressants), alcohol, and poisons that are ingested in food, such as insecticides, or produced by the body through normal metabolism. When glutathione encounters toxic compounds in the liver, it attaches itself to them, making them more water-soluble. This allows the toxins to be flushed out through the kidneys. Liver damage occurs when the liver is so overwhelmed by toxins that it cannot produce enough cleansing glutathione. As I will discuss in Chapter 11 ("Getting Healthy with SAM-e"), SAMe has been used as an effective treatment for liver disease, especially alcohol-induced liver damage.

PROTECTS DNA. Glutathione protects DNA from damage by free radicals, which can contribute to diseases such as cancer and premature aging.

BOOSTS THE IMMUNE SYSTEM. Glutathione is also important for a well-functioning immune system, the body’s defense against disease. Interestingly, several studies have documented a link between depression and weakened immune function. Although it has never been studied, the decline in immunity seen in depression could be related to a scarcity of glutathione caused by a deficiency in SAM-e.

REDUCES INFLAMMATION. Another vital function of glutathione is the role it plays in the reduction of inflammation, which is the primary cause of discomfort in osteoarthritis, a condition caused by the wearing down of the cartilage (the protective covering on bones). As noted, SAM-e is also a highly effective treatment for osteoarthritis, which could be due in part to its glutathione-boosting effect. (For more information on SAM-e and arthritis, see Chapter 11, "Getting Healthy with SAM-e.")

Without SAM-e, the body could not make adequate amounts of glutathione. In the process called transsulfuration, SAM-e helps produce the precursor to glutathione, the amino acid cysteine. Cysteine combines with two other amino acids, glutamic acid and glycine, to form the precious glutathione. Although glutathione is sold as a supplement, there is controversy about whether it can be used by the body in that form. Many scientists believe it breaks down in the stomach before it can reach the bloodstream. Therefore, one of the few effective ways to boost glutathione is to take supplemental SAM-e.

In addition to its ability to boost glutathione, SAM-e is also essential for the production of another type of compound found in the body called polyamines. The polyamines spermidine and spermine are involved in cell growth and cell differentiation. They also have an antiinflammatory effect.

Although SAM-e performs hundreds of roles in the body, its ability to boost glutathionine is one of its most important. But there is still more to report on the incredible SAM-e story.

The SAM-e/Homocysteine Connection

Recently, an amino acid called homocysteine has gained notoriety as a recognized risk factor for heart disease, stroke, and even some forms of cancer. What isn’t widely known is SAM-e’s key role in helping to control homocysteine.

Homocysteine is produced by every cell in the body as a normal part of the methylation cycle. Like free radicals, homocysteine can actually be useful in small amounts, but if allowed to accumulate, it can be terribly dangerous. Folic acid and Vitamin B12 can reduce homocysteine by converting it to methionine, the building block of SAM-e. SAM-e, in turn, helps remove homocysteine by increasing the activity of an enzyme (cystathione-beta-synthetase) that converts this potentially harmful amino acid into the beneficial glutathione.

Here’s another reason to keep your SAM-e levels high. Low SAM-e levels often go hand in hand with high homocysteine. Even slightly elevated levels of homocysteine are believed to increase the risk of heart disease and other problems:

• Homocysteine is toxic to the endothelial cells that line blood vessels. Damaged endothelial cells may lead to the formation of plaque in the arteries, causing heart attack and stroke.

• Homocysteine may increase the risk of blood clots.

• The Stroke Prevention in Young Women Study revealed that young women with levels of homocysteine in the top tenth percentile had nearly triple the risk of stroke-a risk comparable to that of smoking a pack of cigarettes daily.

High levels of homocysteine and a low intake of B vitamins are now believed to be risk factors in several other diseases, including reproductive cancers in women and cancers of the colon. More recently, they have been shown to be risk factors for Alzheimer’s dementia.

There is also a link between high levels of homocysteine, low levels of SAM-e, and depression. Terry’s research found low levels of folate and SAM-e in the red blood cells and spinal fluid of depressed patients. This was associated with high levels of serum homocysteine. Terry suspects that elevated levels of homocysteine as well as the deficiencies in these key B vitamins may hamper methylation, which could explain their destructive effects on the body and mind.

The homocysteine connection in both heart disease and depression raises some intriguing questions. As noted in Chapter 2, people with depression are at greater risk of developing heart disease, just as people who have heart disease are at risk for depression. In fact, about twenty percent of all heart patients receive a diagnosis of major depression, and as many as one third will have a major depression within one year after their heart attacks. Until recently, the depression associated with heart disease has been dismissed as that which often accompanies any chronic illness. After all, being sick is very stressful and stress is a key trigger for depression; chronic illness is hardly a happy event. However, recent studies show that about half of all patients with heart attacks have had bouts of depression prior to the onset of heart disease. Could treating your depression early in life by taking SAM-e prevent heart disease from striking down the road? Although this question has never been studied, we believe it is possible that early intervention could make a difference.

This complicated set of chemical reactions means that SAM-e works on many different systems of the body. As a result, it has been used as a treatment for many different and seemingly unrelated medical problems, including osteoarthritis, liver disease, and fibromyalgia.

SAM-e may help protect the brain against age related destruction of the cells responsible for mood, memory, and learning. As Terry noted in a recent study published in Nutrition Reviews (Vol. 54, No. 12), SAM-e has been shown to be reduced in the cerebrospinal fluid of patients with Alzheimer’s dementia, which suggests that methylation in the brain may be important for some forms of dementia. Currently, I am investigating the use of SAM-e as a treatment for Parkinson’s disease. (For more information, see Chapter 11, "Getting Healthy with SAM-e".)

The fact that SAM-e is involved in so many different life processes has made it the subject of intense scientific scrutiny. In fact, as noted in Chapter 1, SAM-e has been the subject of thousands of scientific studies, making it the only natural substance to have been so thoroughly researched in both Europe and the United States. In addition to numerous laboratory studies exploring the biochemistry of SAM-e, there have been thirty-nine published clinical studies on the use of SAM-e to control depression. While thirty-nine clinical studies may not seem like a lot, it’s actually more than most prescription drugs can boast when they go on the market!

• Close to 1,400 patients have participated in carefully controlled clinical trials on depression alone.

• In several studies directly comparing SAM-e to standard tricyclic medications, SAM-e did as well as or better than these drugs, without the side effects.

• Most of these studies involved severely depressed patients who often did not respond to other antidepressants, but nevertheless did surprisingly well on SAM-e.

• SAM-e has an excellent safety record. It has undergone rigorous testing and is approved as a prescription drug in Italy, Germany, Spain, and Russia.

But what about in the real world? Well, there are hundreds of thousands of patients around the world taking SAM-e for depression. As you know, it outsells Prozac in Italy. SAM-e’s worldwide reputation is excellent, and I have had amazing results with hundreds of patients taking it in my practice.

SAM-e’s remarkable antidepressant properties were discovered somewhat serendipitously. Although SAM-e was first identified in 1953, it was not until 1973 that researchers tested it as a treatment for schizophrenia, a disease many believe stems from a glitch in the methylation cycle. While SAM-e did not help to control the symptoms of schizophrenia, researchers were intrigued by one interesting finding. Unexpectedly, the schizophrenic patients treated with SAM-e became less depressed. Since then, scores of studies have investigated SAM-e’s role as an antidepressant, and the results have been quite extraordinary.

We’re not entirely sure yet how it works, but we do know this: Long-term treatment with SAM-e in animals has been shown to increase brain concentrations of norepinephrine, dopamine, and serotonin. Studies in humans have shown similar results. In one study reported in the journal The Lancet, Terry showed that depressed patients treated with SAM-e over a fourteen day period had a significant increase in cerebrospinal fluid concentrations of a key metabolite that is used as a marker for serotonin levels in the brain. Other researchers have also found that when depressed people are treated with SAM-e, their cerebrospinal fluid levels of the marker for dopamine increase too. The exact way in which SAMe does this remains unclear, but an increase in these two markers is often associated with antidepressant effect.

Study after study has confirmed that SAM-e excels when tested against a placebo, an important way to test the efficacy of any antidepressant. You may wonder why it is considered important that a drug outperform a placebo, or sugar pill. It may surprise you to learn that at least thirty percent of the effect of any antidepressant - for the first few weeks - is attributed to the so-called placebo effect. In other words, if you believe that a drug will work, it will. Even though the placebo effect wears off within a few weeks, it does underscore the power the mind can hold over the body. Therefore, in order to be certain that a drug and not the placebo effect has brought about a good response, the drug must consistently outperform a placebo by a substantial margin. When matched against a placebo, SAM-e wins hands down.

SAM-e not only outperforms a placebo but can hold its own among other antidepressants. Numerous studies have confirmed that when tested against several of the tricyclic antidepressants, SAM-e does as well, or nearly as well, with virtually no side effects. Also, since with SAM-e few patients drop out because of side effects or delay in onset of action, more people have a chance to respond to it.

Here are some of the research highlights that have advanced our understanding of SAM-e. We’ve only chosen a few of the many that have been done. (For a more complete list of studies, see the bibliography on page 245.)

THE FIRST SUCCESS. The first double-blind, placebo controlled study of SAM-e was conducted in 1973 in Verona, Italy. (Neither the researcher nor the patients knew who was taking SAM-e and who was taking the placebo.) Such double-blind, placebo-controlled studies are the gold standard of medical research. The study involved thirty depressed patients ill enough to be in psychiatric hospitals. Twenty of them were given SAM-e for up to fifteen days; the remainder were given a placebo. Based on the Hamilton Rating Scale, the most respected professional index of depression, researchers reported that one hundred percent of the patients, every single one of them - showed improvement in depressed mood while taking SAM-e. Only thirty percent of patients taking the placebo improved. In the researchers’ own words, "SAM-e acts favorably and significantly on specific depressive symptoms (depressed mood, work, and interests; suicidal tendencies) which, in a high percentage of patients, were greatly improved." In particular, researchers marveled over how fast SAM-e worked.

"The rapid action of the drug should be stressed since in some cases almost all of the symptoms had disappeared after 4 days of treatment, and in general, after 6 or 7 days ... No untoward side effects were observed in the patients to whom SAM-e was administered." (Journal of Psychiatry Research, 1976, Vol. 13.)

SAM-E WINS OVER ANOTHER ANTIDEPRESSANT. Researchers from the University of California’s Irvine Medical Center studied eighteen patients suffering from major depression. Nine of the patients were given a two week course of imipramine, a widely used tricyclic antidepressant. The other nine were given SAM-e for the same length of time. By the end of the fourteenth day, fully two-thirds of the SAM-e patients had shown a significant improvement in depressive symptoms. Only twenty-two percent of the imipramine patients had the same relief. "It appears," concluded the researchers, "that S-adenosylmethionine is a rapid and effective treatment for major depression and has few side effects." Noting that SAM-e worked faster than imipramine, the researchers added, "This characteristic of the drug may be a considerable advantage, considering the known risk of suicide during the early phase of treatment with tricyclic antidepressants." In other words, because it works so quickly, in some cases SAM-e could make the difference between life and death. (American Journal of Psychiatry, "SAdenosylmethionine Treatment of Depression: A Controlled Clinical Trial," September 1988, 145:9.)

SAM-E AT MASS GENERAL. Researchers at Harvard University’s affiliated Massachusetts General Hospital studied the effect of SAM-e on twenty patients, nine of whom had been classified as treatment-resistant because they did not improve on other antidepressants. The patients were given oral doses of SAM-e for up to six weeks. Researchers noted, "The group as a whole significantly improved with oral SAM-e." Of the eleven patients who were not treatment-resistant, seven showed a full antidepressant response on the Hamilton Rating Scale (an improvement of fifty percent or better). Two others showed major improvement but did not achieve a full response. Even more surprising, two of the nine treatment-resistant patients showed a full antidepressant response. Considering that very little works with treatment-resistant patients-people for whom standard antidepressants have been ineffective, this is an excellent result. What makes SAM-e’s performance even more significant is the fact that not one patient dropped out of the study because of side effects. (Acta Psychiatry Scandanavica,"The Antidepressant Potential of Oral S-Adenosyl-lMethionine," 1990:81, 432-36.)

MAJOR STUDY’S EXCELLENT RESULTS. A major multicenter study evaluated SAM-e in 195 outpatients in Italy. The subjects were given daily 400mg injections of SAM-e for fifteen days. At the end of the study, 163 patients were evaluated (the rest were excluded either for lack of compliance or because it was determined that they did not meet the criteria to participate in the study in the first place). The senior researcher, Dr. Maurizio Fava of the Depression Research Center of Harvard’s Massachusetts General Hospital, and his Italian co-researchers reported that depressive symptoms were significantly reduced after seven days for more than half of the patients who completed the study. In fact, ninety patients showed more than a fifty percent improvement on standard assessment tests. This is considered an excellent result. No severe side effects were reported, an encouraging and unusual finding for such a large study involving an antidepressant. (Journal of Psychiatry Research, 1995:56, 295-97.)

DESIPRAMINE OUTPERFORMED BY SAM-E! In 1994, a research team headed by Kate M. Bell at the University of California, Irvine Medical Center compared SAM-e with desipramine, a tricyclic antidepressant. Twenty-six patients were involved in a double-blind study comparing oral SAM-e with oral desipramine. At the end of four weeks, sixty-two percent of the patients taking SAM-e and fifty percent of the patients taking desipramine showed significant improvement.

The researchers also investigated whether there was a correlation between blood levels of SAM-e and mood. One interesting finding: Regardless of which drug they took, patients showing a fifty percent improvement or better in the Hamilton Rating Scale score-which is considered a full response, an excellent result-had a significant increase in blood plasma levels of SAM-e. As the researchers noted, "We found a significant relationship between change in plasma SAM-e concentration and clinical improvement.... In summary, the significant correlation between plasma SAM-e levels and the degrees of clinical improvement regardless of the type of treatment suggests that SAM-e might play an important role in regulating mood."

THE CHRONICALLY ILL HELPED BY SAM-E. As noted earlier, depression and illness often go hand in hand. But many people who are ill cannot tolerate antidepressants, or may experience particularly bad side effects from drug interactions. As the researchers in this study noted, in some cases, as with some forms of heart disease, antidepressants may make the chronic illness worse. "The 20 cardiovascular patients in our study were regarded as high-risk subjects because developing depression may cause suicidal ideation with further deterioration of quality of life. Tricyclics and monoamine oxidase ... inhibitors may be detrimental to cardiac patients because of their toxic cardiovascular side effects." It’s a catch-22: Treating severe depression may not only hurt the quality of life but also be life-threatening, yet treating with standard antidepressants may bring about the same result. For these people, SAM-e may be the treatment of choice. Forty-eight patients with major depression and concurrent serious illnesses were given up to 800 mg of SAM-e daily. The results as described by the researchers were excellent: "Response of patients treated with SAM-e was quite rapid and many were still improving at the end of the 28-day trial." As noted, patients not only improved quickly on SAM-e, but did not experience any untoward side effects that could worsen their preexisting medical problems. (Current Therapeutic Research, June 1994, Vol. 5 5, No. 6.)

A MAJOR REVIEW OF THE STUDIES. A metaanalysis, a major review of the published clinical studies on SAM-e, published in Acta Scandinavica Neurologica in 1994 assessed the efficacy of SAM-e in the treatment of depression. What makes this study so important is that all of the clinical trials of SAM-e published between 1973 and 1992 were analyzed. In eleven studies, SAM-e was tested against a placebo. In fourteen studies, SAM-e was tested against a standard prescription antidepressant. In another thirteen studies known as open studies, SAM-e was given to depressed patients without testing it against either a placebo or an antidepressant. The patients were monitored to assess improvement. In every study involving placebos, SAM-e was found to be more effective than the placebo. In fact, the author of the study notes that SAM-e does better on the placebo test than most other prescription antidepressants! In every study involving prescription drugs, SAM-e was found to be as effective as tricyclic antidepressants. In the open studies, patients also showed significant improvement. The review study concluded, "In summary, this meta-analysis shows that the efficacy of SAM-e in treating depressive syndromes and disorders is superior to that of placebo and is comparable to that of standard tricyclic antidepressants. Since SAM-e is a naturally occurring compound with relatively few side-effects, its antidepressant effect makes it a potentially important tool in the armamentarium of the modern psychopharmacologist."

TWO MULTICENTER STUDIES. In a 1997 review article published in Expert Opinion in Investigational Drugs, Terry outlined SAM-e’s potential as a treatment for psychiatric and neurological disorders. He reported on two as yet unpublished clinical trials on SAM-e conducted at several research centers in Europe involving 197 severely depressed patients (based on the Hamilton Rating Scale). In the first study, involving seventy-five patients, SAM-e was tested against a placebo. Both compounds were given intravenously. Patients taking SAM-e had an average improvement rate of 40.8 percent compared to patients taking the placebo, who improved by only 27.6 percent. Considering how severely ill these patients were, this is an excellent result.

In the second study, SAM-e went head-to-head with clomipramine, perhaps the strongest drug in the antidepressant arsenal. Although clomipramine is highly effective, recovery often comes at the cost of terrible side effects. In fact, many patients simply won’t stay on the drug. In the trial, 122 patients were given either SAM-e or clomipramine intravenously for three weeks. Patients taking SAM-e had an average improvement rate of 36.5 percent compared to 48.8 percent for the patients on clomipramine Even though SAM-e did not outperform clomipramine it did bring about a major improvement in these severely depressed patients, and it achieved this good result with virtually no side effects. As Terry noted in his review, "The drug related adverse events and dropouts for adverse events were significantly lower in SAM-e than in clomipramine." In other words, many patients did not continue to take clomipramine because they could not tolerate the side effects. If the dropouts had been factored into the final result as nonresponders, clomipramine would not have fared as well.

From these studies, it’s apparent that although SAM-e may be a powerful antidepressant, it works gently in the body. SAM-e can hold its own among even the strongest of the prescription drugs, yet it does not have any of the onerous side effects...

The preceeding was one chapter from the book, Stop Depression Now, by R.Brown, M.D., T. Bottiglieri, Ph.D., and C. Colman, Putnam Sons, 1999.

See also

"Willner Window" Radio Show - SAMe for Depression
This is an excerpt from The Willner Window radio program, originally broadcast on January 16, 2005.


posted by Sepp Hasslberger on Sunday June 11 2006
updated on Monday September 29 2008

URL of this article:


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Readers' Comments

This idea has been related to autism if of interest.

Impaired transsulfuration and oxidative stress in autistic children: Improvement with targeted nutritional intervention

Posted by: Cal Crilly on June 15, 2006 12:00 AM


I came across this article and while I dont have AIDS, I have had many stress factors along with several back injuries, that have fatigued my immune and energy systems. I test very strongly for Cortisol in my system. Even though I have been taking a high complex B combo for Womens stress,liquid minerals and antioxidants such as Mangosteen, (most effective), golden seal, blueberry juice, wheat grass, I am still tired, which I consider long term depression.
I am losing muscle, my weight is 139 at 5'9' and I am 59.
There is much I want to do but I just have a hard time staying motivated, thinking clearly and not feeling overwhelmed. Any feedback?

Posted by: Katherine Kemick on December 26, 2006 02:41 PM


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