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Life Extension Magazine

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April 2007

By Tiesha D. Johnson, BSN, RN

In 2004, the FDA mandated that all antidepressants carry a “black box” warning on their labels following the discovery of a heightened risk of suicidal thoughts among children taking the pills.1 In December 2006, following a huge federal analysis of hundreds of clinical trials, FDA regulators for the first time acknowledged that the drugs can trigger suicidal thoughts among patients older than 18.1

Prescription antidepressants have brought relief to millions of people who suffer the debilitating symptoms of depressive disease. However, reports linking these drugs to a heightened risk of potentially dangerous side effects have led scientists to continue to search for natural agents that safely and effectively elevate mood.

One the most advanced mood-elevating therapies available today is S-adenosylmethionine, a natural compound that the Life Extension Foundation introduced to American consumers back in 1996. Long prescribed in Europe to alleviate depression, SAMe has been demonstrated to be as effective as certain pharmaceutical drugs in improving mood and a host of other conditions—without the side effects often associated with such drugs. In addition to relieving depressive symptoms, SAMe has shown efficacy in fighting liver disease, relieving arthritis pain, and even supporting healthy endothelial function.

In this article, we bring readers up to date on research findings attesting to the many diverse health benefits of SAMe.

S-adenosylmethionine (SAMe) is a natural compound found in nearly every body tissue and fluid, where it participates in myriad life-sustaining biochemical reactions.2

In fact, scientists have discovered that SAMe has many of the same beneficial effects in the body as drugs prescribed for numerous health disorders.3-5 Not only does SAMe have a 30-year history of effectiveness in treating depression,6 but growing evidence attests to its efficacy in preventing and treating several types of liver disease.7 Moreover, SAMe has been shown to be at least as effective as most nonsteroidal anti-inflammatory drugs (NSAIDs) in treating arthritis.5 Couple these benefits with its outstanding safety profile, and it is easy to see why a growing number of health professionals regard SAMe as a first-line therapy in managing a host of health conditions.

SAMe Boosts Mood, Complements Prescription Antidepressants

Depression is a major public health problem that afflicts adolescents and children as well as adults. Successive generations of antidepressant drugs, such as tricyclic antidepressants and serotonin reuptake inhibitors (SSRIs), have been hailed as breakthroughs in the treatment of depressive illness.

Tricyclic antidepressants (such as imipramine, amitryptiline, and others) fell out of favor in the early 1990s, after growing evidence that they induced numerous serious side effects and were often poorly tolerated.8 These side effects appeared to be absent in the newer SSRIs that became hugely popular in the 1990s and remain so today. However, recent findings indicating that SSRIs appear to increase the risk of suicidal ideation in some patients have been the source of both concern and controversy.9 In 2004, the FDA placed a “black box” warning on SSRIs, indicating that the drugs may increase the risk of suicidal thoughts in children,10 and the agency has continued to warn about possible side effects in patients of all ages. These developments pose a vexing dilemma for patients as well as their doctors, who wish to successfully manage depression yet avoid the potentially fatal side effects associated with prescription antidepressants.

To safely and effectively manage depression, more people are turning to SAMe. Although SAMe has been used to treat depression for more than a quarter of a century,11,12 it has received relatively little attention in the mainstream medical literature until recently. Today, however, growing evidence suggests that SAMe works as well as certain antidepressants, while demonstrating a superior safety profile.

SAMe influences the metabolism of the brain neurotransmitters dopamine and serotonin, both of which help control mood.13 It also crosses the nearly impenetrable barrier between the blood and the brain, an obstacle that prevents many drugs from acting on the central nervous system.14 Naturally occurring levels of SAMe are lower in the spinal fluid of people suffering depression,15 and increasing blood levels of SAMe have been found to produce improvements in depressive symptoms.16 Scientists have also discovered a clear link between SAMe and folic acid, demonstrating that the two nutrients work together to beneficially affect monoamine neurotransmitters, thereby providing support for healthy mood and optimal cognitive and nervous system function.13

In a small open trial in 1984, researchers treated nine depressed inpatients with SAMe, and seven showed improvement in or resolution of their symptoms.17 In another open trial in 20 outpatients, treatment with SAMe completely resolved depressive symptoms in 7 of 11 patients who had no history of poor response to antidepressants, and in 2 of 9 patients who had failed previous treatments with antidepressants.18

Several studies in the late 1980s found SAMe to be as effective as tricyclic antidepressants8 in fighting depression. In one double-blind, controlled trial of patients with major depression,16 nine were given intravenous SAMe and nine took imipramine for 14 days. Improvement was seen in the SAMe group by the end of the first week, and by the end of the trial, 66% of the SAMe group had exhibited significant improvement, compared to only 22% in the imipramine group.

More recently, Italian researchers published the results of two multicenter trials comparing SAMe with oral imipramine.3,19 In the first trial, 143 patients took 1600 mg of SAMe orally each day, while 138 took 150 mg a day of imipramine. In the second trial, 147 patients received 400 mg a day of SAMe by intramuscular injection, and 148 took oral imipramine. Researchers then compared the patients’ scores on two standard scales of depression. While the results of treatment were the same for patients receiving SAMe and imipramine, the SAMe patients experienced significantly fewer side effects.

As many as 46% of patients with major depressive illness show either a partial response or no response to antidepressant therapy, highlighting the need for strategies to improve the efficacy of treatment for depression.12 In 2004, researchers studied the complementary effects of SAMe and modern antidepressant drugs.20 Thirty patients who had incomplete responses to SSRIs or venlafaxine (Effexor®) were administered 800-1600 mg per day of SAMe for six weeks. Fifty percent of these treatment-resistant patients improved with the addition of SAMe to their therapy, and 43% experienced remission of symptoms. The authors concluded that augmenting antidepressant therapy with SAMe might well be effective in alleviating treatment-resistant depression.

A quick onset of action is particularly important in therapies to treat depression. While most prescription drugs take up to three weeks to produce significant effects, injections of SAMe (at 400 mg per day) in 195 patients21 reduced depressive symptoms after just seven days, with further improvement by 15 days—nearly a week before improvement might be expected with prescription medications. In depressed patients with HIV/AIDS,22 SAMe treatment also reduced depression symptom scores after just one week of treatment, with steady improvement continuing for all eight weeks of the trial.

SAMe has also been demonstrated to speed the onset of action of standard antidepressants. For example, in a double-blind study of 40 patients beginning treatment with 150 mg a day of oral imipramine,23 injections of SAMe (at 200 mg a day) decreased depressive symptoms faster than imipramine alone.

Fibromyalgia, a crippling condition marked by severe musculoskeletal pain and frequent sleep disturbances, often results in marked mood changes, including depressive symptoms. SAMe at doses of up to 800 mg a day has shown promise in alleviating fibromyalgia symptoms such as depression, fatigue, and morning stiffness—presumably as a result of its anti-inflammatory and mood-elevating properties.24,25

  • Long used in Europe as a prescription drug to fight depression, S-adenosylmethionine (SAMe) was introduced to the US in 1996 by the Life Extension Foundation.
  • SAMe participates in many essential biochemical reactions in the body, contributing to antioxidant protection, cell signaling, and production of neurotransmitters and hormones.
  • SAMe quickly and effectively elevates depressed mood, with an efficacy comparable to that of prescription drugs and minimal or no side effects. It may even help manage cases of resistant depression.
  • SAMe offers numerous benefits for those with liver and gall bladder diseases by enhancing bile flow and protecting the liver against toxin-induced damage. It also alleviates the pain and inflammation of arthritis, with effects comparable to those of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen.
  • SAMe supports healthy endothelial function and may one day be used to protect blood vessel linings against the dangerous effects of ischemia (oxygen deprivation) that occurs with heart attack, stroke, and transplant surgery.