ack to December 2010
New Human Study Confirms Potent Antidepressant Effects of SAMe
December 2010

By David Hoffnung
New Human Study Confirms Potent Antidepressant Effects of SAMe

Life Extension® introduced SAMe (S-adenosylmethinone) in 1997. Back then it was enormously popular in Europe, but unknown in the United States.

The National Institute of Mental Health decided to fund a double-blind, placebo-controlled trial that would evaluate SAMe as an additive therapy in those suffering major depression who were resistant to FDA-approved drugs.

Researchers at Harvard Medical School and Massachusetts General Hospital gave patients 800 mg of SAMe twice daily along with a selective serotonin reuptake inhibiting drug (SSRI).

Relative to placebo, patients who received the SAMe showed a 105% higher response rate and a 121% higher remission rate.1 Said differently, add-on therapy with SAMe in patients with drug-resistant depression produced double the response rate AND remission rate compared with placebo within a 6-week period.

This study was published in the August 2010 issue of the American Journal of Psychiatry.1 It was a follow-up to a 2004 pilot study that showed greater benefits when antidepressant drugs were combined with SAMe than when the same drugs were taken alone.2

National Institute of Mental Health

For the past 13 years, SAMe has been on Life Extension’s TOP TEN list of the most important steps to take to ensure optimal longevity. SAMe has been recommended to aging individuals not to just feel better, but also to protect the brain, liver, joints, and other tissues of the body like no other substance.

This article reviews and updates the many studies documenting the anti-aging properties of SAMe.

A listing of all the drugs the FDA has approved to treat depression would fill several pages of this magazine. A major problem with these antidepressant drugs is that they fail a significant number of patients—up to 30%, by some accounts.3 In many cases, the drugs make depressed individuals feel worse, and FDA-mandated labeling now requires a warning that use of some antidepressants increases suicide risk—which is an incredible contradiction considering that suicide is a leading cause of death amongst depressives.

An equally disconcerting issue is the many side effects associated with antidepressant medications such as weight gain, constipation, dry mouth, and other symptoms that cause many depressives to stop using them.

There is thus an urgent need for a new approach to treating those who fail to respond to currently available antidepressant medications. Encouraging news from a recent study shows that the addition of S-adenosylmethinone (SAMe) to a serotonin reuptake inhibitor drug markedly improves the percentage of severe depressives who are relieved of their disorder.

Unlike synthetic prescription drugs that induce unintended side effects, SAMe is a naturally-occurring agent in the body that performs a multitude of beneficial functions, such as boosting glutathione levels in the brain and liver. The anti-aging properties of SAMe are so profound that non-depressives take it each day (in lower doses) just like they do their other dietary supplements.4,5
Antidepressants Don’t Work
Antidepressants Don’t Work

As a team of Harvard researchers noted in a remarkable 2010 study published in the Journal of Clinical Psychiatry,6 “The majority of depressed patients will not experience remission when treated with a first-line antidepressant.”

In other words, antidepressants don’t really work for most patients. More is needed to help depression’s victims.

This is where SAMe comes in.

In modern high-tech imaging studies of healthy human brains, SAMe produces effects typical of several classes of antidepressant drugs7—but unlike those drugs, SAMe has remarkably few side effects and is well-tolerated even in elderly subjects.8

People with depression may exhibit a variety of biochemical imbalances, but the most common and best-known has to do with neurotransmitters like serotonin (involved in mood, sleep, appetite, and learning) and norepinephrine (involved in heart rate, blood pressure, and the fight-or-flight response). These chemical messengers belong to a class of molecules known as monoamines, and their synthesis in brain cells is largely controlled by the presence of folic acid, vitamin B12—and SAMe.9-12 When released into the space between brain cells (the synapse), monoamines exert stimulating or inhibiting effects on postsynaptic neurons.

With too little serotonin or norepinephrine available, the brain cannot sustain a positive mood—and depression results. Virtually all antidepressant drugs work to boost levels of these neurotransmitters within the synapse. And therein lie many of their limitations—and the causes of many of their side effects.13

SAMe operates through a completely different mechanism than these drugs. A molecule derived from the sulfur-containing amino acid methionine, SAMe is found in every living cell and plays a central role in cellular function.14,15 In addition to being required for monoamine synthesis, it also affects cell membrane fluidity, which may in turn influence how well a neuron transmits an electrical signal.16 Recent studies have shown that SAMe is also involved in the so-called “epigenetic” control of cellular function—the ability of cells to activate or suppress specific genes based on environmental influences—by its effects on proteins associated with chromosomes.17

These multi-targeted effects, coupled with an extraordinary safety profile, make SAMe a compelling treatment for a wide variety of brain disorders, from depression and cognitive decline to congenital metabolic dysfunction.18,19 SAMe crosses the blood-brain barrier, making it readily available to the brain and nervous system.10 This is vital: SAMe levels in the spinal fluid of depressed individuals have been shown to be significantly lower than those of healthy people.11

Animal models of depression shed additional light on how SAMe works in the brain. More than two decades ago Japanese scientists demonstrated a reduction in aggression in rats treated with SAMe as a result of its action in the central nervous system.20 By the turn of this century, researchers in Italy and Spain showed that SAMe reverses experimentally-induced depression in rats, at a rate faster than that of the prescription antidepressant imipramine, the first tricyclic antidepressant developed, and without apparent side effects.21,22 And in a remarkably detailed study, the Italian group showed that SAMe restored diminished brain levels of “polyamines,” essential brain molecules that are reduced in depressed patients.23

In 2007 a team of scientists at the University of Massachusetts launched a study using a combination of SAMe with N-acetyl cysteine (NAC) and acetyl-L-carnitine.24 Their subjects were aging mice with neurodegeneration similar to Alzheimer’s disease, in which depression is often a major manifestation. The combination rapidly enhanced cognitive function and prevented or reduced aggression in the animals, an effect that was rapidly reversed when the combination was withdrawn. The combination also prevented a decline in levels of the neurotransmitter acetylcholine, while contributing important antioxidant effects as well.
What You Need to Know: SAMe

SAMe Dramatically Improves Therapeutic Outcomes

A landmark study funded by the National Institute of Mental Health revealed that the addition of S-adenosylmethionine or SAMe produces compelling results in people taking SSRIs, the majority of whom do not experience relief when taking the drug alone.

SAMe is a naturally occurring molecule found in all living cells; it supports a host of chemical functions necessary for normal brain activity.

SAMe acts by several distinct and independent mechanisms to target multiple sites of action in brain cells that are involved in producing depression.

In clinical trials, SAMe has been shown to be at least as effective as prescription antidepressants, but with far fewer side effects.

Because of its strong safety record, SAMe should be part of any regimen for brain health, particularly when depressive symptoms are present—and when prescription drugs alone don’t work.

SAMe has also been shown to confer enormous benefits to the brain, liver, and joints, halting and even reversing various degenerative conditions, from osteoarthritis and neurodegeneration to nonalcoholic fatty liver disease.

Let’s turn now to the clinical realm and examine how well SAMe actually functions in humans suffering from depression.
SAMe Dramatically Improves Therapeutic Outcomes

Clinical trials have repeatedly demonstrated the benefits of SAMe in patients with major depression in a variety of populations: doses of 400-1,600 mg daily consistently resulted in rapid improvement in depressive symptoms and side effects that were mild and transient.25-27

SAMe is even effective in patients previously labeled “nonresponders” to conventional drug treatment.25 This led first to additional studies of SAMe compared with standard drugs rather than placebos, and later to studies in which SAMe was used in addition to such drugs.

SAMe consistently performs as well as or better than older-generation antidepressants such as imipramine and desipramine, drugs which are highly effective but have an unfavorable safety profile.28-30 In every case, the side effects of SAMe were trivial or mild. Interestingly, one such study found that regardless of whether patients received SAMe or the drug, their levels of SAMe in blood rose significantly as their depressive symptoms improved.28