Life Extension Magazine®

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Beyond Depression... SAMe Broad-Spectrum Protection Against Disorders Of Aging

Research has shown that SAMe is often just as effective as certain drugs in alleviating depression and boosting mood health. Going beyond depression, scientists have now found a wealth of anti-aging benefits of SAMe in protecting against Alzheimer’s, osteoarthritis, liver disease, and encouraging critical DNA repair.

Scientifically reviewed by: Andrew Roberts Jr., MPH in Global Health, MS in Medical Health, in August 2023. Written by: Michael Downey.

Beyond Depression SAMe Broad-Spectrum Protection Against Disorders Of Aging  

SAMe (s-adenosylmethionine) originally gained notoriety as a safe and effective alternative to anti-depressant drugs.

Research demonstrated that SAMe was equally effective as certain drugs in alleviating depression, without the side effects often associated with these antidepressants.1,2 SAMe’s wide-ranging systemic health benefits are less well-known.

In addition to boosting brain chemicals important to mood health, SAMe promotes the synthesis of other compounds that are crucial to functions such as gene expression and DNA repair.3

As a result of these many biochemical effects, scientists have demonstrated that SAMe may play a unique role in preventing, treating, or reversing numerous disorders of aging—including Alzheimer’s, fibromyalgia, inflammatory bowel disease, insomnia, osteoarthritis, and liver disease.3

In this article, we will explore SAMe’s range of anti-aging benefits throughout the body.

How SAMe Inhibits Diseases Of Aging

The compound SAMe, (S-adenosylmethionine) is found in virtually every tissue and fluid in the body, and it is required in a myriad of biochemical reactions.4,5 Since SAMe occurs in virtually all living cells, scientists believe that it has long assisted cells in defending against destructive influences.6

One of the most important processes SAMe is involved in is methylation, in which it acts as a methyl donor to support a multitude of chemical reactions.7-9 Vital biochemical processes in the body rely on methylation. These include the synthesis of nucleic acids (DNA and RNA), proteins, phospholipids, and neurotransmitters. SAMe and the methylation reactions it promotes help regulate gene expression, lipid and mineral metabolism, membrane structure, and fluidity.3,9-11

SAMe contributes to the production and recycling of our body’s signaling molecules such as hormones and neurotransmitters, including serotonin, dopamine, and noradrenaline (also known as norepinephrine).3

Your body’s ability to appropriately methylate may decline with age, leading to increased risk of many chronic age-related diseases including cancer, neurodegeneration, and autoimmune disease.9-11 SAMe’s critical methylation effect can block disease and slow certain aging processes.

In addition, SAMe is necessary for the synthesis of glutathione, which means it plays an important role in protecting the body from free radical-induced aging.3,9 Glutathione is crucial for liver function. The liver is the organ most responsible for purifying toxins in the body.3 SAMe plays an important role in enhancing the antioxidant power of superoxide dismutase (SOD).12

Lastly, SAMe is required for synthesizing a group of compounds known as polyamines.3,8 Polyamines are critical for the effective regulation of normal cell growth,3,9 and evidence suggests they play a role in programmed cell death (apoptosis).13

Polyamines facilitate DNA repair, gene expression, neuron regeneration, and protein phosphorylation (the addition of a phosphate group to a protein). One particular polyamine, spermidine, has been called a “universal anti-aging drug” because of its longevity effects across a number of experimental models from single-cell organisms such as yeast to more complex mouse models.14

These many biochemical reactions triggered by SAMe provide protective benefits well beyond the antidepressant effects for which it is best known—and help explain why SAMe has such a wide range of anti-aging and anti-disease activities.

SAMe Blocks Aging Diseases—From Alzheimer’s To Arthritis

SAMe is present in virtually every body cell. It promotes the synthesis of compounds that are critical to vital functions such as gene expression and DNA repair. These favorable mechanisms reveal how SAMe can exert potent defense against a spectrum of chronic diseases associated with aging.4,5 Following, is a discussion of the benefits of SAMe against seven diseases of aging.

1. Alzheimer’s Disease And Dementia

Alzheimer’s Disease And Dementia  

Recently, dementia was estimated to afflict 36 million people globally, a toll that is expected to more than triple by 2050, according to the group Alzheimer’s Disease International.15 However, in a promising development, experts have recently discovered a crucial finding that gives us a clue to an underlying cause of Alzheimer’s disease. It turns out that Alzheimer’s patients have severely low levels of SAMe, even significantly lower than those found in patients with depression.16,17

Since SAMe beneficially promotes an important chemical reaction known as methylation,7-9 lack of SAMe could lead to disturbances in this methylation process, which could be a key driver behind Alzheimer’s disease.16 In fact, one theory suggests that impaired methylation occurs in several different neurological and psychiatric disorders.18 There is even evidence that the gradual loss of the methyl group contributes to the aging process itself!16

SAMe has also been found to have a beneficial effect on two of the proteins associated with Alzheimer’s disease, beta-amyloid and tau.19

In an animal study, scientists found that SAMe reduced production of amyloid plaque, increased spatial memory, and inhibited tau phosphorylation, the process behind the accumulation of intracellular proteins known as neurofibrillary tangles that are characteristic of Alzheimer’s. Furthermore, SAMe treatment reduced plaque spreading. The researchers encouraged further studies to evaluate the use of SAMe “…as a potential candidate drug for the treatment of the disease.”19

Another study conducted on mice showed that SAMe supplementation decreased brain deposits of beta-amyloid plaque by 80% after just one month of treatment!20

As an added bonus, scientists believe that supplementation with SAMe can improve cognitive function and reduce depression—both of which are common symptoms associated with Alzheimer’s.1,16

Supplementing with 1,200 milligrams of SAMe daily for four to six months increased the level of SAMe in cerebrospinal fluid in patients with Alzheimer’s by 62.5%.16

What You Need to Know
SAMe’s Biochemical Effects Block The Diseases of Aging

SAMe’s Biochemical Effects Block The Diseases of Aging

  • Since Life Extension introduced SAMe to American consumers 17 years ago, it has become established as a potent, natural antidepressant.
  • However, scientists now know that SAMe promotes the synthesis of chemicals throughout the body that are critical to vital functions such as gene expression and DNA repair.
  • Extensive research now demonstrates that SAMe is powerfully effective at safely preventing, treating, and/or reversing numerous diseases. These include Alzheimer’s, Parkinson’s, fibromyalgia, inflammatory bowel disease, insomnia, osteoarthritis, liver disease—and even the root of aging itself!
  • Although SAMe was a relatively expensive nutrient when first introduced to the US market, the cost of producing pharmaceutical-quality SAMe has been greatly reduced—making SAMe an essential addition to every well-rounded supplement regimen.

2. Parkinson’s Disease

The second most common neurodegenerative disorder after Alzheimer’s is Parkinson’s disease, which is estimated to affect about 7 to 10 million people worldwide and as many as 1 million Americans.21,22 As with Alzheimer’s, research reveals a direct correlation between levels of SAMe and Parkinson’s disease.23

In aging individuals stricken with Parkinson’s, increased markers of neurodegeneration have been found when methylation factors such as SAMe are low.23 Conversely, cognitive function is better when levels of SAMe are proportionally higher.23

SAMe has a number of underlying mechanisms that help support healthy brain function. SAMe supports the brain through the key process of methylation.7-9,18 SAMe also supports brain levels of glutathione and enhances the antioxidant power of superoxide dismutase (SOD).12 These twin capabilities further help explain SAMe’s potency as a neuroprotective compound.

3. Fibromyalgia

Fibromyalgia is a disorder characterized by musculoskeletal pain, fatigue, and mood changes. Although there is no known cure for this disease, SAMe has been found to be effective against some of its worst symptoms.

In a double-blind human trial, scientists gave fibromyalgia patients either 400 milligrams of SAMe twice daily or placebo. SAMe produced improvements in pain, fatigue, morning stiffness, and mood. 24,25
In other studies, SAMe showed similar benefits, and appears to provide safe and effective management of fibromyalgia.26,27

SAMe Boosts Neurochemical Synthesis To Block Depression
SAMe Boosts Neurochemical Synthesis To Block Depression

SAMe has been demonstrated to play many essential roles in the body, but these functions have been greatly overshadowed by its well-established effects against depression.

Perhaps that’s because SAMe fills the growing need for depression therapy more effectively1 and much more safely2 than available drug options.

Depression is a major public health problem that afflicts about 10% of American adults.51 However, Harvard researchers found in 2010 that “the majority of depressed patients will not experience remission when treated with a first-line antidepressant.”52 In other words, antidepressant drugs will not work for most people.

Even more alarming, a 2011 review of seven double-blind clinical trials53—conducted by researchers affiliated with Eli Lilly, the company that makes the antidepressant duloxetine (Cymbalta®)—reported that over 23% of those taking antidepressant medication failed to respond to the treatment!

But modern high-tech imaging of healthy human brains revealed that SAMe delivers potent antidepressant effects equivalent to certain antidepressant drugs. 1 And unlike those drugs, SAMe has remarkably few side effects and is well-tolerated.1

In clinical trials, doses of 200 to 1,600 milligrams of SAMe daily consistently resulted in rapid improvement in depressive symptoms and produced side effects that were mild and transient.1,54,55 For example, in 2004, a team of Harvard psychiatrists gave 800 to 1,600 milligrams of SAMe daily to 30 patients shown to be resistant to treatment with antidepressant drugs.56 The researchers found that 50% of these patients responded to treatment, with a remarkable 43% experiencing remission of symptoms!56

Then, a 2010 study funded by the National Institute of Mental Health evaluated SAMe’s benefits in augmenting existing drug treatments in patients who were resistant to FDA-approved antidepressant drugs.57 This double-blind, placebo-controlled trial involved giving test patients 800 milligrams of SAMe twice daily along with a selective serotonin reuptake inhibiting drug (SSRI). Compared to the subjects on placebo, these previously resistant patients who received the SAMe-plus-drug therapy showed a 105% higher response rate and a 120% higher remission rate57—more than double the response and remission rate within just 6-weeks of treatment!

4. Inflammatory Bowel Disease

Supplementing with SAMe could also be beneficial for patients suffering from inflammatory bowel disease. Scientists found that these individuals have low concentrations of SAMe, suggesting that insufficient SAMe levels may play a role in distinguishing influences such as sulphur toxicity as “a causative mechanism in inflammatory bowel disease.”28 A subsequent study revealed that SAMe supplementation in combination with other antioxidants improved inflammatory factors and intestinal symptoms and returned low blood levels of glutathione to normal values in an animal model of severe colitis.29

5. Insomnia

SAMe has a beneficial effect on those suffering from insomnia. It plays an important role in the synthesis of melatonin, a hormone associated with sleep.30 Melatonin has been studied as a treatment for insomnia, delayed sleep-phase syndrome,and circadian rhythm sleep disorders.31 However, production of this hormone appears to decrease with age.32 Fortunately, SAMe promotes the function of the enzyme that converts N-acetylserotonin to melatonin.33

Furthermore, by promoting melatonin production, SAMe may be inhibiting the process of aging itself! Melatonin is a recognized geroprotector34—a therapeutic agent that targets the root cause of aging and age-related diseases, and thus prolongs life span. Melatonin has been demonstrated in animal studies to prevent premature aging and carcinogenesis and to increase average life span.34

6. Osteoarthritis


SAMe is known to target osteoarthritis, which affects over one-third of those over age 65.35 In a comprehensive meta-analysis, scientists found that SAMe was as effective as NSAIDs (non-steroidal anti-inflammatory drugs) in alleviating pain and optimizing joint function— but without the adverse effects that come with taking NSAIDS.36

When compared to ibuprofen, SAMe was found to be as effective,37 or more effective,38 in reducing painful joint manifestations—including morning stiffness, pain during rest and motion, swelling, “cracking” sounds, and limited range of motion in arthritic joints.37,38 Yet side effects were three times more common with ibuprofen.38

Confirming these effects, subsequent clinical trials demonstrated that SAMe blocks pain and stiffness in aging individuals with osteoarthritis.39 Remarkably, in vitro and animal studies indicated that SAMe stimulates cartilage production—crucial to halting and reversing arthritis.39

7. Liver Disease And Gallstones

Because the liver has over 500 critical functions, from synthesizing compounds to removing contaminants, diseases that impair the liver’s ability to carry out these functions can be life-threatening.40 Without SAMe, liver cells are less efficient at performing vital detoxification reactions—but scientists found that cirrhosis patients have alterations in the pathway that produces SAMe.41

Insufficient SAMe levels are linked to various liver diseases, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.42,43 In multiple studies, patients with various liver problems (including drug toxicity) responded well when administered SAMe, showing signs of improvement in liver function and in some cases restoration of normal liver function.5,44-46 In a trial of patients taking 1,600 milligrams of SAMe daily, scientists found that evidence of liver damage was greatly reduced, including decreased blood bilirubin levels.47

SAMe was shown to treat alcoholic liver disease by at least four mechanisms: increasing glutathione levels, repairing glutathione transport into mitochondria, reducing toxicity of inflammatory cytokines, and increasing DNA methylation.48 Furthermore, SAMe may help prevent liver disease by increasing gene expression within liver cells involved in alcohol metabolism, boosting alcohol elimination rate after binge drinking.49

SAMe could also help prevent gallstones in women. In a controlled study of women taking oral estrogen contraceptives, 600 milligrams of SAMe daily reduced bile cholesterol, suggesting SAMe may also prevent gallstones in women with increased estrogen levels.50


Since Life Extension® introduced SAMe to American consumers 17 years ago, it has become well-known for its potent antidepressant effects.1

However, decades of accumulating studies indicate that this remarkable natural compound promotes the synthesis and reactions of chemicals throughout the body that are critical to key functions such as gene expression and DNA repair.4,5

As a result, scientists have now demonstrated that SAMe is effective in safely preventing, treating, and/or reversing numerous diseases, including Alzheimer’s, Parkinson’s, fibromyalgia, inflammatory bowel disease, insomnia, osteoarthritis, liver disease—and even the root causes of aging itself!5,12,16,20,23,24-27,29-31,34,37-39,44-47

Although SAMe was a relatively expensive nutrient when first introduced to the US market, the cost of synthesizing pharmaceutical-quality SAMe has now been greatly reduced—making SAMe a more affordable addition to a well-rounded supplement regimen.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.


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