Life Extension Magazine April 2014
Beyond Depression... SAMe Broad-Spectrum Protection Against Disorders Of Aging
By Michael Downey
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
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
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.
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
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
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
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