Life Extension Magazine®

Woman on phone in good mood after supplementing with  SAMe

Wide-Ranging Benefits of SAMe

SAMe has demonstrated a new anti-aging mechanism via its ability to improve DNA methylation. This adds to previously demonstrated effects of improved mood, reduced joint discomfort, and cartilage regeneration.

Scientifically reviewed by: Dr. Heidi Yanoti, DC, in August 2023. Written by: Christian Mendez.

Since Life Extension® first introduced SAMe (S-Adenosyl-Methionine) back in 1997, it’s become popular for boosting mood.

In addition to fighting depression, SAMe also stimulates the production of new cartilage in animals and improves symptoms and functioning in osteoarthritis patients.1-3

In a recent study SAMe was shown to increase lifespan of yeast.4

What’s the common link between these benefits and SAMe?

SAMe is a cofactor involved in a process called DNA methylation, which regulates gene expression.5 In doing so, it can help fight against some of the causes of age-related disease—and it may prolong life itself.6,7

Understanding DNA Methylation

Genes are stretches of DNA that determine our traits, from hair and eye color to susceptibility to certain diseases and even lifespan potential.

Genes can also be active or inactive. The science of epigenetics studies how and why genes are expressed, or not.8

One of the main “switches” that modulates the way genes are expressed is DNA methylation, which occurs when methyl groups are added to the DNA.9

SAMe (S-Adenosyl-Methionine) is a nutrient found naturally in the body that serves as the primary methyl donor. That means it’s involved in practically all methylation reactions.9-12

If we don’t have enough of it, the body cannot methylate properly. That can lead to chronic inflammation, tissue damage, and age acceleration.13,14

One lab study showed that treating human cells with SAMe increased DNA methylation and modulated the expression of genes associated with inflammation.15

This has shown benefits in multiple disorders and has the potential to prolong life.

plants growing in a beaker

What You Need to Know

How SAMe Helps Our Genes Fight Disease

  • Humans have about 20,000 genes. Our bodies turn them on or off as necessary.

  • One of the main switches that modulates the way genes are expressed is a process called methylation, in which methyl groups are added to the DNA.

  • The nutrient SAMe (S-Adenosyl-Methionine) is the body’s preferred methyl donor.

  • If we don’t have enough of it, the body cannot methylate properly.

  • Two seemingly unrelated conditions, osteoarthritis and clinical depression, both involve improper methylation. In human studies, both are improved by treatment with SAMe.

  • Preclinical studies indicate that increased SAMe also contributes to longer life and improved health.

Osteoarthritis Improvement

plants growing in a beaker

Osteoarthritis is the most common and disabling joint disease.16 It can cause loss of the cushioning cartilage that eases joint movement, eventually damaging underlying bone.

It’s chronic and has no known cure.3,16 But there is new hope for treating it.

Scientists have discovered that abnormal methylation in osteoarthritis patients affects genes that promote inflammation, which in turn promotes the painful swelling that typifies the disease.17,18

By donating methyl groups and getting the methylation cycle back on track, SAMe may modulate those genes and suppress inflammation.19

Improper methylation disrupts healthy cartilage cells’ activity, leading to cartilage damage that further erodes bone tissue.16,20

Numerous studies have shown that SAMe may help treat osteoarthritis. Among the results:

  • SAMe stimulates production of new cartilage in animals.3 This is crucial to slowing or reversing the progress of osteoarthritis.

  • In short- and long-term studies, patients reported improvement of symptoms.21,22

  • Osteoarthritis patients treated with SAMe experienced pain relief as strong as that delivered by nonsteroidal anti-inflammatory drugs (NSAIDs), with improvement lasting longer after treatment.1,2,23

  • A meta-analysis of 11 studies showed that SAMe improved functioning in arthritis patients and was comparable to NSAIDs for pain, without the side effects common with NSAIDs.24

In one study, SAMe also reduced the depressive feelings associated with osteoarthritis.21 That is likely because it eased symptoms of the arthritis and because SAMe has a direct impact on mood disorders.


plants growing in a beaker

Clinical depression affects more than 16% of U.S. adults over a lifetime.25

Stress is a contributor to mood and anxiety disorders. Researchers have found that it drives epigenetic changes in the brain that can alter normal methylation patterns.26

In fact, abnormal methylation has been linked to depression and mood disorders in multiple ways:

  • Prenatal and early childhood exposure to a mother’s depression affects methylation patterns in the infant’s brain.27

  • Childhood trauma leads to methylation defects, which can be related to long-term mood and mental health problems.28

  • Altered methylation is seen in people at high genetic risk for mood disorders, including bipolar and major depression, even before they develop symptoms.29

SAMe helps regulate the production of neurotransmitters that produce feelings of well-being, potentially alleviating depression.30,31

Clinical trials have shown that:

  • SAMe improves memory-related cognitive symptoms in depressed patients.31

  • Over 12 weeks, SAMe (1,600 mg/day-3,200 mg/day) proved superior to both a placebo and the prescription antidepressant escitalopram (20 mg per day) at improving scores on the Hamilton Depression Rating Scale. Remission rates were 34% for SAMe, 23% for escitalopram, and 6% for a placebo.32(Later analysis suggested that the effects were only significant in men, and researchers are exploring the reason for that.33)

  • Adding 800 mg of SAMe to antidepressant medications improved results on standard measures of depression.34

Life Extension® encourages individuals interested in adding SAMe to their regimen to discuss it with their treating physician.

Prolonging Life

plants growing in a beaker

Methylation isn’t just linked to the development of age-related diseases. It also has a direct impact on lifespan itself.35,36

Studies show that aging is associated with alterations in DNA methylation.35,37

This causes pro-inflammation and disease-causing genes to be expressed and tumor-suppressor genes to be silenced, increasing cancer risk.

Studies of long-lived animal strains show that they use SAMe much more efficiently than their shorter-lived relatives, leading to activation of lifespan-extending genes, such as those involved in chemical stress defenses.38,39

Studies have demonstrated just how SAMe might extend life:

  • Stimulating SAMe synthesis in yeast extends their lifespan by activating the youthfulness-promoting enzyme AMP-activated protein kinase (AMPK).4 In humans, AMPK helps the body use calories more efficiently, reduces fat accumulation, and enhances cleanup of cellular “junk.”

  • Short-term SAMe use in tumor-prone mice prevented liver tumor development, in part by restoring methylation and turning on tumor suppressor genes.40


plants growing in a beaker

The way genes are expressed has a great impact on our health and longevity.

DNA methylation is a process that regulates gene expression.

SAMe (S-Adenosyl-Methionine) is an essential factor involved in DNA methylation.

Defects in methylation can lead to diseases.

Increasing SAMe intake provides the body with a critical methylation nutrient, which can help modulate the way genes are expressed.

SAMe has so far shown clinical success in treating osteoarthritis and depression. Early studies suggest SAMe’s status as the body’s preferred methylation nutrient may also protect against other diseases and contribute to longer lifespan.

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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  2. Kim J, Lee EY, Koh EM, et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther. 2009 Dec;31(12):2860-72.
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  39. Dziegelewska M, Holtze S, Vole C, et al. Low sulfide levels and a high degree of cystathionine beta-synthase (CBS) activation by S-adenosylmethionine (SAM) in the long-lived naked mole-rat. Redox Biol. 2016 Aug;8:192-8.
  40. Stoyanov E, Mizrahi L, Olam D, et al. Tumor-suppressive effect of S-adenosylmethionine supplementation in a murine model of inflammation-mediated hepatocarcinogenesis is dependent on treatment longevity. Oncotarget. 2017 Dec 1;8(62):104772-84.