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SAM-e: Worth the Hype or Waste of Money?


SAM-e - Dr. Axe

Have you heard the hype about SAM-e? It’s a dietary supplement that has been on the U.S. market for only 20 years, long after it was discovered in Italy in 1952. Although it’s only available by prescription in Europe to treat conditions like depression and arthritis, the supplement is becoming more and more popular in the United States for a number of health concerns.

SAM-e is made in the body from methionine, an amino acid that’s found in foods like egg whites, wild-caught fish, oats and sesame seeds. Your body needs it to make certain chemicals and to regulate key functions in our cells. Although SAM-e is found naturally in our bodies, the supplement you buy in stores is only a replication of the compound.

So is SAM-e worth the hype? It appears that the compound has potential as a natural anti-inflammatory, pain-relieving and mood-boosting agent, but more human studies are needed to determine how exactly we should be using it. Until then, you should use it with caution and under the care of your health care provider.

What Is SAM-e (S-adenosylmethionine)?

The brain synthesizes SAM-e, or s-adenosylmethionine, from methionine, an essential amino acid that plays an important role in the growth of new blood vessels, and adenosine triphosphate, an energy-producing compound that acts as a source of fuel within our cells. It is made naturally in the body, and it has been found to regulate key functions in our living cells.

S-adenosylmethionine is involved in a vital process called methylation, which supports a number of biochemical reactions that take place in the human body, and is involved in gene expression, DNA repair, maintaining cell membrane fluidity, synthesizing proteins and neurotransmitters, and metabolizing fats and minerals. In fact, a recent review published in the Journal of Psychiatry & Neuroscience mentioned over 35 methylation reactions that involve SAM-e. (1)

Scientifically speaking, S-adenosylmethionine is a methyl-group donor in the biosynthesis of DNA and RNA nucleic acids, proteins, phospholipids, epinephrine, creatine, melatonin, and other molecules. (2) What does this mean? Basically, SAM-e is involved in many metabolic processes throughout the body, and it plays a role in the formation, activation and breakdown of many chemicals, including hormones and proteins.

SAM-e increases the turnover of serotonin and may increase levels of dopamine and norepinephrine. It’s been shown to exhibit anti-inflammatory and analgesic effects and is often used to relieve pain while improving physical function. (3)

When doctors found that conditions like depression and liver disease were associated with abnormal levels of S-adenosylmethionine in the body, researchers began to investigate the efficacy of SAM-e in the treatment of these types of health concerns. Overall, there has been evidence that SAM-e helps improve a host of conditions, including depression, liver disease, osteoarthritis and fibromyalgia. However, researchers agree that more studies are needed to fully understand the mechanisms and medicinal potential of the supplement. (4)

7 Potential Benefits of SAM-e

  1. Works as an antidepressant
  2. Relieves osteoarthritis
  3. Improves symptoms of fibromyalgia
  4. Supports liver function
  5. May improve brain function
  6. Works as natural pain reliever
  7. May improve asthma symptoms

1. Works as an Antidepressant

Several placebo-controlled studies have demonstrated the antidepressant properties of S-adenosylmethionine, but as of now, the evidence is not conclusive. Research shows that SAM-e levels tend to be lower in depressed individuals compared to individuals who don’t report signs of depression, so it’s believed that it does have beneficial effects when used for depression, but most of the trials that have been conducted only lasted a few weeks and included a small number of participants.

A 2016 comprehensive review published in CNS & Neurological Disorders Drug Targets found that numerous studies show SAM-e affecting critical components involved in the pathophysiology of major depressive disorder, and several randomized controlled trials have supported that S-adenosylmethionine is superior to placebo and tricyclic antidepressants. Researchers also indicated that recent findings demonstrate SAM-e’s efficacy in patients that are non-responsive to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. (5)

An interesting study conducted by researchers in Melbourne, Australia, found that when SAM-e was used to treat major depressive disorder in adults, it was superior to the placebo among males but not among females. This double-blind, randomized clinical trial suggests that gender might impact the antidepressant efficacy of SAM-e, with greater therapeutic effects found among males. (6)

That being said, more research is needed to fully understand the potential of S-adenosylmethionine as a treatment for depression and keep in mind that some of these studies involve using intravenous SAM-e rather than oral forms that are taken by mouth.

2. Relieves Osteoarthritis

Researchers are still looking into whether or not S-adenosylmethionine is an effective dietary supplement for the treatment of osteoarthritis, or degenerative joint disease. Animal studies show that SAM-e stimulates the production of cartilage, which is critical in reversing the disease process. It may also help reduce pain and stiffness because of its anti-inflammatory properties and its ability to increase glutathione levels. (7)

A 2002 study published in the Journal of Family Practice found that SAM-e appears to be as effective as NSAIDs in reducing pain and improving functional limitation in patients with osteoarthritis. Plus, those taking SAM-e were less likely to report adverse effects when compared to patients using NSAIDs for osteoarthritis. (8)

3. Improves Symptoms of Fibromyalgia 

Fibromyalgia is chronic and widespread pain in the muscles and connective tissue. People with this condition often suffer from long-term pain, fatigue, depression and mood disorders.

Some evidence shows that S-adenosylmethionine has some beneficial effects on fibromyalgia symptoms, including a double-blind clinical evaluation that was conducted at Frederiksberg Hospital’s Department of Rheumatology in Denmark. When 800 milligrams of SAM-e were administered orally for six weeks, patients with fibromyalgia reported improvements in clinical disease activity, pain experienced during the last week, fatigue, morning stiffness and mood when compared to patients receiving a placebo. (9)

4. Supports Liver Function

Research suggests that SAM-e biosynthesis is depressed in patients with chronic liver disease, and this depression may exacerbate liver injury. For this reason, it’s believed that SAM-e supplementation may represent a useful therapy for liver disease.

Researchers “support the efficacy and safety of SAM-e for the treatment of chronic liver diseases.” S-adenosylmethionine appears to be particularly useful in helping improve liver function and can be used as part of a medication regime for liver health; however, studies show that it does not improve outcomes or reduce the occurrence of adverse events for chronic liver diseases. Overall, more research is needed regarding the basic treatment of liver disease with SAM-e before concrete recommendations can be made. (10)

5. May Improve Brain Function

S-adenosylmethionine plays a role in methylation, a vital process that supports a number of biochemical reactions in the body, including the brain. Because the ability to methylate declines with age, the risk of neurodegenerative diseases, like Alzheimer’s, increases. Evidence indicates that SAM-e levels are lower in patients with Alzheimer’s, which may compromise their metabolism and brain function. (11)

Also, S-adenosylmethionine is involved in glutathione production, a powerful antioxidant that works from within the cell. Studies suggest that decreased glutathione levels may be involved in the pathology of Alzheimer’s and other neurodegenerative diseases. (12)

Like most benefits associated with S-adenosylmethionine, it’s still unclear whether or not the supplement can definitely improve cognitive impairment in humans, but there are some promising animal studies on the topic.

An animal model meta-analysis that was published in PLoS One evaluated the effect of SAM-e on cognitive ability as measured by maze performance in mice. Maze performance is used to measure a rodent’s spatial learning and memory. After reviewing 13 experiments, researchers indicated that supplementing with SAM-e improved cognitive performance, especially in mice that were deficient in folate. They concluded that S-adenosylmethionine “may be useful in improving spatial memory in patients suffering from many dementia forms including Alzheimer’s disease.” (13)

6. Works as Natural Pain Reliever

SAM-e supplements have become known for their pain-relieving effects, which is why people often take them for lower back pain relief, joint pain, PMS symptoms and abdominal pain.

Researchers are still collecting evidence on the analgesic properties of S-adenosylmethionine, but there are some promising studies out there. A 2013 pilot study conducted at the University of California found that oral SAM-e was able to reduce stomach pain among children. Eight children with functional abdominal pain received a median dose of 1,400 milligrams daily for a two-month period. Researchers reported an improvement in self-pain reports after the treatment period with SAM-e. (14)

7. May Improve Asthma Symptoms

A 2016 animal study published in Experimental and Molecular Medicine found that S-adenosylmethionine had a suppressive effect on airway inflammation and fibrosis in mice with chronic asthma. Researchers concluded that SAM-e may have potential as a novel therapeutic agent for patients with chronic asthma symptoms, but more human studies will be needed to test SAM-e’s ability to reduce oxidative stress and positively impact airway inflammation. (15)


SAM-e - Dr. Axe

SAM-e Dosage Recommendations

SAM-e can be taken orally, intravenously or with a muscular injection. In the U.S., it’s sold over-the-counter as a dietary supplement and can be found online or in health food stores.

When taking SAM-e supplements by mouth, the dosage recommendations range from 400–1,600 milligrams per day, depending on the condition being treated. Many doctors recommend starting with a smaller dosage of 400 milligrams a day and then increasing the dosage slowly if you are tolerating it well. (16)

When using S-adenosylmethionine, read the label carefully to determine the best dosage for your age, weight and condition. SAM-e should be taken on an empty stomach, but keep in mind that it can be stimulating, so consider taking it earlier in the day so that it doesn’t disturb your sleep.


The side effects of SAM-e appear to be uncommon. When they do occur, they are usually minor complains like digestive issues or nausea, but there have been cases of SAM-e triggering side effects like anxiety, insomnia and nervousness.

S-adenosylmethionine may worsen symptoms of mania, so it’s advised that people with bipolar disorder do not take the supplement unless it’s under the supervision of their health care provider.

SAM-e may interact with certain medications or supplements, especially those that increase serotonin levels, such as St. John’s wort, L-tryptophan and antidepressant medications.

There’s also concern that SAM-e enhances the growth of Pneumocystis carinii, which can be dangerous for people who are immunocompromised, such as people who are HIV positive. Although more research is needed on this topic, anyone with a compromised immune system should not take S-adenosylmethionine unless doing so under the care of his or her doctor.

More research is needed to know whether or not it’s safe to use SAM-e during pregnancy or when breastfeeding. Studies involving children using SAM-e have been conducted and resulted in minimal toxicity, but do not start your child on SAM-e or any supplement without consulting his or her pediatrician first.

Final Thoughts

  • SAM-e, or s-adenosylmethionine, is a compound that comes from methionine, an essential amino acid, and adenosine triphosphate, an energy-producing compound.
  • SAM-e is made naturally in the body, and it has been found to regulate key functions in our living cells.
  • Today, it’s widely available as an over-the-counter dietary supplement that’s a synthetic form of the natural compound.
  • Although more research is needed to determine the exact mechanisms and benefits of SAM-e, there is evidence that it may serve as a potential therapeutic agent for the following conditions:
    • depression
    • osteoarthritis
    • fibromyalgia
    • liver disease
    • cognitive impairment
    • chronic pain
    • asthma

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