The Mental Health Benefits of SAMe

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S-adenosyl-L-methionine, more commonly known as SAMe, is a dietary supplement available in the United States. It's also known as S-adenosyl methionine and S-adenosylmethionine. Like with many nutritional supplements, your body naturally produces SAMe and uses it to regulate cell function.

Abnormal levels of SAMe have been observed in people with medical conditions like liver disease and depression. Research into the benefits of SAMe suggests that the supplement can help alleviate symptoms of these conditions. 

Health Benefits 

Research into the benefits of SAMe has revealed that the supplement has many benefits to the body and mind. SAMe has been shown to benefit people with the following conditions. 


The effectiveness of SAMe for alleviating depression symptoms in people with the condition has been inconclusive. While some studies show that the supplement can have significant advantages, others show it may not have that many benefits. SAMe also seems most effective when administered as an injection instead of orally for depression. 

A 2020 study showed that when SAMe was taken alongside selective serotonin reuptake inhibitor (SSRI), it had some promise for treating people with major depressive disorder. People who don't respond well to antidepressants may also benefit from using SAMe. It would be best if you didn't take SAMe with antidepressants without your doctor's go-ahead. Some antidepressants increase your serotonin levels, and so does SAMe. Elevated serotonin levels could cause symptoms such as anxiety, heart palpitations, and shivers. 

In a 2017 review of studies on the effectiveness of SAMe in treating neuropsychiatry conditions, researchers observed that the supplement showed some promise in treating symptoms of depression and improving symptoms in people with substance use and psychotic disorders. The supplement was administered once a day for three months to sixty participants, and minimal to significant improvement was observed. 

Liver Diseases 

Research shows that SAMe could be of benefit to people living with different forms of liver diseases. According to scientists, the supplement may increase liver function in people with chronic liver diseases like cirrhosis.

In a 2015 review of twelve clinical trials, it was observed that using SAMe significantly reduced bilirubin and aspartate transaminase (AST), two markers of liver damage. 


Some research shows that SAMe could be as effective in relieving pain in people with osteoarthritis as nonsteroidal anti-inflammatory drugs (NSAIDs).

In a 2002 review of studies into the effectiveness of SAMe for pain relief, researchers observed that it was just as effective as NSAIDs, without the side effects that make it an attractive alternative to NSAIDs for the treatment of osteoarthritis. Osteoarthritis is a condition that affects the joints in your knees and hips, causing pain and reducing mobility.

NSAIDs are known to cause troubling side effects such as stomach ulcers, headaches, drowsiness, and dizziness. SAMe doesn't cause these side effects, leading some scientists to propose using SAMe as an alternative to NSAIDs. 

Alzheimer's Disease 

Alzheimer's disease is a condition that causes a person to experience symptoms of memory loss, cognitive difficulties, and difficulty making decisions.

In a small 2008 study, 14 people with early-stage Alzheimer's disease were administered supplements that contained SAMe, folate, vitamin B6, vitamin E, N-acetylcysteine, and Acetyl-L-carnitine. An improvement in symptoms was observed; although SAMe alone can't be credited, it was likely a combination of all the active ingredients. The combination showed promising effects for delaying cognitive decline and improving mood and daily functioning in people with Alzheimer's disease.

Possible Side Effects

Taking SAME supplements can cause side effects in certain people. More research also needs to be done to understand the long-term effects of taking SAMe; studies into the supplement have involved taking it for short periods.

SAMe has been shown to worsen symptoms of mania in people with bipolar disorder and other mental health conditions which may cause mania. In general, it's rare for people to experience side effects when taking SAMe.

SAMe has also been shown to contraindicate with specific supplements and medications. For instance, in people with Parkinson's, SAMe may reduce the effectiveness of L-dopa (levodopa), a drug used to boost dopamine and manage symptoms of tremors, stiffness, and difficulty with movement. In people with Parkinson's. Possible side effects that have been identified include: 

  • Digestive difficulties 
  • Dry mouth
  • Headache 
  • Nausea
  • Skin rash 
  • Dizziness 

While there's no evidence to show that SAMe is unsafe for pregnant people, avoiding this supplement when pregnant or breastfeeding is advisable.

Dosage and Preparation 

Unlike many dietary supplements, SAMe can't be derived from any food source. The only way to address a SAMe deficiency or imbalance is by taking supplements. Supplements are available in tablet and capsule forms, which helps you regulate your dosage.

SAMe pills should be stored in a cool, dry place and left in their original packaging until you are ready to take them.

It's often recommended to start with a low dosage to avoid side effects. Some researchers also recommend that you take SAMe alongside vitamin and mineral supplements like folic acid and vitamin B12 to aid absorption into your body. Speak with your healthcare provider to determine the appropriate dosing of SAMe for you. There have been conflicting suggestions on the proper dosage of SAMe for different conditions. 

What to Look For 

Supplements are largely unregulated by the US Food and Drug Association, making it crucial to ensure that you only purchase your supplements from reputable sources.

It's essential to store SAMe properly; when exposed to moisture and air, it can change color and become less potent. Some experts advise buying the supplement in blister packs instead of bottles for this reason. 

Other Questions 

Do I need a prescription for SAMe? 

While you don't need a prescription to purchase SAMe in the United States, speaking to your doctor before taking the supplement is highly advisable.

SAMe has been shown to contraindicate with certain medications and worsen symptoms in people with conditions like bipolar disorder

Can SAMe replace my medication?

You shouldn't stop taking the medication for any condition that has proven beneficial when SAMe is used. If you are experiencing troubling side effects when taking SAMe with particular medicines, the supplement may be contraindicated with said medication. Clear any supplements and dosages with your doctor before you start. 

7 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Sharma A, Gerbarg P, Bottiglieri T, et al. S-adenosylmethionine (Same) for neuropsychiatric disorders: a clinician-oriented review of research. J Clin Psychiatry. 2017;78(06):e656-e667.

  3. Guo T, Chang L, Xiao Y, Liu Q. S-adenosyl-l-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis. Bruns H, ed. PLoS ONE. 2015;10(3):e0122124.

  4. Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy of S-adenosylmethionine (Same) for osteoarthritis. J Fam Pract. 2002;51(5):425-430.

  5. Remington R, Chan A, Paskavitz J, Shea TB. Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer's disease: a placebo-controlled pilot study. Am J Alzheimers Dis Other Demen. 2009;24(1):27-33.

  6. National Center for Comprehensive and Integrative Health. S-adenosyl-l-methionine (Same): in depth. January 2017

  7. Cleveland Clinic. S-adenosyl-L-methionine, SAM-e oral dosage forms.

By Toketemu Ohwovoriole
Toketemu has been multimedia storyteller for the last four years. Her expertise focuses primarily on mental wellness and women’s health topics.