Is the natural antidepressant SAMe a safe option for depression, arthritis and other health problems?

A natural compound in our body’s cells called SAMe, pronounced ‘Sammy’, has been shown in some studies to be safe, fast-acting and effective for treating depression.

“SAMe has been hailed as the safest and most effective natural antidepressant ever used”, according to Marios Kyriazis, MD. He says it’s one of the best all-round anti-aging supplements available. In his book The Anti-Aging Plan he claims SAMe is one of the six key ingredients of the modern equivalent of the ‘elixir of youth’.

Like other antidepressants, SAMe can have side effects and it isn’t for everyone. Can SAMe benefit you?

What is SAMe and how does it help relieve depression?
What evidence is there that SAMe works for depression?
Why might people be low in SAMe?
What are other uses of SAMe besides relieving depression?
What are the side effects of SAMe?
Who should avoid or be cautious about taking SAMe?

What is SAMe and how does it help relieve depression?

SAMe, short for S-adenosylmethionine, is a natural substance found in our body’s cells. According to Kyriazis, SAMe boosts mood and reduces depression by enhancing dopamine, serotonin and other neurotransmitters in the brain. This is how most antidepressants work.

SAMe is an important methylating agent in the brain. It is a methyl donor, meaning it provides methyl groups to various molecules in our bodies. Methyl groups are needed for good health and many chemical reactions in the body.

A lack of methyl groups can cause depression and other brain and nerve diseases. Methylation is vital to maintain active neurotransmitters, hormones, and phospholipids. These help make our brains sharp.

SAMe is also an antioxidant that protects brain cells from damage.

What evidence is there that SAMe works for depression?

Many studies have researched SAMe for depression. Here are some key results.

  • An Italian study found SAMe is as good as the tricyclic antidepressant Imipramine (Desipramine) for depression, but with fewer side effects.
  • Taking 400 mg of SAMe daily has reduced symptoms of depression in seven days compared to the 3 to 4 weeks it takes for tricyclic antidepressants to work.
  • SAMe has been used with prescription antidepressants to reduce the dose needed and provide faster relief from symptoms of depression.

Nutrition specialist Cathy Wong recommends that people already taking an antidepressant should not take SAMe. Little research has been done on how SAMe will interact with other medications. People not currently taking an antidepressant should discuss SAMe and other antidepressants with their doctor.

Why might people be low in SAMe?

Increasing age, dementia, depression and alcohol abuse can cause people to have low levels of SAMe, according to Kyriazis. Lack of folic acid or vitamins B6 and B12 may also cause low concentrations. These vitamins play a vital role in the metabolism of SAMe.

What are other uses of SAMe besides relieving depression?

Besides helping treat depression, SAMe has been reported to:

  • reduce the pain and inflammation of osteoarthritis.
  • help relieve people with fibromyalgia of symptoms of depression, fatigue, and morning stiffness.
  • reduce inflammation in liver cells.
  • help treat cirrhosis and non-alcoholic fatty liver disease.
  • possibly help normalize liver enzyme levels and help with cholestasis, a health condition in which little or no bile is secreted or the flow of bile into the digestive tract is obstructed.
  • improve endothelial function in patients with ischemia.

What are the side effects of SAMe?

According to Mischoulon et al.: “SAMe is well tolerated and relatively free of adverse effects.”

Wong says the side effects of SAMe can include:

  • hyperactivity
  • anxiety
  • insomnia
  • headache
  • digestive complaints, especially nausea
  • skin rash
  • lowered blood sugar
  • dry mouth
  • blood in the stool
  • thirst
  • increased urination

After reading comments from people in depression forums who take SAMe, I have found that using this supplement might also cause the following:

  • irritability
  • erratic or racing heartbeat
  • confusion
  • shakiness
  • chest pain or tightness

The long-term side effects of SAMe are unknown.

Wikipedia says people taking SAMe should ensure they take enough vitamin B6, vitamin B12 and folic acid, otherwise SAMe will not break down properly. This will mean the full benefits of SAMe will not occur and homocysteine might increase to unsafe levels. High levels of homocysteine are linked with heart disease, increased risk of heart attacks, strokes, liver damage, and possibly Alzheimer’s disease. Vitamin B supplements are often taken along with SAMe.

Who should avoid or be cautious about taking SAMe?

People with bipolar disorder (manic depression), anxiety disorders and other mental health problems should only use SAMe under the supervision of their healthcare provider, according to Wong. SAMe has been linked with hypomania and mania.

Children and nursing mothers should not take SAMe because long-term studies in these groups are not available. SAMe should only be used in pregnancy under a physician’s recommendation.

Wong says people with Parkinson’s disease should avoid taking SAMe.


SAMe is a relatively safe natural compound that appears to quickly help relieve depression, but some people should avoid taking it and there can be side effects. Check with your doctor if you’re unsure about whether SAMe can help you.

written by Nyomi Graef

Bressa, GM, 1994, S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies, Acta Neurologica Scandinavica Supplementum, Vol. 154, 7-14

Carper, J, 2000, Your Miracle Brain, New York, USA: HarperCollins

Fava, M et al., 1995, Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine, Psychiatry Research, Vol. 56, Iss. 3, 295-297

Johnson, TD, 2007, SAMe – Safe, Effective Support for Mood and More, LifeExtension,

Kagen, BL et al., 1990, Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial, American Journal of Psychiatry, Vol. 147, No. 5, 591-595

Kyriazis, M, 2006, Depression and SAMe, Offshore Pharmacy,

Mischoulon, D et al., 2002, Role of S-adenosyl-l-methionine in the treatment of depression: a review of the evidence, American Society for Clinical Nutrition, Vol. 76, No. 5, 1158S-1161S,

S-Adenosyl methionine, 2009, Wikipedia,

Wong, C, 2008, What You Need to Know About SAMe,,

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7 Responses to “Is the natural antidepressant SAMe a safe option for depression, arthritis and other health problems?”

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  5. ken Burnett says:

    I take sam-e for depression it helps me but I think I might need to increase my dosage ,I have been taking it for quite some time and would recommend it depression but not bi polar or worse mind problems.

    The only part of depression I have not beaten is Fatigue and the need to sleep a lot,


  6. ken Burnett says:

    I took myself of sam-e for about 6 months.I found in the last 2 months I was feeling really bad well my depression was running very bad,so I put myself back on and within 2 days I was calm,relaxed and back to my old self & happy plus loving life.

    One thing I started doing is juicing ,carrots ,celery,broccoli,apple,orange,ginger (small amount) strawberries ,cucumber.

    This has made a big difference to me feeling tired. I make a big lot 2 bottles and drink in the morning and at night.

    Try it

  7. Nyomi says:

    Hi Ken,

    I’m glad you’re feeling better and SAMe appears to be helping you. Yes, drinking freshly squeezed juice has benefits. Your juice sounds delicious! I love the touch of ginger too – I really like ginger.

    Thanks for commenting, and all the best.

    Kind regards,

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