SAMe (S-Adenosylmethionine)

S-Adenosylmethionine (SAMe) is a naturally occurring compound that is found in almost every tissue and fluid in the body. It is involved in many important processes including the immune system, maintaining cell membranes, and production and breakdown of brain chemicals such as serotonin, melatonin, and dopamine. It works with vitamin B12 and folate (vitamin B9) and being deficient in either vitamin B12 or folate may reduce levels of SAMe in your body.


There is good evidence that SAMe is effective in the treatment of depression, and some evidence for effectiveness in osteoarthritis and the pain and fatigue of fibromyalgia.


SAMe  (S-Adenosylmethionine)



SAMe has been shown in multiple studies to benefit mild to moderate depression. It has a more rapid onset than typical antidepressants that take 6-8 weeks before clinical results. Overall, SAMe is superior to placebo in treating depressive disorders and as effective as conventional tricyclic antidepressants.


In several short term studies (ranging 4 – 12 weeks), SAMe supplements were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen and celecoxib (Celebrex) in adults with knee, hip, or spine osteoarthritis. SAMe was as effectives as these medications in lessening morning stiffness, decreasing pain, reducing swelling, improving range of motion, and increasing walking pace. Several studies also suggest that SAMe has fewer side effects than NSAIDs.



Preliminary clinical research suggests SAMe may improve pain, fatigue and mood in fibromyalgia but the research in this area is very limted.



Starting with a low dose (for example, 200 mg per day) and increasing slowly helps avoid stomach upset. It is important to note that many of the studies of SAMe have tested injectable, not oral, forms. It is not as clear how reliable or effective taking SAMe orally is. Small studies suggest that oral supplementation with SAMe is not well absorbed by the body. Clinicians recommend taking oral SAMe with vitamin B12, folic acid, methionine and trimethylglycine to enhance absorption.

Suggested doses of SAMe vary depending on the health condition being treated. The following are guidelines based on the dosages used in studies for each condition:

  1. Depression: 800 – 1,600 mg of SAMe per day, in 2 divided doses (morning and afternoon)
  2. Osteoarthritis: 600 – 1,200 mg per day in 2 – 3 divided doses
  3. Fibromyalgia: A dosage of 400 mg 2 times per day for 6 weeks
  4. Alcoholic liver disease: 600 – 1,200 mg per day by mouth in divided doses for 6 months enhances liver function. For liver disease, a qualified health care provider should supervise administration of SAMe.



Toxicity, Safety and Serotonin Syndrome

In general, SAMe is well tolerated. When they occur, the majority of side effects are mild to moderate in severity and of brief duration, with an overall incidence of <20%. Few patients have withdrawn from trials because of SAMe side effects.


The majority of possible side effects are gastrointestinal (heartburn, nausea, vomiting, diarrhea) but also include insomnia, dizziness, and headache. Allergic reactions been occurred with injectable SAMe. Psychoactivation or a “switch” reaction where depression turns to mania/ hypomania has been documented but the frequency with which this occurs is uncommon.

Taking SAMe at the same time as certain other medications may increase the risk of Serotonin Syndrome (a rare but potentially dangerous condition caused by having too much serotonin):

  1. Dextromethorphan (Delsym, Robitussin DM, other “DM” cough syrups)
  2. Meperidine (Demerol)
  3. Tramadol (Ultram)
  4. Buprenorphine
  5. Levorphanol
  6. SNRI Antidepressant medications (Cymbalta, Effexor, Savella)
  7. SSRI Antidepressant medications (Prozac, Paxil, Celexa, Zoloft etc.)
  8. Tricyclic Antidepressant medications (elavil, doxepin, imipramine)


SAMe has the potential for side effects including h
eadache, irregular or accelerated heart rate, anxiety, and restlessness, as well as the rare condition called Serotonin Syndrome, mentioned above. It is believed that taking SAMe increases the levels of serotonin in the brain, and many antidepressants do the same. The concern is that combining the two may result in a dangerous increase in serotonin levels. Talk to your physician before combining SAMe with prescription antidepressants.


Mechanism of Action

SAMe is believed to raise serotonin levels in the brain, which is how other prescription antidepressants are thought to work.


Emphasis on Education


Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.


For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.


Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.


For more information, please contact Accurate Clinic.


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