What is the role of S-adenosylmethionine (SAM-e) supplement?

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Last updated: February 26, 2025View editorial policy

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From the Guidelines

S-adenosylmethionine (SAM-e) should not be recommended as a treatment for fibromyalgia due to the limited number of trials and participants, and the lack of robust assessment of toxicity and safety, as reported in the 2017 study by De Silva et al. 1. The use of SAM-e as a dietary supplement may have some benefits for depression, osteoarthritis, and liver health, but its effectiveness for fibromyalgia is not well established.

  • The typical dosage of SAM-e ranges from 400-1600 mg daily, usually divided into multiple doses.
  • For depression, starting with 400 mg twice daily and potentially increasing to 800 mg twice daily if needed, may be beneficial.
  • For osteoarthritis, 600-1200 mg daily is commonly recommended.
  • SAM-e should be taken on an empty stomach for better absorption, and the enteric-coated form is preferred to prevent breakdown in the stomach.
  • Potential side effects of SAM-e include nausea, digestive upset, anxiety, and insomnia.
  • SAM-e should be avoided by people taking antidepressants, those with bipolar disorder, and pregnant or breastfeeding women, as reported in the 2017 study by the EULAR revised recommendations for the management of fibromyalgia 1. Some studies have reported mild adverse effects such as stomach upset and dizziness with SAM-e use, but the overall safety profile is not well established, as noted in the study by SAMe evaluation 1.
  • Always consult with a healthcare provider before starting SAM-e, especially if you have existing health conditions or take other medications.
  • The 2017 study by the EULAR revised recommendations for the management of fibromyalgia 1 provides an overview of various treatments for fibromyalgia, including non-pharmacological and complementary therapies, but the evidence for SAM-e is limited.

From the FDA Drug Label

The FDA drug label does not provide information on the role of S-adenosylmethionine (SAM-e) supplement. The FDA drug label does not answer the question.

From the Research

Role of S-adenosylmethionine (SAM-e) Supplement

  • S-adenosylmethionine (SAM-e) is a naturally occurring molecule that has been studied for its potential antidepressant properties 2, 3, 4, 5.
  • SAM-e has been found to be effective in alleviating depression, with some studies showing it to be as effective as tricyclic antidepressants 2, 3.
  • The supplement has been shown to have a faster onset of action than conventional antidepressants and may potentiate the effect of tricyclic antidepressants 2.
  • SAM-e may also have a role in protecting against the deleterious effects of Alzheimer's disease 2.
  • The evidence suggests that SAM-e is well tolerated and relatively free of adverse effects, although some cases of mania have been reported in bipolar patients 2, 4.

Efficacy of SAM-e in Depression Treatment

  • Controlled trials have found SAM-e to be more efficacious than placebo and equal in efficacy to tricyclic antidepressants for treating major depressive disorder (MDD) when administered parenterally 3.
  • Less evidence supports the use of oral SAM-e, although some trials have demonstrated its efficacy as well 3.
  • A systematic review and meta-analysis found that SAM-e may provide relief of depression symptoms similar to imipramine or escitalopram, but the results should be interpreted with caution due to the small number of studies and the large range of SAM-e doses used 6.

Safety and Tolerability of SAM-e

  • SAM-e is generally considered safe and well tolerated, with few adverse effects reported 2, 4.
  • However, patients should discuss treatment options with their doctor before taking SAM-e, as it may interact with other medications or have adverse effects in certain individuals 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

S-adenosylmethionine and depression.

Australian family physician, 2002

Research

S-adenosylmethionine in the treatment of depression.

Neuroscience and biobehavioral reviews, 1988

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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