Product Reviews
SAMe (S-adenosyl-methionine) Supplements Review

HereInitial Posting: 1/16/16 Last Update: 9/25/18 Sam-e supplements reviewed by

Sections: Jump to a section by clicking on its name.
  • SAMe is a compound which naturally occurs in the human body (see What It Is).
  • As a supplement, it has two major uses (see What It Does).
    • It is effective as a treatment for osteoarthritis and associated joint pain, stiffness, and inflammation. It may take longer to work than leading anti-inflammatory drugs but the benefit seems to last longer with fewer side effects.
    • It is an effective antidepressant in treating major depression and may be particularly useful for people who do not respond to prescription treatment.
  • Choose SAMe products carefully because it is an expensive ingredient (companies may put in less than listed) and is sensitive to breakdown if exposed to heat or moisture. Look for a product packaged in a blister pack (see What to Consider When Buying). Generally, it should also have an enteric-coating to protect it from degradation by stomach acids which can render it ineffective. (See Quality Concerns)
  • Among the 10 products selected by CL for testing, one contained only 76.5% of its listed SAMe and provided an unusually small dose. (See What CL Found).
  • Daily dosage shown to be effective in clinical trials ranges from 800 mg to 1,600 mg of SAMe (See ConsumerTips for details).
  • See Top Picks for products which passed testing, were enteric coated, and provided SAMe at lowest cost. All of these are packaged in blister packs for stability.
  • SAMe should not be used by people with bipolar disorder (See Concerns and Cautions for more information.)
What It Is:
A naturally occurring compound, SAMe (also known as SAM-e, S-adenosyl-methionine, or S-adenosyl-L-methionine) is found in every cell in the body, where it's manufactured from the essential sulfur-containing amino acid methionine. Protein-rich foods are sources of this amino acid.

What It Does:
SAMe assists the body in producing a wide range of compounds, including neurotransmitters (such as dopamine and serotonin) and cartilage components (such as glycosaminoglycans). When natural SAMe levels are low, supplements may facilitate the production of these compounds.

SAMe, typically at a dose of about 1,200 mg per day, has been shown to be effective as a treatment for osteoarthritis of the knee, hip, hand and spine and associated joint pain, stiffness, and inflammation. Several studies suggest that SAMe is about as effective as many of the leading anti-inflammatory drugs -- it may take longer to work but the benefit seems to last longer and has fewer side effects (Kim, Clin Ther 2009, Najm, BMC Musculoskelet Disord 2004, Domljan, Int J Clin Pharmacol Ther Toxicol 1989, Muller-Fassbender, Am J Med 1987, Caruso, Am J Med 1987).

SAMe is one of the most studied natural therapies for treating major depression. Several studies have shown that it is as effective as tricyclic antidepressants in treating major depression (Delle Chiaie, Am J Clin Nutr 2002; Salmaggi, Psychother Psychosom 1993; Kagan, Am J Psychiatry 1990). One study (Papakostas, Am J Psychiatry 2010 clarified in Fleish, Am J Psychiatry 2010) found that it may be helpful in patients with major depressive disorder who did not respond to prescription treatment with a serotonin reuptake inhibitor (SRI). In the study, 800 mg of SAMe was given twice daily (a total daily dose of 1,600 mg) along with an SRI for six weeks: 46.1% of patients receiving the combination benefited, versus 35.8% receiving an SRI and a placebo supplement. The results suggest that SAMe may be an effective and safe adjunctive treatment for SRI non-responders. However, a lower daily dose of SAMe (800 mg -- plus 500 mcg of folinic acid and 200 mcg of vitamin B12) did not improve symptoms more than placebo in men and women with major depressive disorder who were taking antidepressant medication (including selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), selective noradrenergic reuptake inhibitors (NaRI), tetracyclics (mirtazapine) or 5-HT2c antagonists (agomelatine)) (Sarris, Eur Neuropsychopharmacol 2018).

Other potential applications of SAMe include the treatment of fibromyalgia, liver disease, AIDS-related myelopathy, Parkinson's disease, and attention deficit-hyperactivity disorder (ADHD) in adults.

For more information about clinical studies with SAMe see the article in the Encyclopedia. For information about other supplements for osteoarthritis see the Joint Supplement Review (covering glucosamine, chondroitin, and MSM products). Other supplements used to prevent or treat depression are St. John's Wort, 5-HTP, and Vitamin D.

Quality Concerns and What CL Tested For:
SAMe is an expensive ingredient, so experts have been concerned about the actual quality and quantity of SAMe in supplements. Another concern is that SAMe is very susceptible to heat and moisture, both of which can cause it to degrade resulting in less ingredient than what's stated on the label. Many manufacturers will enteric coat SAMe pills and/or package the product in blister packs as a way to protect products from degrading throughout their shelf-life.

SAMe can also be destroyed by stomach acid. The same enteric coating used to protect the product on the shelf can also help protect the product from stomach acid so that it can be absorbed in the intestines.

A stabilizing molecule is always added to SAMe products, often making it unclear as to the true weight of active SAMe because the weight of the inactive stabilizer may be included in the labeled amount. In fact, when first tested by in 2000, nearly half of the products were found to contain significantly less SAMe than they claimed. This has improved over time.

No government agency is responsible for routinely testing SAMe supplements for their contents or quality. However, independently evaluated several leading SAMe products to determine whether they contained the SAMe amounts stated on their labels. All tablets and caplets were also tested to be sure that they would properly disintegrate ("break-apart") and, if enteric coated, properly released their ingredients after withstanding one hour in a simulated gastric environment. (See How Products Were Evaluated for information on testing methods and standards.)

Join |  Sign In
Join Us on Facebook! Join Us on Instagram! Join Us on Twitter! Join Us on YouTube! Join Us on YouTube!
Product Tests
Brands Tested
Health Conditions
CL Answers
Clinical Updates
Recalls & Warnings
Where to Buy Products
Raw Materials Tests
Testing Program
How Products Were Tested
Join CL Today
Join Free Newsletter
Group Subscriptions
Gift Membership
About Us
The CL Seal
CL Survey
Privacy Policy
Contact Us/Help

©2019, LLC. All rights reserved. A single copy of a report may be printed for personal use by the subscriber. It is otherwise unlawful to print, download, store or distribute content from this site without permission. name and flask logo are both registered trademarks of, LLC. This site is intended for informational purposes only and not to provide medical advice.
Join our FREE Newsletter and Become a Member to View
SAMe (S-adenosyl-methionine) Supplements Review!
First Name 
Last Name 
Retype Email* Member Benefits:

Instant Access to All Product Review Reports Covering Over 1,000 Products
Quality Ratings and Product Comparisons by Brand
Expert Tips on Using Supplements
Membership fee required for full benefits.
Price Checks on Popular Brands
e-Newsletter with Updates and Alerts
New and Archived Recalls and Warnings