S-Adenosylmethionine: SAM-e Helps Support a Healthy Mood‡

Feb 09, 2022

S-Adenosylmethionine: SAM-e Helps Support a Healthy Mood‡

What Is SAM-e?

SAM-e is a key compound found in every cell in the body and is essential to many processes in the body.† SAM-e is synthesized from  the amino acid, methionine, which is found in protein-rich foods, along with adenosine triphosphate (ATP): 

 SAM-e Helps Support a Healthy Mood‡

Why is SAM-e Important? 

METHYLATION: SAM-e donates its methyl group to a variety of reactions, which makes SAM-e a powerful methyl donor. This is important because in SAM-e methylates the phospholipid bi-layer and helps to maintain the cell wall structure and fluidity of cell membranes. This allows for nerve-cell communication from the neurotransmitters, serotonin and dopamine. In the brain, SAM-e helps maintain the membrane coating of nerve cells and plays a role in the production of neurotransmitters that nerve cells use to communicate. This includes the conversion of norepinephrine into epinephrine and serotonin into melatonin.†1 SAM-e has shown to help support a healthy mood, as documented in a number of studies involving adults.†1-5 

TRANSULFURATION: SAM-e incorporates sulfur into proteoglycans to help support joint tissue and cartilage.   During this process, the amino acids cysteine and glutathione are formed.6-7

Metabolism of SAM-e

Why May SAM-e Be Beneficial?

Age and nutritional status (e.g. poor diet) can affect the amount of SAM-e your body makes. This is one reason why a mood supplement such as SAM-e supplements may be helpful in replenishing the necessary supply of SAM-e your body needs to support health and wellbeing, including your mood.†2-5 SAM-e may also be helpful as an additive therapy for those with major depressive disorder who may not be responding to traditional prescription antidepressants (Selective Serotonin Reuptake Inhibitors or SSRIs). A clinical study on patients taking 800 mg of SAM-e twice daily + an SSRI over 6 weeks showed a significant response rate and remission compared to traditional anti-depressant therapy. In fact, the beneficial effects from SAM-e were observed sooner than SSRIs taken alone.1

SAM-e also helps support joint health by providing a dietary source of sulfur, which is needed for the body to build collagen, connective tissue, and joint cartilage.†6-7   

It is important to note B vitamins help support SAM-e synthesis in the body.†8 SAM-e can form methionine, however, this can only occur in the presence of adequate amounts of B vitamins, especially vitamin B12 and folic acid.

Other benefits of SAM-e:

  • Fast-acting: works in as little as 7-14 days when taken daily†9
  • Not known to have significant side effects
  • Not known to interact with most medications*
    *except Monoamine Oxidase Inhibitors (MAOIs)


Adults start by taking one tablet (400 mg) daily with water on an empty stomach. If benefits are not achieved within two weeks, a higher level of supplementation may be needed. To determine the proper level for you, gradually increase the number of tablets (maximum of 1600 mg/day) until benefits are achieved.

Who Should Take SAM-e?

Those who want to support a healthy mood† and/or joint health.

SAM-e Safety

The AHRQ (Agency for Healthcare Research and Quality) report concluded that “the side effects of SAM-e seem relatively minor.”10 Mild side effects that define AHRQ have been reported from SAM-e trials in adults include: mild insomnia, lack of appetite, constipation, nausea, dry mouth, sweating, dizziness, heart palpitations and anxiety/nervousness. These effects similarly occurred among patients in the same studies who had received placebos.

SAM-e has been well-studied and is a safe, effective supplement to help support a healthy mood.10‡†

Although generally considered safe, SAM-e has not been extensively evaluated in children or pregnant or lactating women.

Use with caution in people with bipolar (manic) depression or in those having suicidal ideations. SAM-e should not be considered without consultation and monitoring with a healthcare professional.

Should I Add a Sam-e Supplement to My Daily Routine?

It’s important for patients to communicate with their healthcare professionals about any changes to their daily regimen including dietary supplements. Work together to understand personal nutrition needs as well as current dietary patterns to identify nutrient gaps. For those who are still unable to meet their nutrient needs from diet alone, it’s important to discuss the need to fill any potential nutrient gaps with dietary supplements, as a safe and effective way to ensure adequate intake of all essential nutrients.

About Nature Made®

Over the last 50 years, Nature Made has been a trusted leader in the wellness industry. They have helped pioneer quality standards for vitamin, mineral and herbal supplements, and remain dedicated to formulating products backed by science. Committed to Good Manufacturing Practices (GMPs), Nature Made’s quality extends to every aspect of our production, from purchasing high-quality raw materials to routine testing for purity and potency. In fact, they were the first national supplement brand to have a product verified by United States Pharmacopeia (USP), and it is the national supplement brand with the most products carrying the USP Verified Mark, verification that products meet stringent quality criteria for purity and potency. Nature Made is also the #1 Pharmacist Recommended Supplement Brand in 9 Categories**

These materials are intended for educational purposes only.
†These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.
‡In as little as 7-14 days when taken daily†
*Find those Nature Made USP verified products on NatureMade.com/USP
**Based on US News & World Report – Pharmacy Times Survey, Nature Made is the #1 Pharmacist Recommended Brand in Nine Categories –Letter Vitamins, Omega-3/Fish Oil, Coenzyme Q10, Flax Seed Oil, Herbal Supplements, Cholesterol Management-Natural, Garlic, Diabetic


  1. Papakostas GI et al. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry 2010;167:942- 948.
  2. Mischoulon D et al. A double-blind, randomized, placebo-controlled clinical trial of S-adenosyl-L-methionine(SAMe) versus escitalopram in major depressive disorder. J Clin Psychiatry. 2014; 75(4):370- 376.
  3. Papakostas GI et al. Folates and s-adenosylmethionine for major depressive disorder. Can J Psychiatry. 2012;57(7):406-13.
  4. Papakostas GI. Evidence for S-adenosylmethionine (SAM-e) for treatment of major depressive disorder. J Clin Psychiatry 2009;70(Suppl5):18-22.
  5. Mischoulon D and Fava M. Role of S-adenosyl- L-methionine in the treatment of depression: a review of the evidence Am J Clin Nutr. Nov 2002;76(5):1158S-1161S.
  6. Kim JY et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther. 2009;31:2860-72.
  7. De Silva V et al. Arthritis Research UK Working Group on Complementary and Alternative Medicines. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology (Oxford). 2011;50(5):911-20.
  8. Bottiglieri T. Folate, Vitamin B-12, and S-Adenosylmethionine. The Psychiatric clinics of North America. 2013; 36(1):1-13.
  9. Alpert JE et al. S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine. J Clin Psychopharmacol. 2004;24(6):661-4.
  10. Hardy M et al. S-Adenosyl- L-Methionine for Treatment of Depression,
  11. Osteoarthritis, and Liver Disease. Summary, Evidence Report/Technology Assessment: Number 64.AHRQ Publication No. 02-E033, August 2002. Agency for Healthcare Research and Quality, Rockville, MD.