Sanesco Blog

SAMe: Ingredient Overview & Clinical Value of Supplementation


S-adenosyl methionine (SAMe) is a compound found in every cell of the human body.[1] It was discovered in 1952 and has since been researched as a potential supplement for alleviation of depression.[2] Early studies conducted on the efficacy of SAMe may have been limited by the rapid degradation of some SAMe formulations.[3] Newer formulations of SAMe, along with proper handling and packaging, have shed light on the benefits of this compound.

SAMe & Methylation

Dozens of biological processes require a methylation step to work properly. Methylation simply means the donation of a methyl group (CH3) from one molecule to another. SAMe is made from methionine, and the synthesis of SAMe requires adequate folate and vitamin B12.[4] 5-methyltetrahydrofolate (5-MTHF) transfers a methyl group to homocysteine to form methionine in a process requiring vitamin B12.  The methionine is then converted to SAMe, which is then used in methylation processes. The product of all methylation cycles is S-adenosylhomocysteine, which is then converted back to homocysteine. Homocysteine can then be used to make methionine, which can then make more SAMe.[5]

Clinical Value of SAMe Supplementation

While methylation typically occurs as a natural cycle in the body, trouble with methylation processes can influence mood, aches and discomfort, fatigue, and even cause dysregulated DNA expression. Serotonin is an important inhibitory neurotransmitter, low levels of which are associated with low mood and anxiousness. SAMe has been shown to potentially increase serotonin concentration in the brain.[6] Some studies have found that dysregulated methylation cycles can influence Schwann cell myelination, which can impair neuron firing.[7]

Interestingly, SAMe requires folate and B12 for optimal function, and deficiencies of these vitamins are strongly associated with low mood.[10] When supplementing with SAMe, it is important to include vitamin B12 and folate as well. Some researchers have even postulated that supplementing with SAMe in the absence of B12 and folate may be dangerous.[11] Additionally, SAMe is contraindicated in bipolar disorder and may exacerbate manic bipolar symptoms.[12]

SAMe supplementation may be beneficial for a wide array of symptoms and conditions, but should be taken under a practitioner’s supervision. For more information on methylation pathways, see Sanesco’s blog post about the methylation cycle.

MethylMax™ contains a branded version of SAMe known as Adomix®. This version of SAMe is unique because it is stable at room temperature. However, MethylMax offers more support for methylation than SAMe. It is a comprehensive methylation support product.* MethylMax contains:

  • B vitamins (B6, B9, and B12) help maintain healthy homocysteine metabolism.*
  • Betaine, also known as trimethylglycine (TMG), and SAMe are methyl donors in the homocysteine cycle.*
  • In fact, TMG methylates homocysteine ultimately generating SAMe.*


[1]Mischoulon, D., Alpert, J. E., Arning, E., Bottiglieri, T., Fava, M., & Papakostas, G. I. (2012). Bioavailability of S-Adenosyl Methionine and Impact on Response in a Randomized Controlled Trial in Major Depressive Disorder. The Journal of clinical psychiatry, 73(6), 843.

[2] Williams, A. L., Girard, C., Jui, D., Sabina, A., & Katz, D. L. (2005). S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clinical and Investigative Medicine, 28(3), 132.

[3] Mischoulon, op. cit.

[4] Williams, op. cit.

[5] Mischoulon, op. cit.

[6] Kadakia, K. C., Loprinzi, C. L., Atherton, P. J., Fee-Schroeder, K. C., Sood, A., & Barton, D. L. (2016). Phase II evaluation of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes. Supportive Care in Cancer, 24(3), 1061-1069.

[7] Varela-Rey, M., Iruarrizaga-Lejarreta, M., Lozano, J. J., Aransay, A. M., Fernandez, A. F., Lavin, J. L., … & Wagner, C. (2014). S-adenosylmethionine levels regulate the schwann cell DNA methylome. Neuron, 81(5), 1024-1039.

[10] Williams, op. cit.

[11] Mischoulon, op. cit.

[12] Williams, op. cit.

Clinical Contributor

Sophie Thompson

Clinical Support Specialist at Sanesco International, Inc.

Sophie recently obtained her degree in Biology from UNCA in Asheville. Born and raised in Asheville, her hobbies include painting, writing and spending quality time with her dog and her family.



Ramona Richard, MS, NC

Ramona Richard, MS, NC

Ramona Richard graduated with honors from the University of California with a Bachelor’s Degree in psychology and graduated summa cum laude with a Master’s Degree in Health and Nutrition Education. She also holds a Standard Designated Teaching Credential from the State of California, is a California state-certified Nutrition Consultant and a member of the National Association of Nutrition Professionals.

Ramona has participated in nutrition education in both public and private venues, including high school and college presentations, radio and public speaking for the past 20 years. She is the owner of Radiance, a nutrition consulting company, the Director of Education for Sanesco International, and a medical technical writer.

Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

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