SAMe supplement

SAMe: Ingredient Overview & Clinical Value of Supplementation

Posted Ramona Richard, MS, NC Blog

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. Sanesco uses SAMe in its targeted nutritional therapy (TNT) MethylMax™, due to the important role SAMe plays in methylation pathways.

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 depression, pain, fatigue, and even cause dysregulated DNA expression. Serotonin is an important inhibitory neurotransmitter, low levels of which are associated with depression and anxiety. 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] Methylation problems may even influence diseases such as diabetes and Alzheimer’s.[8] One study found that 34% of depressed patients supplementing with SAMe went into remission, while only 23% of those using escitalopram (a common anti-depressant) went into remission.[9] Interestingly, SAMe requires folate and B12 for optimal function, and deficiencies of these vitamins are strongly associated with depression.[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 methylation and migraines:, and for more information about MethylMax™, see


[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.

[8] Varela-Rey, Ibid.

[9] Sarris, J., Price, L. H., Carpenter, L. L., Tyrka, A. R., Ng, C. H., Papakostas, G. I., … & Mischoulon, D. (2015). Is S-adenosyl methionine (SAMe) for depression only effective in males? A re-analysis of data from a randomized clinical trial. Pharmacopsychiatry, 48(04/05), 141-144.

[10] Williams, op. cit.

[11] Mischoulon, op. cit.

[12] Williams, op. cit.

Clinical Contributor

Sophie Thompson

Sophie Thompson

Clinical Support Intern at Sanesco Health
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.
Sophie Thompson

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    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.