[SAMe, S-adenosylmethionine]
Side effects, Health Benefits Research Finds

Updated on April 17, 2018
S-adenosyl-L-methionine [SAMe, S-adenosylmethionine]

S-adenosyl-L-methionine is not abundant in the diet. It is normally produced in the liver from
methionine. Foli acid and vitamin B12 are needed for the synthesis of S-
adenosylmethionine. Deficiencies of these vitamins always lead to low concentrations of S-
adenosylmethionine in the central nervous system [1]. Low blood or central nervous system
levels of S-adenosylmethionine is also associated with cirrhosis of the liver, coronary heart
disease, Alzheimer's disease and depression [2-4]. S-adenosylmethionine participates in
over 40 essential biochemical reactions including detoxifications and in the manufacture of
some brain chemicals, antioxidants, joint tissue structures [5,6]. S-adenosylmethionine may
also raise levels of dopamine [7,8], thus S-adenosylmethionine may be an effective
treatment for depression [9-15, 16, 17]. S-adenosylmethionine is also found to be anti-
inflammatory, pain-relieving, and tissue-healing, S-adenosylmethionine may support the
joint health [18-27, 28]. S-adenosylmethionine may also be helpful in various liver conditions
such as cholestasis, Gilbert's syndrome, alcoholic liver injury, and cirrhosis [29-31]. S-
adenosylmethionine may also increase sperm activity in infertile men [32]. Consequently, S-
adenosylmethionine is marketed as a nutritional supplement for a range of conditions such
as liver disease, depression, osteoarthritis, fibromyalgia, and dementia.


It is because S-adenosylmethionine is marketed as a supplement for brain health,
particularly for depression. My literature review for 2018 updates on S-adenosylmethionine
focuses its application on mental conditions particularly depression. Here is my review

Depression and Neuropsychiatric Conditions
In 2017, Martínez-Cengotitabengoa M and González-Pinto A from Spain summarized
reasons why we repeatedly believe that S-adenosyl methionine is a remedy for depression.  
And they are: (1) patients with depression have low levels of S-adenosyl methionine in the
CSF and (2) S-adenosyl methionine can alter the neuronal membrane fluidity, which  
would affect the functionality of certain membrane proteins, including the monoamine
receptors and transporters. Further, there is also a study in which it has been seen that S-
Adenosyl methionine administered as coadjuvant to escitalopram compared with placebo
shows greater antidepressant efficacy but only in the case of male patients. (2018-2) In the
same year, a group of the American Psycliatric Association Council on Research published
a systematic review on S-adenosylmethionine for treatment of neuropsyhiatric conditions.
Totally, they reviewed 115 clinical studies and 17 preclinical studies, and they concluded
that the use of S-adenosylmethionine in treating major depressive order was promising but
there was limited evidence of its efficacy and safety. They also described its potential side
effects or toxicity in the article. They wrote, "preliminary evidence suggests that S-
adenosylmethionine may ameliorate symptoms in certain neurocognitive, substance use,
and psychotic disorders and comorbid medical conditions." However, they also commented
that the body of evidence has limitations. (2018-1)

Alzheimer's Disease

In 1988, Cohen and colleagues reported that S-adenosylmethionine produced neither
improvement nor worsening of symptoms in patients with Alzheimer's disease. (2018-11)
But in 2002, Eto K at National Center of Neurology and Psychiatry, Japan, reported his
observation that S-adenosylmethionine is much reduced in the brain of patients suffered
from Alzheimer’s Disease. (2018-12) Further, there are some non-clinical studies
supporting the hypothesis that S-adenosyl methionine may have health benefits on
Alzheimer’s Disease. For example, it is known that Vitamin B deficiency induces an
exacerbation of Alzheimer’s Disease in animals, and supplementation of S-
adenosylmethionine may counteract this effect through a modulation of DNA methylation
and antioxidant pathways. (2018-13), And, Montgomery SE and colleagues conducted a
comprehensive literature review up to April 2014, they found S-adenosylmethionine
supplement was associated with improvements in cognitive performance of mice. They
believed S-adenosylmethionine might be useful in improving spatial memory in patients
suffered from dementia forms. (2018-14)


DNA hypomethylation coordinately may target various signaling pathways involved in tumor
growth and metastasis. Thus, S-adenosylmethionine may have anti-cancer activities. In fact,
as early as in 1996, Simile MM et al, Universita di Sassari, Italy has already reported S-
adenosylmethionine’s anti-cancer effects in rat studies. (2018-6) Then there are multiple cell
and animal studies on S-adenosylmethionine, how it affects the cancer progress. Recently,
a group of scientists led by Mahmood N. at McGill University, Canada, verified the
hypothesis with two different human breast cancer cell lines (MDA-MB-231 and Hs578T). In
2017, they reported-gene expression analyses validated the ability of S-
adenosylmethionine to decrease the expression of several key genes implicated in cancer
progression and metastasis in both cell lines and breast tumor xenografts. (2018-3) About
the same time, another group from McGill University and Chinese Academy of Sciences
demonstrated S-adenosylmethionine selectively inhibits growth, transformation and
invasiveness of hepatocellular carcinoma cell lines. (2018-4) A group from L.A. also found
S-adenosylmethionine’s anti-cancer activities on down-regulated in colorectal cancer cells.
(2018-5) In 2015, Shen Feng from Eastern Hepatobiliary Surgery Hospital reported that
they were prepared a phase 1 study on S-Adenosyl Methionine, the objective is to
investigate if S-Adenosyl Methionine has an effect on improving patients’ recurrence after
curative resection of hepatocellular carcinoma. Based on their plan, they should complete
this study by December of 2017. (2018-7)

Liver Damage
About 15 years ago, Stickel F and colleagues from Germany suggested that S-
adenosylmethionine might have health benefits on liver conditions, particularly alcoholic liver
damage, because (2018-8) In 2016, Vincenzi B and his group performed a literature review
on anticancer induced liver toxicity, they noticed S-adenosylmethionine might have
hepatoprotective effects based on the results of some small studies. (2018-9) Then in 2017,
a group of scientists in Kentucky suggested treatment involving supplementation of S-
adenosylmethionine may help prevent or attenuate some types of alcohol-induced organ
damage. (2018-10)

S-adenosyl-l-methionine has been marketed as a supplement promoting heart conditions, I
then ran a literature review on its effect on blood pressure. Three researchers from The
Medical University of Warsaw, Poland, reported that infusion of S-adenosylmethionine in
rats led to a reduction of blood pressure. The effect was dose-dependent. (2018-15)

Kidney Disease
Antoniv A and colleagues from Ukraine conducted a study on the potential benefits or
efficacy of S-adenosylmethionine on patients with non-alcoholic steatohepatitis in
comorbidity with obesity and chronic kidney disease (CKD) of the 1st-2nd stages in 2017.
This is what they reported, “S-adenosylmethionine (ahepta) in a dose of 600 mg sublingually
in patients with non-alcoholic steatohepatitis on the background of obesity and chronic
kidney disease of the 1st and 2nd st. produces powerful membrane-stabilizing effects on
the affected hepatocytes, stably eliminates the clinical manifestations of the disease, the
intensity of cytolysis, cholestasis, mesenchymal-inflammatory syndrome, inhibits the
progression of hepatic and renal dysfunction (increases the albumin-synthesizing function of
the liver, the velocity of glomerular filtration) by optimizing the control of fibrosis of the liver
and kidneys”. (2018-18)

Imhoff DJ and his group from University of Illinois evaluated the effect of S-
adenosylmethionine on osteoarthritis in a dog study. They could not conclude that S-
adenosylmethionine has a benefit on dogs suffered from osteoarthritis after a six-weeks of
treatment. (2018-19)

Sarac AJ and Vur A from Dicle University, Turkey stated that Some herbal and nutritional
supplements (magnesium, S- adenosylmethionine) and massage therapy have the best
evidence for effectiveness with fibromyalgia. (2018-20) However, more studies are needed
to confirm such benefits.

In 2008, Valli A and co-workers reported that both S-adenosylmethionine and S-
adenosylhomocysteine were found to be higher in chronic kidney disease. (2018-17) In
2013, Alsayed R and colleagues from Damascus University, observed that children with
congenital heart defects had a higher plasma S-adenosylmethionine. (2018-16) It is unclear
the exact mechanism and relationship between S-adenosylmethonine and these conditions,
users must consult with their medical providers before taking this supplement.


Toxicity / SIDE EFFECT

Goren JL et al, McLean Hospital, Massachusetts, concluded that oral dosages of 1600
mg/day of S-adenosylmethionine appear to be significantly bioavailable and nontoxic (2018-

However, S-adenosylmethionine may cause Parkinson's disease-like syndromes [33]. As
discussed in other sections, S-adenosylmethionine may also have some other side effects
or toxic effects. Though S-adenosyl methionine is a naturally occurring chemical in our body,
how it affect
ing our body depends on our body condition and its amount present in our body.
Again, we must discuss
this supplement with our medical provider before taking it.



1. Bottiglieri T, Hyland K, Reynolds EH. Drugs 1994;48:137-52 [review].2. Osman E, Owen
JS, Burroughs AK. Aliment Pharmacol Ther 1993;7:21-8 [review].3. Loehrer FM, Angst CP,
Haefeli WE, et al. Arterioscler Thromb Vasc Biol 1996;16:727-33. 4. Bottiglieri T, Godfrey
P, Flynn T, et al. J Neurol Neurosurg Psychiatry 1990;53:1096-8. 5. Chiang PK, Gordon RK,
Tal J, et al. FASEB J 1996;10:471-80 [review]. 6. Bottiglieri T, Hyland K, Reynolds EH.
Drugs 1994;48:137-52 [review]. 7. Fava M, Rosenbaum JF, MacLaughlin R, et al. J
Psychiatr Res 1990;24:177-84. 8. Bell KM, Potkin SG, Carreon D, Plon L. Acta Neurol
Scand 1994;154(suppl):15-8. 9. Bell KM, Potkin SG, Carreon D, Plon L. Acta Neurol Scand
1994;154(suppl):15-8. 10. Bressa GM. Acta Neurol Scand 1994;154(suppl):7-14. 11.
Salmaggi P, Bressa GM, Nicchia G, et al. Psychother Psychosom 1993;59:34-40. 12.
Kagan BL, Sultzer DL, Rosenlicht N, et al. Am J Psychiatry 1990;147:591-5. 13. Fava M,
Rosenbaum JF, Birnbaum R, et al. Acta Psychiatr Scand 1992;86:42-5. 14. De Vanna M,
Rigamonti R. Curr Ther Res 1992;52:478-85. 15. Fava M, Giannelli A, Rapisarda V.
Psychiatr Res 1995;56:295-7. 16. Tavoni A, Jeracitano G, Cirigliano G. Clin Exp Rheumatol
1998;16:106-7 [letter]. 17. Tavoni A, Vitali C, Bombardieri S, et al. Am J Med
1987;83(suppl 5A):107-10. 18. Schumacher HR. Am J Med 1987;83(suppl 5A):1-4 [review].
19. Harmand MF, Vilamitjana J, Maloche E, et al. Am J Med 1987;83(suppl 5A):48-54. 20.
Domljan Z, Vrhovac B, Durrigl T, Pucar I. Int J Clin Pharmacol Ther Toxicol 1989;27:329-33.
21. Muller-Fassbender H. Am J Med 1987;83(suppl 5A):81-3. 22. Vetter G. Am J Med
1987;83(suppl 5A):78-80. 23. Maccagno A. Am J Med 1987;83(suppl 5A):72-7. 24. Caruso
I, Pietrogrande V. Am J Med 1987;83(suppl 5A):66-71. 25. Marcolongo R, Giordano N,
Colombo B, et al. Curr Ther Res 1985;37:82-94. 26. Glorioso S, Todesco S, Mazzi A, et al.
Int J Clin Pharmacol Res 1985;5:39-49. 27. Montrone F, Fumagalli M, Sarzi Puttini P, et al.
Clin Rheumatol 1985;4:484-5. 28. Jacobsen S, Danneskiold-Samsoe B, Andersen RB.
Scand J Rheumatol 1991;20:294-302. 29. Angelico M, Gandin C, Nistri A, et al. Scand J
Clin Lab Invest 1994;54:459-64. 30. Frezza M, Surrenti C, Manzillo G, et al.
Gastroenterology 1990;99:211-5. 31. Bombardieri G, Milani A, Bernardi L, Rossi L. Curr
Ther Res 1985;37:580-5. 32. Mato JM, Cámara J, Fernández J, et al. J Hepatol

(2018-1) J Clin Psychiatry. 2017 Jun;78(6):e656-e667. (2018-2) Actas Esp Psiquiatr. 2017
Sep;45(Supplement):8-15. Epub 2017 Sep 1. (2018-3) Oncotarget 2017 Dec 26;9(4):5169-
5183. doi: 10.18632/oncotarget.23704. eCollection 2018 Jan 12. (2018-4) Oncotarget.
2017 Dec 5;8(67):111866-111881. doi: 10.18632/oncotarget.22942. eCollection 2017
Dec 19. (2018-5) Oncotarget. 2017 Aug 12;8(45):78851-78869. doi: 10.18632/oncotarget.
20234. eCollection 2017 Oct 3. (2018-6) Carcinogenesis. 1996 Jul;17(7):1533-7. (2018-7)
ClinicalTrials.gov Identifier: NCT02586285. (2018-08) Z Gastroenterol. 2003 Apr;41(4):333-
42. (2018-9) Expert Opin Drug Saf. 2016 Sep;15(9):1219-38.  (2018-10) Alcohol Res.
2017;38(2):289-302.  (2018-11) J Clin Psychopharmacol. 1988 Feb;8(1):43-7. (2018-12)
Biochem Biophys Res Commun. 2002 May 24;293(5):1485-8. (2018-13) J Alzheimers Dis.
2015;44(4):1323-31. (2018-14) PLoS One. 2014 Oct 27;9(10):e107756. (2018-15) Amino
Acids. 2016 Jul;48(7):1581-90. (2018-16) Metabolism. 2013 Aug;62(8):1074-80. (2018-17)
Clin Chim Acta. 2008 Sep;395(1-2):106-10. (2018-18) Georgian Med News. 2017 Dec;
(273):31-36, (2018-19) Vet Surg. 2011 Feb;40(2):228-32. (2018-20) Curr Pharm Des.
2006;12(1):47-57. (2018-21) Pharmacotherapy. 2004 Nov;24(11):1501-7.

Does SAMe [S-adenosylmethionine] have health benefits on depression?