Endogenous Metabolite
- Methyltransferases (including DNA methyltransferases and histone methyltransferases) as a methyl group donor
- Methionine adenosyltransferases (MAT) encoded by MAT1A and MAT2A
- Glycine N-methyltransferase (GNMT)

- In hepatocyte models, SAMe regulates methyl group transfer reactions, supporting transmethylation of DNA, proteins, and phospholipids. It enhances glutathione synthesis and reduces oxidative stress markers .
Ademetonine, also known as S-Adenosyl-L-methionine tosylate, is involved in three primary metabolic pathways: 1) methylation, which is the body's primary source of methyl groups; 2) transsulfuration, in which Ademetonine forms S-Adenosylhomocysteine (SAH), which is subsequently transformed into homocysteine (Hcy), which can be transformed into cystathionine, and finally into cysteine and sulfate (SO4) to supply additional metabolic intermediates; and 3) Aminopropylation, as Ademetonine is crucial to the synthesis of polyamines, which in turn forms and recycles methionine [2]. Studies conducted in vitro with human articular chondrocytes have demonstrated increases in rabbit proteoglycan production and proliferation rates driven by S-Adenosyl-L-methionine [2].

- In patients with depression, SAMe (200–1600 mg/day, oral or parenteral) significantly reduces depressive symptoms, with efficacy comparable to tricyclic antidepressants and a faster onset of action .
- In a double-blind crossover trial for osteoarthritis, SAMe showed comparable efficacy to celecoxib in relieving pain and improving joint function, as assessed by validated clinical scales .
- In MAT1A knockout mice, SAMe supplementation mitigates hepatic oxidative stress, steatohepatitis, and reduces the incidence of hepatocellular carcinoma (HCC) .
- In GNMT knockout mice, excessive hepatic SAMe levels induce liver injury, fibrosis, and HCC, which can be partially reversed by dietary methionine restriction .
Hepatic S-Adenosyl-L-methionine levels are decreased in mice lacking methionine adenosyltransferase 1a (Mat1a), and they also experience oxidative stress, steatohepatitis, and hepatocellular carcinoma (HCC). On the other hand, persistently elevated liver S-Adenosyl-L-methionine levels may potentially result in damage and HCC. Therefore, to preserve liver health and guard against harm and HCC, appropriate hepatic S-Adenosyl-L-methionine levels are required [3].

- Methyltransferase activity assay: Recombinant methyltransferases are incubated with SAMe and substrate molecules. Methylation efficiency is quantified by measuring S-adenosylhomocysteine (SAH) production or radiolabeled methyl group incorporation .
- MAT activity assay: Hepatocyte lysates are incubated with methionine and ATP in the presence of SAMe, and enzyme activity is determined by measuring SAMe synthesis .

- Hepatocyte culture: Isolated hepatocytes are treated with SAMe to assess changes in glutathione levels, oxidative stress markers (e.g., ROS, lipid peroxides), and gene expression related to methyl metabolism .

- MAT1A knockout mouse model: Mice are administered SAMe via oral gavage or intraperitoneal injection at varying doses for 4–12 weeks. Hepatic tissue is collected to evaluate histopathology, oxidative stress, and gene expression .
- GNMT knockout mouse model: Mice receive SAMe supplementation in drinking water or diet. Liver triglyceride levels, mitochondrial function, and citric acid cycle flux are measured after 8–16 weeks .

Absorption: Due to extensive first-pass metabolism in the liver, the oral bioavailability of SAMe is low. Distribution: Primarily concentrated in the liver, where approximately 85% of transmethylation reactions occur. Metabolism: Converted to SAH by methyltransferases, and further metabolized to homocysteine.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
SAM-e (S-adenosylmethionine) is a naturally occurring methyl radical donor involved in enzymatic transmethylation reactions in humans and animals. SAM-e has no specific lactation-related use, but it has been used to treat postpartum depression, cholestatic jaundice, osteoarthritis, and many other conditions. SAM-e has low oral bioavailability. SAM-e is generally well tolerated in adults. The most common adverse reactions are gastrointestinal reactions, such as nausea. Skin rashes have also been reported. There is currently no clinical information regarding the use of SAM-e during lactation. However, it is not expected that SAM-e taken by breastfeeding mothers will have any adverse effects on breastfed infants, especially if the infant is older than 2 months. Dietary supplements do not require extensive premarket approval from the U.S. Food and Drug Administration (FDA). Manufacturers are responsible for ensuring the safety of their products but are not required to demonstrate the safety and efficacy of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and there is often a difference between the ingredients listed on the label and the actual ingredients or amounts. Manufacturers may commission independent bodies to verify the quality of their products or their ingredients, but this does not necessarily mean that the product has been certified safe or effective. Given the above issues, clinical trial results for one product may not apply to other products. For more detailed information on dietary supplements, please visit other pages on the LactMed website.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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- Chronic excess levels of SAMe (e.g., GNMT deficiency) can lead to liver damage, fibrosis, and hepatocellular carcinoma.
- SAMe was well tolerated in clinical trials with rare adverse reactions; manic episodes have been reported in patients with bipolar disorder.
- No significant hepatotoxicity was observed at therapeutic doses in humans.

[1]. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl. 1994;154:7-14.

[2]. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]. BMC Musculoskelet Disord. 2004 Feb 26;5:6.

[3]. S-adenosylmethionine in liver health, injury, and cancer. Physiol Rev. 2012 Oct;92(4):1515-42.

Mechanism of Action: As a major biological methyl donor, it regulates epigenetic modifications, redox balance, and neurotransmitter synthesis (e.g., serotonin, dopamine). Clinical Applications: Approved in Europe for the treatment of depression, osteoarthritis, and cholestasis; used as a dietary supplement in the United States. Liver Health: Essential for maintaining hepatic methyl homeostasis; deficiency is associated with the progression of liver disease. A physiological methyl radical donor involved in enzymatic transmethylation reactions, it is present in all organisms. It possesses anti-inflammatory activity and has been used to treat chronic liver disease. (Excerpt from Merck, 11th edition)

C22H30N6O8S2

570.64

570.156

52248-03-0

S-Adenosyl-DL-methionine;17176-17-9;S-Adenosyl-L-methionine disulfate tosylate;97540-22-2;S-Adenosyl-L-methionine iodide;3493-13-8;S-Adenosyl-L-methionine;29908-03-0;S-Adenosyl-L-methionine (1,4-butanedisulfonate);200393-05-1

10153079

White to yellow solid powder

1.339

5

13

7

38

726

5

C[S+](CC[C@@H](C(=O)[O-])N)C[C@@H]1[C@H]([C@H]([C@H](N2C=NC3=C(N)N=CN=C32)O1)O)O.CC1=CC=C(C=C1)S(=O)(=O)O

VHPOFDUCFKOUHV-XKGORWRGSA-N

InChI=1S/C15H22N6O5S.C7H8O3S/c1-27(3-2-7(16)15(24)25)4-8-10(22)11(23)14(26-8)21-6-20-9-12(17)18-5-19-13(9)21;1-6-2-4-7(5-3-6)11(8,9)10/h5-8,10-11,14,22-23H,2-4,16H2,1H3,(H2-,17,18,19,24,25);2-5H,1H3,(H,8,9,10)/t7-,8+,10+,11+,14+,27?;/m0./s1

[(3S)-3-amino-3-carboxypropyl]-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-methylsulfanium;4-methylbenzenesulfonate

52248-03-0; AdoMet; DTXSID40436187; RefChem:553108; DTXCID70387012; ((3S)-3-amino-3-carboxypropyl)-(((2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl)methyl)-methylsulfanium; (2S)-4-(((2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl)methyl-methylsulfonio)-2-azaniumylbutanoate; 5'-[[(3S)-3-Amino-3-carboxypropyl]methylsulfonio]-5'-deoxy-Adenosine tosylate;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: 150 mg/mL (262.86 mM)

Solubility in Formulation 1: 100 mg/mL (175.24 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)