S-adenosylmethionine

    Researchedby:
    Thomas Solomon

    Fact-checked

    by:

    Katie Jantz, Conni Covington
    Last Updated: September 2, 2024

    S-adenosylmethionine (SAMe) is a metabolite in the body that helps maintain several important biological reactions. Low levels of SAMe in the body are associated with several conditions, including liver conditions, chronic kidney disease (CKD), coronary artery disease (CAD), depression, and neurodegenerative conditions like dementia and Alzheimer’s disease. Supplementation with SAMe might improve liver health and depression, but further high-quality clinical trials are needed to confirm those benefits.

    What is S-adenosylmethionine?

    S-adenosylmethionine is made in the body from ATP and methionine and is produced, broken down, and regenerated in a series of steps known as the SAM (S-adenosylmethionine) cycle.[1][2][3] S-adenosylmethionine circulates in the blood and cerebrospinal fluid, and its major role is as a “methyl donor”, where it provides a methyl group (CH3; three hydrogen atoms attached to a carbon atom) for important biological reactions in the body.[1][2][3] However, it can also donate adenosyl groups, amino groups (NH3), and more in other enzymatic reactions.[4]

    S-adenosylmethionine regulates several important biological processes including DNA methylation, immune responses, and amino acid metabolism[1][2][3] and is sold as a food supplement claimed to improve several conditions. In some countries, S-adenosylmethionine is also available as a prescription drug.

    What is the SAM cycle?

    What are S-adenosylmethionine’s main benefits?

    Low levels of S-adenosylmethionine have been found in people with liver conditions (nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cirrhosis, etc.),[1][5][6] chronic kidney disease (CKD),[7] coronary artery disease (CAD),[8][9] depression,[10][11][12] and some neurodegenerative conditions like dementia and Alzheimer’s disease.[12][13] These observations suggest that supplementation could help treat such conditions. However, while S-adenosylmethionine has shown therapeutic effects in cell-culture experiments and animal models,[1][5][14] its therapeutic benefit in humans is less convincing.

    Current evidence shows that S-adenosylmethionine might help treat depression[15][16][17][18] and might improve liver health and survival in people with liver conditions like cirrhosis.[19][20][21] However, due to the low quality of evidence, further large, double-blind randomized controlled trials are needed to clarify the clinical efficacy of S-adenosylmethionine.

    Does S-adenosylmethionine treat osteoarthritis?

    What are S-adenosylmethionine’s main drawbacks?

    Despite the popularity of S-adenosylmethionine as a dietary supplement, the main drawback is the lack of high-quality evidence supporting its claimed clinical efficacy (as discussed above). Furthermore, some case studies of patients with underlying conditions have reported serious adverse effects, including manic episodes with suicidal thoughts.[22][23][24][25] For this reason, people with bipolar disorder should consult their doctor before considering using S-adenosylmethionine.

    Other studies have reported side effects including headaches, insomnia, and nausea,[26][15][27] while further studies have highlighted safety concerns when S-adenosylmethionine is consumed in excess.[28] However, adverse effects are rare and side effects are uncommon, so S-adenosylmethionine is generally considered safe to consume.[24][26][15][27] That said, Cochrane reviews on S-adenosylmethionine note that studies in this field rarely document adverse events.[15][27]

    How does S-adenosylmethionine work?

    S-adenosylmethionine regulates biological processes by transferring methyl groups, adenosyl groups, amino groups, and more to proteins, lipids, nucleic acids (e.g., DNA), and several other metabolites in many enzymatic reactions.[1][4][2][3]

    Because several conditions — liver disease, kidney disease, heart disease, and neurodegenerative conditions, etc. — are associated with low levels of S-adenosylmethionine in blood or tissues,[1][5][6][7][8][9][12][13] supplementation might help restore normal levels. However, even if this is possible, the evidence supporting the therapeutic efficacy of supplementation with S-adenosylmethionine is weak (as described above).

    What are the pharmacokinetics of S-adenosylmethionine?

    What are other names for S-adenosylmethionine

    Note that S-adenosylmethionine is also known as:
    • SAM
    • SAMe
    • SAM-e
    • Adomet
    • Ademetionine
    • S-adenosyl-L-methionine
    S-adenosylmethionine should not be confused with:
    • Methionine

    Dosage information

    Formulations: Tablets taken orally, or liquid injected intravenously or intramuscularly.

    Range of dosages studied: 45 to 3200 milligrams per day (mg/day).

    Dosage recommendation: In some studies, the dosage range that has been found to improve depression is approximately 200 to 1,600 mg/day. In some studies, the dosage range that has been found to improve liver health in people with chronic liver conditions is approximately 800 to 1,200 mg/day

    Take with food: S-adenosylmethionine can be taken with or without food.

    Safety information:

    S-adenosylmethionine can interact with several drugs including drugs that affect serotonin, including Selective Serotonin Reuptake Inhibitors and Monoamine Oxidase Inhibitors. Due to the increased risk of mania, S-adenosylmethionine is not recommended for people with bipolar disorder.

    Frequently asked questions

    What is S-adenosylmethionine?

    S-adenosylmethionine is made in the body from ATP and methionine and is produced, broken down, and regenerated in a series of steps known as the SAM (S-adenosylmethionine) cycle.[1][2][3] S-adenosylmethionine circulates in the blood and cerebrospinal fluid, and its major role is as a “methyl donor”, where it provides a methyl group (CH3; three hydrogen atoms attached to a carbon atom) for important biological reactions in the body.[1][2][3] However, it can also donate adenosyl groups, amino groups (NH3), and more in other enzymatic reactions.[4]

    S-adenosylmethionine regulates several important biological processes including DNA methylation, immune responses, and amino acid metabolism[1][2][3] and is sold as a food supplement claimed to improve several conditions. In some countries, S-adenosylmethionine is also available as a prescription drug.

    What is the SAM cycle?

    The S-adenosylmethionine (SAM) cycle is a series of metabolic steps that produce, break down, and regenerate S-adenosylmethionine.[1][2][3] The SAM cycle converts S-adenosylmethionine to S-adenosylhomocysteine to homocysteine to methionine and back to S-adenosylmethionine using various enzymes.[1][2][3] The enzymatic conversion of homocysteine to methionine in the SAM cycle uses vitamin B12 as a cofactor and links the SAM cycle to the folate cycle to make up a complex series of metabolic pathways known as one-carbon metabolism.[29] It is called one-carbon metabolism because these processes produce and provide one-carbon methyl groups (CH3) for several important biological processes (DNA synthesis, DNA methylation, immune function, amino acid metabolism, etc.).[1][2][3][29]

    What are S-adenosylmethionine’s main benefits?

    Low levels of S-adenosylmethionine have been found in people with liver conditions (nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cirrhosis, etc.),[1][5][6] chronic kidney disease (CKD),[7] coronary artery disease (CAD),[8][9] depression,[10][11][12] and some neurodegenerative conditions like dementia and Alzheimer’s disease.[12][13] These observations suggest that supplementation could help treat such conditions. However, while S-adenosylmethionine has shown therapeutic effects in cell-culture experiments and animal models,[1][5][14] its therapeutic benefit in humans is less convincing.

    Current evidence shows that S-adenosylmethionine might help treat depression[15][16][17][18] and might improve liver health and survival in people with liver conditions like cirrhosis.[19][20][21] However, due to the low quality of evidence, further large, double-blind randomized controlled trials are needed to clarify the clinical efficacy of S-adenosylmethionine.

    Does S-adenosylmethionine treat osteoarthritis?

    S-adenosylmethionine is claimed to improve joint pain and function in people with knee or hip osteoarthritis. However, studies in this field are small, and their methodological quality is generally low. Consequently, higher-quality evidence is needed to make clear conclusions.[26][27]

    What are S-adenosylmethionine’s main drawbacks?

    Despite the popularity of S-adenosylmethionine as a dietary supplement, the main drawback is the lack of high-quality evidence supporting its claimed clinical efficacy (as discussed above). Furthermore, some case studies of patients with underlying conditions have reported serious adverse effects, including manic episodes with suicidal thoughts.[22][23][24][25] For this reason, people with bipolar disorder should consult their doctor before considering using S-adenosylmethionine.

    Other studies have reported side effects including headaches, insomnia, and nausea,[26][15][27] while further studies have highlighted safety concerns when S-adenosylmethionine is consumed in excess.[28] However, adverse effects are rare and side effects are uncommon, so S-adenosylmethionine is generally considered safe to consume.[24][26][15][27] That said, Cochrane reviews on S-adenosylmethionine note that studies in this field rarely document adverse events.[15][27]

    How does S-adenosylmethionine work?

    S-adenosylmethionine regulates biological processes by transferring methyl groups, adenosyl groups, amino groups, and more to proteins, lipids, nucleic acids (e.g., DNA), and several other metabolites in many enzymatic reactions.[1][4][2][3]

    Because several conditions — liver disease, kidney disease, heart disease, and neurodegenerative conditions, etc. — are associated with low levels of S-adenosylmethionine in blood or tissues,[1][5][6][7][8][9][12][13] supplementation might help restore normal levels. However, even if this is possible, the evidence supporting the therapeutic efficacy of supplementation with S-adenosylmethionine is weak (as described above).

    What are the pharmacokinetics of S-adenosylmethionine?

    In humans, intravenous administration of S-adenosylmethionine (100 mg, 500 mg, and 0.5 mg/kg of body weight) directly into the bloodstream has a half-life of approximately 80 to 100 minutes.[30][31] Furthermore, there are detectable increases in S-adenosylmethionine concentrations in the blood and the cerebrospinal fluid after oral, intravenous, and intramuscular administration, suggesting that S-adenosylmethionine crosses the blood-brain barrier.[32]

    In humans, intramuscular administration of S-adenosylmethionine (0.5 mg/kg of body weight) shows approximately 80–90% bioavailability — i.e., 80–90% of S-adenosylmethionine injected into a muscle appears in the blood.[30] However, when orally administered in humans, the bioavailability of S-adenosylmethionine is poorer,[32][24] as low as 2–3% in some studies.[33] However, some studies show that enteric-coated capsules of S-adenosylmethionine, which are protected from degradation by stomach acid, have improved bioavailability in humans when compared to uncoated S-adenosylmethionine.[34][35] Novel formulations such as phytate salts[36] and solid lipid nanoparticles[37] have further improved oral bioavailability in rodents, but these formulations remain to be tested in humans.

    Update History

    References

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