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SAM-e
SAM-e is a naturally occurring1 compound found in all living organisms.2 It was discovered by Giulio Cantoni in 1952. People generally use it to treat depression, osteoarthritis, and liver disease,3 although its effectiveness for these conditions remains uncertain.1 Supplements commonly come in enteric-coated tablets.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Duration
Subjective Effects
Pharmacology
Pharmacodynamics
SAM-e acts primarily as a methyl-group donor, supporting the methylation of nucleic acids, proteins and phospholipids, as well as the synthesis of molecules such as epinephrine, melatonin and creatine. These reactions contribute to cellular growth, repair and membrane maintenance. SAM-e also participates in transsulfuration and supplies aminopropyl groups for polyamine synthesis after decarboxylation. It activates the enzyme cystathionine beta-synthase4 and has reported antioxidant, anti-inflammatory and neuroprotective actions, including a role as a glutathione precursor. Its participation in nicotinamide methylation may help limit choline loss from neurons, although this proposed contribution to its cognitive effects remains uncertain.
Pharmacokinetics
Oral SAM-e is absorbed in the small intestine and has low bioavailability, reported as 2-10%, with substantial first-pass metabolism in the liver. Approximately 50% is metabolized in the liver, and its highest tissue concentrations occur in the liver and brain. Metabolism proceeds through methyl-group transfer, followed by hydrolysis by S-adenosylhomocysteine hydrolase; subsequent pathways either regenerate methionine or produce cysteine. The cysteine pathway requires vitamin B6, while methionine regeneration involves folate, vitamin B12 and betaine. SAM-e weakly inhibits CYP2E1 in vitro.5 Enteric-coated oral tablets reach peak plasma concentrations after three to five hours, and the elimination half-life is about 100 minutes.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.
Harm Potential
Addiction & Dependence
Psychological
Extremely LowSAM-e is described as non-habit-forming, with little abuse potential and no apparent tendency to cause psychological dependence.
Physical
Extremely LowSAM-e does not appear to cause physical dependence.
Toxicity
SAM-e can irritate mucous membranes and the upper respiratory tract.
SAM-e can cause central nervous system depression, and supplementation has been associated with uncommon manic episodes, including in people without a history of mania.
SAM-e consumption can cause gastrointestinal disturbances, including dyspepsia, constipation, and nausea.
Excess SAM-e produced harmful effects in laboratory mice, and toxicity was also observed in cultured human cells.
SAM-e has weak DNA-alkylating activity.8
History & Culture
Giulio Cantoni first discovered S-adenosylmethionine (SAM-e) in 1952.9 Earlier observations in 1947 had linked the SAM cycle to liver disease through the accumulation of methionine in the blood of people with alcoholic cirrhosis.…
Legality
By Country
References
Source Pages
Citations
Further Reading
Article Status
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