S-adenosylmethionine (SAMe) is an amino acid that is used in the treatment of many conditions including liver disease, osteoarthritis, depression, fibromyalgia, schizophrenia, migraine headaches, and to increase bile flow. Other names for SAMe include: S-Adensyl Methionine, L-Methionine, Adomet, and Ademethionine.

SAMe was discovered in Italy about four decades ago (Cantoni, 1952). However, the first clinical study of SAMe's use for depression was not completed until the 1970s (Agnoli et al., 1976). At that time there were no usable oral preparations and early studies had to use intravenous [IV] and intramuscular [IM] delivery. SAMe was first introduced into the U.S. dietary supplement market in 1999. However, it has been available in Europe since 1975. Today an oral form is used that is more resistant to oxidation and gastric enzyme degradation. Thus, allowing the SAMe to actually pass through the digestive track and into the blood flow.

SAMe (also known as SAM or AdoMet) is a derivative of the amino acid, methionine. It's formed when methionine combines with adenosine triphosphate (ATP), a nucleotide present in all living cells. ATP is the major source of cellular energy. The liver uses this process to make SAM, as much as 8 grams of it every day, when the liver is perfectly healthy. Liver disease, osteoarthritis and the overuse of prescription drugs or over-the-counter medications can diminish the body's SAM production. A small amount of SAMe is found in food, but it is highly unstable and an unreliable means of increasing blood levels.

As a methyl donor, SAMe "donates" units called methyl groups, which contain hydrogen and carbon atoms, to other substances. This process is methylation, and it is one way in which the body protects itself from damage on the cellular level. Methyl donors help to protect against cancer, heart disease, neurological disorders, and many age-related problems, and facilitated the manufacture of DNA and brain neurotransmitters. It is involved in more than 50 methylation reactions in the body, including the regulation of various hormones and neurotransmitters such as serotonin, melatonin, and dopamine.

Once SAMe donates its methyl group to choline, creatine, carnitine, DNA, tRNA, epinephrine, and other compounds, it is transformed into S-adenosyl-homocysteine, (SAH). SAH donates its sulfur molecule to sulfur-containing amino acids such as cysteine, from which glutathione is formed. SAH then gives up its adenosine molecule to yield homocysteine. Homocysteine is a potentially toxic amino acid and an independent risk factor for coronary disease. Folic acid, choline, or betaine can change homocysteine back to methionine in the presence of vitamin B12, or convert homocysteine into cysteine and glutathione in the presence of vitamin B6.

SAMe is particularly important for the liver because glutathione is synthesized from it. Glutathione is crucial for liver function. A good portion of liver SAMe is turned into glutathione. Glutathione is the liver's natural antioxidant.