indication

S-Adenosylmethionine (SAMe) is used as a drug in Europe for the treatment of depression, liver disorders, fibromyalgia, and osteoarthritis. It has also been introduced into the United States market as a dietary supplement for the support of bone and joint health, as well as mood and emotional well being.

pharmacology

S-adenosylmethionine is an intermediate metabolite of methionine. Its involvement in methylation assists in cellular growth and repair, maintains the phospho-bilipid layer in cell membranes. It also helps in the maintenance of the action of several hormones and neurotransmitters that affect mood. Highest concentration are found in the brain and the liver.

mechanism of action

S-Adenosylmethionine (SAMe) is a natural substance present in the cells of the body. It is a direct metabolite of the essential amino acid L-methionine. SAMe plays a crucial biochemical role in the body by donating a one-carbon methyl group in a process called transmethylation. SAMe, formed from the reaction of L-methionine and adenosine triphosphate catalyzed by the enzyme S-adenosylmethionine synthetase, is the methyl-group donor in the biosynthesis of both DNA and RNA nucleic acids, phospholipids, proteins, epinephrine, melatonin, creatine and other molecules.

toxicity

Irritating to mucus membranes and upper respiratory tract. Can cause CNS depression.

biotransformation

Significant first-pass metabolism in the liver. Approximately 50% of S-Adenosylmethionine (SAMe) is metabolized in the liver. SAMe is metabolized to S-adenosylhomocysteine, which is then metabolized to homocysteine. Homocysteine can either be metabolized to cystathionine and then cysteine or to methionine. The cofactor in the metabolism of homocysteine to cysteine is vitamin B6. Cofactors for the metabolism of homocysteine to methionine are folic acid, vitamin B12 and betaine.

absorption

S-Adenosylmethionine is absorbed from the small intestine following oral intake. As absorption is affected by food, it is best to take on an empty stomach. Bioavailability is low following oral intake.

drug interactions

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Ginkgo biloba: Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Ketoprofen: Increased risk of bleeding due to additive antiplatelet properties of the two agents. Concomitant therapy should be avoided or monitored carefully for bleeding, bruising and altered mental status, which may be caused by CNS bleeds.

Sulindac: S-adenosylmethionine may enhance the anticoagulant effect of sulindac. Increased risk of bleeding, bruising and altered mental status due to CNS bleeds. Concomitant therapy should be avoided.

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Warfarin: Additive anticoagulant effects increase the risk of bleeding. Concomitant therapy should be avoided.

Zolmitriptan: Use of two serotonin modulators, such as zolmitriptan and S-adenosylmethionine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.