SAMe (S-adenosylmethionine)
What is it?
S-adenosylmethionine (SAMe) is an endogenous metabolite involved in several metabolic pathways that utilize methyltransferases to donate methyl groups to enzymes, receptors, DNA, cellular membranes, and neurotransmitters. Methylation reactions can alter enzymatic activity, regulate cell membrane structure, regulate membrane receptor activity, and activate or deactivate DNA. SAMe can also methylate other metabolites such as free amino acids or neurotransmitters, and it is a precursor to the antioxidative metabolite glutathione. Dysregulation of balanced methylation reactions may lead to a number of conditions related to liver, musculoskeletal, or neurocognitive dysfunction. (6)(33)(35)(36)(60) In the United States, SAMe has been available as a dietary supplement since 1999, while in Europe, various pharmaceutical formulations have been available for decades. (6) As a complementary and alternative medicine, SAMe may not be widely covered by health insurance; however, it may be a viable substitution for expensive prescriptions, including those used to treat depression. (60)
Main uses
Formulations
Dosing & administration
Adverse effects
SAMe is considered safe with a mild and non-clinically relevant side effect profile. Some common adverse effects may include anxiety, dizziness, gastrointestinal symptoms, insomnia or restlessness, sweating, tachycardia, and vertigo. (12)(60) However, compared to a placebo, SAMe does not increase the prevalence of adverse effects in conditions it is commonly used to treat, including chronic liver diseases (27), osteoarthritis, (55) or major depression (23). Additionally, there was no difference in the number of dropouts compared with various antidepressant medications including tricyclic antidepressants or when used as an adjunct to SSRIs (e.g., escitalopram) compared with a placebo. (23) In patients with depression, SAMe has been linked to an increased risk of switching between hypomanic or manic states, but this is mainly observed in bipolar disorder (10)(60) or when using intravenous or intramuscular administration rather than oral formulations. (47)(57)
While there may be speculative concerns that SAMe administration may lead to increased homocysteine, and thus higher cardiac risk, there was no significant elevation in total homocysteine when SAMe was provided to patients with depression (800-1,600 mg) over six weeks (43) or to healthy subjects using 800 mg per day for four weeks. (66)
Pharmacokinetics
Absorption
Distribution
Metabolism
SAMe’s metabolism involves the donation of its methyl group via three potential pathways (below):
- Methylation: SAMe donates its methyl group to DNA, proteins, phospholipids, neurotransmitters, etc., producing S-adenosylhomocysteine and, subsequently, homocysteine. Homocysteine may be metabolized to methionine (using vitamin B12) or undergo transsulfuration.
- Transsulfuration: Homocysteine can be metabolized to cystathionine (using vitamin B6), eventually leading to the production of the antioxidative nutrient glutathione.
- Aminopropylation: Leads to the production of polyamines that regulate cell growth and may provide analgesic or anti-inflammatory effects. SAMe is decarboxylated, a process during which its aminopropyl group is utilized to also eventually produce methionine.
- Note that SAMe can be resynthesized from methionine. (6)(13)(41)