What is S-Adenosyl-L-Methionine?
S-Adenosyl-L-methionine (SAMe) is a compound that is naturally produced in the body. It is involved in many biochemical reactions, including those that affect mood. SAMe has been studied as a treatment for depression, osteoarthritis, and liver disease.

Health Benefits
SAMe is thought to have a role in the treatment of depression. A review of studies found that SAMe may be as effective as tricyclic antidepressants, such as amitriptyline, for treating depression.
SAMe has also been studied as a treatment for osteoarthritis. A review of studies concluded that SAMe may be more effective than placebo in reducing pain and improving joint function in people with osteoarthritis.
SAMe has also been studied as a treatment for liver disease. A review of studies found that SAMe may help to protect the liver from damage and improve liver function in people with hepatitis C.
Side Effects and Safety
SAMe is POSSIBLY SAFE when taken by mouth appropriately. The most common side effects are gastrointestinal, such as nausea and diarrhea. SAMe can also cause dry mouth, anxiety, headache, and dizziness.
SAMe is LIKELY UNSAFE when injected into the veins. There have been reports of death, coma, and seizure after people injected SAMe intravenously (by IV).
Special Precautions & Warnings:
Pregnancy and breast-feeding: SAMe is POSSIBLY SAFE when taken by mouth in small amounts during pregnancy. However, larger amounts might increase the risk for miscarriage. It’s best to avoid using SAMe during pregnancy unless you have a medical need. not enough is known about the safety of taking SAMe by mouth or injecting it intravenously (by IV) during breast-feeding. Stay on the safe side and avoid use.
Dosage
The following doses have been studied in scientific research:
BY MOUTH: For depression: 200-1600 mg of SAMe daily, divided into 2-4 doses.
For osteoarthritis: 200-400 mg of SAMe daily for up to 3 months.
For liver disease: 600-1200 mg of SAMe daily for up to 6 months.
INJECTION INTO THE VEINS: There is no safe or effective dose for injecting SAMe into the veins.
Some people take a lower dose of SAMe (100-200 mg per day) for maintenance purposes.
To reduce the risk of side effects, it’s best to start with a low dose and increase gradually as needed.
Mechanism of Action
The exact mechanism of action of SAMe is not known. It is thought to work by affecting neurotransmitters, such as serotonin and dopamine. SAMe may also have antioxidant effects.
Interactions
SAMe might increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin), and antiplatelet drugs such as clopidogrel (Plavix). Ask your healthcare provider before taking these medications together.
SAMe might also interact with certain antidepressants, seizure medications, Parkinson’s disease medications, and other drugs.
Pharmacokinetics
SAMe is rapidly absorbed from the gut and peak levels are reached in 1-2 hours. SAMe is broken down in the liver and excreted in the urine.
Half-life: 2.5-4 hours
Elimination: Urine (70%)
Alternatives to SAMe
St. John’s Wort
5-HTP
Omega-3 Fatty Acids
Zoloft (sertraline)
Wellbutrin (bupropion)
Is St. John’s Wort more effective than SAMe for depression?
There is some evidence that St. John’s Wort is more effective than SAMe for depression. A systematic review of studies found that St. John’s Wort was more effective than placebo and as effective as tricyclic antidepressants, such as amitriptyline, for treating depression.
Is 5-HTP more effective than SAMe for depression?
There is some evidence that 5-HTP is more effective than SAMe for depression. A systematic review of studies found that 5-HTP was more effective than placebo and as effective as tricyclic antidepressants, such as amitriptyline, for treating depression.
Is omega-3 fatty acids more effective than SAMe for depression?
There is some evidence that omega-3 fatty acids are more effective than SAMe for depression. A systematic review of studies found that omega-3 fatty acids were more effective than placebo and as effective as tricyclic antidepressants, such as amitriptyline, for treating depression.
Is Zoloft (sertraline) more effective than SAMe for depression?
There is some evidence that Zoloft (sertraline) is more effective than SAMe for depression. A systematic review of studies found that SSRIs, such as sertraline, were more effective than placebo and as effective as tricyclic antidepressants, such as amitriptyline, for treating depression.
Is Wellbutrin (bupropion) more effective than SAMe for depression?
There is some evidence that Wellbutrin (bupropion) is more effective than SAMe for depression. A systematic review of studies found that bupropion was more effective than placebo and as effective as tricyclic antidepressants, such as amitriptyline, for treating depression.