SAMe
TL;DR
Universal methyl donor involved in 200+ metabolic reactions. Prescription drug in Europe for depression and liver disease. Supports methylation, cartilage repair, and liver function.
Safety: Generally well-tolerated. GI discomfort, anxiety, insomnia possible. May trigger mania in bipolar disorder. Not for use with bipolar.
Cost: approximately $30-60/month.
Best for: Liver disease
What the research says
Prescription drug for liver disease in Europe. Multiple trials show benefit for intrahepatic cholestasis and alcoholic liver disease. Supports glutathione production.
Primarily studied for depression. Some evidence that mood improvement translates to cognitive benefit. Limited direct cognitive decline data.
SAMe on Amazon
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Safety & practical info
GI discomfort, anxiety, insomnia possible. May trigger mania in bipolar disorder. Not for use with bipolar.
Risk of serotonin syndrome with serotonergic drugs. May reduce levodopa effectiveness. Do not combine with MAOIs.
Expensive. Requires enteric coating for stability. Quality varies.
Sources for this page include published meta-analyses, systematic reviews, and NIH dietary supplement fact sheets. All claims reflect the evidence as of early 2026.
This is not medical advice. Consult your healthcare provider before starting any supplement, especially if you take medications.