Methyl Donor Compound
SAM-e
Also known as: S-Adenosyl Methionine
A compound your body makes naturally that helps produce mood-related brain chemicals.
KÖGN Health grades SAM-e as A (Strong evidence) and rates it 4.2 out of 5.
Last reviewed · June 2026
Primary effects
- Mood support
- Cognitive stability
- Reduced fatigue
How it works
Supports methylation processes affecting mood, cognition, and neurotransmitter balance.
Overview
SAM-e plays a key role in methylation, which is essential for neurotransmitter production and overall brain function. It is most commonly used for mood support, with evidence suggesting benefits in depressive symptoms. Its cognitive effects are indirect, primarily driven by improved emotional balance and neurochemical regulation.
The evidence
SAM-e (S-adenosylmethionine) is a methyl donor involved in making neurotransmitters. Its best evidence is for depression: meta-analyses suggest benefit over placebo and as an add-on to antidepressants, though results are mixed and the trials vary in quality. It is best understood as a mood agent rather than a focus or memory enhancer.
How to dose it
Depression trials commonly use 800–1,600 mg/day of an enteric-coated form, sometimes split and titrated upward.
When to take it
Chronic — effects build over a few weeks.
Safety & side effects
The usual effects are GI upset, insomnia, and an activating or anxious feeling, more likely at higher doses.
Who should avoid it
Can trigger mania in people with bipolar disorder, and carries a risk of serotonin syndrome with antidepressants (SSRIs, SNRIs, MAOIs) — do not combine without medical advice. Caution in pregnancy.
References
Related ingredients
Graded entries that target the same cognitive goals.
Categories
Draft — the dose, safety and evidence notes on this entry were prepared from the published literature and are pending editorial and clinical review.
Educational information, not medical advice. The evidence grade is KÖGN’s editorial assessment of published research, not a health claim. Speak to a qualified clinician before changing what you take.