SAM-e

A methyl donor with genuine antidepressant and osteoarthritis evidence — effective, pricey, and serotonergic.

Overall grade: Grade B
Last revised: Jul 10, 2026; 2
graded outcomes: 0
references listed

A structured monograph in Prometheus's bundled library. Its grades are the monograph's own reading of the evidence, not a peer-reviewed review.

2 at grade B — 2 graded rows

What is known

Each outcome with its grade (how strong the evidence is, A to D), the size of the effect where the entry records one, and how often studies agree.

Outcome	Grade	Effect size	Agreement
DepressionIncl. add-on	Evidence grade B	Moderate	mixed
Osteoarthritis painNSAID-comparable	Evidence grade B	Moderate	mixed

DepressionEvidence grade B
Incl. add-on
Moderatemixed
Osteoarthritis painEvidence grade B
NSAID-comparable
Moderatemixed

What is uncertain

Read off the same rows as above. Nothing here is added that the entry does not itself record.

Studies disagree: Depression (mixed agreement); Osteoarthritis pain (mixed agreement).
Caution with SSRIs / SNRIs: Serotonergic — serotonin-syndrome risk; only with a prescriber.

Interactions

Documented pairings with supplements and medicines. A medicine on this list is a conversation for whoever prescribes it.

SSRIs / SNRIsCaution
Serotonergic — serotonin-syndrome risk; only with a prescriber.

The evidence in words

What it is

S-adenosylmethionine (SAM-e) is the body's universal methyl donor, sold for depression and joint pain.

How it works

It drives methylation reactions that make neurotransmitters and maintain joint cartilage.

What the evidence shows

Meta-analyses support SAM-e for depression (comparable to some antidepressants, and useful as an add-on) and for osteoarthritis pain (similar to NSAIDs with better tolerability). Real efficacy; cost and instability are drawbacks, and it's serotonergic.

Safety & interactions

Can cause anxiety/insomnia and, being serotonergic, must not be combined with antidepressants without a prescriber; caution in bipolar disorder. ssri — Serotonergic — serotonin-syndrome risk; only with a prescriber.

Bottom line

One of the better-evidenced natural antidepressants and a real OA option — but expensive and serotonergic. Never stack with antidepressants unsupervised.

Entries that share this one's tags or conditions.

SAM-e for DepressionEvidence grade B — Incl. add-onEvidence grade B
SAM-e for Osteoarthritis painEvidence grade B — NSAID-comparableEvidence grade B
SAM-e: side effects, safety & interactionsCan cause anxiety/insomnia and, being serotonergic, must not be combined with antidepressants without a prescriber; cautEvidence grade B
Curcumin (Turmeric)A genuine anti-inflammatory for joints and mood — if you solve its terrible absorption; ignore the cancer-cure hype.Evidence grade B

Sources

This entry lists no references of its own.

Last revised Jul 10, 2026. A grade is this entry's reading of the evidence, not medical advice.