SAMe (S-adenosyl-L-methionine)
Methyl-donor cofactor with antidepressant RCTs comparable to SSRIs and additional signal for osteoarthritis pain.
Why
S-adenosyl-L-methionine (SAMe) is the universal methyl donor in human biochemistry. Two RCT bodies are relevant. In depression: an AHRQ systematic review and individual RCTs report effects comparable to imipramine and escitalopram, including as augmentation of SSRI non-responders. In osteoarthritis: a Cochrane review found broadly similar pain reduction to NSAIDs with fewer adverse events. SAMe is unstable as a raw molecule; stabilised salt forms and enteric coating matter.
How it works
Donates methyl groups for synthesis of monoamine neurotransmitters (serotonin, dopamine, noradrenaline) and for the methylation of phospholipids, DNA, and cartilage proteoglycans.
Expected onset · Mood: 2–4 weeks. OA pain: 1–2 weeks for symptom reduction.
How to take
Dosage
Depression: 800–1,600 mg/day divided. OA: 600–1,200 mg/day. Start at the lower end and titrate.
Timing
Morning and midday on empty stomach; can cause activation late in the day
On the label
Look for 'SAMe tosylate' or 'SAMe butanedisulfonate' in enteric-coated tablets, with stated milligrams of active SAMe (not total salt weight).
Ideal for
Adults with mild-to-moderate low mood who want fewer drug interactions than St John's wort, or with osteoarthritis pain when NSAIDs are poorly tolerated.
Safety
Evidence
Sarris 2010 Am J Psychiatry double-blind RCT (n=73): SAMe 800 mg twice daily added to SSRI in non-responders gave significantly higher HAM-D response (36%) and remission (26%) vs placebo over 6 weeks. Cochrane 2009 SR on SAMe for hip/knee OA found symptom benefit comparable to NSAIDs with fewer adverse events, though the authors flagged small trial sizes.
Where to get it
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