Dosage protocol

SAMe dosage

Evidence-based dose range, timing, and adjustment guidance for SAMe. Always start at the low end and titrate; individual response varies and dose-response curves are not always linear.

Starting dose

Start at 400 mg — the lower end of the clinical range — for the first 3–7 days to assess tolerance and individual response. Most people who do not feel the expected effect at the low end need to titrate up to the midpoint (~1000 mg) over 1–2 weeks before evaluating whether SAMe works for them. Some users — particularly those with smaller body mass or sensitive baseline neurochemistry — find the low end fully sufficient.

Timing

Recommended timing: AM, empty stomach.

Half-life context: unknown — assume cautious 8-hour buffer between doses.

With or without food

before food: Take 20–30 minutes before a meal for clean absorption. Eating immediately after dosing can blunt peak plasma concentration through competition with food amino acids or by slowing gastric emptying.

Dose adjustment

• ·Body weight: Doses in the clinical literature are typically calibrated to a 70 kg adult. Smaller users (under 60 kg) often respond at 70–80% of the standard dose; larger users (over 90 kg) sometimes need 110–130%.
• ·CYP1A2/CYP2D6 metabolism: Caffeine, modafinil, and most racetams are CYP1A2-metabolised; slow metabolisers need lower doses and longer dose intervals. Yohimbine and several stimulants are CYP2D6-metabolised. Genotyping (23andMe raw data → Promethease) reveals these polymorphisms.
• ·Tolerance management: Receptor-binding compounds (stimulants, GABAergics, opioidergics) develop tolerance with daily use. Cycling 5 days on / 2 days off, or 4 weeks on / 1 week off, preserves response. Foundation supplements (omega-3, vitamin D, magnesium) do not require cycling.
• ·Concurrent stack: Effective dose can fall when stacked with synergistic compounds. The classic example is caffeine + L-theanine, where 50–100 mg caffeine often outperforms 200 mg solo on subjective focus measures.

When to reduce or stop

• Persistent headache, GI upset, or sleep disruption that does not resolve over 5–7 days suggests a dose reduction or compound change.
• Any cardiovascular symptoms (palpitations, chest tightness, blood pressure spikes) — stop immediately and reassess. Re-introduce only at half the original dose.
• Mood changes — apathy, persistent anxiety, agitation, or depressive symptoms emerging during a new protocol warrant immediate review with a clinician.

Dose ranges on this page reflect the clinical and supplement literature for healthy adults. They are not medical advice. Individual response varies; pregnancy, lactation, prescription medications, and pre-existing health conditions can all change the appropriate dose. Coordinate with a qualified clinician before establishing a personal protocol. See our full disclaimer.