SAMe
Sold for low mood, joint pain and the liver. The depression trials are low in quality, it costs $60 to $120 a month, and it has been linked to mania.
At a glance
| Our verdict | Low-quality evidence, high cost, and reports of mania. |
| Sold for | Low mood and joints (claimed) |
| How sure the evidence is | Low |
| Cost a month | About $60 to $120 |
Written for adults in Canada. It explains the evidence; it is not advice for you personally. Last reviewed 20 October 2026.
Supplement Check
Is it right for you?
SAMe can trigger mania and can add to the effect of antidepressants. Your check reads your mood questionnaire and your medicines first, and tells you what would work better. Our Supplement Check looks at:
- Bipolar disorder (mania)
- Pregnancy and breastfeeding: no data
- Parkinson disease treated with levodopa
- Anyone taking an antidepressant
- Low mood most days, or any thoughts of harming yourself: see a doctor first
- Every medicine you take
Coming soon. The Supplement Check and the Online Health Assessment open once our safety testing is complete.
$59 when it opens, paid once. Adults 18 and over, anywhere in Canada. While the service is new, Dr. French reads every report himself, and your report arrives within 3 working days. More about the Supplement Check
What it is
SAMe is the body's main methyl donor: a molecule the body makes and uses to build and adjust many others. Supplements contain it as a tosylate or butanedisulfonate salt. It is unstable, so a usable product is enteric-coated and blister-packed, and many products are under-dosed.
How it acts
It supplies methyl groups to the pathways that make the brain's chemical messengers (the monoamines) and to the fats in cell membranes (phospholipids). This is mechanism, not proof that it helps mood.
What it is used for, and what the evidence says
Our review looked at depression. SAMe is also sold for osteoarthritis pain and liver disease; we did not review those uses.
| Use | What the trials found | How sure we are |
|---|---|---|
| Depression, against placebo | A Cochrane review (2016) found the evidence low in quality and could not reach a firm conclusion that SAMe works better than placebo. [1] | Low |
| Depression, against antidepressants | The same review could not reach a firm conclusion against antidepressants either. [1] A 2025 network meta-analysis (a review comparing many treatments at once) suggested a benefit, but from small trials. [2] | Low |
| Mania in the trials | Mania or hypomania (an abnormally high, driven mood) occurred in 2 of 441 people in the Cochrane trials. [1] | Low |
How sure we are: High means further research is very unlikely to change the answer; Moderate, it might; Low, it may well change; Very low, we are very unsure. These follow the GRADE method that guideline panels use.
Benefits
- Uncertain. No firm conclusion for depression, against placebo or against antidepressants. [1]
Risks and side effects
- Gut upset.
- Anxiety and poor sleep.
- Mania or hypomania: 2 of 441 people in the Cochrane trials. [1]
- Unreliable products. SAMe breaks down easily and many products are under-dosed.
Interactions with medicines
Our review found no information on whether SAMe changes how the liver clears medicines (no enzyme induction or inhibition was reported). The known interactions are with serotonin medicines and with levodopa.
| Medicine | What can happen | What to do |
|---|---|---|
| Antidepressants and other serotonin medicines | Serotonin syndrome (case reports) | Do not take together |
| Levodopa (Parkinson disease) | May reduce levodopa's effect | Do not take |
Who should not take it
- Bipolar disorder (mania).
- Pregnancy and breastfeeding: no data.
- Parkinson disease treated with levodopa.
- Anyone taking an antidepressant.
- Low mood most days, or any thoughts of harming yourself: see a doctor first. If you are thinking about suicide, call or text 9-8-8 (Suicide Crisis Helpline) now, any time; in immediate danger call 9-1-1.
- Under 18: outside the Supplement Check, which is for adults.
Dose and timing
We do not recommend a dose. For reference, trials used 800 to 1,600 mg a day, enteric-coated, on an empty stomach.
If you take it now, the way to judge it is a depression questionnaire (PHQ-9) at the start and again after 6 to 8 weeks.
What we know about Canadians
No Canadian data on SAMe use in our review.
Low mood is common in Canada. In 2022, 7.6% of Canadians aged 15 and older had a major depressive episode in the past year and 5.2% had generalised anxiety disorder, up from 4.7% and 2.6% in 2012. The rise was steepest in young women aged 15 to 24, in whom generalised anxiety tripled and depression doubled. Fewer than half (48.8%) of people with a disorder spoke to a health professional about it in the past year. [3]
Most at risk: women aged 15 to 24, unemployed people, and people who use substances (half of whom also have a mood or anxiety disorder). [4]
How sure are we: high. Statistics Canada Mental Health and Access to Care Survey 2022, a national survey with a structured diagnostic interview; nothing on SAMe itself.
An honest comparison: low mood
Same outcome (depressive symptoms), cost a month in Canadian dollars. Exercise trials cannot be blinded, so their effects include expectation; supplement and medicine trials are placebo-controlled. Read the certainty column before comparing sizes.
| Option | Effect | How sure we are | Cost a month (CAD) |
|---|---|---|---|
| SAMe 800 to 1,600 mg a day | No firm conclusion against placebo or antidepressants [1] | Low | $60 to $120 |
| Walking or jogging, hard enough to breathe hard | About 3 points lower than control groups on the 27-point depression questionnaire (PHQ-9); 218 trials, 14,170 people [5] | Low | $0 |
| Strength training or yoga | About as much as walking (effect size about 0.5) [5] | Very low | $0 to $21 (classes cost more) |
| Mediterranean-style eating with a dietitian | 32% recovered against 8% in one small 12-week trial of 67 people [6] | Low | About $30 |
| SSRI antidepressant (sertraline or escitalopram, generic) | 1.75 points more than placebo on the clinician-rated Hamilton depression scale; about 15% have a large response to the drug itself; [7] all 21 antidepressants studied did better than placebo [8] | Moderate | $8 to $12 |
Read honestly: SAMe costs up to ten times as much as a generic antidepressant and has weaker evidence. Exercise you find a bit hard is the best-studied thing you can do yourself, and it costs nothing.
Why we don't recommend it
We do not sell SAMe and our check never recommends it. The evidence for depression is low in quality, it is expensive, and it has caused mania.
Already taking it? Stop it and tell your doctor if you have bipolar disorder, take an antidepressant or levodopa, or are pregnant or breastfeeding. If your mood is low most days, a doctor's assessment comes first; if you have thoughts of harming yourself, call or text 9-8-8 now, any time.
For low mood, SAMe has no firm result against placebo or against antidepressants, and the trials are low in quality. A generic antidepressant costs $8 to $12 a month with better evidence; SAMe costs $60 to $120. Mania was reported in the trials. Exercise does at least as much for nothing. Dr. French approved this verdict with the 20 October 2026 evidence review.
Supplement Check
Before you buy it, get it checked
SAMe can trigger mania and can add to the effect of antidepressants. Your check reads your mood questionnaire and your medicines first, and tells you what would work better. Our Supplement Check looks at:
- Bipolar disorder (mania)
- Pregnancy and breastfeeding: no data
- Parkinson disease treated with levodopa
- Anyone taking an antidepressant
- Low mood most days, or any thoughts of harming yourself: see a doctor first
- Every medicine you take
Coming soon. The Supplement Check and the Online Health Assessment open once our safety testing is complete.
$59 when it opens, paid once. Adults 18 and over, anywhere in Canada. While the service is new, Dr. French reads every report himself, and your report arrives within 3 working days. More about the Supplement Check
Disclosure of financial interest
White Pine Medical earns money from products bought through our Fullscript dispensary. Dr. French's Code of Ethics requires him to tell you this. You do not have to buy anything from us: every product is named by its ingredient and dose so you can buy it at any pharmacy, and the advice is the same wherever you buy it, or if you buy nothing.
References
- Galizia I, Oldani L, Macritchie K, Amari E, Dougall D, Jones TN, et al. S-adenosyl methionine (SAMe) for depression in adults. Cochrane Database Syst Rev. 2016;10(10):CD011286. doi:10.1002/14651858.CD011286.pub2. PMID 27727432.
- Cheng et al. Network meta-analysis including SAMe for depression. Psychol Med. 2025;55:e134. PMID 40314175. (Full citation not recorded in our 20 Oct review.)
- Statistics Canada. The Daily, 22 Sep 2023: Mental Health and Access to Care Survey, 2022. https://www150.statcan.gc.ca/n1/daily-quotidien/230922/dq230922b-eng.htm
- Halladay J, Ji C, Georgiades K, Slade T, Chapman C, Sunderland M, et al. Co-occurring mood, anxiety, and substance use disorders in Canada 2022: prevalence, patterns, correlates, and changes over time. Psychiatry Res. 2026;365:117370. doi:10.1016/j.psychres.2026.117370. PMID 42603524.
- Noetel M, Sanders T, Gallardo-Gómez D, Taylor P, del Pozo Cruz B, van den Hoek D, et al. Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2024;384:e075847. doi:10.1136/bmj-2023-075847. PMID 38355154.
- Jacka FN, O'Neil A, Opie R, Itsiopoulos C, Cotton S, Mohebbi M, et al. A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial). BMC Med. 2017;15(1):23. doi:10.1186/s12916-017-0791-y. PMID 28137247.
- Stone MB, Yaseen ZS, Miller BJ, Richardville K, Kalaria SN, Kirsch I. Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis. BMJ. 2022;378:e067606. doi:10.1136/bmj-2021-067606. PMID 35918097.
- Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357-66. doi:10.1016/S0140-6736(17)32802-7. PMID 29477251.
Costs marked as estimates are typical Canadian retail or pharmacy prices, before any drug plan. Certainty grades are ours unless the review gave its own.