Does SAMe work?
Not proven for anything yet. SAMe is a chemical your body makes. It’s been tested for depression, joint pain and liver disease. And in one group, it may push mood too high.
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What is SAMe, and does it work?
SAMe is short for S-adenosyl methionine. Your body makes it from methionine, a building block of protein found in food.
It’s been studied most for depression, joint pain from osteoarthritis and liver disease. For all three, the US centre for complementary health (NCCIH) says research has not conclusively shown it helps.
| Use | What trials found | Good to know |
|---|---|---|
| Depression | Many trials looked hopeful. Most were small, lasted a few weeks and weren’t top quality. | It may make high moods worse in bipolar disorder. |
| Joint pain (osteoarthritis) | Eased pain about as well as anti-inflammatory painkillers. Not consistently better than a dummy pill. | Cochrane says don’t use it routinely yet. |
| Liver disease | Benefit in people not established. | Results for an itchy liver problem in pregnancy conflict. |
| Migraine, fibromyalgia, Alzheimer’s and others | Not enough evidence to say. | It didn’t help people quit smoking. |
Sources: NCCIH; Cochrane 2009
Lots of short, small trials are like lots of quick test drives. They hint at how a car handles. They can’t tell you how it copes over years, or whether it suits you.
So SAMe may help some people. No one can promise it will help you. Read who should not take it before you buy.
Does SAMe help depression?
Maybe, but the proof is weak. A 2016 Cochrane review (a group that pools the best trials) pooled 8 trials in 934 adults with major depression. It found no high quality evidence and could not draw firm conclusions.
| SAMe compared with | Trials (people) | What Cochrane found |
|---|---|---|
| A dummy pill | 2 (142) | No clear difference. Very low quality evidence. |
| Imipramine, an older antidepressant | 4 (619) | A similar effect. Low quality evidence. |
| Escitalopram, a common antidepressant | 1 (129) | Little difference. Low quality evidence. |
| A dummy pill, both added to an antidepressant | 1 (73) | SAMe did better. Low quality evidence. |
Source: Cochrane 2016
Some depression trials gave SAMe as an injection, not a tablet. So the results may not match a pill from a shop.
A bigger 2024 review pooled 23 trials and 2,183 people. It found SAMe on its own may help moderately, compared with a dummy pill. Added to an antidepressant, it made no clear difference.
Think you may be depressed? The NHS says see a GP, and don’t delay. See signs of depression, blood tests for low mood and saffron for low mood.
Does SAMe help joint pain?
Only a little, if at all. A Cochrane review looked at 4 trials in 656 people with knee or hip osteoarthritis. The trials were poor quality.
On a 0 to 10 pain line, people on SAMe ended up on average about 0.4 lower than people on a dummy pill. That’s like a 6 becoming a 5.6.
Even that small gap may be chance. It made no clear difference to how well people could move.
The reviewers said routine use of SAMe should not be advised until bigger trials are done.
The NHS calls exercise one of the most important treatments for osteoarthritis, along with a healthy weight. Ask your GP or a physio for a plan. Compare other options in our joint supplements guide.
Who should not take SAMe?
That group is people with bipolar disorder. NCCIH says they should only take SAMe for low mood with a doctor overseeing it, as it may worsen mania (a very high mood).
In the Cochrane trials, there were 2 reports of mania or a milder high among 441 people taking SAMe.
| If you | What NCCIH says |
|---|---|
| Have bipolar disorder | Only take it for low mood with a doctor overseeing it. It may worsen mania. |
| Take an antidepressant, St John’s wort or L-tryptophan | SAMe might interact with things that raise serotonin, a brain chemical. |
| Take levodopa for Parkinson’s | SAMe may make levodopa work less well. |
| Are pregnant or breastfeeding | Safety in pregnancy has not been established. Talk to your doctor first. |
| Have a weak immune system, such as from HIV | A theoretical concern: SAMe helps a germ that can infect them to grow. |
| Want to give it to a child | Talk to the child’s doctor first. |
Source: NCCIH
Signs of a high mood include feeling very excited or very irritable, racing thoughts, talking fast and not needing much sleep.
Never stop or change a prescribed medicine without your prescriber. Take a medicine or another supplement? NCCIH says talk to a health professional before SAMe.
How much SAMe do people take?
Depression trials used 200 to 3,200 mg a day, for 2 to 12 weeks. That’s what was tested, not a safe or proven dose.
Side effects are uncommon, and usually minor, such as feeling sick or an upset stomach. Little is known about long-term safety, because most people in trials took it for a short time. In one 2-year liver study, no serious side effects were reported.
Before you try SAMe
- Think you may be depressed? See a GP first. Don’t use SAMe to put off seeing a doctor.
- Take an antidepressant, St John’s wort or L-tryptophan? Talk to your GP or pharmacist before SAMe.
- Have bipolar disorder? Only take SAMe for low mood with a doctor overseeing it.
- Take levodopa for Parkinson’s? Ask your doctor first, as SAMe may make it work less well.
- Pregnant or breastfeeding? Talk to your doctor or midwife first.
- Tell any doctor treating you that you take SAMe.
Comparing mood supplements? See supplements for stress and anxiety. For liver products, see do liver supplements work?
When to speak to a GP
Book an appointment if:
- You think you may be depressed. The NHS says it’s best not to delay.
- You take an antidepressant, levodopa or another medicine and want to try SAMe.
- You have bipolar disorder and want to try SAMe for low mood.
- Your mood feels very high: very excited or irritable, racing thoughts, or not needing much sleep.
- You have thoughts of ending your life. Call a GP for an emergency appointment, call NHS 111, or call Samaritans on 116 123.
If you have seriously harmed yourself, or feel you may be about to, call 999 or go to A&E.