SAMe

What SAMe is

SAMe, short for S-adenosyl-L-methionine, is a chemical that is found naturally in the body. Your body makes it from methionine, an amino acid that comes from food. It was first discovered in the 1950s, and a synthetic version is sold in the United States as a dietary supplement, most often for mood, joint health, and the liver.

This page is general education about SAMe as a supplement. It is not a recommendation that you should or should not take it; that is a conversation to have with your clinician about your own situation.

What it is used for

The use people ask about most in a psychiatric setting is depression, and it is honest to say the evidence that oral SAMe helps depression is not conclusive. Many studies have been done, but a lot of them were brief, were small, or used an injected form rather than the capsules sold over the counter, which makes it hard to draw firm conclusions about the supplement.

Outside of mood, SAMe has been studied for osteoarthritis, where the results are mixed, and for liver conditions, where a benefit has not been established. For a number of other conditions, including fibromyalgia, migraine, schizophrenia, Alzheimer’s disease, ADHD, and quitting smoking, there is not enough evidence to say it helps.

In a psychiatric setting, SAMe is something we might consider as an add-on for some people, not as a stand-in for the treatment that actually addresses what you are working on, and with real caution if you have bipolar disorder. Whether it makes sense for you depends on your history, what else you take, and what you are hoping it will do. That is decided case by case, and it is reasonable to bring it up alongside guides like depression and bipolar.

How it might work

The honest answer is that the way SAMe might lift mood is not well worked out. What researchers have noticed is that unusual levels of SAMe in the body have been reported in both liver disease and depression, which is part of why it drew interest in the first place. That makes a role plausible, but plausible is not the same as proven, and how much it helps a given person, if at all, is individual.

How people take it

There is no single right way to take SAMe, and the details are worth talking over with your clinician or pharmacist rather than copying a number from a label. A few general points apply:

• The form studied is not always the form sold. Much of the more encouraging research used an injected form, while what you buy is an oral supplement, so do not assume the bottle matches the studies.
• It is not a set-and-forget supplement. Because of the interactions below, especially with antidepressants and in bipolar disorder, it is one to use under guidance rather than on your own.
• More is not better. Stay with what you and your clinician agree on rather than stacking products.

What to expect

This varies from person to person. If SAMe helps your mood at all, it works as an add-on alongside the rest of your plan rather than as something dramatic on its own. Give any honest trial a fair amount of time and pay attention to how you actually feel. If you notice nothing after a reasonable stretch, that is useful information, not a failure, and it is fine to stop and look at other options together. As always, this is case by case.

Possible side effects

Side effects of SAMe are uncommon, and when they happen they are usually minor. The long-term safety of taking it is not well known. The lists below are possibilities, not certainties.

Possible more common side effects:

• Nausea
• Digestive upset such as stomach discomfort or diarrhea

Less common, but concerning signs that could need urgent care:

• Signs of an allergic reaction: rash, hives, or swelling of the face, lips, tongue, or throat
• Signs of too much serotonin, which is a risk if SAMe is combined with an antidepressant or another serotonin-raising product: agitation or restlessness, a fast heartbeat, a high temperature, sweating, shivering, stiff or twitching muscles, or confusion

For any of these, use the help options at the bottom of this page: call 911 or go to the nearest emergency department for a medical emergency or severe reaction, or call or text 988 for a mental health crisis.

Interactions and safety

This is the part most worth reading. SAMe carries a few specific cautions that matter in psychiatry:

• Bipolar disorder. SAMe may worsen symptoms of mania, so people with bipolar disorder should not use it for their depressive symptoms except under a clinician’s supervision. This is the caution to take most seriously.
• Other serotonin-raising medicines and supplements. SAMe might interact with things that increase serotonin, including antidepressants, the supplement L-tryptophan, and St. John’s wort. Combining them can raise serotonin too high, which is uncommon but can be serious, so this combination needs to be checked rather than assumed safe.
• Parkinson’s disease. SAMe may reduce the effect of levodopa, a medicine used to treat Parkinson’s disease.
• Pregnancy and breastfeeding. The safety of SAMe during pregnancy or while breastfeeding has not been established, so that is a conversation to have first.

The simplest safeguard is to tell your clinician and pharmacist everything you take, including supplements and over-the-counter products. Knowing the full picture lets us catch a problem before it happens and decide together whether SAMe fits your plan.

When to contact your clinician

For routine questions, mild side effects, or whether SAMe fits with the rest of your plan, send a message through the patient portal or bring it to your next visit. These are part of your ongoing care and are answered in the normal course of a few business days, so they are best for things that are not urgent.

If something feels urgent, you do not need to wait for a reply. The fastest way to get care is 911 or the nearest emergency department for a medical emergency, a severe reaction, or the signs of too much serotonin listed above, or 988 any time for a mental health crisis or thoughts of self-harm.

Questions to ask your clinician

• Is SAMe a reasonable thing to try in my situation, and what would we be hoping it does?
• I have bipolar disorder; is there any safe way for me to use it?
• Does it interact with my antidepressant or any other medicine I take?
• What symptoms would mean I should stop it and get help right away?
• How long should I try it before we decide whether it is worth continuing?