Is SAM-e safe to use or can it cause adverse effects? According to research and user reviews, SAM-e is generally well tolerated, but some people may experience gastrointestinal distress, nausea, headache or nervousness at high doses.
SAM-e, which stands for “S-adenosyl-L-methionine,” is a naturally-occurring molecule that was discovered in the early 1950s. This molecule is produced in the human body from a reaction between methionine and adenosine triphosphate.
According to the Natural Medicines Database, SMA-e is used for a variety of purposes, including seizures, multiple sclerosis, attention deficit-hyperactivity disorder, premenstrual syndrome, liver disease, bursitis, depression, anxiety and more. At this time, the United States Food and Drug Administration has not approved SAM-e for the treatment of any of these conditions.
However, studies have found very few serious side effects associated with SAM-e, and it is considered likely safe when used appropriately. Nonetheless, because SAM-e side effects and drug interactions may occur, consumers are encouraged to be cautious when using supplements for any purpose.



- Enhances mood & promotes cognitive health
- Essentual for dopamine, serotonin & norepinephrine metabolism
- Promotes joint comfort & liver health
Effects of SAM-e
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S-adenosyl-L-methionine has a number of important functions in the body. It is a major methyl donor, involved in the synthesis of neurotransmitters like norepinephrine, dopamine, and serotonin.
SAM-e also plays a role in trans-sulfuration reactions, which are necessary for the production of cysteine and glutathione. As a result, it is purported to promote liver health and detoxification.
As a dietary supplement, SAM-e tablets are most commonly taken to alleviate symptoms of depression and to maintain healthy joints.
The American Psychiatric Association lists SAM-e as an alternative treatment for patients with major depressive disorder. The Natural Medicines Database also rates SAM-e as Likely Effective for depression and osteoarthritis.
According to the Natural Medicines Database, SAM-e may have several effects on the body. In research studies, some of the effects of SAM-e that have been shown include:
- Neuronal effects – SAM-e may reduce the activity of glutathione S-transferase.
- Cardiovascular effects – Studies have shown that SAM-e may dilate the blood vessels and decrease blood pressure.
- Antioxidant effects – Research indicates that SAM-e may act as an antioxidant.
- Anti-inflammatory properties – Several animal studies have shown that SAM-e may reduce inflammation.
- Analgesic properties – Animal studies have also shown that SAM-e may reduce pain sensations.
- Antidepressant effects – Research has shown that SAM-e may act as an antidepressant, although the exact mechanism is not known.
Is SAM-e Safe?
The Natural Medicines Database reports that SAM-e is likely safe when used intravenously, intramuscularly or orally, as long as the supplement is also used appropriately.
The supplement is possibly safe for children, as well as for women in the third trimester of pregnancy, when used under medical supervision.
However, information regarding the safety of SAM-e for these populations is limited. It is not yet known whether SAM-e is safe for women who are breastfeeding.
The most common gastrointestinal problem reported in research studies in nausea. People with bipolar disorder may also experience anxiety and/or hypomania while taking this supplement.
According to the Mayo Clinic, some of the other possible side effects of SAM-e include:
- Weight gain or loss
- Low blood pressure
- Low blood sugar
- Vein inflammation
- Sleep problems
- Shortness of breath
- Shakiness
- Increased serotonin levels
- Restlessness
- Night sweats
- Nervousness
- Low energy
- Increased thirst
- Dry mouth
- Hair loss
- Irritability
- Aggression
Side Effects of Too Much SAM-e
Research indicates that SAM-e overdose is unlikely. In the many clinical trials that have been conducted, no reports of serious toxicity have been made. These trials involved over 22,000 individuals who took varying amounts of SAM-e for a few days to as long as two years.
However, individuals may still experience enhanced SAM-e supplement side effects if they take too much at one time. While some of these side effects, such as high serotonin levels, may be dangerous, others are merely bothersome.
Taking SAM-e Safely
Even though SAM-e overdose and other serious adverse effects seem unlikely, it is still important to use this supplement cautiously. In addition, using this supplement properly will help to reduce the risk of SAM-e side effects.
SAM-e can be taken intravenously, in the form of an injection or as an oral supplement. Most over-the-counter preparations of SAM-e are oral.
Regardless of the preparation you choose, you should always follow the instructions on the label when taking SAM-e.
SAM-e products may interact with some medications you are already taking, including demerol, levodopa, dextromethorphan, tramadol, pentazocine, monoamine oxidase inhibitors and some antidepressant drugs, such as SSRIs. Avoid taking SAM-e with these medications unless otherwise directed by a doctor.
You should also avoid taking SAM-e in combination with any other supplement that raises serotonin levels in the body. In serious cases, this could result in a condition known as Serotonin Syndrome where levels of this neurotransmitter become dangerously high.
People with Parkinson’s disease or bipolar disorder may experience enhanced SAM-e side effects. Check with your doctor before using this supplement.
Recommended SAM-e Dosages
Taking the proper dosage of SAM-e reduces the risk of SAM-e side effects. Because the FDA has not approved SAM-e for the treatment of any conditions, standardized dosing information is not currently available.
However, according to the Natural Medicines Database, the following dosages have been well tolerated in past clinical trials.
- Liver disease – 400 to 1200 mg daily for up to 24 weeks.
- Fibromyalgia – 400 mg twice daily.
- Cholestasis – 1600 mg daily for up to two weeks.
- ADHD – Up to 2400 mg in divided doses daily for up to four weeks.
- Smoking cessation – 400 to 800 mg twice daily for eight weeks.
- Sexual function – Up to 1600 mg in divided doses daily for six weeks.
- Schizophrenia – Up to 80 mg daily in divided doses for seven weeks.
- Osteoarthritis – 600 to 1200 mg in divided doses daily for up to 84 days.
- Neurologic disorders – Up to 800 mg daily.
- Depression – 800 to 1600 mg daily for six weeks.
Many individuals experience gastrointestinal side effects related to the digestion of oral SAM-e supplements. If you are regularly experiencing stomach pain, nausea or diarrhea following the use of a SAM-e supplement, consider switching to a different supplement brand or taking this supplement with food.
- SAMe. Mayo Clinic. Cited June 6, 2016.
- SAM-e. WebMD. Cited June 6, 2016.
- S-adenosylmethionine (SAMe). Drugs.com. Cited June 6, 2016.
- Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl. 1994;154:7-14.
- Young S. Are SAMe and 5-HTP safe and effective treatments for depression? J Psychiatry Neurosci. 2003.
Article last updated on: March 12th, 2018 by Nootriment
2 Comments
can i safely take sam-e and korean ginsen ?
SAMe had a horrible effect on me. I have MTHFR deficiency. I’m not sure if MTHFR had anything to do with my reaction. 200mg doctor’s best – just 1 pill – i became extremely agitated and aggressively suicidal that day of taking it. I have never felt such an effect from a supplement ever before.
I locked myself in one room all day and night because there was no knowing what i would have been inclined to do as i felt like throwing myself under a bus etc – it really did induce ‘violent suicide ideation’ in me which i never experienced before.
Never took it again – never experienced those symptoms since.