The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.


Avoid if allergic or sensitive to S-adenosyl-L-methionine (SAMe). There have been reports of dizziness, heart palpitations, memory and concentration problems, nausea, and skin flushing and redness.

Side Effects and Warnings

SAMe has been found to be generally well tolerated. Common side effects include anxiety and skin rashes. Some studies report that significant side effects related to SAMe given through tube feeding are lacking in general.

SAMe is likely safe when taken by mouth in doses of 400-600 milligrams daily for up to two years; when taken by mouth at doses of 800-1,600 milligrams daily for up to 42 days; and when given through IV in doses up to 800 milligrams daily for up to 21 days.

SAMe is possibly safe when used during the third trimester of pregnancy in doses of 800 milligrams given through IV daily for short periods of time (less than four weeks). Use cautiously in pregnant women. SAMe should only be used in pregnancy if the benefits clearly outweigh the risks. More safety information is needed on the use of SAMe during pregnancy other than the third trimester, during breastfeeding, and in children and the elderly.

SAMe may lower blood sugar levels. Caution is advised in people with diabetes or low blood sugar and in those taking drugs, herbs, or supplements that affect blood sugar. Blood sugar levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

SAMe may affect blood pressure. Caution is advised in people with high blood pressure or those taking drugs or herbs and supplements that affect blood pressure.

Use cautiously in people who have anxiety disorders, bipolar disorder, and depression.

Avoid if allergic or sensitive to SAMe. There have been reports of dizziness, heart palpitations, memory and concentration problems, nausea, and skin flushing and redness.

Avoid in people who have bipolar disorder. SAMe has been linked to mood changes in people with and without a history of bipolar disorder.

SAMe may also cause abscess (buildup of pus) at the injection site, abnormal heart rhythm, agitation, aggression, anorexia, bloating, bloody stool, blurry vision, changes in urination, changes in weight, congestion, constipation, a crawling feeling on the skin, decreased appetite, diarrhea, difficulty breathing, drowsiness, dry mouth, fatigue, a feeling of weakness, gas, hair loss, headache, heartburn, high levels of liver enzymes, hives, increased saliva, increased suicide risk, increased sweating, increased thirst, irritability, itchy ear, jitteriness, low energy, nervousness, night sweats, numbness or pain at injection site, queasiness, restlessness, serotonin syndrome (drug reaction), shakiness, shortness of breath, skin itching, sleep problems, soft stools, stomach pain, vein inflammation, and vomiting.

Pregnancy and Breastfeeding

There is a lack of scientific evidence on the use of SAMe during the first and second trimesters of pregnancy or during breastfeeding. SAMe has been used in the third trimester for the treatment of bile flow problems, with a lack of side effects in mothers or babies. However, all studies were short-term (less than four weeks). Information on long-term safety is still needed.

This evidence-based monograph was prepared by The Natural Standard Research Collaboration