S-Adenosylmethionine (SAMe) is a naturally-occurring compound found in almost every tissue and fluid in the body. It is involved in many important processes. SAMe plays a role in the immune system, maintains cell membranes, and helps produce and break down brain chemicals, such as serotonin, melatonin, and dopamine. It works with vitamin B12 and folate (vitamin B9). Being deficient in either vitamin B12 or folate may reduce levels of SAMe in your body.
Several studies show that SAMe helps relieve the pain of osteoarthritis. Other studies suggest that SAMe may help treat depression. Researchers have also examined SAMe's use in the treatment of fibromyalgia and liver disease with mixed results. Many of the early studies used SAMe given intravenously or as an injection. Only recently have researchers been able to look at the effects of SAMe taken by mouth.Depression
Some research suggests that SAMe is more effective than placebo in treating mild-to-moderate depression and is just as effective as antidepressant medications without the side effects (headaches, sleeplessness, and sexual dysfunction). In addition, antidepressants tend to take 6 to 8 weeks to begin working, while SAMe seems to begin more quickly. Researchers are not sure how SAMe works to relieve depression. But they speculate it might increase the amount of serotonin in the brain just as some antidepressants do.
Many studies have examined injectable forms of SAMe, not oral supplements. More research is needed to determine whether SAMe works for depression. Because serious depression is a dangerous illness, you should seek help from your doctor before taking SAMe or any supplement.Osteoarthritis
A number of well-designed studies show that SAMe may reduce pain and inflammation in the joints, and researchers think it may promote cartilage repair. In several short-term studies (ranging from 4 to 12 weeks), SAMe supplements were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen and naproxen) in adults with knee, hip, or spine osteoarthritis, in lessening morning stiffness, reducing pain and swelling, improving range of motion, and increasing walking pace. Several studies also suggest that SAMe has fewer side effects than NSAIDs. Another study compared SAMe to celecoxib (Celebrex), a type of NSAID called a COX-2 inhibitor, and found that over time SAMe was as effective as celecoxib in relieving pain. Other studies show no differences in pain relief or tolerability between treatment with SAMe or habumetone over 8 weeks in people with knee osteoporosis.Fibromyalgia
SAMe can be effective in reducing symptoms of fibromyalgia, including pain, fatigue, morning stiffness, and depressed mood. But most studies used an injectable form of SAMe. Among studies that examined doses of SAMe by mouth, some found it was effective at reducing these symptoms while others found no benefit.Liver disease
People with liver disease often cannot synthesize SAMe in their bodies. Preliminary studies suggest that taking SAMe may help treat chronic liver disease caused by medications or alcoholism. A study of 123 men and women with alcoholic liver cirrhosis (liver failure) found that SAMe treatment for 2 years improved survival rates and delayed the need for liver transplants better than placebo. Other studies show that SAMe may help normalize levels of liver enzymes in people with liver disease. Studies in mice show that SAMe protects against and can also reverse liver damage. However, these studies have been small and of short duration. Larger and longer studies are needed to confirm these findings.Dementia
Preliminary evidence suggests that SAMe may improve cognitive symptoms, such as the ability to recall information and remember words. Researchers suspect SAMe acts on regions of the brain that regulate gene expression of amyloid proteins, one of the hallmarks of Alzheimer disease.Other
Some studies suggest SAMe can effectively inhibit cancer tumor cells. Other studies suggest that taking the drug levodopa (L-dopa) for Parkinson disease may lower the levels of SAMe in the body, which may contribute to depression and increase the side effects of L-dopa. However, researchers have also found evidence that taking SAMe may make L-dopa less effective. If you have Parkinson disease, do not take SAMe without talking to your doctor first.
SAMe is not found in food. It is produced by the body from the amino acid methionine and ATP which serves as the major energy source for cells throughout the body.
SAMe is available in tablets or capsules, which are more stable and may be more dependable in terms of the amount of SAMe in the pill. They should be stored in a cool, dry place, but not refrigerated. Tablets should be kept in the blister pack until you take them.
How to Take It
Starting with a low dose (for example, 200 mg per day) and increasing slowly helps avoid stomach upset.
It is important to note that many of the studies of SAMe have tested injectable, not oral, forms. It is not as clear whether taking SAMe orally is as reliable or effective. Small studies suggest that oral supplementation with SAMe is not well absorbed by the body. Clinicians recommend taking oral SAMe with vitamin B12, folic acid, methionine, and trimethylglycine to enhance absorption.
SAMe should never be given to a child without your doctor's supervision.
Recommended doses of SAMe vary depending on the health condition being treated. The following list gives information on the dosages used in studies for each condition:
- Depression. 800 to 1,600 mg of SAMe per day, in 2 divided doses (morning and afternoon).
- Osteoarthritis. 600 to 1,200 mg per day in 2 to 3 divided doses.
- Fibromyalgia. A dosage of 400 mg, 2 times per day for 6 weeks.
- Alcoholic liver disease. 600 to 1,200 mg per day by mouth in divided doses for 6 months enhances liver function. For liver disease, a qualified health care provider should supervise administration of SAMe.
Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.
Side effects may include dry mouth, nausea, gas, diarrhea, headache, anxiety, a feeling of elation, restlessness, and insomnia. Sweating, dizziness, and palpitations have also been reported. For this reason, you should not take SAMe at night.
Large doses of SAMe may cause mania (abnormally elevated mood). Start at a low dose and gradually increase it. DO NOT exceed recommended doses.
Pregnant and breastfeeding women should not take SAMe.
People with bipolar disorder (manic depression) should not take SAMe since it may worsen manic episodes.
SAMe should not be combined with other antidepressants without first consulting your doctor.
People taking SAMe may want to take a multivitamin that contains folic acid and vitamins B12 and B6.
If you are being treated with any of the following medications, you should not use SAMe without first talking to your health care provider.
Taking SAMe at the same time as these drugs may increase the risk of serotonin syndrome (a potentially dangerous condition caused by having too much serotonin in your body):
- Dextromethorphan (Robitussin DM, other cough syrups)
- Meperidine (Demerol)
- Pentazocine (Talwin)
- Tramadol (Ultram)
SAMe may interact with antidepressant medications, increasing the potential for side effects including headache, irregular or accelerated heart rate, anxiety, and restlessness, as well as the potential fatal condition called Serotonin Syndrome, mentioned above. Some experts theorize that taking SAMe increases the levels of serotonin in the brain, and many antidepressants do the same. The concern is that combining the two may increase serotonin to dangerous levels. Talk to your doctor before using SAMe if you are taking any medications for depression or anxiety.
SAMe may reduce the effectiveness of this medication for Parkinson disease.
Medications for diabetes
SAMe may reduce levels of blood sugar and may strengthen the effect of diabetes medications, which increases the risk of hypoglycemia (low blood sugar).
Alpert J E, Papakostas G, Mischoulon D, Worthington J J, Petersen T, Mahal Y, et al. S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine. J Clin Psychopharmacol. 2004;24(6):661-4.
Bottiglieri T. Folate, Vitamin B12, and S-Adenosylmethionine. Psychiatric Clinics of North America. W.B. Saunders Company. 2013:36(1).
Chavez M. SAMe: S-Adenosylmethionine. Am J Health Syst Pharm. 2000;57(2):119-23.
Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L- methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr. 2002;76(5):1172S-6S.
Dey A, Caro AA, Cederbaum AL. S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G91-103.
Fetrow CW, Avila JR. Efficacy of the dietary supplement S-adenosyl-L-methionine. Ann Pharmacother. 2001;35(11):1414-25.
Kim J, Lee EY, Koh EM, et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis; an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther. 2009;31(12):2860-72.
Li T, Yu G, Guo T, et al. The plasma S-adenosylmethionine level is associated with the severity of hepatitis B-related liver disease. Medicine. 2015;94(4):e489.
Lieber CS. Hepatic, metabolic, and nutritional disorders of alcoholism: from pathogenesis to therapy. Crit Rev Clin Lab Sci. 2000;37(6):551-84.
Luo J, Li YN, Wang F, Zhang WM, Geng X. S-adenosylmethionine inhibits the growth of cancer cells by reversing the hypomethylation status of c-myc and H-ras in human gastric cancer and colon cancer. Int J Biol Sci. 2010;6(7):784-95.
Mato JM, Lu SC. Role of S-adenosyl-L-methionine in liver health and injury. Hepatology. 2007;45(5):1306-12.
Mischoulon D, Alpert J, Arning E, et al. Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder. J Clin Psychiatry. 2012;73(6):843-8.
Morelli V, Zoorob RJ. Alternative therapies: Part 1. Depression, diabetes, obesity. Am Fam Phys. 2000;62(5):1051-60.
Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. BMC Musculoskelet Disord. 2004 February 26;5:6.
Rakel, D. Rakel Integrative Medicine. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012.
Ringdahl E, Pandit S. Treatment of knee osteoarthritis. Am Fam Physician. 2011;83(11):1287-92.
Stern. Massachusetts General Hospital Comprehensive Clinical Psychiatry. 1st ed. Philadelphia, PA: Elsevier Mosby; 2008.
Review Date: 11/6/2015
Reviewed By: Steven D. Ehrlich, NMD, Solutions Acupuncture, a private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.