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A Hard-Working Molecule that May Help Ease Pain & Brighten Mood

  [ 111 votes ]   [ 2 Comments ]
By Karen Lee Richards* • • December 23, 2010

A Hard-Working Molecule that May Help Ease Pain & Brighten Mood

Clinical trials have shown SAM-e to be comparable to prescription antidepressants for depression and as effective as NSAIDs for osteoarthritis. But, as SAM-e supports the body’s natural mood and inflammation modulating functions, it doesn't have all the negative side effects associated with those drugs.

SAM-e (S-adenosyl methionine) was first discovered in Italy in 1952 by G.L. Cantoni. An Italian firm developed it as a pharmaceutical in the early 1970s but it wasn't brought to America until 1999. Although SAME-e has been approved as a drug in at least 14 countries, it is sold as a dietary supplement in the U.S.

Unlike most supplements, SAM-e is not an herb or a vitamin. It is a molecule naturally produced in all living cells. It is formed when methionine reacts with adenosine triphosphate (ATP). SAM-e plays an essential role in the biological process called methylation, which promotes healthy cells, regulates the expression of genes, and helps with the synthesis of various hormones and neurotransmitters, including serotonin, melatonin, dopamine and adrenaline.     

Thousands of research studies have been conducted all around the world on SAM-e, investigating its supportive effect in those with many different diseases and conditions, including depression, osteoarthritis, chronic liver disease, and fibromyalgia.  

Significant Improvement Seen in Major Depression with SAM-e

Because 29% to 46% of patients with major depressive disorder have no response or only a partial response to pharmaceutical antidepressants, SAM-e has been studied extensively as a possible option for those with major depression. The results are three decades worth of impressive literature suggesting the mood supporting efficacy of SAM-e.(1)

•  In an open trial, 20 outpatients with major depression were given SAM-e, beginning with 400 mg/day and gradually increasing to 1600 mg/day by day 12.  Nine of the participants had a prior history of not responding to traditional antidepressant treatment. All 20 patients showed significant improvement with SAM-e, including seven of the non-treatment resistant and two of the treatment-resistant patients who experienced a full antidepressant response.(2)

•  A double-blind randomized trial compared the efficacy of supplemental SAM-e with the antidepressant desipramine in 26 patients with major depression. At the end of four weeks, 62% of those given SAM-e had significant improvement compared to 50% of those taking desipramine.(3)

Impressive Results in Osteoarthritis Patients Using SAM-e

An estimated 27 million people have osteoarthritis, making it the most common form of arthritis. The pharmaceutical treatment for osteoarthritis is non-steroidal anti-inflammatory drugs (NSAIDs) – either over-the-counter medications like aspirin, ibuprofen and naproxen, or prescription medications like Celebrex, Relafen, Daypro, etc. While NSAIDs can be effective pain relievers, their regular use can result in some devastating side effects such as ulcers and other gastrointestinal problems, increased blood pressure and kidney damage.

If that weren't enough, in the long run NSAIDs may actually worsen joint problems because they slow the production of collagen and proteoglycans, which help to make cartilage an effective shock absorber.  

By contrast, SAM-e seems to support an anti-inflammatory response equivalent to the effect of NSAIDs but without the toxic side effects. SAM-e does not harm the digestive tract, nor does it contribute to the breakdown of cartilage. Instead, one study shows it may actually help the body restore damaged cartilage.  

•  A meta-analysis of 11 clinical trials involving 1,142 patients was done looking at SAM-e for support of osteoarthritis symptom relief. The study authors concluded, “SAM-e appears to be as effective as NSAIDs in reducing pain and improving functional limitation in patients with OA without the adverse effects often associated with NSAID therapies.”(4)

•  A randomized double-blind cross-over study of 56 patients diagnosed with osteoarthritis of the knee compared SAM-e (1200 mg) with the prescription drug celecoxib (Celebrex 200 mg). The results showed no significant difference between the two – both patient cohorts demonstrated significant improvements in pain and joint function – leading the researchers to conclude that SAM-e was as effective as celecoxib in managing the symptoms of knee osteoarthritis.(5)

•  In a German study, 21 patients with finger osteoarthritis were given SAM-e for three months. MRI scans done on their hands both before and after the treatment period revealed significant structural improvement in the cartilage.(6)

SAM-e Promotes Liver Health

The liver is unique because it is the only internal human organ capable of regenerating itself. As little as 25% of a liver can regenerate into a whole liver again, and SAM-e plays a leading role in that regeneration. The third highest amount of SAM-e in the body is found in the liver. Only the adrenal and pineal glands contain more.  

SAM-e is thought to be beneficial for those with liver disease by acting as a precursor of antioxidant glutathione; repairing the mitochondrial glutathione transport system; inhibiting the toxic effects of proinflammatory cytokines; and increasing DNA methylation.(7)

There are nearly a thousand published studies documenting SAM-e's ability to support prevention and improvement in liver disease.  

•  In a study of hepatic glutathione levels in patients with liver disease, participants were divided into four groups. Nine patients with alcoholic liver disease were given SAM-e; seven patients with non-alcoholic liver disease were given SAM-e; 8 patients with alcoholic liver disease were given a placebo; and 15 normal subjects served as a control group. Prior to beginning treatment, all patients had very low hepatic glutathione levels compared to controls. Following treatment, patients receiving the SAM-e had a significant increase in their hepatic glutathione levels compared with both the placebo-treated group and controls.(8)

•  When SAM-e was given to 62 patients with alcoholic cirrhosis in a clinical trial, they were significantly less likely to die or require a liver transplant within the next two years, compared with 61 patients who had received a placebo.(9)

SAM-e Is Promising for Fibromyalgia Patients

Although SAM-e has not been studied yet as much for support of fibromyalgia patients as for those with some other illnesses, the results thus far are encouraging. In one double-blind study of 44 patients with primary fibromyalgia, improvements were seen in the areas of clinical disease activity, pain, fatigue, morning stiffness and mood.(10)

Facts About SAM-e You Need to Know

Dosage: Recommended therapeutic doses usually range between 400 – 1600 mg a day, although some individuals may require higher doses. Studies suggest that 400 mg per day may be adequate for osteoarthritis patients, while up to 1600 mg a day is often needed for mood support. The usual dose for those with liver disorders has been 1600 mg a day. (As with any addition to your health support regimen, supplementation with SAM-e should be considered only with the approval of your professional healthcare team.)

How to Take SAM-e: SAM-e works best when taken on an empty stomach. Because it is absorbed mainly in the intestine, enteric-coated tablets that allow it to pass through the stomach intact are preferable. Leave tablets in their foil or foil blister packs until you are ready to take them in order to maintain their stability.

Adverse Effects: There seem to be few adverse effects with SAM-e, even at high doses. Occasionally mild gastrointestinal distress has been reported. Since SAM-e can sometimes lead to insomnia, it is usually best to take it early in the morning. Because it plays a role in mood support, SAM-e may trigger manic episodes in people with bipolar disorder.   

Contraindications: While there are no confirmed drug interactions with SAM-e, individuals using prescribed medications such as antidepressants, including serotonin re-uptake Inhibitors and MAO inhibitors, should consult a physician before using. Individuals with Parkinson's disease, bipolar disorder or manic depression should not take SAM-e.

In Summary

More than three decades of solid research support the use of SAM-e to help promote natural improvement in symptoms of osteoarthritis, depression and liver disease. Ongoing research is also revealing its promising potential for those with a number of other conditions.  


1.  Williams AL, et al. “S-adenosylmethionine (SAMe) as treatment for depression: a systematic review.” Clin Invest Med. 2005 Jun;28(3):132-9. 

2.  Rosenbaum JF, et al. “The antidepressant potential of oral S-adenosyl-l-methionine.” Acta Psychiatr Scand. 1990 May;81(5):432-6. 

3.  Bell KM, et al. “S-adenosylmethionine blood levels in major depression: changes with drug treatment.” Acta Neurol Scand Suppl. 1994;154:15-8. 

4.  Soeken KL, et al. “Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis.” J Fam Pract. 2002 May;51(5):425-30. 

5.  Wadie IN, et al. “S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial.” BMC Musculoskelet Disord. 2004;5:6. 

6.  Konig H, et al. [Magnetic resonance tomography of finger polyarthritis: morphology and cartilage signals after ademetionine therapy] Aktuelle Radiol. 1995 Jan;5(1):36-40. 

7.  Purohit V, Russo D. “Role of S-adenosyl-L-methionine in the treatment of alcoholic liver disease: Introduction and summary of the symposium.” Alcohol. 2002 Jul;27(3):151-4. 

8.  Vendemiale G, et al. “Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease.” Scand J Gastroenterol. 1989 May;24(4):407-15. 

9.  Mato JM, et al. “S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial.” J Hepatol. 1999 Jun;30(6):1081-9. 

10. Jacobsen S, et al. “Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation.”  Scand J Rheumatol. 1991;20(4):294-302. 

11. Morrison LD, et al. “Brain S-adenosylmethionine levels are severely decreased in Alzheimer's disease.” J Neurochem. 1996 Sep;67(3):1328-31. 

12. Tchantchou F, et al. “S-adenosyl methionine: A connection between nutritional and genetic risk factors for neurodegeneration in Alzheimer's disease.” J Nutr Health Aging. 2006 Nov-Dec;10(6):541-4.

* Karen Lee Richards is Lead Expert specializing in Fibromyalgia and ME/CFS, for HealthCentral's ChronicPainConnection ( Karen is co-founder of the National Fibromyalgia Association (NFA) and was Executive Editor of Fibromyalgia AWARE magazine for four years.

Note: This information has not been reviewed by the FDA. It is general and is not meant to diagnose, prevent, treat or cure any condition, illness, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

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Article Comments Post a Comment

research using SAM:e
Posted by: kailew
Mar 17, 2010
Having waited 4 years in pain with back and leg pains, inability to function normally and trying back surgery for a stenosis, I have started with the pain again after the surgery on my spine, I welcome any medication that might allow me to live relatively pain-free and without prescription morphine pills every day. I hope it will be successful in helping many people. To make things worse, depression is almost expected with the severe pain that we have to live with. Good luck with your future endevours to help people.
Reply Reply

research using SAM:e
Posted by: kailew
Mar 17, 2010
Having waited 4 years in pain with back and leg pains, inability to function normally and trying back surgery for a stenosis, I have started with the pain again after the surgery on my spine, I welcome any medication that might allow me to live relatively pain-free and without prescription morphine pills every day. I hope it will be successful in helping many people. To make things worse, depression is almost expected with the severe pain that we have to live with. Good luck with your future endeavours
Reply Reply
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