Subscribe to a FREE Supplement Research Update newsletter. Each month we email a brief abstract of several studies on various supplements and natural medicine topics, including s adenosylmethionine, and their practical interpretation by Ray Sahelian, M.D.

S-Adenosylmethionine has even been tested in depressed postmenopausal women. Researchers from the University of La Sapienza in Rome, Italy gave SAM-e for thirty days to eighty women between the ages of 45 and 59 with depression following either natural menopause or hysterectomy. There was a significantly greater improvement in depressive symptoms in the group treated with SAM-e compared to the placebo group. Side effects were mild and transient.

SAM-e has been found to improve mood in those with Parkinson's disease.

Sam-e, 200 mg,  20 Enteric-Coated Tablets - Source Naturals
S - Adenosyl Methionine • Pharmaceutical Grade, Stabilized
 
This S-Adenosylmethionine product is a stable, bioavailable form of S-adenosyl-L-methionine. These tablets are enteric coated and blister packed to prevent breakdown and inactivation of the ingredients. Dozens of clinical studies have demonstrated that SAMe supports joint comfort, function and mobility in the spine, hips and knees. It is important to the joints because of its critical role in cartilage formation. Studies also show that SAMe helps support a positive outlook. It is able to cross the blood-brain barrier where it affects the synthesis and activation of various proteins, such as neurotransmitters.

S-Adenosylmethionine is present in every living cell in the body. However, levels of SAMe tend to decline with age.   SAM-e 200 is manufactured under low temperature and low humidity and is enteric-coated to ensure a biologically active product.

Click here to purchase Sam-e or to see a complete list of discounted products
Plus: sign up to a free Supplement Research Update newsletter. Twice a month we email a brief abstract of several studies on various supplements and natural medicine topics -- including S-Adenosylmethionine -- and their practical interpretation by Ray Sahelian, M.D.

SAM-e Availability
A major drawback to the use of S-Adenosylmethionine is cost. The retail price of SAM-e is a little less than a dollar per 200 mg pill. The suggested dose of S-Adenosylmethionine in the therapy of depression ranges from 100 to 400 mg a day, although many individuals do well with even less than 100 mg. Since the lowest dose over the counter is 200 mg, one could bite off half or a portion of a tablet.
   Many nutrients work is a similar fashion to S-Adenosylmethionine, particularly other methyl donors such as DMAE, TMG, DMG. In fact, B12 and folate help the body produce SAM-e. Therefore, your dosage of SAM-e should be reduced if you are taking other methyl donors.

S-Adenosylmethionine and Arthritis
S-Adenosylmethionine helps support the incorporation of sulfate groups into proteoglycans which help maintain cartilage and protect joints. Some studies have suggested that S-Adenosylmethionine possesses anti-inflammatory and tissue-healing properties that may help protect the health of joints, and perhaps may lessen pain. It is quite possible that SAM-e may be useful for people with osteoarthritis, although more research needs to be done in this area.

S-Adenosylmethionine Caution and side effects
High doses can lead to anxiety and restlessness, and even insomnia. Long term side effects are currently not known. The effects seem to be additive over several days of use, hence dosage may need to be reduced with time. Some do well on even 50 or 100 mg (one quarter or one half of a 200 mg pill) per day.
   S-Adenosylmethionine may induce a manic swing in those with bipolar disorder.

S-Adenosylmethionine Research Update
S-Adenosylmethionine (SAM-e) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. 
Najm WI, Reinsch S, Hoehler F et al. BMC Musculoskelet Disord. 2004 Feb 26
S-Adenosylmethionine is a dietary supplement used in the management of osteoarthritis (OA) symptoms. Studies evaluating S-Adenosylmethionine in the management of OA have been limited to Non Steroidal Anti-inflammatory Drugs (NSAIDs) for comparison. The present study compares the effectiveness of S-Adenosylmethionine to a cyclooxygenase-2 (COX-2) inhibitor (celecoxib) for pain control, functional improvement and to decrease side effects in people with osteoarthritis of the knee. A randomized double-blind cross-over study, comparing S-Adenosylmethionine (1200 mg) with celecoxib (Celebrex 200 mg) for 16 weeks to reduce pain associated with OA of the knee. Sixty-one adults diagnosed with OA of the knee were enrolled and 56 completed the study. Subjects were tested for pain, functional health, mood status, isometric joint function tests, and side effects. On the first month of Phase 1, celecoxib showed significantly more reduction in pain than S-Adenosylmethionine. By the second month of Phase 1, there was no significant difference between both groups. The duration of treatment and the interaction of duration with type of treatment were statistically significant. On most functional health measures both groups showed a notable improvement from baseline, however no significant difference between S-Adenosylmethionine and celecoxib was observed. Isometric joint function tests appeared to be steadily improving over the entire study period regardless of treatment. S-Adenosylmethionine has a slower onset of action but is as effective as celecoxib in the management of symptoms of knee osteoarthritis. Longer studies are needed to evaluate the long-term effectiveness of SAM-e and the optimal dose to be used.

S-Adenosylmethionine improves depression in patients with Parkinson's disease
Researchers at Beth Israel Medical Center in New York report a study of S-adenosyl-methionine in 13 depressed patients with Parkinson's disease. S-Adenosylmethionine is an amino-like nutrient naturally present in the body and available as a supplement in health food stores. All patients had been previously treated with other antidepressant agents and had no significant benefit or had intolerable side effects. S-Adenosylmethionine was administered in doses of 800 mg per day for a period of 10 weeks. Eleven patients completed the study, and 10 had at least a 50% improvement on the Hamilton Depression Scale. One patient did not improve. Two patients prematurely terminated participation in the study because of increased anxiety. One patient experienced mild nausea, and another two patients developed mild diarrhea, which resolved spontaneously. Although uncontrolled and preliminary, this study suggests that S-Adenosylmethionine is well tolerated and may be an alternative to the antidepressant agents currently used in patients with Parkinson's disease.
   Dr. Sahelian says: S-Adenosylmethionine is a available over the counter in a dose of 200 mg. It is widely used in Europe to treat depression and has also been somewhat helpful in treating alcoholic liver cirrhosis and osteoarthritis. I often start my patients with 100 mg in the morning and build up to a maximum of 200 mg three times a day. High doses can lead to anxiety and restlessness. Prolonged use of SAM-e should only be done under medical supervision.

Emails and comments
Q. Dear Dr Sahelian, I had heart by pass surgery. For my low mood, my Doctor suggested I try Lexapro. Before doing that I did some research on natural products I had heard about. I read your extensive report on 5-HTP and less extensive one on SAM-e. I want to try SAM-e as it appears least side effects. However I have the following question: 1. I have bought 200mg tabs made in Italy. I want to start with may be 50mg. You have mentioned that one can bite off the pill. SAM-e is enteric coated as it is supposed to act in the intestines. If one bites off a pill, will the exposed portion have any negative effect? I am very impressed with you. Very many prominent Doctors make reference about your books and works.
   A. As to the question of biting a piece of the tablet, as long as the same S-Adenosylmethionine piece is used within a few days it should not be a problem. For extra care, that bitten off piece could even be wrapped with a small amount of clear plastic wrap.

I took Sam-e several months ago for about a month or so and found it to be amazing stuff!  I had to quit because of gastro intestinal problems, mainly gas and loose stools.  However, after reading your info. on it, I may try it again in a lower dose.  I was taking 400 mgs SAM-e a day.  All in the morning 30 minutes before breakfast.  I even tried splitting it up in two doses, morning and before lunch, as recommended by it's manufacturer, to no avail.  I was having phenomenal results for my depression with it, but was experiencing what might be classified as anxiety later in the day.  No sleep problems, however.  I saw it as more hyperactivity, though.  The package warns that people with bi-polar disorder not use it, because of mania that could be experienced with it.  I have to say that may be what I was experiencing, even though I had only been diagnosed with major depression.  Recently, however, I was diagnosed with ADHD, which I think has been a major contributor and cause of the depression for all these years.  I do believe it helped me focus much better and my concentration was better over all.  I can't say it cured me of all of my ADD symptoms, but I felt better while taking Sam-e than I have in years!!  Simply amazing stuff and I think I am going to try the lower doses, as you recommend, to see what happens.  I was put on Ritilan last week, but had to stop it after two days due to severe anxiety from it.  I go back to my ADHD specialist tomorrow and I am going to see what he says about trying Sam-e.  A well known specialist in the field actually recommends Sam-e in one of his books for one of his six types of ADHD, which I happen to fall under.  Must explain why it worked so well for me.  Now, if I can only quell those bad gassy effects!

Q. You mentioned that Sam-e may cause anxiety in some. Does this mean that if you have anxiety you should not take it? Will the anxiety subside once the body adjusts to the supplement?
   A. Anxiety is dose dependent, 50 or 100 mg should not cause anxiety, and it is difficult to predict in each individual how they will respond to S-Adenosylmethionine, whether anxiety will develop or not.

Q. I've been doing some research on SAM-e. What surprises me is the dosage you suggest. Other websites, studies and merchants uniformly recommend that therapeutic levels for depression are 800 to 1600 mg/day. I even found one site that said that dosages of 400mg to 800mg SAM-e recommended by some manufacturers are NOT usually therapeutic and not to get discouraged if you don't notice results using label recommendations.  Have you had patients who only responded to higher doses?
   A. It is possible that severely depressed patients may need up to 800 mg a day, however, most patients with mild to moderate depression respond on 100 to 200 mg a day, and the effects of S-Adenosylmethionine are enhanced over several days of use. If too much is taken side effects, including insomnia, occur, which is counterproductive to mood enhancement. Many studies are done short term and use high doses to elicit a response, but this does not mean that high doses should be taken forever.

Q. Can Sam-e cause high blood pressure in individuals who had previously had a history of low blood pressure?
   A. One small study did not indicate S-Adenosylmethionine raised BP, however, it is possible that some individuals who respond with higher bp after Adenosyl methionine intake.

Q. It was suggested for me to take 25mg of Zoloff for a week then increase to 50mg for mild depression.  I preferred to take a natural substance and I did some research on Sam_e and purchased 20 200mg of Sam-e.  I took two 200mg this morning now this afternoon I'm experiencing anxiety.
   A. Anxiety is a very common side effect of S-Adenosylmethionine in doses greater than 100 or 200 mg.

Q. Quick question: I want to take 100mg of same but I can't find anyone that sells it. The minimum dose seems to be 200. Can you give me any leads?
   A. Unfortunately, I don’t know any company that sells the 100 mg. I recommend patients bite off half a pill.

Q. I am now 77 years old and have had fibromyalgia for more years than I would like to remember. Am in my third year of taking guaifensin under Dr. St. Amand's care with what I feel, think, and know are excellent results. Since Dr. St. Amand's office said sam-e would not block guai I tried it on 2/18/03. Without having done too much research I had taken 2 (200 mg) pills in the AM on an empty stomach. I was very surprised and almost frightened with an anxiety reaction the first day. However, my pain was relieved and my sense of well being was very good for a change, altho I am on Zoloft 200 mgm daily. I then cut the pill in half and have taken a half for three days. Very little anxiety if any, and pain is diminished. Have read of this side effect on maybe only one other internet article. Thank you for pointing out this reaction.

Q. I was interested in what  you had to say about SAM-e. I appreciate your caution and emphasis on the fact that little is known. I had a very bad reaction on 800 mg. a day. Had 5 months of severe gastro-intestinal disturbance, and severely high blood pressure (which rapidly abated when I discontinued the SAM-e). I was also taking B-complex daily but homocystiene apparently built up anyway. Also, had bad withdrawal when I quit the stuff. About 4 or 5 days of high anxiety, mustle twitching, and depression. In my opinion, SAM-e is bad stuff.
   A. Actually a nutrient or herb can be beneficial or a poison depending on dosage. For many people, daily doses greater than 100 or 200 mg of S-Adenosylmethionine can cause side effects in the long run.

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Q. Thank you for your great website and for the extensive information you provide. I have taken S adenosylmethionine supplement over the past few weeks. At first, dosage at 200 mg (1 AM, 1 PM) made a decent difference in my depression. However, after 4-5 days, I started getting horrible headaches within 30 minutes of taking it. I also have developed symptoms of increased joint pain, and have problems with my eyes not wanting to focus and hurting. Have you ever heard of these symptoms coming from S-Adenosylmethionine supplement?
   A. Yes, headaches and blurred vision are common with excess S-Adenosylmethionine dosage. Many people do better with this supplement when they take 50 mg or 100 mg.
 
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S-Adenosylmethionine is the major biological methyl donor. S-Adenosylmethionine's methyl group arises both from the diet (eg, methionine, choline, and betaine) and from de novo synthesis. At least 50 Adenosylmethionine -dependent methylation reactions have been identified in mammals, and genomic analyses suggest that the final number will be much higher. Such methylation reactions play major roles in biosynthesis, regulation, and detoxification. Creatine synthesis is thought to account for the use of >70% of S-Adenosylmethionine -derived methyl groups in humans. This is not consistent with recent studies in mice, in which the phosphatidylethanolamine methyltransferase gene was deleted (PEMT–/–). Loss of this hepatic enzyme resulted in a 50% decrease in plasma homocysteine, which suggests that it accounts for a major component of whole-body AdoMet utilization. A reexamination of human creatine metabolism showed that dietary creatine can account for as much as 50% of daily creatine requirements in nonvegetarians and, therefore, that estimates of creatine synthesis need to be reduced. We suggest that creatine synthesis is responsible for a smaller proportion of AdoMet-derived methyl groups than has been suggested and that phosphatidylcholine synthesis via phosphatidylethanolamine methyltransferase is a major consumer of these methyl groups.

Q. I am an engineer and I really appreciate the well-documented and well-attributed information on your website. I especially value the attribution of pieces of information as either general explanation of the effects of the product, study-based information (along with the occasional helpful evaluation by Dr. Sahelian), anecdotal information from users, or Dr. Sahelian's own experience. The more general information concerning how to select, experiment with, and choose supplement plans is also very helpful. I really appreciate fact-based sales approaches, as opposed to the usual propaganda. I am currently breaking 200mg S-Adenosylmethionine tablets in half and taking one a day. I concerned that since I break the enteric coating of the tablet, the S-Adenosylmethionine will be dissolved and destroyed by the stomach, thus reducing the bioavailability of the S-Adenosylmethionine and also preventing me from accurately judging the dosage that I am taking. Your site says nothing of an enteric coating being necessary, only that the half of the tablet that is not taken immediately should be plastic wrapped to avoid exposure to air (oxidation?). Is the "enteric coating" advertised for some S-Adenosylmethionine tablets actually useful as an enteric coating, or is it just to keep the S-Adenosylmethionine from being exposed to air? If the enteric coating is required to get the S-Adenosylmethionine past the gastric juices in the stomach, please ask your staff to help me find an enteric coating that can be applied at home. I found many commercial enteric coatings, but for various reasons, I cannot use these products at home.
   A. For practical purposes we have found that it is not necessary to have an enteric coating when using a S-Adenosylmethionine supplement. The wrapping of the half tablet is to prevent oxidation, and this probably is not necessary either if the half tablet will be taken the next day. S-Adenosylmethionine is best taken with breakfast and the benefits seem to occur whether it is enteric coated or not. The important factor is that each tablet be individually sealed in a foil pack when you buy it as a supplement. The effects of S-Adenosylmethionine add up over several days of use and you may find you need a lower dosage over time otherwise side effects of insomnia, anxiety, and restlessness could occur.