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SAM-e (short for S-adenosylmethionine, also spelled SAMe) is made from the amino acid methionine and ATP. SAM-e is a methyl donor involved in the making of dozens of important compounds in the body. SAM-e has been available by prescription in Europe for many years as an antidepressant but has been available over the counter in the US only since about 1996. Dr. Ascanio Polimeni, a friend of mine who is a physician in Rome, Italy, says, "Some doctors in Europe prescribe SAM-e  for the therapy of many conditions, including depression, chronic fatigue syndrome, and fibromyalgia." We suggest reading the SAM-e side effects discussed below and using low dosages since high doses of SAM-e cause side effects in many people. See the link for depression on natural ways to address this problem. Sleep has a strong influence on mood. See sleep for natural ways to fight insomnia.

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SAM-e is present in every living cell in the body. However, levels of SAM-e 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.

SAM-e Supplement Facts
SAM-e - 200 mg

Usage: Take half or 1 SAM-e tablet a few minutes before breakfast, or as directed by your qualified health consultant. High doses of SAM-e can lead to insomnia and anxiety. Many people do well with half a tablet or even less, or half a tablet every other day.

CAUTION: Anxiety, mania or manic episodes may occur if you take high doses of SAM-e. Once you have enough SAM-e in your system, you may only need to take 100 mg every day or every other day.

Sign up to a FREE Supplement Research Update newsletter. Once or twice a month we email a brief abstract of several studies on various supplements and natural medicine topics, including SAM-e, and their practical interpretation by Ray Sahelian, M.D.

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Mind Power Rx- Formulated by Ray Sahelian, M.D.

SAM-e Research Update
S-Adenosyl methionine ( 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 
SAM-e is a dietary supplement used in the management of osteoarthritis (OA) symptoms. Studies evaluating SAM-e in the management of OA have been limited to Non Steroidal Anti-inflammatory Drugs (NSAIDs) for comparison. The present study compares the effectiveness of SAM-e 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. METHODS: A randomized double-blind cross-over study, comparing SAM-e (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. RESULTS: On the first month of Phase 1, celecoxib showed significantly more reduction in pain than SAM-e. 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 SAM-e and celecoxib was observed. Isometric joint function tests appeared to be steadily improving over the entire study period regardless of treatment. CONCLUSION: SAM-e 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 ( SAM-e ) supplementation for treatment of chemotherapy-induced liver injury.
Anticancer Res. 2003 Nov-Dec;23(6D):5173-9.
Liver toxicity can be observed during treatment with most chemotherapic agents, and represents one of the principal causes of dose reduction or chemotherapy delays. SAM-e plays a critical role in the synthesis of polyamines and provides cysteine for the production of glutathione (GSH), the major endogenous hepatoprotective agent. Our study was aimed at assessing the protective effect of SAM-e supplementation in cancer chemotherapy-induced liver toxicity. Fifty cancer patients who developed, for the first time, anticancer chemotherapy-induced liver toxicity were studied. Enrolled patients received oral SAM-e supplementation. RESULTS: AST, ALT and LDH levels recorded at the moment of the recognition of liver toxicity were significantly reduced after one week of SAM-e therapy . AST, ALT and LDH decrease was confirmed after two weeks of treatment. Furthermore, the effect on these enzyme levels persisted in the following chemotherapy courses, permitting our patients to perform the scheduled chemotherapy courses with a minimal number of dose reductions or administration delays. The efficacy of SAM-e supplementation was not influenced by the presence of liver metastases, and no appreciable side-effects were recognized. CONCLUSION: The results of our study clearly demonstrate a protective effect of SAM-e in cancer chemotherapy-induced liver toxicity. Further large phase III studies are required to assess the real clinical benefit associated with SAM-e supplementation.

A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAM-e) versus imipramine in patients with major depressive disorder.
Int J Neuropsychopharmacol. 2002 Dec;5(4):287-94.
SAM-e is a natural substance which constitutes the most important methyl donor in transmethylation reactions in the central nervous system. Several clinical trials have shown that SAM-e possesses an antidepressant activity. This multicentre study was carried out to confirm both efficacy and safety of SAM-e in the treatment of major depression. SAM-e was given intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d oral Imipramine (IMI) in patients with a diagnosis of major depressive episode, with a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of >or=18. A total of 146 patients received SAM-e whereas 147 received IMI for a period of 4 wk. The two main efficacy measures were endpoint HAMD score and percentage of responders to Clinical Global Impression (CGI) at week 4. Secondary efficacy measures were the final Montgomery-Asberg Depression Rating Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of at least 50% with respect to baseline. The analysis of safety and tolerability was conducted in all treated patients. SAM-e and IMI did not differ significantly on any efficacy measure, either main or secondary. Adverse events were significantly less in patients treated with SAM-e compared to those treated with IMI. These data show 400 mg/d i.m. SAM-e to be comparable to 150 mg/d oral IMI in terms of antidepressive efficacy, but significantly better tolerated. These findings suggest interesting perspectives for the use of SAM-e in depression.

SAM-e improves depression in patients with Parkinson's disease
Researchers at Beth Israel Medical Center in New York report a study of SAM-e in 13 depressed patients with Parkinson's disease. SAM-e 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. SAM-e 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 SAM-e is well tolerated and may be an alternative to the antidepressant agents currently used in patients with Parkinson's disease.
        Dr. Sahelian says: SAM-e 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 twice a day. High doses can lead to anxiety and restlessness. Prolonged use of SAM-e should only be done under medical supervision.

SAMe better than Prozac?
A couple of issues ago I mentioned the role of SAM-e in joint health and how Vioxx, the so called arthritis wonder drug, got kicked out since it was causing an increased risk of heart attacks. This week new research indicates that SAM-e, also spelled SAM-e, may give the boot to Prozac and other SSRIs. Actually I'm being a little premature. Researchers at the Massachusetts General Hospital in Boston found out that SAM-e carries quite a punch. When standard medication with selective serotonin reuptake inhibitors (SSRIs) such as Prozac, Paxil and Zoloft, failed to improve depression symptoms in 30 patients, adding the dietary supplement SAM-e saved the day. The researchers found that when they added the dietary supplement SAM-e to the patients' treatment for six weeks, half saw their symptoms improve and 43 percent had a complete remission. SAM-e, short for S-adenosyl-L-methionine, is a substance produced naturally in the body that is involved in a number of biochemical processes including the making of several brain chemicals that relay messages between nerve cells. A larger trial is being conducted with more patients, and the scientists will also test the combination of SAM-e together with standard antidepressant therapy.
     My comments: I have personally taken SAM-e just to see what it would do, and it is quite a powerful mood lifter. Perhaps I'm sensitive to nutrients, but I notice the effects on 100 mg, sometimes even less. Almost all the tablets on the market are SAM-e 200 mg. If you plan to take SAM-e under medical guidance, here's a few tips your doctor may not know. It's best taken in the morning before breakfast for a quick absorption, or it can be taken with breakfast if you want to slow the effects. I notice within one to two hours being more alert and more motivated to do things, and in a better mood. Many of the clinical studies have used several hundred mgs, but in the long run this can cause side effects. The most common are overstimulation, insomnia, and headache. You can actually feel anxious and restless if you take too much. If you wish to take a small amount, bite off half or a third of a 200 mg SAM-e tablet and use the rest the next day. You may need to adjust your dose down over the next few days since it can start building up in the system, or you can take a day or two off. Each person is unique in their response.

Sam-e Emails and comments
Q. it seems that sam-e and the antidepressant wellbutrin both relieve depression by increasing norepinephrine and dopamine levels. Do they work similarly on the brain, then? (I ask because I am currently taking wellbutrin and am thinking of switching to sam-e.)
     A. To the best of my knowledge, the mechanism of action of Wellbutrin is still not very clear, but it does involve the adrenergic system. SAM-e helps the brain make more of certain neurotransmitters. My guess is that the mechanism of action of SAM-e is different than Wellbutrin. Now, it may be that they both provide good anti-depressant effects, which is the final objective. As to switching from Wellbutrin to SAM-e, that we would be a decision you would make in cooperation with your doctor.

Q. I am trying SAM-e instead of Wellbutrin to attempt to counteract atypical depression which has bothered me for years. I went off of 150 mg of Wellbutrin 2 weeks ago, and have been taking 200 mg of SAMe in the am. Perhaps I am sensitive to drugs ( I think I am), and I think it is affecting my sleep, as I can not sleep more than 2-3 hours at a time, and then I wake up in the am with some scary anxiety.

Q. Is it okay to combine SAM-e with Paxil or other SSRIs?
     A. We do not recommend such combination. They are both potent and the combination could lead to overstimulation and other side effects.

Q. For depression, should one try 5-HTP or SAM-e?
     A. 5-HTP converts into serotonin while SAM-e can raise levels of several brain chemicals including norepinephrine, dopamine and others. Each person responds differently. Some may be very deficient in serotonin and benefit from 5-HTP, while others may benefit from SAM-e. There's really no good blood test that can tell who will respond to what.

Q. I've just purchased some Sam-e for depression as I experience too many side-effects with anti-depressants. I have read that it is wise to take additional B vitamins, particularly B6, B12 and folic acid, when taking Sam-e in order to prevent toxic build-up of homocysteine. Apparently these vitamins assist in the breakdown of homocysteine which is formed when Sam-e breaks down.
     A. We're not totally sure whether extra B vitamins are needed if someone is taking SAM-e. Perhaps it depends on one's diet and biochemistry. It would not hurt to take 1 to 3 times the RDA of the B vitamins.

Q. Got my first newsletter since signing up. Excellent! Will Sam-e cause similar sexual side effects as prescription antidepressants (like decreased libido)?
     A. Not likely, if anything there may be a slight increase. 5-HTP, on the other hand, by converting into serotonin, may decrease sex drive.

Q. I am considering purchasing some of your products, one being sam-e.  I understand that sam-e has some neurotransmitter effects.  Would there be any adverse interactions between sam-e (@approx 1 g/ed) and deprenyl( @ 1-2.5 mg/ed), or can they be taken together with no problems?
     A. SAM-e has a stimulatory nature and even 200 mg can be a lot for some people. Deprenyl can stimulate dopamine levels, the combination may be too much and overly energizing, however if dosages are kept very low for both, it may work, under medical supervision.

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 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.

Q. 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 SAM-e, 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 severily 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 SAM-e 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 higher blood pressure in individuals who had previously had a history of low blood pressure?
     A. One small study did not indicate sam-e raised BP, however, it is possible that some individuals who respond with higher bp after sam-e 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 SAM-e 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.

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 homocystine 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 SAM-e can cause side effects in the long run.

Q. As far as I understand SAM-e comes in enteric coated tablets and should not be broken.
     A. We are familiar with the SAM-e manufacturers recommendations, however we have found that taking the half SAM-e pill the next day is effective, and if taken with a little bit of food, it slows the absorption. You can wrap the half pill with plastic wrap.

Q. I took sam-e a few years ago and it was amazing. It really took away my depression and I felt great-the best I remember in a long time. Unfortunately, it really upset my stomach so I had to stop. I would like to try it again and wonder if you know of any way to take it to avoid stomach upset or if there is a sam-e formula that you know of that is less upsetting on the stomach. I did find a liquid sam-e but it was a fortune and I found that I was going through a bottle every other day and at $40 a bottle, I couldn't afford it. So my question is - do you know of any way to take sam-e to avoid the stomach upset and do you know if it eventually subsides with time and if your body gets used to it? I am also wondering why I am now reading on some web sites that sam e helps people with gastrointestinal irritation.
     A. SAM-e may cause gastrointestinal symptoms, and one way to avoid it is to take a smaller amount, such as 50 or 100 mg and to take SAM-e with food. It would be quite unusual if SAM-e continued causing stomach problems on this low dosage.

Q. Sam-e has been effective for my mild depression. I very much appreciate your information on smaller doses. I'm very sensitive to most meds, herbal or otherwise. The first time I used sam-e I tapered on very slowly: 50 mg with food for several days, then 50 mg on an empty stomach. My best dose eventually became 100 mg with food to slow the absorbtion. The second time I used sam-e I tried 100 mg on an empty stomach. Mistake! I had tremendous anxiety that persisted for several hours. I've learned my lesson to taper on slowly to everything I try, which is in line with what previous doctors had suggested to me as well.
     A. Thank you for the feedback. Most of sam-e tablets on the market are 200 mg and that may be too high a dose for some people.

Q.  I read your website on Same-e. I am a doctor who works in Hawaii and recently began taking the nature made sam-e product for some back pains, and much to my surprise it worked almost immediately. If it is a placebo effect, which i doubt, i am just as thankful. However, I note you caution folks about anxiety on higher sam-e dose. I have been using sam-e 400 mg a day, and as a very anxious person am happy to say my anxiety has diminished by 50-70%. Of course we all know that drugs can have these sorts of effects on small groups of people. But it is fascinating to see it alleviate my anxiety as a nice pay off!
     A. There is a wide range of dosage responses to sam-e and I am quite sure it is not a placebo response, SAM-e really works. Be on the lookout for insomnia or irritability since SAM-e has a way to add on itself and have a cumulative effect over time building up on the dosage from the day before. Less of a SAM-e amount may be needed as the days and weeks go on.

Q. I am interested in knowing whether it is okay for a woman to continue to take Sam- e while pregnant. Are there any studies?
     A. We are not aware of studies with SAM-e and pregnancy but SAM-e is powerful and influences body chemistry to a great extent and we suggest you discuss with your doctor. We are not in a position to make individual recommendations.

Q. I have a 15 year old son who suffers from anxiety and I would like to know if any research has been done on children taking SAM-e.
     A. We have not seen studies regarding children and SAM-e. If you child's doctor approves, a quarter or third of an adult dose can be temporarily used to elevate mood, but there are better options for anxiety than SAM-e.

Q. Could you please tell me if it is safe to take Sam-e with Lorazepam?
     A. Lorazepam (Ativan) is an antianxiety drug used for the management of anxiety disorders and anxiety associated with depression. SAM-e is quite potent and could lead to anxiety if used in high doses. Your doctor should be aware you are using SAM-e.

Q. I have been taking Sam-e for about 4 years now. I have tried to come off it but I became became very depressed so I would go right back on it.. However, that is not my question. I was sent to a hemotologist because my white and red blood count was very low. I was wondering if you have any studies showing that this is a side effect of Sam.e. I know my doctor is going to research this for me, but I am not going to see him for tow weeks and that is to have a bone marrow biopsy. I thought if you knew if this was a sam-e side effect, perhaps it would determine if I need the biopsy or not. I would like to avoid the test if this is a known side effect of the sam.e. I was so glad to find this site because I have had so many guestions about sam.e but did not know where to get answers. Sam-e has really helped me with depression, but Im not sure how long is considered safe to take it.
     A. We have not seen any long term studies with SAM-e, and don't know anyone who has taken it for this long without a break, so we really don't know if SAM-e had an influence on the red blood count.

Q. I have been taking Sam-e for about 4 years now. I have tried to come off it but I became became very depressed so I would go right back on it.. However, that is not my question. I was sent to a hemotologist because my white and red blood count was very low. I was wondering if you have any studies showing that this is a side effect of Sam.e. I know my doctor is going to research this for me, but I am not going to see him for tow weeks and that is to have a bone marrow biopsy. I thought if you knew if this was a side effect, perhaps it would determine if I need the biopsy or not. I would like to avoid the test if this is a known side effect of the sam.e. I was so glad to find this site because I have had so many guestions about sam.e but did not know where to get answers. It has really helped me with depression, but Im not sure how long is considered safe to take it.
     A. We have not seen any long term studies with SAM-e, therefore we really can't say whether long term use of SAM-e is involved in this matter of low white and red blood cell count.

Q. Is it okay to combine St. John’s Wort and Sam-e or better to take one or the other? I am experiencing a loss of libido and wondering if this combo is doing it. Can’t find any info on this on the internet.
     A. Unexpected side effects can occur when strong herbs and supplements are combined. As a rule I prefer not mixing potent supplements, such as St. John's wort and SAM-e unless a person is fully aware of how each one influences their body. Overstimulation and insomnia are common side effects from the combination of St. John's wort and SAM-e.

Q. I am taking 5-htp for anxiety/depression and weight loss. I would like to add SAM-e to help with hip pain. I have used SAM-e in the past and had great results with it for my hip, but didn't notice that it affected my mood, so I am wanting to continue the 5-htp. Can I use both together?
     A. Unexpected side effects can occur when potent nutrients are combined, therefore caution is advised. SAM-e can cause a great deal of stimulation, and the effects are additive over several days, so the dosage may need to be reduced. The effect of 5-HTP may be altered when used the same day as SAM-e, and it is difficult to predict how mood will be affected since each person may react differently, and the dosage used can make a difference. Furthermore, it is possible that an initial reaction with the combination may be different several days later even if the same dosage is used. Hence, caution is advised, and always use low dosages until you have a full understanding on how these nutrients are influencing your brain chemistry.

Q. I was wondering why SAMe s-Adenosylmethionine is not for the bipolar person? I have a friend on Lamictal and SAMe and she seems to be fine on it. It is listed that it can induce mania. How so. Is there
health risks with SAMe? 
     A. SAM-e can induce a manic state in some people therefore dosage and use needs to be constantly evaluated to avoid sending someone into a manic phase.

Q. I am having a very good response to using SAM-e for about a month for mild depression (which I have had for years). At the low doses Dr. Sahelian recommends I am having no trouble with it and I am very pleased because many supplements (other than straight vitamin/mineral supplements) recommended to help often cause me a lot of trouble in the way of irritability or nervousness or even more depression. But please tell me – would there be problems to suddenly stopping SAM-e? Does it have a rebound effect? If so, is there a way around this? I appreciate any info you can give me. And thank Dr. Sahelian for his wonderful advice.
     A. Thus far we have not seen a rebound effect to SAM-e or any significant problems when SAM-e is stopped, but there could be exceptions in rare individuals.
          Q. Thank you for answering! I am so happy that I’ve finally found something that helps (and no way was I going on any prescription drugs). I literally feel like a new person and this sorry old world looks like a beautiful place again.

Q. Recently I have come off of antidepressants, particularly Effexor. The reactions to coming off the meds were horrific. I still deal with severe joint pain and fatigue. However, recently I was introduced to a Sam-e product called Me-Cofactors by Dews. The manufacturer claims this combination of Sam-e is superior to others due to the inclusion of other factors. I've only been able to determine the "other factors" in Me-Cofactors by Dews as being Xanthosine (as derived from caffeine). Perhaps the inclusion of the B vits is considered to be a selling factor as well. I realize the B vits are very important in helping to keep the homocystine in check. My question, since I don't understand chemistry all that well, is what benefit does the xanthosine contribute? I have a sensitivity to caffeine and have found some difficulty in breathing and the usual "tingle in the veins" when using this particular product. However, my sense of energy and well-being have improved. Joint pain is a huge
problem for me. And I believe this pain has contributed to my "depression". How much pain can a person endure without being depressed? Seems to be a Catch22.
     A. An internet search reveals Me-Cofactors by Dews to have the following: One Caplet Me-Cofactors by Dews provides: Vitamin B6 10 mg; Folate 100 mcg; Vitamin B12 7 mcg; Purine Alkaloids Complex (Adenosine and Xanthosine compounds) 128 mg; Methionine 72 mg; Curcumin Extract 25 mg.
     It does not appear Me-Cofactors by Dews has actual SAM-e itself.

Q. SAM-e seems to really work for my depression but causes severe gastro-intestinal upset even in lower doses, is there anything I can take to counter act this negative side effect? Any advise would be appreciated since SAM-e is the only thing that seems to work for my depression.
     A. Taking it with a good sized breakfast may help, and perhaps drinking ginger tea in the morning or taking a capsule or two of ginger may be helpful. You could also try even lower doses of SAM-e.

Q. I am a medical doctor and understand that SAM-e can cause anxiety at higher doses. But SSRIs can help anxiety, so could SAM-e also be used to treat anxiety at 50-100mg per day rather than the higher 200mg-1600mg doses I have seen? Could low doses of SAMe be used for anxiety?) I am hesitant to prescribe 5HTP because of its side effects. SAMe seems to have a much better side effect profile. Do you have any other specific supplements that you would recommend for the treatment of anxiety? I prefer to recommend supplements that have little potential for drug interactions (unfortunately, many herbs do). SAMe has few common drug interactions, assuming you are not prescribing psychoactive drugs.
     A. SAM-e is low doses may not cause anxiety initially, but there is a potential that it's effects may accumulate over several days, and even though the first few days of low dose may not cause anxiety, it could build in the system and eventually cause restlessness and irritability and tenseness.

Q. Can you tell me if OptiForm Sam-e, made in India is a reliable source of Sam-e?
     A. We have not heard of OptiForm SAM-e, and we do not test products not formulated by us, so we can't give any advice on this question.

Q. Hi, I took  200mg of sam-e for a couple of weeks and felt great , but had some trouble with anxiety and and depression and started to take 400mg and smptoms seem to get worse, what would be the best  dose  I should  decrease to ? also I read that sam-e can cause a rare but dangerous reaction in some called serotonin  syndrome what is it ?
     A. Usually SSRIs cause serotonin syndrome. SAM-e influences many brain chemicals, not just serotonin. High dosages of SAM-e can cause anxiety, I prefer using 100 mg or less.

Q. I love the anti-depressant effects of SAM-e; however, the anxiety and restlessness gets so bad (even at 50 mg) that I am ready to get off of SAM-e. Do you have any suggestions of what people have done in the past to bring down the anxiety effects of SAM-e? From what I'm experiencing, SAM-e might only be good for those who have ONLY depression. Is that true?
   A. Yes, anxiety is a SAM-e side effect, and some people prefer to use it every other day or take even less on a daily basis or take it with food.

Q. Dr. Sahelian, I have recently heard about Sam E and would like to try it for joint and back pain. I don't take any other prescription medications. I do take Centrum multivitamins (high performance) and right now I live on Ibuprofen. Every article I have read says Sam E is natural, I think if it is natural then you should be able to take anything else with it but I'm not sure, so I have a question. If I start taking Sam E can I still take the vitamins, probably won't need the ibuprofen. Could you please let me know, if Sam E works I am really looking forward to getting out of bed in the mornings without 5 or 10 minutes of struggling.
   A. We can't give individual advice, but if you were to take sam-e, and your doctor approves, most people need only a portion of a tablet since side effects can occur on a full tablet. You may also consider having your doctor read the jointpowerrx page.

Q. Goodmorning Mr. Sahelian, I am from Netherlands and I want to report you the very good results by taking SAM-e for several weeks now. (about 8 weeks) My mood has made improvements, I have much more energy, a clearer mind and less problems with the poly arthrosis i'm suffering from.
Also my husband has good results with his muscle problems and energy. I take 100mg each day. I'd like to continue this supplement the rest of my life. My question to you: is it harmful to use this supplement for years? I tried 200 mg. first, but I lowered to 100 mg, cause that also had good effects to me and its cheaper of course. Thanks a lot for your answer, PS I tried a lot of supplements in my life, but this is the first supplement I really experience the results (even on to the very first day).
   A. Not enough is known regarding the long term use of SAM-e. To be on the safe side, I prefer taking a day or two off each week, and a minimum of 4 days off each month. I try to be cautious about using the same supplement all the time.

Q. I saw a promotion for SAMe Tosylate Disulfate. How different is this from regular SAM-e supplement?
   A. Tosylate disulfate is a stabilizing agent. It does not seem that the tosylate disulfate has much of a contribution based on one study listed below, although we don't have much knowledge about this form of SAM-e and whether clinically it offers a better alternative to regular SAM-e. SAM-E is available in many forms. In order to stabilize the SAM-E molecule, and preven degradation, an additional compound is attached the SAM-E molecule. These compounds include tosylate, disulfate tosylate, disulfate ditosylate, and 1,4-butanedisulfonate and are typically written immediately after the chemical name of SAM-E. Some inaccurately labeled products combine the weight of the stabilizing compound with the weight of the "free" SAM-E. A product claiming to have 200 mg. SAM-E may in fact contain only 100 mg. "free" SAM-E and 100 mg. of the stabilizing compound. Consequently, a tablet containing 200 mg of S-adenosyl-methionine disulfate tosylate will contain only 100 mg of SAM-E. This may end up being a good thing since most people are taking too high a dosage of SAM-e.

Protective effects of S-adenosyl-L-methionine against enzyme leakage from cultured hepatocytes and hypotonic hemolysis.
Japan J Pharmacol. 1990 Jan;52(1):45-9. Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.
Effects of S-adenosyl-L-methionine disulfate tosylate salt (SAMe ST) and L-methionine (L-Met) on rat erythrocytes and primary cultured hepatocytes were studied. SAM-e-ST in concentrations of 0.2 to 5.0 mg/ml protected erythrocytes from hypotonic hemolysis. Almost an identical level of protection was provided by SAMe chloride, suggesting that this protective effect is due to the SAM-e moiety itself but not its sulfate or tosylate moiety. L-Met also showed a slight protective effect, but at higher concentrations, it slightly enhanced hemolysis. When the cultured hepatocytes were treated with SAM-e-ST, the leakage of enzymes from the hepatocytes were significantly decreased compared with that in the control. L-Met also showed similar protective effects, but to a lesser degree than in the case of SAMe-ST. SAMe-ST significantly increased Na+.K(+)-ATPase activity. The present results indicate that SAM-e remarkably inhibits hypotonic hemolysis and enzyme leakage from cultured hepatocytes and that its mechanism is probably related to a change in the membrane property.

Q.  Just wanted to ask a few questions about SAM-e. I started taking Karuna brand 200 mg twice a day. But my dr. wanted me to increase it to three. When I increased it, boy did I get a reaction in the gut. So I cut it back and still have lingering stuff with the gut. Now, my questions are. Is the gut reaction a detox response? Will it go away with time? My dr. says that the hydrochloric acid will destroy it in the stomach that's why its enteric coated but Dr. Sahelian says that you can split a 200mg. which I have done and that it builds up in the body. So how do you know how much you should take? Its really confusing. I have a genetic defect that I dont convert methionine into SAM-e and my norepinephrine is high and causing anxiety. My dr. says that SAM-e does the converting into epinephrine. So, any help would be appreciated.
   A. One of the SAM-e side effects is nausea, and we prefer people use smaller amounts of SAM-e since it builds up in the system over several days of use. If 200 mg was fine the first day or two, it may not be the third or fourth day since it builds up from the previous days. The side effects are not a detox reaction.

Q.  Does SAM-e make more "alert" and pushes you ? I have light Depression, but also bad Sleeping Problems, so i cant cool down in the Evenings well. I ask myself, if SAMe is the right way, if it gives you good sleep or if its more alerting like your TMG - test? Would you recommend it if a patient has sleeping problems (problems falling asleep).
   A. SAM-e is not a good option to those who have sleep problems. It causes alertness.

Q. Recently I bought a large quantity of sam-E and B multivitamins. In May, 2007 I was diagnosed with an 8cm mass protruding from my stomach. I started 5 different alternative cancer killers . The Dr still does not know if it is benign or active, so he is ordering a new Cat scan. Is Sam E is safe to take with a benign or active cancer? Thanks and Have a Wonderful Forth of July. I did 30 years in the United States Air force so we could keep this most wonderful country on God's Green Earth FREE!!!
   A. SAM-e and B vitamins have not been tested in cases of cancer treatment and we don't know if they would benefit or harm an existing tumor growth and how they would interact with various chemotherapy medicines. To be on the safe side, it is best to wait until the cancer is treated, or to take only minimal amounts, such as portions of tablets or capsules, with frequent days off. We wish you optimal healing.


SAM-e 200 mg, 20 tablets and SAM-e 200 mg  60 tablets