SAM-e supplement for depression - Benefits and risks of SAM-e supplement

SAM-e is a supplement used for depression. In high doses SAM-e has side effects of anxiety, restlessness and insomnia. You can purchase Sam-e supplement at Physician Formulas. Additional supplements used for mood enhancement include 5HTP supplement and St. John's wort herb.

Biochemical properties of SAM-e
Unlike other methyl donors where the research is scarce, there have been a number of studies with SAM-e. These studies have shown that SAM-e influences brain chemicals by helping to convert norepinephrine to epinephrine and serotonin to melatonin.
Sam-e is also involved in the production of creatine, which in turn is phosphorylated to phosphocreatine using adenosine triphosphate. Creatine is an important energy reservoir in muscle tissue
Sam-e helps the preservation of glutathione, an important antioxidant.
Furthermore, SAM-e is involved in the formation of myelin, the white sheath that surrounds nerve cells and it can improve brain cell membrane fluidity, thus potentially enhancing the function of receptors.

Q. Thank you for your excellent web site on Sam-e. I have been taking 200 mg per day for about a month. I have noticed in the past few days that I have been developing what appears to be an irregular heart beat, or like a fluttering in my chest like my heart was skipping a beat. I dropped the SAM-e dosage down to 100 mg a day by cutting the pill in half. I noticed that when I stopped taking it that the heart beat problem would go away. Is this possibly one of the side effects of Sam-e?
   A. A side effect of a SAM-e supplement could be heart rhythm disturbances.

SAM-e questions
Q. I was wondering if rapid withdraw from Sam-e can cause lightheadedness, tinnitus and dizziness as the SSRI's do in general.
   A. We have not heard of this, but it could be hypothetically possible to have withdrawal symptoms from SAM-e.

Q. I was reading Emails and comments about Sam-e and there were a couple of comments about Sam-e causing high blood pressure. “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” I’m just wondering what studies showed signs of high blood pressure in relation to Sam-e and what your experience of this is?
   A. Since SAM-e influences levels of neurotransmitters, it could influence blood pressure.

Q. If you have hypertension, is SAM-e safe to take in low dosage?
   A. Hard to say. If mild hypertension and low dose of SAM-e such as 50 mg, perhaps. We are not sure how high doses of SAM-e influence hypertension in the long run.

Q. Can you point me to any information regarding the safety of using SAM-e (as a "pure" product) on a patient with Stage 4 Kidney Disease?
   A. We have not seen such studies regarding SAM-e and kidney disease.

Q. I have been taking SAM-e in a reasonable dosage (200 mg every 3 days) during two weeks against my depression and I obtained very good results so far. In the same time I was reviewing a large number of sites to learn more about SAM-e. But after all I found that your page helps more than the addition of the others. By the way I have a question which is not addressed in your page so please let me ask it directly. Together with taking SAM-e I am feeling a sort of stiffness and tremor in my hand when I am writing and my handwriting is becoming somehow awkward and hasty. Is it just a little bit of excitation, or could it be a Parkinson-style “extra-pyramidal” tremor which is also a side-effect in some prescription antidepressants?
   A. It is possible that high doses of SAM-e could cause slight tremor.

Q. I am currently taking 200 mg of Nature Made Sam-e. Seems to be ok and I noticed that the first week seemed to be the best. I am in my fourth week and because it does not seem that it's doing as good as the first week I have been taking it with another natural supplement called Amoryn. One of the ingredients is 5-htp and also B vitamins. Do you think it is ok to take these two supplements at the same time?
   A. Sometimes tolerance can develop to certain supplements such as SAM-e or it is possible mixing it with other supplements such as 5-HTP could dampen the effect. Taking a break can be helpful. We did an internet search for Amoryn and it appears the main ingredient in Amoryn is hyperforin, from St. John's wort, and Amoryn also has 5-HTP and rhodiola. 
      Q.  I stopped the Sam-e on Monday and Tuesday was a tough day. Today I'm doing better. Any clue as to withdrawal symptoms when you go off Sam-e? Yes if you could look into the Amoryn along with Sam-e that would be great. I looked into some of your testimonials and saw that if you have Anxiety issues that Sam-e may not be good. That would be the major part of my issues. Depression would be the minor part. But definitely have both.
         A. We don't have enough feedback yet from users of SAM-e who have abruptly stopped to determine what kind of withdrawal effects there are, but they should be temporary. SAM-e can increase anxiety and those who are prone to anxiety may do better just using 5-HTP by itself. See anxiety for additional options.

Q. I have just started on Sam-e to treat depression and am starting out very slow. Perhaps 100mg every other day? I’m looking for some suggestions. I am using this to treat depression and anxiety. Anyway, I want to make sure that this doesn’t raise my homocysteine levels or cause any other physical problems. Some suggest using a good B6 or B12 vitamin but I would rather control by dosage. So the question is in general how much should I be taking to avoid this situation? I was formally on Lexapro for anxiety primarily but I really don’t like the side effects (weight gain and tiredness). I really want to get on something safer and less toxic. I noticed that I did have depression when I got off of it as well. I was using St John’s Wart but really don’t like the fact that it slowed me down too much.
   A. Each person needs to find the dosage that works for them best. For some it is 100 mg every other day or every third day, for others it is 200 mg a day. The only way to tell is by trial and error.

Q. My doctor said that as SAM e is produced naturally in the body - if we take external quantities our body may be resistant thereafter to producing it's own quantity of SAM e - it'll get "lazy" - would you kindly comment.
   A. We have not seen any research that would support this claim.

Q. I read your Sam-e article. If you have a quick minute, I am wondering about are typical reactions if someone takes SAM-e and is not depressed. Reason I ask, I do not fit into a clinical depression "box," maybe I am mildly depressed, but I'm not sure. So, after reading your article and doing other research, I started taking sam-e 50 mgs each day. I feel more sluggish and feel maybe a little worse. So, I am curious as to your thoughts about how a hypothetical "non-depressed" person would react to taking Sam-e so I can better diagnose myself.
   A. Most people who are not depressed and take a small amount of SAM-e actually feel a better mood for that day. It could be dose related, you could try lower or a higher dose to see if it makes a difference.
      Q.  it just seems counterintuitive that taking something that boosts serotonin can make me feel depressed rather than the other way around. I have not felt "typically depressed" but decided to try a low dose of sam-e to improve sleep (which I am thinking is from a very mild depression from being in law school). However, 3 weeks later at only 50mgs per day I started to feel drained of all energy. Setting aside coincidences I guess my real question is whether it is possible to feel "depressed" from sam-e?
         A. it is possible that sam-e can accumulate in the system and cause untoward side effects. It is impossible to predict whether a person will respond to 5-HTP which increases serotonin, St. John's wort, SAM-e which influences many brain chemicals not just serotonin, Mind Power Rx, or at times using on supplement that works then later switching to another. It takes time and trial and error to find the one (s) that work and to find the right dosage. It is often a good idea to err on the side of taking less. Taking days off often makes them work better.

Q. I have been taking Sam-e for about 7 weeks, 200 mg per day. I started to up my dose to 300 mg per day for about 4 days at week 5, but started to feel anxious, so I went back to 200 mg per day. However, the anxiety hasn't gone away and has slowly gotten worse. I am also having very bad stomach cramping and pain for about 30-45 minutes after taking the SAM-e pill. I suffer from anxiety and thought taking Sam-e would help, which it did for about a month, then once I increased the dosage it came back. I am going 4 days now without taking Sam-e at all, while the stomach problems stopped immediately, I feel like I am even more anxious and shakey. Sort of like I am withdrawing from the medication. Have you ever had anyone experience this when stopping sam-e? How long can I expect this to last?
   A. We have had few reports of anxiety continuing more than a day or two after stopping SAM-e. It should become less each day that passes. SAM-e is very potent and many people take a higher dose than necessary.

Q. I have begun taking SAM-e after meals and this gets rid of the stomach upset. Does SAM-e have an effect on serotonin levels, or is its activity restricted to dopamine and norepinephrine? If the latter is the case, is it safe to try Zoloft at low dosage while taking SAM-e, or do these interact?
   A. Unexpected reactions can occur when Zoloft or Prozac or another SSRI is combined with SAM-e. Some people may tolerate the combination of low doses of SAM-e and Zoloft, whereas others may have unpleasant side effects.

Q. I have been taking SAM-e, for only 3 days, 800mg per day, and every time I take it I get so tired. Is this normal? I also have been on your web site and you suggest to take less than 200mg a day. Am I feeling miserable because I am
taking to much?. If the SAM-e does not work after a couple of weeks, would you please recommend something for me to take. I'm getting desperate.
   A. High doses of SAM-e can have the side effect of fatigue, we prefer lower amounts such as 100 mg which would require breaking a tablet in half. Please see the page on depression for suggestions you can discuss with your doctor.

Q. I was just reading a SAM-e article where Dr Ray Sahelian recommends biting the tablet in two in order to reduce the dose. I have a better solution as taught to me by my good friend Helen: take a sharp pair of scissors - small ones work best but even big ones do the job - and cut the pill in 2 or more pieces. Knives do not work in my experiece - apart from anything else the tablet pieces fly all over the place!

Q. The affects of SAM-e (800 mg per day) treating my depression have shown great results, however I also suffer from anxiety and panic disorder. I've read that high doses of SAM-e can actually cause anxiety in some individuals. Since I already suffer from anxiety and panic disorder in addition to depression, do you have any suggestions as to an additional supplement to take in addition to SAM-e that can help with anxiety? I recently found a supplement called Inositol, which says is for anxiety and panic attacks. Do you feel this is ok to take along with my daily intake of SAM-e? Do you know of anything else that could be taken in addition to SAM-e for anxiety, since I suffer from both depression and anxiety. Please advise because I really like the effects of SAM-e helping my depression.
   A. We cannot make specific suggestions as to what a person should take or not take. However, as a general rule, if a supplement or medicine is causing a particular side effect, a better option is to reduce the dosage rather than adding another medicine or supplement.

Q. Greetings from the Sonoran Desert! I am a guest reporter on health issues for a couple of magazine and newspaper publications here in Arizona. Recently, the supplement, SAM-e has been brought to my attention as a product to be possibly used as an anti-depressant and I do have one question regarding it. First of all, as SAM-e is described as an anti-depressant, what if anything, can SAM-e do for panic disorders or attacks?
   A. High doses of SAM-e taken daily, sometimes even 200 mg or half a 200 mg tablet, can lead to some patients who are depressed into a manic phase. Those with bipolar disorder should be carefully monitored when place on SAM-e. SAM-e is not recommended for panic disorders since it can speed metabolism and heart rate and overall alertness and restlessness and that is not helpful in a panic attack.

Q. I have been taking Sam-E instead of the overpriced prescription anti-depressant that I used to take. Sam-E has worked just as well if not better that the prescription anti-depressant. I would like to try Passion Rx, but I read that Dr S. doesn't advise taking it with Sam-E. Do you have a product that is safe to take Passion Rx with or on alternating days? Can I take Mind Power Rx and Passion Rx? I did not see that question answered in the online information. I would also like to try Eyesight Rx. Is there any problem with taking all three?
   A. All three products are potent and are strong enough by themselves to increase energy, mental clarity, and their appropriate benefits, including slight mood lift. There is no need to combine them, they can be taken on alternate days.

Q. I am trying to wean myself off of tramadol which I have been taken for pain from a broken tail bone for 1 1/2 years. I thought everything was fine but I started wanting higher doses and I recently was taking quite a bit so I scaled back to only 2 50mgs a day and now I am SICK! I am achy, cant sleep, depressed and so tired. Could Sam-E alleviate my problems or should I just deal with it? Do you know how long these side effects will bother me. It has been 3 days with no relief. I feel like taking more of the tramadol but now I am afraid. Can someone please direct me somewhere.   
   A. SAM-e is an antidepressant and not a pain pill. Sometimes when mood is elevated people don't feel pain as much, but SAM-e is not a pain pill.

Q. My question in regard to SAM-e e involves the fact that I suffer from HEP C, I am currently only a level 1, the Hepatitis virus is in my system but it is not active (I received the disease from a contaminated blood transfusion in 1988). I have mild depression, I currently only take 37.5 mg of Effexor - but would love to get off of this, and WOULD if I am able to take SAM-e. I have bad asthma, I take Spiriva, Advair and Ventolin and I have allergies, I take a no-name brand antihistamine (non-drowsey). Once I get myself OFF of the Effexor, would it be advisable to take the SAM-e even if I have HEP C? Could I still take the SAM-e if I was to go on Interferon to try and cure my HEP C? Would the SAMe be advisable to take given the above complications in my system? Also, degenerative heart disease runs in my family, as well as arthritis. THANK YOU soooo very much if you can help me out with this info, I am extremely appreciative for any help you may be able to provide. I really like what I have read about SAM-e, and would MUCH rather take a NATURAL suppliment rather than the Effexor.
   A. We have not seen any studies regarding SAM-e and its influence on the liver in those who have hepatitis C. SAM-e is a potent mood lifter and it can have side effects when used in high dosages. Please make sure you read all the benefits and side effects of SAM-e and ask your doctor to read them, too. If your doctor decides to use it, he or she may recommend taking half of a 200 mg tablet. The benefits of SAM-e, and the side effects, can accrue over time, it builds up in the system so if 200 mg a day was fine initially, it may quickly turn out to be too much as the dose from one day adds up on the some of the leftover effects from the day before. We don't have any experience or seen research using SAM-e in combination with interferon or other drugs, so caution is advised. Much of the SAM-e effects, or other medicines, is dose dependent.

Q. Is there any reason not to take 200 or 400 mg a day SAM-e with Coumadin?
   A. The whole person has to be evaluated in making such decisions, not just two variables such as the supplement and the medication.

Q. I am currently taking SAM-e -800 mg/day for seasonal affective disorder and osteoarthritis. I have taken it with great results for the last 6 yrs. My knees are pain-free and I can "live through the winter". My Doctor has prescribed Wellbutrin xl for seasonal depression- it has been particularly bad this year. (150 mg and then after 2 wks up the dose to 300mg). Do I need to get off the SAM-e or will they act independently of each other? I'm afraid to get off of the SAM-e b/c it takes weeks for the Wellbutrin to take effect and I am severely affected by the winter depression without it- I also have nightmares when I abruptly change dosage of the SAM-e.
   A. We suggest your doctor read the page on SAM-e. There could be potential danger combining the two, particularly in high dosages.

Q. I am 74 years old, male living in Istanbul Turkey. I am in depression now, it is 4th one in 6 years. Antidepressants never helped me to shorten each period of depression; each depression took 8-10 months at least. During my search in the web I discovered the product SAM-e and purchased it from the US, in order to to try it in addition to my antidepressant. It has not arrived yet. Later I discovered an article of Winston Wicomb, Ph.D http://www.stoneclinic.com/sam_e.htm
saying: “But the most important potential problem: SAM-e is converted into homocysteine in the body. High levels of homocysteine may raise the risk of heart disease. SAM-e is likely to promote higher levels, though no one knows how high. Interestingly, SAM-e breaks down into the potentially harmful homocysteine, which has recently made press as a substance strongly correlated with heart disease if it is left to build up within your cells. The good news is that SAM-e, which is so good for you does NOT have to turn into a toxic build-up of homocysteine. With the proper complement of B-complex vitamins (especially B-6, B-12 and folic acid, which are all methyl-donors), homocysteine is re-methylated into good old methionine (used to produce S-Adenosyl Methionine) or convert to the antioxidant glutathione. People taking SAM e should be well advised to supplement with B vitamins. This will ensure adverse reactions and prevent homocysteine build-up. Thus one health problem is combated only to introduce a different problem? ”
   However my other finding http://www.homocysteine.net/biochemistry.asp looks like saying the opposite of it: “More of the SAM e - the body's best anti-ageing agent If the body then adds a different methyl group it produces a chemical called S-adenosyl methionine (SAM-e), which is a useful natural antidepressant, fights against arthritis and is excellent at lowering homocysteine levels. As levels of SAM-e increase, another vital chemical is produced from homocysteine called glutathione. This is the body's best anti-ageing agent and also works as a detoxifier. A low glutathione level has been linked to an increased risk of death from all common causes. The key to a long healthy life - keep the homocysteine level down and the glutathione level up.” Because of the above apparent discrepancy, could you kindly give me your reply to the following question: when I take SAM-e is it going to be first converted into homocysteine in the body so that it will increase the homocysteine level?
   A. It is yet not clear what happens in the human body when a SAM-e supplement is taken, whether it has beneficial or harmful effects in the long term. However, a more immediate concern with SAM-e is the side effects as listed on this web page. Older individuals, or those taking other medications, should not exceed 100 mg of SAM-e initially and then reduce the dose if there are symptoms of insomnia or being too stimulated. SAM-e is potent. One should not be concerned about the effect on homocysteine since this is not a pill to take for prolonged periods. If you take B vitamins, we suggest not to exceed one or two times the RDA.

Q. is SAM-e ok to take as a supplement if one is on cholesterol lowering drugs like Zocor or Vytorin? Is there any potential side effects to the heart taking SAM-e while on these drugs or would it be better to get off them entirely to use SAM-e.
   A. High dosages of SAM-e could stimulate the heart to beat faster and it can cause insomnia. We are not aware of direct interactions of SAM-e with statin drugs such as Zocor or Vytorin.

Q. I was taking 400 mg Sam-E and i didn't feel right; so I read the article by Dr. Ray Sahelian where he recommended lower dosages. I reduced my Sam-E dose to 100 mg and I now am fine.

Q. SAM-e worked well for mood enhancement for me, but I stopped it because of loose bowels. I tried different doses from 1/2 tablet to 2 and didn't notice much difference in this side effect. St. John's wort seemed to work the first three or four days and then didn't have much effect. It also gives me loose bowels. Does this mean that my neurotransmitters are normal, or I'm just sensitive to herbs. I have been very sensitive to prescriptions, so I wanted to try something natural rather than ask for antidepressants. I am 64, work out three times a week, and use a low-dose estrogen patch (estrogen has helped me a great deal until lately).
   A. It is not possible for us to know without a full history and medical evaluation. Some people may be very sensitive to herbs and supplements and may need even smaller dosages.

Q. Can you tell me if it is safe to take SAM e with taking thyroid medication (medication taken b/c I have no thyroid)?
Also, for a friend of mine, does SAM e interact with other herbs? Is it OK to take a herbal suppliment that contains the following: Black Cohosh, Red Clover, and Kudzu Passionflower, Chasteberry and Wild Yam, Ashwagandh. Would you recommend taking 5HTP with SAM e - if so, in what dosage?
   A. SAM-e is a potent supplement and should be used with caution in those taking thyroid medications since anxiety, restlessness and insomnia could easily occur unless the dosage of the SAM-e is a fraction of the 200 mg pills commonly sold. There are many factors that influence combinations of herbs and supplements and there are no easy answers on combinations since different people react differently.

Q. I have been taking SAM-e for about 5 days now and I have noticed my muscles tighten up very easily when I exercise. I am a runner and I usually run 3-4 times a week several miles. I have been taking SAM-e 400mg every morning and I am wondering if I would benefit from decreasing my dosage and trying only to take SAM-e on the days that I do not exercise? What if any is the link between SAM-e and exercise?
   A. SAM-e does influence several neurotransmitters that could affect muscle tissue but we have not seen any studies specifically addressing the role of SAM-e and exercise or muscle tissue. SAM-e 400 mg is a very high dose.

Q. My 16 year old daughter is on Minocycline, 100 mg. twice a day for severe acne. Is it safe for her to take Sam E for mild depression at the same time?
   A. This is a decision her doctor has to make. We have not seen studies that have combined the use of SAM-e supplements with antibiotics.

Q. I am a 60 year old man who started taking 400 mg of SAM-e pill in the morning before breakfast and another 400 mg SAM-e pill before bed to improve my mood. I took this dose for around 4 months without side effects but discontinued because I felt the effects to be subtle to marginal at best. I have been plagued with untreatable Radial Brachial Pruritus for nearly 20 years and itch free interludes have become increasingly rare and shorter in duration. I experienced almost nonstop excruciating nocturnal itching for the 4 months after I discontinued SAM-e pills. I had become used to this cycle of itching and interlude and never expected that the SAM-e might be effecting the RBP. My wife noticed that my most recent interlude ended when I discontinued SAM-e. I resumed my original dose and the itch abated in 2 days. In the 2 months that I have resumed the SAM-e I have been itch free. Since I have enjoyed itch free intervals for nearly this long I'll be waiting to see what happens.

Q.  I have a very important question about Sam-e and I'm hoping you can help. I have been taking Sam-e for about two years now and I cannot remember ever feeling so great. I take two 400mg tablets every night. However, I am having surgery in two weeks. My doctor advised me to stop taking any herbal supplements. However, without Sam-e or with a lower dosage my depression immediately returns. Is it absolutely necessary to stop Sam-e before surgery? My doctor is not very familiar with the supplement and I'm afraid he is just being overly careful.
   A. Your doctor has to balance the risk from stopping the supplement in terms of depression versus untoward reactions from the use of SAM-e whose role in the body during or after surgery is not fully known.

Q. I was taking Cymbalta and Provigil for depression and it caused me to have a seizure. I am off all medication now but am feeling the depression returning. Is there any research association with Sam-e lowering a person's seizure threshold that you are aware of?
   A. SAM-e influences several neurotransmitters in the brain and, although we have not come across specific research regarding the influence of SAM-e on seizure risk, there is a theoretical possibility that SAM-e supplement use could influence seizure activity.

Q. I work a in a very stressful job and when the stress is at its highest, usually for 6 weeks at a time, I even get muscle twitches around the eyes. The stress causes me too wake up at night and I'm unable to get back to sleep because my brain is racing about work. This lack of restful sleep further compounds the problem. I'm wondering if SAM-e pill would be a good OTC supplement as a natural stress remedy to help manage the stress and help me get a better nights sleep?
   A. It is possible that low dosages of SAM-e pill, at 50 mg taken in the morning, may be helpful, but higher dosages of SAM-e supplement can cause anxiety and alertness late into the night that can cause insomnia.

Q. I purchased SAM-e mood enhancement pills and it says on the box instructions to take two 200mg SAM-e pills a day. Is it best to take them both at once or one in the morning and one at night?
   A. SAM-e is a potent mood enhancer and has side effects if the dosage is too high. Although initially some people may tolerate high SAM-e dosages, the effects soon build up and SAM-e side effects can occur such as anxiety, restlessness and insomnia. Altough at first many people may tolerate SAM-e dosage of 200 mg or 400 mg, after a few days this could be too much. We suggest using as low a dosage as possible, even if it means using a half or a quarter of a SAM-e tablet.

Q.  I've been searching all over the Internet for information on a possible interaction between SAM-e 400mg daily and spironolactone 200mg daily and haven't found any information. I've been taking 200mg of Spironolactone since 2004 for acne, very pleased. I only had menstrual irregularities the first 2 months and afterwards everything went back to normal with a cycle every 4 weeks. However in 2006 I started taking SAM-e pills in addition to Spironolactone, on a daily basis, for depression. Dosage would be from 400mg to 1200mg, however currently at 400mg daily. I have found that when combining these two - my menstrual cycle occurs every other week. It's terrible because I need both of these, as both are very beneficial, however the side-effects are incredibly frustrating. When SAM-e pill is removed my cycle goes back to normal with taking only Spironolactone. Birth Control does not agree with my system so it's not an option. Have you heard of anyone else taking this combination? I am 28 years old; normal weight (slim), no other health issues aside from ADD, in which I take 20mg of Dextroamphetamine (since 2003).
   A. We have not seen any research regarding the combination of SAM-e pills and spironolactone or had any feedback from anyone taking this combination. The interaction between different medications and supplements is difficult to predict and as much as possible dosages and frequency of use should be minimized.

Q. I have been wondering about sam-e, read on the Univ. of Maryland Medical Center website that sam-e levels may be low in people w/ Parkinson's and heart disease. However, experiments in rats have indicated that sam-e supplements may actually cause Parkinson's disease in these animals." Have you heard anything about a connection between sam-e and Parkinson's? Another thing I'm wondering about is which neurotransmitter systems does sam-e seem to target, do we have a clue at this point? My uneducated guess about pharmaceutical antidepressants like the various SSRI's, tricyclics, and MAO inhibitors is there is some knowledge of which neurotransmitters each one tends to affect more strongly; how would sam-e be categorized among these in terms of its effects?
   A. The interpretation of the effects of supplements or medications on rodents is helpful but can sometimes be unreliable since researchers often give the animals dosages that are several fold what humans would ingest per weight ratio. SAM-e is a methyl donor and can influence a number of neurotransmitters. SSRIs mostly influence serotonin levels, MAO inhibitors mostly influence dopamine levels. SAM-e is not easy to categorize since it influences several neurotransmitters.

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