SAM-e supplement for depression, side effects, dosage 100 or 200 mg tablets
Is it safe to take more than 400 mg? by
Ray Sahelian, M.D. author of Mind Boosters: Natural Supplements that Enhance Your Mood, Memory, and Mind
November 18 2017

SAM-e is a powerful natural mood elevator and can be used to treat depression or used in those who have low mood. However you have to be careful. If you take too much you can get anxiety and insomnia.
S-adenosylmethionine is made from the amino acid methionine and ATP. SAMe is a methyl donor involved in the making of dozens of important compounds in the body. This nutrient has been available by prescription in Europe for many years as an antidepressant and has been available over the counter in the US since about 1996.
It is present in every living cell in the body. However, levels tend to decline with age.

My experience
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 200 mg. If you plan to take it under medical guidance, here's a few tips your doctor may not know. It's best taken in the morning before or with breakfast. 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 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.

Buy SAM-e supplement 100 mg per pill - Adenosyl Methionine ē Pharmaceutical Grade, Stabilized

This SAM-e supplement is a stable, bioavailable form. The tablets are enteric coated and blister packed to prevent breakdown and inactivation of the ingredients. Dozens of clinical studies have demonstrated that it helps support a positive outlook. It is able to cross the blood-brain barrier where it affects the synthesis and activation of various brain chemicals, such as neurotransmitters. SAM-e also 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.


Buy SAM-e supplement 100 mg or 200 mg
Supplement Facts
Serving Size: 1 Tablet
  Amount Per Serving %DV
SAMe (S-Adenosyl-L-Methionine) (from 200 mg of S-Adenosyl-L-Methionone Disulfate
100 mg *
* Daily Value not established.

Usage: Take half or 1 SAM-e tablet a few minutes before breakfast, or as directed by your qualified health consultant. High doses can lead to insomnia and anxiety. Many people do well with half a tablet or even less, or half a tablet every other day. Even if the tablet is enteric coated, it should not make a difference if you take half and the rest the next day.

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

Other products sold online
There are liquid forms of sam-e available, a search on google would reveal them, but I have not used them and do not know how stable or effective they are.
Doctor's Best, SAM-e 400, Double-Strength, 60 Enteric Coated Tablets
NutraLife, The Original SAMe (S-Adenosyl-L-Methionine), 200 mg, 60 Enteric Coated Tablets

Report from Europe
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."

Feedback from consumers
I started on a dosage of 400 mg SAM-e supplement daily and after a week felt like I was going insane. So I decided to step down the dosage to 50 mg. It seems though like the 400 mg week long course almost acted like a loading dose. Even stopping for 3 days and trying 50 mg immediately brought me back to the same symptoms I was feeling before - shortness of breath, anxiety, anger, etc. Every time I try and re-challenge with the 50 mg tab the symptoms come back. This is weird since the 400 mg dose was fine for the most part of a week. It could just be I am just sensitive to the SAM-e effects. I also take daily mega doses of B vitamins which could also be extending its effects.
   A. Once the body is loaded up with certain herbs or supplements, smaller amounts can trigger the same effects as higher amounts. This occurs with SAM-e and B vitamins could enhance the effects.

I'm 58 and I began taking 200 mg about a month ago and my life has totally changed! I am thinking clearer, multi-tasking is much easier, I am getting more organized and the best part is that I am getting tired earlier (rather than trying to sleep for hours). The sleep problem was an issue for over 10 years. My mind was racing so it took hours for me to fall asleep. Now I feel so much more calm. I also feel happier, although I never considered myself to be depressed. And I feel like socializing more. I feel alive again! Thank God for SAM-e!!

Mind Power Rx The herbs in this mind formula include: Ashwagandha, Bacopa, Fo-Ti, Ginkgo biloba herb, Ginseng herb, Mucuna pruriens, and Reishi. The nutrients and vitamins in Mind Power Rx include Acetyl-l-carnitine, Carnitine, Carnosine, Choline, DMAE, Inositol, Methylcobalamin, Pantothenic acid, Trimethylglycine, Tyrosine, and Vinpocetine.

This sophisticated cognitive formula combines a good balance of brain circulation agents and neurotransmitter precursors with powerful natural brain chemicals that support:

Memory and Mood
Mental clarity
Alertness and Focus

Arthritis and osteoarthritis benefit
SAM-e helps support the incorporation of sulfate groups into proteoglycans which help maintain cartilage and protect joints. Some studies have suggested that 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 it may be useful for some people with arthritis.

S-Adenosyl methionine versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. BMC Musculoskeletal Disorders. 2004.
The present study compares the effectiveness of SAM-e
(1200 mg) to a cyclooxygenase-2 (COX-2) inhibitor (celecoxib, Celebrex 200 mg) for pain control, functional improvement and to decrease side effects in people with osteoarthritis of the knee. 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.

I 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. Could you please let me know.
   It's difficult to predict an outcome in any one person. You may consider having your doctor read the Joint Power Rx page.

I know you recommend keeping the dose of SAM-e low, but my experience is quite different. I am 66. I started taking 200 mg SAMe daily about 8 years ago for osteoarthritis in my knees, along with glucosamine and chondroitin. It helped slightly. After a few years, and worsening arthritis in many joints, I increased it to 400 daily. Within a couple of weeks at the 400 dose I found I could walk for miles, like I did in my 20's. Then 2 years ago, I developed severe arthritis at the base of my left thumb, causing excruciating pain with the slightest movement, even turning a doorknob or lifting a cup. I couldn't play the guitar any more without wanting to scream, and I'm a guitarist. Not being able to play guitar, after 50+ years as a musician, was breaking my heart. Then 5 months ago, I bought a supply of SAMe at the store, forgetting I'd just ordered a supply of it on line, and suddenly had a great deal of it on hand, so I thought, what the heck, I'll try 800 mg daily. After two weeks I was able to play guitar with far less pain. I've had to modify my playing to avoid bar chords, which require a lot of sqeezing, but I can play guitar enough to enjoy it again, and I'm thrilled. I have no manic symptoms or other problems you mentioned, but I seem to have less anxiety than I used to have, and much better sleep.

S-adenosylmethionine supplementation for treatment of chemotherapy-induced liver injury. Anticancer Research. 2003.
Fifty cancer patients who developed, for the first time, anticancer chemotherapy-induced liver toxicity were received oral SAM-e supplementation. 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 . 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.

Depression, role in mood enhancement
Although most studies have used dosages in a range of 400 to 1000 mg a day for the treatment of depression, I have found that in actual clinical practice much lower amounts are quite as effective. When researchers study the effects of a particular medicine or supplement, they only have a brief period of time to elicit a response since they are limited by funds to keep the study short. However, this does not mean that the dosages the scientists used for a few weeks are appropriate for prolonged use for months or years. Many herbs and nutrients accumulate in the body  -- or at least their affects accumulate. When a person takes a 200 mg pill the first day (this is the most common dosage available over the counter), there usually is some lingering effect the next day. Therefore, when another 200 mg pill is taken the next day, it adds on to some of the one from the day before and so on as the days progress. Hence, if 200 mg was effective the first few days, with continued use it may become too high a dose and side effects could occur. When insomnia occurs and sleep disturbances occur, this can certainly lower mood and energy level and hence this could be counterproductive to fighting depression. I suggest to my patients that if they start noticing these side effects to take a break from SAMe for a day and to resume at half the dosage they were taking.

J Clin Psychiatry. 2014. A Double-blind, randomized, placebo-controlled clinical trial of S-adenosyl-L-methionine (SAMe) versus escitalopram in major depressive disorder. Patients were randomized for 12 weeks to SAMe 1,600-3,200 mg/d, escitalopram 10-20 mg/d, or placebo. Doses were escalated at 6 weeks in the event of nonresponse. The results fail to support an advantage over placebo for either the investigational treatment SAMe or the standard treatment escitalopram for MDD.

Because of its role in the making of neurotransmitters, SAM-e has been tested in the therapy of depression. A number of studies have been published, mostly in Europe, evaluating this nutrient’s role in mood disorders. Back in 1994, Dr. Bressa, from the University Cattolica Sacro Cuore School of Medicine, in Rome, Italy conducted a meta-analysis, which is a statistical pooling of already published research papers. Dr. Bressa concludes, "The efficacy of SAM-e in treating depressive syndromes and disorders is superior to that of placebo and comparable to that of standard tricyclic antidepressants. Since it is a naturally occurring compound with relatively few side-effects, it is a potentially important treatment for depression."

The influence of SAM-e on depression has also been tested in the United States. Back in 1994, researchers at the University of California, Irvine Medical Center, did a double-blind randomized trial involving a total of twenty-six patients. They compared oral SAM-e with oral desipramine (a pharmaceutical antidepressant). At the end of the four-week trial, 62 percent of the patients treated with SAM-e and 50 percent of the patients treated with desipramine had significantly improved. Similar results were found in a 2002 study when it was compared to imipramine.

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. 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. Journal of Clinical Psychopharmacology, 2004.

For depression, should one try 5-HTP or SAM-e?
   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 the latter. There's really no good blood test that can tell who will respond to what.

Testimonial from a doctor
Hello Dr. Sahelian, I too am a physician and recently tried Sam-E after it was recommended for my dog. I researched it for a bit and thought Iíd try it for my chronic dysthymia / depression. I have tried everything else over the years, and I mean everything. The results: 1) My chronic depression has lifted after only about 2 weeks on Sam-E. It has truly been a miracle. No discernible side effects.  I now know what normal feels like. 2) My libido, which has been very low my whole life, has become what I believe is a normal libido (for someone over 60), something I have never felt in my life. Iíve been on everything including testosterone supplements but nothing helped. I gave up on the testosterone years ago. This is NOT placebo effect. I literally even have changes in my skin including very mild acne. I havenít changed anything else in my diet or meds (BP and cholesterol meds). Just wanted to let you know as your web site was informative.

I have been taking SAM-e tablets for approximately three weeks and have had no urges to gamble or drink. I am a recovering compulsive gambler and alcoholic and have had recent bouts with depression. My counselor thought that giving SAM-e tablets a try would help, as she found it to help other gamblers and alcoholics such as myself. It is a blessing for me, as I can focus more clearly on rational thinking day to day instead of the delusional thoughts that compulsive gambling had led me to believe. I will not admit that I am cured but the relief I am experiencing has been amazing to say the least!

Liver health
I was curious about your page on SAM-e and why more of the liver enhancing effects were not mentioned? I appreciate all of the input on the anxiety one can experience on SAM-e. My husband has Hep C and is on a very high potency milk thistle and NAC and I want to put him on SAM-e. I will proceed slowly with him and I do expect it to enhance my husbands liver function.
    The long term effects of SAM-e supplements on human liver function is not clear and we will provide more information as more studies are mentioned. In short term studies there have been some potential hints of it being beneficial in liver health, but longer term trials are needed to determine if liver health improves or whether there are side effects.

World J Surg Oncol. February 2 2014. Protective effect of SAM-e on hepatic ischemia-reperfusion injury during hepatectomy in HCC patients with chronic HBV infection. Preliminary findings suggest that preoperative administration of SAMe is useful and safe for reducing the HIRI in partial hepatectomy, especially for HCC patients whose disease is associated with chronic HBV infection and cirrhosis.

Arkh Patol. 2013. The hepatoprotective activity of remaxol and S-adenosyl-L-methionine for liver damage caused by reserve-series antituberculosis drugs. Experiments on male albino outbred rats investigated the hepatoprotective activity of remaxol and ademethionine in liver damage caused by reserve-series antituberculosis drugs. The test drugs had a mixed action, by reducing the degree of cytolytic and cholestatic syndromes. Remaxol and ademethionine assist in diminishing the degree of liver structural and functional impairments occurring with reserve-series antituberculosis drugs, by restoring the girder structure of lobes and decreasing the magnitude of dystrophic changes to stimulate reparative processes.

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. 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. Most 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.

I have a query regarding the simultaneous use of SAM-e with a MAOI. Is it a general principle not to take these two together?
   I am not aware of research regarding its use with MAOI drugs, but I would not feel comfortable taking them both the same day.

Sexual health and libido
Will Sam-e cause similar sexual side effects as prescription antidepressants (like decreased libido)?
   Not likely, if anything there may be a slight increase. 5-HTP, on the other hand, by converting into serotonin, decreases sex drive.

Sexual dysfunction is a known side effect of antidepressant treatment, affecting the majority of those who take these meds. During a 6-week, single-center, randomized, double-blind trial of SAMe augmentation for SSRI / SNRI- nonresponders. Men treated with adjunctive SAMe demonstrated significantly lower arousal dysfunction at endpoint than those treated with adjunctive placebo. SAMe can have positive benefit on male arousal and erectile dysfunction, independent of improvement in depressive symptoms. Eur Psychiatry. 2012. SAMe and sexual functioning. Department of Psychiatry, Massachusetts General Hospital, Boston, MA.

Smoking, no benefit
J Altern Complement Med. 2012. S-adenosyl-L-methionine (SAMe) for smoking abstinence: a randomized clinical trial. Abstinence and tobacco withdrawal data from this clinical trial suggest that SAMe holds little promise for the treatment of tobacco dependence.

Thyroid, hyperthyroid
I do not suggest using SAM-e in those who are hyperthyroid.

Product availability, dosage
The suggested dose of SAM-e in the therapy of depression ranges from 100 to 400 mg a day, although many individuals with mild depression do well with 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 and wrap it with plastic wrap for use the next day. Remove the plastic before swallowing the leftover half. The plastic is only for storage and avoidance of exposure to air.
   Many nutrients work in a similar fashion, particularly other methyl donors such as DMAE, TMG, DMG. In fact, B12 and folate help the body produce SAM-e. Therefore, your dosage should be reduced if you are taking other methyl donors. However, none of the nutrients mentioned above work as well or as quickly as SAM-e in lifting mood.

Q. 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. 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 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. You say it's OK to split an enteric coated SAM-e tablet in half and having the remainder the next day. My question is that the enteric coating is for getting it through the stomach intact, so once you have broken it in half, there's nothing protecting it from disintegrating in the stomach acids and rendering it useless.
   A. I have not seen any studies with SAM-e enteric coated pills compared to regular sam-e pills so at this point it is up to the manufacturer to demonstrate there is a difference in their use. For practical purposes it is more important, in my opinion, to take less of this natural antidepressant, even if it involves splitting it, than taking a whole pill due to the concerns I have with higher dosages.

SAM-e side effects, risk, danger, safety

High doses can lead to SAM-e side effects of anxiety and restlessness, headache, and cause insomnia. Long term adverse reactions are currently not well known. Some do well on even 50 or 100 mg (one quarter or one half of a 200 mg pill) per day or every other day. Caution is advised when combining it with pharmaceutical antidepressants or other drugs and dietary supplements with a stimulant nature.
   SAM-e side effects may also lead to a manic swing in those with bipolar disorder. Another adverse effect is nausea which can be reduced when it is taken with or after a meal as opposed to an empty stomach. I have also had feedback from some users that they experienced heart palpitations.

My 17 year old daughter has suffered from depression over the past year. She has had bad reactions in the past to some prescription medication- Lexapro side effects. She is under the care of a chiropractor who practices functional medicine. She has not responded to many of the nutritional supplements that are indicated for her. She took the Sam-e under this doctor's care, starting at a low dose of 100 mg and building up over time. After about 3 weeks she started taking 600 mg. She then started to have a racing heart, pounding, anxiety attacks - worse upon awakening but staying to some degree all day. We started out slowly with her- on 100 mg and gradually building up as we saw no response. In the directions on one of the SAM-e boxes it suggests starting at 400 mg and doubling it and higher if the desired effect is not seen. It would be good if manufacturers were more conservative on the box for recommended dosage.

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. 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 was so glad to find this site because I have had so many questions about sam-e but did not know where to get answers.
   I have not seen any long term studies with SAM-e, therefore I really can't say whether long term use is involved in this matter of low white and red blood cell count.

I was taking SAM-E, I believe it was 400 mg a day for mild depression due to back pain and Fibromyalgia. A few days after I started I starting having strange bowel movements. Very large stools (long) and urgent. I would feel tremendous urge to go but would need to drink lots of water to move it out and had to strain. I stopped taking it after a few weeks and from then on have had IBS symptoms Have you ever heard of extreme bowel movements from SAM-E.
   This antidepressant influences a number of neurotransmitters and thus can have an effect on the intestinal system.

I started 100mg once a day for 14 days of SAM-e for mild depression, and on the 15 days I started having mild side effects of mild anxiety attacks, heart palpations, elevated blood pressure to 132/78 and sweating palms, and very mild shakes. I have discontinued taken it on the 15 day. I have only took small does for 14 days, should I stop cold turkey, or taper off?
   A. I can't give specific advice, but in my experience stopping cold turkey has not caused major problems.

I tried taking it several months ago for an enlarged prostate and ended up with blood in my urine. I stopped it for awhile and tried taking it again at a later date and the same thing happened. Have you heard of this before?
   A. I have never heard of blood in urine associated with SAM-e pill usage.

The use of 50 or 100 mg should not cause anxiety if one takes a break of two days a week, and it is difficult to predict in each individual how they will respond to SAM-e, whether anxiety will develop or not.

Q. Having been inspired by many articles on SAM-E, after years of stagnant results of Cipralex, I decided to give it a go. I went straight to 400 mgs of this supplement, and felt great, sharp, energetic, and balanced. Only recently, after 1.5 months on SAM-E, I have been getting horrific anxiety, chest / head pains, mood swings, foggy thinking, and paranoia. I decided to get off the SAM-E. It seems SAM-E is no good with my medication, and I worry if its a safe combination or not. Is there any way to clear It from my body and feel normal again? Doctor's have told me they have no expertise in this field. This is urgent, what can I do to balance out my hormones and everything affected by SAM-E?
   A. Stopping it should take care of the side effects after a few days or a week or two.

Gastrointestinal symptoms
I wanted to see if taken at the 400mg dosage can cause stomach issues - i.e. stomach upset, bloating, indigestion. It has done wonders for my depression, but now I'm experiencing the stomach problems and side effects.
    Yes, it is possible that these pills, in high dosages, can cause gastrointestinal symptoms. Taking it with 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 lower doses.

In your experience are GI side effects (specifically diarrhea and stomach aches) generally transient for those on high doses of SAM-e (e.g. 1200 mg daily) or are they known to persist in a small number of people? Can these side effects be more pronounced when it is used in conjunction with an SSRI / SNRI withdrawal strategy?
    Most likely the GI side effects are likely to continue as long as high dosages are taken but I have not seen studies that have focused on this particular adverse effect. It is possible that the GI symptoms can be more likely when used in combination with SSRI / SNRI drugs or during their withdrawal.

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 nutrient, herb or medication can be beneficial or a poison depending on dosage.

Heart rhythm disturbances, palpitations, tachycardia, fast heart rate
Testimonial received November 2017 - I have osteoarthritis in my 75th year, and a candidate for hip replacement. This motivated me to find ways to stimulate cartilage regeneration, and started me on 200 mg of SAM-e. Paroxysmal tachycardia after a week got me into ER and overnight in a neuro unit hospital ward. Serum analysis revealed low K, 3.7, whereas my norm is 4.2. The staff gave me a 20 meq dose of KCl and sent me home after my sinus rhythm was normalized. After much dietary experimentation, using high doses of taurine, arginine, and enriching my diet with potassium foods, my heart returned to normal and stable function. I had to stay off SAM-e and any methyl donors like TMG. It's been a long struggle, 3 months now, and after several attempts with SAM-e, and other methyl donors like methyl B12, my body is so sensitive to these supplements that just one dose will result in my waking up at midnight with atrial fibrillation. And the popular sulfates like MSM at the high dosage recommended for arthritis also seem to affect my heart rate with frequent ectopic beats.  For the time I did use SAM-e, it helped tremendously with the pain. I so wanted to continue for that reason.

High blood pressure
One small study did not indicate SAM-e raised BP, however, it is possible that some individuals respond with higher bp.

SAM-e is not a good option to those who have sleep problems. It causes alertness.

I started taking 200 mg tabs 13 days ago. I have felt extremely tired in the mornings (hard to get out of bed) and heart palpitations. I don't want to stop taking it but would like to find a way to reduce this negative side of the supplement. I also have noticed reduced appetite. I am wondering if certain supplements should NOT be taken at the same time as SAM-e or which SHOULD be taken at the same time. Can I cut the dose by simply taking it with a meal?
    Each person who uses these pills for mood enhancement has a different need and dosage. It is quite possible that heart palpitations are caused by this natural supplement. Some people find good benefits with a lower dosage or taking the pills every other day. The use of any medication or natural pill for mood enhancement and treating depression varies depending on the severity of the depression and the circumstances that let to it. Some people may only need to take these natural products for a brief period whereas others need to take them off and on for several months or years.

I was diagnosed as Major Depressive. Since I'm very sensitive to medications I asked my psychiatrist not to prescribe the usual drugs. He suggested Sam-e product. I was delighted to take a supplement rather than a drug. Boy, was I surprised! My Dr. wanted me to be on 800 mg/day. I erred on the side of caution and only took 200mg/day for about 2 weeks. I then increased it to 400 for another 2 weeks. He urged me upward and for a few days I took 600 mg. I couldn't sleep and called my Dr. He said take the pills earlier in the day. I still couldn't sleep but I noticed I had desire to get out and do things. The next morning I took my pill and wham! My extremities got cold and I couldn't feel my hands or feet. My heart raced, I grew dizzy and my breathing was rapid. I almost passed out by the time the Paramedics came. In the ER they called it a classic panic attack and I was released to go home.
    You may with to have your doctor read this page regarding dosage and adverse events.

I had a strange reaction the fourth day taking Jarrow sam-e 200mg a day. Have been taking vicoprofen 7.5 twice a day for several months when i started it, it was the most alarming feeling in the brain and seemed almost visual at the same time, it happened twice today. The reaction was so alarming for the maybe minute it lasted i thought well this is it "i am dying" felt slammed into a brick wall., vision seemed off, then like i wouldn't be able to keep breathing and felt sucked back and then as it wore off felt sick and then a little distant the rest of the day.

Bipolar disorder
SAMe could trigger a manic episode even in those who are not predisposed to bipolar disorder. It could make someone act in a way or say things they would not normally do so.

I am not aware of studies with SAM-e and pregnancy and to be safe it is best not to use it unless a doctor approves in low dosages.

I am taking SAM-E with the intention of helping with drug-resistant depression / Bipolar NOS. It hasn't helped with that, however I was very surprised that it helped with my rate sleep disorder called Irregular Sleep-Wake Pattern. I saw that benefit when my dosage reached 2400mg/day. I have been taking it at night. I am now reducing the dosage, due to side effects, and hopefully the benefits will not go away. Anyhow, can the fact that SAM-e helped with the sleep disorder help diagnose the cause of the sleep disorder? For example, does it mean that my brain does not convert a certain substance into Serotonin?
   I have no clue at this time. Most users notice difficulty with sleep on high dosages.

Withdrawal symptoms
Would there be problems to suddenly stopping SAM-e? Does it have a rebound effect?
   Thus far we have not seen a rebound effect or any significant problems when it is stopped, but there could be exceptions in rare individuals.

Biochemical properties
SAM-e influences brain chemicals by helping to convert norepinephrine to epinephrine and serotonin to melatonin.
   It is involved in the production of creatine, an important energy reservoir in muscle tissue. 
   Helps the preservation of glutathione, an important antioxidant.
   Furthermore, it 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.

Summary and review
SAM-e is a useful therapeutic agent for depression and perhaps arthritis and other disorders. Long-term studies are needed before making widespread recommendations for its use. However, short-term human studies thus far have found it to be effective. Many people can do well with less than the normal 200 mg tablets.
   Dr. Bottiglieri and colleagues, from Baylor Research Institute, in Dallas, Texas, published a review article. They summarize, "SAM-e is required in numerous methylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis is intimately linked with folate and vitamin B12 metabolism, and deficiencies of both these vitamins have been found to reduce central nervous system SAM-e concentrations.."

Combining with other dietary supplements

I am taking 5-htp for anxiety/depression and weight loss. I would like to add SAM-e to help with hip pain.
   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.

B vitamins
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 in order to prevent toxic build-up of homocysteine.
   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.

St. John's wort herb
As a rule I prefer not mixing potent supplements unless a person is fully aware of how each one influences their body. Overstimulation and insomnia are common side effects from the combination. If a person does combine both the same day, St. Johnís wort and Sam-e dosages should be a quarter or at most half of the dosage of each taken separately.

Combining with prescription medications:

Beta blockers
As a medical librarian I get all kinds of questions with regard to health. The most recent one was with regard to SAME-e and beta blockers. Is it advisable to take this natural pill if one has to take a beta blocker? I came upon your sight with regard to this natural antidepressant and was impressed with your cautious advice to all questions.
    SAM-e pills increase heart rate and beta blockers can block this effect. I have not seen studies regarding the combination of this medication and natural supplement, but in low dosages I don't foresee any major problems. However, each person is different and may react differently. As a general rule it is best to use each one separately for a week or two, and when combining use low dosages and have medical approval.

SSRIs, Prozac, Zoloft, Paxil, Celexa, SSRI drugs
Is it okay to combine SAM-e with Paxil or other SSRIs?
   We do not recommend such combinations unless the dosages are very, very low. They are both potent and the combination could lead to overstimulation and other side effects.

I am currently on 40mg of Celexa for depression and have been for about 2 years. It has only been mildly helpful. I want to give SAM-e a try, but I canít find any information about how I should make the switch. Do I take both together for a while? Do I taper down the Celexa and then start SAM-e? Do I quit Celexa cold turkey and start the SAM-e immediately? Any information, studies, recommendation would be greatly appreciated.
   As a general rule, it is not a good idea to take a SAM-e supplement along with pharmaceutical antidepressants. SAM-e is powerful and should be considered as potent as a pharmaceutical antidepressant. Ideally a SAM-e pill should be taken alone to determine how it is working by itself rather than being confused on its effects when taken with Celexa or another prescription antidepressant. There are no specific guidelines that apply to every person since much depends on the dosage used of the medication and the natural pill, how long a person has been taking the medications, the severity of the depression and the recovery, other medications used at the same time, other supplements used, diet, activity level, sleep patterns, heart conditions, blood pressure, and other factors.

Over the last few years I've purchased and returned SAM-e several times fearing taking it. The Mayo Clinic website mentions interactions with blood pressure medications, and as I'm taking Cozaar this concerns me. Also, I drink Chamomile tea at night, and take a very small dose of Xanax to help me sleep. At dinner I have a glass of red wine. Also, I take B vitamins, and Acetyl-L-carnitine. I've asked my doctor about SAM-e and he knows nothing about it. I then asked two different pharmacists, each giving me a completely different opinion. One said there are too many interactions with it; the other said it only really reacts with antidepressants and valarian. Is SAMe safe with the following: Cozaar ( for high blood pressure), Xanax (low dose), wine ( at dinner), Chamomile tea ( before bed), Acetyl-L-Carnitine ( for brain health), B vitamins, and multivitamin supplements?
   See above answer.

Q. My question is if there's a problem with taking SAMe together with tramadol, lets say 200mg sam-e with a capsule 50 mg of tramadol a day. I'm trying to build of tramadol use but im doing it slowly.
   A. We would be concerned about serious side effects, both have potent effects.

Wellbutrin medication
I already take Wellbutrin150 mg per day and Prozac 20 mg per day and am considering trying Sam-e pills to help with my PMDD symptoms. What would be your opinion on adding Sam-e pills to my regimen?
    Ideally it should be taken by itself to determine how it is working by itself rather than being confused on its effects when taken with Wellbutrin, Prozac or other prescription antidepressants. There are no specific guidelines that apply to every person since much depends on the dosage used of the medications and the SAM-e dosage, how long a person has been taking the medications, the severity of the depression and the recovery, other medications used at the same time, other supplements used, diet, activity level, sleep patterns, heart conditions, blood pressure, and other factors.

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?
   To the best of my knowledge, the mechanism of action of Wellbutrin is still not very clear, but it does involve the adrenergic system and dopamine. SAM-e helps the brain make more of certain neurotransmitters. Their mechanisms of action are different. They both provide good anti-depressant effects, which is the final objective.

Thyroid medications
Does SAM-e interfere with Synthroid for those who are hypothyroid and are taking Synthroid medication or Levothyroid?
    SAM-e is quite a potent supplement and should be treated as carefully as a prescription medication. In those whose dosage of thyroid medication tends to be slightly excessive, the side effects of SAM-e, such as rapid heart beat, restlessness and insomnia, could be aggravated. Levothyroid (levothyroxine sodium) contains synthetic crystalline L-3, 3', 5, 5'-tetraiodothyronine sodium salt [levothyroxine (T4) sodium]. Synthetic T4 is identical to that produced in the human thyroid gland.

I recently began using SAM-e for depression and anxiety. I also take levothyroxine for hypothyroidism. I was wondering if it is okay to take SAM-e and levothyroxine at the same time, in the morning before breakfast, and if it would influence the levothyroxine absorption / hypothyroidism in general. I take 200 mg a day. I cannot find any information about this online.
    I have not seen studies regarding the use of the natural antidepressant in those with thyroid disorders or on synthroid or other thyroid medications. It would be prudent to use low dosages and monitor carefully for any stimulation or heart rate increase.

Use by children and adolescents
I have a 6 year old daughter approx. 23 kg. in weight, diagnosed with ADHD. The doctor prescribed Concerta and Intuniv. She has meltdowns in the afternoon. I decided to try SAM-e 200mg in the am about 3 days ago. I have a question as to whether sam-e can be used effectively with ADHD medication.
    This supplement is quite potent and 200 mg is a high dose for a child and could cause side effects either by itself and particularly when combined with prescription medications.

mails and comments
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. I was taking 400 mgs a day in the morning 30 minutes before breakfast. I was having phenomenal results for my depression with it but was experiencing anxiety. The package warns that people with bi-polar disorder not use it because of mania. 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 than I have in years!! Simply amazing stuff and I think I am going to try the lower doses 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 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 guaifensin I tried it. 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 mg 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.

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 anti-anxiety 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.

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 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 vitamins is considered to be a selling factor as well. 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?
   A. An internet search reveals Me-Cofactors by Dews to have the following: One Caplet 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.

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?
   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?
   A. I have not heard of OptiForm SAM-e.

Q. Do you know anything about Azendus SAM-e from Extreme V? Can't find anything in the way of reviews.
   A. As of 2017 I have not seen any independent studies about the brand made from Extreme V, Azendus.

I am from Netherlands and I want to report you the very good results by taking SAM-e for several weeks now. My mood has made improvements, I have much more energy, a clearer mind and less problems with the poly arthrosis. Also my husband has good results with his muscle problems and energy. I take 100mg each day. Is it harmful to use this supplement for years? 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 its long term use. 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 SAM-e Tosylate Disulfate. How different is this from the regular type?
   A. Tosylate disulfate is a stabilizing agent. It does not seem that it has much of a contribution based on one study listed below, although we don't have much knowledge about this form and whether clinically it offers a better alternative. SAM-E is available in many forms. In order to stabilize the SAM-E molecule, and prevent 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.

Protective effects of S-adenosyl-L-methionine against enzyme leakage from cultured hepatocytes and hypotonic hemolysis.
Japan J Pharmacol. 1990.
Effects of S-adenosyl-L-methionine disulfate tosylate salt and L-methionine (L-Met) on rat erythrocytes and primary cultured hepatocytes were studied. SAM-e-ST 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.

Q.  I have been depressed most of my life - often severely and being distraught is much worse then depression - many reasons contributed including an extremely poor memory (memory is not addressed in most IQ tests so my IQ was high and I was deemed an underachiever and "anxious"). Anxious my foot as I told my parents since age 10 - a neuro-psychologist tested me 5 years ago and found I do fine under pressure and have a moderate to severe memory problem. Only my high verbal skills save me so that most others think I am bright (but never was told I was bright as a kid and I wasn't) but I can't work or perform most jobs even competently. I noted the SAM-e write-up stressed low dosage - I take 2,000 mg of TMG - I take this in the morning - could some people need high doses of SAM-e pills? You should mention that in at least one case high TMG is needed. SAM-e supplement is the miracle. I would go off other anti-depressants in the past - most didn't work except Luvox helped a little - but now I take cheap SAM-e. I take 2,000 mg of TMG (I don't know the equivalent SAM-e dose) and 1/2 hour later I take all B vitamins (though I've read that folic acid can either be a cure or cause of cancer - particularly anal cancer - so I take grape seed extract and other anti-oxidants to hopefully "cover myself". Anyway for 6 months SAM-e has saved my life and I haven't been severely depressed and no I don't feel over-anxious or stimulated and yes I have my sex drive back (under most anti-depressants, orgasm was an impossible thing).

My husband and I had started taking SAM-e pills a month or so ago. We are both in our mid 50s, overweight, and on daily doses of Lexapro (10 mg for me, 20 for my husband) and have been for 3 years. Neither one of us likes taking it, but when we try wean ourselves off we are reminded very quickly about why we started it in the first place. We started on 200 mg of SAM-e supplement once in the morning at least half hour before breakfast. I had read an article in one of the health journals I get and it said that the dosage should be up to 800 mg daily. We really liked the way we felt at 200 mg but increased it to 400 mg. Whew! Wrong thing to do!! I had a severe anxiety attack one or two nights and my husband had one the night after I did. So we weaned ourselves off. After stopping SAM-e we both noticed that we had actually felt better on it and my knees didn't pain me as much! My niece asked her Naturopathic physician about this for me and I found the term that helped me find out more-- That led me to Dr. Sahelian's site and here we are. This is what I found out: It is best to take SAM-e in low doses and not every day. Maybe 200 mg every other day-- or cut the pill in two and take half one day on an empty stomach and the other half the next day with food. At least once a week, we should take a break and not take it at all. It should not be taken with a prescription antidepressant like Lexapro. is the reason why I am writing to you-- Eventually, we would like to wean ourselves off Lexapro and take SAM-e instead. Is it a long term supplement? I'm talking the rest of our lives? If that's the case, do we continually change the dosage? AND can it be taken with fish oil? There are SO MANY supplements and so many varying opinions on how and why they should be used!!
    Each person is different regarding the dosage of a supplement or medication that works for them and the frequency of use. Long term human studies have not been done with SAM-e antidepressant pills so we don't know what would happen if these pills are taken for many years. The idea is to use the least amount and take breaks from use. The exact regimen varies from one person to another. Fish oils can be safely taken with most supplements if the dosage is less than 3 capsules a day.

Is there any weight gain or loss from the use of SAM-e pills?
    I have not noticed an obvious or very clear effect but I have not looked into this aspect in any great detail.

My wife, who has an ileostomy for many years (at age 19) as a result of a total colectomy performed for ulcerative colitis, has begun taking Sam-e enteric-coated supplements (200 mg/day) on an empty stomach. Occasionally, she will notice that a tablet will pass through her intestinal tract intact. We assume that if a tablet passes intact that it is a wasted dose and are not quite sure how to remedy this. Would it be better to take it with food or perhaps look for a Sam-E formula that is not enteric coated?
   Crushing the tablet before ingestion will likely benefit the absorption. The required dosage is likely to be less since more of it will now be absorbed.

I have been taking Sam-e for about 6 months now and am happy that it deals with my slight depression issues. I take 400 mg daily as recommended by my naturopath. I have experienced gastrointestinal and slight anxiety issues. I have gained 10 lbs since I started taking it.
    SAM-e pills have a tendency to stimulate and perhaps one would unconsciously eat more to help slow down or relax. I have not had such feedback yet regarding its use and weight gain issues but it is possible.

Can you get the same benefits from combining a methionine pill and ATP? Will it convert to give the same effects of SAM-e, or would it be best to just take the mood enhancing supplement itself?
    I have not tested the combination of methionine and ATP supplements, but I would suspect that they would not have the same effect.

I have been taking 200 mg of S-adenosyl-methionine as disulfate monotosylate for ten days now in hopes of helping my mood, mostly during PMS. After six days I felt fairly stable, like it was working, but starting around day nine I have had some moodiness similar to PMS (sensitive, slightly irritable, occasional sadness). I have not experienced any anxiety or unusual insomnia.

Is Sam-e safe to take with Xanax. I will be flying on an airplane in a week and I have a phobia of flying. I can only do it after taking Xanax. If I need to discontinue the Sam-e prior to flying should I do so now or just a few days before flying?
    While on the plane it may be a good idea to just be on the Xanax in order to feel sleepy and take a nap.

Is it ok to take SAM e and Lithium orotate together. I have been on a small dose of SAM e, but it does not seem to help with anxiety, so I have started the Lithium orotate.
   I often suggest people learn how each mood influencing herb or supplement works by itself before combining. It often takes a couple of weeks to learn the full effects of a particular natural supplement. When combined, dosages need to be reduced. Each person has a different metabolism, biochemistry and physiology therefore it is not easy to predict outcomes with combinations.