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.

Q. How long does it take SAM-e to get out of your system. I am going to be placed on an antidepressant and they want me to make sure the SAM-e is out of my system first so I don’t run the risk of serotonin syndrome. I was taking 200 mg a day, then skipped a day, then went to 50 mg a day, and skipped a day.
   A. Usually two or three days is sufficient.

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
Q. 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.

Cancer
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 I’d 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. I’ve 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 haven’t changed anything else in my diet or meds (BP and cholesterol meds). Just wanted to let you know as your web site was informative.

Tolerance
Q. About my wavering success with Sam-e for the treatment of depression. I commenced a daily dosage of 400mg and by the 6th day, i noticed a sudden and drastic improvement in my mood. Over the following 2 weeks, the positive effects had worn off almost completely. I then tried doubling my daily intake to 800mg, and the positive effect returned but also gradually wore off. Is it advisable to increase dosage again until i find a dose that maintains effect?
   A. My approach is to take a break for a week and then resume again since it appears in your case tolerance is developing quite rapidly. I am not comfortable in increasing the dosage. During these breaks another natural anti-depressant can be tried.

Gambling
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 or taking thyroid meds like Synthroid.

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.

Anxiety
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 
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.

I took half of a 400 mg pill. Within an hour my heart started racing. Then I began coughing with shortness of breath and chest discomfort, so I sought care.

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

Insomnia
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.

Pregnancy
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.

IQ. 'm 38 yrs old and have been taking sam-e for 9 wks. This supplement has changed my life and I don't want to ever go back to the darks side. After taking sam-e I feel like i was depressed all my life. However I'm trying to get pregnant again and every research out there that I've read or a professional that I've asked are just saying "there isn't enough research". My logic is, if it is naturally occurring in the body how can it be harmful. Can you please shed some light? I am afraid to stop taking it but at the same time I'm afraid that I might damage the baby.
   A. Unfortunately there is no research regarding the use of SAM-e in those who wish to be pregnant or are pregnant. Its safety during pregnancy has not been determined.

Sleep
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 and herbal extracts

5 HTP
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. John’s wort and Sam-e dosages should be a quarter or at most half of the dosage of each taken separately.

Q. I have recently tapered off Lexapro due to its horrible side effects. Someone told me about CBD hemp oil. I should also mention that I stopped taking SAM-e when they prescribed Lexapro. Now that I am off Lexapro, I want to begin taking SAM-e again, but I’d also like to start a very low dose CBD hemp oil as I hear it is also great for anxiety. What are your thoughts on this and is it safe to take them together at very low doses, i.e., SAM-e at 50 to 100 mg and the oil at low dose.
   A. I am not aware of any studies that have combined them, but it is a good idea to, at first, try each one separately for a week before combining at very low doses.

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 can’t 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.