SAM-e (S-Adenosyl Methionine, Ademethionine, Adomet) is the naturally-occurring amino acid methionine bound to an ATP molecule. And is found in nearly every cell in your body.
SAM-e helps produce and breakdown the neurotransmitters acetylcholine, dopamine, serotonin, norepinephrine and melatonin in your brain. SAM-e maintains cell membranes and plays a role in a healthy immune system.
Studies show that SAM-e is very effective in treating depression without the side effects of prescription antidepressants. And while pharmaceutical antidepressants can take from 6 to 8 weeks to begin working, SAM-e can work much faster.
The latest research shows that SAM-e can be anti-anxiety, reduces pain including in fibromyalgia, and can improve learning, memory and mood.
- Neuroplasticity. SAM-e is involved in the formation of myelin that surrounds and protects axons. And SAM-e can improve brain-cell membrane fluidity. Enhancing the function of neuroreceptors.
- Neurotransmitters. SAM-e is involved in the synthesis of acetylcholine, dopamine, serotonin, and norepinephrine. Helping to normalize mood, moderate behavior, and elevate emotions.
- Neuroprotectant. SAM-e helps produce the powerful antioxidant glutathione through a process called transsulfuration. SAM-e helps stabilize cell membranes and promotes the secretion of bile. And through a process called aminopropylation, SAM-e is converted into the antioxidant methylthioadenosine, which has anti-inflammatory and analgesic (pain-relieving) properties.
Table of Contents
SAM-e (S-Adenosyl Methionine) is a naturally occurring coenzyme that plays many critical roles in your body.
SAM-e is made from methionine and ATP (adenosine triphosphate) during a cycle that recycles the amino acid homocysteine. This cycle requires Vitamin B6 and B12 and folate (B9) to work properly.
SAM-e is a precursor to the crucial antioxidant glutathione which is used in your brain and liver. When glutathione levels drop in your body, liver damage from oxidative stress begins within seconds of exposure to alcohol or toxins.
SAM-e is a methyl donor that contributes to several essential processes in your brain. As a methyl donor, SAM-e is involved in the production and recycling of hormones, cytokines, and the neurotransmitters acetylcholine, dopamine, norepinephrine, and serotonin.
This methyl donor process is call ‘methylation’, and contributes to gene expression. Affecting how your cells work and communicate including your cell DNA.
SAM-e modifies important molecules in cell membranes that control communications within and between brain cells. SAM-e boosts the number of muscarinic receptors in certain parts of your brain which are critical to this cellular communications network.
SAM-e is used to treat depression, anxiety, osteoarthritis pain, fibromyalgia, and liver disease.
SAM-e is sold as an OTC supplement in the United States and Canada. And as a prescription drug in several European Union countries, and Russia. SAM-e is marketed under the brand names Adomet, Gumbaral, Samyr, Heptral, Agotan, Donamet, Isimet and Admethionine.
How does SAM-e work in the Brain?
SAM-e boosts brain health and function in several ways. But two in particular stand out.
- SAM-e helps alleviate depression. SAME-e is one of the main building blocks your brain needs to produce the neurotransmitters acetylcholine, dopamine, serotonin, norepinephrine and melatonin. By raising the levels of dopamine in your brain, SAM-e helps enhance memory, motivation and learning.
Researchers at the West Los Angeles VA Medical Center studied the antidepressant effect of oral SAM-e in a randomized, double-blind, placebo-controlled trial for 15 patients with major depression.
The researchers found that SAM-e is a safe, effective antidepressant with few side effects and a rapid onset of action. And may be useful for those who cannot tolerate prescription tricyclic antidepressants.[i]
- SAM-e directly influences neuronal signaling. SAM-e increases the number of muscarinic receptors in the hippocampus. We have two kinds of acetylcholine (ACh) receptors in our brain. 1) Nicotinic receptors and 2) Muscarinic receptors
Most of the nootropics we investigate here at Nootropics Expert influence nicotinic receptors and ACh. Muscarinic receptors have a very different mechanism of action. They are part of a large family of G-protein-coupled receptors (GPCRs) which are used as an intracellular secondary messenger system.
Your brain has a very complex system of control to regulate different processes going on in different cells at different times. For this to work, there must be a sophisticated means of communication between cells.
GPCRs and their G proteins provide this intercellular communication. And form one of the most important signaling systems in your brain. They are involved in nearly every aspect of your physiology and behavior.
G proteins work by binding neurotransmitters, hormones, growth factors, cytokine, odorants and photons at the cell surface to the GPCR, and activating that receptor. Everything you see, hear, smell, or taste goes through this signaling process.
And SAM-e increases the number of these muscarinic receptors in parts of your brain, including your hippocampus. In one study, aged rats were given SAM-e for 30 days. Supplementation with SAM-e restored the number of muscarinic receptors to levels found in the same areas in young animals.[ii]
Supplementing with SAM-e to increase muscarinic receptors in your brain can boost neuroplasticity and increase learning, memory, mood and even smell and vision.
How things go bad
You have healthy levels of SAM-e throughout your body when you’re young. But as you age, your body makes less of it. This is why young people bounce back from difficult experiences more easily. They’ve got higher levels of dopamine and a higher pain threshold than adults.
SAM-e is a major methyl donor in your body. It is involved in the biosynthesis of hormones, neurotransmitters, proteins and phospholipids.[iii]
SAM-e participates in a sequence of events involving folic acid (folate) and Vitamin B12. Folate converts to 5-MTHF (5-methyltetrahydrofolate) which converts freely circulating homocysteine back into the amino acid Methionine (using Vitamin B12). L-Methionine then binds to an Adenosine group from ATP to create SAM-e.
SAM-e is then able to donate methyl groups (called methylation) to a variety of reactions including the production and breakdown of the neurotransmitters dopamine, serotonin, norepinephrine and melatonin in your brain.
This methylation process degrades SAM-e into S-Adenosylhomocysteine. Which is then fed back into this cycle from the beginning. This process is referred to as a ‘one-carbon cycle’.
If you don’t have enough folate or Vitamin B12 available, this SAM-e methylation process breaks down. And the result can be depression, brain fog, poor recall and memory, and pain.
This lack of folate and Vitamin B12 can affect you regardless of age. This is a big enough problem that the Canadian government mandated folate fortification of all flour, and some corn and rice products to address this issue in 1998.[iv]
Low levels of SAM-e, folic acid, Vitamin B6 and B12 can lead to all kinds of problems. And genetic defects that don’t allow the use of these important vitamins can result in the same symptoms.
↓ Cognition, memory, recall, and mood diminish
↓ Folic acid, Vitamin B6 & B12 absorption declines
↑ Homocysteine levels rise
↑ Pain levels rise
↓ Mental health, language and fine motor skills decline
All of these changes in brain energy metabolism are contributing factors to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, ALS, epilepsy, and dementia.
But even if you’re not concerned with genetic defects, a lack of B-Vitamins, or the effects of aging, SAM-e can help.
Stress-related disorders like anxiety, major depression and PTSD are some of the most debilitating illnesses known to man. And if you’re reading this, and dealing with any of these, supplementing with SAM-e may help.
To cope with stress requires changes in the expression of “immediate-early genes” in your hippocampus. The same area of your brain you use for learning and memory.
Stressful events result in epigenetic (gene) modifications within ‘immediate-early genes’ in your hippocampus neurons. DNA methylation acts to suppress the expression of these genes. This is where SAM-e comes in…
SAM-e is a methyl donor for the enzyme that methylates your DNA. When SAM-e levels are high enough, a stressful event will not result in DNA de-methylation.
Instead, a stressful event enhances DNA methylation of ‘immediate-early genes’. Which suppress their expression and allows you to adapt in a healthy way to this stressful situation.[v]
SAM-e is a powerful antidepressant. In 2005, researchers combed through the databases of Medline, Psychinfo, AMED, and Cochrane Controlled Trials Register. And collated the findings of randomized, controlled trials studying SAM-e for depression through to September 2001.
The team concluded after analyzing all the clinical evidence that SAM-e was effective in treating major depression in adults.[vi]
SAM-e is also a potent pain-killer. A recent study looked at 56 people with arthritis in their knees for 16 weeks. One group took the COX-2 inhibitor Celebrex while the other took SAM-e.
Researchers found that SAM-e was as effective as Celebrex at eliminating pain. And without the potential side effects of heart attack or stroke that can be caused by using Celebrex.[vii]
Another study on the effect of SAM-e with 17 fibromyalgia patients confirmed a close relationship between primary fibromyalgia and psychologic problems including depression.
SAM-e treatment improved the depressive state of these patients. And SAM-e was found to be an effective and safe therapy in the management of fibromyalgia.[viii]
How does SAM-e feel?
For some, supplementing with SAM-e can be life-changing.
SAM-e can have a profound effect on emotions, depression, and feelings of anxiety. You may experience improved concentration, energy, alertness, and feelings of well-being. Even vision can become clearer.
Once you start supplementing with SAM-e, you should experience at the very least, a general sense of well-being.
SAM-e works particularly well for those who deal with depression or anxiety. Neurohackers report that they no longer have panic attacks. And the feeling of doom is gone.
Adding SAM-e to your nootropic stack can improve sociability, and not feeling overwhelmed by life. Brain fog lifts and thinking is clearer and faster.
Others say that the “dark cloud has lifted”, and all the negativity and stress is gone. Things that normally would irritate are just brushed off, and you move on.
One big word of caution: SAM-e needs Vitamins B6 & B12 and folate to work. Or supplementing with SAM-e may be a waste of time and money because without adequate levels of these B-Vitamins it will not provide any benefit.
You’ll notice reference to B-Vitamins several times in this article on SAM-e. It is that important. Use Vitamin B6 & B12 and folate every day that you supplement with SAM-e. Or use a B-Complex formula that contains folate (B9) (avoid folic acid).
SAM-e Clinical Research
SAM-e Lifts Mood
We have made significant progress in the last 100 years in diagnosing and treating depression. And yet, 10’s of millions still suffer from depression. In 2014, an estimated 15.7 million adults in the United States had at least one major depressive episode in the past year.[ix]
In the United States, one in ten Americans are using antidepressants.[x] I don’t have statistics from other countries but I suspect many have similar problems. Unfortunately, antidepressants only work 30 – 50% of the time. And come with a host of side effects.
One reason that many people continue to suffer from depression is that most doctors are not aware of the link between homocysteine and depression.
If you’re dealing with depression and have had little success with antidepressants, you may have something as simple (and as serious) as a folate deficiency. Or low levels of Vitamin B12. Studies show a link between folate deficiency and impaired metabolism of serotonin, dopamine, and norepinephrine.
One study looked at 46 patients with severe depression. 24 of these patients had raised levels of homocysteine. And significantly lower levels of folate, SAM-e, and other metabolites.
The researchers concluded that looking at total homocysteine levels could be a measure of depression. Caused by folate deficiency, impaired methylation (SAM-e), and neurotransmitter metabolism (SAM-e). And a potential benefit to simply using vitamin replacement to treat severe depression.[xi]
Or supplementing with SAM-e to treat depressive symptoms.
SAM-e to Treat Adult ADHD
Ritalin and Adderall are thought to be the most effective treatment in children and adults with ADHD. These stimulants work by potentiating both dopamine and norepinephrine at the synaptic cleft. But stimulant meds for ADHD come with side effects.
SAM-e acts as a methyl donor and is involved in many metabolic pathways. It has both adrenergic and dopamine receptor agonist activity.
A research team at the University of California used SAM-e with subjects diagnosed with Adult ADHD in a 9-week double-blind, placebo-controlled trial.
The research team found that 75% of the patients had a significant improvement in ADHD symptoms while using SAM-e. And the 25% who did not respond to SAM-e, did not respond to Ritalin either.[xii]
SAM-e Treats Depression
Scientists at the US Department of Health and Human Services conducted an analysis of 102 individual studies in 25 databases on SAM-e and depression in 2002. The report distilled data gleaned from published studies conducted around the world up to 2002.
This comprehensive report is called, “S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease.” The researchers found that SAM-e is just as effective as standard antidepressant drugs at treating depression.
The agency concluded, “Treatment with SAM-e was equivalent to standard therapy for depression”.[xiii]
SAM-e Recommended Dosage
Recommended dosage of SAM-e for nootropic benefit is 400 mg per day.
SAM-e for depression: 400 – 1600 mg daily in divided doses
SAM-e for bone and joint health: 200 – 1200 mg daily in divided doses
SAM-e for liver problems: 1600 mg daily in divided doses
Some research and many user reports suggest that once positive effects are achieved, SAM-e doses can be reduced. Some report benefit with as little as 100 mg of SAM-e daily.
Studies show that SAM-e should be consumed with B-Vitamins. When SAM-e donates its methyl group, it breaks down into homocysteine. Elevated homocysteine levels are associated with increased heart disease, birth defects and depression.
Choose a bioactive B-Complex to use with SAM-e. Or a high quality and bioactive Multi like my favorite, the Performance Lab® NutriGenesis Multi for men or women which contains therapeutic amounts of each of the B-Vitamins you need while using SAM-e.
In order to prevent homocysteine accumulating, logic tells us based on its mechanism of action that sufficient levels of B-Vitamins must be present to convert homocysteine into the potent antioxidant glutathione.
Take SAM-e on an empty stomach and an hour before eating any food. SAM-e is best digested in your intestines and not your stomach. Not letting SAM-e settle into your digestive tract could cause stomach upset.
SAM-e Side Effects
SAM-e is produced naturally in your body. So is considered well-tolerated and safe.
If you have bipolar disorder, you could develop mania when supplementing with SAM-e. So check with your doctor before using SAM-e.
If you’re on antidepressant medication, you should check with your doctor before supplementing with SAM-e.
High doses of SAM-e can cause gas, upset stomach, diarrhea, constipation, dry mouth, headache, dizziness, anxiety or skin rashes. SAM-e may also trigger an allergic reaction in some people.
Type of SAM-e to buy
SAM-e is available in 200 and 400 mg tablets.
For optimal effects with SAM-e, stable, enteric-coated tablets are recommended. SAM-e should be taken on an empty stomach, either one hour before or two hours after meals.
SAM-e is highly unstable so check expiration dates. And you should get tablets that are packed in sealed, gel-packs for freshness.
Avoid SAM-e in powder form as you’ll likely be unsatisfied with the results.
Nootropics Expert Recommendation
SAM-e 400 mg per day
I recommend using SAM-e as a nootropic supplement.
Your body does make some SAM-e on its own. But SAM-e levels decrease as we age. And you cannot get SAM-e from food.
SAM-e is critical for the methylation process needed for making important neurotransmitters including acetylcholine, dopamine, serotonin, norepinephrine and melatonin.
SAM-e is also involved in the cycle which produces the critical antioxidant glutathione. And it’s involved in maintaining brain cell membrane integrity and fluidity.
SAM-e increases muscarinic receptors in your hippocampus which boosts the activity of acetylcholine and other critical neurotransmitters in your brain. Leading to improved learning, memory and mood.
SAM-e is especially helpful if you’re dealing with depression. Or having difficulty coping with any kind of stress.
We suggest a dose of 400 mg daily. It may take a while for SAM-e to build up in your system. So be patient. Once you’re achieving the affects you want from SAM-e, you can eventually try scaling back your dose to 100 or 200 mg.
SAM-e needs Vitamins B6 & B12 and folate to work. Or SAM-e may not provide the benefit you are looking for. Most integrative medicine doctors and naturopaths recommend stacking a high quality B-Complex when using SAM-e. So make sure you stack SAM-e with the B-Vitamins listed above, or a good Vitamin B Complex formula that uses folate (NOT folic acid).
Or use a high quality Multi containing these bioactive B-Vitamins like my favorite, the Performance Lab® NutriGenesis Multi for men or women.
[i] Kagan B.L., Sultzer D.L., Rosenlicht N., Gerner R.H. “Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial.” American Journal of Psychiatry. 1990 May;147(5):591-5. (source)
[ii] Muccioli G., Scordamaglia A., Bertacco S., Di Carlo R. “Effect of S-adenosyl-L-methionine on brain muscarinic receptors of aged rats.”European Journal of Pharmacology. 1992 Nov 2;227(3):293-9. (source)
[iii] Park L.K., Friso S., Choi S.W. “Nutritional influences on epigenetics and age-related disease.” Proceedings of the Nutrition Society. 2012 Feb;71(1):75-83. (source)
[iv] Ray J.G., Cole D.E., Boss S.C. “An Ontario-wide study of vitamin B12, serum folate, and red cell folate levels in relation to plasma homocysteine: is a preventable public health issue on the rise?” Clinical Biochemistry. 2000 Jul;33(5):337-43. (source)
[v] Saunderson E.A., Spiers H., Mifsud K.R., Gutierrez-Mecinas M., Trollope A.F., Shaikh A., Mill J., Reul J.M. “Stress-induced gene expression and behavior are controlled by DNA methylation and methyl donor availability in the dentate gyrus.” Proceedings of the National Academy of Sciences U S A. 2016 Apr 26;113(17):4830-5 (source)
[vi] Williams A.L., Girard C., Jui D., Sabina A., Katz D.L. “S-adenosylmethionine (SAMe) as treatment for depression: a systematic review.” Clinical and Investigative Medicine. 2005 Jun;28(3):132-9. (source)
[vii] Najm W.I., Reinsch S., Hoehler F., Tobis J.S., Harvey P.W. “S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial.” BMC Musculoskeletal Disorders. 2004 Feb 26;5:6. (source)
[viii] Tavoni A., Vitali C., Bombardieri S., Pasero G. “Evaluation of S-adenosylmethionine in primary fibromyalgia.” A double-blind crossover study. American Journal of Medicine. 1987 Nov 20;83(5A):107-10. (source)
[ix] “Major Depression Among Adults” National Institute of Mental Health nimh.nih.org Retrieved July 25, 2016 (source)
[x] Rabin R.C. “A Glut of Antidepressants” The New York Times blogblogs.nytimes.com Retrieved July 25, 2016 (source)
[xi] Bottiglieri T., Laundy M., Crellin R., Toone B.K., Carney M.W., Reynolds E.H. “Homocysteine, folate, methylation, and monoamine metabolism in depression.” Journal of Neurology, Neurosurgery and Psychiatry. 2000 Aug;69(2):228-32. (source)
[xii] Shekim W.O., Antun F., Hanna G.L., McCracken J.T., Hess E.B. “S-adenosyl-L-methionine (SAM) in adults with ADHD, RS: preliminary results from an open trial.” Psychopharmacology Bulletin. 1990;26(2):249-53. (source)
[xiii] “S-Adenosyl-L-Methionine (SAMe) for Depression, Osteoarthritis, and Liver Disease” US Department for Health and Human Servicesarchive.ahrq.gov Retrieved July 25, 2016 (source)
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I suspect I have an MTHFR mutation,and accordingly I have been taking a b complex with L-methylFolate. It helps a lot,but something was still quite missing.
I did some research and tried SAMe 400mg a week back.its a good enteric coated tablet,and was blown away with the effect,I actually felt happy, could focus,was calm. I thought I hit the damn jackpot,felt my life had changed.
Unfortunately it only lasted for 2 days,after then,back to normal again.
I have been taking the tablets properly,on an empty stomach,1 hr before a meal . And after about 4 hours,I could literally feel it kicking in.it was surreal how profound an effect it was having .
My question is, since SAMe worked so well for 2 days,it was definitely providing something my body needed,and I felt normal, so why did it suddenly stop working after 2 days?
David Tomen says
Rob, if it worked that well for you but it was temporary the only thing that could have caused that is the dose was too high.
I realize it is difficult to reduce the dose with an enteric coated tablet. The only other option is to use SAM-e once every 2nd or 3rd day and see if that helps.
Thanks,I’ll try 200mg tablets
I wanted to reach out to see if you would be able to provide any insight. I took SAM-E for about 2 weeks. All was well until I experienced a severe dissociation/panic attack. I blamed it on the SAM-E so I stopped cold turkey. Since then, I’ve been experiencing what seems like withdrawal symptoms. It’s been about 3 months now and I still experience symptoms (it’s gotten better but still there). I don’t see many people talking about it so I am assuming I am more of a rare case but wondering if maybe this messed up my methylation cycle or something. Have you seen these cases before and do you have any advice?
David Tomen says
Gabi, you could have undiagnosed bipolar disorder which is the only reason I can think of that would cause that type of effect. And if that is the case it has been my experience that some type of unusual ‘event’ can trigger something that was previously dormant.
If that is the case I highly recommend finding a psychiatrist who is willing to work with you. Explain what happened and ask if they can test you somehow to verify it. Messing up your methylation cycle would be temporary. It wouldn’t hang around for 3 months.
I am an undermethylator, so am taking 800 mg daily S-ame for that for the past 5 months. I know it can take up to a year to truly work for some. Because of being an undermethylator, my doctor says I cannot take folate. My blood shows normal ranges that I assume are from eating my vegetables. I do take a B Complex 3 times a day with extra B1 and B5 at night. I still feel like I am missing something. Still anxious with high cortisol levels for the past 9 months. Should I increase my S-ame to 1200 mg a day? Add more Bs? Any suggestions for lowering cortisol? I take ashwagandha, holy basil, PS100? Any suggestions for relief would be appreciated!
David Tomen says
Alexis, you can safely increase your SAM-e dose to 1200 mg per day. Try it and see if that helps.
You can also lower cortisol with L-Theanine and magnesium (Bisglycinate, Taurate, or L-Threonate).
Enoch Satyananda says
I finally caved (always thought was too $$$) and picked up a bottle at Kroger (Simple Truth brand even) 30x 400mg for about $18… And WOW. Been taking it when I get up in the morning and it makes me feel like a kid again. Not sure how else to explain it/hard to put finger on but it’s as if the weight on my shoulders has been lifted or at least lightened to a noticeable degree!
It’s mildly energizing, slightly euphoric and even has me making funny noises and singing silly songs occasionally. I have not noticed any negative side effects and so far don’t feel I need to take more than one. (Though I might try 200mg x2 if I can get my hands on some)
Also seems to have some type of relaxing effect on my joints and my neck has been popping (in what feels like a good way) more often. (it rarely does)
Worth noting that (after a little research) I am also taking with Alpha GPC 300mg caps which seem to work best double stacked. (i.e. 600 GPC 400 Sam-e) Noticed that drinking alcohol isn’t giving me a gross feeling either.
David Tomen says
Enoch, SAM-e can be life changing for some people while others receive no benefit. You are fortunate to find something that works for you so quickly. But do NOT take more if you are already getting the benefits from SAM-e. More is never better in this business.
I don’t know for sure but I suspect that I have a enzyme deficiency in one or two of the detox pathways in my liver. I took Celexa many years ago and immediately I had a devastating and permanent life altering side effect. I recently read in a medical side-note that where there are 2 compromised methylation pathways, these patients are not to be given Celexa because it will result in the most side effects. I believe the reason for that is because Celexa has a stronger binding agent than some other options.
Anyway, I’ve given up on trying to reverse the damage because I don’t think it’s possible, but what I am now trying to do is feel better, in general. I’ve got all the symptoms of a slow methylater and am working with a dr to find any genetic abnormalities with methylation, etc.
If I take the methylated b vitamins along with the SAMe, am I taking them both together on a empty stomach or vitamins with food and SAMe alone on an empty stomach a few hours before or after?
And if I do have this abnormality, is this the correct protocol to help that or would this cause more irritation?
Thank for hanging in, I know that was long. I do appreciate it!
David Tomen says
Melissa, they are all water soluble. But you may be correct about getting the timing right. This is something you need to work through with your doctor. It is going to take trial and error to get it right and working for you.
What other supplements or nootropics can be added on while taking sam e for depression & anxiety?
Sam e works and I want to continue to stack the odds in my favor for better mood, motivation and energy without all the caffeine…
David Tomen says
Bryan, if SAM-e works then keep on using it. The only recommendation is to add a BioActive B-Complex to support its use and keep homocysteine in check.
I love watching and reading your articles. Can SAMe cause headaches?
I have been taking 400mg of SAMe 1x per day before breakfast, couple of days later I have been developing a low grade headache after midnight which continues until mid morning. After 5 straight nights of these headaches, I stopped taking SAMe, 2 days later my headaches stopped occurring. I took SAMe again, the headaches came back. I’m taking SAMe in hopes to reduce my long term depression, (30 years).
I ordered a different brand of SAMe called (Azendus) which doesn’t have the ingredients mannitol & titanium dioxide, these are 200mg. I took a dose before breakfast and started to have the same headaches, at the same times. I am willing to continue to take SAMe if the headaches are temporary while my body adjusts to SAMe.
I’m 64, at my ideal weight and fairly healthy. Only prescription I take is Latanoprost , a low dose for my glaucoma (high eye pressure) which is somewhat in normal range now. I currently take Performance Lab multi for men 2 capsule 2x per day and Life Extension Bio Active B Complex 1 capsule per day. I also consume Organic Hemp Seeds which has a natural dose of magnesium (167) mg per serving).
I have just ordered from Performance Lab their Sleep & Vision supplements and will eventually add MindPro after I see how my body reacts to Sleep & Vision.
There is a family history of depression. I have tried SSRI a couple of different periods in the past with no positive effects. I have tried many supplements over the decades with no positive or negative side effects, but with SAMe, I may be having my first negative side effect. I’m on a fixed income not wanting to go too overboard on purchasing nootropics. I will add that I have always been a very light sleeper waking up at the minimum 12 times every night but always able to fall back to sleep a few minutes later. My life is fairly calm and I keep to myself since I’m a bit bashful around people including around family.
David Tomen says
Jerome, forgive me if I missed something from your essay. But The thing is Sam-E is not for everybody. A lot of people cannot use it. And it sounds like you’re one of those people.
Hi David, I recently tried SAM-e 200mg (Jarrow branded, it’s in blister packs for freshness), and I find even at that dose I get quite unpleasant GI side effects. It also made me …. sort of exhausted but also jittery? It made me feel so awful that I’m reluctant to take it again. Should I persist? Will that improve? I was hoping it would help with joint pain as well as ADHD and anxiety/depression. I don’t react well to pharmaceuticals, generally speaking. SAM-e reminded me of how I felt on ritalin.
David Tomen says
Jacqui, a lot of people cannot use SAM-e for the reason you just described. It sounds like it is the wrong supplement for you.
My adult daughter (38) has silent ADD since childhood but was not detected. During the past 15 years has problems with focus (works with numbers). She has taken Adder all and that solved the problem but side effects were an issue. After weaning from that about 8 yrs ago she left her job to work in an outside environment. Now back in an accounting position she is having the same focussing issue but is looking for a natural alternativ. She is healthy and takes no medication, and takes vit/min supplements daily. What would be her best alternative in your opinion? Thanks for your feedback.
David Tomen says
Gertrude, this is the ADD protocol I created for my own Adult ADD and is now used by 10’s of thousands around the world to manage their own ADD or ADHD. With or without stimulants. Check the yellow box just below the Table of Contents on this page: https://nootropicsexpert.com/best-nootropics-for-adhd-add/
Harry Rourke says
I was wondering if it is safe to use SAM-E, Rhodiola Rosea and Turmeric together?
David Tomen says
Harry, yes it is safe.
Hi there! Question…. my 21 yr old son is currently taking 20mg 2 x day Adderall and was on Wellbutrin for depression but also suffers greatly from social anxiety/general anxiety and felt he was getting little to no relief with the Wellbutrin and hates the side effects. He has recently gotten off the Wellbutrin and has been taking St J Wort hyperforin (Perika) 3 x day instead for anxiety and depression. He has mentioned wanting to try SAM-E in the past. Which would you recommend would be a better and safe option for him to treat his anxiety and depression, SJW or SAM-E? Reading this makes me feel the SAM-E might be a better fit for him, but wanted your advice. Thank you!
David Tomen says
Angie, the only way to find out is to try it. SAM-e does not work for everyone.
Thank you! Sorry, one more question…. is it safe to take 1 Sam-e with a low dose of St J W?
David Tomen says
Angie, there have not been any studies done on this so I can’t say 100% that it will not be a problem. But as far as I can tell it should not be a problem.
Chris Simonka says
I really appreciate your work as it has helped me immensely. Recently detoxed from years of Suboxone and Vyvanse. Using all sorts of suppliments from B complex to DLPA, Same 400, as well as several others like D3, Magnesium, L Theanine, Ashwaghanda and lyposomal C.
Is this overkill? I’m 42 but in good shape and my will is strong. Just want to get my levels back to normal asap.
Thank you kindly
David Tomen says
Chris, it is not ‘overkill’. They are called “supplements” for a reason. Because either we cannot get adequate amounts from our daily food intake. Or our body cannot make enough of whatever it is we need.
I use a basket of supplements successfully. The key is using only what you need (which can be a lot), make sure you follow dosage recommendations closely, and your liver and kidneys are in good health.
Hi David! I’m 21 and my dopamine is very low. 500mg x3 of NALT don’t do much for me, I’ve ordered L-Dopa (just to try, as far as I know I don’t have to use NADH to convert tyrosine to L-Dopa, so in theory it should be faster and more strong dopamine boost)
I suplement all dopamine cofactors beside SAM-e. Will I gain anything from SAM-e in such a young age?
God bless you David!
David Tomen says
Adam, I doubt you need SAM-e. But you definitely need Vitamins B6, B9 and B12 along with magnesium. So try a bioactive B-Complex like this one: https://amzn.to/36Bm7ZU (Amazon), and a magnesium supplement like this before bed: https://amzn.to/3K0xA33 (Amazon)
I have been talking SAM-e on and off for over four years, and it has made a remarkable improvement in my mild depression and arthritic knee. So, I was shocked and frustrated when I came upon a newly published article by the University of Manchester that says biologists have apparently discovered SAM-e could be toxic. They are claiming it breaks down into adenine and methylthioadenosine , which is a toxic substance.
Can you offer some insight into this claim? I would really like to continue taking SAM-e for my mental and physical.health. I have included a link to the article:
David Tomen says
Zanzara, you have to wonder what that authors of that article agenda is and the very first sentence, “should not be used until it is shown to be safe”. Are they kidding?
I have clinical studies going back to 1990 for use in humans. If it has been working for you then keep on using SAM-e. And please do not lose any sleep over something published by an academic whom you do not know. And likely is pissed because he can’t get a job with a supplement manufacturer.
Thank you so much for your words of reassurance. I have been feeling quite troubled since reading that article and my attempt at discontinuing SAM-e cold turkey was not pleasant, to say the least.
Hi there, I’m just wondering how SAM-e differs from other methyl donors eg DMG, as I note it only has one methyl group where is the DMG has two I’m guessing it’s nowhere near as simple as that but I’m hoping you will be able to tell me what the differentiating factors are. Also should it be stored in the fridge? I note you mention poor stability
Thnaks in advance
David Tomen says
Alex, it’s not a complete explanation of how methylation works but it’ll get you started: https://nootropicsexpert.com/vitamin-b9-folate/. Look at the section called “Problems with MTHFR“.
If you feel like taking a really deep dive into SAM-e and 1-carbon cycle see this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794704/
SAM-e does not need to be refrigerate. But it’s very unstable as a supplement and good quality comes in bubble packs to keep it as fresh as possible. Avoid SAM-s supplements that are loose in a bottle.
F Johnson says
Are there any known contraindications for taking SAM-e and Dopa mucuna at the same time or on the same day? I’ve been unable to find any information about taking these two supplements together. I have been taking 800mg SAM-e for many months and am considering adding Mucuna pruriens 800mg/15% L-Dopa.
Thank you for your very informative article, the best I’ve read so far and I’ve read a lot.
David Tomen says
No problem combining SAM-e with Mucuna Pruriens. But why are you considering using Mucuna?
F Johnson says
I’m working out non-prescription options for addressing depression and anxiety after having tried more than 10 pharmaceuticals, all with disasterous results.
I am a caregiver for my husband who has mild dementia. I’m responsible for more of our lives as we traverse this journey, which sometimes leads to feeling overwhelmed and excessively anxious.
In addition to SAM-e (800mg, which is working better now that I’m adding an appropriate Vit B complex with meals, thank you) I am taking Lion’s Mane for better mental focus and clarity. I do not take SAM-e and Lion’s Mane at the same time. I’ve read that Lion’s Mane combined with Mucuna puriens is helpful for anxiety.
My experience with SAM-e is that it keeps my deep depression at bay. I don’t want to jeopardize that success by taking something that might not be a good fit with it.
David Tomen says
You should be safe using Mucuna Pruriens. But that herb is used for increasing dopamine. I think you’ll find L-Tyrosine easier to use and more forgivable when it comes to figuring out the right dose for you.
F Johnson says
Thank you. I appreciate the suggestion.
William T says
Would there be a risk of serotonin syndrome when taking 5 mg deprenyl twice a week and SAM-e 400 mg daily.
David Tomen says
William, it could be a problem but it hasn’t been reported in studies. Here is a list of all known contraindications Selegiline: https://www.drugs.com/drug-interactions/selegiline-index.html
Has there been any studies for SAMe use in children?
I ask, because it looks like it could be effective for ADD. If so, could it be beneficial for hyperactivity as well?
David Tomen says
Ron, there are plenty of studies using SAM-e with children and depression. But not specifically for ADD or ADHD.
Hi David, hope it’s been a pleasant break for you.
You reference in the article about people lowering SAM-e levels?
I’ve been up at 1600mg but recently feeling a bit too hyped up and been doing 4-800 a day – maybe still too much.
Thinking to do 100-200 a day or 400 every other day? Any insight would be ace or where you got that info from.
Appreciate it’s a less stressful time of year (sort of!).
SAM-e felt like the first nootropic to do ‘something’ so thankful for it!
David Tomen says
Phil, this “holiday” was not much of a holiday here because we moved into a new house. So, there hasn’t been any time to relax as you can imagine. But in the end it is worth the stress.
I did make the statement, “Some research and many user reports suggest that once positive effects are achieved, SAM-e doses can be reduced. Some report benefit with as little as 100 mg of SAM-e daily.”. The user reports would have come from user reviews under a bestselling SAM-e supplement sold on Amazon or one of the other vendors. But I can’t remember where the “some research” reference came from.
Best thing to do is try a lower dose and see if it works for you. Keep in mind your system naturally produces SAM-e as well. So you are “supplementing” what is naturally occurring in your body.
Is it OK if I combine SAMe and Dopa Mucuna?
I use Dopa Mucuna 4 times per week it gives me great mental strength
Thank you very much
David Tomen says
Nancy, SAM-e should support the use of Mucuna Pruriens because it helps with the synthesis and breakdown of dopamine and norepinephrine. Both of which are produced when using L-DOPA as a precursor to dopamine synthesis.
Thank you for all your help
Best wishes for 2022