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.
SAM-e helps:
- 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
Overview
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.
SAM-e to the rescue
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).
The 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]
Dosage Notes
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.
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.
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.
Available Forms
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
We 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).
[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)
Really could use your help. I have 42 yr. Old daughter that was born with brain damage. At a young age she had many seizures, temper tantrums on and on medical problems so the doctors kept adding SSRIs. I had a DNA expression on how different drugs effected her! Dopamine and Serotonin were her biggest problem! But they kept adding. I weaned her off them and she has been on Sam-e with great results for many years. However, she has sleeping problems! She was on melatonin which worked for awhile then not, so switched to L- triptophane. Now not working after 12 months. Switched back to melatonin but not working either now. Yes, need to add B Complex! she takes D3, fish oil supplements, coenzyme, and blood pressure pills. Are her sleep brain waves messed up from lack of the B vitamins? Please can you help with suggestions! ASAP please
Jodie, this is how sleep works: https://nootropicsexpert.com/best-nootropics-for-sleep/.
Certainly a vitamin deficiency could result in all kinds of problems including insomnia.
And SSRIs have also been shown to mess with things like gene expression and disrupting ion channels. That just takes a lot of healing by including nootropics that increase BDNF (https://nootropicsexpert.com/13-nootropics-to-boost-bdnf/) and Nerve Growth Factor.
Brain waves are complicated things that science is still trying to figure out. L-Theanine is a good start to help produce calming brain waves.
Hey David, I do not know if you are still replying to comments however I wanted to ask a question in regards to sam-e’s side effects. I started taking sam-e and nac at the same time and felt almost instant relief from my anxiety and obsessive thoughts within days. Unfortunately the relief came with brain fog and I found myself forgetting things, lacking focus, and being not as motivated. Are there any co-factors that I should take with sam-e? I found that nac contributed to the brain fog even more-so than sam-e and quit taking it, however I still am noticing the brain fog effects are taking sam-e on its own for over two weeks.
I’m am not sure how relevant this information is but I do have a MTHfR heterozygous mutation c667t and have supplemented with methylfolate in the past. Though in the short term I felt great, the methylfolate supplementation eventually became overwhelming and I had severe side effects including anxiety, irritation, and depersonalization.
I love the positive effects of sam-e but is there anyway to downplay the brain fog?
Thank you for your time,
Tony
Tony, SAM-e must be used with a B-Complex which I’ve detailed above. Use a bioactive B-Complex esp. since you have issues with methylation. Choose a B-Complex like this one: https://amzn.to/39lYaUy but just use one capsule instead of the recommended 2 capsules per day. And see if that takes care of the brain fog.
Hello David,
I’ve been taking SAM-e 1600mg on an empty stomach with a Methyl B-complex for 3 weeks for depression and a complete lack of energy. No noticeable effects yet.
I’ve read about DLPA (DL-Phenylalanine)(up to 1500mg) and would like to give it a try. Can it be safely combined with SAM-e, as they both influence serotonin to some degree? I also take L-tryptophan 1000mg, but at bedtime for insomnia (with the B complex, again, no effect). I’m just worried about the Serotonin Syndrome so wanted to double check.
If they can be taken together safely, should I take low doses of both SAM-e and DLPA (say, 500mg) or 1500mg of each?
How will I know whether to continue taking both or just stop at one when effects start to show?
Thank you!
Kate, try DLPA on its own first and see if it agrees with you. If it doesn’t cause any side effects then try a lower dose with the same of SAM-e.
If that does not work for your depression and energy levels then clearly something else is causing it. And it’s likely something other than dopamine.
It’s unlikely that that combo will cause Serotonin Syndrome either. Not unless you are also using a prescription antidepressant.
Fascinating! Thank you!
I’d love to know: Do the B vitamins need to be taken concurrently with Sam-e, or can they be taken with food an hour or so after taking the Sam-e? Or other times during the day? B vitamins can be a little hard on an empty stomach. I’m guessing they can be taken at other times, as long as there are sufficient baseline amounts of them in the body?
Also, I’m guessing that I shouldn’t take digestive enzymes with Sam-e, if it’s better digested in the intestines. Is that correct? I sometimes take a few supplements on an empty stomach in the morning with a couple of digestive enzymes, and I find that it helps with any stomach discomfort the supplements might cause otherwise.
This is really great info. Thank you! I just found your page looking for some info on Sam-e, and I will follow you from now on. I’m also excited to see how it works for pain and arthritis, as I’m feeling arthritis burning in my foot as I write.
Ava, as long as you are taking the B-Vitamins daily you’ll have enough in your system to support SAM-e use.
I don’t see a problem taking anything with digestive enzymes because your system needs to digest them to use them. They don’t magically appear in your bloodstream just by swallowing them.
Thanks! No, of course they don’t. I thought if the extra enzymes were in my stomach at the same time as the Sam-E, they might start the digestive process sooner than desired – if Sam-e is best digested in the intestines, as you say, above. But, great! I’m glad I was wrong about that. This will make it easier to take!
Hi David. What are your thoughts on stacking SAM-e with TMG (betaine anhydrous)? I have read that they have very good synergy together
Bradley, both are involved in converting homocysteine back in to methionine at different parts of this cycle. So it makes sense that there would be synergy in there somewhere. But not sure how this translates into real life and using them in combination as supplements.
Hi David, I need your help please, I have bought the Dr.Best SAM-e that you mention in other comments, but I have the problem that About 1/3 of the entire box is tablets that have turned brown. The expiration date is in one year, so it is not an expiration problem, according to Amazon other buyers have had this problem. The foil packs were not opened, and it was a mixture of good / brown tablets in the same foil pack, would you please know if it would be toxic for me to consume SAM-e under these conditions? (with tablets of different colors)
Bilma, SAM-e that has turned brown means that it is oxidized and should not be used. SAM-e is highly unstable supplement form and why it should be in enteric coated capsules and sealed until ready to use. See if you can return the product.
A better option after more research is a patented version of SAM-e called Azendus which seems to be much higher quality: https://amzn.to/2MBPJfO
Hi David, when you say “before a meal”, do you mean solid food, proteins or anything at all? Is a bulletproof coffee (coffee, full cream milk, turmeric paste, maca, ashwagandha and lion’s mane in my case) considered as a meal? or the same without the milk?
Brigitte, this is what i said about when to take SAM-e and why, “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.”
I’m not sure if Bulletproof coffee would prevent SAM-e from getting to your intestines or not. You could try it with the coffee and see how your tummy feels after taking both.
Hi David
Can I take SAMe with l-glutathione (reduced)? If not, how best to use them? I bought both by mistake. I bought l-glutathione thinking it was something else.
Rica, I’m not aware of any contraindication between the two. Nor is any published. I suggest following the dosage recommendations on the bottle for each.
Hi David can I take Sam-e and L-tyrosine together? And if I can would you recommend taking one before the other? Thanks
Joshua, you can use them together if you like. But SAM-e needs Vitamins B6 & B12 and folate to work. Or SAM-e may not provide the benefit you are looking for.
Hi David, I am wondering if I can take DL-Phenylalanine will taking 400mg of Sam-e?
Joshua, it shouldn’t be a problem. Using SAM-e may even support the use of DL-Phenylalanine although I have no evidence to support this.
Can I take Sam-E alongside tyrosine for my anxiety and depression?
Laura, yes you can take the two together as long as you support SAM-e’s use with a high quality B-Complex supplement.
David, would Rhodiola pose any dangerous interactions with SAM-e? If not, do you think there’d potentially be any synergistic effect if they were stacked? Thanks very much.
Mark, it shouldn’t be a problem. Rhodiola Rosea acts like an MAOI. Which increases dopamine levels. And SAM-e is involved in the production and breakdown of dopamine. So there may be some synergy there. But don’t forget the B-Vitamins if you’re going to use SAM-e.
David, that was my speculation as well, but the affirmation of my thinking is most appreciated.
Hi,
Is SAM-e compatible with Bacopa Monnieri?
In your other article it’s mentioned:
“Bacopa is a powerful adaptogen. Which means it helps increase the effect of certain hormones when activity is low. And will block excess stimulation when activity is high.”
I wonder if this mechanism interferes with how SAM-e works.
Thoughts?
Huss, that’s not how adaptogens work. They’re called “adaptogens” because these supplements bring things back into balance. They don’t “block” your body’s use of natural compounds including SAM-e.
Hi David,
I read your article about SAM-e, really interesting !!
Since childhood I had problems with lack of dopamine and serotonin giving symptoms like sort of depression and lack of attention/memory recall (I did a test and I’m homozyous MTHFR A1298C). I started to take 200 mg of SAM-e and quickly I felt so well, it was fantastic but I noticed it raises my blood pressure a lot unfortunately. I don’t understand why, as my homocysteine levels are 6-7 and I don’t need to take methylated B12/B9/B6 . Why does SAM-e do this effect ?
Lea, it’s a good question and it shouldn’t. The only thing I can suggest is to try using a high quality B-Complex like the Life Extension supplement (https://amzn.to/3nPMOwV).
Because SAM-e donates a methyl group and uses B6, B9 & B12. If any one of those B-Vitamins is not adequate it could cause problems. In you it may be manifesting as high blood pressure.
The B-Complex I suggested is the right form and dose and will not hurt you. It’s worth a try.
Many thanks for your time and answer David
P.S.: I wanted to get “Secrets of the Optimized Brain”, I subscribed but it didn’t work (I tried 2 different email), I didn’t receive anything yet so I think there is a problem, thanks to check
Lea, look in your other folders like Spam. And other folders that you normally don’t check. It’s in there somewhere. If you still can’t find the email let me know and I’ll personally email you a copy.
Hello, I wanted your help to know which of the amino acids that I detail will give me better results to sleep and stay asleep without waking up.
I already tried with gaba supplements and it did not work for me I suppose it is because it cannot cross the blood-brain barrier?
Now I am among these three amino acids that I ask for your help to be able to decide.
I would like to know if the L Theanine, or the L Glycine or the L Tauryne, which of the three will give me the best result? Thank you very much for your generosity, helping us all to learn
Damian, it depends on your own biology but I’d try L-Theanine, L-Tryptophan and possibly L-Glycine.
David, could you please talk about the benefits of consuming Glycin as a supplement? I have seen that you have never dedicated an investigation to them as in other substances
Damian, L-Glycine is on my list of thing to write. Just haven’t got to it yet. But thanks for the reminder!
Agree with this for me..I have a double slow MAOA, yet, i’m still low serotonin (in all irony), b/c i have multiple genes that indicate less than optimal levels with serotonin (receptors, etc) ..and I will agree that my genetic report was spot on. I’m higher dopamine to serotonin with a slow comt. (it explained my panic, anxiety, etc) ..I never knew that high dopamine levels as not balanced with the inhibitory could do that. I’m always “on”…on the plus side, I have incredible focus. So there’s that. The downside is the over stimulation & having a hard time with winding down. I did start to take l methyfolate + a solid B complex that has active P5P for B6 and extra sublingual b12 (mixed B forms) ..these things got my homocysteine down to a 7 (was close to 15 prior) ..(the B vitamins are truly life and crucial for DNA methylation)..I take Sam e on occasion and it really helps me to relax & l tryphophan was a downright savior when it comes to sleep and staying asleep. l theanine helps immensely too…it calms my brain down. i just feel relaxed and 5mg lithium orotate is more helpful than i would have imagined too. (and i love bacopa)…I just feel so relaxed now, yet clear. It took some experimenting, but i found out what works for me. I found your videos & they are so informative. Thank you for what you do!
Tamara, that is the best news I could hear. And thank you for that. Experimenting and finding what works for you with a unique system is key to making nootropics work. Patience helps too! 🙂
Hello David, Recently I started taking sam-e 200 after finding on internet that it can solve my headache and depression problem. I want to know more from you that can it cure me of the headache and depression. I want to lead a headache free life. Also I am taking antidepressants- paxidep 25 and ventab 25 too. Beacuse after two days my headache has increased. Please tell.
Shivam, if you get an even stronger headache after starting SAM-e that’s a good sign that SAM-e is not your problem. And will not likely solve your headache and depression issues.
SAM-e is a naturally occuring amino acid in every cell in your body. It’s likely that your SAM-e levels are fine. And your problems are caused by something else.
Are your headaches actual “headaches” or is it a migraine?
Depression can be caused by a host of things. This post will help you understand what I mean by that. And what you can try through the process of elimination to get at the root cause of your depression: https://nootropicsexpert.com/best-nootropics-for-depression/
Hi David,
Sam E works well to control my anxiety. However, it either upset my stomach badly if I take it right before meal. Or if I take it with empty stomach with meals at least 2 hours afterwards, it hurt my intestine badly. Is there any brand of Sam E that doesn’t hurt digestion system that much?
I read that it may also be taken via injection. Do you recommend this? Where can I get this done?
Thanks!
Carl
Carl, are they enteric coated capsules or tablets? And what size of dose is it?
Some alternative or complementary medicine doctors and clinics offer SAM-e by IV. You’ll need to check around your area.
Hi David,
I use enteric coated tablets 400mg. I do have sensitive digestive system….
Carl, they just be enteric coated capsules and sealed in blister packs because this compound is so unstable.
If SAM-e works for you then I suggest investing in some trial and error and trying a couple of other brands. The only brand I was able to find that had zero “other ingredients” were in capsules in a bottle rather than blister packs. And I don’t recommend them because there is no way they can maintain their potency.
Doctor’s Best SAM-e is only 200 mg and might be worth trying: https://amzn.to/2FsgXlG.
Jarrow Formulas SAM-e is 400 mg and also worth checking out: https://amzn.to/2HbA7wF
If you have a sensitive digestive system you need to find the right “form” of SAM-e and find a supplement with the least amount of “other ingredients” as you can.
I have been taking Sam-e for 60 days. It has been a life changing experience. I have read through the comments and wanted to share that I also, like one other person said, developed a huge headache in the beginning. I found on a different forum where a person experiencing headaches took a lower dose more often during the day and the headache went away. It worked for me. I have worked my dose up to 800 mg a day. If I miss my afternoon dose, I get overwhelmingly tired and the headache is mildly there. I plan on increasing my dosage slowly. I take B vitamins. I wanted to share that my libido has increased tremendously! First time in 25 years I have felt so good. Will this last? On days when I am struggling with the fatigue I add ginkgo. Anything else you can direct me towards? In the past I tried Wellbutrin with minimum results. I tried other antidepressants, they all terribly upset the GI and make me sleep nonstop.
Sherry, thank you for sharing your experience with SAM-e. It’s comments like yours that are a tremendous help to our community.
Ginkgo Biloba acts like an MAOI which boosts dopamine and norepinephrine. If you find it helps that provides a hint that you may be low in dopamine. You can try L-Tyrosine which is a precursor to the production of dopamine.