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)
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.
Hi David, im already taking SAMe. It has been wonderful for my moods and mind. I am wondering how you stop SAMe? I’m assuming you cannot cut the tablets being eccentric coated. Do you taper like a antidepressant or do you to cold Turkey? Can SAMe cause withdrawal syndrome? Or any type of depression once your body is use to it?
Thankyou
Jessie, SAM-e is naturally produced in your body. So quitting supplemental SAM-e should not cause any issues.
Hi David,
I have been benefiting from so many nootropics thanks to you! I want to add SAM-e to my stack. I have a wonderful B-complex from a Canadian company called AOR. It has very nice bioavailable forms of B vitamins but Folic acid instead of Folate. The folic acid is 1000 mcg in this complex, if I add a methylfolate supplement with 400 mcg, would that be too much folic acid and folate for me to enjoy SAM-e benefits?
Thank you,
Rifat
Rifat, it would. The problem is folic acid is the synthetic form of Vitamin B9. And it’s in every kind of processed food you can think of too. Folic acid takes over folate receptors so the folate that your body recognizes gets ignored. And you don’t get the benefits that real folate has to offer.
Hi David
I too use stimulants, but it’s complex. I have tardive dystonia and had akathisia (for 7 years) and anhedonia.
worked very well but after a lot of stress went backwards
Also am MTHFR A1298C so my Folate levels are always low and have started supplementing with that (800mg). (as well as some B12, as that always need some of that (both methyl forms).
But because of the stress I did a catecholamines test and my adrenaline is through the roof. But Domaine and noradrenaline were fine. My HVA is fine but my VMA is low. So I bout some Lithium rotate and is does help somewhat with the jitteriness and agitation I feel, which can set of the dystonia). (to help with COMT)
SAMe is confusing as it seem to transfer noradrenaline to adrenaline but also break down the catecholamines.
Do you think this is a good suppliemt to add to the stack?
Thanks
Russ
Russ, it’s complicated but SAM-e may work and worth a try.
Another way to get epinephrine (adrenaline) under control is with natural beta-blockers which prevent epinephrine from attaching to receptors. I touched on that in my social anxiety post under the section, “Natural Alternatives to Beta-Blockers” here: https://nootropicsexpert.com/best-nootropics-for-social-anxiety/#natural-alternatives-to-beta-blockers
But there are others which used in combo have clinical evidence that they work. Check out the section “Natural Compounds” in this study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989080/
I know that some people that take ADs are worried about taking SAMe because of the risk of serotonin syndrome.
So was I – many years ago. I wrote to a professor who, if I remember correctly, pioneered the use of SAMe. Asked him about the risk of serotonin syndrome.
He said it was safe.
Of course, I can’t guarantee anybody else anything. But I’ve been taking SAMe (only 400 mgs a day so far) with the maximum dose of citalopram, namely 60 mgs, and haven’t had any problems.
It’s been a really good addition for me.
Thank you for sharing your story on this Charlotte. It may help some people.
Hi David,
Can you take SAMe with Bupropion? I am willing to get off from it and thought adding natural alternative like SAM-e.
Thanks for answer in advance.
Albert, I’m not aware of any contraindication. It may support it’s use because SAM-e is a cofactor in the production of dopamine and norepinephrine.
Dear David, Very useful and nice website thanks a lot for this.
I live in Europe and here SAMe isn’t very popular and actually many doctors don’t even know about it and they have never tried it.
Recently my GP gave me as a trial SAMe 800 mg twice per day and to increase up to 1600 mg in 2 weeks and since I started it in first week I didn’t have any side effects with 800 mg. (I am still on 800 mg) after 3 days I added also very good Vitamin Complex which includes strong dosage of Vitamin B’s but I started to suffer from sever headache since last 3 days. Can it be related to SAMe? Or SAMe mixing with Vitamins? As a medication I take Vortioxetine very low 5 mg dosage for general anxiety but my anxiety is under control only headaches are really, really strong especially at forehead like a pressure but when I measure tension all is good. What helps me a bit is Tramadol but it’s quite strong and I don’t wanna take it on everyday basis.
Sorry to disturb you here about my problem but as you have good knowledge about SAMe you might help me. Just here they don’t understand what might have caused these headaches and I don’t wanna give up on SAMe so early as I think I am getting other good benefits of it.
Thanks a lot in advance for your help!
Best Regards,
JK
Jaba, Vortioxetine is a serotonin modulator and stimulator. And SAM-e is involved in the synthesis of serotonin. It could be you’re getting too much serotonin.
And 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.
In the Side Effects section above I also made a note about caution when using SAM-e with antidepressants. Sounds to me like there’s a contraindication going on with the symptoms you describe.
Thanks a lot David for your reply, I appreciate it a lot.
Weirdly after increasing SAMe from 800 mg to 1200 mg per day headache went away.
Also, I take Vortioxetin very, very low dosage (5 mg) so do you think even with this low dosage I might have high levels of Serotonin? Because other than headache I didn’t have any kind of symptoms and as I said now it’s gone.
Also, as I read on Natural Medicines Database very often SAMe is added to SSRI’s in order to improve response and result. So, as I am getting off from Vortioxetin very slowly that’s why I thought SAMe might be good alternative.
Jaba, glad your headache finally went away. While it’s not likely excess serotonin now that you explained the dosage, my experience has been combining some nootropics with certain drugs introduces a ‘wild card’. Because you never know what’ll happen. And it’s bad more often than not.
But you are correct that a very few nootropics can support the use of certain SSRIs. I haven’t seen any clinical studies however using SAM-e with antidepressants. Unless I missed them while researching this review.
However
I do not think however that SAM-e can act as a direct “replacement” for a SSRI. However, there is plenty of clinical evidence showing that SAM-e was effective in treating major depression in adults.
Dear David,
Thanks for your reply, I appreciate a lot the time you dedicate to answer all of us so quickly and it’s really huge contributions towards you to our society!!! Highly appreciable…
I would like to share with you one clinical study which supports SAMe as an adjunctive treatment for current users of SSRI.
https://pubmed.ncbi.nlm.nih.gov/20595412/?dopt=Abstract
https://clinicaltrials.gov/ct2/show/NCT00093847
And also as I disturbed you already with my questions I would like to double check something with you. In most clinical studies they used SAM-e 800 or 1600 mg (Oral SAMe tosylate) per day for 6 weeks. I currently buy Doctor’s Best SAMe (Soloesse) and as in Europe there is not a lot of doctor’s who are familiar with SAMe I think that 4 tablets of 400 mg of Doctor’s Best SAM-e will be the same (1600 mg SAMe tosylate) what was used in trials right? It’s a bit confusing SAMe vs SAMe tosylate.
Thanks a lot once again for your help!
Best Regards,
JK
Jaba, Doctor’s Best SAM-e is tosylate disulfate which is the same SAM-e used in the clinical trials you referenced. They used 800 mg twice per day.
If you’ve not used SAM-e before my I suggest starting out with a lower dose of 800 mg once per day. And see how you react first before going to twice per day. And please use it with a high quality B-Complex once per day to avoid too much homocysteine which can be dangerous.
Hello David,
Can you take SAMe with MACA? Is there possible any interactions?
Tom, I’m not aware of any contraindications. And there is nothing in the research preventing taking them at the same time.
Thanks a lot David for your quick reply. I appreciate it a lot!
I think same thing goes for tongkat ali no? It should not interact with SAMe. I ask you this because I am starting taking SAMe and at the same time I take for my Sport performance Maca product which also includes LJ-100 (Eurycoma Longifolia).
I will appreciate your opinion about SAMe – Tongkat Ali co-administration as well because on net I didn’t find much.
Tom, if you look into the mechanism of action for Tongkat Ali and SAM-e it seems to me they should compliment each other. There’s no clinical evidence of this of course. Just my observation.
David thanks much for your useful observation. So, actually taking together both of them should be even more beneficial if I understood correctly your observation.
Tom, your are correct but keeping in mind this is only my observation after looking at the way each one works.
Hello David,
Really great website.
I got one quick question and I am looking forward to hear from you.
I read almost all comments about SAM-e and still I have one question and would like to clarify.
So after many discussions about the SAMe can we say that need of Vitamin B complex together with SAMe is essential?
And if it’s essential then is it ok to take SAMe first thing in the morning and vitamin B complex within the breakfast? Or is it essential to take B complex with SAMe on empty stomach? Is there really any difference?
Thanks a lot.
Nike, take SAM-e on an empty stomach and an hour before eating any food. The B-Complex can be taken anytime during the day but is usually taken in the morning. The goal is to have sufficient levels of the B-Vitamins in your system so that supplementing with SAM-e does not raise homocysteine.
Thanks a lot David. Very helpful and clear comment.
Dear David,
I asked my doctor to measure homocysteine levels after taking SAMe for a week and results turns normal now. So my question is: how often do you recommend more or less to check homocysteine levels to make sure they don’t go up?
Thanks.
Nike, as long as you’re using a B-Complex daily while using SAM-e I don’t see much point in frequent homocysteine labs. But it’s something to keep an eye on because excess homocysteine for a sustained period can be real bad news.
Hi there – have you heard anything about combining SAMe with Alpha GPC? They both seem to raise serotonin levels, don’t they?
For brain fog SAMe could be combined with Phosphatidylserin can’t it?
Michelle, SAM-e is a cofactor in the synthesis and breakdown of serotonin. It does not “raise” serotonin levels but is needed to produce it.
Alpha GPC is a precursor in the synthesis of acetylcholine and has been found to help release more dopamine. But not serotonin.
If you’re trying to relieve brain fog I suggest reading this post: https://nootropicsexpert.com/best-supplements-for-brain-fog/
Doctor’s best sam-e uses Soloesse, and says it provides a slow targeted release for improved absorption and digestion, does that mean it is time released? Some people react to time release products.
Kelly, Soloesse® is a patented form of SAM-e in enteric coated capsules which delays the release of SAM-e until it reaches your gut. Which does work better for some to experience the benefits of SAM-e.
Hi David, your article mentions that one should take SAM-e one hour before meals. If I have to take a medication (Linzess) half an hour before a meal can I still take the SAM-e an hour before the meal or should I take it 1 hour before the medication? Thanks
Eddie, either way should work because both need to be taken on an empty stomach. It’s nearly always a wild card when inserting a prescription med into a stack. Especially one that may affect digestion. But there’s no other info on this combo as far as I can tell.
Thanks David. I took my first SAM-e pill this morning and about an hour later took the Linzess. The only symptoms I got were a twitching in my shoulder and a flush feeling, like when you take niacin. There is niacin in the B-Complex I took but I normally take it with food. I took my second SAM-e an hour ago, and no symptoms. How long does it take before one finds out if SAM-e will make a difference?
Eddie, if SAM-e is going to work for you it should provide a general sense of wellbeing within an hour or so at the very least. I’d give it regular dosing for at least a few days for a fair trial before you decide if it’s for you or not.
Thanks again.
Hi David. Thank you for the article. I am researching how to help fight my severe depression while pregnant. I feel like Sam-e seems like a good fit for me as a year ago I finally was able to quit using methamphetamine after four years of daily use. Do you have any thoughts on using small doses while pregnant? Thank you so much.
Amy, SAM-e is not contraindicated as far as I can tell for use while pregnant. It didn’t come up in my research. You can check with your doctor to be on the safe side.
Thank you for your time!
You mention that “If you don’t have enough folate or Vitamin B12 available, the SAM-e methylation process breaks down. And the result can be depression, brain fog, poor recall and memory, and pain”. Since I have all these symptoms could this be caused by existing poor methylation?
You noted that SAM-e helps produce and breakdown the neurotransmitters acetylcholine, dopamine, serotonin, norepinephrine and melatonin in your brain. I have low serotonin, GABA and melatonin levels. Would taking SAM-e help balance my low serotonin/melatonin/GABA levels?
Also, you mentioned that Homocysteine levels could rise. Should I have my levels checked before I start the SAM-e or just test them after 3 months? I haven’t tested my Homocysteine levels since 2015 and they were 8.3 umol/L, on a reference range of 0.0-15.0 at that time.
In regards to SAM-e dosage, I want to begin taking one 200 mg pill before breakfast for a week to see how my body reacts. After a week I want to increase the dosage to a 200 mg pill in the morning and another an hour before lunch. I will include one Life Extension B-Complex pill with each SAM-e dosage.
Lastly, is there a possibility that SAM-e could improve my sleep?
Any comments are appreciated. Thanks
Eddie, your symptoms could be because of poor methylation. It’s estimated that up to 60% of people have one or more gene mutations that lead to methylation problems (http://www.altmedrev.com/archive/publications/13/3/216.pdf). SAM-e has some influence on neurotransmitter levels but it’s not possible to say whether using SAM-e will increase each of the neurotransmitters enough if they’re low. For that you’d likely need to use the direct precursor for each neurotransmitter that is low.
If you are following dosage recommendations including using a B-Complex then your homocysteine levels should be fine. Get it tested as you normally would.
SAM-e has been shown to relieve depression, anxiety, brain fog, and pain including arthritic and fibromyalgia pain, improve memory, mood and sociability, and support liver health. But it’s not used for sleep.
Thanks David. If it helps me relieve the symptoms your mentioned that would be a major plus for me. Once other thing, is there anything that might help a low thyroid function? My thyroid panel is in “normal” ranges but not in optimal ranges. From what I’ve read, it appears that my T4 to T3 conversion is not optimal.
Effie, to support your thyroid please my review for iodine here: https://nootropicsexpert.com/iodine/. You need Iodine, selenium and L-Tyrosine to make thyroid hormones.
Thanks David. I am already taking those supplements. Thinking about trying NDT.
Hi
Are there any known concerns or interactions between combining Sam-e and GABA?
Miles, no there aren’t as far as I can tell from my research.
thanks David on the reply of the others supplements.
SAM-e seems to be a complicated case:
“SAME-e is one of the main building blocks your brain needs to produce the neurotransmitters … norepinephrine”
“SAM-e is then able to donate methyl groups (called methylation) to a variety of reactions including the production and breakdown of the neurotransmitters … norepinephrine”
on my search to inhibit or breakdown of norepinephrine, I stumbled on this:
“Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is one of several enzymes that degrade catecholamines …norepinephrine”
“The enzyme introduces a methyl group to the catecholamine, which is donated by S-adenosyl methionine” https://en.m.wikipedia.org/wiki/Catechol-O-methyltransferase
so in theory SAM-e helps enzyme COMT to breakdown norepinephrine.
you mentioned it can also be a building block for norepinephrine.
And you advice to take Vit.B complex with SAM-e (what I did for 1,5y) to prevent homocysteine increasing to much.
I did read on your pages that many of the vit.B’s are co-factors and/or stimulation to make norepinephrine.
David, how do you see this all with SAM-e, will it decrease or increase norepinephrine? Or is it so complex with the vit-B’s that its more rolling the dice for what it will be?
thanks in advance
Wim, I’ve tried to simplify the neuroscience in this review so anyone can understand. But as you point out it’s much more complex that it appears. However, on the subject you mention I encourage to read further down that page because it’s not as simple as inhibiting NE.
SAM-e is a cofactor involved in a ton of enzymatic reactions. And does work the B-Vitamins to complete these processes. If some of the B-Vitamins are not present or insufficient then other systems go haywire. Including raised homocysteine.
Hi David,
I’ve just started using the Performance Lab whole-food Multivitamin that you advised – so far it seems great! I’m also taking DHA, vit D, magnesium, shilajit, agmatine (cycled with citrulline) and pycnogenol.
One question: since the multi already contains all B vitamins in the best form, is it okay to take SAM-e (empty stomach before breakfast) + the Multivitamin (full stomach after breakfast), or should I take also a separate B Complex with higher dosages?
Thanks
Jack, for convenience I take them all together. Because the healthy fat helps deliver the fat-soluble vitamins and minerals. And the water-soluble nutrients get used as needed.
I do use a separate B-Complex just to be on the safe side because they are so critical. Most are water-soluble and in the methyl form so I don’t worry about toxicity if a get a little too much. So far that hasn’t been a problem and I’ve been doing this daily for years. But I split my B-Complex dose with half in the morning and the other half at noon. Because I have a bad skin reaction to niacin if I take more that 50 mg at a time.
Thanks mate.
So is it okay if I take the multivitamin and/or B complex empty stomach? I thought that they needed to take with food.
Since I’m trying to keep it simple and limit the number of total pills (and also the cost of my stack), do you think I could try to take the multi for the Bs and avoid the separate B complex for the moment, and see how I feel? Or is it too dangerous?
Otherwise I could put my multi in standby and take only the B complex, along with DHA, Vit D, shilajit, magnesium, pycnogenol and agmatine. I’m planning about trying also Performance Lab mind in the future.
Jack, depending on your age and state of overall health you should be able to get the B-Vitamins you need IF you’re using the Performance Lab Whole-Food Multi for men. That multi has B-Vitamins in it that are more bioavailable and higher amounts than other multi’s.
And the multivitamin needs to be taken with a healthy fat or meal because some of the vitamins and minerals are fat-soluble.
Awesome, it’s the multi I’m using.
I’ll take SAM-e before breakfast empty stomach and the multi after breakfast, together when Performance Lab Mind.
Thanks David, it’s incredible that you find the time to answer all the comments!
Why avoiding Folic Acid?
Go to this review: https://nootropicsexpert.com/vitamin-b9-folate/. And scroll down to the “overview” section and start reading. All explained in that section.
I have been diagnosed with ADHD but also struggle with clinical depression. The only thing I take is Adderall. Is it okay to take SAM-e and Adderall together?
Aaron, you should be able to. But please look at the stack on this page: https://nootropicsexpert.com/best-nootropics-for-adhd-add/. Which is made specifically to support Adderall and contains two nootropics to help with depression.
For my patient
I prescribe Sam e 400mg
Vit b6 100 m
Folic avid 800 mcg
B12 1000mcg
iOS it optimal
Do I need to use methylated b bits since sam e does provide methyl group
Parvez, I always recommend using the methyl versions of these vitamins because many people have problems with MTFR. And often without knowing it.
And the other problem is many have issues converting synthetic vitamins like Vitamin B9 folic acid to methylfolate. And so many foods contain supplemental folic acid that receptors get ‘plugged up’ and non-receptive so more folic acid does more harm than good.
Is it safe to take this in combination with my Ritalin meds? (Provided I also take the Vitamin B supplements etc).
Johan, yes it is safe to use.
It has been shown repeatedly that SAMe doesn’t raise homocysteine the way that methionine loading does. SAMe up-regulates CBS and inhibits MTHFR to compensate. B vitamins are only required for people with already elevated homocysteine, not everyone who takes SAMe.
Also, taking supplemental folate (of any flavor) will radically worsen symptoms in many people with treatment-resistant depression and anxiety. They still desperately need the SAMe, but the extra folates must be avoided at all costs because folates promote the expression of SERT, NET, and DAT. Unstable depressives can perceive the change in chemistry within hours of folate supplementation.
Homocysteine accumulation is best managed with TMG and B12 in people who have the CBS C699T +/+ upregulation.
Dan, do you have clear, clinical evidence of what you are suggesting? I appreciate your input but need some supporting evidence.
Because Penn State University, Life Extension, Dr. Weil and a host of naturopaths recommend taking SAM-e with either a B-Complex or minimum Vitamins B6 & B12 and folate as suggested in my review. But I’ll gladly update it if you or anyone else can prove otherwise.
Here are a couple of studies on the effects of SAMe administration on homocysteine:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875864/
https://www.ncbi.nlm.nih.gov/pubmed/9262350
Most people who need SAMe need it because they are undermethylated. There is tons of information out there about the negative effects of folates on undermethylated depressives. If you are interested https://www.walshinstitute.org/ might be a good place to start.
The reason that I left a comment wasn’t to say that people shouldn’t combine SAMe with B vitamins. My only issues is that it is presented as being necessary to prevent high homocysteine levels. That isn’t true for most people.
Also, since SAMe upregulates CBS, adding B6 compunds the problems with CBS +/+ SNP.
Dan, I’m aware of those studies and never meant to imply with this review that using SAM-e without certain B-Vitamins was harmful. I appreciate your input and have went back and modified a couple of sections to clarify this.
Dear David,
Does it mean that if we have anxiety we should not take Vitamin B complex? Just the above conversation was a bit complicated to understand for non-medical people. So just to make sure could you clarify please if it can harm anything by taking good Vitamin B complex?
Nike, most of us are low in at least some if not all of the B-Vitamins. Check each vitamin I’ve reviewed to see why they’re so important. Not enough of these critical vitamins cause all kinds of problems. Anxiety can be caused by not enough of certain vitamins including the B’s.
is vegetable magnesium stearate ok?
Barbara, magnesium stearate is a “flow agent” that speeds up the encapsulation process. And prevents powder from sticking to mechanical equipment. And is sometimes used to make tablets easier to swallow.
The problem is magnesium stearate has been found in clinical studies to suppress natural killer T-cells. Which are a key component of your immune system. Some argue that these tests were done with lab mice. And not in humans. So it doesn’t apply.
But my stance is why is it even in there? It’s there to help the supplement manufacturer. Not for our health so why take the chance.
It is possible to produce supplements with zero “other ingredients”. I know because companies like Opti Nutra and a very few others do it every day.
Hi David,
Great article.
Is it ok to take 400mg of SAMe with 250mg of Citicoline and 840mg of Phosphatidyl Choline each day?
Grant, SAM-e needs Vitamins B6 & B12 and folate to work. Or SAM-e will elevate your homocysteine levels. High homocysteine can cause heart attacks. So add Vitamins B6 & B12 and folate to this stack and you’re good.
You say to add folate, is methyl folate ok? I have never seen folate pills other then methyl folate or folic acid…
Richard, absolutely use methyl-folate. Please never use folic acid because it is synthetic and your body has a very difficult time trying to use it.
Issue with methylfolate is it can be very difficult to figure out the dose you can overmethylation yourself very quickly.
Hi,
Do I need to take B vitamins together with SAMe as a part of one dosage?
Is it ok to take SAMe after waking up and a multivitamin after lunch? I mean, multivitamins have fat soluble vitamins.
You have a very informative site, BTW
Oliver, SAM-e needs Vitamins B6 & B12 and folate to be present in your system when you’re using it or it will elevate your homocysteine which is not good.
It really doesn’t matter how those B-Vitamins get there. As long as they do. Just make sure there are high enough dosages of each in the multi you are using. That is not usually the case however.
To be on the safe side I’d use a high quality B-Complex like the one by Life Extension. One capsule in the morning and another at noon.
Thank you for your quick response. It’s amazing that you are taking time out to respond to all the queries.
At what point do you updose?
I see it takes some time Lomé 6-8 weeks (long when dealing with depression).
Is it too soon to try 800 (400 2x per day)?
Is that a AM / Noon or AM / PM ?
Thank you
Anyone can answer
Robert, you can try 400 mg twice a day to start. Once in the morning and again at noon. But make sure you take this size of dose with a good B-Complex. Otherwise, it’ll elevate homocysteine levels which are associated with increased heart disease, and depression.
Looks like Swanson Ultra – is the best quality brand based on your 7 step criteria.
Figured I’d post for readers,
What scare me is the US never lets something that works to be OTC.
My friend back early 90’s was taking SJW from Germany and later they were band and coincidentally a new US brand was launched.
Same thing happened with tryptophan in the 80’s when Prozac came out. Satan really does rule this world.
So I’m Leary of potency and quality of anything anymore.
Question is about initial sensations – like a loopy, buzzy brain feeling. Not intense but it’s all the time. This is 1 week in. (This is a back story) .. as I continued it got so annoying I quit before 2 weeks.
Is it like ADs that have a starting brain battle before it balances?
Robert, in 2018, the U.S. supplement market sales were estimated to be USD 42.6 billion. So there must be something in there that works for someone OTC. But you are correct that this industry’s growth scares the big pharmaceuticals because it cuts into their profits.
For some help in choosing the best or most effect nootropic supplements, see my post; https://nootropicsexpert.com/how-to-determine-a-nootropic-company-reputation/ and https://nootropicsexpert.com/7-tips-for-choosing-the-highest-quality-nootropic-supplements/.
Hi David, thanks for such a detailed article!
Could you recommend a b-complex for taking together with sam-e?
I’ve browsed through some of them and it’s hard to find one with dosages recommended in your b-vitamin articles
which one do you use? 🙂
Eugen, I use this one by Life Extension: https://amzn.to/2XjeyAt
Hi David. I came accross this site while researching Methionine. I was hoping to find answers to my issues (and those of my two boys teenage boys) from the blog. But did not. My story: (After years of depression, anxiety, lack of motivation, arthritis(diagnosed at age 19) bad memory,( I dont even remember people I met in the past) I have found, through research that I have Pyroluria and maybe, Histadelia. We are now on high dose b6, and zinc. As well as Magnesium, Manganese,Vit., C etc. Memory improved a bit. But the Arthritis pain, depression, lack of motivation, sleep disorder are still very present. I am now 52 years and I believe the damage done by this condition is irreversible. I really wish to help my two Sons who have similar symptoms like I do, from this debilitating condition. Do you think adding sam-e would help with Pyroluria. If not, what suggestion do you have? Thanks indeed.
Ade, the only effective treatment for Pyroluria as far as I can tell is Vitamin B3, B5, manganese, zinc, vitamins C and E, omega-3s and cysteine. And zinc depresses copper stores so you need to use 1.5 – 2 mg of copper daily as well.
But because of the complexity of proper levels of these nutrients, they need to be monitored using fairly frequent labs until you get some relief. Then it’s a matter of continuing whatever level of that treatment works.
Dear David.
I’d like to let you know what has happened since the last question(Last year, December 12). I found that after I reduced SJW dosage, I felt better. But after a few weeks, it went bad again, and I reduced SJW dosage again, and I felt better again. So before I tried other supplements, I could keep my mood this way by reducing my SJW dosage.(1800mg->1200->900->600->300) I stopped SJW completely, and a few weeks later, I felt bad again, and I thought I had to try something new. I’m sorry. You said ‘SAM-e is likely not the answer you are looking for’ but I wanted to try SAM-e before I tried L-Tyrosine. I just wanted to try everything to see what would have a long-term effect on me. And I realized that you were right, too. It’s been 25 days since I took 400mg of SAM-e until today, but I’m still not feeling well. And I took NALT(350mg) for five days, but it didn’t work either.
How long does it usually take for SAM-e to respond to depression? Is it possible that if I increase the dose of SAM-e, it will work?
About NALT, If my depression was related to a lack of dopamine, how long does it usually take to respond after taking NALT? If NALT doesn’t work at 350 mg, should I increase the dosage? Or should I change to L-tyrosine? Or is it time to try something else?? And I still have some SAM-e left. While trying NALT, can I continue to take SAM-e? I’m sorry for so many questions.
And I am always very grateful for your help.
Jay, you would know by now if SAM-e was helping you. But with NALT you’d know right away if the dosage was correct. I’d try doubling your dosage first before deciding if dopamine was you problem or it was something else.
But don’t forget that your brain needs the B-Vitamins as well if you want NALT to produce dopamine.
Hi David, I take 15mg of Mirtazapine each night (used to be on 30mg…no effect from it thus far). I have stress/depression induced tinnitus and Mirtazapine was the only option that didn’t have tinnitus as a side effect. But I’m not responding to it, I don’t even have the munchies haha! No sleepiness either from the Mirtazapine, so that was my first indication that it’s not working for me.
Can I safely start up SAM-e together with Mirtazapine? My psychiatrist didn’t even know about SAM-e…so he was of no help.
I’m suspecting MTHFR problems as I have an autistic dad and I suffer from fertility problems (and didn’t absorb folic acid when I was pregnant). I’m neurotypical, but ya know…genes and all 😉
Any advice you can give? Thanks 🙂
Suzy, if Mirtazapine doesn’t work for you it’s likely because your depression is caused by something other than problems with norepinephrine and/or serotonin. Please see this post for more on the different causes of depression: https://nootropicsexpert.com/best-nootropics-for-depression/
Using SAM-e with Mirtazapine shouldn’t be a problem. But it’s not likely to solve your issues either. If you decide to try SAM-e then make sure you use it with a high-quality B-Complex supplement.
Please study that post on depression and consider trying different nootropics that affect other possible causes. If it’s too confusing for you consider scheduling a consultation with me: https://nootropicsexpert.com/personal-consultations/
Hi David,
If one suspects that their anxiety and depression is due to overmethylation, is it contraindicated to use SAM-E?
Thanks,
Kenneth
Kenneth, If you don’t have enough folate or Vitamin B12 available, the SAM-e methylation process breaks down. Which can result in depression, brain fog, poor recall and memory, and pain. Have you thought of supplementing with Folate and methylcobalamin to see if that helps?
I’ve had my B12 tested and its 380ng/ml which is towards the lower level of normal, not sure what my folate level is however. I’m taking a B Vitamin Complex which contains folate and I’ve added methylcobalamin recently but not really noticing any difference. I was given duloxetine last year but found it made me severely anxious which led me to think that my symptoms are not due to neurotransmitter depletion; 5HTP and L-Tyrosine leave me feeling flat. I respond excellently to benzodiazepines which also suggests overmethylation. Niacin produced a good response initially but now I find that 100-200mgs is more than enough to produce a flush, so that makes me think that the Niacin has mopped up the methyl. I’ve recently started NAC and Rhodiola with good results so far. Your thoughts as always are most welcome.
Thanks
Kenneth, benzos work by enhancing the effect of GABA and GABAa receptor in your brain. Have you ever considered trying 500 mg of GABA before bed and seeing how you feel the next day?
Thanks David,
Your website is a fantastic resource and has been a great help.
Is it safe to take SAM-e with CDP/citicoline?
Jeff, it is safe to use these two nootropics together as long as each is dosed correctly. Including the B-Vitamins to support SAM-e.
I have a 26 year old son who is a USMC veteran. He is struggling with PTSD and depression. I am going to start him on several supplements, SAMe being one. I can only get him to take the supplements twice a day. I wanted to put him on 1200 of SAMe. Is it ok to take 800 in the morning and then 400 later in the day? I have also ordered a B-Complex.
Anne, your dosage suggestion is fine as long as it’s taken with a high quality B-Complex supplement. You may find that after a couple of months you’ll be able to reduce the dosage of SAM-e.
Please see my post on best nootropics for PTSD here > https://nootropicsexpert.com/treating-post-hurricane-ptsd-with-nootropic-supplements/. Suggested PTSD stack at the very end of that post. But I suggested reading the entire thing so you have a better understanding on what you are dealing with.
Thank you David. Heading over to read your post now.
Annie
Hi David,
I’m Taiwanese. I extremely appreciate your supplement introduction in your YouTube videos.
My B-complex contains sufficient B6, B9, and B12 which are close to the tolerable upper intake level, so I only need one capsule daily. My SAM-e are 400 mg tablets. Now I want to have a 800 mg dosage of SAM-e. You mentioned that SAM-e should be taken with vitamin B-complex together before a meal. So should I take two tablets of SAM-e with one capsule of B-complex together before breakfast instead of taking one tablet of SAM-e with one capsule of B-complex before breakfast and then another one SAM-e alone before lunch? Thank you very much!
Zhongting, great question and it’s good to be cautious. If your B-Complex is at the tolerable upper daily limit I suggest using the B-Vitamin with your morning SAM-e dose. And take the other SAM-e dose at noon alone but well before a meal.
You may find that once you get your SAM-e levels optimal you’ll be able to reduce your daily SAM-e dose back to 400 mg or even as low as 100 mg per day.
Hi David,
Among Nature Made, Doctor’s Best, Jarrow Formulas, which is your top-recommended brand for SAM-e? Thank you!
Zhongting, anyone of those three manufacturers test their product before shipping. So I wouldn’t recommend one over the other for supplements. But SAM-e is unstable and needs to provided in blister packs. I would use that as a guide along with product reviews by verified buyers to make a selection between these three.
Dear David.
Thank you very much for all your help. I am a Korean and please forgive me for my poor English.
For the last eight months, I’ve taken St. john’s wort (Perika). About five weeks after I started taking 900mg, I felt it was working. At the time, I was convinced that I had finally found a way to deal with depression without side effects. But since then, after about six weeks, I felt that it was no longer working.. so Since then, I’ve increased the dosage every six weeks, and now I take 1,800mg, and it still doesn’t seem to work. and then I noticed you said “St. John’s wort does not work for all types of depression or anxiety.”
In fact, I’ve doubted this before (When I felt that 300mg was no longer working). After analyzing my behavior, I started paying attention to dopamine. So at that time, I added Dopa Mucuna(Now Foods) on 300mg of SJW. But then I felt a headache for a while, and I stopped it. (I don’t know if it’s because I took it at the same time as SJW.)
So now I’m going to try SAM-e. What is your opinion on this point? I’ve taken SJW 1800mg for a few weeks. Do I have to slow down the SJW dose, stop it completely, and then start SAM-e? Or Can I start SAM-e(200mg) on the way to reduce the dose of SJW? I want to see the effects as soon as possible, so it’s not easy to wait until I stop the SJW. Actually, it decreased to 1,200 mg from yesterday. Or IS it better to take both SAM-e and 300mg(SJW) at the same time that I first experienced the effects of SJW? ( keep the 300mg of SJW , Just increase the dose of SAM-e by looking at the situation.) I’d like to hear your opinion on which combination to use. Or should I solve the problem in a way other than SAM-e?
PS. I also have taken Ashwagandha, Bacopa, L-theanine, CoQ10, Magtein, Magnesium(lysinate glycinate), Kelp, Zinc, selenium, vitamin ABCDEK, EPA-DHA(Fish oil), and I’m going to add Valerian, Resveratrol, taurine.
Jay, St. John’s wort inhibits the uptake of serotonin, dopamine, GABA, glutamate and norepinephrine. Which means that more of each neurotransmitter is available in your brain. But the caveat here is if those neurotransmitters are naturally available in the first place.
I can’t say for sure why you grew tolerant to St. John’s wort but it may be because your brain ran low on at least some of those neurotransmitters.
The problem is trying to figure out which neurotransmitters you are low in. The only way to find out is to add a precursor for each one and one-at-a-time so you can know if something is providing a benefit or not.
SAM-e is likely not the answer you are looking for. At least not by itself because SAM-e contributes to the synthesis of some of these neurotransmitters. But is not a direct precursor to their synthesis.
For example, you still need L-Tryptophan for serotonin and L-Tyrosine for dopamine and norepinephrine. GABA is dosed on its own.
Thank you very much for your detailed and kind reply.
OK, I’ll do as you suggest. I’ll start this process you said. ”The only way to find out is to add a precursor for each one and one-at-a-time so you can know if something is providing a benefit or not.”
First, I’ll start with L-Tyrosine. But there’s still one more question left. Should I stop SJW completely and start this process? Or should I proceed with this process on the basis of maintaining some SJW dose(For example, 900mg) ?
Thank you in advance for your answer.
Jay, if you are not experiencing any negative effects with St. John’s wort I think you could continue using it while you are experimenting with other nootropics like L-Tyrosine.
Thanks David for the profound info.
I will add now also SAM-e (Soloesse Italian pure S,S form) to the morning stack before any meal.
From other supplements post of you I understood that also:
-L-tyrosine
-ALCAR
– Alpha Lipoic Acid
also need to be taken on an empty stomach with some coconut oil.
The previous 3 go well together on an emthy stomach with oil.
Is it still ok to add the SAM-e to those 3 at the same moment?
No interactions with those 4 all on same emthy stomach?
On some I read that emthy stomach can also be no protein food or just fruit. Is fruit also ok with SAM-e?
The vitamin-B complex I take 2 hours later with yoghurt & mixed with whey isolate power and stacked extra capsules L-Carnitine Fumarate + magnesium glycinate lysinate chelate + zinc chelated + Q10 Ubiquinol
The B-complex does not need to be taken at same time with SAM-e?
If you see any that better are taken seperare please let me know.
Thanks for the good info
Wim
Wim, I suggest taking SAM-e at the same time as you take your B-Complex supplement. Because it needs B6 and B12 to work properly.
The key here is fat-soluble supplements should be taken with a meal or healthy fat like coconut oil.
But amino acids should be taken on an empty stomach because they compete with other amino acid in your meal. Things like meat. Anything in your meal that provides amino acids will prevent the full effect of an amino acid supplement.
Thanks David.
“SAM-e should be taken on an empty stomach” I read above.
I only have an empty stomach in the morning when I take already the amino acids: ALA,ALCAR, l-tyrosine
And the B-complex is written to take with food on the sticker. It is very strong, colours urine fluorid yellow first 2 hours after.
Not sure if I can take that also in the morning with all the rest together.
Thanks
Wim, there may be something in your B-Complex supplement that is fat-soluble which could be the reason to take it with food. But the B-Vitamins are water soluble and don’t require fat for transport.
I take my B-Complex with the rest of my stack with good results. You can take SAM-e and your B-Complex at the same time as the amino acids and get their benefit.
I have just begun to use both NAC and SAM e. I’m very excited to see its affects as far as realeving PTSD, and brain fog.
Thank you for your YouTube videos!
Hi David,
Love your website and youtube videos.
What do you think about the use of TMG instead of or in concert with SAM-e? From what I’m reading it seems that it would aid in methylation as well.
Jared, Trimethylglycine (TMG) is part of the one carbon cycle prior to the formation of SAM-e. Check out “betaine” in this very complex diagram: https://www.wikipathways.org/index.php/Pathway:WP241. I’ve not done the research but imagine you could use TMG in concert with SAM-e. Not sure what the result would be but if you try it please let us know. Your body needs both.
Hi! I 55 years old.
I use SAM-e for chronic pain and depression, and it helps a lot, but not on my focus and motivation at work.
I add B-1 and B-6, but not B-12, because B-12 changes my mood – irritable/angry.
Also, I changed to Keto diet, which have improved my mobility and mood. (no fish, because I’m allergic).
Can you give any advice on which nootropic I should consider that will enhance what what it is already working for me, without side effects? (specially for focus and motivation).
Yvette, you need ALL the B-Vitamins for your brain to work the way it was designed. Rather than going into specifics here, please concentrate on this section of a post I recently updated on Best Nootropics for 2018 here > https://nootropicsexpert.com/best-nootropics/#vitamin-b-complex. I encourage you to study the rest of that post as well. But for now, put your energy into understanding what each of the B-Vitamins do in your brain. That link has a very brief summary to give an overall idea on how they work together. Then click through each link for specifics and dosage.
Vitamin B12 is likely causing irritation because the rest of the pathways it is required for are out of balance. And you are likely using the wrong kind. You need methylcobalamin and NOT cyanocobalamin. You also need magnesium, zinc and likely lithium. Please see this list (https://nootropicsexpert.com/nootropics-list/) and scroll through to each so you can go to the full review for dosage and types to buy.
Finally, please study this post on motivation here > https://nootropicsexpert.com/hacking-motivation-with-nootropics/. For motivation, you need to encourage stimulation of glutamate AMPA-receptors to in turn, fire up dopamine neurons. And send dopamine on its way to the nucleus accumbens. That is the dopamine pathway responsible for motivation and pleasure.
First take care of the fundamentals I refer to above. Then try iodine, resveratrol, one of the racetams, noopept and Rhodiola Rosea. For the racetams your safest bet starting out is Aniracetam and Piracetam. Iodine and resveratrol are non-negotiable if you want to solve your issues. But for each of the nootropics I mention here and the rest of this comment, you must closely follow dosage instructions (and types to buy) for each to make sure you feel and experience the results you are looking for. For example, the racetams will not work without also using a choline supplement like Alpha GPC or CDP-Choline, the B-Complex vitamins, magnesium, zinc and a healthy fat like coconut oil.
Hi my son is taking Sam-e 200 complex aged 12 for adhd and anxiety is this blend enough as it is
200mg S adenosylmethionine
Folic said 90 mcg
B12 500 mcg
B6 25mg
Riboflavin 10mg
Zinc 5mg
It is brand nutrition care
Should we give Ritalin still until the Sam-e builds up in his system and howling until we should start seeing effects please
Denise, your your son is clinically ADHD it is unlikely that SAM-e and the B-Complex vitamins are going to eliminate all of his symptoms.
Please scroll down the Nootropics List here and see each review for dosages for each of these B-Vitamins: https://nootropicsexpert.com/nootropics-list/
If you want a natural way to help ADHD or a safer way to use Ritalin please see this post: https://nootropicsexpert.com/best-nootropics-for-adhd-add/