SAM-e as a nootropic-improves concentration

SAM-e

David Tomen
Author:
David Tomen
15 minute read
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

Key Takeaways

  1. SAM-e (S-Adenosyl Methionine) is a naturally occurring amino acid crucial for brain health and bodily functions.
  2. It regulates neurotransmitters, impacting mood, memory, and behavior.
  3. SAM-e treats depression and anxiety effectively, faster than traditional antidepressants and without their side effects.
  4. SAM-e enhances neuroplasticity, brain-cell membrane fluidity, and muscarinic receptors, leading to improved learning, memory, and mood.
  5. SAM-e supplementation with B vitamins at recommended dosages of 400 to 1600 mg daily benefits conditions like depression, anxiety, osteoarthritis pain, fibromyalgia, and chronic liver disease.

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.

Overview

SAM-e (S-Adenosyl Methionine) is a naturally occurring coenzyme that plays many critical roles in your body.

SAM-e (S-Adenosyl Methionine) chemical structure
SAM-e (S-Adenosyl Methionine)

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 chronic liver disease.

SAM-e is sold as an OTC dietary 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.

SAM-e supplementation can help prevent depression

How does SAM-e work in the Brain?

SAM-e boosts brain health and function in several ways. But two in particular stand out.

  1. 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]

  1. 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, cytokines, 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]low SAM-e can cause depression

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, methylfolate, 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

↓ Methylfolate, 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, dementia, and other cognitive symptoms.

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 supplements are anti-anxiety

SAM-e benefits

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 group 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.supplementing with SAM-e can increase your sense of well-being

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 methylfolate (B9) (avoid folic acid).

SAM-e improves learning and memory

SAM-e Clinical Research

SAM-e Lifts Mood

We have made significant progress in the last 100 years in diagnosing and treating depression. And yet, 10’s of millions still suffer from depression. In 2014, an estimated 15.7 million adults in the United States had at least one major depressive episode in the past year.[ix]

In the United States, one in ten Americans are using antidepressants.[x] I don’t have statistics from other countries but I suspect many have similar problems. Unfortunately, antidepressants only work 30 – 50% of the time. And often 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. When it is caused by a folate deficiency, impaired methylation (SAM-e), and poor 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 for ADHD in Adults

Ritalin and Adderall are thought to be the most effective treatment in children and adults with ADHD. These stimulants work by potentiating both dopamine and norepinephrine at the synaptic cleft. But stimulant meds for ADHD come with side effects.

SAM-e acts as a methyl donor and is involved in many metabolic pathways. It has both adrenergic and dopamine receptor agonist activity.

A research team at the University of California used SAM-e with subjects diagnosed with Adult ADHD in a 9-week double-blind, placebo-controlled trial.

The research team found that 75% of the patients had a significant improvement in ADHD symptoms while using SAM-e. And the 25% who did not respond to SAM-e, did not respond to Ritalin either.[xii]

SAM-e Treats Depression

Scientists at the US Department of Health and Human Services conducted an analysis of 102 individual studies in 25 databases on SAM-e and depression in 2002. The report distilled data gleaned from published studies conducted around the world up to 2002.

This comprehensive report is called, “S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease.” The researchers found that SAM-e is just as effective as standard antidepressant drugs at treating depression.

The agency concluded, “Treatment with SAM-e was equivalent to standard therapy for depression”.[xiii]

SAM-e Recommended Dosage

Recommended dosage of SAM-e for nootropic benefit is 400 mg per day.SAM-e nootropic dosage

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 function issues: 1600 mg daily in divided doses

SAM-e for alcoholic liver disease: 600 – 1200 mg daily in divided doses

Some research and many user reports suggest that once positive effects are achieved, SAM-e doses can be reduced. Some report benefit with as little as 100 mg of SAM-e daily.

Studies show that SAM-e should be consumed with B-Vitamins. When SAM-e donates its methyl group, it breaks down into homocysteine. Elevated homocysteine levels are associated with increased heart disease, birth defects and depression.

Choose a bioactive B-Complex to use with SAM-e. Or a high quality and bioactive Multi like my favorite, the Performance Lab® NutriGenesis Multi for men or women which contains therapeutic amounts of each of the B-Vitamins you need while using SAM-e.

In order to prevent homocysteine accumulating, logic tells us based on its mechanism of action that sufficient levels of B-Vitamins must be present to convert homocysteine into the potent antioxidant glutathione.

Take SAM-e on an empty stomach and an hour before eating any food. SAM-e is best digested in your intestines and not your stomach. Not letting SAM-e settle into your digestive tract could cause stomach upset.

SAM-e Side Effects

SAM-e is produced naturally in your body. So is considered well-tolerated and safe.

If you have bipolar disorder, you could develop mania when supplementing with SAM-e. So check with your doctor before using SAM-e.

If you’re on antidepressant medication, you should check with your doctor before supplementing with SAM-e.

High doses of SAM-e can cause gas, upset stomach, diarrhea, constipation, dry mouth, headache, dizziness, anxiety or skin rashes. SAM-e may also trigger an allergic reaction in some people.

Type of SAM-e to buy

SAM-e is available in 200 and 400 mg tablets.

For optimal effects with SAM-e, stable, enteric-coated tablets are recommended. SAM-e should be taken on an empty stomach, either one hour before or two hours after meals.

SAM-e is highly unstable so check expiration dates. And you should get tablets that are packed in sealed, gel-packs for freshness.

Avoid SAM-e in powder form as you’ll likely be unsatisfied with the results.

Nootropics Expert Recommendation

SAM-e 400 mg per day

Nootropics Expert Tested and ApprovedI 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 methylfolate (NOT folic acid).

Or use a high quality Multi containing these bioactive B-Vitamins like my favorite, the Performance Lab® NutriGenesis Multi for men or women.

As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.

[i] Kagan B.L., Sultzer D.L., Rosenlicht N., Gerner R.H. “Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial.” American Journal of Psychiatry. 1990 May;147(5):591-5. (source)

[ii] Muccioli G., Scordamaglia A., Bertacco S., Di Carlo R. “Effect of S-adenosyl-L-methionine on brain muscarinic receptors of aged rats.”European Journal of Pharmacology. 1992 Nov 2;227(3):293-9. (source)

[iii] Park L.K., Friso S., Choi S.W. “Nutritional influences on epigenetics and age-related disease.” Proceedings of the Nutrition Society. 2012 Feb;71(1):75-83. (source)

[iv] Ray J.G., Cole D.E., Boss S.C. “An Ontario-wide study of vitamin B12, serum folate, and red cell folate levels in relation to plasma homocysteine: is a preventable public health issue on the rise?” Clinical Biochemistry. 2000 Jul;33(5):337-43. (source)

[v] Saunderson E.A., Spiers H., Mifsud K.R., Gutierrez-Mecinas M., Trollope A.F., Shaikh A., Mill J., Reul J.M. “Stress-induced gene expression and behavior are controlled by DNA methylation and methyl donor availability in the dentate gyrus.” Proceedings of the National Academy of Sciences U S A. 2016 Apr 26;113(17):4830-5 (source)

[vi] Williams A.L., Girard C., Jui D., Sabina A., Katz D.L. “S-adenosylmethionine (SAMe) as treatment for depression: a systematic review.” Clinical and Investigative Medicine. 2005 Jun;28(3):132-9. (source)

[vii] Najm W.I., Reinsch S., Hoehler F., Tobis J.S., Harvey P.W. “S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial.” BMC Musculoskeletal Disorders. 2004 Feb 26;5:6. (source)

[viii] Tavoni A., Vitali C., Bombardieri S., Pasero G. “Evaluation of S-adenosylmethionine in primary fibromyalgia.” A double-blind crossover study. American Journal of Medicine. 1987 Nov 20;83(5A):107-10. (source)

[ix] “Major Depression Among Adults” National Institute of Mental Health nimh.nih.org Retrieved July 25, 2016 (source)

[x] Rabin R.C. “A Glut of Antidepressants” The New York Times blogblogs.nytimes.com Retrieved July 25, 2016 (source)

[xi] Bottiglieri T., Laundy M., Crellin R., Toone B.K., Carney M.W., Reynolds E.H. “Homocysteine, folate, methylation, and monoamine metabolism in depression.” Journal of Neurology, Neurosurgery and Psychiatry. 2000 Aug;69(2):228-32. (source)

[xii] Shekim W.O., Antun F., Hanna G.L., McCracken J.T., Hess E.B. “S-adenosyl-L-methionine (SAM) in adults with ADHD, RS: preliminary results from an open trial.” Psychopharmacology Bulletin. 1990;26(2):249-53. (source)

[xiii] “S-Adenosyl-L-Methionine (SAMe) for Depression, Osteoarthritis, and Liver Disease” US Department for Health and Human Servicesarchive.ahrq.gov Retrieved July 25, 2016 (source)

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Join The Discussion - 367 comments

Kristy
December 21, 2021

Hi! Is it okay to take SAM-e with 5htp, complex b vitamins, l tyrosine, GABA, and L-theanine?

    David Tomen
    December 23, 2021

    Kristy, as long as it works for you it’s OK.

Phil
November 3, 2021

Hi David, I’ve had good success with SAM-e (400-600mg, split dose across the day) – I’ve been diagnosed as an undermethylator (effectively under produce neurotransmitters) plus an out of whack zinc/copper ratio and currently on a nutrient/nootropic plan to fix. I’m also COMT met/met so SAM-e helps in the degradation of catecholamines too.

Do you have any thoughts on supporting methylation or all-rounder type nootropics that can help?

I have a stack including SAMe, ML Pro (2x tabs), Tryptophan, Omega 3, Multivit, VitD, Magnesium, CoQ10 etc all at the right levels so got most of the bases covered.

I suffer from stress-induced anxiety and depression with a bit of ADD and OCD tendencies mixed in.

Any tips would be awesome.

    Phil
    November 3, 2021

    Just to clarify, when I say all-rounder I mean like SAM-e that underpins the ‘system’ is helpful and wondering what else can help bump up all the levels if they are depleted. I’ve got a list of things to try and trying to do it with ones that cover more areas then say targeting one particular pathway (which I know you would recommend for anyone starting out). Thanks

      David Tomen
      November 3, 2021

      Phil, the advantage to targeting one neurotransmitter pathway at a time is it’s the only way to know which you are deficient in. For example, L-Tyrosine increases dopamine. L-Tryptophan increase serotonin. Alpha GPC or CDP-Choline increases acetylcholine. Each of these precursors require specific cofactors as well.

      But there is no “all-rounder” like SAM-e. And SAM-e contributes to the synthesis and removal of these neurotransmitters. But it cannot do it on its own if you do not have enough L-Tyrosine present to produce dopamine as one example.

        Phil Muggeridge
        November 4, 2021

        Thanks David, I thought as much.
        I’m on a plan with tryptophan and MLP currently. Will see how that goes.

Shaan
October 26, 2021

Hey David,

Just wondering if SAM-e would be ok to take on the same day as dextroamphetamine. Pills I’ve got are 200mg and 15mg respectively. I followed everything you said about grabbing the right kind to make sure they actually work too.

Just wanted to know if there’d be any potential risk of SS or mania or anything with this combo. Dex and ginkgo was definitely a bad one, and a few others definitely have not been good too, so, I’d like to know before moving forward with this if this will be ok or if it’s something I should be concerned about/avoid.

Many thanks!
Shaan

    David Tomen
    October 26, 2021

    Shaan, there are no contraindications to using both but you already mentioned your negative experience with Ginkgo Biloba so I wish I could give you a definitive answer. But they only way to find out is to try it to see how it affects you. Just make sure you haven’t anything to do that’s important for the next few hours. 🙂

      Shaan
      October 26, 2021

      Hi David!!

      Many thanks for your quick response :).

      Yes I found ginkgo made it quite panicky and anxiogenic. May have been a one-time thing though; I ought to give the combo another shot some day but as of right now I’m a little worried/sketched out from the last time I did it. Seemed to do what caffeine does to me – made me hypomanic. I don’t think ginkgo’s done that before, but it’s been a while since I’ve last done it (quite a few years). And come to think of it, I don’t think it ever really for along with me anyway, so I’ll probably just end up leaving it.

      Anyway sounds good!! I’ll give it a try and see what happens. Seems to be the standard protocol for most of these eh? :P. I’ll come back and let you know what happens after I’ve done it, which should be relatively soon.

      Cheers again David,
      Shaan

        Dina
        November 9, 2021

        Hi,

        I wanted to add my thoughts here, as I have now tried this combo a couple of times, taking an activated form of a vitamin B complex alongside it to ensure that the sam-e was potentiated, and most recently it made me quite ill. I took sam-e for the purpose of modulating my dextroamphetamine prescription, to smooth out some of the jittery side effects and come-down. About 45 minutes following ingestion of both compounds at the same time; I experienced a racing heartbeat, increased blood pressure, and distinct nausea. Although there are many anecdotal reports indicating that the two should not interact with one another, I had a different experience. Here is some additional color on this:

        https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.29.1_supplement.134.3

        As dextroamphetamine also markedly increases dopamine and to a lesser extent norepinephrine, I do not recommend this combination.

        Anyone with more knowledge and experience, please feel free to correct me, or add your thoughts.

        All the best

        Dina
        November 9, 2021

        PS: for purposes of clarity, I wanted to add that I had taken 400 mg of S-Adenosyl methionine together with 10 mg of dextroamphetamine as a fast-acting tab, alongside a vitamin b compound which contained 45 mg of b6 as p5p. While vomiting helped reduce the nausea, the experience was unpleasant. In the past, taking the sam-e a few hours apart from the dextroamphetamine did not seem to have this effect.

Mark
October 25, 2021

Is Sam-e a substance that I can take daily? Does one develop a tolerance to it over time? Is it difficult to stop taking if you have been taking for a long period of time?

    David Tomen
    October 26, 2021

    Mark, you can use SAM-e daily, you cannot grow tolerant to it, and if it works for you it’s safe to use long-term.

Phil Muggeridge
October 15, 2021

Hi David, thank you for all the information on the site. I have been taking SAM-e about a week, I read a lot about it after being both MTHFR and COMT homozygous. Then read more when looking at the Walsh approach as being methylation tested at the moment.

I am taking 400mg AM and lunchtime, its a Now Foods product that says its stabilized – NOW Foods – SAM-e 400 mg – it has shown some promise so far, it had some initial uplift.

I am taking this multi with it and was interested by your view – think it covers all the bases – Inessa Wellness Advanced Daily Multivitamin

Lastly, the Walsh book ‘Nutrient Power’ talks about Vitamin B5 as actually lowering production of serotonin and dopamine. Seeing a practitioner next week as being tested for methylation.

Any comments would be awesome.

    David Tomen
    October 15, 2021

    Phil, I normally like NOW Foods supplements as long as they don’t include toxic “other ingredients”. But in this case they claim that this SAM-e supplement is stabilized but they don’t say how. And the tablet is not enteric coated. Some I am a little wary about this without further investigation which I suggest you do and find out exactly how they stabilized it.

    The multivitamin you are using contains bioactive vitamins which is good. But it is missing some critical minerals. Please compare their label to this one: https://bit.ly/347dm5M which is the Multi I use and recommend.

    And does Walsh explain why she thinks Vitamin B5 depletes serotonin and dopamine? Because it doesn’t make any sense. B5 is needed for the synthesis of Coenzyme-A which is needed to produce serotonin.

      Phil Muggeridge
      October 16, 2021

      Thanks David, the b5 comment is in a table in the book. I see someone Tuesday so can report back.

      As for the multi, from what I can see it doesn’t have iron (my iron is high), copper (quite high) and Vanadium – not heard of.

      Magnesium I take at a proper dose separately.

      As for the SAM-e I’ve got Doctors Best in blisters in the cupboard so taking 200+200 today.

      The NOW foods one says to refrigerate after opening, I’ll drop them a message.

        David Tomen
        October 16, 2021

        Phil, these are the minerals that should be in your multivitamin and why you want them there: https://nootropicsexpert.com/13-minerals-essential-for-the-optimized-brain/. Not enough Molybdenum and see what goes wrong. It’s this type of thing that is easy to miss but so critical.

        Phil
        October 18, 2021

        Thanks, good to review re Boron (& SAM-e) and Potassium (which I’ve tried to up before).

        By the way had a response from Now Foods on the tablet in their form:
        “In early 2021 we introduced an improved 400mg tablet. Our world-renowned SAMe supplier has done a lot of research on developing a superior product as well as an extended release tablet coating which does an excellent job in protecting the stability and bioavailability, especially when refrigerated after opening*. See more below. We can offer a better value with equal stability compared to blister packaging at increased cost.

        *Store in a cool and dry environment in tightly sealed original packaging at refrigerated conditions 2-8°C (36-46°F)at less than 50% relative humidity.”

        David Tomen
        October 19, 2021

        Phil, what they are saying is likely true because it’s not hard to imagine that an “extended release tablet coating” should protect the ingredient inside that coating.

Tom
October 3, 2021

Can you recommend a Sam-e supplement product? Can this be taken with NAC/ inositol / ashwagandha and Maca?

    David Tomen
    October 4, 2021

    Tom, you can get SAM-e from several good supplement companies like this one: https://amzn.to/3DbsJJf. The tablet must be enteric coated, sealed in bubble packs, and be fresh. This last one is important because SAM-e is very unstable and you can get spoiled supplements even from the most trustworthy companies. So inspect it once it arrives to make sure it’s useable.

    And SAM-e is not contraindicated with any of the the supplements you mentioned.

Dan
September 27, 2021

Hi David,

Would be safe to use Sam-e and l-tryptophan to help with serotonin production?

Preferably sam-e in the morning and l-tryptophan (250mg)before bed.

Many thanks

    David Tomen
    September 28, 2021

    Dan, SAM-e is a methyl donor required for the synthesis of serotonin and works with Tryptophan to do that. The half-life of SAM-e when consumed in an enteric coated tablet is 100 minutes. So I suggest using them together. Possibly SAM-3 a couple of hours before taking Tryptophan.

Yazan
September 22, 2021

Hi David,

Can I use SAM-e with below stack?

Performance Lab Sleep
Performance Lab Energy
Oxiracetam
Aniractem
Ashwaganda
Sulbutiamine
Passion Flowers

Thanks,
Yazan

    David Tomen
    September 22, 2021

    Yazan, you should be able to use SAM-e with that stack. But make sure you also follow dosing suggestions including a bioactive B-Complex supplement.

    And when using the racetams you will get better results by including 300 mg Alpha GPC or CDP-Choline.

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