Table of Contents
Key Takeaways
- SAM-e (S-Adenosyl Methionine) is a naturally occurring amino acid crucial for brain health and bodily functions.
- It regulates neurotransmitters, impacting mood, memory, and behavior.
- SAM-e treats depression and anxiety effectively, faster than traditional antidepressants and without their side effects.
- SAM-e enhances neuroplasticity, brain-cell membrane fluidity, and muscarinic receptors, leading to improved learning, memory, and mood.
- 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 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.
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, 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]
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 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.
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 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 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. Like the high quality B-Complex like Performance Lab® B-Complex which contains therapeutic amounts of each of the B-Vitamins you need while using SAM-e.
In order to prevent homocysteine accumulating, logic tells us based on its mechanism of action that sufficient levels of B-Vitamins must be present to convert homocysteine into the potent antioxidant glutathione.
Take SAM-e on an empty stomach and an hour before eating any food. SAM-e is best digested in your intestines and not your stomach. Not letting SAM-e settle into your digestive tract could cause stomach upset.
SAM-e Side Effects
SAM-e is produced naturally in your body. So is considered well-tolerated and safe.
If you have bipolar disorder, you could develop mania when supplementing with SAM-e. So check with your doctor before using SAM-e.
If you’re on antidepressant medication, you should check with your doctor before supplementing with SAM-e.
High doses of SAM-e can cause gas, upset stomach, diarrhea, constipation, dry mouth, headache, dizziness, anxiety or skin rashes. SAM-e may also trigger an allergic reaction in some people.
Type of SAM-e to buy
SAM-e is available in 200 and 400 mg tablets.
For optimal effects with SAM-e, stable, enteric-coated tablets are recommended. SAM-e should be taken on an empty stomach, either one hour before or two hours after meals.
SAM-e is highly unstable so check expiration dates. And you should get tablets that are packed in sealed, gel-packs for freshness.
Avoid SAM-e in powder form as you’ll likely be unsatisfied with the results.
Nootropics Expert Recommendation
SAM-e 400 mg per day
I recommend using SAM-e as a nootropic supplement.
Your body does make some SAM-e on its own. But SAM-e levels decrease as we age. And you cannot get SAM-e from food.
SAM-e is critical for the methylation process needed for making important neurotransmitters including acetylcholine, dopamine, serotonin, norepinephrine and melatonin.
SAM-e is also involved in the cycle which produces the critical antioxidant glutathione. And it’s involved in maintaining brain cell membrane integrity and fluidity.
SAM-e increases muscarinic receptors in your hippocampus which boosts the activity of acetylcholine and other critical neurotransmitters in your brain. Leading to improved learning, memory and mood.
SAM-e is especially helpful if you’re dealing with depression. Or having difficulty coping with any kind of stress.
We suggest a dose of 400 mg daily. It may take a while for SAM-e to build up in your system. So be patient. Once you’re achieving the affects you want from SAM-e, you can eventually try scaling back your dose to 100 or 200 mg.
SAM-e needs Vitamins B6 & B12 and folate to work. Or SAM-e may not provide the benefit you are looking for. Most integrative medicine doctors and naturopaths recommend stacking a high quality B-Complex when using SAM-e. So make sure you stack SAM-e with the B-Vitamins listed above, or a good Vitamin B Complex formula that uses methylfolate (NOT folic acid).
A high quality B-Complex containing these bioactive B-Vitamins like the Performance Lab® B-Complex .
Join The Discussion - 390 comments
ANASTASIA
July 5, 2021
Hi David,
So glad i came across this article.
I stopped taking Zoloft almost 8 months ago after being on it for 13yrs.
I’ve been taking 5htp 100mg x 2 a day, tyrosine, B-complex, vitamin D, fish oil. L-theanine, probiotics, magnesium glycinate, glycine BUT i can’t seem to shake these intrusive and ruminating thoughts ive been having the past 3.5 months. Do you think SAM-e will help?, I just don’t know what to do anymore.
Thanking you in advance
ANASTASIA
July 5, 2021
*I forgot to mention i am also taking NAC and Ashwagandha
David Tomen
July 5, 2021
Anastasia, ruminating thoughts can be caused by low GABA or L-Glutamine levels. You can try SAM-e and see if it helps. I also suggest trying GABA (PharmaGABA), L-Glutamine, and Lemon Balm extract.
Anastasia
July 6, 2021
Hi David
Thank you for the quick response. What dosage do you recommend?
David Tomen
July 6, 2021
Anastasia, dosage for which supplement?
I include dosage recommendations for each of the supplements mentioned here. You can easily find them by scrolling down this list (https://nootropicsexpert.com/nootropics-list/) and clicking through to each supplement.
Jack
July 2, 2021
Hi David,
I’m suspecting I have some form of undermethylation, since I have anxiety, repetitive behaviors, perfectionism, sleep issues, hay fever, high histamine, high salivation.
I’ve read that SAMe could help. Is it true that SAMe raises homocysteine levels?
If this is the case, would TMG be a better option?
What about inositol, do you think it is good for undermethylation and my other issues?
Thanks A LOT for.your help!
David Tomen
July 3, 2021
Jack, studies show that SAM-e should be consumed with B-Vitamins because When SAM-e donates its methyl group, it breaks down into homocysteine. Increasing your B-Vitamins will counter this rise in homocysteine. Use it with a B-Complex like this one: https://amzn.to/3xk3SQT
Gayla
May 20, 2021
David,
First, I want to thank you for the wealth of information you provide on this site–it has been a huge help to me.
I have been taking SAM-e since last June for depression (Nature’s Way, along with a quality B-Complex) and it has worked quite well for me until recently. It seemed to just stop working, even with an increased (1600) dose. So I have a couple of questions: Is this a common problem and do you know why this could be? I also had seen reference somewhere that possibly a break should be build in, such as skipping a day each week. Do you agree with this? Could simply taking a break from it for a time and resuming cause it to start being effective again?
Thank you so much for your help!
David Tomen
May 21, 2021
Gayla, a couple of thing come to mind. First, has anything changed in your life that coincides with SAM-e no longer working? A change in diet, living environment, etc.
Second, is it possible your last bottle of SAM-e is defective? As a supplement, SAM-e is highly unstable and unless it is packaged and stored properly it can go bad quickly.
We have had major supply disruptions in the last year because of COVID-19. Maybe you just got a bad supplement?
Gayla
May 21, 2021
David, thanks so much for your reply and suggestions. I think the supply should be pretty reliable. I notice now I said Nature’s Way in my comment and I actually meant Nature Made, which is in blister packs and, at least as far as I know, is a dependable supplier of SAM-e. The time span it has been lacking efficacy for me has covered more than one box.
As far as anything changing in my life, nothing recently, really. Perhaps I have allowed the weight of what has gone on over the past year and the continuing political strife in this country to just finally overwhelm my system beyond what SAM-e can help.
Unless you know of something simple I could add or try, maybe I will just give it more time and hope it starts working again. I love to read about the various supplements, but my mind starts whirling when I try to comprehend the complex combinations and how they all work together. I am finding I need to keep things as simple as I can right now. ha!
Thanks so much for your help!
Gayla
May 21, 2021
P.S. I probably should have added that I also take ashwagandha. I originally started taking it simply for general health and don’t think I really considered the depression/anxiety aspect when I started taking SAM-e. I was just reading up on it again and guess I need to take that into consideration as well. (Other than that, I take fish oil, turmeric, multi-vitamin, and vitamin D.)
David Tomen
May 22, 2021
Gayla, it could be so many things that even with trial and error you may never figure out the cause of why SAM-e is now working as before.
SAM-e is involved in the synthesis of all the major neurotransmitters. So you could try testing each one by using a precursor to make dopamine, acetylcholine, serotonin, etc. And see if any of those help you. This article explains how to do that: https://nootropicsexpert.com/best-nootropics-for-anxiety/
Gayla
May 22, 2021
Thank you so much, David–I will start there. I appreciate immensely your taking the time to help me, as well as the expertise you share with all of us via your website. I trust that all the good you do will come back to you in spades.
Mike Carson
May 15, 2021
David,
I haven’t seen any indication that my last two replies were successful, so this is one more attempt to get you the information you asked for regarding SAM-e and compromised immune systems.
Mike
https://www.mskcc.org/cancer-care/integrative-medicine/herbs/sam-e
You are immunocompromised: There is a theoretical risk that SAM-e could enhance the growth of a microorganism called Pneumocystis carinii.
https://www.mayoclinic.org/drugs-supplements-same/art-20364924
If you have a compromised immune system, talk to your doctor before taking SAMe. People who have a weakened immune system may be at increased risk of an infection caused by bacteria known as pneumocystis. SAMe may boost this microorganism’s growth.
https://www.nccih.nih.gov/health/sadenosyllmethionine-same-in-depth
There’s theoretical reason to believe that taking SAMe may promote Pneumocystis infection in people who are immunocompromised, such as those who are HIV-positive.
https://www.cdc.gov/fungal/diseases/pneumocystis-pneumonia/index.html
Most people who get PCP have a medical condition that weakens their immune system, like HIV/AIDS, or take medicines (such as corticosteroids) that lower the body’s ability to fight germs and sickness. PCP is extremely rare in healthy people, but the fungus that causes this disease can live in their lungs without causing symptoms. In fact, up to 20% of adults might carry this fungus at any given time, and the immune system removes the fungus after several months.
Most people who get PCP have weakened immune systems, meaning that their bodies don’t fight infections well. About 30-40% of people who get PCP have HIV/AIDS. 7,9 The other people who get PCP are usually taking medicine (such as corticosteroids) that lowers the body’s ability to fight germs or sickness or have other medical conditions, such as:
• Chronic lung diseases
• Cancer
• Inflammatory diseases or autoimmune diseases (for example, lupus or rheumatoid arthritis)
• Solid organ or stem cell transplant
David Tomen
May 18, 2021
Mike, I’m behind on participating in the comments section so my apologies.
I saw what you posted earlier and checked it out. And my response is the same. These sites mention a “theoretical risk” of using SAM-e in someone who is immune compromised. But so far I have not seen any proof.
And by proof I mean at least one peer-reviewed clinical study in a respected medical journal telling us that if you are immune compromised you should not be supplementing with SAM-e. And why.
You will notice that when someone makes a statement like this it is copy and pasted to other sites. Over and over again with no one taking the initiative to back up what they are saying.
Unless I’m missing something. Am it?
Mike Carson
May 14, 2021
I found your information to be very compelling and am very interested in trying SAM-e. I do have a concern due to something I found during my further research. I am currently taking prednisone, therefore my immune system is compromised. Here is a cut and paste from what I found:
“Pneumocystis pneumonia (PCP) is a serious infection caused by the fungus Pneumocystis jirovecii.
Most people who get PCP have a medical condition that weakens their immune system, like HIV/AIDS, or take medicines (such as corticosteroids) that lower the body’s ability to fight germs and sickness.”
It appears that there is a chance that SAM-e can cause the pneumocystis bacteria to proliferate in the lungs, not something I find appealing. Your thoughts please. And thank you for you informative site.
David Tomen
May 14, 2021
Mike, I have not heard of this. I suggest finding clinical proof that this is true before you take it to heart.
There is a lot of garbage online written and published by people who cannot back up what they say. Unlike here where I back everything with peer-reviewed clinical studies. Not the word of someone else.
If you find the clinical study that supports what you heard please let me know and I’ll update this review. If you can’t find that proof you can assume it was not true.
Mike Carson
May 14, 2021
David,
Taken from The Mayo Clinic website: “If you have a compromised immune system, talk to your doctor before taking SAMe. People who have a weakened immune system may be at increased risk of an infection caused by bacteria known as pneumocystis. SAMe may boost this microorganism’s growth.”
This from http://www.nccih.nih.gov/health/sadenosyllmethionine-same-in-depth: “There’s a theoretical concern about the use of SAMe by people who are immunocompromised (such as those who are HIV-positive). Immunocompromised people are at risk for Pneumocystis carinii infection, and SAMe enhances the growth of this microorganism.”
And this under “warnings” from https://www.mskcc.org/cancer-care/integrative-medicine/herbs/sam-e: “You are immunocompromised: There is a theoretical risk that SAM-e could enhance the growth of a microorganism called Pneumocystis carinii.”
There are more sites that address it, but there does appear that there may be some risk. Thank you for the prompt reply.
Mike
David Tomen
May 17, 2021
Mike, thanks for this. But a big caveat here because, “There’s theoretical reason to believe …”. So far I haven’t seen any proof.
I’m not trying to be a prick here. But the reputation of Nootropics Expert depends on reliable, real, truthful information that is backed by science.
Mike Carson
May 18, 2021
David,
Not trying to be argumentative here. Just felt that if the above linked entities (with several others of considerable reputation) feel that there is enough potential for folks with compromised immune systems (such as myself with Prednisone) when taking SAM-e to develop the described issue, then it seems right to mention it and give them the option of doing their own due diligence.
Appreciate your site and your efforts in helping people.
Mike
David Tomen
May 19, 2021
Mike, I get your point. I do not mention this type of thing because I can’t find any science to back it up.
Most people do not realize that the articles published on those sites are written by paid freelance writers. There is no “authority” behind those sites unless the article is pointing to peer-reviewed clinical studies in respected journals.
Drew
May 14, 2021
Hello David
a few months ago, before reaching your website I have ordered SAMe from the company ‘NOW foods’, didn’t use much of it since didn’t made my due diligence on this supplement.
only while reading your post and the comments here I noticed that there is a little bit of sticky brown liquid on the bottom of the bottle, which turns out to be a rancid tablet.
after a closer look at the rest of the tablets, I noticed that they look a bit dark. decided to open one of them, and it’s brown from the inside – which means it’s oxidized?
what color does SAMe should have when it’s not oxidized?
also, is it only me, or the smell of SAMe is very similar to bee pollen?
and, if you could share your thoughts on the NOW brand regards which i am becoming very skeptical about lately but can’t describe why…
Thanks in advance
David Tomen
May 14, 2021
Drew, SAM-e is highly unstable so check expiration dates. But even then if it has been shipped carelessly and exposed to high heat. Or stored too long. Chances are you’ll end uyp with rancid product.
NOW Foods is a good company. They have a great testing program in place and ship quality product. Chances are good that product was fine when it left their manufacturing facility. But with the COVID mess still going one and shipping messed up who knows what happened to that supplement before it got to you. And how long have you had it sitting around?
Jodie Scheller
April 13, 2021
Really could use your help. I have 42 yr. Old daughter that was born with brain damage. At a young age she had many seizures, temper tantrums on and on medical problems so the doctors kept adding SSRIs. I had a DNA expression on how different drugs effected her! Dopamine and Serotonin were her biggest problem! But they kept adding. I weaned her off them and she has been on Sam-e with great results for many years. However, she has sleeping problems! She was on melatonin which worked for awhile then not, so switched to L- triptophane. Now not working after 12 months. Switched back to melatonin but not working either now. Yes, need to add B Complex! she takes D3, fish oil supplements, coenzyme, and blood pressure pills. Are her sleep brain waves messed up from lack of the B vitamins? Please can you help with suggestions! ASAP please
David Tomen
April 15, 2021
Jodie, this is how sleep works: https://nootropicsexpert.com/best-nootropics-for-sleep/.
Certainly a vitamin deficiency could result in all kinds of problems including insomnia.
And SSRIs have also been shown to mess with things like gene expression and disrupting ion channels. That just takes a lot of healing by including nootropics that increase BDNF (https://nootropicsexpert.com/13-nootropics-to-boost-bdnf/) and Nerve Growth Factor.
Brain waves are complicated things that science is still trying to figure out. L-Theanine is a good start to help produce calming brain waves.
Jodie Scheller
April 24, 2021
These are some of things from Carly my daughter’s phenotype I need to take into account.
Decreased metabolizer- phenotype CYP3A5
SLCSA4
Val/Val high activity
COMT-high activity
CYP2C19 *1/17 ultra rapid metabolizer- (UM)
David Tomen
April 26, 2021
Jodie, this is honestly beyond my area of expertise. But from what I know I’d try magnesium chelated, BioActive B-Complex, L-Theanine, Lemon Balm and still use L-Tryptophan.
But use the B-Complex earlier in the day so it doesn’t interfere with sleep.
Tony
March 25, 2021
Hey David, I do not know if you are still replying to comments however I wanted to ask a question in regards to sam-e’s side effects. I started taking sam-e and nac at the same time and felt almost instant relief from my anxiety and obsessive thoughts within days. Unfortunately the relief came with brain fog and I found myself forgetting things, lacking focus, and being not as motivated. Are there any co-factors that I should take with sam-e? I found that nac contributed to the brain fog even more-so than sam-e and quit taking it, however I still am noticing the brain fog effects are taking sam-e on its own for over two weeks.
I’m am not sure how relevant this information is but I do have a MTHfR heterozygous mutation c667t and have supplemented with methylfolate in the past. Though in the short term I felt great, the methylfolate supplementation eventually became overwhelming and I had severe side effects including anxiety, irritation, and depersonalization.
I love the positive effects of sam-e but is there anyway to downplay the brain fog?
Thank you for your time,
Tony
David Tomen
March 26, 2021
Tony, SAM-e must be used with a B-Complex which I’ve detailed above. Use a bioactive B-Complex esp. since you have issues with methylation. Choose a B-Complex like this one: https://amzn.to/39lYaUy but just use one capsule instead of the recommended 2 capsules per day. And see if that takes care of the brain fog.