The Truth About SAMe: Mental Health Benefits, Genetic Cautions, and Dosing Tips

The Truth About SAMe: Mental Health Benefits, Genetic Cautions, and Dosing Tips

Have you heard of Sam? Well, it’s a natural compound your body makes that might just help lift your mood, sharpen your focus, and boost your energy. And in today’s video, we’ll break down what Sammy actually is, how it supports your mental health, what the research says about using it for depression and anxiety, and how your genetics can make or break your experience with it. I’ll also share practical tips on safe dosing, side effects to watch out for, and even foods that help your body make it more naturally, so stay tuned. Hi, I’m Jazelle Rosa, a board-certified psychiatric nurse practitioner here to help you optimize your mental health through genetics and integrative and functional medicine using a skills before pills approach. So, what is Sammy? Well, esenazylmethionine or Sammy is naturally produced in your body from ATP and methionine and it plays a central role in mental and physical health. It functions as the primary methyl donor and is involved in over 100 essential biochemical reactions. And if you haven’t seen the video on methylation, I advise you go and watch that. But if you have seen it then you know that methylation is crucial for mood regulation, neurotransmitter synthesis, detoxification and cellular repair. So let’s first understand the basics of ATP and methionine. ATP or adenazine triphosphate is the primary energy molecule produced by the mitochondria in our cells. While methionine is an essential amino acid obtained through diet like from meat, fish and eggs and we need both ATP and methionine to produce Sam E. So we need healthy mitochondria and an adequate diet. And we’ll talk more about some dietary interventions later on. But first, let’s talk about Sami’s role in mental health. Well, samine facilitates neurotransmitter synthesis, especially dopamine, serotonin, and norepinephrine. It also supports phospholipid synthesis, which is important for enhancing brain cell membrane integrity. It also boosts glutathione production, which is crucial for reducing oxidative stress in the brain because glutathione is a powerful antioxidant. And so, what is the clinical evidence for Sammy? Well, when it comes to treating depression, studies consistently support Sami’s effectiveness in depression treatment. And a Cochran review, which was a systematic review in 2016, showed significant improvement in depressive symptoms compared to placebo, which were comparable to standard anti-depressant treatments. An earlier study in 2010 which looked at Sammy as an adjunct therapy was a double blind randomized clinical trial and it demonstrated improved outcomes when Sammy was combined with SSRIs for treatment resistant depression. Now, when it comes to anxiety and bipolar disorder, there’s some mixed evidence here where it can be beneficial for anxiety in some cases, but caution is required due to its stimulating effects and it could potentially exacerbate symptoms in bipolar patients. So, now let’s talk about genetic varants where Sammy can actually be used beneficially in certain varants starting with MTHFR. So if you have MTHFR gene variants that reduce your folate metabolism, increasing the need for methylation support, Sammy can actually bypass this bottleneck very effectively. And so those with the MTHFR varants often report clearer thinking and improved mood when supplementing with SAM E. Other genes like mtr and mtrr can have varants that lead to less efficient recycling of homocyine to meththeanine and Sammy supplementation supports this critical biochemical pathway. Now the comp gene valval and if you missed my video on the comp gene I have a video on that. Please go ahead and check it out. But the valval variant means you have rapid dopamine metabolism and Sammy can actually help to maintain optimal dopamine levels. And there are some nuances with compt where you may have the met alil which typically caution is advised due to slower neurotransmitter breakdown which can potentially cause overstimulation with SAM. But there’s a nuance here in the context of additional genes like MTHFR. Sammy might still be beneficial in controlled low doses, but when overseen by a provider who’s familiar with these types of genetic nuances. Now, let’s move on to other genetic variants that may need caution with SAM E. First, let’s talk about MAOA, which stands for monomine oxidase A, which is an enzyme that breaks down neurotransmitters like serotonin, dopamine, and norepinephrine. So your MAOA gene determines how quickly this enzyme works. And there are variants often described as low activity or high activity. And it’s the low activity MAOA variants which lead to slower breakdown of these neurotransmitters. And essentially that means these neurotransmitters linger longer in the brain. And for some this can be beneficial for mood, focus or motivation. But it can also mean a greater risk of emotional sensitivity, irritability, or anxiety if levels get too high. So why does this matter with Sam? Well, Sam acts as a methyl donor that supports neurotransmitter production. So it can boost the synthesis of serotonin, dopamine, and norepinephrine. And if you already have that low MAOA activity, your brain may struggle to clear out the extra neurotransmitter overload. And this can lead to symptoms like anxiety, agitation, restlessness, racing thoughts, or even insomnia. And this is why people with low activity MAOA varants should use SAM E cautiously. It’s also important to mention that low MAOA activity combined with slow compt can increase the risk of this neurotransmitter overload. So now let’s move on to the CBS gene. So something you might see in your genetic report could be CBS upregulation. And CBS stands for cystoion beta which is an enzyme that helps move homocyine down the transuleration pathway which is the process by which your body converts homocyine into cyine and glutathione to support detoxification and your antioxidant defenses. So in simple terms, think of CBS as a gate that diverts homocyine away from the methylation cycle and into making things like glutathione and other sulfur containing compounds. So CBS upregulation means that this gate is wide open and your body pushes homocyine quickly down that path which can lower your homocyine levels but also deplete your pool of methyl donors. So when someone has CBS upregulation, they already may be pushing that homocyine through this pathway quickly enough and then adding high doses of SAM E can further increase this flow and this can lead to excess sulfur metabolites like ammonia or sulfites and this can cause symptoms like anxiety, headaches, gut discomfort, irritability or even feeling wired. So, it doesn’t mean that you can’t ever use Sammy if you have a CBS or MAOA gene variant, but you do need to be cautious. Lower doses, watching for symptoms, and supporting your detox pathways can go a long way. Also, understanding your MAOA and CBS status are powerful examples of how your genetics can help personalize your supplement strategy, making it safer and more effective. And this is why working with a knowledgeable practitioner is so helpful because they can help you figure out if Sammy is right for you and how to use it without causing any of these imbalances. So now let’s talk about one of the major risk of taking Sammy, which is overmethylation, which we’ve talked about in the methylation video and the B12 reaction video. So if you missed those, I advise you check them out. So signs of SAM E overmethylation will include things like anxiety, irritability, insomnia, headaches, migraines, racing thoughts, or even agitation. So if you’re having any of these symptoms and you think you’re overmethylated on Sami, you want to first lower or stop your dose. Take nascin, which can help reduce those methyl groups, and stay hydrated, be calm, and support your nervous system. But most importantly, make sure you’re working with a provider to help you adjust your supplement plan. And so now, let’s talk about proper dosing guidelines when it comes to Sammy. Well, you first want to start with a starting dose of 200 to 400 mg a day, starting in the morning. Then get to a more therapeutic dose from 400 to,200 milligrams to support your mood, which is typically split into 1 to three doses daily. And you generally don’t want to exceed 1600 milligrams a day due to the increased risk of side effects. And gradual increases are recommended in increments of 200 to 400 milligrams weekly. You also want to make sure you’re regularly monitoring for side effects and effectiveness of Sammy. And so possible side effects will include things like insomnia, GI upset like nausea, irritability or hypomomania especially in the bipolar spectrum and anxiety which is especially true in certain genetic variants as we just discussed or if you combine SAM E with highdosese methyl B12 or methylolate. And so now let’s talk about some natural dietary support for SAM E. Well, first you want to focus on methanine rich foods like grass-fed beef, eggs, fish, poultry, nuts, and even seeds. Then you want to focus on supportive co-actors like vitamins B12 and folate, magnesium, and zinc to enhance Sammy production and utilization. It’s also important to note that the Mediterranean diet, which is rich in healthy fats, adequate protein, and antioxidants, naturally supports methylation and SAM E production. So, now let’s talk about potential medication interactions and safety when it comes to SAM. Well, first, careful monitoring is needed with SSRIs, SNRIs, or tricyclic anti-depressants due to the risk of serotonin syndrome. Caution is also advised with Parkinson’s medications, mood stabilizers, and MAOA inhibitors. And it’s contraindicated or cautiously used in bipolar disorder, pregnant or breastfeeding women and children. And this is due to limited evidence. And now for my final thoughts. Well, Sammy is a powerful tool for supporting your mental health. It can help boost mood, improve focus, and support neurotransmitter balance. especially for people with certain genetic profiles or methylation challenges. But like any supplement, it’s not a one-sizefits-all. Your genetics, your biochemistry, and your current medications, even your diet play a role in how SAM will affect you. And that’s why it’s so important to take a personalized approach. So knowing your MTHFR, your COOMT, MAOA, and CBS genetic status can help you predict how you might respond and help you use SAM E safely and effectively. Remember, more isn’t always better. Start low, go slow, and pay attention to your body’s feedback. And don’t hesitate to seek help from a practitioner who understands methylation and neutrogenomics. So, if you found this video helpful, please give it a like and share it with someone who might benefit. And if you’re not already, subscribe to the channel for more sciencebacked holistic mental health insights like these. And if you’re curious about whether Sammy is right for you, or you want to understand your genetic blueprint for mental wellness, check out the links in the description. And let’s take the guesswork out of your mental health journey and help you build a plan that actually works for you. And as always, I thank you for watching. I wish you well on your mental health care journey, and I look forward to seeing you in the next video. [Music]

In this video, board-certified psychiatric nurse practitioner Jezel Rosa breaks down everything you need to know about SAMe for mental health:
– What SAMe is and how it works in the brain
– The latest research on SAMe for depression and anxiety
– How your genes (like MTHFR, COMT, MAOA and CBS) impact your response
– Signs of overmethylation and how to manage it
– Dosing strategies and side effect prevention
– Foods and nutrients that naturally support SAMe production
– Who should be cautious, and how to personalize your plan

Whether you’re navigating mental health struggles or simply looking to optimize brain function, this episode will help you use SAMe safely and effectively. Don’t forget to check out my links below to explore DNA testing, coaching options, and other resources mentioned in this video.

🧬DNA Testing packages: https://2ly.link/261YY
🧪 Mental Health Lab Testing: https://2ly.link/261YZ

⚡Vagus Nerve Device:
Nurosym- use this code for £35 OFF https://bit.ly/Nurosym35OFF

🧠 Happy Mind drink: https://www.amare.com/et/lfnarp/132716

📚 Recommended Reading: https://www.levelheadedmind.com/books

🎥 This video was edited by:
Rahul Kanchi https://www.linkedin.com/in/rahul-kanchi/

🚑 If you are in a mental health crisis, please dial 9-8-8 from the U.S. Or text HOME to 741741 and connect to a crisis counselor.
You can find a list of international crisis lines here: https://blog.opencounseling.com/suicide-hotlines/

References:
Galizia, I., Oldani, L., Macritchie, K., Amari, E., Dougall, D., Jones, T. N., Lam, R. W., Massei, G. J., Yatham, L. N., Young, A. H., & Ferrier, I. N. (2016). S-Adenosyl methionine (SAMe) for depression in adults. Cochrane Database of Systematic Reviews, 2016(10), CD011286. https://doi.org/10.1002/14651858.CD011286.pub2

NCCIH. (2017, January). S-Adenosyl-L-Methionine (SAMe): In Depth. NCCIH. https://www.nccih.nih.gov/health/sadenosyllmethionine-same-in-depth

Papakostas, G. I., Mischoulon, D., Shyu, I., Alpert, J. E., & Fava, M. (2010). S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. The American journal of psychiatry, 167(8), 942–948. https://doi.org/10.1176/appi.ajp.2009.09081198

Young, S. N. (2007). Folate and depression—a neglected problem. Journal of Psychiatry and Neuroscience, 32(2), 80–82. https://pmc.ncbi.nlm.nih.gov/articles/PMC1810582/

Disclaimer: All of the information on this channel is for educational purposes only and not intended to be specific/personal medical advice or substitute for diagnosis and treatment of any conditions discussed herein. Furthermore, watching these videos or getting answers to comments/questions, does not establish a provider-patient relationship. Please consult with your own healthcare provider for proper diagnosis and treatment.

Note: This video is not sponsored. Some of the links provided are affiliate links, meaning I may earn a small commission from purchases made through those links.