51. Methylation Optimisation: What The Biohacking Trend Gets Wrong

Methylation has become one of the hottest topics in functional medicine, biohacking, and wellness. From MTHFR testing to methylated supplements, many people are being told that boosting methylation is the key to better energy, mood, detoxification, hormone balance, and longevity.

But what if more methylation isn't always better?

In this episode, Joanne explores the science behind methylation, the roles of MTHFR and COMT, and why relying solely on genetic reports can lead to inappropriate supplementation. Joanne explains the difference between undermethylation and overmethylation, the symptoms of excess methyl groups, and why many people experience worsening anxiety, insomnia, irritability, and other adverse effects when taking methylated supplements.

Whether you're a practitioner, student, or someone navigating histamine intolerance, hormone imbalances, or chronic health concerns, this episode provides a balanced, evidence-informed perspective on one of today's most talked-about health trends.

In this episode, you'll learn:

• What methylation is and why it's essential for health
• How methylation affects neurotransmitters, hormones, detoxification, and gene expression
• The difference between undermethylation and overmethylation
• The role of MTHFR, COMT, folate, and vitamin B12 in methylation pathways
• Common symptoms of excess methyl groups
• Why genetic testing alone doesn't tell the whole story
• The potential risks of methylated supplements
• A more personalised approach to methylation support

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Transcript

0:00

Hi, it's Joanne. If you've spent any time in the health, functional medicine, or biohacking world recently, you've probably heard people talking about methylation. It's often presented as the key to better energy, improved mood, enhanced detoxification, healthier hormones, and even longevity. And while methylation is incredibly important, I think the conversation has become far too simplistic. What concerns me is that many people are being told they're under-methylating based on a gene report alone and are being encouraged to take high doses of methylated supplements without understanding the bigger picture. In clinical practice, I often see the exact opposite problem. People who are already struggling with excess methyl groups, who become more anxious, more wired, more irritable, and sleep even worse when they take these products. So in today's episode, I want to separate the science from the hype and explain what methylation actually is, why it matters, and why more methylation isn't always better. Welcome to the Histamine Well Podcast. Designed for practitioners and patients alike. This is your trusted source for insights on histamine intolerance, methylation, gut health, women's hormones, and much more. I'm Joanne Kennedy, your host, naturopath, author, and educator, passionate about breaking down complex science into clear, accessible knowledge. Whether you're a health professional or navigating your personal wellness journey, the Histamine Well Podcast bridges the gap between cutting-edge research and practical understanding to empower you with the tools to thrive. Hi, everyone, welcome back to Histamine Well. Today, I want to talk about something that has been absolutely everywhere in 2026, which is methylation optimization. If you've spent any time in health podcasts, biohacking communities, or functional medicine circles, you've almost certainly come across it. The promise is compelling. Fine-tune this one biochemical pathway and unlock better energy, sharper cognition, improved mood, and protection against chronic disease. And look, as someone who works with methylation every day in clinical practice, I have a lot of thoughts on this because the science underneath it is genuinely important and real, but the way it's being talked about right now does concern me. So today I want to give you what I think is a more honest picture, what methylation actually does, why it matters, and where the current trend gets it right and where it gets it wrong. So what is methylation? It is a fundamental biochemical process that happens billions of times per second in every cell of your body. At its most basic level, it involves the transfer of a methyl group from one molecule to another. That sounds very technical, but what it means in practice is that methylation acts like an on-off switch for an enormous range of biological functions. It regulates gene expression, essentially determining which of your genes are active and which are silenced without changing the underlying DNA sequence. This is the basis of epigenetics, and it matters for everything from how your cells develop to how your body responds to stress and environmental exposures. Methylation is essential for producing and balancing neurotransmitters like serotonin, dopamine, and norepinephrine, which directly influences mood, motivation, sleep, and cognitive function. It supports detoxification, helping the body convert toxins and metabolic waste into forms that can be excreted. It's involved in hormone production and metabolism. It helps regulate homocysteine levels, which matters for cardiovascular health, and it supports DNA repair and cellular energy production. So it's not a fringe concept. Methylation is not a fringe concept. It's genuinely central to how the body functions. So I wanna talk about how I think this biohacking narrative is really oversimplifying what we need to do with regards to methylation. this is very simple, this concept. How we make methyl groups is kind of simple. You know, like we have some genes such as MTHFR, MTR, BHMT, and nutrients such as folate, B12, B6, and betaine. if there is a gene mutation on one of those variants or nutrient deficiencies, then people are sort of presuming that they're undermethylating, so they don't have enough methyl groups, therefore taking some methylated B vitamins would be helpful. Helpful for their energy, their mood, their detoxification. However, in many, many, many people, especially women, it doesn't matter if they have a genetic mutation on one of these SNPs, such as MTHFR and the nutrient deficiencies. Because of a gene mutation or enzyme called COMT, catechol-O-methyltransferase, they're often overmethylating. So let me explain this. COMT breaks down dopamine, adrenaline, and estrogen. To do that, it uses methyl groups. If you have a mutation, a slow-acting COMT, or you're female and just really estrogen dominant, that enzyme can be very slow-acting. And when it's slow-acting, you build up these methyl groups. You have more methyl groups than you need. And we call this hypermethylation or overmethylation. And clinically, this presents as anxiety, irritability, insomnia, or that wired but tired feeling, headaches, racing thoughts, a feeling of being overstimulated or unable to settle. Now, many people don't know that they're overmethylating. I see it in men too. Many people are overmethylating and they are told, and I see it in health food stores from people that are really into biohacking are-- they go on like health retreats and are told you have-- that someone looks at their gene report and tells them to take these methylated supplements and they have massive adverse reactions. You know, they can get a worsening of anxiety, irritability. They can get insomnia, headaches, racing thoughts, paranoia, suicidal ideation. So it's not something to play around with. It is something that we need to take quite seriously as the adverse reactions can be quite profound. And as someone who's been doing this for 15 years, most people have poor energy low mood, detoxification issues, hormonal imbalance due to a myriad of different things, not just a methylation imbalance or undermethylating. So it's very oversimplified and it worries me because the supplements that are often prescribed to help someone who inverted commas is undermethylating and they don't even really know can cause massive adverse reactions. Before we go any further, I want to speak directly to the practitioners and students listening. If you're intrigued by histamine and methylation and eager to expand your knowledge in this fascinating area, we offer the Histamine and Methylation Online Group Coaching course. The only program of its kind. It covers everything you need to know about histamine and methylation, providing both the theory and guidance you need to treat these issues effectively in clinical practice. We cover SIBO, hormonal imbalances, oxalates, MTHFR, the four pathways of methylation, including the folate pathway, methionine pathway, tetrahydrobiopterin pathway, and the all-important transsulfuration pathway, and much more. The program is delivered by detailed online webinars and handouts for you to keep, and for eight weeks, you'll meet with me for live coaching calls in a private community space with other practitioners from all over the world dealing with histamine and methylation issues in their patients every day. Together, we learn so much. To learn more and apply, visit joannekennedynaturopathy.com Now, if you're interested in testing a methylation, you can test it at home in real time. This test tells you exactly if you're under or overmethylating and what to do about it. You can access that test via my website, joannekennedynaturopathy.com. You'll see it there. You'll be able to use a discount code. I can't remember what it is to get 10% discount on the test. It's called Mood Sense. So interestingly, when I was talking to the developer of Mood Sense, he was saying that when he's looked at so many gene reports, you can have, say, a mutation on MTHFR, but that's the only mutation on the genes that help make your methyl groups. And there is nothing to slow down the production of methyl groups. And therefore you can have more methyl groups than you like. Also just looking at these genes and enzymes that make methyl groups, it's not considering the genes and enzymes that use methyl groups and that recycle methyl groups. It's just way more complicated than just looking at a gene report or one gene or thinking that you've got some nutrient deficiencies that you're undermethylating. I just wanted to bring this up because the current trend of treating methylation as something to be like optimized, particularly through high dose supplementation based solely on genetic data, misses clinical nuances that actually determine whether these interventions will actually be helpful or harmful. So the goal isn't to force methylation higher, it's often to reduce it. And the goal is also to remove the barriers that are impeding it. Supporting cofactors, supporting, say, the detoxification of estrogen. Getting your methyl groups down, not actually pushing them up. In a lot of cases, we see that people will feel much better when they are reducing their methyl groups, not increasing them. Thank you for joining me. I hope you found this episode beneficial. Be sure to subscribe to The Histamine Well so you don't miss an episode. If this podcast has supported you, one of the most impactful ways to help us reach more people is to leave a review on Apple or Spotify. Take a quick screenshot and email it to us at info@joannekennedy.com.au and as a thank you gift, we will send you a copy of my histamine intolerance e-book. Until next time, take care and be well