Histamine Well Podcast: Exploring Histamine, Methylation & Holistic Health

MTHFR, Methylation, Folic Acid & Folate Testing - A Clinical Perspective

• Joanne Kennedy • Episode 7

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In this episode of The Histamine Well Podcast, Joanne dives deep into the topic of MTHFR, an enzyme crucial for the process of methylation. Joanne explains the significance of methylation in various biochemical and genetic processes such as detoxification, neurotransmitter regulation, and genetic expression. The episode also addresses why methylfolate is essential, discusses common causes of methylfolate deficiency, and highlights why folic acid can be problematic for everyone.

Joanne provides insights into various types of folate testing and offers practical guidance for those with MTHFR mutations and other related conditions. This comprehensive episode is designed to provide actionable knowledge for both practitioners and individuals on their wellness journey.

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Welcome back to the show. Today's episode is all about M-T-H-F-R. And why does this enzyme get a lot of attention. So what's it all about? Why do you need to know about MTHFR. So that's what we are going to cover today. We are gonna be looking at what M-T-H-F-R is and why it's important. It's important because it's essential for methylation. So what is methylation? We'll cover the important roles of methylation. The other reasons you can have a methylfolate deficiency. So it's not just all about M-T-H-F-R. I'll explain why folic acid is a problem for everyone not just people with M-T-H-F-R. Will go over folate testing and the different types of folate testing and what they mean and what to do if you have an M-T-H-F-R gene mutation. 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 are 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. The main reason you need to know about M-T-H-F-R is that it's involved in the process of making SAM e. S Adenysol Methionine, which is the body's major methyl donor. M-T-H-F-R converts folate from food into methylfolate, which is used to make SAM e. And it's the only enzyme that can create methylfolate. And since it's the only enzyme that can do that, issues with the M-T-H-F-R enzyme due to genetic mutations cause like a choke point for getting the methylfolate needed into this methionine pathway to make SAMe. And many people do have mutations on M-T-H-F-R whereby they have a reduction in its function, which can lead to methylfolate deficiency. So methylfolate is one of the methyl donor nutrients required to make SAM e. It's a very important one. And because of genetic mutations and certain environmental impacts on the way the body will absorb folate and convert it through enzymes, different enzymes, and then the M-T-H-F-R enzyme as well. All of these environmental and genetic issues can cause methylfolate deficiency. So we are also gonna be chatting about that. So this episode is also important for people that don't have M-T-H-F-R because it's other environmental things that can also deplete or cause you to have methyl folate deficiency. Why is SAM E so important? Why is methylation so important? So Sam E, as I said, is the body's major methyl donor. And it's involved in a process called methylation. So methylation is a really fundamental biochemical process in the body. Whereby a methyl group, which is simply.. If you get a piece of paper out and write a C in the middle, and then do north, south, east, west, just with lines and put a H on three of those lines. And then you have a spare arm. And so that spare arm goes around the body and it will attach itself to different substrates. Including DNA, RNA, proteins, neurotransmitters, hormones, immune cells, and nerve cells. When this occurs, the chemical compound has been methylated. So essentially allowing that compound to do its job. And importantly, methylation is involved in turning on the process and switching it off. So it's like an on off switch. So it's always the balance. We need things to work, but we don't need them to overwork. So it's all about maintaining homeostasis. So what does methylation do from a biochemical or metabolic point of view? It does many things, but these are some of the big jobs. It's involved in detoxification. So it's involved in a pathway in the liver, which is called the phase II methylation detoxification pathway. And it neutralizes and eliminates environmental toxins and medications. It also detoxifies your estrogen, so when methylation is not optimal, you can get toxin buildup. Symptoms can often be fatigue and brain fog, headaches. You also get estrogen do causing heavy periods, breast tenderness, PMS mood changes. Methylation is important for the production and balance of neurotransmitters. This is key. It's the balancing of the neurotransmitters. So neurotransmitters such as serotonin, dopamine, norepinephrine, melatonin. We need to be making these neurotransmitters, but we also need to break them down. If you have too much dopamine, you can feel really agitated and irritated. If you have too much norepinephrine, you can also get feelings of anxiety. If you have too much serotonin, you can have what's called serotonin syndrome, which is a worsening of depression. So it's the balance and methylation is important for the balance of neurotransmitters, so it's extremely important for mood. One of its big roles is energy production. Methylation supports the synthesis of creatine. And creatine is a molecule critical for muscle energy storage in ATP regeneration. And it uses a significant portion of your methyl groups to make this. So when methylation is impaired, it symptoms like muscle weakness, brain fog, and chronic fatigue. Another super important role of methylation is that it's vital for producing phosphocholine. And phosphocholine is a really important component of cell membranes. so we need healthy cell membranes. This allows proper cellular signaling. Nutrient transport. It also protects the cell from environmental stresses. We can have massive issues with damaged cells and damaged mitochondria if we don't have healthy cell membranes. Methylation is really important for modulating inflammatory pathways and immune responses. It regulates cytokine production. These are your cytokines are released as part of the body's normal response to inflammation and infection. So we need to mount a healthy immune response and have these cytokines released. But we also need to turn it off. Remember methylation on off switch. So poor methylation may lead to chronic inflammation, increased susceptibility to infections or autoimmune conditions. It supports the production of glutathione, which is the body's major antioxidant. Glutathione protects cells, some oxidative damage. Glutathione is used in every single different liver detoxification pathway. There are several, not just methylation. There are other pathways like sulfation. Glucuronidation. Glutathione's used in all of those liver detoxification pathways. So they're just some of the metabolic, biochemical roles of methylation. I also need to chat about what it does from a gene perspective. Because there's, there's a lot of research in this and it's extremely important for genetic expression. So methylation is a master regulator of genetic activity. It determines which genes are expressed and which remain silent. So it ensures proper development. Maintains genetic stability and allows cells to adapt to environmental cues. So some examples of this is that methylation can silence genes that aren't needed. Such as genes for childhood development being turned off in adulthood. It's involved in epigenetic inheritance, which is the passing on of traits or health risks without changing the DNA code itself. So an example of this is a parent's poor diet or exposure to toxins can affect their child's methylation patterns overall influencing their health. It's involved in the imprinting of genes. So this ensures that only one parent's version of a specific gene is active. So for example, the insulin-like two growth factor gene, which is important for growth, is methylation makes sure that it's only active from the father's site or the mother's copy is silenced. It's involved in X chromosome inactivation. So this ensures females don't have double the gene activity from the two x chromosomes. An example is that one X chromosome in females is switched off through methylation to prevent gene overload. It's involved in genetic stability. So it protects the DNA and helps keep it stable during cell division. Methylation silences repetitive DNA sequences that could cause damage or errors in your genetic material. It also plays a role in development and differentiation. So this helps cells specialize into specific types like skin or muscle cells by turning on only the needed genes. An example of this is during pregnancy, methylation ensures that stem cells develop into heart cells, brain cells, and so on. So you can clearly see that it is super important for our overall health and wellbeing. Obviously if you have a mutation, M-T-H-F-R, you are going to be interested in supporting this enzyme. But what if you don't have a mutation on M-T-H-F-R? Good question. First of all, I just need to say that when I was talking about all of these different roles of methylation from a biochemical, metabolic, and genetic perspective. It's not just methylfolate that's required for that in M-T-H-F-R. There are many, many different genes and enzymes that are involved in methylation. But M-T-H-F-R is an important one, and because it is that only enzyme that converts folate into the methylfolate, then having a mutation on it is problematic. However, you can still have methylfolate deficiency without having an MTHFR gene mutation. And this is due to many things. So folate refers to the folate, which is found in foods. And I know people use the term folate to mean all different types but we need to classify that it is what we mean which is from food. And it's predominantly found in green leafy vegetables and legumes. If you do not eat enough green leafy vegetables and legumes, you are very likely not getting enough methylfolate. Because if you don't have the foods that are going to make the methylfolate, it doesn't matter about a gene mutation or not, you can definitely have low methylfolate levels. Now, folate is absorbed via brush border enzymes in the small intestine. Sibo, small intestinal bacterial overgrowth can reduce the production of brush border enzymes. Therefore, reducing the absorption of folate. Celiac disease will do this as well. Now, excessive alcohol consumption will deplete folate levels. And the oral contraceptive pill can also reduce folate levels. If you're not eating folate or absorbing folate, then you can have methylfolate deficiency without an M-T-H-F-R gene mutation. So I can hear you all say, what about folic acid? Folic acid is a synthetic form of folate fortified in wheat in Australia, the US and other countries. Now while folic acid can be metabolized by people, it requires three steps to get it into methylfolate. Once folate from food is absorbed into the intestinal cells, folate is reduced to dihydro folate via an enzyme called the DHFR enzyme. Now that same DHFR enzyme then needs to convert dihydro folate into tetra hydro folate, which is the form that enters the bloodstream. So there's two steps. Dihydro folate. So folate gets converted into dihydro folate. One step dihydro folate into tetra hydro folate. Another step. Now what we need to know about this DHFR enzyme is that it has a higher affinity for folic acid than it does from folate in food. So essentially, folic acid can block the conversion of folate into dihydro folate and tetra hydro folate. Which will lead to a reduction in overall tetra hydro folate, which is the form that enters the bloodstream. Which can be used to make the different types of folate the body needs including methylfolate. And furthermore, the DHFR enzyme is very slow acting. Meaning folic acid can build up in the circulation. And then we've got M-T-H-F-R, which is the final step in this process of converting folic acid into methylfolate. So if you have a SNP on M-T-H-F-R, this is going to compound the problem. Folic acid is just not helpful for anybody. And quite frankly, the foods that it in are in are very inflammatory. Weight is very inflammatory. And the processed foods that it's in. Check your supplements if you're taking folic acid. It could be causing a reduction in your ability or it's hindering your ability to make methylfolate. So how do we know what type of folate we have? Well, unfortunately we can't just rely on the blood test done from the doctor. We have to be looking at using functional medicine lab testing to do that. And I know in naturopath in Australia break down all the different types of folate in their testing, which is really helpful. And I'm yet to find somewhere overseas, but I'm sure there must be a lab in the US that are going to test the different types of folate. So let me explain. Serum folate, which you can get done from the doctor or just order it from labs in the US. You can definitely do that. It measures the amount of folate circulating in the bloodstream at the time of the test. Now the result is the whole pool of all the different folates. Folate from food. Folic acid. Five formal tetra hydro folate. That's folinic acid and methyl folate. So you don't actually know what type you have. Then there's red cell folate. It measures folate stored inside red cells. This includes folate, folic acid, Pi for a tetrahydro folate. It's folinic and methylfolate. So you don't actually know how much methylfolate you have because it's just lumped in there with all the different folates. Now Nutripath offer testing where you can see blood plasma tetrahydrofolate. So it can come from food, it can come from folic acid. We know that. But it also tests blood plasma, folinic acid and it tests blood plasma, methyl tetrahydrofolate methyl folate. So you can see. And when I've done these tests often because someone has M-T-H-F-R, or I suspect they do, or they have high homocysteine, what you so often see is that the levels of blood plasma tetrahydrofolate. Are normal or high is good. But their methylfolate is low. So this is such a classic sign of an M-T-H-F-R gene mutation whereby they have enough tetra hydro folate form, but it's not converting into methylfolate. So Nutripath offer this testing. Well, I have emailed some of the labs in the us. They haven't got back to me. Unfortunately, I emailed them months ago. Genova Diagnostics is somewhere you could try. They do methylation panel testing. I'm certain that when I was looking at last time, they didn't have all these folate testing as part of it. But potentially if you're interested, you can contact them and see if they do run a test like that. Before we go any further, I want to speak directly to the practitioners and students listening. If you are intrigued by histamine intolerance and eager to expand your knowledge, particularly around methylation and how to apply this understanding. In clinical practice, 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. To learn more and apply, visit joannekennedynaturopathy.com so what can you do to support your M-T-H-F-R? Now everyone needs to avoid folic acid. So I really hope I've explained why that is. It doesn't matter if you're M-T-H-F-R or not, it will likely to cause methylfolate deficiency, and you are not doing yourself any service when it comes to supporting your methylation. Obviously, you need to make sure you're consuming a diet that has lots of folate. So folate rich foods, leafy greens, asparagus, broccoli, legumes. It's lentils, chickpeas, and beans. Avocados also high in folate. And you need to make sure you work on your gut. And I can hear so many of you tearing your hair out because you're like, Joe, my gut's bad. I can't even eat any of these foods. And I understand this is a problem. I totally understand this. So if you are not tolerating legumes, that is a massive red flag for sibo. And then if you don't tolerate spinach, that is also a red flag for sibo.'cause it can drop up a histamine. Spinach is high in histamine. If you're not tolerating spinach, it can also be due to it being very high in oxalate. And then if you don't tolerate asparagus or broccoli, they're very high in sulfur. I've done a episode on multiple food intolerances, so you might wanna listen to that and sort of get an understanding of where you should start to unravel this issue. So if that is the case for you, I would be doing this. Okay. Now you don't just go and supplement with methylfolate. And in fact, people that had these multiple food intolerances and chronic gut issues are gonna usually very reactive. Or they're reactive to all supplements. So what we can actually do? You can first of all do the Nutripath test whereby we can look at what your methylfolate levels actually are so we can get an understanding. You can also do a methylation test. So what you can do at home now is you can do the Somaticode mood sense methylation test from home. It's a saliva test and it tells you what is going on with your methylation in real time. Just because you got an M-T-H-F-R gene mutation does not mean that you are an under methylator. It might, but you can very often be over methylating. So you need to be aware that there are so many genes involved in making methyl donors and using methyl donors and recycling methyl donors. So you might have issues with these genes causing you to over methylate. And you don't wanna be taking more methyl because it's gonna make you feel worse. So that test, the mood sense methylation test is available for sale on my website. And I do have a discount code. A 10% discount for listeners, which is HISTAMINEWELL10 so you can get 10% off that test. I use it all the time in my patients. I think it's wonderful. If you are someone that is highly reactive, you've had adverse reactions to methylfolate, but you are homozygous MTHFR, or any M-T-H-F-R and you're concerned about this, then we can go ahead and look at your methylation what's actually happening. Because just taking methylfolate because of a gene mutation is just not gonna fix your health issues, and that's what we wanna do, right? We wanna get to the cause and we wanna get you feeling better. And this is particularly important for menstruating women, as can often push you into over methylation, even with an M-T-H-F-R gene mutation. Now, I've done an episode with Dr. James Bradshaw. He's a scientist in the US and we speak about methylation and over and under methylation. But just as a red flag. Women can often be over methylating. So if you've taken methylfolate and you feel terrible, potentially you are over methylating. The other thing, when you take methylfolate, it pushes methylation, so it will break down histamine, right? That's another thing that methylation does. Breaks down histamine. So it can come out as an adverse reaction, which is a histamine symptom. You might've seen it causes skin issues or makes your skin issues worse. That's a classic sign of just like the breaking down of the histamine. So I know it's overwhelming if you've got M-T-H-F-R and what I've just said regarding what should I do? So I'll just go over this again. If you can eat a whole different range of foods. If your gut is great, fantastic. Just get the green leafies up. Asparagus, broccoli, avocado, and legumes in your diet. Avoid folic acid. This is gonna be very, very helpful for you in supporting your M-T-H-F-R. If you've got gut issues, particularly SIBO or oxalate problems, you need to really work on that and try and get the absorption of these foods up. If you've taken methylfolate already and you feel great on it, fantastic. I'm not here to say don't take it. I'm just here to let people know that it can cause adverse reactions. And if that has happened to you, you don't need to push through because it is not gonna change. If you're having an adverse reaction to it, you're having an adverse reaction to it is a problem. And it can be because you've got too much histamine. Also you could be B12 deficient, so you need vitamin B12 to use methylfolate. So it could be B12 deficiency, or you could actually have other genetic snips in these pathways, which are causing you to build up your methyl groups too much. And then taking more methylfolate is not gonna be helpful for that. 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. Leave a review and you can also share this episode with someone who could benefit. If you have any questions you'd like answered. Or have a topic you'd like me to discuss, please go to my website, joanne kennedy naturopathy.com, where you can provide us with that information. Until next time, take care and be well.