Histamine Well Podcast: Exploring Histamine, Methylation & Holistic Health

Health Implications of Low Homocysteine – A Clinical Perspective

• Joanne Kennedy • Episode 9

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In this episode of the Histamine Well Podcast, host Joanne delves into the often-overlooked topic of low homocysteine levels. 

Joanne explains that while high homocysteine is commonly flagged for its cardiovascular risks, low homocysteine is seldom discussed despite its significant implications for health. 

She explores how low homocysteine can indicate sulfur depletion, often linked to issues such as oxalate toxicity and mold illness. 

The episode covers the methylation process, the importance of methionine, and the roles of cysteine, glutathione, and taurine. 

Joanne also discusses the impact of stress, diet, and poor absorption on homocysteine levels and underscores the connection between oxalates and sulfur depletion. 

Whether you are a practitioner or navigating your personal wellness journey, this episode provides actionable insights into understanding and addressing low homocysteine to improve overall health.

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Joanne Kennedy:

Hi, it's Joanne. If there's one test that's worth its wedding gold, it's homocysteine. But not for the reasons most people think. High levels don't automatically mean you are an under methylator because methylation is far more complex than that. It's a dance between genes and the environment and oversimplifying it does us no favors. What's often overlooked is just how revealing low homocysteine can be. It gives us a powerful entry point into the root causes behind many chronic symptoms, and it's frequently linked to things like oxalate toxicity and mold illness. If that's you, this is an episode you'll want to stick around for, and if you're a practitioner or student, this is an episode you do not want to miss. We're unpacking homocysteine through a clinical lens. Not just as a lab marker, but as a guide to systems thinking. Because understanding what low home cysteine is really telling you can completely shift how you approach your treatment plans and uncover patterns that other practitioners might miss. 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. Hi everyone. Welcome back to the show. Today we are diving into a really important and often overlooked topic, which is low homocysteine. Most doctors only flag homocysteine when it's high, given it's linked to cardiovascular risk. But low homocysteine, anything under six micromoles per liter is not a good thing. In fact, it can be a major red flag for sulfur depletion in the body, which can have really wide reaching implications for your health. In this episode, we're going to explore why low homocysteine matters, what it might be telling us about your health and the common root causes of your health issues. Many of which can lead to chronic symptoms. It's not that low homocysteine itself is making you feel unwell. It's the causes of why you have low homocysteine is what I like to say.'cause often when we're dealing with this in patients that the homocysteine levels might not immediately rise on the blood tests, but they are starting to feel a lot better. So what exactly is homocysteine? Homocysteine is a sulfur containing amino acid that your body produces as part of a larger process, which is actually the methylation process. So it's not something that you can directly get from food like some other amino acids. It's actually made from methionine. Methionine is an essential amino acid. When an amino acid is essential, it means you need to get it from the diet. And methionine is the only essential sulfur based amino acid. And that's key because sulfur is involved in so many critical processes in the body. When you eat methionine rich foods, mainly animal proteins like beef, lamb, chicken, fish, eggs, and cheese, your body uses ATP, your energy molecule to convert methionine into SAM e. S Adenysol methionine. SAM e is the body's major methyl donor. It moves around the body donating methyl groups to support detoxification, neurotransmitter balance, histamine breakdown energy to production, cell membrane formation, and much more. Once SAM e has done this job, it becomes s adenysol homocysteine. SAH. SAH, which is then converted into homocysteine. So if you're not getting enough methionine the diet or not absorbing it properly, you can end up with low homocysteine levels, and that's when we start to see signs of sulfur depletion. If someone presents to you in clinic. Or if you are a a person listening and not a practitioner, you're someone with these health issues and your homocysteine level is under six. Especially if you're dealing with chronic symptoms like histamine symptoms. I'll go through the symptoms of high oxalate, which is a big cause of low homocysteine. Then it's essential to explore these underlying reasons. So before I jump into more complex explanations like oxalates and mold, it's really important to consider the basics, which is diet and digestion. So in clinical practice, I often see patients who simply aren't eating enough methionine rich foods, or they're not digesting them properly. To absorb methionine, you need good stomach acids. That's hydrochloric acid. Hydrochloric acid in the stomach, unravels protein structures, allowing the enzyme pepsin to start breaking them down into smaller peptides. And then these peptides move into the small intestine where pancreatic enzymes break them down further into individual amino acids, including methionine, which is then absorbed into the bloodstream. And so if you're low in hydrochloric acid and you're not able to break down the protein efficiently, then you have a potential to have low methionine. So what causes low stomach acid? Well, stress is one of the biggest culprits. I see it all the time. So many of my patients are highly stressed, often due to chronic illness, health, anxiety. And they're stuck in a state of sympathetic nervous system overdrive. They're not in rest and digest. They're in fight or flight. And this alone can significantly reduce hydrochloric acid production. There are other factors that can cause low stomach acid including aging, zinc deficiency, helicobacter pylori, infections, gastritis, the use of proton pump inhibitors like nexium or pariate. Histamine II blockers like Zantac, and medications like metformin. And these are all really common. The other thing we really need to think about when it comes to diet and absorption of methionine. And actually an oxalate issue is being vegan. So this is where it gets a bit more complex. So you are often not consuming enough methionine to begin with, and you are relying heavily on plant foods, which can be very high in oxalate. Plant-based diets can also reduce stomach acid. So even if someone is technically consuming enough methionine, they might not be absorbing it. And on top of that, the volume of plant foods they're eating might push them towards an oxalate issue, which can further interfere with salt and metabolism, and I'll be talking all about that in this episode. So that said, if someone has a relatively balanced diet but just doesn't eat much red meat under a lot of stress, you might see low B12 in their blood test as well. And they don't show signs or test results pointing to high oxalate or a mold problem. Then low homocysteine might simply be a reflection of poor dietary intake and digestive function. So just to summarize, homocysteine can be low due to methionine deficiency, and then homocysteine can be low due to oxalates and mold, which is way more complicated and I'm gonna talk about all of that in this episode. But you don't wanna jump the gun with a patient and take them down a mold oxalate pathway of treatment and testing when it's simply a dietary and absorption issue. 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, M-T-H-F-R, the four pathways of methylation, including the folate pathway, methionine pathway, tetrahydro biopterin 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 joanne kennedy naturopathy.com. To explain the other main reasons why someone might have low homocysteine levels, we need to talk about the transsulfuration pathway. So there's that word again, the sulfur word. Transsulfuration. This pathway is also called the cystathionine beta-synthase pathway or the CBS pathway. And this is where that CBS enzyme comes into play. A lot of people have heard about CBS, they've done genetic reports where they can see their CBS gene, which codes for the CBS enzyme. But from what I understand that enzyme is, is mainly impacted by the environment, which is what I'm gonna talk about now. So this CBS enzyme, it kicks off this transsulfuration pathway. And this pathway is responsible for taking homocysteine, which is a sulfur containing amino acid. And it converts it into cysteine, which is another sulfur amino acid. So we need to actually zoom out for a second and go back and think, how do I make homocysteine? Oh, I need methionine. Methionine creates, Sam e goes around the body, donates methyl groups, then get converted into SAH, then back into homocysteine, right? So that whole pathway starts with methionine. We've now got homocysteine and homocysteine will then be chopped up to provide the body with cysteine. So cysteine is a really incredibly important. Amino acid. It plays many roles in the body, and one of the biggest roles is the production of glutathione. Your body's master antioxidant. Glutathione helps neutralize free radicals and reactive oxygen species. It's doing this in every cell of your body consistently. It protects your cells from oxidative stress. It also supports liver detoxification pathways, including methylation and sulfation. Cysteine is also used to make taurine. So taurine's another sulfur based amino acid. And taurine acts as an inhibitory neuro transmitter in the brain, so it helps calm down overactive neurons. It also binds with bile acids in the liver to form bile salts, which are really important for fat digestion and absorption. It's got many other roles, taurine. But they're some of the important ones. So we need to think, how does the body get taurine? It needs to be made from cysteine and cystine needs to come from methionine, and we need to eat it. Okay, so we can see that this whole process is all linked and it's all shows you how important sulfur is. Now, another big job of cysteine is that it gets converted into sulfate. And sulfate is used in the sulfation pathway being a major liver detoxification pathway. Detoxifies hormones like estrogen, testosterone. Detoxifies neurotransmitters like dopamine, serotonin, adrenaline. It helps the body clear environmental toxins like plastics, pesticides, herbicides, including glyphosate. Medications including codeine and morphine, aspirin, Panadol and Tylenol. It also helps the body clear salicylates. So that's in the liver. And sulfation also plays a really important role in the gut. It helps produce glyco amino glycan, so we'll just call them gags. And gags are a key part of the mucus layer that lines the gastrointestinal tract. And the mucus layer is like a protective barrier. It traps and expels unwanted pathogens. It provides lubrication to keep food moving smoothly. Gags also support the body, the gut epithelium holding onto water. So it helps keep the gut hydrated. And interestingly, gags also interact with the gut microbiome. So they influence which microbes thrive and how they behave. So this is all sulfur. It's crucial for the body. It's actually the second most abundant element in the human body, and it's involved in countless processes way more than what we've even touched on here. When the body starts to run low on sulfur, it has to find it somewhere. And one place it's going to draw it from is from homocysteine.'cause remember, homocysteine is a storage molecule for sulfur. So if you see low homocysteine in a test, it could mean that the body is dipping into the reserves. It's a sign that sulfur stores are being depleted. So we understand the dietary component of this. We now need to understand that it can be due to a depletion, not necessarily a lack of intake and absorption. And one of the main reasons for sulfur depletion is oxalates. So high oxalate levels in the body can dump sulfur in the urine. So this all gets really sciencey. But I'm gonna say, I'm gonna talk about it'cause it's really important to understand. You've obviously got the transcript where you can read it, so I'm just gonna read it for you. Oxalate and sulfate actually share the same transport pathway. It's called sulfate and iron transporter, or SAT one. And this transporter is found in key organs including the liver, the kidneys, and the colon. And the thing is this transporter works in both directions. So for every sulfate. Iron moving in one direction, an oxalate ion can move in the other direction. So it's like a molecular seesaw. That means if there's a high concentration of oxalate on one side of the membrane, it can start to pull sulfate out from the other side. In the kidneys, this can lead to excessive dumping of sulfate into the urine. Which is one way sulfur gets deplete. Meanwhile, the body retains the oxalate. A similar thing can happen in the colon, and instead of absorbing the sulfate it needs, the body ends up taking in oxalate instead. And to make things worse, high levels of oxalate can also block the uptake of sulfate into cells. So we are not only losing sulfur through the kidneys, we're also not absorbing enough of it at a cellular level. So I often explain this to my patients by saying oxalates and sulfate share the same carrier. And oxalates are hogging up all the seats on the bus. There's no room left for sulfur to get in, so it gets kicked out and we lose it. Now, here's where it actually gets really interesting, even more interesting, is the body is so incredibly adaptive and when sulfur levels drop too low, the other place it can get it from is the gut microbiome. So the gut microbiome can start upregulating sulfur producing bacteria to compensate. And these bacteria, when they're too high, are gonna cause too much sulfur in the gut. And this is where you can start reacting to sulfur rich foods, which is such a problem because you know, methionine is high in sulfur and you need it. You can't have it. The brassicas, cruciferous vegetables are also really high in sulfur. So when you are reacting to sulfur foods, then it's... in my mind, yes, it can be just a simple overgrowth of sulfur bacteria. It can be hydrogen sulfide, sibo. But I'm always thinking, oh, why is the gut upregulating this sulfur bacteria, is there an oxalate problem? The other thing we really need to understand about oxalates is that they're highly inflammatory. So when there's inflammation, oxidative stress occurs. The more oxidative stress, more inflammation, more oxidative stress like it's a really vicious cycle. And what's important for getting that under control is glutathione. And glutathione is a sulfur molecule. So when the body is high in oxalate and it's depleting all that sulfur, then it's causing a reduction in the sulfur available to make glutathione. And this is where you can really start seeing people with homocysteine levels like two, like really, really low. So let's talk about symptoms. Because I know a lot of you're thinking, well, I've got low homocysteine. How do I know if I've got an oxalate problem? Well, you can test, you can do a organic acids test to have a look at that. They usually show up high. Sometimes they simply don't. So you potentially have urinated out the oxalate before it gets caught in that test. But usually we see it high. But this list of symptoms is very telling for having an oxalate issue. So I'm gonna start with the urinary tract,'cause this is where oxalates can really cause havoc. You might see things like frequent urination, urgency, kidney pain, lower back pain. People can report like a burning redness or discomfort in the pelvic or genital area. There can be bladder pain, interstitial cystitis, inflamed prostate, vulvodynia. You can also notice cloudy or foul smelling urine, blood in the urine, recurrent urine tract infections. And kidney stones are actually caused from oxalate. They're not something that I see clinically a lot'cause they're usually picked up from allopathy, but they are often caused from high oxalate. The gut symptoms. They can kind of mimic SIBO or IBS, such as bloating, diarrhea, constipation, reflux. The classic sign of high oxalate is pain, sharp pain. They can also cause rectal burning. People can describe like a gritty consistency to stools like sand or black and white flex in their stool. Musculoskeletal. You can often get joint pain, creaky joints, tight or sore muscles, gout, weakness, tremors, and poor coordination. Some people also report burning feet. They all can be slow healing injuries. Over time, oxalates can actually contribute to osteoporosis on the skin. They'll cause rashes, hives, worsening of eczema, psoriasis, flares, acne, bumpy or crystal like lesions that can literally push sharp oxalate crystals through the skin. I know that sounds wild, but it does happen. Dry skin is also common. There are also these sort of random symptoms. Raised lymph nodes, flu-like symptoms and even hiccups is actually a symptom or can be a symptom of high oxalate. And oxalates are gonna drive up histamine. So you can get like the headaches and the migraines, the anxiety, the heart palpitations. I mean, I've mentioned all the skin and gut issues. It's gonna wreak havoc with your hormones. So you can get a worsening of your histamine symptoms at ovulation or before menstruation, simply'cause of this oxalate issue driving up all the histamine. Now, if you've had mold illness and you're not feeling better. You've had mold treatment. You're out of the mold. Then looking at oxalates is really, really important because there are some mold species. Aspergillus and penicillin are known to produce oxalates. So anyone that is going through a mold treatment now, if you know you're in mold and you haven't done an organic acid test, you really need to do that. Because it's gonna show up if you have an oxalate problem, and they often go hand in hand. It's very, very common and often people are sicker from the oxalate issue more than the mold. Now another big giveaway that you might have an oxalate issue is that you are going to react to very high oxalate foods such as nuts, nut butters, turmeric, spinach, sweet potato, beetroot, buckwheat, quinoa, carrots, celery. These are all very high oxalates. So we often see people. They will remove grains from their diet and have almond meal and almond flour with everything. They remove dairy from their diet, and they're gonna have almond milk instead. They're putting turmeric on everything because they've heard it's anti-inflammatory. They juice spinach. They swap out the the wheat to buckwheat and quinoa. They juice the carrots, they juice the celery, they juice, the beetroot. And we end up with a huge amount of oxalate coming into our gut. And we simply can't break it down. So sometimes it's a dietary problem. Now if you think that's you, I urge you do not just stop eating very high oxalate foods because that will initiate oxalate dumping, which will cause you a lot of pain and misery. Really don't do that. You need to do it slowly. I really recommend you do that with a practitioner because it can cause, gosh, it can just, it can cause. You to want to go to the emergency at the hospital and they're not gonna know what you're talking about. I really urge you not to do that. If you wanna look at all the foods that contain oxalate, there's a website called lowoxalate.Info. You can look at the list. It's usually the very high oxalate foods that are the problem, and the one that you do need to remove very slowly. If you're gonna do it yourself, only five to 10% per week. So just to recap. Low homocysteine can be due to low methionine intake and poor absorption. And it can often, very often because from oxalates and mold. Now for sure, anything else that's causing a lot of inflammation and oxidative stress in the body and really requiring a lot of glutathione has a potential to also cause low homocysteine. Things like heavy metals, I'd say. Any sort of chronic inflammatory disorder that's really causing havoc in your body has the potential. But I just see it all the time. I mean, it's always oxalate. When Mel and I see this all the time, it's just like, it's a diet or it's just an oxalate problem. And combined with a mold problem. Now there is one more thing that can cause low homocysteine, and that's from taking a homocysteine lowering supplement. Either for way too long or you never had low homocysteine in the first place. Now I know people get excited when they first find out about MTHFR gene, and I do see a lot of practitioners just putting their patients on a homocysteine lowering supplement with methyl without actually testing the homocysteine levels. For sure people are doing that themselves. People in health food shops, they might not understand. They're often putting people on a B complex with methyls that's specifically designed to lower homocysteine. So check the bottle. It will often say for cardiovascular risk or to lower homocysteine. If you're not sure, call the supplement company or email them and ask. So the take home message for everyone is that Low homocysteine gives us a lot of valuable information. It's something that I look at straight away. When I get a blood test done, a panel of blood tests come in. From my patients and there's a homocysteine test I look straight at that if it's low. That's where I'll start directing questions. Like I will straight away want to know about mold exposure and oxalate symptoms. Because this is so fundamentally important. Because people goes missed so often. These are the patients that come to me who are up late at night Googling. They find me all over the world. Palestine, Libya, the Philippines. They find me in Northern Europe. They find me in Bulgaria, Poland. Everywhere guys up everywhere, right? These people find me'cause they've got low homocysteine and they're a bucket of histamine and mold and they've had these issues for so long and no one is putting the pieces together. So you really need to look at these, this test in your patients if you're a practitioner, because if they're full of histamine. You can't just think, oh, this is a SIBO case. Or I'm gonna put them on a low histamine diet. You definitely need to be working with a homocysteine test at least so that you can get an understanding of actually where to start with these patients. Just remember, we are here to help, whether it's histamine, oxalates. If you do have low homocysteine, if you're interested in working with us regarding your methylation or your biochemistry, your hormones, you can absolutely book an appointment with us. We see patients globally via Zoom. Or if you're working with another practitioner and you have low homocysteine and it hasn't been addressed, I encourage you to bring this up with them. Ask them to do an organic acid test to look for oxalates. Because if oxalates are an issue and they're not being addressed, it can keep your system in a chronically inflamed state. And I see this all the time. So don't let that be you. Get the test done. If you've already done it, find someone who knows how to interpret it and guide you through the process of supporting your body gently and safely out of the oxalate burden.'cause it can really make all the difference. 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.