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B9 Causes RLS · Common Sense Health

• Stephen Thomas BSc. Hons: Hello. You know that feeling when you take a supplement that's... supposed to help you feel brilliant and everyone has recommended it and instead of feeling brilliant, you're lying awake at 3 a.m. with restless legs wondering if your shins have suddenly developed a mind of their own. Well, this video is going to talk about what I call the methylation or methyl folate paradox. Now, I recently had the pleasure of listening to a fascinating conversation between Michaela Peterson and Dr. Chris Masterjohn, a PhD nutritionist with serious credentials in my And around the 10-15 minute mark, they delved into something that had me reaching for my notepad. It was about the intricate dance between methylation, sulphur metabolism and why some of us react to certain B vitamin supplements like we've been electrocuted. Remember, this is simply me reporting on what I've heard and adding a little bit of my own knowledge. But I reckon it's information worth sharing, particularly for those of us in the low carb, keto or carnivore community. because some of us have had inexplicable reactions to supplements that are supposedly good for us. So first things first, as I always like to do, go to the basics. Not all folate, vitamin B9, is created equal. There are three main forms that you'll encounter. Folic acid. That's the synthetic form found in fortified foods and basic supplements. The body has to convert this through several steps before it can use it. Now, many people are moving away from this form and for a very good reason. It requires multiple enzymatic conversions that some people's genetics just don't support efficiently. Then we come on to methylfolate, 5MTHF. Now, this is the active methylated form that's already been converted and is ready to rock and roll in your methylation pathways. It's often touted as the superior form because it bypasses the need for the MTHFR enzyme, which is a thing that many people have genetic variants. you know, that don't help it. So that sounds brilliant, doesn't it? But hang on a minute. We've also got fulinic acid. Now, this is what Dr. Mastogen called the form of folate that's not related to methylation. It's a different active form that your body can convert into the form it needs without forcing the methylation pathway into an overdrive situation. And here's where it gets interesting, because Michaela mentioned she could only tolerate fulinic acid after trying methylfol. folate and folic acid and she experienced disastrous results. Exactly what we talked about. Insomnia, restless legs and agitation. And it took her eight attempts to find this out. Her father experienced even worse reactions, by the way. Now, let's talk about what's actually happening beneath the bonnet. Now, Chris Mastodon explained something crucial and he said this. If you're eating a high red meat, low carb diet, you're setting up a very specific biochemical environment. red meat is extraordinarily rich in sulfur containing amino acids, primarily methionine and cysteine. Now these are the building blocks your body uses for all sorts of critical processes, including making proteins, antioxidants like glutathione and supporting methylation pathways. But as Shakespeare said, here's the rub. When you're on a very low carb diet, your body still needs to make some carbohydrates and glucose and then process is called gluconeogenesis, making new sugar. And one of the ways it does this sometimes is breaking down sulfur-containing amino acids to create that carbohydrate. So you're already in this baseline situation where you're consuming lots of sulfur amino acids from all that beautiful red meat, and your body is actively breaking them down to make glucose. This breakdown process is intimately connected to, you guessed it, methylation. Methylfolate is directly involved, as the name implies, in the methylation cycle. Specifically, it helps to regenerate methionine from home assisting. So when you add methylfolate supplements on top of the diet already high in sulfur amino acids and already predisposed to breaking them down, Dr. Mastrogin described it as pouring fuel on the fire. that in the video. You've got two reasons your body is ramping up sulfur amino acid breakdown. The first one is the dietary pattern, which is simple high meat, low carb. The extra methylation push from methyl folate supplements is the other one. So when sulfur metabolism gets pushed too hard and the breakdown pathway doesn't proceed smoothly to completion, you could end up with slightly toxic sulfur metabolites accumulating. One particularly nasty compound mentioned is called S- Sulfocysteine which acts as a glutamate receptor activator. Right, what does that actually mean? It stimulates your nervous system and this manifests itself as you can probably guess not sleeping, insomnia, restless leg syndrome, agitation, anxiety and a general feeling of being wired but tired and in some cases you can get some neurotoxicity. Now Dr. Masterjohn stated quite plainly when you get too much broken down sulfur you wind up having chondral toxicity, but you also have independent neurotoxicity going on as well. Now, this is a key insight. The folinic acid doesn't directly participate in the methylation cycle the way that methylfolate does. So while your body can convert folinic acid into the forms it needs, including eventually some methylfolate that is required, it doesn't force feed the methylation pathway. It's like the difference between gently suggesting your metabolism do something versus grabbing it by the shoulders and shouting, hey, you got to do So for someone like Michaela on a carnivore diet with a family history of methylation sensitivities and a background of course of medication use that may have affected mitochondrial function, folic acid provided the folate her body needed without triggering the sulfur metabolism cascade that was provoked by the methylfolate. This is me reporting by the way. So let me get a bit more technical for those that want the full biochem picture. So are we ready? The methylation cycle involves folate as five methyl tetrahydrofolate, donating a methyl group to convert homocysteine back into methionine. Now, methionine then gets converted to a compound called SAMe, which is your body's universal methyl donor for literally hundreds of reactions. And then we get the trans-sulfuration pathway. And this is where excess homocysteine gets shunted. ⁓ you don't need more methionine, gets converted through several steps into cysteine and eventually into either glutathione, your master antioxidant, or taurine, or it gets broken down completely for energy or, as we mentioned earlier, gluconeogenesis. Now, when you're on a high protein, low carb diet, you are already ingesting large amounts of methionine. Your need for glucose production is a little bit higher because there's no dietary carbs coming in and the transulphuration pathway gets a bit taxed, sulfur metabolites can accumulate if the pathway becomes overwhelmed. Now adding methylfolate accelerates the methylation cycle, which means more homocysteine is being shuttled through your system. If your trans-sulfuration pathway is already working over time, or if you have genetic variants affecting the enzymes involved like CBS, you can't process all that sulfur efficiently. So what's the result? Well, you get toxic sulfur intermediaries like sulfite and sulfide and they build up and these are directly neurotoxic and toxic to the mitochondria. Folinic acid by contrast can be converted to tetrahydrofolate THF and then to other folate forms as needed but it doesn't directly push the methylation homocysteine methionine cycle. It's a gentler more versatile form that gets your body to regulate the process. rather than forcing it, as I say, down one particular metabolic motorway. Now, unfortunately, fulenic acid is not abundantly available in a carnivore diet, but quite frankly, it is not in most foods. The richest food sources of fulenic acid are beef liver and other organ meats. Now, beyond liver, other carnivore-friendly sources include kidney, heart, and other organ meats, though in significantly smaller amounts. Eggs contain modest levels of various folate forms and even muscle meat has some trace amounts, though you'd need to eat probably a heroic quantity to get the meaningful folinic acid from just steak alone. Now, that said, there's a compelling argument that the established RDAs for folate and many other nutrients may simply not apply to those eating a carnivore or low-carbohydrogenic diet, because when you're in a state of nutritional ketosis with minimal systemic inflammation, extraordinarily high nutrient bioavailability from animal sources and non plant anti nutrients blocking that absorption, your body's actual requirements may be substantially lower than the population wide recommendations which are designed for people eating inflammatory grain based diets. So it is entirely plausible that the modest amounts of folate, including some fulinic acid found in noctetal carnivore approaches, particularly if you're including in eggs and the occasional serving of organ meats might actually be perfectly adequate when inflammation is low and nutrient utilisation is optimised. Now, this is just another example of why blindly applying standard nutritional guidelines to the carnivore or keto context simply doesn't make physiological sense. Interestingly, Michaela mentioned she initially couldn't tolerate liver well, which Dr Masterjohn suggested might have been a B vitamin issue. because we know liver is extraordinarily dense in B vitamins, including various forms of folate. So for someone with sulfur metabolism sensitivity, even the natural folates in liver, which include both methylfolate and other forms, might have been overwhelming. Now the reality is that whilst organ meats provide some folate, including potentially small amounts of folinic acid, you're unlikely to get therapeutic amounts of folinic acid, specifically from food and alone, especially if you're avoiding liver or can only tolerate it in very small quantities. I particularly like lambs liver, but I wouldn't eat it every day. Now, this is one of those instances where maybe supplementation could be helpful, providing you use the right form, which is what we're talking about, for lytic acid rather than methyl folate or folic acid. And you start with very small doses. You work your way up gradually, which is a very sensible way to approach anything, any supplement, to be honest. So Chris Masterjohn mentioned that many people who a supplement intolerant should get out of the framework of I need to take this supplement and instead focus on gently increasing micronutrients through their food. But he acknowledged that for some people with specific issues, targeted supplementation done carefully can be beneficial. I'm with that wholeheartedly. Always try food first. And he gave the example of someone who had catastrophic reactions to high dose B vitamins, but actually just a tiny bit in their diet. So the lesson, just because 200 milligrams of something makes you feel dreadful doesn't mean you don't need an extra two milligrams. Now, this is crucial. Interpreting blood results in the context of a carnivore or ketogenic way of eating is absolutely essential as well, because the standard reference ranges and conventional medical interpretation often don't account for the metabolic state of nutritional ketosis for a start, which you happen to be in a meat-based diet or in a keto diet. For example, homocysteine levels might be interpreted differently when methylation is being pushed hard by diet. B vitamin levels in the blood don't always reflect intracellular function. ⁓ You could do some genetic testing for methylation SNPs like MTHFR, which we mentioned, or CBS. And that becomes clinically relevant more possibly when you're on a high protein diet. Now, the mitochondrial testing that Dr. Masturgeon's company offers is MITO.me offers this thing and it looks at those pathways and are they actually functioning, not just what your blood levels are. That functional assessment can reveal why someone like Michaela tolerates folinic acid, but not methylfolate. It's not just about deficiency, it's about metabolic flow and where the bottlenecks are. I have no affiliation with that, by the way, I'm just telling you what was in the conversation. And what made the conversation particularly compelling was the connection Dr. Masterjohn drew between early inflammatory disease like Michaela's juvenile arthritis, medication use like biologics and then SSRIs, mitochondrial dysfunction and sulfur metabolism issues and obviously the supplement intolerance that she mentioned and he explained that many medications including SSRIs and benzos as well are mitochondrial drugs ⁓ ways that no one prescribing them actually understands because they affect cellular energy production and when people withdraw from them, especially after years of use, they can develop new onset mitochondrial dysfunction. Again, I'm just reporting what was going on in this conversation. And this creates a situation where the medications may have impaired mitochondrial function. The dietary changes like going carnival helped restore some function but underlined genetic or acquired vulnerability. still remain. And these vulnerabilities are then exposed when trying to supplement with things like methylfolate. So it's it's all joined up. And I like a joined up common sense way of thinking about chronic illness. You know, the way that he was looking at the whole biochemical picture rather than isolated symptoms is exactly how I like to look at things. So what are your practical takeaways? If you're on a carnivore or ketogenic diet and you've had bad reactions to B vitamin supplements, particularly methylfolate, there are some things you could consider. obviously the first one is try folinic acid. You start with a very low dose, perhaps even opening up the capsule and just taking a portion and then work up slowly. And you can look at things like calcium folinate, which is a pharmaceutical name. If you can't get folinic acid over the counter, you could consider your sulfur intake. If you're eating predominantly red meat, you are getting loads of sulfur amino acids. This isn't necessarily bad, but it's a metabolic reality that affects how you respond to methylation support. You could look at the whole picture, basically. So medication history is particularly important. They mentioned SSRIs and benzos as well, or medications that suppress your immune system. Mold exposure was mentioned, chronic stress and inflammatory conditions. They all affect mitochondrial function and by extension, that will mean it will affect methylation and sulfur metabolism. You can think about mitochondrial testing as well. Functional testing that looks at how your mitochondria are actually performing can provide insights that standard blood tests will miss. always go with the fact you don't necessarily need to start on a mega dose. The supplement industry loves high dose formulations, but for some people more can be genuinely harmful. Gentle food based increases or very low dose supplementation might be the answer. We all know why they push high doses obviously. And be patient with all the meats. If you've reacted poorly to liver, it might be a dosing issue. One liver capsule or a tiny amount of pate might be a better starting point than a full serving. And remember context matters. know go on about this all the time. Interpreting bloods or symptoms and supplement responses in the context of your dietary approach is crucial. What's normal for someone on a standard diet may not apply to you. Now the health and wellness space loves to tout optimal solutions. Methylated B vitamins being a prime example. Methylation or methyl folate is the active form. Everyone should take it. But biochemistry doesn't work that way. What's optimal for one person can honestly be toxic for another. And it depends on things like their dietary pattern, genetic variations, medication history, very important, toxic exposures and current metabolic state. Now, the carnivore and keto communities have learned this lesson repeatedly. We're not following the standard playbook. So the standard solutions, they definitely don't always apply. Now, Dr. Chris Masterjohn's explanation of the methylfolate sulfur connection provides a mechanistic understanding of why some of us feel like we've been plugged into the mains when we take what's supposed to be a very helpful supplement. It's not in our heads. It's not just anxiety and it's not mysterious. It's biochemistry that makes perfect sense once you understand the underlying pathways. Hopefully this video has helped you understand that. Now for Michaela, discovering that phylloic acid worked where methylfolate failed was a transformation for her. For others reading this or listening to this, it might be the missing piece of your own health puzzle. And if you're a clinician reading this or listening to this and thinking, ⁓ crikey, I've been recommending methylfolate to all my patients on a high protein diet without considering sulfur metabolism. Well, firstly that's a bad impression, and secondly, perhaps it's time just for a rethink now. Hope you enjoyed that. you excuse me, I'm off to have a word with my supplement cupboard, that bottle of methylfolate, and I need to have a chat about boundaries. I am definitely one that's talked about methylfolate in the past, and I think it was worth having a little reflection on the conversation between Michaela Peterson and Chris Massagen. And you can find it on the Michaela Peterson podcast, episode 231, if you want to listen to it. And for a proper assessment of your individual situation, consider working with a qualified practitioner who understands metabolic As always, interpreting bloods in the context of a carnivore or ketogenic way of eating is crucial. If you want to check out my book, that would be great. By the way, the mitochondrial testing is at MITO.me. think it's simple as that. And Dr. Masterjohn Substack, which I did definitely ⁓ recommend recently. I've been a subscriber for a while. I think that's worth tracking down. I know there's a lot of people that don't think he's great, but I particularly do like the way he thinks and the way he's... stands his ground. that's the end of that waffling on. Now, if you got to the end of this and you liked it very much and thought it was informative, that's great. So please consider liking, sharing and subscribing. If you're still here and you did not like a word of what I said or the way I said it, well, thank you very much for sticking with it and you're a sucker for punishment. Maybe, just maybe, I will do better on the next one. So do check in again because it might be a video that you enjoy the next time. Thank you very much for listening. listening.