This past Saturday, we all showed up live on Facebook so you could ask me anything about methylation. Here’s the video, and the audio recording as a podcast.
Don’t forget this Wednesday (at the time this post is published, that’s tomorrow!) at 5:00 PM eastern time you can show up live again to ask me anything about vitamins A, D, and K! Here is the full schedule of upcoming Facebook Live events.
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Show Notes for Episode 17
In this episode you can find the following:
- 0:00 Intro, announcements about ChrisMasterjohnPhD.Com and my experience so far with US Wellness Meats liverwurst.
- 9:05 Figuring out apparently choline-induced headaches
- 12:20 An MTHFR mutation (e.g. C677T) could, even with normal homocysteine, be taxing your choline supply and causing you to waste away glycine into your urine. Boosting choline and glycine supply, and, perhaps most surprisingly, even supplementing with creatine, could help.
- 30:03 Using SAMe supplementation to diagnose methylation issues.
- 34:12 Choline and fatty liver disease
- 36:28 Why serum B12 shouldn’t be used as the primary marker of B12 status and how to get MTHFR genetics tested
- 39:03 COMT mutations regulating (via dopamine) the balance between mental stability and mental flexibility, whether 5-methyl-folate supplementation could hurt mental health in those with low MTHFR activity but high COMT activity. Potential relation to obsessive compulsive disorder (OCD).
- 55:36 How to get choline if you’re allergic to eggs?
- 57:33 Strange ammonia scent in the urine
- 1:01:29 If someone eats a diet low in muscle meat, is it still important to eat collagen-rich animal foods?
- 1:06:38 My serum B12 is off the charts and I’m not even taking a supplement. What gives?!
- 1:09:32 MTHFR mutation, no gall bladder, and high liver enzymes on a high-fat diet: choline support seems in order, but rethinking the high-fat diet in this particular case is also wise.
- 1:11:48 My thoughts on fasting for general health
- 1:14:00 Post-traumatic stress disorder (PTSD)
- 1:15:41 Thyroid autoimmunity
- 1:20:24 Nutritional support for nitric oxide production
- 1:25:13 Supporting glutathione status
- 1:27:26 What is the best selenium supplement to take?
Here are relevant links:
- My posts on choline and fatty liver disease
- Meeting the Choline Requirement
- Resources for measuring methylation genetics: 23andMe, MTHFR Support, Genetic Genie, NutraHacker (ignore all of the recommendations in the right column of the report)
- The Pursuit of Happiness, my article on methylation of dopamine and the balance between mental stability and flexibility
- MMA test for vitamin B12 status
- Selenocysteine — This is my preferred form of supplemental selenium. For someone taking it as extra insurance, I believe one capsule every two days is a reasonable dose. For someone with evidence of selenium deficiency (ideally this means plasma glutathione peroxidase activity or plasma selenoprotein P are low), I think it is reasonable to take one capsule every day. Higher doses should require supervision and regular monitoring of selenium status.
Transcript of Episode 17
This transcript was generously provided by Cassandra Barns.
0:00 Intro, announcements about ChrisMasterjohnPhD.Com and my experience so far with US Wellness Meats liverwurst.
This is Chris Masterjohn and you’re listening to episode 17 of Mastering Nutrition.
Alright, the episode that you’re about to listen to is the third of my Facebook live broadcasts. This time it was a Q&A session that was all about methylation, that’s nutrients like vitamin B12, folate, choline and much more.
Before we get into that, a few announcements. As a reminder, this podcast is now housed along with my blog at chrismasterjohnphd.com. If you go to that website, you can click on Blog for the blog, click on Podcast for the podcast or simply type in the URL chrismasterjohnphd.com/blog for the blog and /podcast for the podcast. But there’s also a cool little tool: thedailylipid.com/the episode number will redirect you to the show notes for a specific episode of this podcast. Thedailylipid.com is not a website – it doesn’t have any content, it is my 301 redirect playground and you are invited to the fun. That means that since this is episode 17 of Mastering Nutrition, that if you just type in thedailylipid.com/17 that will redirect you to the podcast show notes for this episode. It’s just a little toy – it’s something that is meant to be easy to remember to help you get to what you want faster.
Update: this has now been changed to chrismasterjohnphd.com/n
Okay so other announcements include. I caved in and got the subscription to Headspace. Meditation is an important part of my morning routine. I’ve upped my game from 10 minutes to 15 minutes. I will have more to say about that in the future. I will report on my experience, but I’ll leave it at that for now. I told you that I was going to be consuming US Wellness Meats liverwurst for breakfast every morning and I have started that, and I’m excited. I have always felt best when I combine liver and heart as the dominant source of meat in my diet. So usually, historically I’ve eaten maybe a 3 to 1 ratio of heart to liver, maybe a 2 to 1 ratio depending on the day, and it’s always made me feel much more energetic, much easier to go between meals while fasting, and the only way I’ve been able to replicate that with supplements is to take coenzyme form B vitamins, R lipoic acid, acetyl-L-carnitine and coenzyme Q10. That is a hefty, hefty price because you don’t get any calories or protein from those supplements. So what I’m doing now is I’m eating 6 ounces of US Wellness Meats liverwurst every morning and I’m really happy with the results in terms of actually getting to feel those benefits again. Then not only that, but now I’m not just getting liver and heart but I’m getting kidney in the mix, and it’s so much easier. I know, I know, I know so well that I feel better when I eat this diversity of organ meats and yet it’s always been so hard for me to keep up the habit because it’s really difficult to prepare liver and heart and certainly kidneys, and make it taste palatable and make it something that you can sustain every day. So being able to get this precooked frozen mixture of everything all ground up and just, you know, unfreeze it the night before and cut off 6 ounces and just eat it like that, really fits in with what I’m trying to do to make my breakfast really quick and easy so I can get into my productive workday right away if it’s not a rest day for me. And really has helped me get to feeling that level of energy and that level of easiness between meals again. If you want to check out the liverwurst yourself, you can go to chrismasterjohnphd.com/liverwurst. If you don’t know how to spell that, liverwurst is like liver + WURST, so that’s chrismasterjohnphd.com/liverwurst.
Alright, those are the announcements, let’s talk about the show. In the show what you can expect to find are answers to questions such as these. If you have an MTHFR mutation, even if you have normal homocysteine, you could still be taxing your supply not only of choline, but you could be wasting glycine and spilling it out into the urine and you should consider creatine supplementation to reduce your demand for methylation – something usually only considered by bodybuilders and other people interested in athletic performance, but it could be helpful in that situation as well. We talk about how to use foods and supplements in these cases to help. Whether we can use SAMe, a pretty expensive supplement, to help diagnose problems and get us into a position where we can use whole foods to treat issues. Choline and fatty liver disease. Why is my vitamin B12 levels in my blood through the roof even though I don’t take supplements. COMT mutations – the balance between mental rigidity and mental flexibility, and the potential harms of methylfolate supplementation in people who are predisposed to greater methylation of dopamine in the brain. How to get choline if you aren’t eating eggs. Should you take gelatin even if you’re not eating a lot of muscle meat. And if you have elevated liver enzymes and an MTHFR mutation, should you reconsider your high-fat diet. All this and much more, so without further ado, here is the full episode.
Alright, I am live on Facebook for the third time. Many of you know who I am. For those of you who don’t, my name is Chris Masterjohn. I have a PhD in Nutritional Sciences. I’m currently Assistant Professor of Health and Nutrition Sciences at Brooklyn College in Brooklyn, New York. I’m here to represent only my own views and not those of any institutions with which I’m affiliated. Also, I’m not a medical doctor. We will talk about health but my expertise is academic in nature, so I can provide a lot of insight into how the body works but I can’t diagnose or treat anyone. You can ask about health conditions, but in any cases where I discuss them, I’m discussing it from an educational perspective in a way that you might be able to use information to – in conjunction with a healthcare provider to help with that management, but we’re not actually managing here, so I’m not giving medical advice or practice. Today we’re going to talk about methylation, and I’ll give you a very very very short introduction to that in a moment. If you are watching this Saturday, June 25 at around 2 PM, you are watching it live; if you’re watching it after the fact, you’re watching a recording. Either way, you can like or share the video if you want to promote it. I would love that, so we can get more participation. You can also subscribe to the videos so you always get a notification whenever I go live. If you are here now, you have the special opportunity be able to ask questions. This is a Q&A session and so the questions that you ask will become the show. And so let’s just get right into it.
So very very briefly, methylation is a process whereby we add a carbon to something. It’s involved in the synthesis of many compounds, it’s involved in the regulation of many compounds, and so it hits all kinds of health end points. There’s a lot of nutrients that are involved, most prominently vitamin B12, folate and choline, but there’s actually a lot of other nutrients. And that’s it, that’s my introduction. So I’m gonna try to move on and do what I can to answer questions. I do want to point out that I don’t know everything about methylation, I’m not gonna pretend that I do. It’s extremely complex, so I can’t promise to answer every question perfectly. What I can promise to do is provide – do my best to provide whatever insight I’ve been able to glean from studying this topic.
Alright, let us move forward. Spencer Jensen says, “Will taking organic sulfur or MSM sourced from pine trees cause problems if you have trouble with methylation?” Not that I know of, but I haven’t studied that in particular. So if you know of a particular reason, hit me up and tell me about it, but I don’t know one off the top my head.
9:05 Figuring out apparently choline-induced headaches
Renee Culver says, “My MTHFR C677T is double bad for me. In your first live Facebook you said that there is a choline connection because if your body is not processing folate correctly it relies on choline. Choline-containing foods like liver and eggs give me a headache. I must be very deficient in choline since I avoid these foods. I’m not sure how to proceed. I usually listen to my body and stay away from foods that give me a headache. Perhaps I should make some tiny liver pills and try to work up very slowly, or what insight can you give me on this?” Renee, I would love to be able to give you the answer, but to be honest based on that information, all I can do is guess. So, I mean, one thing you would want to do I think is try to see if it’s actually related to choline, or if it’s something to do with other components of choline-rich foods. So for example liver and egg yolks are very rich in choline, but they’re also very rich in cholesterol, they’re also very rich in biotin. They’re also very rich in a – you know, each one of them is rich in many different things. So the first thing that I would do is, you know, providing that you stay away from doses that you know are really going to debilitate you, is just experiment and see if, does a lecithin – an animal-based lecithin like egg yolk lecithin where it’s mostly phosphatidylcholine – does that in its largely pure form give you the same result? And then if that’s the case I would just try a choline salt, either – well you could try choline bitartrate, or CDB choline or alpha GPC or something like that, and see if the reaction is the same. In particular, there is a form of choline called alpha GPC. If you could see if your response differs between that and lecithin, that might give you some insight into – I mean, assuming that pure any form of pure choline causes this problem, trying alpha GPC and lecithin and comparing them might give you some insight into the mechanism. Because alpha GPC, if I recall correctly, is the only form of choline that’s clearly shown to increase acetylcholine production in the nervous system. And given that, you know, it’s possible that there’s something related to acetylcholine signaling that is causing your headache like, you know, regulation of blood vessel constriction or something like that. And if that’s the case, that would provide some initial insight. I don’t know exactly what the practical impact would be, but you may find for some reason that phosphatidylcholine is the worst one. In which case, I don’t even know what the explanation would begin to be, but that would – I think that would be a first step in trying to figure it out. But it’s – you know, it sort of like, we’re playing detective work here and guesswork with something that’s not obvious, so if you are able to provide me any more detail about experiences related to that, maybe I can further speculate, but hopefully that’s enough to start you off on the right track in investigating. Thank you, Renee, for your question.
12:20 An MTHFR mutation (e.g. C677T) could, even with normal homocysteine, be taxing your choline supply and causing you to waste away glycine into your urine. Boosting choline and glycine supply, and, perhaps most surprisingly, even supplementing with creatine, could help.
Chris Hoffman says, “I think two of the most talked-about MTHFR mutations are 677T and 1298C. I am heterozygous for 1298C. I was wondering if you knew much about these mutations, and if you could give some translation and practical advice to people with them.” Alright, so let me give you some background here, because I want to hopefully – you know, everyone can understand what I’m saying here, and that requires a little bit of background. So the one of the principal roles of folate is to provide a methyl group to vitamin B12, which then provides a methyl group to homocysteine, which then regenerates methionine, which then acts as the principal methyl donor throughout the body. And in order to get the methyl group on to folate in the first place, it’s derived from amino acid metabolism. So serine and glycine but probably – in total it’s probably the amino acid serine that is the principal source of those methyl groups. But they aren’t just – it’s not like there’s just a methyl group you take off of serine; you actually have to construct the methyl group in a set of reactions. And there’s basically two principal reactions: one is to take formate from the mitochondria and rearrange it into the methyl group, and the other is to go about a – take it directly from serine in a – you first create a CH2 group, which is a methylene group, and then you add a hydrogen, which makes it CH3 group, which is a methyl group. And MTHFR is the end-stage enzyme – regardless of which set of processes you’re engaging in, MTHFR is the last enzyme involved in constructing that methyl group, regardless of whether it’s taken from either of those pathways. And so if that enzyme works less effectively, then that means that, in theory what should be happening – and of course what actually happens is more complicated because all we’re talking about here is a genetic predisposition but, if that enzyme is less effective then what’s gonna happen is that you will be less able to use that pathway. And there are a few consequences that come from that. The most obvious one is that your homocysteine should elevate and that’s because you are not as efficiently recycling it. So there’s a couple – now there are a couple less obvious things that would come as a consequence. One is that, because you are not producing methylated folate, ordinarily when you have an excess amount of methyl groups coming into the cell, the amino acid glycine takes those methyl groups and acts as a buffer. And usually, high concentrations of methyl groups are associated with high concentrations of methylfolate. So it’s actually high concentrations of – excuse me, I have that backwards – usually when you have an excess of methyl groups in the cell, there is feedback that tells MTHFR to stop making methylfolate. And it’s that feedback inhibition that actually indirectly initiates using up glycine as a buffer. If you have a genetic polymorphism in MTHFR, then you have low concentrations of methylfolate when you’re not supposed to have them, and so you have constant activation of that signal to use up glycine as a buffer, even when you don’t have the ordinary situation in which that occurs, is when you have too much methyl groups. So one of the consequences of having a less effective MTHFR that is generally neglected in most discussions that I’ve seen, is that low concentrations of methylfolate due to genetic reasons will cause an inappropriate signal that’s telling – it’s confusing the cell, and making the cell think that there’s plenty of methyl groups around, and that is causing inappropriate utilization of glycine to suck up methyl groups. So you wind up in a situation where that compounds not having enough methyl groups, and it also wastes glycine. So when that happens you’re basically gonna methylate glycine into metabolites that, many of which are going to spill over into your urine. And then the other consequence that I think gets intermediate attention and also deserves more attention is that MTHFR is only one way that you can provide those methyl groups; there’s an alternative pathway that relies on choline. So you basically – you can supply methyl groups through the MTHFR-mediated pathway that depends on folate and depends on vitamin B12, or alternatively, you can supply methyl groups from choline. And if your MTHFR does not work as well, your body starts using up choline more. And if you – and in that case you are taxing the choline supply. So when you have a less effective MTHFR, you are not only having fewer methyl groups around but you are also wasting glycine and using up choline.
So there are a few strategies by which you can approach this, that each have their own strengths and limitations. I mean, the first most basic one is make sure you eat more folate. So the – MTHFR is basically recycling your folate and helping you use one molecule over and over and over again. If you look at any of the studies – you know, the 1298C one is maybe more serious, but clearly with the C677T one, you’re usually seeing effects primarily mediated by having that polymorphism plus a low intake of folate. And so if you have a greater compromise in the system, then just throwing folate at it doesn’t make much sense. But it does make sense to make sure that you’re not eating a diet that’s deficient in folate. I would say the three L’s are liver, legumes and leafy greens. For the average person, try to eat liver once a week, for legumes and leafy greens I would say work them into your diet every day. If there’s some reason you can’t tolerate one of those foods, you can rely more on the other but, you know, eating a lot of those foods guarantees a lot of folate. Folate’s very sensitive to cooking and to even frozen storage, so raw fresh foods are best but, you know, it’s not totally degraded so if you are – most – according to the USDA database most cooking is destroying 20 to 40% of the folate in a food so, you know – cooking the food is gonna help you eat a lot more of it, right, so probably with green leaves like, I eat a ton of salads with lots – I just rotate different types of greens, and so I’m probably eating, you know, like 10 or 15 or 20 large handfuls of raw leafy greens a day. But then I also work cooked leafy greens into batch starches that include lentils, and so those are pretty good sources of folate as well. But that’s like – that’s number one strategy, is just make sure your diet is not deficient in folate. One potential strategy that you could use here is to supplement with 5-methylfolate. And actually methylfolate is – you know, the two popular supplements are 5-methylfolate and folinic acid. Those are actually the two forms of folate that predominate in foods, so don’t think that you’re getting anything special by paying big money for those supplements. What you – the only thing you’re gonna get out of that is a dose much higher than what you could get from food. And if you have a genetic polymorphism it may make sense to supplement with 5-methylfolate – makes more sense to do that than folinic acid, because folinic acid is actually upstream from MTHFR, and so I wouldn’t use that, I would use 5-methylfolate. And one of the nice things about 5-methylfolate is that it will act as the signal to shut off the inappropriate glycine wasting. And so in that sense, it might be getting closer to the root of the problem than any of the other approaches. The drawback is that you’re not really re-creating the normal physiology, because the normal physiology is that you take a small amount of folate and then you recycle it with methyl groups derived from your protein, over and over and over again. Here you are inputting 5-methylfolate that you can’t recycle, and you’re just blasting the system with far more folate than it would usually have in there. So you aren’t – so I would say try that – use that as a tool in your kit but watch out to see what kind of results you get from it, because it’s not a perfect replication of the normal physiology.
Tool number two is paying more attention to getting glycine in your diet. If you are wasting glycine, then try to replete that glycine. I would say for someone who doesn’t have any problems, the normal historic glycine intake for humans means eating nose to tail. So it means, you know, half of your animal foods are collagenous animal foods. So I would say use a rich supply of bones and bone stocks, insect exoskeletons if you’re into the EXO bars and, you know, all these are potential sources of skin and bones to supply that glycine. If you’re in a case where you have a severe issue with the MTHFR and maybe you have more predominant glycine wasting, then maybe what you should be doing is supplementing with 1, 2 or 3 tablespoons of gelatin or hydrolyzed collagen. Again, you’re not replicating the normal physiology: the glycine wasting is persisting without the 5-methylfolate – you know, unless you’re doing both of them together – and you are adding glycine to compensate, so you’re trying to get close to the root of the problem but you’re not – in no way are you… you know, if the problem is genetic, only gene therapy is the root of the problem, and I am not comfortable – I mean I’m not comfortable even on the next 10 year horizon of saying we should be treating anything with gene therapy, actually, but, unless it’s severe – this, I don’t think so.
Anyway, and then the third potential strategy is that you supply the choline. Right, we know with the – even with the C677T polymorphism, which is actually really common, we know that if we take those people, it seems like we can best protect the DNA and best protect those people from poor liver function by giving them way more than the RDA for choline. And some of these studies go up to 2 grams of choline per day.
So I would say those are the three – so for 1298C, you know, maybe it it’s not going to be as effective, but these are the tools that are available I think with any decrease in MTHFR activity. So I would say, you know, start at the baseline of just securing these things in the diet with whole foods. But then look at things like, are you really affected by this? So is your homocysteine elevated? Is your mean corpuscular volume on your complete blood count elevated? Do you have mood problems or anxiety problems or depression problems that could be related to methylation factors regulating the neurotransmitters? Do you have problems with body composition, particularly problems gaining lean mass or problems accumulating liver fat? That could mean that your choline supply is being taxed or your creatine is not being synthesized well. Actually, strategy number four I should’ve mentioned that I didn’t get to. The other thing that you can do is try to reduce the demand for methylation in your body. And the simplest one thing that you can do to do that is to get a lot of creatine in your diet. 45% of your methylation demand is to synthesize creatine. Whole body creatine synthesis on average is about a gram and a half of creatine per day, and you can get that amount of creatine by eating 12 ounces of meat – of animal flesh per day. Now in the studies that quantified that, I think they were looking at people who were already eating maybe close to that amount of meat. So that might mean that you’re looking at a pound and a half of meat per day that you want to eat. There may be reasons that you don’t want to eat that much meat, in which case supplementation with creatine may make sense. In that case I would start with a gram or a gram and a half of creatine, but there is at least one case study suggesting that someone with MTHFR mutation and really high homocysteine was able to cut the homocysteine in half using 5 grams of creatine per day. So I would put that in – tool number four in the kit. And I would say you really have to self-experiment with these things and see how they impact the parameters that you’re trying to deal with, because it’s not straightforward and obvious like – there’s this mutation and therefore you should do these things; how that mutation expresses itself is dependent on complex things going on in your body, and each person is gonna be a little bit different. So I hope that starts you out with some tools you can use, Chris, thank you for your question.
Mike Buchanan says, “Hey Chris, just found out I carry a MTHFR gene mutation. Any suggestions on supplementation to prevent elevated homocysteine levels and other issues associated with MTHFR gene mutations.” Well, I just answered that in the previous question. Since you’re asking specifically about elevated homocysteine, I would just add that we dispose of homocysteine when it accumulates by converting it into cysteine which can be used for glutathione synthesis, and that’s a process that depends on serine, glycine and vitamin B6, so you might want to look at your vitamin B6 status. The best – in this case, elevated homocysteine could be taken as a basis for trying vitamin B6. The best marker of status would in my opinion be erythrocyte transaminase activity, not to be confused with serum transaminase activity which is a marker of liver or other tissue damage, and that would be low if you’re low in B6. I think the best form to supplement with is pyridoxal. The one thing I really don’t like about pyridoxal supplements is they come in ridiculous doses. My preferred B vitamin supplement is Coenzymate B by Source Naturals because the forms are better, and the doses are more reasonable. So again, the tools that I discussed earlier plus the B6 could be useful in trying to deal with elevated homocysteine.
Debra says, “What’s the cause of cancer?” Debra, thanks for your question. That’s a little bit too open-ended for me to give a good answer to. I would say it’s complicated, because there’s a lot of different types of cancer, and they don’t all have one specific cause. There’s probably – there’s definitely different subsets of cancer that have different driving factors. There’s some commonalities that probably across – that probably could be said of most cancers, so for example, DNA damage due to oxidative stress and methylation deficiencies could be at the root of initiation of cancer, but environmental exposures to carcinogens is certainly important. For certain subsets of cancers, the internal hormonal milieu, particularly with sex hormone-responsive cancers is relevant. Once you have cancer – you know, once you have the initiation of cancerous lesions you have a whole different set of causes that are causing that to progress into actual cancer, and that’s a whole other barrel of worms. So maybe further along there’ll be more specific causes of cancer that would allow me to go into more detail, but I would say that kind of sums up the modifiable risk factors. The real obvious non-modifiable risk factor is age: getting older is probably the single most important cause of cancer, but it’s not something that any of us can do anything about. So I think those other things are better targeted to actually, you know, things that are actionable for us. Thank you for your question, Debra.
30:03 Using SAMe supplementation to diagnose methylation issues.
Melody Scott Smith says, “What are good diagnostics to check whether impaired methylation is causing a problem? In other words, since gene status, expression, and activation are involved, it seems shortsighted to intervene based simply on presence of an SNP (a Single-Nucleotide Polymorphism), for example MTHFR C677T. For example, what do you think of taking a broadly acting methyl donor like SAMe 1200 mg daily for a month as an initial diagnostic, while observing symptoms and/or markers, and what would they be?” I think that’s a great idea and an expensive one. So, I mean, before you take SAMe, it makes sense to check your diet, right? So SAMe is a form of methionine and methionine comes from protein and it’s twice as abundant in animal proteins as plant proteins. So, I mean, if you’re – if you are eating a diet that’s extremely low in animal protein, then no I don’t think it makes sense to spend a boatload of money on SAMe as an initial diagnostic. I think it makes sense to bring your, you know – ethical issues notwithstanding, I mean if you have no ethical problems with it, the far better – the far more sensible initial thing to do is bring your animal protein intake up to 1 or 1.2 g per kilogram lean mass, if you’re not eating that. And’s that’s number one. And if you’re not eating liver, legumes and leafy greens, fix that. If you, you know, if you’re eating a nutrient-poor diet, fix that. But if you’ve hit all those bases and you have a specific problem that you’re trying to solve, then – and it sounds reasonable that deficient methylation is possibly at the root of it, then I would say absolutely take that dose of SAMe, which is the principal methyl donor that this whole pathway is trying to support. Take that and see if it fixes the problem; if it fixes the problem, that tells you this is a problem of deficient SAMe. And then the question becomes, well, how can we greater analyze this to see what we can do to support endogenous production of SAMe. I mean some people, if they have the money, may want to just stick with the SAMe, but I prefer using it in the way that you are suggesting, which is see if that fixes the problem – that tells you a lot about what more natural strategies you can use to endogenously support methylation. And your point is very well taken that just having the genetic polymorphism doesn’t tell you what’s going on in your body. I think that nutrigenomics is the future. We’re starting to head into that era, but even at its peak we will never be determining diet based on an algorithm derived from genetics, and trying to do so is a total waste of time and is gonna be counterproductive precisely for the reason that you state – the genetic polymorphisms can give us insight in terms of a larger picture about what to do if we see a problem, but it doesn’t tell us whether the problems we’re looking for are there. And we have to look at the total metabolism, so we combine genetics with signs and symptoms and clinical history and blood markers of nutrient status and blood markers of metabolites in the various pathways that we can construct together into a large big picture of what metabolically is going on, and it is from that that we begin to deduce solutions if there are problems that we need to fix. Thank you, Melody, for your question.
34:12 Choline and fatty liver disease
Neil Quinn says, “I’ve heard that choline can help prevent fatty liver disease. True or false? Better to supplement with eggs before or after drinking alcohol?” True – choline protects against all forms of fatty liver disease, whether they’re caused by sugar, fat or alcohol, and absolutely choline is king. This video will become a podcast, probably released on Monday, and the show notes will be available at my website, chrismasterjohnphd.com/podcast, and I will link there to the choline articles that I’ve written, which are very extensive, but I think that when you read them you will agree with me that choline is definitely king when it comes to fatty liver disease. There are other issues, right. In the small minority of cases, alcohol is important, and that’s really important if you’re an alcoholic, it’s not really important if you’re having, you know, an occasional set of drunkenness with friends or, like, one glass of wine each night five days a week or something like that. In most cases, the issue is non-alcoholic regardless of whether the person has some alcohol in their diet. And in that case body composition and insulin sensitivity are just as important as choline. And finally, oxidative stress is – oxidative stress is also just as important as choline. And I would say in general most people who have oxidative stress going on in their liver, in the general population that’s also because of body composition and insulin sensitivity, and combined with a nutrient-poor diet. In terms of using eggs before or after drinking alcohol, I think that’s a red herring: the timing is not important. What is important is your overall choline status. I would – you know – I mean, I’m all for being weird, but like, I could keep it normal here – eat the eggs the next morning for breakfast. Thank you for your question, Neil.
36:28 Why serum B12 shouldn’t be used as the primary marker of B12 status and how to get MTHFR genetics tested
Karla says, “Hi Chris! My daughter had a B12 deficiency. Her levels were 108 and giving her grass-fed beef liver and a B12 supplement as methylcobalamin helped her increase it to 1400. I have suspected she has an MTHFR gene issue but given we addressed the deficiency with food and supplementation, does that mean MTHFR is not applicable in her case? Thank you so much for all the work that you do.” Thank you Carla, I’m glad to produce valuable work for you. So first of all, I don’t support using tests of serum vitamin B12 – I’m assuming that’s what you mean here. I think that, you know, clearly if that’s low and it responds to supplementation, that means the B12 is getting into the body, but I don’t – I mean I think it’s borderline outrageous that that’s used for routine screening of vitamin B12 deficiency. I would support looking at – I don’t think holotranscobalamin II is ready commercially, if it is, that’s good; I definitely know that you could get methylmalonic acid or maybe they call it methylmalonyl CoA, MMA, various names, it’s all the same thing. That’s a functional marker of vitamin B12 deficiency. If it’s high then vitamin B12 status is poor. And that’s really important because, like, high B12 in the blood, it’s sort of like, who cares – maybe you have a backup in utilization of that B12. So, I mean, it’s great that you’re increasing the levels, but I would strongly suggest that you measure MMA – and I don’t mean mixed martial arts, I mean methylmalonic acid. I would strongly suggest measuring as a functional marker of B12 status. If you suspect she has an MTHFR gene issue, find out if she has an MTHFR gene issue. So get 23andMe and send your raw data to MTHFR Support, Genetic Genie or NutraHacker. And if you send it to NutraHacker, ignore everything in the right column of the report that tells you what to do with the information, and only look at whether the polymorphisms are there. If you find out her genetic status, that may give you a better idea of what to do. But, you know, right now I don’t think you should do anything until you have more information about that. Thank you for your question, Karla.
39:03 COMT mutations regulating (via dopamine) the balance between mental stability and mental flexibility, whether 5-methyl-folate supplementation could hurt mental health in those with low MTHFR activity but high COMT activity. Potential relation to obsessive compulsive disorder (OCD).
Deborah Gordon says, “Hi Chris, nice to see you on FB and great podcast.” Thank you, Deborah, it’s great to see you on FB as well. “What do you think of Ben Lynch’s cautions that excess methylation in folks with COMT snp’s? Quite a different approach than methylation-savvy internists who just think everyone can be on high dose methyl folate if they have MTHFR snp’s. Thoughts?” I don’t – so I don’t know that I agree with either of these things. So first of all, methylation-savvy internists blasting people with high doses of methylfolate, that sounds exactly like someone who graduated from a pharmacologically oriented institution and decided to practice integrative medicine by integrating nutrition supplements as their drugs. I apologize to everyone that I just insulted who’s really trying to do great work here, it’s not a personal thing, but – that’s a drug-based approach, it’s not a nutritionally oriented approach. It’s not even – I wouldn’t call that functional medicine either, because, you know, it’s not sort of – what you want to do is try to get a full picture of the metabolism going on and see, you know, what are the actual issues being expressed when we look at the big picture of metabolism and then, you know, what are the things that we can do that get closest to the root of the problem to fix those things. And looking at an MTHFR SNP and then blasting it with 5-methylfolate doesn’t get – it’s not even like – they’re in totally different categories of approaches.
So first of all, I don’t know that I entirely agree that 5-methylfolate is going to harm someone with a COMT SNP. But let’s – I need to give background information on COMT to get everyone on the same page. Alright, so COMT is catechol-o-methyltransferase. And it’s really – it does quite a few things, but it’s really important in the nervous system for regulating neurotransmitters, and I would say overwhelmingly in terms of personality and psychology, the – I don’t want to give the idea that this is the only thing it’s impacting, but I really think that the strongest thing that’s relevant is dopamine. And if you look at the general population, you can basically have an intermediate methylation COMT genotype, which is 50% of people; you can have a low methylation COMT genotype, which is 25% of people; and you can have a high methylation COMT genotype which is 25% of people. If you look at that distribution, what that strongly suggests is that there’s pressure – that there’s evolutionary pressure that’s consistently been acting through human history right up until now, to try to keep people away from the extremes of methylation in the nervous system with respect to these neurotransmitters, particularly dopamine. And if you look at why, a great introduction to this from a sort of moderately technical baseline would be my article “The pursuit of happiness” from a few years ago, where I talked about the importance of dopamine in regulating mental fluidity and mental rigidity. So if you think about how this is impacting dopamine in the brain, you basically have two pools of dopamine in the brain. One is the amount of dopamine that’s always there in the background, and we call that tonic dopamine; the other is the pool of phasic dopamine – these are huge spikes of dopamine that come in response to novel stimuli that you’re experiencing, that last only milliseconds. And those phasic pulses of dopamine are what allows you to change your mental state and adapt to new stimuli. And when your brain perceives the phasic pulse of dopamine, it reads it on a background of the tonic dopamine. So if you imagine, say here we have a solid body of water, and then imagine my microphone – if you’re watching the video here, is a wave that comes up, the microphone goes [….], and those are like the phasic pulses of dopamine. If we raise the level of tonic dopamine and the microphone comes up in a wave, it’s coming up just the same amount, but what the brain is perceiving is that tiny bit that’s popping above the background of tonic – excuse me, the brain is perceiving that tiny amount that’s popping up against the background of tonic dopamine. Now, methylation mediated by COMT is what controls the level of tonic dopamine. So more methylation from COMT means more breakdown of tonic dopamine, and that means that the background noise of dopamine is lower, and that those phasic impulses of dopamine are going to look larger. What that means is that your mental state is more fluid, and you can more easily adapt to new stimuli. On the other hand, if you have a low methylation phenotype specifically with COMT, you’re gonna have less breakdown of the tonic dopamine, the tonic dopamine level will be higher, those phasic impulses of dopamine will look smaller to the brain, and you will have more rigidity, and you will be less adaptable to new stimuli. Now, being flexible is great, but when you’re too flexible, that means you’re too easily distracted, and you can’t focus on anything. By contrast, when – you know, having stability is good, but when you’re too stable and you’re too rigid, you can’t let go of any ideas. So anxiety and depression seem to be strongly associated with the low methylation COMT genotype, and that’s because if something that causes you negative emotions enters your brain and you have too much rigidity in your mental state, then that image comes in and it stays there. And if it stays there, your next line of defense is try to wrestle with it mentally, and if you can’t force yourself to get rid of the image through cognitive – use of cognitive force, then it stays there until your amygdala – the emotional center – lights up and fires up and produces an emotional response. So if that image is something that causes you anxiety and you have a low COMT methylation phenotype, your – instead of that image coming in and going out like a healthy – you know, the healthy psychology says, I see the image, I don’t care, I don’t like it, goodbye, and it goes away. Right, what you get with low methylation COMT is a predisposition for that image to come in, and you say, I don’t like that image, and the image stays there, and you say, I don’t like that image, I’m going to make it go away! And if that doesn’t work, it stays there, and then you get emotional response. And that could be an anxiety-promoting image, it could be a set of thoughts that make you depressed, and so on and so forth. And so you can take that, and you can say, oh, let’s have lots and lots and lots of COMT methylation. But there is also evidence that when you have a high methylation genotype with COMT, then the end result that you get is you can’t focus, so what problems do you have when you can’t focus? You don’t do as well in academics, for example. If you look at severe psychological disorders, what you would get in the high flexibility phenotype is flight of ideas, like, to a pathological, completely debilitating level, you know, each new stimulus comes in and goes, comes in and goes, comes in and goes, comes in and goes. And every possible stimulus enters your brain and does something and leaves and goes on to the next one, and that drives you crazy, and it drives you just as crazy as having the opposite pathological phenotype, where you’re subject to mental rigidity and these ideas are staying there and gripping hold of you to the point where it’s totally debilitating.
So yeah, we want intermediate methylation and I would totally agree with Ben Lynch on that, for those reasons. But, you know, how important is throwing 5-methylfolate into this? I don’t think that throwing 5-methylfolate into this is going to cause over-methylation. What – you know, the way that methylation is regulated is, it’s all based on, the body is supposed to take the raw materials and regulate it itself. It’s not – I don’t know where – I don’t know how people study this for years and years and years and then come out thinking that you – that the body has no homeostasis and you can just, like, pull this lever and make that thing happen, pull that lever and make that thing happen; that’s not how it works – it’s a system that’s highly regulated, and if you have a problem in it, it’s either because the raw materials aren’t there, or it’s because something is thrown off in the regulation. It’s not because you weren’t pulling the right levers with which supplements you were throwing at it. So to describe this briefly, how this would work is, if you have too many methyl groups coming in, then the extra SAMe, the principal methyl donor, offers feedback to – offers feedback to lower the production of 5-methylfolate. But then if you – but then that depletion of 5-methylfolate is driving wasting of glycine through the – it acts as the signal to waste glycine through the buffer system that I was talking about before. And so, you know, actually I guess now that I’m thinking about this, I think that if you were to get the excess of 5-methylfolate into that actual point in the system, it probably could shut down the natural buffering system and, yeah, you know, maybe – the more I think about this, the more I think maybe Ben Lynch is right on point with this. Yeah, so, I mean maybe that’s – maybe that would cause that problem. But I would back up and I would say that first of all I’m not quite sure the degree to which putting 5-methylfolate into the system actually causes the accumulation of 5-methylfolate right in that spot in the cell. Off the top my head I would suspect that there are regulatory processes that are gonna mitigate, that but I’m not 100% sure what they are. But I would definitely say that what you want to have in place to get that balance is lots of the raw materials, including the glycine to act as a buffer. And so, yeah, you don’t want to get super-physiological amounts of 5-methylfolate into that place, because that could disrupt the signaling. But, you know, it’s – so it’s a tough game to play if you have someone with the MTHFR defect where they’re subject to constant abnormal decrease in the 5-methylfolate, because that decrease is also throwing off the signaling. So I think, you know, from a supplementation perspective, you want to say, how can we bring it up to normal. And I don’t really know that you can – you know, at best right now what you could do is try to look at that in red blood cells, but that’s not telling you what’s going on in the brain, so I would say you want to take this on a – you want to take it on a psychological basis, right? If the person is subject to excess mental flexibility or rigidity or other problems that be related to methylation regulation of neurotransmitters under the control of COMT, then look at the results of the methylfolate. Is the person having decreased anxiety and depression? Is the person have having increased distractibility? And take those signs as how to adjust the treatment. But definitely don’t just think that you can throw unlimited doses of 5-methylfolate at the problem. Alright, thank you, Deborah, for your question.
Anton has the next question. “Is there any association between OCD and methylation?” Off the top my head – it’s been years since I looked at this and I think that OCD is associated with low methylation, along the lines that I was talking about before. But I don’t remember the specific data to back that up. But I would say that – I know in my particular case, I was vegan and I definitely had symptoms of OCD that totally disappeared when I started eating animal foods including a lot of liver, and a lot of bones, and a lot of plant foods including leafy greens. And you could make a really strong case that what my diet was doing was causing massive support to methylation that wasn’t there before. So altogether my very strong suspicion is that low methylation phenotype predisposes to OCD. Thank you, Anton, for your question.
Catherine Graham Peterson says, “I’m having trouble finding much information about the 1298C mutation. Do you know why that is? Is the other mutation more common? I would like to find out more about it.” Yeah, the other mutation’s way more common. Hopefully what I said at the beginning of the show offers you some help in getting started thinking about that, but you will definitely not find that there’s as much information about that is the more common one, simply because the more common one is more common. And probably also because I think there’s maybe a bias towards this of saying – I think, you know, part of the reason that there’s more about the C677T is not just that it’s more common, it’s also that it’s more controversial. Right, like, everyone’s always arguing – no one’s arguing about whether a rare severe mutation is having an effect on homocysteine, but, like, everyone’s always arguing about does the C677T – you know, like, one of the debates is should we care about it all, and then there’s like the sub-camp that says – or the camp that says yes, we should care about it, and then there’s, you know, lots of disagreement and conflicting studies about why we should care about it. Is it affecting red blood cell volume, is it affecting homocysteine, is it affecting the choline requirement? And so there’s all these competing hypotheses about it and I think that also is what drives the research, right? If no one is gonna argue about it, then people are, like, oh, we found the answer, let’s move on. And, you know, probably that confidence is exaggerated, but it’s what happens in science – there’s a limited amount of money and time and, you know, people prioritize and triage what they’re going to research. Thank you, Catherine, for your question.
55:36 How to get choline if you’re allergic to eggs?
Spencer Jensen says, “Chris, what’s your take on sunflower lecithin versus choline/egg-based lecithin? I avoid soy lecithin due to the GMO concerns and I’m allergic to eggs, I take sunflower lecithin in place soy and eggs.” I don’t know of a – I mean if it were me, I would take the egg, but if you’re allergic to eggs I don’t know of a particular reason to be scared of the sunflower lecithin, so – you know, I would say – I wouldn’t overlook liver in this, but, you know, if you’re trying to… and also, you know, if – it’s not like – so, liver and egg yolks are by far and away the richest source of choline, but there’s also a very wide variety of vegetables and nuts that are, you know, kind of abundant in choline as far as plant foods go. And there are also, you know, if you have an issue with choline intake and you don’t have an issue with folate metabolism, then more folate can compensate for not as much choline. So there are a variety of ways to approach this from a natural foods-based way as well, and I don’t – I wouldn’t say take the lecithin unless you have a clear evidence that either there’s a problem it could resolve or you – either there’s a problem in that it could resolve or you find through experience that you know that it provides a benefit from taking it. But I wouldn’t take it only because you are allergic to eggs. When this comes out as a podcast I’ll post in the show notes at chrismasterjohnphd.com/podcast my article about meeting the choline requirement so that can help you figure out a few different ways to use natural foods to meet your requirement as well. Thank you for your question, Spencer.
57:33 Strange ammonia scent in the urine
Bette Houston says, “Hi!” Hi, Bette. “I have my DNA results and apparently have many potential methylation issue SNPs. Overwhelming, but I’m working on learning. My ongoing concerning mystery for years is occasionally having a very strong ammonia scent to my urine. Where would you suggest I start with this?” To be honest, I’m not sure that I can provide anything more than a guess. But I would say a urinary organic acids test might provide some insight into what’s going on, and it would be sort of data mining, but I would start by looking at any abnormalities of the stuff that’s in your urine. If it actually is ammonia, then it’s probably ammonia that’s in your urine, but then the question is why? So I mean either you – the most – the thing that sort of jumps into my head as an obvious guess is that for some reason you are relying to a greater degree on protein catabolism for your energy. And I don’t know why that would be unless you are eating a high-protein, low carbohydrate, low-fat diet and particularly if you’re also simultaneously trying to lose weight. Either that or there’s some metabolic abnormality. But yeah, I would start with getting everything that you can get analyzed in your urine and see what the abnormalities are, and I think a typical urinary organic acids test would provide some specific metabolites relevant to nitrogen metabolism that could give you some idea as to what’s going on. Thank you, Bette, for your question.
Kira Miftari says, “I have the same question as Deborah Gordon, above. I’ve heard that choline can help prevent fatty liver disease, true or false?” Kira, true.
Spencer Jensen: “Chris you and your accumulated knowledge and research is amazing.” Thanks, Spencer. “I’ve learned a lot from you and sharing your knowledge has made a great difference in my life. You are very much appreciated.” Thank you very much, Spencer, I’m glad I could be of value to you.
Leandro Oliviera… and thank you Spencer for showing up here, it’s great to have – you’re providing value to me by coming. Leandro Oliviera says, “If a person doesn’t react well to eggs, what’s the best other option to get choline?” In terms of abundance, liver, right? But hardly anyone would eat as much liver as they could eggs. So, again I will direct you to my article on meeting the choline requirement that I will post in the show notes to this episode when it comes out Monday, at chrismasterjohnphd.com/podcast. But I would say apart from supplements very briefly, liver, obviously, but meats are pretty high and low-starch vegetables, like, you know, for example broccoli is pretty high, and certain nuts are pretty high compared to a lot of other vegetable foods. So those would be your natural choices, and of course there’s always choline supplements. I would not use the choline supplements unless you – again, as I said before, unless you have a specific reason to do so. I wouldn’t take it just because you don’t eat eggs. Thank you, Leandro, for your question.
1:01:29 If someone eats a diet low in muscle meat, is it still important to eat collagen-rich animal foods?
Thomas… apologize for dropping the phone, it’s one of the costs of doing Facebook live. Okay, sorry folks, where was I. Alright, Thomas Reinan says, “Hi!” Hi, Thomas. “It is my understanding that the metabolic pathway involved in getting rid of excess methionine uses up glycine in the process.” Your understanding is correct, Thomas. “So in the context of a diet low in methionine (a diet low in muscle meat), would it still be beneficial to include foods like gelatin or oxtail-soup?” Yeah, for sure. So I don’t know that anyone has really produced a quantitative analysis of to what degree is our glycine requirement dependent on methionine. In principle, yeah, a low-methionine diet will spare the need for glycine. But the problem is that ever since the early 20th century, we’ve been biased by this idea that glycine isn’t an essential nutrient and therefore it’s not important. And we started out saying let’s define everything that promotes growth in rats as an essential nutrient and define everything that doesn’t as not. And then we sort of moved on to a mature – a more mature understanding that was still somewhat naïve, which was, let’s see biochemically if we can synthesize this thing or if we can’t. And then we started to move on to a more mature understanding after, like, 80 years, which was let’s see if under all conditions we can always make enough of this to support optimal health. And when we reached that point, that’s when we started rethinking things and saying hey, maybe we need to eat glycine, hey, maybe we need eat choline. And now choline is an essential nutrient but that wasn’t shown until – it was in the 2000’s that choline was first recognized as an essential nutrient, if I remember correctly – maybe I’m confusing that with the 90s, but I think it was the 2000’s, it was when they showed that on TPN you develop fatty liver that would go away when you supplement with choline. Anyway, quantitatively, it has been estimated that we fall short of our glycine requirement in endogenous synthesis by 10 grams per day. Most of us are not eating 10 grams per day of glycine. And if you’re eating less protein, that’s even more true, because if you’re eating low animal protein, that it’s not that plant protein is any less high in glycine than muscle meat, but plant foods that are high in protein for plant foods are lower in protein than animal foods, and the protein is less bioavailable. So just by switching over to a plant-based diet you’re decreasing your methionine intake and your glycine intake. And in that case I think that it’s not obvious how much of that 10 grams – if we assume that’s an accurate number – you spared. So, yeah, I think it would be great to consume oxtail and other collagen-rich proteins. That is – you know, that’s what’s been the typical norm in human society. Maybe you ate a lot of meat, maybe you ate meat once a week but, you know, if you ate any meat, like half of what you were gathering from the animal was stuff that makes collagen-rich foods. So I don’t think that just because you eat less animal flesh that you should not eat collagen-rich foods. If you eat a lot of meat, then that probably means you want to focus more on making sure you also eat a lot of gelatin, but I think that gelatin – I mean, I would say it’s a food group, in my opinion. Thank you, Thomas, for your question.
1:06:38 My serum B12 is off the charts and I’m not even taking a supplement. What gives?!
Matthaios says, “Chris, why would all of my serum B12 labs come back off the charts elevated even before any exogenous doses? I have 1298C heterozygous and chronic Lyme disease.” If you mean your serum B12 is really high, then my guess is that there’s a backup in B12 utilization. As I said before, I’m sort of – I don’t understand what the point of measuring serum B12 is. Maybe this is the point, right? Like, maybe this unexplainable high serum B12 that rarely occurs is the point. But I still don’t see the point of it, because no one in clinical use is doing anything with that information, that I’ve seen. I see people come back with high serum B12 and it’s like, oh, stop taking B12 or whatever. So first of all, if you want to know anything about your B12 status, measure MMA. If it’s available, holotranscobalamin II. I don’t know if anyone’s made that available yet. Measuring everything else in the methylation pathway could be valuable. I don’t – honestly I don’t – there’s probably something to do with Lyme disease here that I can’t answer because I don’t know enough about Lyme disease. So I’m sure that I’m overlooking something here, but if – let’s see, if folate – if folate is not passing on methyl groups to B12, then that means that you’re not going be able to utilize B12 in that pathway, but I don’t know that that means that you’re not going to be able to transport B12 into the cell for utilization. Maybe there’s some feedback saying, hey this B12 is not doing anything in the cell, therefore why bother taking in more B12, and it winds up in your blood. I don’t know enough about the transport mechanisms to say whether that is probably the case, but it’s the only thing that I could think of if we’re gonna assume that your MTHFR mutation is at the root of it. But maybe your MTHFR mutation is not at the root of it. So definitely measure MMA to further understand B12 status. I think this is a case – you know, if you have a – I wouldn’t recommend it for everyone but if you have a mystery case in a possible methylation-related issue, I would recommend – as I recommended last episode, the European Laboratory of Nutrients Health Diagnostics and Research Institute methylation pathway panel. I think that could show – better characterize what that metabolic pathway looks like, and might be able to provide better information to help you understand that. Thank you, Matthaios, for your question.
1:09:32 MTHFR mutation, no gall bladder, and high liver enzymes on a high-fat diet: choline support seems in order, but rethinking the high-fat diet in this particular case is also wise.
Dani says, “Hi Chris. I have high liver enzymes. I have a 677T mutation. How can I bring these enzymes back to normal? Thank you.” Steven Zeisel’s research would suggest… you have a car in your picture, I’m guessing by the spelling of your name that you are female? I don’t know how old you are. Anyway, there is a gender effect and there’s a menopausal effect based on estrogen. But in general, people with the 677T mutation have a greater tax on their choline supply to make up for the methylation demand. And that causes depletion of choline, which then causes accumulation of liver fat and hepatic dysfunction. And that can be – although liver enzymes are not a specific marker for fatty liver disease, there is evidence that – oh, also there is a there’s a genetic polymorphism that could be relevant called PEMT, and PEMT is regulated by estrogen, which is why –which is why there’s an association of menopausal status in females with the choline requirement but it’s also the case that the polymorphism that decreases the activity of PEMT is really really common. And so what that means is that in general, premenopausal women with healthy estrogen levels are protected from choline deficiency by the expression of PEMT, but if they have the PEMT polymorphism, then estrogen is not beneficial to them. So you could either have hormonal issues that are affecting your choline requirement, or you could have a polymorphism in the PEMT gene that’s affecting it. But regardless of anything that I just said that causes a change in the choline requirement, it’s probably the case that boosting your choline nutrition can help you with your liver function. And in that case, I will also direct you to my article on meeting the choline requirement for more information. Thank you, Dani, for your question.
1:11:48 My thoughts on fasting for general health
Basheer says, “Hi Chris, your thoughts on fasting in general for health. There’s the higher carbers who kind of despise the idea yet the low carbers and keto guys praise it. Thank you, really appreciate your work.” Thank you, Basheer, for your question. I’m going to answer it, but I’m gonna answer it really quickly because this episode is dedicated to methylation. A great place to ask that for more detail would be in the – not next episode but the one after that, where the theme is gonna be ask me anything about anything. And, so right now I’ll just say really quickly that I find it absolutely true that there is a strong association of bias for or against fasting based on bias for or against carbohydrate. That’s a very astute observation of you, but in general there is a paradigm network where people who are biased against carbs are biased in favor of fasting, and people who are biased in favor of carbs are biased against fasting. That’s so true, that’s so absolutely true. Very quickly, very quickly – fasting is good for you, fasting is bad for you, it depends on the context. The biggest context that is important is your cumulative allostatic load. You can think of that as your “stress bucket”. Fasting is a stress, exercise is a stress, carbohydrate deprivation is a stress, ketogenic diet is a stress, challenges in your life are a stress, like, there’s nothing good or bad about stress, but how you respond to it is important and the cumulative load is important. And although each stress is different and has a different set of parameters in terms of what is too much, what is the wrong context. A very large driver of whether things that are stresses are good or bad for you is your cumulative allostatic load, so to some degree it’s important to put everything in one bucket and then ask yourself, how full is my bucket, and can I fit fasting? Thank you, Basheer, for your question.
Anton Dietzen says, “Thanks Chris, makes sense with the info you gave on carb flexibility.” Thank you, Anton, glad that was helpful.
1:14:00 Post-traumatic stress disorder (PTSD)
Sarah Walter says, “Could you shed some light on the tie between PTSD and COMT SNPs and methylation? It sounds like dopamine is very much involved based on what you were saying earlier. The hallmark of PTSD seems to be the mental rigidity and overactive amygdala.” Yeah, you said it, right? I mean, PTSD is – there’s some overwhelming stress that stays in your mind and doesn’t leave and after that trauma you have a stress disorder – I mean it’s all sort of spelled out so clearly right there. And everything that I said about dopamine is so relevant to that. I’m not really sure that I can say more about that, I mean, as you correctly observed that is another application of what I was saying before, and I think that’s great. So, you know, addressing the methylation is one part of that. That’s only addressing the biochemical predisposition. Cognitive therapy is just as important, but it’s like – you know, cognitive therapy is acting on the background of the physiological predisposition. So how effective is the cognitive therapy? That depends on whether the physiological background is favorable to the cognitive therapy or not. So don’t expect methylation to fix PTSD, but don’t expect cognitive approaches to fix PTSD if your physiology is haywire and you’re not doing anything about it, right? So I think a multifaceted approach that addresses it from every angle is the best one.
Carmen Hunter says… thank you for your question, Sarah.
1:15:41 Thyroid autoimmunity
Carmen Hunter says, “What are your thoughts on the relationship between thyroid autoimmunity and methylation SNPs 1298 and 677?” I don’t know, I haven’t looked into that specifically – I would say that in general thyroid autoimmunity probably has multiple things going on, but one of them is oxidative stress in the thyroid gland. And there’s – you know, the thyroid gland produces copious amounts of hydrogen peroxide in order to make thyroid hormone. That’s very dangerous. It is only safe when there’s a very strong antioxidant support in the thyroid gland, principle of that is selenium and glutathione. So for example, there’s some evidence that selenium supplementation can be helpful in Hashimoto’s thyroiditis. Similarly, you know, selenium is only being helpful there because of glutathione. If you – so the MTHFR SNP shouldn’t be a main thing causing you to not be able to synthesize glutathione, but it could be causing homocysteine to accumulate which causes oxidative stress and could deplete glutathione, so that’s a potential connection. Clearly there are so many roles of methylation that I don’t know that I can – will by no means say that’s the answer, but it might be part of it, and if there’s more to it I would need to study it more to understand what that more is. Thank you, Carmen, for your question.
Mark says, “Hi Chris, I just joined in here and had a question about B12. I recently had a B12 blood test that came back elevated at 1152 pg/mL. I was doing some sublingual supplementation but not excessively. Is that dangerous or might there be another reason it would be that high?” Mark, I addressed that earlier in my responses so I’ll leave it at that, my answer to you would be the same. If you came in late and you missed it, when I post the show notes Monday at chrismasterjohnphd.com/podcast, there will be a time-based map that shows you when you can skip to in the audio or video to find that specific question. If you were already here, then hopefully you got what you were looking for out of my answer before.
Keith Bell provided a link. I appreciate it, Keith, but I can’t look at links while I’m doing Facebook live – sorry that that’s the case. Derek Walton meant SNP, okay, great.
Dani – oh, Dani says, “I’m male at 41, I’m on a high-fat diet and I had my gallbladder removed.” Okay, so everything that I said about estrogen and menopause regulation of PEMT doesn’t apply but everything else does. So it’s still the case that choline is really important. I would say, you know, think carefully about why you’re on a high-fat diet. I mean, you’re in a position where you had your gallbladder removed. The gallbladder’s really important in digesting fat. You’re not in the best – doesn’t sound like you’re the best candidate for a high-fat diet. It’s worth looking at whether you have hepatic fat accumulation – you can do that with biopsy, I wouldn’t recommend it, both because it’s invasive and it’s also – you know, it could hit or miss in terms of whether you get the right section of tissue. Ultrasound is probably the least invasive way to do it, in terms of the best balance between invasiveness and sensitive information, MRI or MRS would be the best way to do it, but look at liver fat. Choline would help. You know, in all honesty, think carefully about why you’re on a high-fat diet and think about whether you’re gonna lower the fat because if – particularly if you don’t have a gallbladder, and then particularly if you don’t have enough choline, then more fat fluxing through the liver from dietary fat is sort of – I’m not saying that a high-fat diet is intrinsically bad, it’s just that in a situation with poor liver function and no gallbladder, it’s sort of the most likely type of diet to make everything worse. So I would consider – I mean, try choline supplementation and see if everything disappears; if everything doesn’t thing doesn’t just disappear with choline supplementation, rethink your macronutrient ratios. A diet that’s higher in starch, lower in fat, moderate or low in natural sugars and very low in refined sugars would probably be the one that is most gentle to the specific situation that you’re in. Thank you, Dani.
1:20:24 Nutritional support for nitric oxide production
Ron Culbertson says, “I seem to have the MTHFR gene problem and hence poor methylation and high homocysteine. Also familial hypercholesterolemia type IIa. B12, pyridoxal-5-phosphate and methylfolate help homocysteine numbers. With MTHFR, nitric oxide production seems to be low because of MTHFR. What would be a good strategy to increase NO production?” I don’t know that much about MTHFR and nitric oxide production, and if I remember correctly this is one of those things where I tried looking it up and came away a bit sceptical about what everyone was saying about it. But I will say that not knowing much – if anything – about the connection, but knowing a little bit about nitric oxide, it’s possible that if you don’t have any viral issues, L-arginine supplementation would be useful, and supporting the antioxidant defense system, which is a very complicated topic but – for another time, but – supporting antioxidant support can also be useful. Thank you, Ron, for your question. Sorry I couldn’t give you more definitive detail.
Liz says, “Are you familiar with sulfation, and if so, in your opinion what is the best way to regulate the sulfation pathway to reverse or treat sulfur and salicylate intolerance?” I’m not sure I totally understand your question. So the transulfuration pathway is very closely related to the methylation pathway, and that is that when you have high homocysteine concentrations due to a high influx of sulfur amino acids, then instead of recycling it to methionine what you do is, in a vitamin B6 and serine-dependent manner, you convert homocysteine to cysteine and that allows you to produce taurine, it allows you to produce sulfate and it allows you to produce glutathione. Glutathione is the master antioxidant of the cell and takes priority, so you will synthesize glutathione up until the point where you either – where your body either perceives that it doesn’t need any more glutathione, or that it can’t make any more glutathione because are other things that are limiting, and then whatever spills over from that produces taurine and sulfate. I don’t – sulfur intolerance, I don’t know what’s at the bottom of that, I’m not familiar with that. I would think that – I can’t say anything about sulfur intolerance. Salicylate intolerance – the things that are useful for getting rid of salicylates are glycine and glucuronide. We make our own glucuronide and there is also a little bit in kombucha, I don’t know that that’s really gonna – you could try that but I wouldn’t take more than a few ounces a day, and I don’t know that that’s enough to really provide enough glucuronide to make a difference. And I don’t know that someone who is intolerant of salicylates is really a good candidate in general to drink kombucha, but – apart from that I would say that salicylate intolerance I think probably has a lot of other things going on in it, including changes in metabolism that don’t have anything directly to do with salicylate detoxification. So, for example, salicylates may be – you may have a –differences in how you metabolize arachidonic acid. So for example if you have upregulation of enzymes that make inflammatory compounds that are not – so arachidonic acid goes through two metabolic pathways: one set, broadly speaking, is the COX enzyme and the other set, very broadly speaking, is – if I remember right, leukotriene synthesis. And so if you don’t have leukotriene synthesis upregulated, salicylates blocking COX is not gonna be bad, but if you have the enzymes upregulated to make leukotrienes and then you throw salicylates in at lower COX, then basically leukotriene synthesis is – all of your arachidonic acid goes in that way and that provokes an inflammatory reaction. So a lot of this has nothing to do with methylation, really. So I’ll leave it at that and then either in the “ask me anything” episode we can talk about that, or maybe we can do a food intolerances-themed episode. Thank you, Liz, for your question.
Ellie Jo Smith says, “Is there a relationship between H pylori and methylation?” Probably, but I don’t know what it is, sorry that I can’t offer more information, Ellie. But thank you for your question.
1:25:13 Supporting glutathione status
Carmen says, “Do you prefer liposomal glutathione?” Prefer it to what, I mean, it depends on the situation. So in the typical person I would prefer that the person eat a nutrient-adequate diet, that the person maximize their body composition into ideal levels and that the person maximize their insulin sensitivity, largely driven by improvements in body composition, and that the person eat a nutrient-dense and well-rounded diet that contains enough protein, that contains a lot of fruits and vegetables, that contains a broad spectrum of micronutrient adequacy including all the B vitamins, it includes organs and bones. You know, that’s the – that’s the first line of defense for glutathione. Second line of defense is try supplying gamma-glutamyl cysteine bonds – those can be found naturally in raw milk or raw egg white. Raw egg white has some drawbacks – that could be debated endlessly, and so it may be the case that you wouldn’t digest the protein very well, it may be the case that if you’re not also consuming the yolks, you get a biotin deficiency from that. In general I prefer raw milk in that sense, but I don’t drink raw milk because even with the raw milk lactase, I don’t tolerate the lactose very well. I eat aged cheese and the aged cheese doesn’t have those proteins at all. So if you’re not doing that either way, then whey protein is the next best supplement. And then after that, you say, okay, do you have poor glutathione status, then maybe it’s time to take liposomal glutathione. I would say liposomal glutathione is a very good tool if you have a specific reason for it, and that specific reason should be what motivates you to pay the hefty amount of money that it’s gonna cost and to deal with the bad taste in your mouth every morning or however often that you take liposomal glutathione. So, yeah, it has its utility, but shouldn’t be the first line of defense for anyone. Thank you, Carmen, for your question. Mark… Carmen says, thank you. You’re welcome.
1:27:26 What is the best selenium supplement to take?
Marc Kaiser says, “Is there a particular form of selenium that is best for supplementation? Thanks Chris.” Mark, I would prefer selenocysteine. I don’t know that I’ve ever seen a selenium supplement that I actually liked. If anyone knows of a good selenocysteine supplement, please let me know about it, and I will popularize that and promote it. Short of that, you’re probably looking at selenomethionine. I don’t like selenomethionine, but it does the trick if you’re trying to fix a selenium supplementation. Thank you, Mark, for your question.
Angela Larson says, “My vitamin D level was 40.6 when I had it tested recently. I am nursing my 20 month old and plan to become pregnant again soon. I currently take one teaspoon of Green Pastures fermented cod liver oil each day in addition to a multivitamin with about 400 IU vitamin D. I live in Texas and I get a fair amount of sun exposure in the summer from gardening. How much vitamin D would you recommend that I take? What do you consider an optimum range for vitamin D in lab results?” For the average person I think the optimal range is probably 30 to 40 ng/mL of 25(OH)D. If you are dealing with a lab outside the United States that uses nanomoles per liter, multiply that figure by 2.5. I – you know, honestly, I am not a fan of measuring 25(OH)D and determining from that some precise amount to supplement vitamin D. I actually am a strong advocate of better characterizing the pathway. If it’s low, including measuring parathyroid hormone, if your 25(OH)D was 40, that was – I can’t – you said it was recently so I guess that would be the low end because – well I don’t know how recently it was. Anyway maybe that’s your intermediate end and it would probably be highest at the end of the summer. I would be really surprised at that level if your PTH were high, but that would indicate that there’s a problem there. I would say you could probably cut back on the vitamin D, but you know, you’re gonna be pregnant – your last trimester of pregnancy will suck out a lot of that vitamin D. So, you know, keep an eye on it, but maybe you’re in a good position to sort of withstand pregnancy and not need any extra vitamin D. But definitely I wouldn’t purposefully bring your vitamin D any higher than that. All of that is subject to of course the caveat that specific people with specific problems with probably specific gene mutations might need more vitamin D. What I’m saying to you applies to you assuming that you are the average person; none of us are average, but I should say that you behave like the average 25(OH)D response. Alright, Angela, thank you for your question.
Teresa says, “Do you do individual consultations?” Yeah, you can go to chrismasterjohnphdphd.com and right on the menu you will see Consultations, press there, use the link to schedule it, only after you read the very short list of terms and conditions that are there, if you agree to those then schedule the consultation. I will note that I have some major products coming up and I’m probably gonna drop consultations to once a week for the rest of the summer pretty soon, but yeah, you should be able to find – you should be able to find a spot at some point, even if it’s not right away. Thank you, Teresa.
Angela Larson says, “I’m a dietitian and I do speaking engagements where I teach the public about vitamin K2. Do you feel”… I see we’re at the end of the questions so I guess I will just answer questions about anything for the next minute or two. “…I’m a dietitian so I do speaking engagements where I teach the public about vitamin K2. Do you feel that there is any upper limit to safe segmentation? How much K2 supplementation do you recommend for an elderly population who has a history of heart disease?” I would say it’s – you know, unless you have a specific reason it’s better to keep it at food doses. So aged cheese and egg yolks frequently, or natto and goose liver weekly and – plus lots of vegetables including green leafy vegetables and other fermented foods, in the average person I think is good. If you’re dealing with someone who has heart disease, there’s good reason to want to further look into that. I personally take 1 mg of vitamin K2 from Thorne in the MK4 form because I have a polymorphism in vitamin K oxidoreductase or VKOR, which decreases my recycling of vitamin K and increases – presumably increases my need for it. I think that’s why I’m very vulnerable to tooth decay when my diet is suboptimal. So I have that specific reason, but I actually take one drop, which is – the dose on the label is 15 drops. I take the lowest dose that I can, because I really think that 1 mg is sort of pushing it in terms of a nutritional intervention. I think when you get higher than that you’re moving into super-physiological doses that are pharmacological in nature. If I could sort of pick – if I could sort of make my own vitamin K2 supplement, I would make a daily dose of around 4 to 500 micrograms, with maybe three quarters of that being MK4, and the rest MK7. That would be my sort of favorite K2 supplement if I were to make one. There are upcoming tests that should be available, but are not yet, to look at vitamin K status in the blood vessel wall. Keep a lookout for me for potential propagation of those tests if they become available in the United States. Probably they will become available in Europe first but right now it’s possible that I could work together with like a team of clinicians to collect blood samples and send them en masse into the Netherlands for analysis, but what we would really want to do is look at the carboxylation status of matrix GLA protein circulating in plasma or serum as a marker of vitamin K status in the blood vessel wall, and use that to assess whether someone’s vitamin K is adequate for the purposes of cardiovascular disease. Thank you, Angela, for your question.
Sean Roberts says, “What are your current recommendations for those lacking a gallbladder? Mine was removed mistakenly when I was 25 turns out…” You know, Sean, your question is – I need to wrap this up because of the time limit and your question is not quite methylation, so why don’t you come back with that question on the – two episodes from now when it’s ask me about anything.
Alright, thank you so much everybody for your questions. Remember that, first of all, you can you can click the Follow button to get an automatic notification to your phone whenever I go live. You can go to chrismasterjohnphd.com/podcast and – or just chrismasterjohnphd.com/blog, in either case you should easily find your way to the schedule of upcoming Facebook live events. Please check that schedule and if you love this, come back for it. Remember that chrismasterjohnphd.com/podcast probably around Monday will have the show notes for this episode. If you go into your favorite podcast app and search for Mastering Nutrition, that is the podcast in which you will find it, you can listen to it then as a downloaded audio on your phone while you’re commuting. Thank you so much for everyone for showing up, this was great – you know, your questions make the show so I really, really, really appreciate and value your participation – without you, this would not be what it is so, you know, like, we’re a team, right? It wouldn’t be this without me, it wouldn’t be this without you, so I hope that you found this as valuable and fun as I did, and I hope that this is really useful to you. Okay, so in the future, yeah, continue to follow me at chrismasterjohnphd.com and on social media, Twitter, Instagram, Facebook and Snapchat, and I will see you later, thank you so much.
There you have it folks. If you liked this episode, then come to the next Facebook live episodes live on Facebook. Just search Chris Masterjohn on Facebook and find my public figure page. Wednesday, June 29 5 PM Eastern time, ask me anything about vitamins A, D and K, live. Saturday, July 9 2 PM Eastern time, ask me anything about health, fitness and nutrition, it’s a free-for-all like the first episode. Remember these are in Eastern daylight time so adjust your time zone if necessary. If you are enjoying this podcast, please help spread the word by reviewing it in the iTunes store, by downloading the episodes, sharing the episodes on social media or subscribing in the iOS app or your favorite podcast app. You can find me on social media, Facebook, Instagram, Twitter, and Snapchat. But you can also find my new website chrismasterjohnphd.com, and that hosts the blog at chrismasterjohnphd.com/blog, the podcast at chrismasterjohnphd.com/podcast. And if you click on podcast, you can easily find this episode by scrolling to it and finding the show notes where I post the time map so you can easily find where you are in specific episodes or look for specific things in those episodes. And it’s where I post relevant links to the things that we talk about, the resources that we talk about in the podcast. And you can also use the little trick that I developed by going to thedailylipid.com/episode number in order to get a shortcut to the specific episode that you’re looking for. So, for example, this is episode 17 of Mastering Nutrition. You go to thedailylipid.com/17 and that will redirect you right to the show notes for this episode on chrismasterjohnphd.com. (Update: this has now been changed to chrismasterjohnphd.com/n) If you want to see me speak in person come to the Ancestral Health Symposium in Boulder, Colorado August 11 through 13 and come to Wise Traditions, the annual conference of the Weston A. Price Foundation in Montgomery, Alabama, November 11 through November 14. Alright, that’s it, and I will see you guys next episode, thank you so much.