Mastering Nutrition

Question: Why does estrogen regulate tryptophan metabolism? Chris: I think that it's basically the body trying to make sure that the baby has enough niacin because chronic estrogen exposure would occur during pregnancy. When I was doing my niacin research, one thing that I found is that women seem to need more total niacin than men, but they seem to be better at making niacin from protein. What's really interesting is that the studies that were done that were used to make the RDA, there weren't comparisons in men and women, but two of the studies were men and two studies were in women. The standard deviations, meaning how much variation there was person to person, in how much niacin that they needed to normalize what they were looking at was way bigger in men than it was in women. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/10/19/ask-us-anything-hormones-dr-carrie-jones-may-10-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a ====== DISCLAIMER: I have a PhD in Nutritional Sciences and my expertise is in performing and evaluating nutritional research. I am not a medical doctor and nothing herein is medical advice. PLEASE NOTE: As a result of the COVID-19 crisis and the time I am committing to staying on top of relevant research, as well as the high volume of questions I receive, it may take me extra time to respond to questions here. For an up-to-date list of where I respond to questions most quickly, please see the contact page on chrismasterjohnphd.com. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Insomnia is different between people who are and aren't on HRT? Carrie: Yes, sort of. If it's strictly a hormone issue, if she says, "I've never had insomnia. I turned 45 and I got insomnia. And, oh, by the way, I'm also having irregular periods and hot flashes and night sweats and all this stuff," I find that going on HRT generally resolves their insomnia. If they've had insomnia their whole life and, by the way, they're having hormonal issues as well or they're perimenopausal, going on HRT may or may not help their insomnia because their insomnia may be induced by, of course, other things; cortisol, blood sugar, parasites, hypothyroidism, hyperthyroidism. Then I find that it's much more systemic as opposed to just the women who say to me, "I turned 40 and can't sleep," or "I turned 56 and I can't sleep." I'm like, "Oh, perimenopause." This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/10/19/ask-us-anything-hormones-dr-carrie-jones-may-10-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&ahttps://chrismasterjohnphd.com/q&a ====== DISCLAIMER: I have a PhD in Nutritional Sciences and my expertise is in performing and evaluating nutritional research. I am not a medical doctor and nothing herein is medical advice. PLEASE NOTE: As a result of the COVID-19 crisis and the time I am committing to staying on top of relevant research, as well as the high volume of questions I receive, it may take me extra time to respond to questions here. For an up-to-date list of where I respond to questions most quickly, please see the contact page on chrismasterjohnphd.com. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: The use of pregnenolone to manage perimenopausal symptoms, particularly insomnia. Carrie: Well, so here's the thing about pregnenolone. Oral or sublingual, so if you've got drops or little tables you suck on. Pregnenolone and progesterone, when they go through first pass, so you swallow them and then you go through first pass, they turn into other metabolites. One is called allo, which is short for allopregnanolone. Allo binds to your GABA receptors in your brain. Allo can cross the blood-brain barrier, binds to GABA. GABA, of course, is your calming, relaxing, everything is going to be okay hormone. Pregnenolone, oral pregnenolone and oral progesterone actually work on the anxiety and on the insomnia from a GABA point of view. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/10/19/ask-us-anything-hormones-dr-carrie-jones-may-10-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a ====== DISCLAIMER: I have a PhD in Nutritional Sciences and my expertise is in performing and evaluating nutritional research. I am not a medical doctor and nothing herein is medical advice. PLEASE NOTE: As a result of the COVID-19 crisis and the time I am committing to staying on top of relevant research, as well as the high volume of questions I receive, it may take me extra time to respond to questions here. For an up-to-date list of where I respond to questions most quickly, please see the contact page on chrismasterjohnphd.com. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Guidance on what time of day it is best to take T4 and/or T3? Carrie: It actually depends if you're taking immediate release T4 or T3 especially or sustained release because T4 has a much longer half-life which is why we traditionally say to take it in the morning since it helps with energy and metabolism and all those things. Although I do know some people choose to take their T4 at night before bed. But T3 has a very short half-life, and so what I'm finding is some practitioners are now doing what's called a sustained release T3. They take their T3 and it helps sustain longer throughout the day, or they will take their T3 twice. They'll take it in the morning and then they'll sort of take it again in the mid-afternoon. Now, if you're taking a combination T4/T3 such as Armour or Nature-Throid, you can't get the sustained part. I do know some people who will take their Armour or their Nature-Throid in the morning, and then they will take in additional dose of T3 in the early afternoon like an extra, whatever it is, 2.5 or 5 micrograms of T3. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/10/19/ask-us-anything-hormones-dr-carrie-jones-may-10-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a ====== DISCLAIMER: I have a PhD in Nutritional Sciences and my expertise is in performing and evaluating nutritional research. I am not a medical doctor and nothing herein is medical advice. PLEASE NOTE: As a result of the COVID-19 crisis and the time I am committing to staying on top of relevant research, as well as the high volume of questions I receive, it may take me extra time to respond to questions here. For an up-to-date list of where I respond to questions most quickly, please see the contact page on chrismasterjohnphd.com. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: A rant on why many people use "MTHFR" to slap a label on their health problems. I put MTHFR in quotes because I meant it the way that people mean when they say, "I have MTHFR." Everyone has MTHFR. What people mean by that is they have these MTHFR polymorphisms. What I meant by that title is that there's a very compelling—It's not totally airtight. It's not completely proven. There's a very compelling argument that the low activity of the C677T polymorphism in MTHFR is exclusively a result of mediocre riboflavin concentrations. That's what I meant by just your MTHFR in quotes means the polymorphism, the result of the polymorphism. Just riboflavin means that the enzyme activity is only lower as a result of that polymorphism because of the mediocre riboflavin concentrations. To them, MTHFR doesn't mean the rate of the MTHFR enzyme. It's a general label for all their health problems that they put Band-Aid solutions on like these tedious distinctions between these different forms of B vitamins and stuff like that that in a healthy well-balanced system don't matter. If people are hypersensitive to little distinctions in the type of B vitamins they're taking like this, their problem is not just MTHFR. Their problem might be related to methylation. They probably have mineral deficiencies, or other genetic polymorphisms, or other health problems, thyroid-adrenal stuff that are causing that. The reason that MTHFR isn't simply about riboflavin for those people versus the well-controlled studies of showing that riboflavin supplementation specifically lowers homocysteine 40%, specifically in people with MTHFR C677T homozygous, specifically with poor riboflavin status. When you're out there saying that overmethylators can't tolerate methylcobalamin or they get terrible reactions to this, you're slapping overmethylator label on someone whose problem is that they just don't have a rational strategy for dealing with their MTHFR. Because no one is an overmethylator or an undermethylator, unless it's a collection of symptoms of a poorly managed methylation system. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Are there safety concerns in supplementing cyanocobalamin rather methylcobalamin in those with MTHFR polymorphisms? If you're concerned about methylation-related issues, you would want to be careful with methylcobalamin supplementation in a way that you would not need to be careful about hydroxocobalamin supplementation. If you don't have a specific methylation-related goal, then I think hydroxocobalamin is the default because that's the sort of like metabolically neutral B12 in that it's not predisposed to any particular system, and it's not going to affect any system in a specific way apart from just being nutritional B12. Then the second thing is "if you had MTHFR, is it dangerous to supplement with cyanocobalamin?" It doesn't matter. I don't think MTHFR has anything to do with methylcobalamin really. If you don't have malabsorption of everything else, you should look at the specific causes of B12 malabsorption, which are pernicious anemia and gastritis, including subclinical gastritis driven by H. pylori in the stomach. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: What about pyroluria and measuring kryptopyrroles? I think it's fairly harmless to increase zinc and B6 as a test of whether that's true and see if you get results from it. But I wouldn't treat it like a diagnostic value because no one has followed up any science on that disorder in the decades since it's been proposed. Kryptopyrroles are very similar to porphyrins, that LabCorp has a whole series of tests on. I would go to LabCorp's site, go to Test Menu and then search it for porphyrin, and you'll see a bunch of things that come up. Some of the concerns are relatively similar in terms of zinc and B6 that come up with those. But in my view, the pyroluria thing is to the extent it has merits probably has some relation to the porphyrin disorders and maybe is one. I'm not sure. But I would definitely, like if you're going to investigate the issue, I would investigate it with those. I can say that from the porphyrin disorders, some of them will cause various things to happen in the skin ranging from the skin turning brown when exposed to sun, to pain in response to sun exposure, to the skin turning red in response to the sun. Not a usual red, but a weird red. Some of them will cause red to brown discoloration of the urine, but some of them don't cause any colors because there's a whole category of porphyrin disorders that are all in the same pathway and some of them are sun sensitive, some aren't; some accumulate in the skin, some don't; some of them try to change color; some of them cause pain, some don't; you can't really go exclusively on those symptoms. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: How to manage blood levels of omega-3 and omega-6 fatty acids. I don't specifically want to look at the omega-3-to-omega-6 ratio. The AA/EPA ratio, I do not believe in wanting to get it low enough to prevent inflammation. I don't believe in using it that way. But I do believe that if it were too low, it could cause problems. I don't know what the cutoff would be. But if you're on the low end of normal, then I would think about cutting back your intake of EPA. But my main concern would be if you're in the low or even middle end of the normal range for either arachidonic acid or DHA, I think you want to increase your intake of those. Particularly if your intake is already high, look for the cause of low levels. Especially if both of them are low, that could be caused by inflammation or oxidative stress. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Can PEMT genetics cause fat malabsorption, mineral deficiencies, and oxalate problems? First of all, saponification of minerals, the point here is that if you have malabsorption of fat, the fatty acids are going to bind to any positively charged minerals in your diet. This has been particularly well studied in preterm infants where the poor absorption of fatty acids causes the fatty acids to bind to the calcium that have lower bioavailability. Yeah. If you surpass your ability to absorb the fat, the fatty acids can bind minerals and induce mineral deficiencies. I agree with this. PEMT polymorphism is a marker of poor synthesis of phosphatidylcholine. That will impair export of fat from the liver. Low phosphatidylcholine synthesis due to PEMT. I was thinking of it as a direct marker. It's not a direct marker, but it could theoretically impact. This is probably especially true if you have a low phosphatidylcholine intake. Probably eating phosphatidylcholine protects against this. But yeah, low phosphatidylcholine levels in the liver partly as an interaction between low activity in the PEMT enzyme and low intake of phosphatidylcholine from food could cause bile acid issues, which could in turn cause fat malabsorption. If you have fat malabsorption and you have enough digestion of the fat to release the free fatty acids from triglycerides, but you don't have enough absorption of those fatty acids, the fatty acids will bind calcium. They won't bind oxalate, they can't. Binding the calcium will lower the calcium absorption, and it will also prevent the calcium from binding oxalate. Calcium binding oxalate is what prevents oxalate absorption, so yes, I would think that would increase oxalate absorption. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Could an elevated BUN indicate protein malabsorption and low stomach acid? I get the Heidelberg test. That's the only accurate way to assess stomach acid. If you want to do something else, it would be better to use the kitchen techniques, like take half a teaspoon of baking soda and see how long you take to burp, or take HCl with your meal and keep adding capsules and see how many capsules you can take without reflux. That's probably both more accurate than using BUN. I find it almost certainly the case that a slightly high BUN would never be a useful marker of low stomach acid and would never be a good marker of poor protein digestion. If you want to know if you have poor protein digestion, measure the protein in your stool. Get a GI stool test that looks at what you're not absorbing. That's how you test that. The reason that this sounds nuts to me is maybe you are allowing the protein to ferment in your gut and generate urea from the microbes that you're absorbing, like maybe. But where does most of the urea come from that's in your blood? It comes from the urea cycle, which is how you get rid of ammonia. How do you get ammonia in your body that goes into the urea cycle? You digest protein into amino acids, you absorb the amino acids, and then you break them down so that you can either burn them for energy or turn them into glucose or turn them into certain neurotransmitters or whatever, and then you lose ammonia that you put into the urea cycle. Why wouldn't the urea be a marker of having good digestion? I'm not even sure that we could say it could be an equally useful test of good digestion and bad digestion of protein. I don't know if it's as good a marker of bad digestion of protein as it is of good digestion of protein. But even if it were just as good a marker of bad digestion of protein as it is of good digestion of protein, something that's an equally good marker of two opposites is not a good marker of anything. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Are bilirubin and uric acid useful markers of antioxidant defense and oxidative stress? What are better markers? I think intracellularly where most of antioxidant support is highly relevant, then they're not that big a deal. In the plasma, they can be a big deal. It's quite possible that uric acid is one of the most important antioxidants in plasma. But I would say it's highly debatable whether we put uric acid into the blood specifically to achieve that versus that happens to be an accidental sort of just incidental to making uric acid during the excretion of purines, which make up the building blocks of DNA and ATP and things like that. I think the best marker of oxidative stress in plasma is the cysteine to cystine ratio. Cysteine is the reduced form of the amino acid cysteine. Cystine is the oxidized form. There are good studies at a general population level showing that that is the major specific indicator of oxidative stress that takes place in the plasma. The glutathione couple, glutathione reduced versus oxidized, is probably the best marker in the blood of what's happening with oxidative stress intracellularly. Unfortunately, the only test that looks at this is HDRI. I feel very, very torn about whether we should be working with HDRI because I know a lot about measuring glutathione. I've had some clients who got their glutathione test. What you need to do to accurately measure glutathione to preserve the sample, according to my client who did the test, is not at all part of the instructions or process that they use, so I am very skeptical of using them. No one else offers the reduced to oxidized version of glutathione. So, what I would recommend to assess oxidative stress would be Genova's Oxidative Stress 2.0 panel. It does give you the cysteine to cystine ratio. I'll put a note to put a link to that in the show notes. I think that's the best marker. They do have glutathione on there, and they do have a bunch of other things that can be useful in assessing oxidative stress. I would use that. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Does it matter what form of B12 you take? Cyanocobalamin is cheap and there's not really any clear evidence that it's harmful, but I just don't like the idea that it is cobalamin bound to cyanide. It's not found in the food supply. Forming cyanocobalamin and peeing it out is actually one of the main ways you detoxify cyanide. Hydroxocobalamin is also relatively inexpensive. It's relatively easy to get as injections. It is not an end product of detoxification. It is found in very high concentrations in the food supply. The normal forms of vitamin B12 that you find in the diet from food are hydroxocobalamin and methylcobalamin in milk, and hydroxocobalamin and adenosylcobalamin in meat. Hydroxocobalamin is the most universal food form of cobalamin, and it is always a substantial part of the food supply. I'm pretty sure it's cheaper than methylcobalamin, so I would use intramuscular injections of hydroxocobalamin. Most B vitamins start their absorption in the stomach and then mostly absorb in the small intestine. In the case of B12, when you're dealing with food, you're absorbing it in the small intestine almost exclusively with intrinsic factor that's produced in your stomach. Start with a milligram of oral hydroxocobalamin. Test that against your serum B12. If it's not moving your serum B12, see if 2, 3, 4, 5, 6 milligrams do. Because if they do, then taking that every day is going to be probably easier. Well, I mean, it depends on what you like. But you're probably going to like taking oral B12 more than you're going to like getting intramuscular injections. I would see if raising the dose works first. I'd use oral hydroxocobalamin. Then if you have to use intramuscular, I will use hydroxocobalamin. I guess you just have to judge it against from a medical perspective they're always worried about compliance, because unlike the people who are showing up to this AMA, the general population has very low motivation compared to us. Injection is preferable from that standpoint because there are fewer things to do. Plus, you have an accountability buddy because someone's got to inject you. You get an accountability buddy to do something once a month versus you have the personal responsibility to do something every day. From a compliance perspective, it's vastly superior, the getting injected. But if you're already taking 15 supplements every morning, then it's probably way easier for you to just add megadose of B12 in with those oral supplements than to get intramuscular injection. I'd prefer it. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Is it useful to measure urine pH? The urine pH is telling you the acid burden that your body has been subjected to. It's telling you, you can make an inference about the compensations that your body has had to engage in. You can also make an inference about the limitations of your body in compensating for that because even your urine pH should be buffered. It's not the case that you put a little bit of acid in the urine and then boom your pH is going to go down. It's the case that your body has a whole bunch of systems to buffer even the urine pH as you excrete acids from your body. The system is, like in your blood, the tiniest, tiniest change in your pH is immediately going to set in motion a change in your breathing rate that is going to cause you to either increase or decrease the exhalation of carbon dioxide in order to adjust the pH of the blood. Then there's going to be a longer-term compensation where you're going to take some of those acids and pee them out. When you pee them out, your kidney is going to buffer those acids in the way of preserving the urine pH. If your urine pH goes down from 6.5 to 5.5, it tells you that your urine pH is like ten times more acidic, but it doesn't tell you that your blood is ten times more acidic. The critics of using urine pH will point that out. But what it does tell you is that your body has been subjected to a rather enormous acid burden, number one; and number two, that you're even starting to overwhelm your kidney's ability to buffer the urine and prevent the pH of the urine from changing. And so it does tell you about the stress put on the system. A high potassium intake would be the number one thing that would acutely affect it apart from taking the bicarbonate. By the way, always take bicarbonate on an empty stomach away from food. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Why AGEs and deficient insulin signaling are the main problem in diabetes. The reason that methylglyoxal, which I did my doctoral dissertation on, the reason that methylglyoxal, which is quantitatively the most important form of advanced glycation end products in diabetics, the reason that it is elevated is not because of hyperglycemia. It's because of deficient insulin signaling. That is for two reasons. One is that you can derive methylglyoxal from glycolysis. You can derive methylglyoxal from ketogenesis. You can derive methylglyoxal from protein, specifically from the amino acid threonine. Insulin prevents you from making methylglyoxal in the glycolytic pathway no matter how high the glucose level is. Insulin, what it does in glycolysis is at the step where the intermediates spill out to generate methylglyoxal, insulin stimulates that enzyme that sucks the intermediates down. Diabetes, you have lower expression of that enzyme, and you have greater spillover out of glycolysis into forming methylglyoxal. In untreated diabetes, you can have blood glucose that goes up five times normal. That will be a factor that is influencing you to make not just five, maybe ten or far more times methylglyoxal on glycolysis. But the reason the glucose is elevated is because of deficient insulin signaling. No matter how much glucose you have or don't have, once the glucose gets into the glycolytic pathway, insulin is protecting against methylglyoxal by clearing the glucose down. The role of methylglyoxal starts at the first instance of hyperglycemia to cause the development from an acute first ever instance of hyperglycemia through the pathway of developing diabetes. Then in diabetes, methylglyoxal is overwhelmingly responsible for causing the cardiovascular complications, the complications in the eyes, and the neurological complications of diabetes, cataracts, all of these things. And so I think it's a huge mistake to think that the spiking glucose is the thing going on rather than the deficient insulin signaling. Now, if you want to use a rule of thumb that is not individually tailored to you, then the answer is use the 140 limit. But you follow that up with, is there evidence to support this? No, I think the evidence says that this is a mediocre approximation of how to identify whether there's a problem. But a good way to try to identify whether you're having a problem with glucose spikes is the GlycoMark test. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Nutritional recommendations for MTR and MTRR polymorphisms. In the methylation cycle, I've talked a lot about MTHFR, which helps finalize the methyl group of methyfolate. But then folate has to donate that methyl group to vitamin B12 in order for vitamin B12 to donate it to homocysteine. In that process, that's how you clear homocysteine primarily in the fasting state rather than the fed state. It's also how you recycle homocysteine to methionine to use for methylation, again, primarily in the fasting state rather than the fed state. If your MTHFR is working fine, then the creatine is much less relevant, and the glycine really isn't that relevant. Glycine is still important for everyone, but it's not specifically relevant because of the genetic variations. With that said, I do think that because some tissues rely more on folate and B12 than they do on choline that there might be some tissues that would benefit from supplementing creatine, so you could play around with it. I supplement creatine, and I don't have any problems. I mean, there's no harm in trying out the creatine. In my view, there's no blanket recommendation for someone with MTRR polymorphisms. What I say is because in theory you will be bad at repairing B12 when your B12 gets very damaged, you should thoroughly look at your B12 status at least once. Then every time you enter a new health era, you should monitor your B12 status again. What I mean by health era is your health changes or your developmental stage changes in a way that could impact your health. So, change in health eras, and I'm making this term up, this is not a medical term, but the change in health eras means you get sick with a sickness you never had before. That's a change in your health era. Or you go through puberty. That's a change in your health era. You go through menopause. That's a change in your health era. Or you go on birth control. That's a change in your health era. Look, my MTRR, as I said before, looks terrible on paper. I measured everything I could think of about my B12 status, and everything looked fine. I'm not talking about just serum B12. I'm talking about all the functional markers too. They looked just fine. That just reinforced my belief and the observational data that these things are so common. If these things dramatically impacted your B12 status in a very negative way most of the time, not many people would have the polymorphisms. And yet, they're very common. Those are huge reductions in activity. They're very, very common. So, I think it's ridiculous to make a generalized nutritional protocol around either of those. MTR, it gives you a couple ideas you can experiment with. MTRR, be proactive about monitoring your B12 status. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Nutrition for children with ADHD. In adults 100 to 800 milligrams per day has been used in a couple studies showing effects in the brain. One of the things that's going wrong in ADHD is that the brain is not getting dopamine's signal that something is valuable enough to keep paying attention to it. I think the drugs that are used to treat ADHD are increasing the tonic level of dopamine in the frontal cortex, and they're increasing the tonic level of dopamine in the basal ganglia. In the frontal cortex, the increased dopamine is basically making more stable mental states. If you focus on something, you will hold on to that better. In the basal ganglia, increasing the tonic dopamine is making it harder for a new thing to grab your attention, which reinforces the fact that you are more focused. Anything that increases dopamine is going to be good. There's that. Should we just use the glycine to promote sleep, or should I also use it in the morning? I would say, ultimately, you have to judge it based on the results you get, but you should try it at other times during the day because one of the roles of glycine would be to provide the buffer against excess methylation. For dopamine to make you pay attention to something that has value, you must have GABA suppressing attention to everything else. Dopamine cannot be a meaningful signal of the value of placing attention on something unless you have adequate GABA to suppress your attention paid to everything else. Because if you're paying attention to your schoolwork while you are also paying attention to your video games and to the mosquito in the corner equally as much, then you're not actually paying attention to your schoolwork. So, I think that anything that would boost GABA would be helpful. So, yes to the glycine during the day. Yes, you do want to keep choline levels up. But remember that choline is a methyl donor. Choline is a double-edged sword here. First of all, the choline is needed for acetylcholine. When dopamine tells you to pay attention to something, once you're paying attention, you need acetylcholine to sustain your attention on that thing and get results. Dopamine is the signal that that thing has value to pay attention to. Acetylcholine is what you actually use to pay attention to it and get results. You do want to help his acetylcholine levels, but you have to remember that choline is a methyl donor and that the more choline you have, the more important it becomes that the glycine is kept high enough to buffer excess methylation. Otherwise, choline could act as a double-edged sword and potentially wind up reducing dopamine levels. The other thing that I would add is the GABA. Maybe start at 100 milligrams a day and work your way up to 800 and just be careful with the low dose. See what results you get. If it seems promising, try increasing the dose. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Here's what I'm doing about the coronavirus: chrismasterjohnphd.com/covid19 Here's my 41-page 92-reference guide, The Food and Supplement Guide for the Coronavirus: chrismasterjohnphd.com/coronavirus Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Nutrients important for neuroregeneration. Iron, phosphorus, and sulfate are very important for regenerating nerves. Magnesium. Acetylcholine is a major factor in regeneration of nerves, and so choline is important. If you were to use a supplement, alpha-GPC would be the ideal choline supplement to use because it's superior at generating acetylcholine. Vitamin A and zinc are very important for nerve regeneration. DHA, which is one of the omega-3 fatty acids that you find in fish is very important. Vitamin B6. Possibly GABA supplementation can help. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Advice for what to do after suffering a transient ischemic attack. A TIA, a transient ischemic attack, is like a mini stroke, but they all kind of fall into the same category where the development of plaque is a very significant part, is the major thing disposing you to having an event like that. Nutritionally, the major factors in blood pressure are potassium is the biggest one, the salt-to-potassium ratio, not eating too much. Some people are salt-sensitive, some aren't. But the major factor is really the salt-to-potassium ratio. Some of the other minerals like magnesium and calcium are important. But then stress and physical activity are huge in blood pressure as well. Assuming that's under control, the main nutritional factors that you want to pay attention to are things that get the blood lipids under control and then things that get the process of calcification and inflammation under control. The reason that the lipids are problematic is because they're getting damaged by free radicals and other damaging molecules, so things like vitamin C and E, glutathione, fruits and vegetables supplying polyphenols, all the minerals like zinc, copper, iron, manganese, selenium, all those things are important. Figuring out whatever the limiting factor is and managing the details is a really big project. There are some simple rules of thumb like getting regular exercise, provided that the doctor okays it. Obviously, with cardiovascular issues, you have to do that, but whatever is safe for him to engage in. If needed, meditation or stress reduction on the blood pressure. And then just cut the junk food out and include a well-balanced diet. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: When on a ketogenic diet, it is a problem if ketones are going up to 5 to 6 millimoles per liter? One of the popular ketogenic advocates was saying that if the ketones are getting above 3, then it's from not eating enough protein. I don't really see it that way. I think that protein will suppress ketogenesis, and so will carbs. Five to 6 millimoles per liter is what you see in therapeutic ketogenic diets. In terms of how you could bring the ketones down, more carbs or more protein are going to bring them down. Between the two of those, probably protein would be the most important thing to increase as a means of protection against lean mass loss and as a means of keeping neurotransmitters and all the other things that you do with protein healthy. But you could raise the carbs a little bit too. Because remember that your carb demand even on a ketogenic diet is definitely not down to 20 grams of carbs. That's not even feeding your brain on the ketogenic diet. If you have room to increase carbs, then I think would be great to get the carbs up to at least 30 and then maybe use protein going up to supply the rest of that. Then also pay attention to micronutrients. Do a dietary analysis. If there are certain nutrients that this person is not really getting in that more vegetables would help those micronutrients, then increase the vegetables and the carbs along with them for that purpose. But just on macros alone, I would say go up at least 10 grams on the carbs and go up to, if you can get there, a gram of protein per pound of body weight on the protein, and that will bring the ketones down. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Are there any solutions to getting nauseated from zinc supplements even at low doses and even when the zinc comes as oysters? With the zinc, my general recommendation is to take zinc on an empty stomach. The thing that is not controversial is that phytate is the principal inhibitor of zinc absorption. Phytate is found in whole grains, nuts, seeds, and legumes. I think there's a very broad agreement across the zinc research community that taking zinc not with a meal that contains whole grains, nuts, seeds, and legumes is going to lead to higher zinc absorption. Then there's some controversy. Does it matter whether the zinc is on an empty stomach compared to a phytate-free meal, which would be a meal that doesn't have any whole grains, nuts, seeds, and legumes? Because there's a gray area there, I say if you can, take it on an empty stomach. If you can't, take it with a phytate-free meal. Generally, it's the case that if someone takes 15 milligrams of zinc with a full glass of water, they are very unlikely to get nauseated from it. Whereas if almost anyone takes 50 milligrams of zinc with a full glass of water on an empty stomach, they're almost definitely going to get nauseated from it. I would get nauseated from it. Taking the low dose should allow you to take it on an empty stomach, but for some people, they do get nauseated even taking only 15 milligrams on an empty stomach. Well, you have two options. The ideal thing would be figure out the lowest amount of food that it takes to. If you eat the oyster at the end of a phytate-free meal, is it still making you sick? If so, I don't think that's the zinc. I think it's something else. And your digestive system might not be up to the task of eating oysters right now at this moment. But if at the end of a phytate-free meal if you can fit in one or two oysters and it doesn't make you nauseated at all, then I think that's great. Oysters are probably the ideal zinc supplement if you can get them in. A couple of oysters a day goes a long way to getting your zinc in. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Could low LDL hurt female fertility? I haven't seen evidence of it, but that would not surprise me at all given that cholesterol is what you make sex hormones from. If you see levels that low, I don't know that it's intrinsically a problem. You kind of want to start looking at what are the reasonable things you could expect to happen from that that affect female fertility? Fat-soluble vitamins could be relevant. Sex hormones could be relevant. I'd start looking at those things. I doubt that the LDL being that low itself in and of itself is going to be the thing that compromises fertility. This is the thing. Is the LDL low because of really good clearance from the blood, or is it low because of really low production? If it's low because of really low production, then you definitely have problems with fat-soluble vitamin transport. Because if the liver is not making lipoproteins as much, the fat-soluble vitamins are staying trapped in the liver and they're not getting to other tissues that need them. While there's no evidence for it, it makes perfect sense that dietary cholesterol would help that because dietary cholesterol is very helpful in Smith-Lemli-Opitz syndrome, where the exact same defect is 1,000X to produce a devastating result. It makes total sense that in someone who is a carrier for SLOS, Smith-Lemli-Opitz syndrome, who has defective cholesterol synthesis in their gonadal tissues and therefore has defective sex hormone synthesis, it makes total sense of eating cholesterol would help those people. So, I would try it. Egg yolks. That's what most people are going to eat for cholesterol. But this all hinges on the question of the LDL is low, so what? Is it because it's being cleared rapidly or because it's not entering the blood due to lack of synthesis? Whether that person is going to have infertility as a result of it and whether that's going to be helped by dietary cholesterol, it's all going to get a hinge on that. But the good news is for both people, it's probably completely harmless to eat some eggs. Eating eggs might just be the thing that helps. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Is it safe to take creatine when nursing?If you felt fatigued and you took the creatine and all of a sudden that started reversing, then you either felt fatigued because you had low creatine synthesis, or you felt fatigued because you had a methylation problem. Those aren't mutually exclusive. If you're not methylating well, the most sensitive thing that will happen is you'll synthesize less creatine. But I mean it could have gone beyond creatine. It could have been that you're synthesizing less creatine, and you're not regulating your dopamine properly and things like that. But certainly, you're addressing a methylation issue/a creatine deficiency issue. I don't know the exact cause and effect scenario that would lead to ovulation, but it makes sense that you ovulate. Think about the regulation of fertility, the whole thought process of the body's regulation of fertility. All of it comes down to energy. It comes down to the fact that when you get pregnant, you're investing -- I don't remember what the numbers are off the top of my head -- something like 50,000 kilocalories in the pregnancy. Then in lactation, you're investing another I think thousand kilocalories a day or something like that. The whole hypothalamic regulation of sex hormones and thyroid hormone is all regulated by leptin and insulin as signals of long-term and short-term energy status. Insulin and leptin are hormones. Endocrine hormones are between tissues. But what happens at the cellular level is I think it's very plausible that something that's happening at the cellular level and the recognition of what those hormones mean to communicate that energy is present, sufficient for fertility is going to be ATP dependent. If you're missing creatine, then you're going to have a drop in the power of the ATP signal and the recycling of the ATP. This is the basis for why creatine is used for muscular power, but it's also the basis for why creatine is used to use energy in producing stomach acid or to communicate or to transmit light and dark signals through your eye to your brain to make vision. All over the place, creatine is super important to the cellular utilization of energy. My guess is it's correcting a response inside the cell to the leptin and insulin. In terms of safety in breastfeeding, I don't think there's any evidence one way or another. It's probably safe because you could get this from meat, and there's no evidence of harm. But if you wanted to be hyper careful, I don't think you need to do this, but if you wanted to be like super, super careful, what I would do is divide the 5 grams over three or four meals evenly on the basis that there are very, very trace amounts of byproducts of high-dose creatine. Five grams will cause extraordinarily tiny amounts of toxins that appear in the urine. I mean, not toxins at the level that we're talking about, but I doubt it's a risk. But if you wanted to be hyper careful, divide the dose up evenly. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Can you explain plant polyphenols and hormesis? In brief, our detoxification system didn't evolve to handle the toxins of modern society. Modern society invents a new chemical. Our body knows it's a toxin, but it doesn't know it because we were exposed to it for millions of years. It knows it because it has similarity to other toxins. That similarity may be weaker or stronger depending on the toxin. Our bodies do evolve to be bad at detoxifying. They evolve to be good at detoxifying. Our system is not designed to get sick when we encounter toxins. It's designed to get healthy when we encounter toxins. The way that works is throughout most of our evolutionary history, the toxins we were exposed to were the toxins in plants. Most of them are polyphenols. Most of them are the things that we ascribe health benefits to. A lot of those health benefits come from the fact that these are the toxins that our bodies are designed to work with. Xenobiotic defense -- xenobiotic is something foreign -- this defense system is this giant umbrella system that in a very general level assesses the likelihood of how much energy should we invest in keeping that system running based on how much toxins are we exposed to and uses that metric to invest the energy in that entire machinery. We're not investing in getting rid of a specific toxin. We're just taking the collective toxin and investing in the collective detoxification machinery, the collective antioxidant glycation-defense machinery. Because fruit and vegetable polyphenols were the major toxins, our system is designed to be very highly responsive to them, to use them as that metric. Now, in the modern society, what do we do? We invented new toxins. By the way, the fruit and vegetable polyphenols, what happens if you just take a bunch of them and you dump them on cells? You kill the cells. What happens when we eat them? Ninety-nine percent of them don't get absorbed. Why? Because the intestinal cells have a detoxification pathway that's just like the liver's. I think where you cross the line is, what you don't want to do is isolate those things into a pill and megadose them. That's why people, when they ask me about sulforaphane and milk thistle, my view of that is that that's what you do when you can't eat a high volume of unrefined plant foods with five to nine fruits and vegetables. But what you don't want to do is say, "Well, if the bottle says one capsule milk thistle a day is good for me, then ten capsules of milk thistle on top of ten servings of fruits and vegetables is good for me." Then you're in the zone of who knows what that's doing to you. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: What to do when serum magnesium is high but RBC magnesium is low? The magnesium in the blood and the hair is high. When you say blood, I'm assuming this is serum or plasma because the RBC magnesium is low. I'm hoping that's not whole blood magnesium in which case it would be hard to separate from the RBC magnesium. But I mean even for whole blood, if the RBC magnesium is low and the blood magnesium is high, then the magnesium that's in the blood that's high is in the serum or plasma, not in the RBCs obviously. Clearly this means that you're deficient in magnesium transport. You're not deficient in magnesium. So, the last thing that you should do is start blasting high-dose magnesium at that. Because not only is it not going to help, but you basically have two or three times the risk of harm from supplementing high-dose magnesium, because the harm of high-dose magnesium comes when your serum levels go to double the upper limit of the reference range. If your serum level is high, and your RBC is low, and you start blasting. B6, even if it's adequate, maybe try 10 milligrams. Work your way slowly up to 100 milligrams of P5P. See if that helps. If it doesn't, you probably have a more serious issue with magnesium transport. You might have a rare genetic defect in a magnesium transporter. Off the top of my head, I'm not sure how to manage that. There's probably things you can't do. It might come down to just maximizing all the different possible ways that you can get magnesium into your system and cells. That might mean that you want a modest hypermagnesemia. In other words, you want your serum magnesium to be a little over the top of the upper reference range in order to try to drive magnesium into the red blood cells. But you still need to measure it regularly so that you know that you're not anywhere near twice the top of the upper reference range. Then just do what you can to maximize the other factors. Insulin, salt, and B6 is what I think there. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Is there a potential for adverse effects of 5-10 mg of folate for heterozygous MTHFR? Is there a potential? Yeah. The tolerable upper intake level for folate was set at 1 milligram on the basis that there are rare hypersensitivity syndromes that have caused reactions to 1 milligram or higher. On the basis that in numerous case reports, supplementation of more folate than that has been the factor that appears to precipitate the neurological degeneration in B12 deficient patients. It seems like if you're B12-deficient and you add a megadose of folate, there might be something causal about adding the folate precipitating the B12 deficiency. That makes sense. Folate and B12 participate together in methylation. The neurological degeneration specific to B12 deficiency is probably mostly due to the non-methylation functions of B12. That's why it doesn't happen in folate deficiency. If you add folate, you're going to probably redirect some of the B12 into the methylation pathway, rob it from the other pathway, which is metabolizing methylmalonic acid into the citric acid cycle. You do that and you provoke the specific neurological degeneration of B12 deficiency.The flipside of this is someone could say, well, there's no evidence that outside of these rare things that 50 milligrams of folate causes harm. That's true. There isn't a well-characterized harm from it. But I still think that it's stupid, it's stupid. Why would someone with a heterozygous MTHFR SNP need 10 milligrams of folic acid or methylfolate? That makes no sense biochemically at all. It makes no sense. First of all, are they compound heterozygous or are they just heterozygous for the SNP? I don't know if it's harmful, but it's irrational to take high-dose methylfolate for this purpose or high-dose folic acid is irrational. It's on the basis that it's not effective. It is five to ten times the Institute of Medicine's tolerable upper intake level. It's not that I know it will cause harm. It's just that it's way into the territory of what has the possibility of harm in some people. Why for no benefit would you take yourself deep into the territory of possible harm? This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Is folate unstable in frozen liver or just in frozen veggies? The answer is folate is stable in frozen liver. It is not stable in frozen greens. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: How much vitamin C should I take with collagen? There's no evidence that you need to take vitamin C with collagen. There is a study by Keith Baar, who showed that 15 grams of gelatin, not collagen, but I suspect the collagen is exactly the same, 15 grams of gelatin but not 5 grams, the dose is important, with 50 milligrams of vitamin C taken before exercise improved collagen synthesis in the tendons. They included 50 milligrams of vitamin C because it's made for collagen synthesis, but they don't show that you needed the vitamin C. They just had the vitamin C in there. I don't know if it even matters in that context whether you need the vitamin C. I also have no reason to think that you need 50 milligrams instead of 10 or that 100 milligrams wouldn't work better because they didn't test the different doses. They tested the different doses of gelatin. I see no reason to think a high dose of collagen is any different in this respect. Let's assume that it's the same. What that means that I'm very confident that you need 15 grams instead of 5 grams when you take it before exercise to increase synthesis of collagen in tendons if that's what you care about. I have no confidence about how much vitamin C you need if you need any. But if you want to do what they did, then I do feel confident that 50 milligrams is enough to get some effect. I just don't know if it's enough to get maximal effect and I don't know if it's necessary at all or in that dose to get that effect. If it's for joint health and if it's taken before exercise, the timing is important because what you're trying to do is leverage the exercise to get more blood flow of the nutrients to the joints. That's why the timing matters. In that case, you take the vitamin C with the collagen, 50 milligrams is the dose we know works. We don't know if it's necessary, and we don't know if it's optimal. We just know that it works. If you're not taking it for joint health and you're not taking it specifically before exercise, you still need vitamin C. But the timing doesn't matter and pairing it to the collagen doesn't matter. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Are liver capsules as good as eating liver? Liver pills are mainly for people who are not going to eat liver. That's the first thing. The second thing is, there are advantages to taking the dosing schedule of a little bit of liver every day. Probably the ideal thing would be to have 10 to 20 grams of fresh liver every day. But the number of people who are going to do that are even smaller than the number of people who are going to eat the fresh liver. What the liver pills do is, number one, they give people who don't eat liver that frequently to get the nutrients that have absorption caps that are better off gotten in small doses at a time to get those every day. It gives people who are not going to eat liver at all a way to get liver in. I don't know. I mean, it's a tradeoff. Probably almost no one is going to eat 10 to 20 grams of liver every day. If you don't, are you better off taking the capsules or are you better off taking liver once a week? You're probably better off taking half and half, like take three capsules every day and still eat liver once a week. It's probably the best thing to do in that case. I don't recommend anyone who would otherwise eat liver stop eating liver and take the capsules, but I do recommend the people who won't eat liver take the capsules. I think it's a nice thing to do. If you eat liver but take the capsules anyway, then take that in a lower dose because you eat liver. Like I said, eat one serving of liver once a week or twice a month and take two, three, or four of the capsules instead of six; two, three or four capsules every day. I think that's a happy medium that can have best approximates the best thing which is the 10 to 20 grams of liver a day. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Should I take 3 grams of leucine per meal? Leucine is metabolized into a leucine metabolite that is the signal of protein synthesis. It's the thing that tells your muscles whether they should be synthesizing protein. But do you synthesize more protein when you upregulate all the factors of muscle protein synthesis? Well, that is entirely dependent on the amount of amino acids you have supplied. Think about it this way. Why is leucine used as the marker to determine how much muscle protein to make? Because usually when you get leucine, it's with high-quality protein that has all the other amino acids that you need to make muscle protein. Now, the question is, is meat better than isolated protein? The research is pointing in the direction that at least some whole foods are just better than protein supplements, number one. Perhaps as a general principle, perhaps whole protein foods are better than protein supplements, number two. Number three, taking leucine or the leucine metabolite that regulates muscle protein synthesis is not going to be better than getting whole proteins even from protein supplements when you get enough protein to provide that leucine because the leucine and its metabolite don't actually achieve peak muscle protein synthesis unless you supply the protein with it. If you supply the protein with it, you do get the leucine. There probably are questions that can still be worked out about this, but it's probably going to wind up being that it's a waste of time to take the leucine if you're getting enough protein, and it's stupid to take the leucine and not get enough protein. You should just eat a lot of protein is where I think this is going. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: What are your thoughts on root canals? Before Weston Price embarked on his journeys that led to the publication of Nutrition and Physical Degeneration, which is an epic pioneering work in nutritional anthropology, before he did that, he spent 25 years as the first research director for what became the American Dental Association, researching in laboratory science and clinical science what were the causes of tooth decay and the consequences of tooth decay. Price's argument was that no matter what you do to get the infection out of the main areas of the teeth, you are never going to get it out of the nooks and crannies of the dental tubules. If you basically try to get rid of the infection and then you stuff something in there and make sure it never comes out, you create a hypoxic environment that basically causes whatever is in there to mutate in worse possible form. George Meinig wrote a book called Root Canal Cover-Up. He was a root canal guy, an endodontist. Now, the endodontists say that Price's work was discredited a long time ago and that this is complete BS. Now, the problem is I have no idea to what degree modern science has adjusted to this. Now, I can't even ask Meinig to what degree has the evolution of endodontal techniques since you wrote the book, to what degree had they changed how we should view this, because he's not alive anymore, and I don't know anyone who can fill his shoes. Look, if you want a personal story on how conflicted I feel about this, I literally have two root canals in the same teeth on each side of my mouth that were the legacy of my veganism. My suspicion is I wish I could give you a black and white answer. I know that it's not that useful to have an answer that's just nothing but gray zones. But I'm very skeptical of how good root canals are. I'm not so terrified that I'm highly motivated to get the other one taken out even though it probably is the last thing in my life that I should do more research on what to do about. I'm sorry, I can't give you a better answer than that. All I can say is yes, it is justified to be worried about the risks of root canals. I can say this totally unambiguously. What you should absolutely definitely not ever do is make your decisions about something that has any potential to be a root canal situation without a dentist. The whole point of Price's work was they're serious from whole body health. Price was a pioneer in so many things. This is another one. Now, there's increasing evidence that inflammation in your mouth and decay in your mouth is tied to other diseases. Like periodontitis is tied to heart disease for example. Price was the pioneer of saying that the infections in your mouth are causing other diseases in the rest of your body. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: What does it mean when histamine intolerance and blood sugar dysregulation occur together? Well, if his blood sugar is no longer as stable and he has histamine intolerance, then that drug probably interferes with vitamin B6 metabolism. Let me try to take one minute to see if I can find quick information on this. I can't. I can't find it quickly. My instinct is to say that the drug is affecting vitamin B6 metabolism on the basis that 80% of the vitamin B6 in the body is used for glycogen metabolism in liver, which is the thing that stabilizes your blood sugar between meals. If your blood sugar is not stable between meals any longer, then yeah, it could be a hormonal thing. What it really probably means is that there's something wrong with the liver's ability to store glycogen or to access the glycogen when it's stored because your blood sugar is stabilized between meals exclusively by the liver's glycogen metabolism. How does that relate to histamine intolerance? They're both caused by B6 deficiency. That's my take. I'd measure his blood levels of pyridoxal 5'-phosphate. Off the top my head, I believe LabCorp has a test for that. It would be helpful to look at his excretion of xanthurenate, kynurenate, and quinolinate in organic acids test. The Genova ION has all three of those. I don't think the other one is available to have all three. But every urinary organic acids test has some of those. I would go from there. I mean, if you want to save money, just trial a pyridoxal 5'-phosphate, which is the active form of B6. Trial a supplement of that to see if it helps. I would do that at, maybe start with 10 milligrams, but feel free to work up slowly over a few weeks to 100 milligrams. If a few weeks at 100 milligrams doesn't treat that and he's off the drug, then there's something else going on and I don't know what it is. But that would definitely be first line thinking for me. Thank you, Jennifer, for your question. I'm glad that was helpful. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: If PTH is mid-normal, do I need a calcium supplement? I'm assuming that by midrange you mean it's 30. If you mean it's 40, then no, you're deficient or you're probably deficient. You need to test how you respond. But what I would say is, it would still be good for you to try increasing that and see if the PTH goes down anymore. Because my baseline for where I suspect that someone's PTH is maximally suppressed is 30. But the evidence that it's maximally suppressed is that it doesn't get suppressed by more calcium and vitamin D. If it goes down in response to calcium and vitamin D, then it wasn't maximally suppressed. Where you want to be is not 30 to 20. It's the point of maximal suppression. Then the final thing is magnesium deficiency can compromise your ability to make PTH. I don't think that the average person in our society is deficient enough in magnesium for that to be relevant on the basis that population-wide most people have too much PTH. That contributes osteopenia and osteoporosis. But the big caveat here is if you are magnesium-deficient, then that might invalidate most of what I said if you're deficient enough to affect PTH. If your PTH is around 30 and not higher than that, you're probably fine. But it's good to know your magnesium status because if it's really bad, that could change that interpretation. It's also good to know if adding more calcium suppresses your PTH further, because if it does, that's probably calcium that you need. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: What to do about sky-high pyroglutamate? Pyroglutamate, its other name is 5-oxoproline. It is something that is primarily produced when you are synthesizing glutathione, but you do not have enough of the second step in glutathione synthesis to keep up with the first step. Maybe you need more glycine, but your glycine isn't low enough to cause orders of magnitude higher pyroglutamate. It's almost certainly the case that you have a glutathione synthetase deficiency, unless you have extraordinary levels of oxidative stress. I think that would be easy to test for because I just can't imagine that your glutathione levels -- I guess it's not that easy to test for because if you have a glutathione synthetase defect, you're going to have bad glutathione levels. If you have a tremendous amount of oxidative stress, you're also going to have low glutathione levels. If you have low glutathione levels, that's going to cause a tremendous amount of oxidative stress. I think if it's not a glutathione synthetase defect, then it becomes a lot harder to figure out what it is because it probably means you have massive oxidative stress from somewhere and there's a lot of things that could cause that. That would be a potential Pandora's box of questions that would come out of that. But definitely the first step would be to look at glutathione synthetase. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: In hemochromatosis, why would ferritin be low but transferrin saturation high? Ferritin is your long-term iron storage. Transferrin is your short-term iron storage. The problem with hemochromatosis is that usually in a normal functioning system, there is a hormonal regulatory system that prevents you from absorbing iron from food when you have enough iron that when you have too much iron, shuttle the iron into ferritin which is protective both against pathogens eating the iron to grow and against oxidative stress, which free iron causes, which if you don't know the details about can be thought of as wear and tear on your tissues over time. In hemochromatosis, normally the way you judge how much iron you have is in the circulating transferrin pool, which is your short-term storage. How full is it? The defect in hemochromatosis is that when the short-term storage, transferrin, starts getting fuller than usual, you don't notice it, so you don't stop absorbing iron from food that makes the transferrin saturation go up even further. But you don't shuttle the iron into ferritin. That makes ferritin lower. What people get confused by is that historically, we have only paid attention to hemochromatosis when it's too late, when the person has been suffering for it from 30 or 40 years and they need organ transplants. What happens at that point is that the ferritin is very, very high. Why is the ferritin high? Not because you had too much iron. The person without hemochromatosis has the ferritin go up when they have too much iron. The defect in hemochromatosis is that you do not stop absorbing from food when you have enough, and you do not put the iron into ferritin when you have too much. The reason that ferritin is high in someone who's had hemochromatosis for 30 or 40 years is not because they have too much iron. It is because they have oxidative stress and damage caused by that iron. Oxidative stress and damage cause ferritin to go up no matter how much iron you have. So does infection, no matter how much iron you have. Essentially, what you have is ferritin is not the fireman that he should be to put out the fire as it starts, and the smoke detectors go off. Ferritin hemochromatosis is the cleanup crew who got to the fire after the house burned down. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Does folic acid act differently in the body than natural folate? | Masterjohn Q&A Files #68They don't really. Everything that is said bad about folic acid is sort of true to an extent but has been completely exaggerated in some circles. What happens is you have an enzyme called dihydrofolate reductase, or DHFR. Its purpose is not to metabolize synthetic folic acid obviously because that folic acid molecule doesn't exist in the food supply. Its normal purpose is that every time that you use folate to participate in processes outside of methylation, such as DNA synthesis, you wind up producing dihydrofolate as a byproduct. DHFR recycles that and turns it into tetrahydrofolate, or THF. Tetrahydrofolate is what has the methyl group added to make methylfolate. The question is, does that synthetic folic acid, we call that unmetabolized folic acid, does that cause harm? There are scientific hypotheses that it might, and it might, but there's no conclusive evidence of that. That's one side of the argument against synthetic folic acid. The other side of the argument is now that you are giving the DHFR enzyme more work, that means that might be detracting from the work that it has in recycling dihydrofolate that came out of the DNA synthesis reactions to make tetrahydrofolate. People think that they just cut out white flour and therefore they're better off. No. You cut out white flour, now you need to do more work to make sure that you are actually getting your nutrients from whole foods because if you were eating six pieces of white toast that you didn't have to worry about getting nutrients from whole foods and now you do. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Can frozen vegetables be trusted for folate? You absolutely cannot trust frozen vegetables as a source of folate ever. That's because folate is extremely unstable in the freezer, and you have no idea how old the vegetables are. If they were fresh-frozen yesterday, they'd probably have plenty of folate. But if they were fresh-frozen three months ago, they may seem completely fresh and yet they don't have any folate in them. I'm not a fan of frozen vegetables mainly on the folate issue, on the basis that many people believe they are getting folate from their vegetables. If they're eating frozen vegetables, they may not be. I'm very worried that there are a lot of people out there who believe that they are doing something good by cutting out refined flour from their diet and starting to eat lots of vegetables. But when they come as frozen vegetables, you may be cutting out a lot of folate from the form of synthetic folic acid added to the enriched flour that you had been eating and cut out of your diet and then not getting anything from the frozen vegetables, and that's a recipe for folate deficiency. There are a lot of people out there who think folic acid is some kind of toxin. It's not a toxin. It's effective at treating folate deficiency. It is effective at preventing neural tube defects. That's why it's added to flour. It is not the ideal form of folate. There's no question about that. But this is like calcium. People are saying that calcium supplements are bad. Well, not as bad as not getting any calcium. It's the same thing with folic acid. Folic acid is not the ideal form of folate, but it's a lot better than a folate deficiency. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: How much spinach, broccoli, and kale is too much? Cruciferous vegetables have an issue with potential goitrogens. At serving sizes like this, the only issue with cruciferous vegetables is that they increase your iodine requirement. In theory, if you are juicing cruciferous vegetables to have like ten servings a day, in theory, you might get to the point where you cannot overcome the goitrogenic effect with iodine. That is based entirely on animal experiments that were done a long time ago, and we have no human data on where you cross that threshold. But in this case, I think two or three servings of cruciferous vegetables basically just means you need to pay a little bit more attention to your iodine status. In particular, you want to make sure that you're eating some seafood. If you're eating some seaweed in your diet, you're getting plenty of iodine in most cases. If you're not sure if you're getting enough iodine, then I would say 200 to 400 micrograms of iodine from a kelp powder-based supplement would be fine. Also, as a seasoning, you can get Maine Coast Sea Seasonings where you can just sprinkle seaweed onto your dishes as a flavor. It's like a salt shaker so it's really easy to use. Using that if you don't mind the taste is a great way to get iodine. I think that's really only the main concern there. The spinach is not a cruciferous vegetable, so it's not really contributing to this problem. It is high in oxalates and so it has its own problem. As long as you're getting calcium with the oxalate, for most people, there are exceptions to this. But if you don't personally have an oxalate issue, meaning a high risk of kidney stones driven by high oxalate levels in your urine or potentially behavioral issues in children some people are tying to oxalates. But if you don't have a specific issue with that, then I think really the only issue with oxalate is you want to make sure that you're consuming calcium in the meal that you're getting it in. The spinach has calcium, but it's only about 5% bioavailable so you should basically discount the calcium in the spinach. The kale and broccoli have bioavailable calcium. If you're mixing them together, that's probably a great way to do that, but you might not be hitting 300 milligrams of calcium in a meal. I think if you have a lot of oxalate in a meal, you probably really want to make sure you hit 300 milligrams of calcium in that meal. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Certainly, the fat-soluble vitamins, vitamins A and D, both important. Lauric acid as a fat. Coconut oil might be a good fat choice for the fat in your diet. Monolaurin would be a very good choice for a supplement. Lauricidin is the best monolaurin to take, 3 to 10 grams a day. Be careful of your bowel tolerance, spread it out among your meals, and cut back if it starts to loosen your stool. Elderberry, which has mostly been studied in the context of flu, that probably has good antiviral properties. Garlic. Garlic appears to require very high doses if you're just taking a garlic extract. If you're taking stabilized allicin, 180 micrograms a day is good. But you could raise the question what if you're missing on some of the other important compounds in the garlic. I'll debate with some of my friends about that, but what's really been tested is 180 micrograms of stabilized allicin. Then zinc for sure in the immune response is super important. Then you get back to nutrient density. Although I'd give special importance to vitamins A and D, arachidonic acid just mentioned, zinc and copper, both, and then those supplements. If you're missing any one particular nutrient, then you're going to wind up with a specific vulnerability that will persist until you fix that one nutrient. Thanks, anonymous. This Q&A can also be found as part of a much longer episode, here: https://themasterpass.chrismasterjohnphd.com/products/mastering-nutrition/categories/2811841/posts/9361575 Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Can you give any suggestions for increasing delta-6 desaturase activity? There's a bunch of nutrients involved in that, so many that you basically just need to do a comprehensive nutritional screening for whether something is missing there. You might just have low activity by genetics. It's probably not worth solving that problem. The big governor though is if you have if you have insulin resistance or you have low insulin levels from chronic carbohydrate restriction, that might increase it. But you also look at your inflammation because you might have some of the higher fatty acids being depleted from inflammation or oxidative stress. I mean, more nutrient-dense diet across the board, more carbohydrate, if that doesn't do it, then just maybe take a supplement or increase the liver and egg yolks to the point where the arachidonic acid is normal. Measure your CRP. If that's high, address inflammation. In the Testing Nutritional Status: The Ultimate Cheat Sheet, I have a big section on oxidative stress. I go through that testing. A starting point might be Genova's Oxidative Stress 2.0 blood panel. But if inflammation and oxidative stress are the things, work on those. If those aren't issues, then more nutrient density across the board, fix any nutrient deficiencies you find, increase carbohydrate if you're on low-carb. If none of those things work, then just increase your arachidonic acid level in your diet. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: What are the pros and cons of boosting sulforaphane? Sulforaphane, the nice thing is it promotes detoxification. The bad thing is it raises the need for iodine. I don't know what ratio to take, but you definitely want to make sure that you're getting some kind of iodine into your diet, whether it's through like 200 micrograms of iodine from a kelp powder supplement or you experiment with milligram amounts from a broken up Iodoral tab or whatever. Because I don't know the dose, I'm just going to say work slowly and work your way up. Certainly, if you have any signs of hypothyroidism or you have any brain fog, increase the iodine or decrease the sulforaphane would be my opinion. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Is it true that we can't absorb more than 1.5 grams of creatine at one time? I don't think that's true. From what I looked at, it looked like the absorption of creatine was really, really good. I don't know if someone was arguing maybe that we don't retain more than that. But I think the retention of your muscles is going to be best with creatine if you take it post-workout and if you take it with carbohydrate to stimulate insulin. But on the whole, I think that the absorption and retention is good enough that it's more a matter of how fast will you get to peak muscular creatine than it is about where you get in the long-term. Maybe if you follow all the best procedures to absorb and retain creatine, you'll get to the 30% increase in muscular creatine in two weeks taking 5 grams a day instead of four weeks. Maybe someone who doesn't follow any best practices takes six weeks. But ten weeks later, you're probably going to be at peak effect if you just take 5 grams of creatine at a time without paying attention to all the details around absorption. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: NMN vs. NR: What's better? And is TMG necessary? Yeah. There are no human studies looking at NMN and how it's metabolized. There are studies of NR. No one has showed any positive benefits of supplementing NR in humans yet, but they haven't really done any long-term studies or looked at many things, and they really haven't looked at anything that I would really want to see for NR. They've looked at things like glucose and lipids and other metrics of metabolic health doesn't really do anything for that. This is what I would say. My strong suspicion is that NMN is not absorbed intact. It's broken down into NR and it's absorbed intact as NR, while NR is just absorbed intact in NR. I believe that both of those supplements are going to lead to NR getting into the liver. I mean, I would use NR because there's more data on NR, and I wouldn't use NMN because there isn't any data on it. But it probably makes no difference at all because they're probably both absorbed as NR. Maybe if your digestion is weaker, you're going to do better within NR than NMN because you probably almost certainly are not absorbing NMN intact. If you're not digesting it, then you're absorbing less of it. But probably for most people, it makes no difference. I believe that both of these are going to generate NAD levels in the liver much more effectively than nicotinic acid or niacinamide would, the two common niacin supplements that are available on the market now and have been taken for ages. I think it will be better at boosting NAD levels in the liver. I think that will allow the liver to nourish many other tissues in the body to get a better NAD response in those tissues. My suspicion is that this is going to have a positive effect for anti-aging, for cellular repair. I think it's probably going to have a lot of promise for mental effects in the brain where there's high NAD turnover for neurotransmitter release. I think it's going to have probably really good effects in the gut where there's high NAD turnover because the gut faces so much damage by just being forced to deal with everything that you put into your body, unlike everything after the gut, after absorption, which has really high quality control. I think it's going to be great for skin issues. I think that in order to get the best NAD response and to tax the methylation system the least, you want to take a smaller dose with every meal rather than taking a higher dose once. I would take like 150 milligrams max at a meal. If you're going to take 450 milligrams, I'd take 150 at each of three meals. If you want to take less than that, you either use the powder or empty half of it out in a capsule. Like take half the capsule, empty it out into your mouth with a meal, 150-milligram capsule to do that. It will give you 75 milligrams. Take that three times a day. Then there's no good test to really see whether it's doing anything for you. You really have to judge it by your response. Are you getting tangible benefits from it? If so, then I think it's fine to keep it up. But yeah, I would take 100 milligrams of TMG for every 200 milligrams of nicotinamide riboside or nicotinamide mononucleotide. Personally, I wouldn't use the NMN and use the NR because there's more data on it. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: What to do about cataracts. Carl Rayner says, "Cataract in one eye becoming noticeable. This eye had a posterior detachment about 11 years ago, which is basically healed. I've been on a low-carb diet for over 40 years. Eat raw cream cheese, eggs, meat and liver. In the past few years, adding fasting and more keto diet. Saw your thoughts about glutathione on the cheat sheet and interview with Wendy Myers. Am I on the right track and what else could I do? Grain intolerant. What testing beyond normal tests might be helpful?" I believe that cataracts in the eye are largely driven by the glycation of lens proteins. The glycation of lens proteins is largely driven by methylglyoxal, which I did my doctoral dissertation on. In direct contradiction to much of the low-carbohydrate literature, glycation is not all driven by carbs. Methylglyoxal is quantitatively the most important source of advanced glycation end products in the body. Methylglyoxal can be derived from glucose, or it can be derived from ketones, or it can be derived from protein. No one has ever done a very good study to determine whether you have more methylglyoxal on a ketogenic diet versus a high-carb diet. But there was one poorly designed study where they took a small handful of people. They said, "Here's the Atkins diet, new diet," Or what is it called? Atkins New Diet Revolution or whatever that book was called. They said, "Here, read this, go forth and do it." They went home, presumably they read the book or part of it, and they tried to do it. They came back, they lost weight, they had elevated ketones and guess what? They also had significantly higher methylglyoxal. Also, everything in the pathway that leads from ketones to methylglyoxal was elevated. I would say the data were very strong that in those people, they had higher levels of methylglyoxal because they had higher ketone levels that were generating it. They went on the Atkins diet, and they worsened their glycation risk by making a lot more of the thing that causes most advanced glycation end products and the thing that is probably overwhelmingly driving cataracts. But they didn't show any health consequences, and they certainly didn't measure cataracts in that study because that wasn't the point of it. They left more questions than answers. For example, what if they had a control group that lost the same amount of weight on a high-carb diet? My suspicion is that methylglyoxal would have gone up during weight loss but just not as much. I also think that if those people stabilized their new weight and then they worked carbs back into their diet, their methylglyoxal would go back down. In fact, I have a consulting client who developed cataracts that corresponded very well with when he started intermittent fasting. He did have poor glutathione status. We were able to improve his glutathione status, but the cataracts didn't go away. Todd Becker asks, "How do you test methylglyoxal levels?" You don't. You become a guinea pig in a lab because doing a study on it. That's about it. Look, I'm not against keto and I'm not against intermittent fasting. But if you're specifically talking about dealing with cataracts, you're probably not going to get the cataract to go away, but you probably can stop them from getting worse and stop them from forming. I think intermittent fasting and keto is probably going in the wrong direction. One thing that I do think, I don't think you're going to measure your methylglyoxal levels, but I think you should test your glutathione levels because glutathione is what detoxifies methylglyoxal. If you listen to my riboflavin podcast, we talked about cataracts being a sign of riboflavin deficiency and also being one of the things that's being investigated for whether riboflavin supplementation can help it. Why does riboflavin supplementation help that? For the exact same reason as when I went on that big, longwinded answer about glucose-6-phosphate dehydrogenase deficiency at the beginning, the riboflavin is there to boost glutathione recycling. I think the whole story, all these pieces knit together to a very, very, very nice story, clean story saying what you want in your eye to avoid cataracts from forming and getting worse, forming in the first place and getting worse, is you want low levels of methylglyoxal in your lenses. How do you get that? You have very good glutathione status. The keto thing is a maybe. There's no maybe that maybe keto makes that better, but there's a maybe that maybe keto makes that worse. You can't test the glutathione levels in your lens proteins, but you can test the glutathione levels in your blood. I would use the cheat sheet in a very targeted way for everything that's relevant to your glutathione status. I would follow the recommendations in there about how to boost your glutathione status. I would use your blood levels of glutathione as a metric. Rather than getting them in the normal range, I would try to get them as high

Question: What can be done nutritionally to specifically improve antiviral immunity? Certainly, the fat-soluble vitamins, vitamins A and D, both important. Lauric acid as a fat. Coconut oil might be a good fat choice for the fat in your diet. Monolaurin would be a very good choice for a supplement. Lauricidin is the best monolaurin to take, 3 to 10 grams a day. Be careful of your bowel tolerance, spread it out among your meals, and cut back if it starts to loosen your stool. Elderberry, which has mostly been studied in the context of flu, that probably has good antiviral properties. Garlic. Garlic appears to require very high doses if you're just taking a garlic extract. If you're taking stabilized allicin, 180 micrograms a day is good. But you could raise the question what if you're missing on some of the other important compounds in the garlic. I'll debate with some of my friends about that, but what's really been tested is 180 micrograms of stabilized allicin. Then zinc for sure in the immune response is super important. Then you get back to nutrient density. Although I'd give special importance to vitamins A and D, arachidonic acid just mentioned, zinc and copper, both, and then those supplements. If you're missing any one particular nutrient, then you're going to wind up with a specific vulnerability that will persist until you fix that one nutrient. Thanks, anonymous. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: If free T3 looks good, why is TSH still a little high? Why hasn't the T3 brought it down enough? Your thyroid gland makes thyroid hormone. Thyroid hormone increases your metabolic rate and does a lot of related things. Your hypothalamus is governing that by controlling your pituitary, the master endocrine gland, and its secretion of TSH, which is what controls the thyroid gland and makes it make more thyroid hormone. The way that the feedback occurs is that the circulating T4 is converted to T3 inside the cells of the pituitary. That is what suppresses the production of TSH, which is basically the pituitary monitoring the thyroid hormone levels to know whether the thyroid has done its job. If the pituitary, the master endocrine gland, decides that the thyroid has done its job, it takes down TSH, the signal to make more thyroid hormone. You really are not looking at whether the free T3 is suppressing the TSH. Ninety percent of that suppression comes from circulating T4 that's converted to T3 inside the pituitary gland. You really are looking at whether the T4 is on the high end of normal or not. If your reverse T3 is on the higher end of normal, then that explains it. You basically have your brain telling your thyroid gland that it needs more thyroid hormone, but you have much of the rest of your body deciding that it's not in the position to carry out the effects on the metabolic rate that the thyroid hormone is demanding. It's converting the thyroid hormone into reverse T3, which is basically a thyroid antagonist. If your reverse T3 is high, then I think you want to look at things like calorie intake, carb intake, and stress levels because I think those are the main things that might make your body want to resist the signal of thyroid hormone by making the reverse T3. If the reverse T3 is good, meaning it's pretty low, then I think that means that there is something either in your brain, specifically in the hypothalamus or in the pituitary or somewhere in the combination where they're just deciding that your body needs more thyroid hormone than you have. My suspicion is that that's going to relate to how sensitive your cells are to the thyroid hormone, if your cells are somewhat resistant. Remember in the last AMA, this got brought up, and I talked about zinc deficiency and high free fatty acids being the primary things that are going to reduce sensitivity to thyroid hormone or cellular uptake. There are some indications that high free fatty acids might also decrease cellular uptake, but not much is known about what governs cellular uptake. In fact, there are some genetic variations in cellular uptake. If the thyroid hormone levels are high in your blood because they're not getting into the cells, then that could easily explain everything. It's just that your problem seems pretty moderate because you're not saying that your thyroid hormones are sky high and your TSH is sky high. You're just saying everything is a little on the high side of normal. It sounds like there's not a big problem, but that something somewhere your body is determining that you need a little bit more thyroid hormone. If you can address zinc, free fatty acids, and I would address zinc and free fatty acids as the top things, unless the reverse T3 is high, target carbs, calories, and stress. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: What food supplements and training programs are good for developing muscle mass? Overwhelmingly, what matters for muscle mass is working out, eating enough protein, and eating enough calories. You want to try and hit 10-20 sets per muscle group per week with eat set hitting within 80% of failure. So, if your doing a set of 8 reps but you could have done 20 reps with your chosen weight, that doesn't count. You would want to pick a weight that you can lift no more than 10 times. Ideally, you'll do some sets in the 5-rep range, 10-rep range, and 15-rep range. For protein, you probably want to be up around 1 gram per pound of body weight or per pound of target body weight. Then calories, you do need a caloric excess, but you don't want to get fat. If you know how many calories you need to be weight-stable, I recommend titrating the calories up 100 calories a day and then track your progress if you are gaining waist circumference. I know this is a little bit harder when you're a woman because you're going to have more fluctuations in water weight, but in terms of simple things to do to track your progress, waist circumference is valuable, and looking in the mirror is valuable. If you can get an actual Bod Pod or DEXA scan, then that would give you more reliable information. There's a device called Skulpt. It's bioimpedance, I believe, but it's taking it at many different points where you take so much data that it actually becomes pretty accurate, but it's very time-consuming. Anyway, take your choice of what you're going to use to track your progress. If you're not gaining any fat, you can very slowly add your total calories. If you are gaining fat, you need to cut back on the calories. But you need to have a caloric excess to maximize your muscle gains. That right there is probably 90% of it and anything else is probably completely pointless unless you are a very good athlete, in which case you're going to be looking for what's the next. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: Should I manage my total cholesterol of 305 just for my doctor or should I be doing it for my own sake? If so, how should I do it? You should want to improve your lipid profile for a lot more than to please your doctor. Let's revisit this from a cholesterol skeptic point of view. Uffe Ravnskov, he wrote a book called The Cholesterol Myths. In that book, he shows a graph from the Framingham study where he maps out the people who have heart disease and the people who don't. If you look at that graph, one thing that you see is that everyone who had total cholesterol over 300 had heart disease and no one who didn't have heart disease had cholesterol that high. Look, the only way to have a total cholesterol of 300 or more in most cases is to either have a thyroid disorder or to have a familial hyperlipidemia. We're talking about fasting levels here. You should want to manage your blood lipids for your own sake because people with familial hypercholesterolemia have a dramatically increased risk of having heart disease decades earlier than it becomes normal for the general population. I'm not saying it's 100% certain that if you have a cholesterol of 300 you will have heart disease, but you are way disproportionate in risk for that reason. You definitely want to address this for the sake of your health. I think that if you have weight to lose, that losing weight should be one of the first things that you do to normalize your blood lipids and your inflammation. Being overweight also contributes to elevated free fatty acids, and elevated free fatty acids do raise your blood lipids. That's, in fact, the entire rationale of using high-dose niacin to lower LDL-C is by suppressing free fatty acid release. It's also important to address any inflammation in your gut. You might have microbiome issues, and working more high-fiber vegetables into your diet and diversifying across the different plant fibers is a great way to nourish your microbiome, reduce inflammation that comes from the intestines that would negatively affect your blood lipids. If these things that we just talked about aren't enough to get the blood lipids into the normal range, then I think you want to experiment with eating more carbohydrate and a low-fat diet, but selecting those foods to maintain nutrient density. You could add something like psyllium husk fiber , which might be both good for your gut and the inflammation coming from your gut. It will also help reduce your cholesterol by making bile acids go into your feces and making your liver draw cholesterol from the blood. If those natural things don't get your blood lipids into the normal range, then I think that you should consider being open to pharmacological methods. I've gone through all the cholesterol-skeptic literature and I'm against demonizing cholesterol. I do not believe that high cholesterol is the cause of heart disease. But if your lipids are that high, it's overwhelmingly because you are not clearing them from the blood, and not clearing them from the blood is the single most important risk factor for them oxidizing, and them oxidizing does cause heart disease. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: "Do you have any recommendations on how to get enough calcium on a low-carb, no-dairy diet? I've read that vegetables provide calcium, but bioavailability is poor." The bioavailability of calcium from different vegetables is highly dependent on the specific vegetables. Cruciferous vegetables have very good bioavailability. It's better than from milk. Spinach has like close to zero bioavailability. It's terrible and you shouldn't even count it. Nuts and seeds have about 20% of the calcium being absorbed. If you compare that to milk --- milk is probably going to be like 30% or 40%. Cruciferous vegetables are going to be like 50% or 55%. The real problem is the volume. If you look at broccoli or kale and you look at how much volume of those foods do you need to eat in order to get 1000 to 1500 milligrams of calcium a day, which is the target, it's a ridiculously high volume. I'm a bit skeptical that you want to eat more than say 200 or 300 grams measured cooked of those foods a day because they're increasing your iodine requirement. At some point, they become a liability for your thyroid gland. I think it's best to eat two or three servings of those cruciferous vegetables a day, and that's basically maxing out the calcium that you can get from them. You're just not going to get anywhere near the 1000- to 1500-milligram target. A low carbohydrate, non dairy containing diet is emulating the traditional diets of the Arctic where plant foods were very limited. How did they get their calcium? They crushed up fish bones. They freeze-dried fish bones, they pulverized them, and they ate the bone powder. Bone meal is a traditional food. Some consider it as a supplement but it is the historic source of calcium in traditional diets that were low-carb. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Question: What should people with glucose-6-phosphate dehydrogenase deficiency be doing not just about glutathione, but about folate, vitamin K, fatty acids, and neurotransmitters? G6PD, glucose-6-phosphate dehydrogenase deficiency, is an inborn error of metabolism. It's the most common one in the world. About 8% globally have some impairment in this enzyme. The reason that it's important is because glucose-6-phosphate dehydrogenase is the enzyme that allows you to make NADPH, which is a specific derivative of niacin that's involved in antioxidant defense, detoxification, synthesis of neurotransmitters, and synthesis of nucleotides, which are needed for cell division because they're parts of DNA. Someone with G6PD deficiency is vulnerable to hemolysis, or the destruction of red blood cells, because of glutathione deficiency. Glutathione reductase uses energy and NADPH, the thing that you can't make, to recycle glutathione. But it also uses riboflavin. So, one of the adaptations that someone with this impairment has to try to protect themselves is for the glutathione reductase enzyme to hog all the riboflavin so that it says, "I don't have enough of the raw material I need to make this happen, so I'm just going to make myself get way better at using what I do have." That's an adaptation to compensate for not being able to make NADPH is just to get way better at using NADPH to recycle glutathione. Supplementing glutathione is not necessarily a bad idea. You just have to be aware that at a certain point you just can't solve every one of the dozens of problems that are happening. I think that you should measure your glutathione status. Probably the best test available, not because it's the best we could have available but because there's nothing better right now, is LabCorp's test for glutathione. If that looks low, then I would supplement with glutathione to try to bring that up to normal. For the folate recycling, you have to consider this basically as if you had a really bad MTHFR polymorphism because G6PD is needed to make the NADPH that MTHFR uses, again, with the help of riboflavin to make the methyl group on methylfolate. You can take some methylfolate, but as I've made the point in my MTHFR protocol at chrismasterjohnphd.com/methylation, you have to take 18,000 times the RDA to compensate for the 18,000 times a day that you add a methyl group to the folate molecule using that enzyme. It's not safe to take anywhere near that much folate. What I would do is just very strictly follow the MTHFR protocol that I have at chrismasterjohnphd.com/methylation, and that involves doubling your choline intake because you don't need NADPH to use choline to support methylation. Just as if MTHFR didn't work because of genetics and not enzyme, what you would do is you double your choline utilization for methylation because you're not good at using folate. On recycling vitamin K, it probably just means that you need a high amount of vitamin K in your diet. I think it's probably similar as if you had a bad VKOR polymorphism. VKOR is the enzyme that recycles vitamin K using NADPH that you got from this pathway that's not working right when you have G6PD deficiency. In terms of all this stuff that you are not good at synthesizing, like cholesterol, fatty acids, nucleotides, and neurotransmitters, I think the only thing that you can do for that is to try to eat a lot of these things preformed. That means eating a diet rich in relatively lean animal foods because they have a lot of preformed stuff, like cholesterol, in them and mainly in the flesh, not the fat. With plants, you want to eat mostly fibrous vegetables because they are highly cellular and rich in nutrients that you can't make. You don't want to go extremely low-fat, but if you eat a diet fairly rich in animal foods, you're going to get a lot of the specific fatty acids that you can't make. A high-fat diet is mostly giving you just a bunch of fat that you could have made yourself. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.