In this episode, I am speaking with Dr. Chris Masterjohn—who has a Ph.D. in Nutritional Science and is widely regarded as one of the top nutritional biochemistry experts in the world—about the science on detoxing, MTHFR, fatty liver how to fix it, and more.
In this podcast, Dr. Masterjohn will cover:
- Why most protein recommendations are misguided
- What are the primary causes of fatty liver? (And how to fix it)
- Why “the liver is a filter” is false
- Does high protein consumption cause ammonia build up in the body?
- The role of protein in cancer growth (The answer will likely shock you!)
- How the body has evolved to detoxify toxins found in plant foods
- What current studies show on MTHFR and B vitamins
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The Science On Protein, Detox, MTHFR, Fatty Liver (And How To Fix It) and More with Dr. Chris Masterjohn Ph.D. – Transcript
Ari Whitten: Everyone, welcome back to the Energy Blueprint Podcast. I am here yet again for the now fourth time with Dr. Chris Masterjohn. A quick intro for him. If you guys haven’t listened to the previous Podcasts, he’s got a Ph.D. in nutritional sciences and he is widely recognized as one of the world’s top experts in nutritional biochemistry. And obviously, the reason I’m having him on so many times is because I think very highly of him as well.
One quick thing before we get into it, if you haven’t already picked up a copy of his “Cheat Sheet,” the “Testing Nutritional Status: The Ultimate Cheat Sheet,” go do that. It’s 24 bucks after you get a 20% off discount. And it is just an invaluable resource. If you’ve listened to the previous Podcasts you guys now understand why I say that. This is a must have for everybody who is concerned about their health or are trying to figure out what is the source of their symptoms. And it’s 24 bucks, guys.
So, there’s no reason not to get this thing. It’s, to be honest, it’s way too cheap. I think it should be priced more like 97 bucks. It’s definitely worth a lot more. So, you can get that at chrismasterjohnphd.com/ari. Or just you can get it at his site if you don’t want to get the $6 off. But if you go to “/ari” then you get a discount that he’s giving all the people who are listening to the Energy Blueprint Podcast. So, Chris, welcome back yet again. Podcast number four, my friend.
Dr. Chris Masterjohn: We are on a roll.
Ari Whitten: Okay. So, we’ve now covered, past three Podcasts, the first one was we covered a lot of new details of nutritional deficiencies that could potentially arise, how they relate to various symptoms and fatigue in particular and related symptoms to fatigue.
The second one we covered a lot around cholesterol and heart disease and some stuff related to niacin and nicotinamide riboside and NAD+. The third one, which we just recorded, we covered the internal antioxidant system and the building blocks of that system and how to prevent oxidative damage at the cellular level. Now I have a whole bunch of other smaller topics that are disconnected that I want to get into.
What science says on protein
The first one is protein and, you know, this is a somewhat controversial topic. There’s a lot of sort of different opinions out there from different health gurus. Some people are saying, “Hey, protein accelerates aging. It activates mTOR. You get, if you eat too much protein, then you get increased ammonia levels and ammonia is toxic.”
Animal protein, in particular, some people really demonize. So, there’s kind of those ideas out there that we should be limiting our protein intake and protein is bad for us for various reasons. It causes cancer, accelerates aging, etc.
But there are also people who are advocating higher protein consumption and you are one of them. I am one of them. Why do you think the arguments for protein restriction are misguided?
Dr.Chris Masterjohn: I would start on a sort of even higher-level issue, which is that mTOR is, which is one of the things that you mentioned, is one of several kinds of… There is a web of regulatory sensors and regulators that respond to alternations between having low energy levels during fasting and having lots of energy and abundance in the fed state. And there are processes that the fasting state is optimized for it.
And there are other processes that the fed state is optimized for. And so, for example, autophagy, which is breaking down tissues, preferentially tissues that you don’t want anymore that might be defective or, you know, bad in some way or just not as useful as other tissues. Autophagy is mainly done in a fasting state. And, however, repair processes and protection processes are done in the fed state. And so, if you have a neurological problem and you want to regenerate your nervous tissue, you best be trying to maximize mTOR because mTOR is one of the key drivers of neuro-regeneration.
If you want to build muscle mass, then you best be trying to maximize mTOR because mTOR is one of the key increasers of muscle mass. And even antioxidant protection. The last hour that we spent on antioxidant production, one thing that we didn’t talk about is that antioxidant protection is a function of the fed state. All the genes that regulate autophagy are opposed to the genes that turn on the antioxidant system.
Why? Because, well, in the last Podcast that we recorded, we talked about how you ultimately, if you are protecting your cell membrane you are deriving that protection from glucose, right?
So, the thing that requires energy to invest in repair and protection are fed state processes. And things, where you break down old stuff, is fasting state processes.
Now, the issue is you don’t want to be in the fed state all the time. You don’t want to be in the fasting state all the time because you don’t want to build things up and never tear down the old bad things. And you can kind of think like, there are so many analogies you can make. Like, your closet, right? If you’re only buying new clothes, you’re not going to be able to find any of your new clothes eventually because all your old clothes are going to be in the same closet. Whereas if there are times where you say, “You know, money is a little tight right now, take all the clothes I don’t care about in my closet,” and then sell them off and get a little extra money. Then times get good again.
Now I have enough money, my closet is half empty, I’m going to go buy some clothes I really like. Then all of a sudden, your closet is great because you go in there and only you see your best clothes. It is like a business, right?
A business that is never exposed to tough times is going to be bloated with all kinds of inefficiencies. They might even produce less than a business that went through tough times, had to cut out all the crap that they don’t need. And then when money came in, made really good choices in who they hired and what they invested in. Same thing with our bodies. We want to tear down the old crap and then build up new crap, but we don’t want to be tearing down everything all the time or we are going to tear down ourselves. And so mTOR is not something that we want minimized.
It is something that we want to cycle through going, you know, fasting state low mTOR, fed state high mTOR and cycle back and forth like that. And in fact, Chad Macias who does sports science research and some other stuff, I had him on…
Ari Whitten: He is a cancer researcher.
Dr. Chris Masterjohn: Yeah. But in this context, I had him on my show to talk about sports nutrition and he made a point that I didn’t realize before, which is that having low mTOR levels before your workout actually potentiates the anabolic response to high mTOR levels after your workout.
So, if you are never in the fasting state, you are not going to get as much out of your post workout protein dosing that is going to rise your mTOR because you want to have that super high mTOR spike calibrated against a very low baseline, right?
So, you need to enter the fasting state, but you don’t stay there. So that is a big part of why this is misguided. But I think…
Ari Whitten: Just to rephrase or add to that, basically what you are saying is there’s a lot of people out there who are advocating that even when you are in a fed state, you should try to minimize mTOR. Basically, they are saying you should try to keep mTOR low all the time, 24 hours a day. And even during the feeding window when you’re eating meals, it should still not be elevated.
Dr. Chris Masterjohn: Right. Because no one eats protein when they are fasting because then they wouldn’t be fasting. Right? So, the question of when to eat protein is what to do in the fed state. So, you’re saying don’t eat protein because it activates mTOR then you’re saying don’t eat protein in the fed state, right?
Now, another reason that it is misleading is that if you take an animal model and you are like, “Well what makes this worm live longer?” Which is actually a stunningly large proportion of longevity research, you are not looking at what causes human death, right?
So, you know, maybe restricting protein would cause a human who never got in a car accident, never picked up an illicit drug, never got heart disease, never got a hip fracture, you know, maybe by that point overall mTOR signaling might become the most important dictator of your future longevity after all that. The reality is that a lot of people, and like obviously it’s not diet and nutrition, but a lot of people die from trauma. But you exclude those, and you just talk about things that are relevant to diet and lifestyle. People are dropping dead of heart disease first.
A stunningly high people who get a hip fracture when they have osteoporosis die in the year after. And you know, you can debate like why that is, but you could regard hip fracture as a major driver of death in that way. And if you look at like the question like, “Do elderly people need more protein or less protein?” All of the research on protein needs says the older you get the more protein you need. And if you don’t get that protein, what do you get? Sarcopenia and osteoporosis. And when we get sarcopenia and osteoporosis what happens to your risk of fracturing your hip and dying a year later? Ridiculously up, right? And muscle mass isn’t just about protecting your bones and looking good and carrying yourself. Muscle is a major disposer of glucose. And so, what happens to your diabetes risk if you have sarcopenia? It goes way up, right?
So, on every metric of thing that people are actually dying from, the concern really isn’t overall mTOR at those points. I think the concerns about heart disease is a different set of concerns. The concerns about osteoporosis and sarcopenia are more about how do you raise mTOR than they are how do you lower it? Right? Yet probably cancer, you know, by the time you clear out osteoporosis, heart disease and all these things as major drivers, by the time you get to cancer probably then you’re really thinking about mTOR because your overall level of growth everywhere is going to leak, kind of leak its way into how much does your cancer grow? But then take a look at, for example, T. Colin Campbell’s research on protein fueling cancer growth. I think probably Campbell before anyone, the author of “The China Study “popularized the idea that protein, especially animal protein promotes cancer growth, probably single-handedly by him.
Other people have taken that up. But Campbell’s really the one. So, I went back and I after… When I was doing a critical analysis of the book, “The China Study,” I went back and read every single paper that Campbell ever published in his animal models showing that animal protein causes cancer growth. One of the things that he showed that he never talks about is that if you fed high animal protein before he fed the carcinogen, it was a powerful protector against cancer. And if he fed the high protein during the exposure to the carcinogens, it was a powerful protector against cancer. And if he fed the high protein after he dosed the carcinogen, it promoted the cancer growth. And so, after he found that he developed the model where he fed low protein before and during the carcinogen dosing to maximize the amount of cancer that was initiated.
Why? Because protein helps you detoxify carcinogens, right? And so, by feeding low protein the carcinogens accumulate. You don’t metabolize them, probably don’t get rid of them. You have maximal cancer initiation. Once you have that cancer, protein fuels the growth. Now the question is what happens if your exposure to carcinogens doesn’t occur because the researcher injected you with a bunch of them in a very defined time period, which is most of us who are exposed to little bits of carcinogens, you know, all the time. Well, there’s only a couple of studies that ever looked at that question and they found that the higher the protein, the less cancer. Why? Probably because you have to initiate cancer in order to fuel its growth. And if the high protein is protecting against cancer initiation, there are no cancers to feed the growth up. And so, just one last like big level point. The diet that prevents cancer is not the diet that cures cancer. If I had cancer, I’d be thinking a lot about whether I wanted to lower my protein intake. But I don’t have cancer yet. And so, I’m actually thinking more about whether I can prevent it by eating enough protein.
Ari Whitten: Okay. So that was exactly where I was going to go when I was about to interject. So, basically if what you’re saying is true, then there are a lot of people who are very misguidedly keeping their protein intake very low in an effort to prevent cancer and might, that might not only be ineffective but actually counterproductive.
Dr. Chris Masterjohn: Yeah. I think it is counterproductive with the caveat that, well with a couple of caveats. But the main one being that you probably will fuel cancer growth with higher protein if you have cancer and you might not know you have cancer when you have cancer. So…
Ari Whitten: Right. I’m specifically talking about prevention.
Dr. Chris Masterjohn: Yeah. But I think from prevention, you probably do want to cycle through lower protein intakes occasionally. But you know, apart from just going through a normal fasting state overnight and things like that. And that might be just, you know, you may practice occasionally longer fasting than overnight and that would be a great time to include that lower protein intake there. But I think low protein all the time is very misguided.
Ari Whitten: Okay. So, one more thing I want you to address. One more argument related to why people should not eat a lot of protein is ammonia. Some people claim that if you eat too much protein, it increases ammonia levels and that’s toxic to the body. What’s your take on that?
Dr. Chris Masterjohn: What do you do with, when you burn protein for energy is you convert the ammonia into urea which is not toxic. And if you go to the doctor and get your BUN checked, your blood urine nitrogen, that is urea and that’s nontoxic and excreted in your kidneys. They have studied the limits of the urea cycle in humans. And the limits of the urea cycle are it would be impossible to eat that amount of protein from whole foods. If you ate like 2000 calories of protein, you would not exceed the limits of the urea cycle. There’s an exception to that, which is that…
Ari Whitten: Just to convert that, it is about 500 grams of protein per day.
Dr. Chris Masterjohn: Right. Yeah. And so that’s not even saying if you ate all your calorie allotment as meat. That’s saying if you ate all your calorie allotment as protein, right? So that’s like whey protein or beef protein isolate. Right? Now there’s an exception to that, which is that there are rare genetic defects in the urea cycle and rarely someone can die from eating that much protein. But that’s, we’re talking exceedingly rare and they can die from normal amounts of protein. But there are genetic polymorphisms in the urea cycle, and these are more common like 20 or 30% of people have a polymorphism in the urea cycle that has not been studied for its interaction with protein. But it is at least theoretically plausible to say that there are certain people who won’t tolerate protein as well because of that. And so, I do think that there might be case by case basis where some people might develop too much ammonia from a high protein diet. They’re not the majority of people. They’re probably a pretty slim majority. And there’s actually probably things that you can do to alter that like supplementing with citrulline or arginine could probably allow you to tolerate that protein load.
Ari Whitten: Okay. So big picture sort of wrap up of this, protein is important for various purposes. It, you know, as we talked about in the last Podcast, helps to build the internal antioxidant defense system. Also important for muscle mass maintenance and avoiding sarcopenia. I’m sure there are many other things that we could sort of list off as far as the benefits, but it’s important for many roles in physiological health or in health more broadly. And the downsides of high protein intake you think are speculative and overblown and maybe in some cases range from just completely untrue, like for example, the idea that higher protein intakes are causing tons of ammonia buildup in the body, to potentially totally wrong and counterproductive with the idea that protein avoidance may potentially even make you more likely to have cancer potentially.
Dr. Chris Masterjohn: Yes. Right. With the one caveat that once you know you have cancer, things change.
Ari Whitten: Right. Okay. So, and once you, if you had also a genetic defect in the ability to convert ammonia to urea then things change in that context as well. Okay. Excellent. So, I want to sidestep, shift to a completely different topic here. I want to talk about glutathione. I want to talk about detoxification and liver function. And I’ll mention a meme that you promoted recently called, you know, you were like, “Say it with me now, the liver is NOT a filter.” You know, to [crosstalk] the idea that the liver is a filter, which is how many people think of it. So, explain what you mean by that and then we’ll go from there and kind of dig into some of the topics related to detox.
Dr. Chris Masterjohn: Yeah. So, it’s very common to explain the liver as a filter because the liver reduces the amount of toxins that are circulating in your blood. And a lot of clinicians find it a useful analogy in talking to their patients to tell them that their liver filters their blood because like if their car filter goes bad, their oil gets dirty. If their fish tank filter goes bad, their fish tank gets yellow. And there is, you know, it just is a convenient way to explain it. But you won’t talk, you won’t find any like legit medical textbook talking about liver filtration in the way that they talk about kidney filtration. And, you look at any textbook on the liver, you’re going to find a very consistent picture of what the liver is actually doing.
And it is not like any human made filter the way that we would usually think of them in the sense that pretty much any filter that is responsible for cleaning anything or keeping something clean is doing so by retaining the bad stuff inside itself. It Probably needs to be changed periodically. Like I just changed my air filter, my home air filter, and the liver doesn’t retain toxins like that. And I brought this up in the context of people who say, “I’m not going to eat liver because the liver is a filter and it’s full of toxins,” which is ridiculous because the liver doesn’t hold on to toxins. What the liver does is it engages in a three-step process to prepare the toxin to be metabolized and metabolizes the toxin in a way that makes it easier to excrete and also reduces its toxicity. And then phase three is it gets rid of it. And I’m happy to go into any more detail on any of those phases if you’d like, but that’s the big picture of it.
The science on detoxification
Ari Whitten: Yeah, well so let’s talk about kind of conventional thinking around this topic of detoxification more broadly and some of the kind of detox protocols that are out there. I’m curious what you think of them and where you think they might be…
Dr. Chris Masterjohn: Wait a second. What do you think of as conventional?
Ari Whitten: Well, not conventional medicine. So, I’m talking about like sort of, I guess yeah, maybe I shouldn’t use that word conventional. But typical thinking within some of the holistic health functional medicine circles.
Dr. Chris Masterjohn: Yeah. Okay. I think that is really hard to pin down because there is so much that probably has no merit and there is so much that almost certainly has merit, right? So, you know, on the one hand, like there’s no evidence that if you take a boatload of olive oil and lemon juice and then you have things that look like rocks coming out of your poop that you detoxed anything from your, like you didn’t clean out your liver. Probably that olive oil like congealed into something that looked like something bad to you. That’s probably what happened. On the other hand, if you go to Vitamin Shoppe and you look at like detox supplements, you go to Amazon and you search for detox supplements, probably most of the stuff there at least has merit in principle. There might, you know, you might have questions on whether it’s the best formulation, but most of those things have things known and shown to be hormetic stressors that upregulate the production of not just antioxidant protection but also detoxification, precursors to glutathione, which is one of the things that help you get rid of toxins and other things known to be relevant.
And so, it’s very possible that they’re overpriced. It’s very possible that they’re poorly formulated. But most of those things are not going to be totally meritless in how they are designed.
Ari Whitten: Okay. So, I’m going to ask this a little different way. So, there are some people sort of in the hardcore evidence-based communities that just scoff at the whole concept of detoxification and think it’s all just, any mention of detox is immediately pseudoscience. It’s quackery. The thinking there is sort of like, “Hey, our bodies come built with a liver and kidneys and, you know, I don’t need any detox protocol because I’ve got a liver and kidneys.” So, what’s your take on that?
Dr. Chris Masterjohn: I call those people evidenced based Internet trolls or EBITs. And on that…
Ari Whitten: That’s not a bad term, by the way.
Dr. Chris Masterjohn: Yeah, and so an EBIT is basically a person who is so obsessed with the idea that they are policing what is evidence based that through their own presuppositions and complete unawareness of the science behind the things that they criticize, they just label anything that doesn’t fall into their bucket of what they know to be evidenced based as not evidenced based and quackery. And these people almost universally don’t know jack about like conventional medical understanding of how the liver functions. And the dumbest most like, I’m sorry, to be like real political about this…
Ari Whitten: No, please, please, they deserve it.
Dr. Chris Masterjohn: But this is brain dead level of BS. To say that the way you detox is to have a liver is like the dumbest thing that anyone has ever said about detoxification. That is dumber than, like on a practical level it’s not dumber than actually taking a bunch of olive oil and lemon juice and watching things come out in your poop.
But intellectually it’s like dumber than that. You know, at least someone like played around with something and looked at what came out the other end and made an idea about it. Like at least they were opened minded, you know, but it might be totally meritless as a practical thing. But these people are completely closed minded. And they are not just closed minded to a new idea, they are closed minded to the existing known science about detoxification. Like it’s just a ridiculous level of BS.
So, the idea that the reason that to say the way you detox is to have a liver, the reason that is stupid is that your liver doesn’t detox by being a liver. Your liver…And actually, someone in the comments to one of my posts made a very perfect analogy here which is, “You never see any of these EBITs trolling the fitness people.”
And of course, quite often they are the fitness people. You never see them trolling the fitness people saying, “Why are you taking all of that protein? The best way to build muscle is to have a muscle.”
Ari Whitten: Yeah, exactly. The best way to bench press 500 pounds is to have muscles.
Dr. Chris Masterjohn: Yeah. You would never see these EBITs trolling the bodybuilders saying, “Why are you in the gym? Why don’t you just have a muscle?” You know? And the liver’s ability to detoxify toxins is dependent on number one, the hormetic stress input of toxins that tells the liver how much of the detoxifying enzymes it needs to produce. And then the raw materials that support those enzymes. So, if you don’t eat enough protein, you’re not going to build muscle in the gym, and you are not going to detoxify anything in your liver because you need protein to make glutathione.
But not just glutathione. You need protein to make every enzyme in your body because every enzyme is made out of protein for the most part. There are some obscure enzymes made from RNA. But all these proteins that help you detoxify, excuse me, all these enzymes that help you detoxify are proteins that are made out of the protein you eat. And so, you need to eat enough protein.
But not only that but they, these enzymes have cofactors. So iron is a very common cofactor in detoxification. If you don’t have iron, you are not going to detoxify anything. If you are anemic, you are just looking at what’s going on in your blood. But probably in your liver, your detoxification is sinking. Riboflavin is not as common, but there are key enzymes that are dependent on riboflavin. But then there, you know, that process, before I had described the process in more simple terms. But phase one is oxidation.
That’s where iron and riboflavin are usually coming in. Phase two is called conjugation. What you do is you take this toxic molecule and you tag it with something that does two things. One is it helps you make it easier to excrete. The other thing is that neutralizes its toxicity. Most things that you conjugate it to are where many other nutrients come into play. So, you know, one of the roles of protein is how we make glutathione.
Glutathione is one of those things. Sulfate is one of those things, you need to eat enough sulfur. A lot of the sulfur that you get comes from animal protein. A lot of the sulfur that you get comes from cruciferous vegetables. But that sulfur input has to be there. Glycine is another one that you would use.
And glycine, you can make some glycine, but you also get glycine from the diet. Really skin and bones, the sort of like eating nose to tail is the best way to improve your glycine status. And you can go on and on. There are different things that come into play in that process. Methylation is another part of phase two and methylation is supported by folate which is vitamin B9, vitamin B12, choline. A bunch of the B vitamins sort of are in the background supporting the methylation process. So, there is a diversity of things that are involved in phase two, but that really opens the door to a lot of nutritional effects. And then that, what we’ve been talking about is mostly detoxing organic molecules, which are large carbon-based molecules. There are also means by which you have to detoxify metals and arsenic is detoxified by methylation.
There are human studies showing that giving people nutrients that support methylation increases the amount of arsenic that they excrete in their urine, like human trial data showing this.
Ari Whitten: I don’t need your B vitamins. I’ve got a liver.
Dr. Chris Masterjohn: Yeah. And then more broadly, one of the things that you do with heavy metals, in general, is you have this chelator that you make yourself called metallothionein. And if you have more mercury, for example, you make more metallothionein to bind it up. But your ability to respond to the heavy metal by making more metallothionein is completely a linear function of your zinc status across the range of deficiency, through healthy amounts of zinc through super-physiological amounts of zinc.
So even if you’re not zinc deficient, it’s almost, I don’t know of any human trials showing this, but based on the biochemistry it’s almost certainly the case that adding a zinc supplement would add to your ability to get rid of most heavy metals.
And so, when you combine that all together, what you’re doing is showing that there is an incredible array of things that you can do to modify how well your liver gets rid of toxins. And so, the idea that you detox by having a liver is like you didn’t say anything. You have liver. So, what are you going to do with it?
The positive benefits of hormesis
Ari Whitten: Right. Now, I want to, you’ve mentioned, you’ve alluded to this a couple times, but I want to connect the dots a bit with the last Podcast and the concept of hormesis and the internal antioxidant defense system. Just briefly, just to connect some dots here, but some of the pathways that are up-regulated by hormetic stressors whether it be exercise, sauna exposure, fasting, phytochemicals, part of that process of the nrf2 pathway that impacts on up-regulating the internal production of antioxidants, also that ties into detoxification at the cellular level. Correct? Can you talk about that?
Dr. Chris Masterjohn: Yeah. So nrf2 is a master regulator that is governing antioxidant defense and xenobiotic metabolism. Xenobiotic means a foreign molecule that gets into your body and should not be there. And so that is drugs, environmental toxins, and even phytochemicals. Phytochemicals are regarded as xenobiotics by the body to be gotten rid of and that’s why they up-regulate this process.
And so, it is just broadly true that when you’re exposed… Like exposure to oxidants is going to increase your detoxification capacity and exposure to xenobiotics is going to increase your antioxidant capacity mainly because it’s often xenobiotics that are causing the oxidative stress. So, there is a general broad… This broad umbrella of genes that are regulated under this umbrella includes antioxidant detoxification. And one of the, and that’s highly fortuitous to us because that means that we can eat somethings that are not that toxic, that are very good at up-regulating that pathway and increase our ability to deal with everything else. And so, phytochemicals…
Ari Whitten: And actually, if I can interject one thing on that, just to give some context for that statement. So, like not all toxins or not all xenobiotics are treated by the body in the same way. There is sort of a profile of the degree to which they are up-regulating the antioxidant and detoxification defense systems and the degree to which they can cause harm or the ease in which they are toxic and causing damage. And some things up-regulate the system very well without causing any significant harm. And other things have a much higher potential for harm and much lower potential to up-regulate the system. Is that…?
Dr. Chris Masterjohn: Yeah, exactly. So, what you, for maximizing health what you are thinking about is the ratio between hormetic effect and toxic effect. High hormetic to toxic ratio is net hormetic and good for you. High toxic to hormetic ratio is toxic and bad for you. Now if you think, like if you think about where did we get a detoxification system from? Well, first of all, this goes back way more than 200,000 years or 2 million years because this basic system is shared by most other animals.
So, we are talking like, you know, way before humans were ever on the face of the earth. And the question is why do we have this detoxification system? Well, it’s not because our genes foreknew that we would develop gasoline. Right? The detoxification system is not designed to handle the toxins of the modern environment. It is designed to handle the toxins of the ancient environment which are food toxins and the fact that there is no food that’s not toxic.
And what our goal was, not just us as humans, but what the goal of any animal is, is to navigate through and find the plant foods that are safest to eat because they are highest in nutrients relative to toxins and then deal with the fact that even those plants have toxins in them.
And so that is the function of the detoxification system. And so, it has been very well crafted over like hundreds of millions of years at least to respond to the natural toxins in plants, particularly the plants that we would eat. Because if we recognize a plant as completely toxic and avoid it, we mainly relying on our recognition of that plant through taste or visual cue or just learning and accumulating a body of knowledge that we don’t eat that thing.
So, our detoxification system is, yes, it’s designed to handle the rare case where you might get a little bit of that thing that is super toxic. But what it’s really handling most of the time is the everyday load of the things that we learned that we do eat to get the nutrients and distal the toxins. And so, because, now imagine if the ability to get rid of one toxin was limited to that toxin, we wouldn’t exist because the first person who ate something else would be dead.
And if no one ever ate anything else, everyone would be dead. Right? So, by nature, our detoxification system had to be broad enough that you could have one thing that detoxified lots of other things. And hopefully you generalized from the things you had adapted to the things you’re likely to encounter in the future. And because you can generalize, that means that when we invent industrial things that introduce new manmade toxins, our detoxification system can respond to that. But guess what?
If that’s a new toxin that we made in the last hundred years, our system is not evolutionary designed for it and it isn’t optimized for it. It is optimized for toxins in nutritionally healthy plant foods. And so, we are so good at detoxifying the things in the healthy foods that we can reap benefit from it. Like there’s extra hormesis, like the toxin values is like this and the hormesis value is this like this. So, we can take that…
Ari Whitten: Right. Just real quick, so this is why a lot of the thinking out there, whether they are trying to… You see people looking at specific foods and saying this food has this toxin in it and so it should be avoided because it’s got this toxin. But the context is for most of these cases, the actual toxic component of it is greatly outweighed by the beneficial component to it that is being provided by the…
Dr. Chris Masterjohn: The beneficial component of that toxin, right? Of the hormetic response to that toxin. And that is what’s kind of like really mind boggling to people. I think it is hard to get their mind around is that you can talk about like cruciferous vegetables and their cancer protective properties and they are goitrogens. What you don’t realize is that the cancer protective compounds are the goitrogens. And so, there are potential downsides to all of these things if, you know, in certain contexts. But in general, for most people most of the time for most of these foods, it’s that bad thing that’s giving you the benefit. And you, if you get this much toxicity this much hormesis, that hormesis doesn’t just cover the toxicity in that plant.
You can sort of use that account balance of extra hormesis to cover all the modern, all the toxins in the modern environment. And so, one of the best things that you can do to be able to handle those toxins is to get the hormetic stress of the thing that your system is well designed for, which is the toxins natural in plant foods.
Ari Whitten: Yeah. And as you pointed out before, there’s also overlap here where resistance to that one hormetic stressor extends resistance to a broad range of other stressors. So, for example, you can consume sulforaphane, you can consume this phytochemical and get some hormesis from that phytochemical and that can extend to, for example, increased resistance of your skin to UV radiation from the sun. You can take in more ultraviolet light on your skin and not get as easily burned from it. So, you know, one kind of hormesis translates into this resistance to a broader range of other stressors.
Dr. Chris Masterjohn: Yeah. So, I think what that represents or illustrates, in that case, is the fact that detoxification overlaps with antioxidant protection and repair processes. So, your sunburn in response to the sun is really more about antioxidant protection and repair processes, less about detoxification. But the fact that you needed to detoxify the sulforaphane means you up-regulated the big umbrella that includes both detoxification and antioxidant protection and repair.
MHTFR – Is this something we need to be concerned about?
Ari Whitten: Yeah. Very, very well explained. Okay, another shift here. You talked briefly about MTHFR there. There is a lot of hype around MTHFR, a lot of people talking about it, a lot of people making a very, very, very big deal about MTHFR. And you see people sort of being “diagnosed” with having certain MTHFR variants and then you sometimes see people sort of walking around, you know, convinced they’ve got some terrible genetic disease if they have certain MTHFR variants.
I know that you did an article or a podcast recently or both with a mutual friend of ours, Alex Leaf, where you talked about some new research around MTHFR variants and certain specific B vitamins that is not the typical thinking around the subject. So, can you talk about that research and what this new study showed?
Dr. Chris Masterjohn: Yeah. Real quick before I do that, no one gets diagnosed with MTHFR. Diagnosed is a terrible word to use for that because it is not a disease.
Ari Whitten: Right, now for everybody not watching the video, that is why I used air quotes.
Dr. Chris Masterjohn: Right, right, right, right. Well, I want to just interject to support your air quotes. Although there is an exceedingly rare genetic defect that is a disease that’s not what anyone is talking about. What Alex and I uncovered that I think is, you know, we didn’t come up with it but it’s very underappreciated that we kind of uncovered when we were extensively investigating riboflavin is that these MTHFR polymorphisms, which are variations in a gene… Well first of all going back to the diagnosis thing, these things are so common, only about 10 or 15% of people don’t have at least one of them.
And so, what you actually see is just six combinations that cause an even spread in MTHFR activity across the population. So just some people are at 100%, some people are 25%, some people are at 45%, some people are at 65%.
Ari Whitten: I think that’s an important thing to understand because a lot of the people who are sort of finding this information out about themselves when they do this genetic analysis then are convinced that they are the 2% of the population that has this screwed up MTHFR variant. And they don’t realize that they actually, this is the majority of the population that has at least something going on there.
Dr. Chris Masterjohn: The reason that none of their, that none of the people at church school and work have MTHFR is because none of them went to that functional doctor that you got and had their genes analyzed. That is the only reason that you stick out like a sore thumb. Yeah. So, I mean, interestingly I don’t have any of the polymorphisms in my MTHFR, but…
Ari Whitten: I do.
Dr. Chris Masterjohn: But I’m in the very minority on that. So, but yeah, so what Alex and I uncovered is that it appears what these variations are doing is decreasing the enzyme’s binding ability to bind the riboflavin to the vitamin B2 which is an essential cofactor for MTHFR. So, everyone thinks of MTHFR as involved in folate metabolism and that’s because that is what it does. It converts one form of folate to another in order to support the methylation process.
But it can’t do that without riboflavin. And so, if the enzyme has a lower binding affinity for riboflavin, which means it doesn’t bind to it as tightly, then you’re more likely to have more MTHFR that’s not bound to riboflavin and is not functional at a normal sort of baseline of riboflavin. But like let’s say the person who has no, for people who are watching the video I’m just setting my hands at different levels. Imagine the person who doesn’t have MTHFR polymorphisms is, their riboflavin requirement is here, and the average person has a riboflavin requirement here just slightly above that. Well, if the riboflavin need comes up to here, which for people who are just listening to the audio system is just a slightly higher riboflavin requirement, that just happens to be above what everyone is eating, then all of a sudden those people are not meeting their riboflavin requirement for MTHFR.
So, what you see when you look at the activity is their MTHFR activity is low. But if you just raise the riboflavin level up to meet the need, then you don’t see that the activity is lower. And so, there are some pretty good studies on this both. There are studies on the mechanistic front, you know, showing that the binding affinity is different in that you just need more riboflavin to saturate the ability of it to bind riboflavin. Then there’s also human studies showing that when people with these polymorphisms specifically, a small amount of riboflavin will lower homocysteine into the normal range. And that in fact when you lower homocysteine in people with MTHFR like almost all of the homocysteine lowering is isolated to the people who had poor riboflavin status. And if you take the general population and you look at who has elevated homocysteine, it basically falls into people who have MTHFR and poor riboflavin status.
So, it all lines up very well supporting this idea on that. It may be the case where it’s definitely the case that some of the lower activity is a result of poor riboflavin status and you can fix it by just getting enough riboflavin. And it might be the case that all of the loss of activity is only a matter of poor riboflavin status. And if you just get enough riboflavin you can bring that activity up to normal. Now, it doesn’t mean that methylation is only about riboflavin because just having normal MTHFR activity does not excuse you from needing nutritional support for your methylation. But it may well be the case that the first and foremost thing we should be thinking about with MTHFR is getting enough riboflavin.
The primary causes of fatty liver and how to fix it
Ari Whitten: Okay. Excellent. Excellent stuff. Okay, so shifting again, I want to talk about, let’s see, on my list here, I think I have two more topics. One is fatty liver and the other one is nutrition as it pertains to neurotransmitters. So, which one do you want to dig into first? Those are the last two things on the list here for this Podcast.
Dr. Chris Masterjohn: Fatty liver is simpler. Neurotransmitters are harder for me to imagine how to make it simple.
Ari Whitten: Okay. So, let’s go to fatty liver first.
Dr. Chris Masterjohn: Okay.
Ari Whitten: So yeah, so to get specific there, so what’s your take on sort of the key causes of fatty liver? It’s obviously sort of…
Dr. Chris Masterjohn: Fatty liver is extremely simple. It’s more fat going into the liver that is coming out.
Ari Whitten: Okay. So how does that happen and what are the dietary factors or lifestyle factors that act on that because there is obviously sort of an epidemic of people who are [crosstalk] fatty livers. What do people need to know about the causes and how to fix it?
Dr. Chris Masterjohn: Right. So, there are a few ways that fat gets into your liver. The majority of fat that gets into your liver is actually just caused by you releasing fatty acids from your own adipose tissue that will go to the liver, get made into triglycerides and go back to the adipose tissue and then get stored. It’s a cycle that’s just always happening. And, if your liver can export triglycerides, fine, triglycerides are the main fat molecule, you don’t get fatty liver. But if your liver can’t export them, they get stuck there and they cause fatty liver. The second most important source of fat in the liver is dietary fat. Dietary fat is, you are going to eat it, it is going to travel through your lymph system, it is going to go to your circulation. How much your liver sees are going to depend on how much your other tissues take up.
And so, your liver is going to see a lot more of it if you are sort of in chronic energy excess than if you are not. But dietary fat is always going to make its way into the liver. If you are… And then the minority of it, so maybe like 5% in a healthy person and 15% in someone who is metabolically dysfunctioned is going to come from de novo lipogenesis which is the process of converting carbohydrate into fat. That is never a major factor. Right? So, like in a healthy person maybe it is 5% of liver fat and it doesn’t matter because they are healthy, and they can export the fat. So, de novo lipogenesis is never the major factor. And you can see, even though in people with fatty liver disease it might be tripled from normal, it’s going basically from 5% to 15%.
And so, it is going to make a contribution. But a lot of people who advocate low carbohydrate diets as the thing to resolve fatty liver disease focus very much on that 15% when the other 85% is a lot more important quantitatively.
Ari Whitten: If I can interject one thing here, there is, you know, kind of within a lot of sort of popular nutrition thinking right now there is… A lot of what you just said will kind of be counter to some of the ideas that people have been exposed to recently. So, the idea that fat doesn’t make you fat, sort of, you can consume all the dietary fat you want, and it just gets burned off while carbohydrate is really the thing that’s getting turned into fat. So just if you could comment on why that is not accurate.
Dr. Chris Masterjohn: Yeah. It’s not accurate at all. Even if someone is getting fat from eating too much carbohydrate, they are getting fat, most of the fat that is going in their adipose tissue is dietary fat. And like if you take someone with caloric balance and then you add 300 calories a day of carbs, they are going to get fat from eating too many carbs because that is the thing that you added. But the adipose tissue is going to be almost exclusively derived from dietary fat. And the way that that carbohydrate makes you fat is to prevent you from burning the fat in your diet and locking that fat in your diet in adipose tissue. So, if you, and you know, adiposity or obesity is extremely strongly correlated with fatty liver like nothing else is. And the main reason for that is that when you exceed what some people now are calling your personal fat threshold, which is the point at which you can handle all the excess energy and efficiently store it as fat.
When you exceed that point it becomes harder and harder for you to store the energy, that fat is floating around. And particularly in visceral abdominal fat, that fat pad empties directly into the liver. It doesn’t even go into the blood circulation first.
So, the main reason obesity is associated with fatty liver is that the visceral abdominal fat is just constantly flooding the liver with fatty acids that can’t get out. However, it’s also the case that when you are in a caloric excess then all these other things start, you know, start becoming more significant. So, you are going to have more de novo lipogenesis if you are in a caloric excess, not a lot, but you are going to have more.
And you’re just going to have lower ability to store and or dispose of all that energy and some portion of that energy is going to wind up going to the liver at some point. And if it can’t get out, then boom. But so that is the fat in the equation. The fat out equation is basically determined by two things. One is your choline status because choline is part of, the simplest way to put it is choline helps you get fat out of the liver.
And then oxidative stress, which we’ve talked about a little bit in this show and the previous show we did. Oxidative stress damages the ability to get fat out of the liver. So, choline and oxidative stress are the two major things controlling that. But do a little math here. In the person with fatty liver disease, their ability to take fat out of the liver is 75% reduced.
So that means… Now de novo lipogenesis, which is converting carbs to fat is tripled to about 15%. And so, if that 15% is 75% reduced, then you are talking about, you know, I don’t know what that is, 3 or 4% of that is getting trapped in the liver. Now, just circulating fatty acids from your adipose tissue back and forth is the source of something like 60% of fat that is going through the liver. If your ability to export fat from the liver is reduced 75%, it’s 75% of that 60% number that is contributing to that liver fat.
If dietary fat is coming in at, you know, 30 something percent or you know, 20 or 30%, then 75% of that is more significant than the de novo lipogenesis. But it’s still not as significant as just the circulating fatty acids, which by the way, are a lot higher when you are obese, and you have crossed your personal fat threshold. So, you can talk about lots of ways of resolving fatty liver. The most important thing out of everything is to attain a healthy body composition.
It doesn’t matter how you do it. To get from obese to healthy weight is the single most important thing that you can do to resolve fatty liver. If you are obese, which, you know, something like I think two-thirds of obese people have fatty liver and 76% of people who have fatty liver are obese. So, most people that applies to.
But then after that, you know, if you lose weight on a low carb diet or you lose weight on a low-fat diet, either way, is going to really help your liver. But then after that, you are talking about dietary fat is going to be more important than de novo lipogenesis. So, you can ramp the de novo lipogenesis as high as it will go on a high carbohydrate diet, it’s still not going to be anywhere near as high as even fat coming into your diet.
So dietary fat is way more predisposing to fatty liver than dietary carbohydrates ever can be. But among carbohydrate, fructose is more lipogenic. And so, if you just cut out the sugar, that’s going to do a lot of help. So, minimizing, taking fat down and sugar down. But the big elephant in the room that most people don’t talk about is that if you just get rid of that 75% decrease in the ability to export fat from the liver, you export all the fat. It doesn’t matter where it came from. It doesn’t matter if you drank three 40s, every day, and it’s all coming from alcohol. It doesn’t matter if you eat sugar all day long. I’m not saying you just need choline and you can eat all the sugar you want. I’m not. But you’re not going to get fatty liver from sugar if you have enough choline and you have enough antioxidant production in your liver.
So, the real big thing that, and you know, you should lose weight, you should eat a healthy diet. But you really have to fix the choline and antioxidant production of this to just get the fat out of the liver. That addresses all the fat no matter where it came from.
The MUST-HAVE The Testing Nutritional Status Cheat Sheet
Ari Whitten: Finally, I want you to just say a quick word. You know, I’ve already talked about your “Testing Nutritional Status Cheat Sheet,” but I want people to hear directly from you in your words, like why you think this is so important and what it can do for people.
Dr. Chris Masterjohn: Yeah. You know, I think it’s important because you can do everything right with your diet and then at the end of the day, there are just two key principles that stand out that means we need to individualize things. And one of those is that your needs are not mine.
Mine are not yours. Ours aren’t the listeners. So, everyone is different. And then the other is that my needs aren’t what they were 10 years ago and yours aren’t what they’re going to be in 10 years.
Everyone’s needs change over time. And so, if everyone’s needs are different and everyone’s needs change over time, then no matter how perfect you make your diet according to generalizable principles, you still need to individualize it to yourself. And you can run a genome scan or something like that. That can give you valuable information but that’s not going to give you that much information. Genetics tells you your potential. Most of what it means is not very well studied. You have to know what’s actually going on in your body. And to know what’s actually going on in your body really requires you to collect three kinds of data.
And those are, you know, subjectively what’s happening to you. What are the things you experience, that’s your signs and symptoms? And I’ve collated 180 signs and symptoms of nutritional deficiencies, toxicities or imbalances into an alphabetical list inside this. It’s a digital resource and it hyperlinks from the symptom to the, all the sections on the individual nutrients related to it, which I think that is huge.
Because I mean, if you like, the time that I went through to create an index, the signs and symptoms of nutritional deficiencies, like that’s an insane amount of work. I mean I did an insane amount of work and then I had an assistant who put a couple of hundred hours into it. So, you know, you can like Google the symptoms but you’re not going to get an efficient guide to easily see which deficiency is causing what. So, there’s signs and symptoms, but then there’s what does your diet look like?
And I think that’s a part where people don’t really need my “Cheat Sheet.” I think there’s valuable advice about how to use that information in the “Cheat Sheet.” But, you know, there’s really good tracking apps where you can input your stuff. The “Cheat Sheet’s” role is really to integrate that leg of information with the other ones. And then finally there is the lab testing. And the lab testing I think is the most difficult part to navigate because number one, there’s a lot of tests out there and some of them are good and some of them are bad. And so, one of the things that I was doing that eventually led me to produce the “Cheat Sheet” was I was doing really in depth like two hour long podcasts on individual nutrients involving incredible amounts, like a couple hundred hours of research that would go into each one.
And one of the things that I was looking at is what do we know about the markers of nutritional status, what’s most validated and what’s not and if it is valid. And by validated, what I mean is you take someone in a controlled setting, you take the nutrients out of their diet, you see that marker change. You see that that marker changing correlates not just with taking the nutrient out, but that how much it changed can tell you how long of the way are they towards developing symptoms.
If they, you know, there are really great studies with zinc. Take the zinc out, watch the plasma zinc fall. At this level of plasma zinc, you get patches of dry skin. At this level of zinc, you get sore throat. At this level of zinc, you get diarrhea. So that’s a very well validated marker.
You can put the zinc back in, see it change and how that correlates with how cured are you from the deficiency. But there are tons of markers out there that are not validated at all or markers that they were validated that it goes up and down, but they weren’t validated like where does it go and what does it mean? And so, if it takes me a couple of hundred hours for each nutrient to be confident in what I’m saying is the best marker for that nutrient, how the hell is anyone who doesn’t have thousands of hours to devote to this going to get the right tests. Right? And so, and this is huge because… Oh, and so there’s getting the right tests, but then there’s also, and I think this is a really big one, navigating when you should get the test given the amount of money that you can invest.
So, I have, part of the reasons it’s called a “Cheat Sheet” is like one page is hyperlinked comprehensive nutritional screening that puts together all the best markers. But you only do the comprehensive nutritional screening if you’re doing the comprehensive or time-saving approach. Most people are going to use a cost saving approach because most people don’t have the insurance coverage to cover all of the tests. A lot of people will have insurance coverage for the ones that come from LabCorp and Quest if they get their primary care physician to sign off on all of them.
A lot of people aren’t going to get that to happen. So, if they want to get it, they’re going to have to go direct to ConsumerLab, in which case their insurance might not cover it at all. Right? So, there’s a huge number of people that have to be negotiating the cost. The problem is a lot of people, the way they negotiate the cost is they look at, “What is going to give me the most numbers for the fewest dollars?”
So, for example, I know a lot of people that go out and get a $390 panel because it gives them all of the nutrients for that $390. The problem is it’s not validated at all. And there are good science fact reasons to think that some of the values it gives you don’t mean anything. And so if you are, if you don’t understand in depth the lab test and you don’t understand the tradeoff of money, you would be much better off taking the cost saving approach, not getting the $390 panel, using the signs and symptoms and analysis, then getting directed to say, “You know what, here is the time to get the $60 iron panel because my signs and symptoms line up with having too much iron or not enough. And knowing whether I have too much or not enough is a critical decision about whether I do something that’s harmful or helps.” And that’s when you spend $60 on an iron panel. And so, walking you through those steps. If that was the only thing you got out of this $24 thing, you would have just saved yourself $330 by not getting a useless giant panel and getting the $60 iron panel that was the thing that you needed to make life changing results in your health. Right? So even if that’s the only thing you do, come on $24 to save $330, how is that not a bargain, right?
Ari Whitten: Yeah, 100%. I mean, and there are many cases where someone can, as you said, just not only save money but even skipping some of the lab tests, look at signs and symptoms and at least experiment with, you know, going, “Hey, this lines up with a deficiency in this and maybe I should try to consume some more of these.” Like it doesn’t have to involve, you know, kind of spending hundreds or thousands of dollars on a million different tests. There are applications to use this information and just start doing some experimentation with…
Dr. Chris Masterjohn: Yeah. And on that note, I think one of the helpful things that I did was I brought together the things that we know are symptoms of deficiency with the things that it makes sense that they would be based on how it works. And so, it’s tired as well-established signs of deficiency, possible signs of deficiency. And that really opens up what people are able to investigate.
Because for example, we were talking earlier about vitamin C, copper and zinc being involved in neurotransmitters that are needed to stop you from peeing when you go to sleep. You’re never going to find that in a list of vitamin C deficiency signs. So to have that as your problem and have that, you know what I did with just harvesting all this stuff about how the system works to get some speculation in there and mark it and tag it as speculative, I think it really opened up a window to you solving problems that you wouldn’t otherwise be able to solve.
Ari Whitten: Yeah. 100% and again, everybody listening, this is an amazing, invaluable resource. It’s 24 bucks. It’s worth obviously hundreds of, hundreds of more dollars than that and can potentially give you life-changing information. This is a must-have. Do yourself a favor, just go grab a copy of this.
And you can get it, it’s 30 bucks normally you can get it for 24 bucks right now. Go to chrismasterjohnphd.com/ari. Chris, thank you so much again, this has been a blast and we will have to do another fifth Podcast at some point, maybe in a few months.
Dr. Chris Masterjohn: For sure, man.
Ari Whitten: Awesome and enjoy the rest of your night and great chatting with you.
Dr. Chris Masterjohn: Yeah, you too.
The Science On Protein, Detox, MTHFR, Fatty Liver (And How To Fix It) and More with Dr. Chris Masterjohn Ph.D. – Show Notes
What science says on protein (02:22)
The science on detoxification (20:48)
The positive benefits of hormesis (30:30)
MHTFR – Is this something we need to be concerned about? (39:20)
The primary causes of fatty liver and how to fix it (45:41)
The MUST-HAVE The Testing Nutritional Status Cheat Sheet (55:25)