 Thank you very much everyone. I want to start out by saying that I believe for most people high protein diets are safe and I also believe that diets that most people would consider high in protein are optimal for satiety and body composition for anyone trying to gain muscle mass or lose body fat and in fact I Eat what most people would consider a high protein diet right now. I'm trying to put on some muscle mass I'm gaining about 1.75 pounds of muscle per week right now and I'm eating 4,000 calories and 2 to 300 grams of protein per day, which most people would consider really high in protein and it's working for me in general when I'm eating 2400 to 3200 calories, which is more maintenance for me I still tend to get a hundred fifty grams of protein or so so I'm not coming here Protein phobic by any means or preaching against protein, but nevertheless I think that this question is really worth asking and that's what I want to convince you of by the end of this and I'll be clear at the outset that my title ends in a question mark and my abstract ends with a Sentence saying that something is deeply unexplored, but desperately needs to be explored So what I'm going to conclude with is more questions than answers But nevertheless, I hope this is really thought-provoking and I will also conclude with with what I think will be some practical Suggestions that are useful to people in a variety of contexts or your nutritional doing nutritional advising or anything like that So if we look at what protein does in the body, it plays a lot of beneficial roles that go way beyond body composition proteins are important as Structure and contractile units obviously, but also our enzymes receptors that regulate our metabolism pumps and channels for ions all kinds of things in the body and all proteins are made of amino acids and Those amino acids in their free state or when bound together in small strands called peptides can be used as hormones neurotransmitters and other signaling molecules and on top of all of this we can use amino acids to turn them into glucose during times of glucose deprivation and We can burn them for energy But all of this comes at a cost because all of these roles of protein require the nitrogen that's in protein and Amino acids carrying nitrogen is one of their most unique properties and if we're going to burn amino acids for energy or Use them to make glucose, which doesn't have any nitrogen Or we just consume more protein than we need and we have nothing to do with it Then we're going to have to get rid of it somehow and if we get rid of it Or we turn it into glucose or we burn it in energy because we're in a low energy state We have to do something with the nitrogen and that poses a unique metabolic danger and cost Because when you release nitrogen from an amino acid and do nothing else with it what you get is ammonia and Even slight elevations in blood ammonia levels increase ammonia levels in the central nervous system and are acutely toxic hyperamonemia causes tremors slurred speech drowsiness vomiting swelling of the brain and blurred vision and it can be fatal so over the course of our evolution we've needed to deal with that and in fact preventing hyperamonemia requires metabolic pathways that we have because we would not be able to survive as a species without them and principally the liver converts nitrogen to urea which is a non-toxic byproduct they can be very rapidly excreted in the urine and This is very simplified, but in principle what you're doing in the urea cycle is You're taking bicarbonate Which comes from the carbon dioxide that's released during our energy metabolism and that carbon dioxide dissolves in water and produces bicarbonate this is the same bicarbonate that you'd have in baking soda as a sodium salt and two nitrogens and you put those together to make the urea molecule and It goes from the liver into the urine and you get rid of it and this is the basis for despite the poisonous nature of ammonia We have studies indicating that at least in athletic populations You can consume massive quantities of protein at least for months with zero toxic effects So if you go to PubMed right now and you put in Jose Antonio High protein and you use the best match sorter what you get is what's on the screen Jose Antonio is the CEO of the International Society of Sports Nutrition And he thinks that you can and should if you're an athlete eat a lot of protein And so he's done a lot of studies. You can see a high protein diet has no harmful effects That's a one-year study. There's that study used over three grams per kilogram body weight The RDA for protein is 0.8 grams per kilogram body weight The average person winds up if they're eating the RDA winds up eating like 50 or 60 grams of protein per day and so he's testing levels that are five six or more times the RDA which is a lot of protein hundreds of grams per day for the average person and some of these go up to 4.4 grams of protein and in all of these these and these are all in athletic populations But in all of these cases there's been no signs of liver toxicity kidney toxicity Changes in blood lipids or anything that you might look changes in a comprehensive metabolic profile like anything that you would Use as a standard measure of someone's health does not seem to be damaged in athletic populations consuming really massive quantities of protein Because of the area cycle Nevertheless, you will sometimes see articles like this one that came out a couple years excuse me a couple weeks ago About a bodybuilder mom who dies from too much protein before a competition This was in the New York Post and you can see the bodybuilder mom on the left Megan Herford a mother of two and bodybuilder died after an overconsumption of protein shakes supplements and protein-rich foods She was found unconscious in her apartment in West Australia and was quickly transported to the hospital where she was declared brain-dead She passed away two days later She was competing as a bodybuilder since 2014 Also ramping up her gym routine in the weeks before her death The 25 year old mom and paramedic trainee had put herself on a special restricted diet While she was preparing for a bodybuilding competition in September upon her death Doctors discovered Hefford had been living with a rare disorder a urea cycle disorder Which stops the body from being able to break down protein? The disorder can lead to fatal levels of ammonia in the bloodstream and excessive fluid on the brain What I want to do with this talk is use extreme examples like this that are obviously rare and Work backwards from them to see if there's something that we can apply to a lot more people than we see in these very rare Disorders, but briefly to take a look at another example. That was quite similar that was published in a case published in the literature in 2015 here we have a fatal coma in a young adult due to late onset urea cycle deficiency Presenting with a prolonged seizure and in this case a 17 year old white man Previously healthy was admitted following a reported new onset generalized tonic-clonic seizure The seizure was witnessed by his mother She reported a continuous convulsion lasting for almost six minutes associated with urinary incontinence Prior to admission he had generalized body fatigue Intermittent nausea and vomiting for one week without any associated features such as fever chills diarrhea or abdominal pain chest Chains chest pains shortness of breath and weight loss He was diagnosed as gastritis in a primary health care clinic and was treated symptomatically upon further inquiry he reported recently joining a local fitness club and Starting on high protein supplement for one week prior to the development of the presenting symptoms and I don't have the whole case obviously, but you can see in the first word of the title this guy died at 17 and Granted not all the cases come from gyms but this is not a random sample of cases of hyperamonemia, but They all share the characteristics of someone who's not diagnosed with anything and then is Presented with these stresses so if you have free amino acids and The let's suppose on the left part of this diagram We could say that what we generally are doing with amino acids is stuffing them into our proteins But or using them as neurotransmitters, but if we're going to tax the urea cycle We're going to do it in the following ways, so if we have amino acids. We have The nitrogen that's what gets released as ammonia and then the rest of the molecule we call the carbon skeleton That carbon skeleton can be burned for energy It can be used for gluconeogenesis or it can be used for biosynthesis If you're in a very hyperchloric state that could mean synthesizing fat with it But it could mean synthesizing many other things that the body would need that doesn't contain nitrogen And when you do any of those things you release ammonia and they have to go into the ammonia has to go into the urea cycle So what that means is that anything that increases your need for energy utilization anything that increases your need for gluconeogenesis or anything that Increases your need for biosynthesis Kind of if the biosynthesis is coming from protein such as on a really high protein diet Or just needing to do something with the amino acids that you can't fit into your muscles is Going to increase the tax on the urea cycle and so those conditions are listed here on the bottom if you're fasting If you're dieting if you have an illness that increases your need for energy or some other kind of stress exercise any of those things can pose catabolic stresses that Increase your need for energy utilization, which could come from protein if you have a high protein intake that can drive these Processes or if you're on a low carbohydrate diet and you're restricting glucose that can drive these processes all of these things are totally Safe in a healthy person fasting isn't toxic. It shouldn't kill you But if you go back and look at these cases, it's not in both of these cases It's not just that they were taking whey protein It's that they were taking whey protein and they were going on an increased exercise regimen They were exercising more. Maybe they were dieting right so you have all these catabolic stresses plus this extra protein intake and You have this person who has a rare disorder that no one would have caught in the decades before in their life Because it's not severe enough to do anything to them when they're a baby or when they're seven or when they're 12 and then suddenly they put them into these these extreme stresses and They get revealed as this rare case Which obviously our diagnostic procedures are totally inadequate to find Because both of them were diagnosed after they died and then and then even in the acute symptoms They're going to emergency care and being treated for gastritis Right like I go in with the thing that will kill me and I have gastritis So it's a rare problem, but it's a really bad problem if you're one of these people So let's look at what can really go wrong and there's not a lot of biochem, but there's a little bit here, so if We are going to use the urea cycle We are going to have two inputs of nitrogen into that cycle one of them comes from aspartate and One of them comes from free ammonia What's not shown here is that there's 20 amino acids that occur in proteins There's other amino acids that occur in the body There's lots of metabolic pathways by which you could convert them and get the free ammonia or the aspartate But once you have those two inputs every time you run the urea cycle you need to input a Nitrogen from aspartate and you need to input a nitrogen from free ammonia You make a chemical called carbonyl phosphate and you use the ATP the energy from ATP and the bicarbonate to get that The carbon of the urea molecules shown up here is coming from bicarbonate The two nitrogens in the urea molecule are coming from aspartate and from free ammonia and because you're building up Something here by assembling molecules. You're using energy from ATP and When you do that you take ornithine, which is an amino acid derived from this process and make citrulline And then you take the nitrogen from aspartate add it to the citrulline and you make arginosuccinate Every time you the two steps that require you to build up bigger things from smaller things require ATP energy and Once you have arginosuccinate you then convert it to arginine you release part of the molecule Arginine is an amino acid you can get in the diet You can also make it the urea cycle is one of the ways that you make arginine In fact arginine can leave the cycle and do other useful things If you're going to cleave off ammonia you cleave it off of the arginine and you generate ornithine and ornithine can then Go through the cycle over and over again There's two Transporters that are needed one to get ornithine into the mitochondria where all the initial steps happen to form citrulline One to get citrulline out of the mitochondria Shown on this screen are five steps of the urea cycle Five out of the six that are important the next one's on the next screen plus two transporters. That's seven things that can go wrong There are seven categories of urea cycle defects and There are dozens if not hundreds of different mutations that can make every single one of these things go wrong Most of them are called private mutations because they're so damaging to reproductive fitness That the effect of natural selection is not to use them to do something with our species After generations it's to get them the hell out of the gene pool as fast as possible because This these defects obviously don't prevent you from having kids But in terms of general probability, they're really bad for your reproductive fitness if you die at 17 you're probably not having any kids In our society anyway Now notice that ATP energy is used here. So not only does catabolic stress Increase your need to burn proteins for energy and use the cycle But when you're exercising and you're in a caloric deficit your ATP levels go down and when you're in a well-fed rested state Your ATP levels go up because on a cellular level energy coming in energy going out So if you have catabolic stress that's inducing ATP depletion that Will decrease the activity of the urea cycle Because you have less ATP to run it on top of needing to use it more part of the regulation comes from a compound called an acetyl glutamate and Anacetyl glutamate is an activator of carbamoyl phosphate synthetase We come back to here what carbamoyl phosphate synthetase is doing is catalyzing the first step of the reaction To initially make carbamoyl phosphate So that's the first energy and it's the first step. It's energy intensive The body wants to regulate things that cost energy and make you devote chemicals to a certain pathway So you regulate it with an acetyl glutamate You make an acetyl glutamate from acetyl coa and from glutamate you get rid of it with a hydrolase that releases acetate so in order to make an acetyl glutamate you need acetyl coa and Arginine stimulates this By increasing the activity of an acetyl glutamate synthase There's two things to note here. One is that this is an eighth category of urea cycle defects It's probably the rarest one, but it exists. You can have a genetic defect in this too The other thing is that arginine is a stimulator here and probably activating is a symbol of having High protein intake, but this is something we can come back to in thinking about Treating these things are the effective protein in the diet on top of urea cycle defects There are many other categories of metabolic disorders that are also rare That all hurt the formation of an acetyl glutamate and cause secondary hyperamonemia and that's because You need acetyl coa to make an acetyl glutamate if you're burning fatty acids for energy and you have that pathway backed up all the Coenzyme a starts joining to fatty acid intermediates and you deplete the pool of coenzyme a you can't make acetyl coa and You can't make an acetyl glutamate so urea cycle stops running Also, some of those metabolic intermediates inhibit the activity of this enzyme because of toxic effects these are most common in disorders of fatty acid metabolism or disorders of protein metabolism, especially branch chain amino acid metabolism all Of those have everything we said about these each enzyme has its own genetic defect There's hundreds of different every all of that is true of all of those things so there's like dozens of different Rare metabolic disorders each of which has hundreds of mutations that can't be screened for in a genetic analysis Because most people that get diagnosed have a different one than everyone else and it's newly discovered So so far what we're looking at is Rare however Think of a few things about this rarity. I think everyone who learns about this is tempted to dismiss it because it's so rare So the first problem with that we already saw is that you diagnose people after they're dead That's a that's a rare problem, but it's a real one the second problem is that if you have a Rare mutation that causes a total defect in the enzyme and kills a baby and Then decades later you start discovering that there's all kinds of people who have rare mutations that cause a 20 or 30 That cut well Let's say a 50 or 60 percent decrease you have 30 or 40 or whatever percent residual activity And they have to be under severe environmental stress to die Then why then how on earth could it not be the case that there are lots of other? Mutations that are equally rare that cause 50 percent or 40 percent or 20 percent decreases in activity How can it not be the case that there's some spectrum? Where you get from the person who is diagnosed and treated who's in a bad position? But at least they get treatment the person who dies because it wasn't recognized Which is that most terrible position? What about the people who have such moderate mutations that? they feel really bad and something's really wrong, but they never get a coma and They're really difficult to diagnose because all of the signs are like all of these Diagnoses are based on pediatric cases where they look at the most extreme example and the things you pee out in your urine And if you take one of the best Books on textbooks on inborn errors of metabolism that exists which is by saw to Bray and colleagues in born errors of Metabolism 6 edition it's in now They say that the person who wants to study these in adults is hampered by the fact that there exists no reliable Information about what those urinary profiles are in adults because everyone is treated based on pediatric cases and Most pediatric cases aren't diagnosed because the kids go in with chronic diarrhea and they're diagnosed with Celiac disease with dairy allergies with all kind not that those things aren't real and more common But but people look at this and they look at what it looks like right and so they're Has There has to be cases at least that are rare that are more numerous that are more moderate where people aren't catching them The people who are in the worst position are the people that are in Undiagnosable, but feel terrible because they have no hope of Getting any solution because no one understands the situation and Yet they don't feel good most of us are lucky enough to be over where we feel okay We feel great. We feel amazing and somewhere over here is Hypocondriasis because you got complaints all the time and everything in your pee in your blood says you're normal So that's that's one aspect of why this needs more attention. The other is that It is very unlikely that These disorders have no analogs in common polymorphic genes that can do something to your urea cycle, but will never put you in the emergency room and If you look at cases of urea cycle defects one that I didn't put up here said they it was another fatal case They said in retrospect There were earlier signs that this guy had a urea cycle disorder because he did he never ate meat because he felt light-headed When he ate meat and also his brother got us flew out of nowhere and died when he was 15 and If eating meat can cause lightheadedness. Well, what else does it cause? you know if ammonia at toxic conditions causes tremors and Coma there must be some moderate level of ammonia that just makes you feel like crap and Decreases your cognitive function and so on and so I would suspect that these can be harbingers of What's really underneath that's more common, which is we all have different abilities to deal with this cycle and studying that can can help us Improve more people's health and we can learn from these things So if you're studying something more moderate you have to think beyond just what are the toxic effects of ammonia? Because the urea cycle is part of how you synthesize arginine Doesn't always operate as a cycle some of these enzymes in exist in other tissues where they're functioning to make arginine to get Rid of it, and you don't have the complete urea cycle But throughout the body those enzymes are important to arginine synthesis arginine is important for Amplifying glucose-stimulated insulin secretion Arginine has to be made into proteins and in fact arginine is one of the most common amino acids in the active sites of enzymes and in Receptors where they're bind to whatever activates them and plays a key role in all of those things actually working right Arginine is how we make nitric oxide nitric oxide Contributes to vasodilation if you don't get enough vasodilation you can get vasoconstriction and high blood pressure Nitric oxide is important for the immune defense and immunity to pathogens if you make nitric oxide with arginine What you get left over is citrulline it goes back to the urea cycle arginine can leave the urea cycle to do that over and over again there are some studies of Polymorphisms in these pathways I'm not going to comprehensively review them I'm going to say that there are not many studies and I want to pull out the one that I think is most illustrative of the point that I'm trying to make about how we can generalize or Not generalize, but how we can learn from these rare defects that I showed you To understanding how this might affect more people more commonly So one polymorphism that's shown here on the screen has been studied. This is an ornithine trans carbonylase and That's the second enzyme of the cycle that takes carbonyl phosphate and ornithine and citrulline This is going to be important for making arginine because if you don't make citrulline you're not going to go up to arginine This is excellent. So it's primarily affecting males and I don't know globally, but there are two French cohorts consisting of a couple thousand people each That showed that this is present in 25 to 30 percent of the population There's nothing remotely rare about that It caused it is People with this mutation have a 45 percent increase in the risk of hypertension One possible explanation of that is they don't make enough arginine and they don't get enough nitric oxide for vasodilation so in order to develop more support for that they took a subsection of The population they studied and they injected them with vasoconstrictors that went into their coronary arteries and Measured the amount of a yeah, I'm surprised they could do that It was measured the amount of vasoconstriction that they got no one died in the study and What they what they found was that it increased they had more vasoconstriction in response to that So one plausible hypothesis is that they couldn't make enough nitric oxide to counter the effect of that pharmacological vasoconstrictor This is also associated with a 20% increase in the risk of Alzheimer's Doesn't necessarily mean that that what we just went through is the cause of that but Hypertensions associated with Alzheimer's so maybe that causal pathway is how you could explain this What no one has studied to my knowledge is how does this affect protein tolerance? because if This truly does affect vasoconstriction and hyper tension because it Quantitatively impacts how much arginine you can make How can it not also? Quantitatively impact how much ammonia you can get rid of Because you need this enzyme to get rid of ammonia in fact this gene is the most common urea cycle defect out of all of them all of the rare ones So if the rare severe defect causes hypermonemia and the common polymorphism affects the pathway enough To affect the formation of arginine How can it not affect the disposal of ammonia now? I don't know that that means that ammonia rises maybe you have other compensatory mechanisms But maybe they're bad for you. It probably does something to your ammonia handling and So I'll conclude from this with more questions and answers, but I'll run through What I think this means for a few categories of us The first is for researchers From a nutritional science perspective does this or other such polymorphisms affect your tolerance to protein? Are people who have that more likely to feel worse or have less cognitive function when they eat higher protein diets? Do they spontaneously avoid the gyms that everyone was studied from showing that four grams per kilogram body weight is fine? Because catabolic stress doesn't make them feel as well From an evolutionary perspective Can we explain why 25 to 30 percent of at least the French population that was studied has this? Throw out a free hypothesis so some people or there's Considerable evidence that at least some viruses thrive on arginine Could a wave of some virus select for people who couldn't make enough arginine because they were protected from that virus Even though it's bad for vasodilation, but maybe it wasn't enough There was maybe wasn't bad enough for vasodilation to give them a rectile dysfunction and they still had enough reproductive fitness So I think this is really right for research The second set is The second set is practical conclusions So first of all just in general diverse and balanced diets are the most robust to deficiencies and toxicities Doesn't mean you have to eat of 40 30 30, but you when you avoid extremes It's the best baseline if you don't have reasons to go to extremes. I think it's why To test how you respond to your macronutrient ratios Many of us do things because we're supposed to or we think it's good And we don't even notice that it makes us feel like crap. I think that's wise for people who counsel other people in nutrition I think it's super informative to look at the inborn errors of metabolism and say I'm not a you know, well, there are there are physicians, right? So consider these before people are dead is is one rule But I think much more broadly if you're advising someone on what to eat There's people all over the place who don't feel well and no one can figure it out And they went to 12 functional medicine doctors who ordered them a Genova ion profile and ordered them this Urinary organic acids test and that plasma amino acids test and they have all this stuff. I Don't know. I obviously you know, I'm pretty much out of time. I want to open up for Q&A I can't explain everything that you could look for here but Study this stuff because if you see signs that have all their branch chain amino acid Metabolites are building up because they're not metabolizing the protein You don't need to diagnose them with a disorder to say hey, maybe you're eating too much protein Maybe maybe knock it down and see if that impacts how you feel so why ignore all of that stuff and And many of those reports actually say like this is high take carnitine take vitamin B6 Like but you should we should be able to look at that and say hey Maybe you're not tolerating this macronutrient ratio. Let's change it and see what happens and see if it improves anything So I'll be talking a lot more about this in my masterclass of masterjohn energy metabolism Which is on YouTube Facebook and my website. I also have these other things that are listed there You can take a screenshot of that if you want to find out how to contact me and of course here On the bottom right is my business card if you want to keep in touch and with that let's open it up to Q&A Thank you so much If you have a question Can you please go to either that microphone if you're on this side of the room and if you're on this side I will bring the microphone to you Quick question about acetyl CoA If you're on a ketogenic diet or a high-fat diet that's going to affect your acetyl CoA levels How do you see that impacting? in for most people I don't because Everything that you break down in energy metabolism you wind up making acetyl CoA with and so that's the most basic intermediary so You if everything's working normally then if you're in caloric balance You should have pretty similar flux of acetyl CoA in one place or another But let me let me use that as an excuse to riff on one of these rare genetic disorders so there's one called there's there's one called thylase 2 deficiency T2 deficiency and this is where You have an enzyme that's very similar to thylase 1 which you use in ketogenesis but it helps you metabolize leucine one of the branched chain amino acids and If you have a moderate decrease for genetic reasons in the activity of that enzyme You can use the enzyme that's involved in ketogenesis thylase 1 to do everything you need to do with leucine But if anything pushes you into ketogenesis you can lose that compensatory mechanism Because that T1 is is involved in ketogenesis. It doesn't have any room to help you with leucine And all the sudden you lose your tolerance to branch chain amino acids and so that's an example Where you know in rare cases going ketogenic could cause a problem with forming an acetyl glutamate, but I think for Most people if they're healthy and of course it's not just genetic defects You can have nutritional deficiencies that impact these things and other things But for most people if you're on keto or you're on high carb or you're in the middle You should be making enough acetyl coated to deal with this if things are operating smoothly We have time for probably just one more question so we can stay on time All right, so you say you ingest about 200 to 300 grams of protein a day. Is that correct? Yeah So what is the strat are you how you consuming that? What's the strategy and is there a more effective way of doing that if you're trying I don't I don't I don't really have a strategy behind that It's more of a byproduct of eating 4,000 calories a day Though it just happens naturally with whatever you eat it really does I mean my strategy is when I eat I try to hit 30 grams of protein And I can't eat three meals a day and get 4,000 calories in so I'm doing that a lot And so I generally don't eat a meal that has less than 30 grams of protein But if I eat a piece of fish I take out whatever that piece of fish is and sometimes if it's eight ounces of fish And I had other things that had protein in that meal it winds up kicking that pretty pretty high Right, and if you find someone that's doing like a more of a zero-carb approach and getting that in Are you finding any issues or have you come across any issues of just bolstering up high protein? But going zero-carb, so yeah, I mean I don't work with anyone consulting who does zero-carb But I think that I think that for anyone who is on zero-carb They should be airing on the side of high protein not low protein because carbohydrate spares your need for protein and And if you care about your body composition like you have specific goals in mind Then the less carb you eat the more you need to air the more The less latitude and flexibility you have with your protein intake someone can put on a lot of muscle and not You know they could stay at 1.2 grams per kilogram body weight and get away with it because their workout Facilitates that like if they're on high carb, and I think that becomes less and less likely the less carbs you eat So for those people if they feel good and everything indicates that they're healthy I think for a body composition goal. It's more important for them to hit higher on the end of protein Cool. Thanks We have we have like any more really short ones. We can squeeze one in my answers are the very Great talk Chris as always. Thanks. I was paleo nothing against Lauren Cordain. I love them It's great spaces probably why we're all here, but his first book was a low-fat kind of version and when you Go paleo you sort of go low carb. I think by default a lot of us maybe So I think I was eating a lot of protein and I can remember smelling on my breath ammonia and also when I Bathroom it smelled like ammonia. Are there any compensatory mechanisms to literally breath or Well, it's it's ball so in your urine the main reason you excrete ammonia is because of acidity Because ammonia is basic and then feces though. I could smelled it when you're on your feet and my breath Well, I mean if it's coming out in your breath, you were hyper ammonemic I don't know if you were clinically hyper ammonemic, but your ammonia level was high enough in the feces It it would light Well, if you're not you live you're not handling the ammonia. I guess the ammonia could could go into the feces but also Urea in the feet so in the liver the liver makes urea the liver doesn't really just go straight into the kidney It feeds the general circulation and so any pretty much anything in the liver can go into the bile And it can go in the gut and then either go into the feces or get reabsorbed and then go into the general circulation Go into the urine so even urea if your gut bugs metabolize urea could be liberating ammonia from the urea But if the ammonia is going to your liver and it's not being properly utilized Then I don't see why it couldn't escape through the bile ducts and get into your feces But your breath I mean if it's going out in your breath then it that was because it was in higher concentration in your blood I can't think of any other reason