Exclusive Dr. Hyman+ Functional Medicine Deep Dive: Where Genetics and Epigenetics Intersect

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Hey everyone. This is Tom Molter. I'm a educator for the Institute of Functional Medicine. I've known Dr. Mark Hyman actually for over 15 years now through the Institute of Functional Medicine and you are blessed to be in his tutorage and a student of his amazing man and the people that he attracts are fantastic. So I'm hoping that I can offer some, I would say enlightenment from what I have learned in my clinical practice and through my clients teaching me And we're looking at something that's fascinating today. We're looking at epigenetics and genetics and how they intersect. So let's jump to it. Let's get right to the slide deck here. All right, so the interesting piece about genetics versus epigenetics is that we're looking at the things that our cells make, and in this case, it's proteins primarily or enzymes. And how our ability to make those things will allow them to be efficient or non-efficient. And the more efficient they are, the less concern we have for needing support for those enzymes. The problem becomes when the body goes to look at the template of proteins, which is the DNA, and it pulls open the DNA, and it tries to then read it, and then make a protein from it. And when it goes to make a protein from it, if it has a variance in it, what we oftentimes will call a single nucleotide polymorphism, but it could be a different type of variance. But when it has a different structure to the template, the protein that is made slightly off. When you have a misshapen protein, that protein can't do its job. So in nature, form equals function, right? So if you have a certain structure to a enzyme, that structure allows for then the attraction to the substrate to the enzyme, and then it carries out a reaction. The attraction, the entire function of taking something and binding to the enzyme and changing its shape and moving it on, and not occur very well if that enzyme doesn't have the right shape. There are two primary things that allow for an enzyme to be in the right shape. is the template itself. Two is usually a coenzyme or cofactor. So for example, let's look at magnesium. Magnesium is considered the most important mineral in the human body. Why? Because every single reaction in the human body that relies upon ATP relies upon magnesium. ATP has this negative phosphate group and if If ATP were to approach an enzyme, oftentimes that negative charge would be repelled unless that enzyme had positive charges in it from magnesium to draw the ATP in. What am I trying to say? I'm trying to say form equals function, information. Every form is allowed to mate with another form based on its structure. When the structure is changed due to genetics or the structure is changed due to a lack of specific nutrition, so B6, for example, or copper or magnesium in the case of ATP. If the enzyme doesn't have a coenzyme or co-factor available to change its shape, it cannot function very well. So that leads to disease. All right, let's jump in and I'll show this example in a case. Okay? I used to work for Seeking Health. I was the director of education there. Dr. Ben Lynch is the owner and amazing company, amazing guy. The Nutraceutical Company, Gene Analysis Company, of course we sold supplements and we also did gene analysis. So what you're going to see today are both the supplements I used when I was working there quite a bit, as well as the gene analysis tool that was called Strategy that was promoted by Seeking Health. Now, I get no financial backing for this. I have no connection with Seeking Health whatsoever other than kudos to my friend Ben. So at this time, I have my own practice, I'm doing my own stuff, there is no conflict. Okay, disease is caused by two primary things. I know Mark teaches this to you all the time, right? He says, you know, Dr. Sid Baker says, you know, if you have too much of something you don't need and not enough of something you do, you can slide into a state of disease. Meaning, if there are too many things in your environment that are irritating you, and not enough things that are supporting you. We're going to be talking about nutrients today, so we'll use nutrients as an example. If you have too many irritants and not enough nutrients, you can slide into a state of disease. Let's use histamine intolerance as our guide today as an example of disease. An intolerance basically means you have too much of something that you cannot process well, and therefore it creates an irritation. Histidine is an amino acid, it's found in a lot of high protein foods. Histidine with the help of histidine decarboxylase, which is a B6 dependent enzyme, can turn into histamine. Now let's just use this as an example. If that protein was at the wrong shape due to genetic variance and you didn't have enough B6, histidine couldn't make histamine very well. We're going to talk about these connections to these fascinating. Now, once you have histamine, we all know what histamine is, right? Histamine is the thing that kind of keeps you alert and awake. It's the thing that can give you hives. It's the thing that can cause intestinal permeability problems, gas and bloating, it can cause dizziness, it can cause insomnia. There's a lot of different things that histamine does in the human body. It's a very important cell communication molecule. We know of an allergy in the case of basophils and mast cells secreting histamine and leading to that redness, swelling, heat and pain that we know of for allergies. There's a lot of other things histamine does. Now, what could be problematic is if you're exposed to lots of histamine, like let's say through your diet, then you can't break it down very well. It absorbs into the system and now you have this systemic histamine response as if you have an allergy response. That wouldn't be so beneficial and it happens all the time. Look at the example of champagne. When you drink champagne, how do you feel after champagne? Nobody feels good after champagne. We all have headaches, we all have gut bombs, we all feel miserable. And if you start a night drinking with champagne and you drink anything else, you're a mess, right? Everybody thinks, oh, it's the alcohol. No, it's the histamine. Histamine and champagne is through the roof. Okay, so histamine intolerance, more histamine in your system, you can metabolize safely. Makes sense, right? Mostly reserved for excess histamine in the intestinal tract. Now, mind you, if you look at more modern research, it would say both inside the intestinal tract. And also, if you're lacking an enzyme called HNMT or histamine N-methyltransferase, it could be throughout the entire system. So we're going to talk about the two primary enzymes, one in the intestinal tract called diamine oxidase, the other one externally or systemically, which is called HNMT or histamine N-methyltransferase. So normally we think of a DAO insufficiency, normally we think of a histamine access. as leading to histamine intolerance. So let me give you an example. You have a person who needs to break apart histamine via an enzyme called diamine oxidase. So just like histidine decarboxylase broke apart histidine to histamine, we have DAO, which breaks apart histamine into an aldehyde. So diamine oxidase is secreted from the intestinal lining. Diamine oxidase also needs a coenzyme or cofactor. In this case, it's a cofactor called copper. In fact, if you have a copper deficiency, if you see someone with a frank copper deficiency, ceruloplasmin is off, their copper is off, whether you're looking at red blood cell or otherwise, hair, whatever, if the copper is low, non-existent, one of the first things that happens, boom, DAO shuts off. Copper deficiency can shut off the enzyme that degrades histamine leading to a histamine intolerance. Now, if it's secreted from the intestinal lining and the intestinal lining is not healthy, we can have problems. I have seen clients with celiac, Crohn's, cystic fibrosis, with SIBO, with C. diff who have had problems with histamine intolerance. Inhibited by substances. Now, this is the interesting thing. Both prescription medications and aldehydes. Aldehydes coming from environmental pollutants or aldehydes coming from alcohol, can cause severe DAO insufficiency. You can lead to histamine intolerance due to prescription meds and alcohol consumption and or aldehyde exposure. Where are we getting prescription meds? Come on. Some of the most common meds, even metformin, inhibits DAO. Interestingly enough, H1 blockers or histamine antihistamine meds, they block DAO. Valproic acid, the seizure meds, holy smokes, 90% inhibition of DAO. So if you're a geek like me, you want to go and you want to dive deep, you want to know the exact medications, you want to know the exact foods, you want to know the aldehydes in the environment, you want to know all that. I'm starting a website, it's called histaminesolutions.com, I'm going to have a certification program on there, just a couple months out, so I'll give you a QR code on the last slide if you want to geek out with me, great, come, but let me give you the basics right now, I want you to understand this. So, aldehydes and alcohol have a negative feedback loop. Once you degrade with DAO, histamine, you produce an aldehyde. When you have a lot of aldehydes building up, it will come back and block DAO function because you don't want to build up too many aldehydes in the cell, it will cause damage. It's an automatic negative feedback loop. You consume lots of alcohol, you're going to produce acetaldehyde or acetaldehyde. Once you produce an aldehyde, you have to get rid of that aldehyde, otherwise it will go back and shut down DAO function. That's the primary DAO inhibition pathway. Number one, you're not making enough DAO, that could be genetic. Number two, you don't have enough cofactor. Number three, you have some sort of intestinal lining issue that degrades the ability for you to make and secrete DAO. And then there are inhibiting substances, particularly prescription meds and or aldehydes and alcohol. Histamine N-methyltransferase is the second enzyme. Now, HNMT, as we know it as, needs a very important cofactor called SAMe or S-adenosylmethionine. Now, we all know about that through homocysteine and the methionine cycle and everybody, including my friend, Dr. Ben Lynch, I've been talking about this for a very, very long time. So whether we're talking about the 677T or the A1298C variances, you pretty much have to have homozygotic in one or both to have severe shutting down of this process. It's interesting, I don't see that as much. I don't see that genetically. I don't see that nutritionally. And when people have genetic challenges, oftentimes I will see them consuming enough folate or taking folate supplements and bypassing it. And when I run nutrient panels to see where their folate metabolism is at and looking at things like figlu or homocysteine, they seem to be fine with the folates in a lot of cases. So while it's theoretically an issue, I don't really see clinically it manifests as frequently as B12 problems. So We know that through the methylation cycle, we're going to look at some graphics of this. In the methylation cycle, we start with methionine, we go to SAMe, we go to SAH and then homocysteine, and then we go from homocysteine back to methionine with the help of folate and B12. And folate will donate the methyl group, B12 has to accept it and pass it off. But due to poor acid, due to poor protein consumption, due to a lot of different issues, we're seeing a lot of B12 insufficiency in clinical practice these days. While 5-MTHF is important, yes, you should test, yes, you should look, but it may not be the primary thing I'm seeing in my clinical practice with histamine intolerance. History and intolerance basically is going to be too many things you don't need and not enough things you do. Too many things that can irritate you, not enough things that can nourish you. So let's look at this in this context of histamine intolerance. You could be consuming alcohol or fermented beverages like champagne, wine, beer, et cetera, or meats. So spoiled fish is kind of where we found out about histamine intolerance. You have terrible symptomology with fish that has been left out too long to interact with microbes or bacteria with high histidine D carboxylase. And then all of a sudden, boom, you have these extreme high levels of histamine. and people can get sick. A lot of gastrointestinal issues there. Now, the interesting piece is if you get your fish and you immediately freeze it, flash freeze it, right? And you keep it frozen and then you just let it thaw enough and then eat it, the level of histamine is not gonna be too high. But if you leave it out, it's warm, it's stinky, right? Then that could be problematic. Cured meats, salami, smoked meats, deli meats, those are all quite high in histamine. So if you're consuming those, you could hit a threshold by consuming too many of those. And once again, an intolerance is a threshold disorder. So if you have too much of one thing in a sitting and then another thing in a sitting and another thing that's sitting, forget about it, you're gonna go over that threshold. So if you're having spoiled fish and you have an alcoholic beverage, oh, your sonk, if you had champagne and pretty much anything else, you're probably so. So when you're going to New Year's and you do this champagne toasting with a chartreuse board, you know, forget about it, right? Okay, so fermented foods, cheese, yogurt, sauerkraut, and vinegar. Now, you'll hear vegetables and the vegetables you'll hear will be avocado, there'll be spinach, there'll be eggplant, those, and tomatoes. Those are definitely foods that contain histamine, but you'll see variation in studies. And if you look closely, once again, if you want details, come check out my program. But, you know, I dove into all the food studies and really the levels on certain vegetables will vary a lot. You know, avocados have to be left out longer and there's just a lot of different things. So I worry about these foods first and then other foods second. Okay, cool. Now, the symptoms that you're looking for, if someone has too many of these things, and you're going through a dietary intake and you're like, whoa, you're eating a lot of histamine and you start saying, hey, what are you suffering from? Ah, dizziness and headaches. Okay, post-nasal drips, congestion, sneezing, aha, itching, flushing, eczema, yep, bloating, fullness, diarrhea, abdominal pain, constipation. Bing, bing, bing, bing, bing, bing, bing, right? I want your little, your spidey sense, your, your diseo-o-meter going through the roof and kind of, you know, tapping you on the shoulder and saying, hey, you know, that little voice is telling me I need to look at histamine. Okay? Now, if a pertinent, not pertinent, a person is, you know, alert all the time. They're having a hard time getting to sleep, insomniatic, headaches, whatnot. And you give them an antihistamine, and all of a sudden, boom, they're gone. They're, like, super out, they're chill, they're drowsy, you know, all their symptoms go away. You might be on to something, right? But. Recognize the opposite of too much histamine is not having histamine. And that's being like dead, like really dead tired, not dead dead, but just tired, right? So the primary symptom, if you give somebody antihistamine, is they'll get drowsy, okay? So recognize the opposite when you see it and think, oh, could that be? Look at the gut too. The gut symptoms are prominent.

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