Recently, I interviewed Dr. Sam and we discuss the role of genetics and methylation in health and thyroid conditions specifically. We talk about why Dr. Sam recommends comprehensive genetic testing for most of his clients, the need for personalized health strategies based on individual genetic profiles, how we can integrate genetic and functional medicine testing, the long-term benefits of genetic testing, and more. If you would prefer to listen to the interview you can access it by Clicking Here.
Dr. Eric Osansky:
I am excited to chat with today’s guest, Dr. Sam Shay. We are going to be talking about genetics and methylation. It’s going to be a fantastic conversation.
Let me dive into Dr. Sam’s bio here. Dr. Sam Shay solves health puzzles for busy, health-conscious moms, mompreneurs, and adults with Asperger’s, so they can exit survival mode and reenter community. Known as the “Friendly Lab Nerd,” Dr. Shay specializes in functional lab and genetics analysis for data-driven results. Dr. Shay is also a stand-up comic, using clean, observational comedy to educate and entertain. Thank you so much for joining us, Dr. Shay.
Dr. Sam Shay:
Thank you, Dr. Osansky. I’m really happy to be here. My hope here is to clear up a lot of confusion around the concept of methylation. I know your specialty is thyroid. I have been on multiple Hashimoto’s summits and have a big interest in various parts of thyroid health and Hashimoto’s. We’ll focus on methylation.
The reason why is there was a podcast late last year where Gary Brecka went on to Joe Rogan and talked about methylation. He spoke about how these five methylation genes are all you need. I just wanted to create a bit more of a rounded picture on the concept of methylation because I do respect Mr. Bracka’s ability to take complex information and simplify it and make it very teachable and understandable.
The overall criticism is he vastly oversimplified and frankly ignored some higher-level genetic phenomena that is more important than methylation. There are things that are more important than methylation. The way we know more things are important than methylation is the body will pivot and shift methylation processes because these other things are more important that they have to address.
There is a lot of complexity in the fields. I brought with me a presentation to show my homework, why I disagree on certain facets of Mr. Bracka’s work. Again, he is a great educator. I don’t take that away from him. He has a fascinating background. As a medical actuarial, he worked for the insurance companies as this weird hybrid between insurance adjuster and actuarial. I respect his perspective, but he vastly oversimplified, and I wanted to, in my opinion, correct the record.
Dr. Eric:
You hear a lot about methylation. As you mentioned, it’s not the most important pathway. I don’t want to say it’s hyped, but why are so many practitioners, including myself, talking about methylation compared to other things you’ll bring up here?
Dr. Sam:
Methylation is extremely important. For people who don’t know, methylation is referring to a methyl group. A methyl group is a single carbon with three hydrogens attached to it. It’s like the simplest addition you can make to a molecule next to having a straight up hydrogen.
What methylation is is a complicated form of tagging to molecules to mark them for starting or stopping certain things. The reason why when you add just one carbon atom with three other hydrogen atoms attached to it, how is it possibly that important? Structure dictates function in the human body. When you alter the structure of a molecule, even by just one carbon with three other hydrogens linked to it, you alter its function.
Methylation is critical for signaling to other systems of the body that this molecule is now earmarked for this purpose or is quarantined away for the purpose it was originally for. Very important.
The problem is that it’s like the founder effect. MTHFR was one of the first most famous genes that got into the public consciousness when genetic testing became more available to the wider public. Because the MTHFR gene just rocketed up as one of the most significant early access genes available to test, it just became this fixture in not only the scientific community but in the public consciousness.
Many other genes in my opinion are much more important than MTHFR. That founder’s effect has lasted. We are dealing with this genetic inertia of the founder effect of the MTHFR gene. That’s my opinion. I’d be happy to see evidence to persuade me otherwise, but that’s what I think happened.
Dr. Eric:
I agree. A lot of people, including patients, just know about MTHFR. They bring it up. Even when it comes to methylation, I think you’d agree that MTHFR is a component of it, but there is a lot more-
Dr. Sam:
We will see a giant schema of a dozen and a half genes, and MTHFR is going to be way off in a corner. I agree with you.
Dr. Eric:
Yeah. Can you briefly talk about, as far as how many genes are out there so people can get an idea? Out of those genes, how many on average do you normally test for?
Dr. Sam:
There is approximately 25,000 genes in the human genome. I have seen numbers ranging from 25,000-30,000, but the point is there is a lot.
The criteria for understanding what are the best genes to test for, I come at it from four specific prioritized filters.
The first one is the genes I am testing as it relates to health and being. I am looking for not the disease genes; I am looking for the drivers of disease. I am not looking for the cancer gene, the heart disease gene, the stroke gene, the Alzheimer’s gene, the dementia gene, the diabetes gene. I am looking for the genes that control the drivers of all of those.
There are seven major drivers that when activated will poke down on these “disease genes” downstream. Those seven drivers are inflammation.
Your ability to quench free radicals in the mitochondria, where 95% of all free radicals are generated.
Your ability to detox properly phase one, phase two liver.
Vitamin D receptors, your ability to use Vitamin D, not synthesize Vitamin D from the sun, which is important, but to actually get the Vitamin D once it’s in the blood, whether it’s from sunlight, supplements, or food, and get those Vitamin D molecules into the cells.
Then methylation is underneath that. Those four processes are super ordinant above methylation.
Then there is cardiovascular circulation.
Then there is fat and energy metabolism. Those are the seven drivers.
I am looking for genes that are controlling those seven drivers of disease. More importantly, I am looking for the ones that are looking at the genes that are upstream. There are hundreds of genes that relate to inflammation directly and indirectly.
But there are 15 that are up up upstream, the generals, that control all the foot soldiers underneath. I want to look at the top 15 controlling genes, not the hundreds of genes that are diffuse across the whole inflammatory pathway. That applies to free radical damage, liver detox. There are all these different genes we talked about. What are the most important genes amongst the seven drivers?
The third criteria is of the remaining genes, which genes show up in at least 10% variation in the general population? I don’t want to test for super obscure genes that only .001% of the population have. For those people who have them, they are very important.
I am talking about for the purposes of general health and wellbeing. What is the type of genetic tests that I believe everyone should have? I want to look at genes that minimum 10% of the general population may have variance on, as there is a really good chance that if there is something awry, we can catch it and not have to go down these super obscure genetic rabbit holes.
The fourth criteria is once you have figured out the genes that fit the seven drivers, you find the genes that are upstream in those genetic drivers. The upstream genes in the genetic drivers have at least 10% variance in the population. Which of those genes remaining have peer-reviewed scientific research in top-tier journals done on humans, not wombats or nematodes, that lifestyle, diet, nutrition changes alone will shift the epigenetic expression in the direction we want?
Those are the four criteria. When you boil it down, there is 100 or so. Like 100ish, plus. Not a couple thousand, not a couple hundred, not even 200. Certainly not just five that Gary was pushing. There is about 100. Those are the genes that I look at.
Not to the exclusion of other nice genetic tests. For those who want to find out genealogical data, what percentage Irish you are, or whatever. That’s fine, but that’s not the testing that I am interested in. It’s these genes that are the highest priority as it relates to all facets of health.
At the moment, I test for 110, which is one reason why I was very uncomfortable with Gary’s assertion that all you need is these five. Those five he mentioned, one of the five is not worth testing I think because it doesn’t fall into that 10% variation.
In fact, AHCY is one of the most conserved genes across the mammalian project we have out there. Even the answer to that is literally the only thing you can do is B3, which should be in anyone’s multivitamin anyway, so it seems like a really silly thing to test to begin with. There is hardly any variation, and the answer should be a part of your stack regardless of whether you tested for it or not. I even have quibbles with the five he chose.
Dr. Eric:
Pretty much you are looking for drivers and not genes that are determining if you’re at risk for cancer or heart disease. For those listening to this who want to know if they have a genetic predisposition for Graves’ or Hashimoto’s- Most people already know, but you are not looking to measure genes to tell a person if they have a disease. Just the drivers of certain conditions.
Do you do genetic testing on everybody? It sounds like you do.
Dr. Sam:
I do genetic testing on almost everyone. Some people don’t want to do it because they get squirrely about having their genetic data tested. The value of genetic testing is both short-term and long-term. It’s the highest value test of any test out there I think in existence because the value of the data doesn’t decay over time. You can run a genetics test once, and those results stay the rest of your life unlike say, a thyroid test, which you have to get retested whether it’s several times a year or at least once a year. You have to keep retesting.
Genetics, you spend $1,000 on a genetics test. You amortize that over 20 years, and it’s $50 a year. Over time, the cost is negligible. The functional tests, you have to keep repeating.
The value of doing functional tests in tandem with genetics tests, what genetics tests will tell you is where is your ideal? Where is your ideal diet? What are the hard-wired food triggers you have? What are the hard-wired issues you have with inflammation, free radical damage, Vitamin D receptors, all those things I mentioned? What are the genetic fault lines you’ve inherited that you can shore up? It’s giving you where is your ideal, and where are the things you can shore up.
What genetics doesn’t do is give you the thumbprint of what your biochemistry is doing now. It doesn’t tell you what amino acids you’re deficient in, what your thyroid levels are, what infections you have in your gut, what cortisol levels are over the course of a day, what your sex hormone binding globulin is, what your blood sugar is. All those functional tests are great. If you are doing an ion panel from Genovva or a NutriStat, the genetics test is not the thumbprint; it’s the filter in which all your physiology is translated through. So they go together.
People who choose to delay genetics testing often have some really acute issue going on that they have to allocate their resources in the moment toward what is going on functionally? What’s going on in my gut right now? What’s going on with my thyroid right now? What’s going on with my adrenals right now? What’s going on with my mitochondria right now? I know genetics are important, but I have to prioritize the resources to figure out the thumbprint of what is going on with my physiology right now because I am in a real or perceived crisis that I need to get figured out. We’ll do the genetics once things have calmed down. Those are the cases where I don’t run genetics on everyone right away.
Dr. Eric:
Okay. Most people, you do. Some people, you don’t. It sounds like either way you integrate functional medicine testing. It’s not like your patients just get genetic testing, and that’s it. You’ll also recommend other testing as well.
Dr. Sam:
Genetics is one of those things where people can come in and get their genetics regardless of their age, state of health, or health objectives. It’s the one thing I’m quite comfortable with people who want to come in and get their genetics tested, and they have their info and are on their way. That makes sense for me in that the data and recommendations don’t necessarily change if we are just purely looking at the recommendations on the genes alone, regardless of their health state.
What happens is people can try to implement the genetics ideally with support. I have a six-month program where people have support implementing. There is a back-end course. There is an option for office hours. There is a way to support people through integrating all of their genetics recommendations.
If people run into roadblocks, but they only wanted to do genetics, and the genetics recommendations hit a plateau of where they want to go, that is the time they have to examine: Do I really need to take a closer look at my other lifestyle recommendations that aren’t tethered to genetics? Do I need some deeper functional medicine testing to see if something is going on that is blocking my ability to help me benefit from these genetics recommendations?
I’ll give you two real examples. One of the genetics tests I run is looking at are you keto, paleo, Mediterranean, or high carb? This is not a test you can get off of 23andMe or Ancestry. It’s not looking at variant analysis; it’s looking at copy variant analysis. It’s looking at the number of duplicates of a gene, not the version of the gene.
There is a particular gene that looks at your ability to generate the enzyme that breaks down carbohydrates. It’s the duplicates that matter, not the variation. When you run the instructions, we need to make these enzymes to break down carbohydrates. That enzyme runs through all the copies.
Imagine my digestive system is a fort. There are Visigoths, barbarians charging the gate; these are carbs. I have cannons lining the fort to keep them away. The cannons are these genes that are made spitting out these enzymes that break down carbohydrates.
Now, the red dot, or the bad version of the cannon, shoots 90 bullets a minute, where the yellow dot is 95 and the green is 100. In this particular case, the version of the cannon doesn’t really matter. But there is a big difference between one cannon and 10. If I had a red dot for 90 bullets per minute cannon, times 10, that’s 900 bullets versus one green dot, which is 100. I would rather have 900 than 100.
It’s the number of the duplicates that matter. The lower number of copies you have of this gene, the more you are trending toward a paleo or keto lifestyle. The higher number is more of a Mediterranean or higher carb.
I had a perfect Mediterranean diet. I knew the names of my farmers and their chickens. I was still having problems with my digestion and energy crashes. It wasn’t making any sense. When I ran my genetics, I realized I had the second lowest carb tolerance you could have. I had two cannons. That’s it. I am more of a keto straddling paleo diet. When I shifted my diet, my digestive problems of 20 years went away. It wasn’t a carb quality issue; it was a carb quantity issue.
If I know my genetic tolerance for carbohydrates, I can radically shift my diet to what I am supposed to have from a carb tolerance level. If I know all of these things about me genetically, I know my ideal.
Tying it back to the question of if things plateau, if you know your ideal, but it doesn’t work out. If I am a very low carb person genetically, meaning I have to have a higher fat, higher protein diet, but I have a problem with my gallbladder or my ability to absorb fats across the intestines or a problem with my carnitine shuttle or my mitochondria to burn fat, then genetically, I prefer fat, but metabolically, I can’t process it. Now, we have a conflict. These are the people who say “No matter what diet I try, it doesn’t work.” They can do higher fat genetically, but they can’t do higher fat metabolically.
On the flip side, some people are high carbs. They need higher carbs genetically. What if they have a candida infection? It causes all the candida or other infections in the gut to bloom. They have a conflict where they need high carbs genetically, but they can’t process higher carbs metabolically. Again, these are the people who say they have tried every diet, and it doesn’t work because they are in conflict no matter where they go.
These people need to have one strategy. They need to deal with their functional issue first with one diet and protocols to clear up the problem, whether it’s fat digestion issues with the gallbladder or pancreas or absorption or carnitine shuttle or mitochondria. Or they have a high carb issue and need to clear up the infection. Once you have cleared those up, now you can switch your diet to your genetically ideal diet and go from there.
This is what I mean by people can find out their genetics. They can implement. If they hit a plateau, that is when functional testing will come in. The problem is when people only do functional testing, but they never do their genetics, the diet they did to help them get off the functional issue will eventually backfire because genetically, they are not optimized for the diet that was useful to get rid of the functional issue.
Even if people who just do functional, they need to do their genetics eventually. They are more likely to run into problems, and they won’t see the weaknesses they have inherited that will manifest most likely in the future.
I recommend everyone does their genetics. They keep an open mind to doing functional testing down the line if they hit a plateau.
Dr. Eric:
Makes sense. Also, detoxification, which methylation is part of phase two detoxification. You could also get a good amount of information from the genetics and see if someone has the genes that cause problems with producing glutathione.
Dr. Sam:
Oh, we didn’t talk about that. I can pull up my presentation and discuss that directly.
Dr. Eric:
If you’re ready to do that now, let’s go for it.
Dr. Sam:
Great. What we’re looking at here, the reason we are talking about this is Gary Brecka’s 10x gene test, etc. This is coming from his work. He tests for MTHFR, MTR, MTRR, AHCY, and COMT. His claim was these are the five most important genes. Get these five done, and they will help you forever. These are the most important genes, not only for methylation but for genetics, which I disagree with, and here’s why.
This is methylation. This is not even showing all the genes associated with it. The genes are very complicated. MTHFR is just over here. That is MTHFR2. There is a second one. There is a sequel that is also involved there. Here is MTR. Here is COMT. I have to add in AHCY over here in the corner because it wasn’t significant enough to even include in some of these genetic methylation cycles.
What you are looking at here, the whole point is how do you deal with homocysteine? It’s such a damaging molecule. The body has three separate ways to get rid of it. We have the direct pathway, which is the folate cycle, which is where MTHFR became most famous.
We have the indirect pathway, up here through BHMT, which is burning a lot of resources, but it’s a way to quickly get rid of it.
Then there is a way to turn homocysteine into glutathione. You need to go through the transsulfuration CBS pathway. You have to go through some liver genes over here, including a couple glutathione genes, to synthesize glutathione. This is a phase two pathway.
When Gary asserts it’s MTHFR, MTR, COMT, and AHCY, it’s like no. There is a lot more going on here. Additionally, there are other processes afoot.
I talked about inflammation as one of the seven drivers. These are references to articles on PubMed that show how inflammation controls methylation. At a minimum, inflammation and methylation are bidirectional, so they control each other back and forth. There are very clear cases where inflammation actually controls methylation directly; it’s not a two-way street.
These are the examples I mentioned, like the top 15 genes that are the most important 15 genes for inflammation. Here is a list of them. People can spend time going through the hexadecimal hieroglyphics here. All these different names and subnames of all of them.
It’s looking at the interleukin 1s, the interleukin 6, interleukin 8, 18, TNF alpha, three CRP genes, two COX genes, and interleukin 10s. A lot of gene tests don’t even include the interleukin 10s, which is baffling to me. The interleukin 10s are the genes that are responsible for putting out inflammation. I want to know if I have a squirt gun or fire engine on patrol to put out inflammation.
Then we have oxidative stress with its own control over methylation. This is controlling free radical damage in the mitochondria. More reference articles here. Here is a direct quote, “Oxidative stress on complex traits and disease may be partly mediated through changes in epigenetic markers, EG, DNA, and methylation strategy in the body.” If you control free radical damage, then you change how methylation even works.
Then we have the details of that. For people who want to understand what dealing with free radicals actually means, the mitochondria is a very complex electricity factory. It takes carbs, proteins, and fats combined with oxygen and burns them to make electricity, what we call ATP. When you burn things in this factory, you make a lot of sparks. Those sparks are the free radicals. You need janitors to run around and put out the sparks, so the factory doesn’t get caught on fire.
The superoxide enzyme, MNSOD, who I have jokingly called Mr. Sod, he is the head janitor. He takes two of these sparks and combines them together to form hydrogen peroxide. Then his two subordinate janitors, GPX1 and GAT (glutathione peroxidase and catalase), they take two hydrogen peroxide molecules and convert them to oxygen and water. If we pause to think about it, that’s amazing. Your body will take free radicals and convert them to oxygen and water, which is incredible.
These janitors are really important. If you have variations, if you have a red dot with Mr. Sod, like I do, then your head janitor is limping along and is not able to keep up very well. I need to implement lifestyle and diet strategies to give Mr. Sod the support he needs to work efficiently to prevent the mitochondrial factory from catching on fire.
Now, we can relate your expertise in thyroid health. Inflammation, I’m sure you have multiple podcasts on the role of inflammation and how it affects thyroid. Am I right? Just tons and tons, right?
If inflammation is so important with thyroid health, wouldn’t it be important to know if you are a hyperinflamer like myself? Are you more prone to inflammation than other people? You can implement additional genetic strategies, so the other strategies that people are doing to improve their thyroid health work better. That is the connection between genetics and thyroid health or anything else.
If you can help the inflammatory pathway, then all the other things, the specialized things for whatever organ du jour you’re looking at, be it thyroid, adrenals, gut, etc., then it all will work better.
As it relates to mitochondria, the best way I’ve heard it described is the mitochondria are the business end of the thyroid. The mitochondria is the end organ of the thyroid. What is the target of T4 floating around?
By the way, I describe it as T4 is this four-wheeled car that drives around the bloodstream. It pulls over into the cell right next to the mitochondria factory. It opens one door, and you hear the Transformers noise. It turns into a T3 engineer. It button mashes on the controls of the mitochondria to dial up the activity and burn rate of the mitochondria.
The issue is you can have great engineers button mashing on the control panel. But if the mitochondria is broken in some way, then the thyroid hormone engineers aren’t here to fix the thyroid. They are there to dial it up and dial it down. That is why mitochondrial health is critical for thyroid health.
One of the links of genetics and thyroid health is that if your janitors inside the factory can’t keep up with things catching on fire, then you’re going to have problems implementing any successful thyroid strategy because the end organ of the thyroid hormone is on fire because there is sparks flying everywhere.
Dr. Eric:
Makes sense. If you have certain genetic variations on inflammatory markers, like an oxidative stress marker, it will be very difficult to reduce inflammation, reduce oxidative stress. You can get mitochondrial dysfunction, which in turn can affect thyroid function. Most people with thyroid conditions have thyroid autoimmunity, which is associated with oxidative stress and inflammation. I definitely understand.
Dr. Sam:
Awesome. We will jog quickly into liver in a second. First, we are going to talk about Vitamin D utilization. These are citations that Vitamin D has a role in regulation of gene expression, including DNA methylation by the Vitamin D receptor.
The big thing to understand about Vitamin D is it has been estimated between 3-5% of your human genome is controlled by Vitamin D. That is 1/33-1/20 of all your DNA is influenced by this one molecule. I would put Vitamin D as one of the most important molecules in the entire human body as it relates to health.
The main function of Vitamin D is regulating inflammation and immunity. Its bone formation is one small piece of it, but it’s not the whole story. People’s ability to utilize Vitamin D is critical. In fact, this double red dot here is a pattern I’ve seen when running tests on hundreds and hundreds of people. Almost always when someone has a chronic issue or autoimmune issue, they have double red dots or double yellow dots in their VDR and VDR2 genes.
I notice this as a pattern. I also found the exception proves the rule. I had one client who had really terrible long-term health, all sorts of stress, and had a double green dot. That person went through a massive, utterly life-changing, formative, long-term stressful event and series of events. The chronic breakdown was vastly influenced by an acute and chronic stress response. Everyone else who had struggled chronically with their health, I have seen a pattern of double red dots, double yellow dots in the Vitamin D receptor genes.
I went back to the chief scientist and said, “I want you to look at your primary database. I want you to talk to your other practitioners who do a lot of the gene tests. I want you to check if I am making this up. Do you also see a correlation between chronic issues like autoimmunity and these Vitamin D receptor genes?”
Months later, he came back to me and said, “You’re exactly right. They see the patterns. I see the patterns. This is something very significant.” It’s the inability to use Vitamin D as massive ramifications for long-term health. And it also at a minimum is bidirectional to the relationship with methylation and also at times has control over methylation.
For anyone watching or listening to this, I really encourage people to get clear on their Vitamin D receptor genes. The answer is not just taking Vitamin D. That is helpful. But there are other things you have to do in order to increase the expression of the Vitamin D receptors on the surface of the cell so it can capture more Vitamin D. Simply taking Vitamin D may not be enough.
Dr. Eric:
That was actually going to be my question. Taking massive amounts of Vitamin D, like 10,000 IUs, it’s not a long-term solution obviously. But the question was can you change anything because it’s genetic? But the answer is you can change the expression. It’s not permanent.
Dr. Sam:
Absolutely. That was the fourth criteria of what genes to pick. You don’t pick any fatalistic genes. “Oh my god, you have this gene. You’re done. You might as well write your will now. You may keel over tomorrow. Bye.” I call that 23andMe syndrome, where people get their genetics report and freak out. They are not empowered to actually know what they can do about it.
None of the genes I’m showing you are fatalistic. You actually can do things to support the expression the way you want.
You mentioned detoxification. There are eight major genes in liver detoxification. Three in phase one, five in phase two. We already saw three of them up above in the methylation pathway here. DCL, CAGCL, GCP1 genes in the formation of glutathione. This is very interesting diving into the effects of methylation and detox.
Here are a couple quotes. “Environmental toxicants such as toxic metals can alter epigenetic regulatory features such as DNA methylation.” Right off the bat, it’s saying that toxins can change how you methylate. If you’re not able to detox properly, then it’s going to change your methylation status.
The other thing that Mr. Brecka talked about is he said the AHCY gene was the main gene for understanding people’s mental moods. There are other really important genes out there like MAOA. The issue with AHCY is the main answer to it is B3. There are very uncommon mutations of the AHCY gene to begin with. I think there is better genes to pick. The ones he did pick, B3 is all I can find. If he has something else, I’d love to see the citation, but I couldn’t find one. All I saw was B3, and away you go. If there are other things, that’s good to know. It didn’t seem that practical.
The MAOA genes are really interesting. There is a very high correlation with different predispositions to different moods. Exercise and stress management help a lot. Different combinations mean different things.
This one is a public service announcement. People who have MAOA with one red dot and MAOA 2 green dot, alcohol is particularly dangerous for them because these are the people who can get violently drunk. This particular combination is really bad for people who drink alcohol. This is a no-go zone when I see this combination in the clients who I run their genetics for.
There are certain things that help. It’s not just do something, but to avoid something. Alcohol is one of those things in this case.
In summary, in terms of Gary’s work, I think it’s way too simplistic. He just picks five genes for methylation when in fact there is about a dozen and a half. Also, methylation is subordinate to all these other processes, like inflammation, free radical damage, Vitamin D receptors, and liver detox. There are other better genes looking for mood than AHCY.
Those are my thoughts about this whole methylation fiasco that was released into the zeitgeist late last year. I just want to pause there. Do you have any other comments or thoughts you wanted to discuss around methylation?
Dr. Eric:
First of all, great presentation. Thank you for sharing. I think as practitioners, a lot of us, including myself, talk about the impact of methylation on detoxification since it’s part of phase two detox, but then you mentioned that the toxins themselves can have a negative effect on methylation. If you have heavy metals and exposure to other environmental toxins, that could be-
Dr. Sam:
Also, inflammation is above detoxification. The best example I can think of: If you are in the kitchen, and there is a garbage can full of garbage, you have a priority to take out the garbage. What if you walk in the kitchen, and the kitchen is on fire? What is the priority? Putting out the fire or taking out the garbage?
I gave a lecture at a genetics conference called Exercise-Induced Obesity, which sounds like a funny title. What happened is I saw a pattern in certain clients where the more they exercised, the fatter they got. It was this kind of inflammatory weight. It was water puffy weight.
What happened is they had a certain combination of genes where they were hyper-inflammatory. Plus they had genetic variations in their liver detox genes, particularly GSTP1, which was the limiting step to glutathione synthesis. They were overexercising.
One person in particular, she joined a Crossfit gym, and they’re nuts. She was overexercising like an hour a day. It was stupid. Their trainer was being really dumb. Overtraining became proinflammatory. Her whole body became inflamed. When your body becomes inflamed, you retain water to dilute the inflammatory chemicals to prevent them from damaging your cells and tissues. You basically retain water to buy your liver and kidneys time to flush out the inflammatory chemicals.
She was proinflammatory, particularly in the CRP genes, which are right here. They are the ones that control the acute phase inflammatory proteins in the liver. It was a perfect storm. If you create massive amounts of inflammation, you overproduce the acute phase inflammatory protein in your liver, and you have problems genetically detoxing, what is going to happen is that your body’s priority is now to get rid of all the inflammation, not to detox estrogen. Not only did she put on puffy weight, but her cycles went off.
For the men who had this same genetic pattern, they didn’t have a cycle to go off, but they all developed man boobs. They had increased inflammatory weight. They couldn’t get rid of the estrogen that was building up. The estrogen stayed in their system and repositioned fat in their body onto their chest.
The answer for them was not fewer calories and more exercise to drop weight. It was to drop the inflammatory input, stop overexercising; get them on an anti-inflammatory, liver detoxing, anti-estrogen diet; remove all the exogenous estrogens, plastics, and other culprits of exogenous estrogen.
Her muscle tone came back. Her cycles normalized. One gentleman lost over 40 pounds in one month. The other gentleman lost one kg, which is about two pounds a week, for 14 weeks or so. The man boobs went away, and the belly fat went away. They were overweight, but they were overweight genetically because they were proinflammatory, and they couldn’t detox properly.
I had to give them different protocols other than exercising harder and starving yourself. The weight wasn’t calorie-based; it was inflammatory-based. Exercising was the trigger, not the solution, to the weight.
This is where getting your genetics tested is super important. People have different styles of weight gain. Some people are inflammatory water weight gainers. Some people are hormonal toxic weight gainers. Some people are fat calorie weight gainers, which are the ones we typically think about. But the vast majority of people I have seen who have stubborn, puffy weight are not fat calorie weight gainers. They are inflammatory water weight gainers with hormonal toxic weight gainers.
Dr. Eric:
You mentioned the CRP genes. If someone has genetic variations, they might be more likely to have acute inflammation, thus having positive CRP. Every now and then, I’ll come across someone, not uncommon to have people with high CRP, but sometimes it’s more challenging to decrease. Sometimes, it can be a challenge finding out the source of the inflammation. Could it also be partially that it’s a genetic problem, too?
Dr. Sam:
That’s what’s written right here. “CRP is mainly triggered by interleukin 6, socio chronic of many diseases.” Orange and particularly red dot indicate increased production of CRP and increased risk of inflammation. People who have variations can overproduce CRP. The answer is absolutely yes in my opinion, based on the genetic research.
Dr. Eric:
One other question with this: Since there are other genes associated with inflammation, just because someone has a negative CRP and let’s say a negative ESR, that doesn’t mean they’re inflammation-free.
Dr. Sam:
No, because inflammation takes on many different forms, and there are multiple molecules associated with it. ESR is triggered by so many different things, it’s almost a non-helpful marker because it’s so non-specific. There are other more specific inflammatory markers to look at. Some people are more genetically prone to creating certain inflammatory processes over others.
Dr. Eric:
I wanted others to hear. Some people will get a CRP. They see it’s negative. Once they understand that it’s associated with inflammation, they might assume everything is good to go. They don’t have inflammation. Just wanted you to reinforce there are other inflammatory markers.
Dr. Sam:
There are many more things to look for than just CRP. I wanted to share if people were interested in getting genetics labs for themselves.
Dr. Eric:
I was just going to ask you: If people are interested in learning more about this, what can they do?
Dr. Sam:
The 110 genes that I run, they are broken up into six different panels. I am not picking out individual genes. I do all of them. They are broken up into six different parts.
One is the find your ideal diet, which is the one I described before about the number of cannons. That is to determine if you are more keto, paleo, Mediterranean, or high carb, or some variation in between.
By Mediterranean, I don’t mean the ingredients. I am talking about the carb density of people who are Mediterranean. There are plenty of other people around the world who don’t have foods of the Mediterranean diet, but they have a similar carb ratio panel. That’s what I mean. Figuring out what your carb tolerance is is crucial.
Trigger foods. There are some hard-wired food triggers. Some people can’t tolerate histamines, or they can’t tolerate gluten because they risk developing Celiac. They can’t break down the lactose enzyme. Some people can’t tolerate alcohol.
Some people can’t tolerate caffeine, which may be hard to hear. There is a certain percentage of the population, myself included, that get what’s called “caffeine-induced anxiety and depression.”
When I talk to a room of entrepreneurs, and I mention that there is at least 10% of them who have this variation where they get caffeine-induced anxiety and depression, you can hear the stress response just go in the whole room. Everyone believes that their entire business runs on coffee.
That’s a very confronting set of genes. I have those genes. I have found non-caffeine-based ways to support my energy systems. It doesn’t matter how much coconut oil or MCT oil you put in your coffee. The caffeine will screw you up if you have these genetic variations.
There are the Vitamin D absorption genes. That is not only how you are able to utilize Vitamin D to get into your cells, but also the sunlight pathway. There is about a half dozen genes between sunlight and your bloodstream in terms of synthesizing Vitamin D.
There is also eating behaviors. Some people are genetically wired not to feel full as readily when they eat food because fullness is not in the stomach; it’s in the brain. It’s the signal from the stomach to the brain.
Some people are genetically wired to crave more sugar or overeat sugar or avoid or not mind bitter foods. All of these things really influence how you eat. For some people, “Wait a minute. You said there is no fatalistic genes you test for, but some people are prone to craving sugars. Isn’t that fatalistic?” No, it’s just that if you have the hard-wired genetics for that, then you don’t try to control your willpower; you control your environment.
I don’t keep bread in the house because it won’t last half a day. I’m not stronger than bread; I’m smarter than bread. It’s controlling my environment. That’s how you can be empowered by these seemingly fatalistic behavioral genes. Don’t bother with willpower; just control the environment. There are very specific strategies with that.
There are immunity support genes, which is looking at immunity genes. In particular, there are lots of Vitamin C and zinc genes. Some people need more Vitamin C and zinc.
There is the achieve your natural weight genes. This is the big panel that has the genes that have those seven drivers: inflammation, free radical scavenging, liver detoxification, Vitamin D utilization, the dozenish methylation genes, the cardiovascular blood pressure genes, and the fat energy metabolism genes. That’s in this one.
This is the one where you look at what can I do to shore up those genetic fault lines? What do I need to do from a genetic point of view to normalize and optimize my weight and decrease inflammation?
That’s how the 100 or so genes are broken down. This is just more of a write-up of what all the different gene panels do.
If people want to learn more, the next step is to go to my website DrSamShay.com. There are several e-books there on genes. There will be an invitation there to join a webinar or schedule a call to discuss the best option for you.
I also have on my website a Genetics+ program, which is a way for people to learn their genes either in a DIY model, where you get the gene reports, the customized report, and then a back-end portal with lots of detail on all the major gene categories as a self-paced learning program.
There is also an office hours model if people want to have an option to be in group dialogue about genetic questions.
People need to give themselves six months to implement genetic changes. Once you implement them, you have them for life. These recommendations are based on science and your genes, which don’t change. If people lock in these lifestyle changes, they have these benefits for life.
Genetics testing is the single highest value per dollar investment in health anyone can ever do. The results do not change over time. The recommendations do not decay over time. You get this test once, and you’ve got the recommendations and the decision trees for life. Especially critical if you want to find out your ideal diet, what your genetic baseline is. I very much encourage people to at a minimum get their genes tested.
Dr. Eric:
All right, thank you so much. Anything else that you wanted to cover or summarize before we wrap it up?
Dr. Sam:
I’d say that the genetics is a very fraught ecosystem, where everyone has a very strong opinion. If you talk about any individual gene, it’s going to sound like the most important thing ever, like MTHFR. It’s going to come across as magic bulletism. “Oh, if you just deal with that one gene, it will solve all the things.” That is simply not true.
This is why I recommend if you are going to get genetics testing, make sure there is a priority filter put on the genes. You’re looking at the highest priority genes as a whole, and you have a logical, science-based read-out of the things to implement in order of priority, and not fixate, like a dog on a bone, on one gene, or even five. Really look at the highest-level collection of all the genes.
And really look at how you can best support your lifestyle over the long term. Genetics testing will give you a road map long-term. If you hit a plateau, make sure you open up your mind to you may need to get some other things attended to in order to further benefit from genetic lifestyle.
The genes themselves are not a magic bullet. It may seem strange for someone talking about genes for an hour to say genes aren’t the magic bullet. They’re not. They’re a very critical part of someone’s entire health plan, their entire wellbeing plan. Whatever your objectives or performance goals are, genes must be a part of it, but it is not the exclusive part of it.
Dr. Eric:
All right. Just as important, I realized on that slide, was a link to your stand-up comedy clips.
Dr. Sam:
Of course. Laughter is the best medicine. Don’t let the academic veneer fool you. My comedy is very clean, observational comedy, modeled after Seinfeld and Jim Gaffigan with the story arcing of Seth Meyers. It’s clean, observational comedy that is very internal.
The primary things I focus on are the ridiculousness of the people in the health industry and consumers, whether you’re in Boulder or Austin.
I primarily focus on what it’s like to have Asperger’s. I don’t like the term “neurodivergent;” I like to think of myself as “neurodistinct” or “neurospicy.” I use standup comedy to educate the normies on what it’s like to live in their world. It gives language to the other Aspies; we have a shared reality, and here is a way to explain it in a way that’s palatable. I use standup comedy to make the topic palatable, and then use social media to make it scalable.
I am currently working on finishing an hour special just on Asperger’s, which hopefully will be first performed this upcoming summer.
Dr. Eric:
All right, wonderful. You’re doing that live?
Dr. Sam:
Yeah. At this time of recording, I am waiting to hear back from the Denver Fringe Festival if I was accepted to have an hour slot in June. I won’t know until early March. If I’m not accepted for whatever reason, fine. I’ll find another venue, or I’ll have more time to work on it.
I do MC work, and I also do standup comedy at conferences that are relevant to the conference at hand. I recently gave a five-minute talk on how to put humor into your messaging for increased rapport, so people could really resonate with the material and receive it better. There is actually a structure to incorporating comedy into your messaging. I love comedy. That’s another topic we can talk about.
I’m sure we can have a whole thing just talking about thyroid. That’s another separate discussion. That’s more on the functional side. That’s going through all the tests around thyroid that a lot of people who are struggling with thyroid miss. Thyroid and gut connection, thyroid and adrenal connection, thyroid and estrogen connection, thyroid and other irons and other nutrients connection, thyroid and mitochondria connection, which we discussed albeit briefly today. Knowing the constellation of thyroid tests and tests that surround the thyroid and connect to it, if people want to get a full view of how to optimally help their thyroid from a functional medicine lens.
Dr. Eric:
Might have to get you back for that. Thanks, Dr. Sam, for sharing a lot of great information about genetics, including methylation. Definitely check out Dr. Sam’s website. It was a pleasure chatting with you.
Dr. Sam:
Same. Thank you so much for doing this. I really enjoy teaching, and I really love sharing this. I am so grateful to people like you who are doing the yeoman’s work of educating the public at scale and helping empower people with great information from all the guests you bring on.
Dr. Eric:
Thank you so much.
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