Have you ever thought about what powers are inside your body? In this video, Dr. J and Evan talk about mitochondria and how to boost them.
When we talk about your body's powers, the easy answer is nutrients, of course! Our body transforms those nutrients into energy, and it's that energy that boosts the cells in our body. All types of cells have small generators called mitochondria that, in many ways, are their sources for life. Mitochondria are the only part of the cell where our basic life requirements — food and air — are combined to make energy in a process known as the Krebs cycle.
Dr. Justin Marchegiani
In this episode, we cover:
0:00: Introduction
1:30: The role of creatine in mitochondria
6:34: Energy pathways
14:47: Cell Danger Response
16:07: Citric Acid Cycle
Dr. Justin Marchegiani: Mitochondrial function, your mitochondria, little the powerhouses in your cell and they help generate ATP which is the cellular currency of energy so to speak. And we're going to talk about natural ways to improve mitochondrial function, Evan, and how we doing today, man.
Evan Brand: Doing really well. I think first, let's dive into some of the big assaults that we have as a modern society on mitochondria. And that could be anything from viruses, bacteria, parasites, gut infections, pesticides, herbicides, heavy metals, plastics, phthalate's, the BPA, the BPS, flame retardants, nonstick chemicals, car exhaust, air pollution. That I miss any I mean.
Dr. Justin Marchegiani: Like you hit a lot of I would say being sedentary. There's a lot of mitochondria in your muscles. And if you don't do enough, you'll put enough force to those muscles, they will atrophy. And so just not doing enough about creating enough stimulus on your body. That could definitely we can and decrease your mitochondria in your muscles. So, I would say, sedentary and in active resistance through your muscles.
Evan Brand: OK, OK that's a good point. That's a good point. So, you're saying that, like, just in general, you have to have some level of physical stimulation physical activity to keep the mitochondria working. I guess it's kind of like an old car that you've sat there…
Dr. Justin Marchegiani: All your muscles at least. Yeah, 'cause if you decrease, you know your muscle levels via just atrophy due to lack of use. Yeah, your muscles will shrink absolutely and that's your mitochondria will shrink for.
Evan Brand: Sure, what about creatine? Do you know anything about the role of creatine in mitochondria? 'cause I know when I'm taking creatine, I just I feel stronger? Obviously, there's creatine's used a lot in like bodybuilding world, but there's gotta be a mitochondrial mechanism there because I'll tell you I feel like. I can lift, you know, at least a good 1020 pounds heavier on particular exercises with creatine in my system.
Dr. Justin Marchegiani: Yeah, me crazy definitely has an effect on growth hormone and improving growth hormone stuff that will help with muscle. Creatine is like instant energy for the muscle. So, it's it's there. It's ready to be used right away in that first 10 seconds or five, five to 10 seconds of muscle use or like explosion movement through that muscle. So, that definitely plays a role in muscle. I'm not sure how it plugs in 100%. I see 'cause really you know with ATP right in the mitochondrial function? If you look inside the mitochondria you have glycolysis and then you have the electron transport chain. Or I'm sorry, you have the Krebs cycle citric acid cycle and that plugs into the electron transport chain. So, glycolysis that's going to be utilizing the carbohydrate in the muscle right glycogen in the muscle. Fast immediate source. I think creating plugs into that top part. And then you have the Krebs cycle citric acid cycle, where B vitamins, magnesium. All these different things kind of plug into that and with that. With the citric acid or Kreb cycle, that didn't mean the same thing. Essentially, they're grabbing hydrogens, right? So, there it's it's a reducing agent, so it's just grabbing reproduce. Reduction is a gain in electrons and so you have NAD goes around. Then it grabs NADH so you get 3 NADH and I think 1FADH2 so you have FADH. And it grabs another hydrogen and that becomes FADH2, and so it's grabbing all these hydrogens. And then it's essentially bringing those hydrogens downstream into the electron transport. Jane and Beta fatty acid oxidation there and so yeah, I think you generate was at 36 to 39 ATP through the Krebs cycle and the electron transport chain.
Evan Brand: Unless you're in like chronic fatigue stayed, this cell danger response, and I think you're spitting out something low like 2 maybe 3 ATP. I've read about this cell danger response. They just call it HDR in the literature, but it talks about how. The cell danger response, could be initiated by trauma or a car wreck or even mold exposure or tick-borne illnesses, or viruses. There's a lot of you know, Epstein Barr. You'll see the link between like mono and chronic fatigue. It said that these people are in this state of just a low power output, or even if you have the nutrients, you're just not generating the ATP with some I don't know if it was Caitlyn or somebody that you and I had looked into where there was a talk on this about. How the w the the ATP was literally in the single digits. The low single-digit output in some of these states. So, the message here is that for people that have chronic fatigue, you got to realize there is a mitochondrial component to this. Why don't we talk about testing a little bit? The main thing that you and I are going to look at is going to be the organic acids. I know there are some other tests out there. I'll admit I've had clients send them to me such as the mito swab. I've not run the model swab. Personally, I don't know enough about it to speak on it much, but I'll just say that it does exist. I believe it is a a mouth swab and it's probably looking at just a couple generic markers in the saliva. But we like to use the organic acids test because, as you mentioned, there's the Krebs cycle metabolites on there. We can look into the supinate or what some people call succinic acid. You've got the malic acid. You've got fumarate. There are other markers on there, and we we see when people have talks and exposure. Like I said in the beginning, the heavy metals, the mold, the pesticides will see those. Mitochondrial markers go up. And the higher the numbers go, generally, the more tired someone is because that indicates more damage to that Krebs cycle. So, the oh is huge, and then obviously we'll look at stool too. Now the stool test you don't measure like the stool tests we're running. You're not measuring mitochondrial function, but I look at it in a roundabout way. Meaning if you have all these gut infections producing toxins that could be damaging mitochondria as well, so we know that when we clear the gut out, we see the mitochondrial function improve.
Dr. Justin Marchegiani: 100%. Yep 110%. I want to just put something on screens. People can see it here I guess is really helpful.
Evan Brand: Have you seen or heard about that my to swab before? Have you seen anybody send you those?
Dr. Justin Marchegiani: I have, I've ran up. Fulham, it's kind of a binary test. It gives you a result my the issue I have it's not a lot of actionable information. It's like OK, you know there's some issues there, but then now what's, what's the remedy that you're going to plug in from a diet lifestyle supplement? Toxin reduction execution right? What's the next step on it? So that's the problem with some. Of those tests, I always. Look and I always ask well what's the corrective action based on the test showing uses a concern.
Evan Brand: Yeah, yeah
Dr. Justin Marchegiani: That makes sense.
Evan Brand: That's the problem with a lot of them like I've seen a lot of these stool testing companies. Same thing there's like so much data. Well, this percent of this bacteria and this percent of that. It's like, what do I do with that? Is that an infection? Is that not an infection? So you and I've seen the same problem in other categories of health tests do.
Dr. Justin Marchegiani: 100%. I want to show a couple things on screen here? Just so it's crystal. Where the mitochondria is and how all these different energy pathways plug in, I think it's important I'm going to pull it up here on screen in just a second so people can see it.
Evan Brand: Yeah, people listening on audio, they're going to be lost. So just look up Doctor Justin YouTube page and you'll be able to view some of this stuff. Some stuff, like mitochondria, gets a bit geeky. The the main thing here is toxins are a big factor in damaging this cycle and you gotta get toxins out. Reduce exposure where you can and we can run actually chemical test on your current too so we could talk about that in a minute.
Dr. Justin Marchegiani: Absolutely, and so if you look here right. Do you have the mitochondria right here. Some middle part, the mitochondri. The outer part is the cytosol. So, from what I understand, like creatine is going to plug more into the cytosol and glycolysis, OK, but then you're going to see you get about two ATP which is adenosine triphosphate. And this gets broken down into ADP and you get energy right? And so, you have glycolysis which generates a little bit of ATP 2. And creatine to plug more on the outside then that goes into your mitochondria. Now you have the Krebs cycle and the electron transport chain electron transport chains part of also the beta fatty acid oxidation. That's how you burn fat for fuel. OK, so Krebs cycle that churns around twice, and essentially what you're doing is you're gathering NAD and FADH2. NAD&FADH are grabbing hydrogen so and a design to grab a hydrogen making NAD. HFADH is going to grab a hydrogen, making FADH2, so I think you're going to grab it's like two or three. NADH is, and then one FADH2. And all those hydrogens then go into the electron transport chain here and this is where you generate most of your ATP. And again, what comes out, oxygen comes and this is why, if you're like anemic right? And you're not carrying oxygen. Well, that's why you're going to get tired and this is going to have an effect on your thyroid and your adrenals because the mitochondria is important for energy at all levels. And so if we have anemic issues or were inflamed because inflammation is going to make it harder to carry oxygen all. And also nutrition, because this electron transport chain, when we run the organic acid test, we can look at citrate, malate, fumarate, succinate. These are important metabolic essentially inputs into the Krebs cycle that correlate with certain nutrients like amino acids, alpha-lipoic acid, magnesium B vitamins, and so we can get a window on how this. Krebs Cycle was functioning based on the organic acid testing at some of those compounds and then all sister connotate citrate, right? These are really important, and then electron transport chain we can get a window into things like carnitine and Co Q10 'cause they also play a major role in the electron transport chain. So we get a good window with how the mitochondrial function functioning by looking at the B vitamins and looking at a lot of these nutrients and so essentially things that can impair this. As you mentioned, pesticides. Heavy metals, mold toxins, antibiotics, and all these things have a negative impact. But that's kind of how things look, so we have. Glycolysis is the first part that then goes into the mitochondria, and then we have Krebs cycle and electron transport chains. These are the big three. If you can kind of zoom out and see how it looks and how it makes sense. That should hopefully make more sense, so on that front. Any question that, Evan?
Evan Brand: Well people listening to that. They're going to be like wow, this sounds like a really crazy rare problem, right? This must be just rare. This must be like a one in million case and I would say. Not going to say 99. I would say 90% of the people we work with. I see some level of mitochondrial dysfunction or damage either on the chemical profile test, so that's something I alluded to earlier. We can run chemicals so we can look at gasoline. We can look at xylene. We can look at phthalates, all sorts of organophosphates. 24D is a major herbicide. I still see people at Lowe's and Home Depot in the Garden Isle buying grass seed. That's called weed and feed, weed and feed is a grass seed mixed with three different types of herbicides. It's 24D, I believe it's dicamba and glyphosate. Wait, I could have mixed one of those up, but either way, it's three different chemicals, very toxic substances mixed with grass seed, and that's like people just buy it and they don't think anything of the term weed and feed. That means you're going to be killing all the good stuff in your soil and poisoning yourself at the same time. It's just not smart. So this mitochondrial thing. My point was, this is not rare, like when you show that image and people see that like. Oh no, that's not happening to me. It's like it happens every day, all day. I had mitochondrial damage, my latest test shows our mitochondria are much, much better, but I had significant mitochondrial damage from my mold exposure.
Dr. Justin Marchegiani: Very interesting, I want to highlight one thing here so you can see creatine does primarily exist here in the cytosol, right? So if we zoom out, right cytosol is outside of the mitochondria, right? Right glucose, pyruvate here, so just so you guys can highlight here, creatine does go from the cytosol and it can go into the mitochondria. So, we did talk about creatine. It does primarily happen more in the cytosol outside the mitochondria, and it can go in via this. Mi-CRT kind of transport. Compound, so yeah, so creatine is a compound that we talked about that goes outside but can also go inside the mitochondria. To yeah Doctor Neil Nathan.
Evan Brand: That's awesome! Doctor Neil Nathan did a huge thing for 155-page slide show that people can look up just called the Cell Danger Response. It's very complex stuff. There's going to be maybe a few geeky on that. People want to dive into that, but for your average person there's not much takeaways built into that. But if you want to look into more of like the biochemistry side of it, then then you could look at it. But I think the big summary is it's all. It's all the Chemicals, and this is a relatively new problem I mean we face now over 80,000 chemicals are in the environment. Depending on what number you read, there's only a small amount of those that are even tested. You'll see stuff in Europe like oh Europe has banned these chemicals and makeup and personal care products, but the US was very far behind. And if you look at the environmental working group, they have a water testing report. You can look at and you can plug in your zip code. I mean just the amount of trihalomethanes's pesticide herbicide residue pharmaceutical drugs that are in the municipal tap supply in your city are massive and you're getting hit with this all the time. If you go to a restaurant and you eat rice, what do you think they make that rice with? They make it with tap water so you're getting exposed to it that way too, which is why if I go out to eat, I don't really do rice that often anyway. But if I do it, It's going to be at home with good, clean filtered water.
Dr. Justin Marchegiani: I like it. Anything else you want to say on that, so obviously get the toxin exposure. Super important hydration obviously really important to anything else you want to say on that?
Evan Brand: Yeah, you hit you hit the the Co Q10. You mentioned some of the markers we're going to look at on the oak test, so we will use those. We have a formula. I believe you've got 1/2 mines called my to boost. It's essentially like a multi for the mitochondria with all the Co Q10, ribose, carnitine B vitamins. So, when we see mitochondrial dysfunction, we can supplement that and we tell people this is a band-aid for your mitochondria. This is not some of it is the root cause, right? If you just are simply low and depleted in Co Q10, one could argue supplementing Co Q 10 is the root cause, but in reality it was usually. Oh here we go. Let me see if I can share this slide with you. Mainly it was the the toxins that led to this so let. Me share my screen really quick.
Dr. Justin Marchegiani: And there is going to be because we do make Co Q10 on our own via the mevalonic acid pathway. And of course, as you get older, just like stomach acid, you're gonna make less of it and so there there could just be a depletion based on age as well.
Evan Brand: Does that show up at all on your side? The video is that screen share show.
Dr. Justin Marchegiani: Try again.
There's like a little bell there. Let me let me pop it up again. How about that, yes? Oh yeah, let me let.
Dr. Justin Marchegiani: Me highlight it, go ahead.
Evan Brand: Yeah, there we go. So, this is this is kind of what I was alluding to, and many many other people may have different ways to look at this, but this is from Neil Nathan. He had a great paper on this cell danger response and it just shows at the top here. Basically, everything I already mentioned like a flame. Heavy metals, pesticides, infection, so that would include viral issues as well. Mass cells, NK killer cells, cytokines, the microbiome. All these issues here are what really breaks this role. You know, the one of these is the final straw that breaks the camel's back and then you end up in this what's called the cell danger response phase. And then that's where you get the issues with the mitochondria down regular. So there's more in that. Like I said, it's 155 pages. It's like you got to be, you got to be, you know, have your bulletproof coffee before you look through that.
Dr. Justin Marchegiani: No, that makes a lot of sense, so your kind of really focusing on the toxicity and how that negatively impacts it. I want to just kind of tie in the dietary component. Why is food so important to enhancing the mitochondria? Let me let me break that down for a second here. This is important. OK, so this is really important. We talked about like Kreb cycle right? And so like this is our zoom out right? What's happening here? We have glycolysis, Krebs cycle, electron transport chain outside of the mitochondria with the cytosol inside. Now check this out. This is a good one. This is from textbook of functional medicine, so. We have fats, carbs and proteins. These are our primary nutrients where everything comes from right. Fast could be coconut oil, grass fed butter could be fats from. Uhm, grass fed meat right? Our carbs can be vegetables, fruit, starch and our proteins could be protein powder or it could be animal protein, right? All of these essentially shuttled downstream. Fats get carried into the mitochondria via carnitine, so if you go into any biochemistry textbook, it's called the carnitine. Shuttle right. Every medical doctor, doctorate level person would studied this at a graduate level. I studied as well now in the textbook of I think that guidance Physiology, but there's another textbook of biochemistry that's common at the graduate level. You know what the rate limiting amino acids to make carnitine are. It's methionine and lysine and so really important.
Dr. Justin Marchegiani: Guess what some of the rate limiting amino acids are in a vegetarian diet.
Evan Brand: Oh yeah, well.
Dr. Justin Marchegiani: Medallion Leisinger actually very deficient in vegetarian diets, and so this whole process of a carnitine shuttle here that helps bring carnitine converts it into acetyl Co A. So then the actual it can get inside the mitochondria. And run through the citric acid cycle again. That's the same thing as Krebs Cycle. They have multiple names. In medicine for the same thing, it's just meant to confuse people. So citric acid cycle or the Krebs cycle. This is how we get fat inside the mitochondria is via carnitine. So very important, right so if we zoom out. Here, we have energy out here, fat. We get it inside via the carnitine shuttle. Super important there and then you see carbs. Right glucose, other sugars. We go pyruvate to lactate and we need guess what B vitamin? So if we're putting in lots and lots of refined processed sugar and we're insulin resistant, we can actually deplete B vitamins. And we can actually deplete a lot of magnesium and other nutrients downstream. So, this is really important. Too much carbs, too much sugar, especially if you're insulin resistance and you're putting on weight due to too much carbs. That's going to be a problem, and you're going to deplete nutrients now. Then we have proteins, amino acids. These all get converted downstream. We also need B itamin to support that now the difference is if you're eating high quality protein. Guess what? You're getting good quality B vitamins in that. Protein if you're doing a lot of refined processed sugar, guess what? You're not getting vitamins and nutrients with it. So carbohydrates, it's possible to eat a lot of empty carbs that are actually going to deplete your nutrient levels. Protein not as much if it's grass fed and organic right now, really, you're taking all these nutrients, fats, carbs and proteins. You're converting them into acetyl Co A. OK, you're converting it to acetyl Co A and again we spit off beta-hydroxybutyrate what's that? That's a ketone now this is important. If we keep our carbs in check we can use ketones for fuel, so this is a really important fuel source or people that are going to be lower carb because we're going to be more keto adapted. We're going to be able to use that and then you can see here that acetyl Co A. Runs around the Krebs cycle. Twice we go 2 turns. Guess what, we need cysteine amino acid iron really important. So if you're a female you have heavy bleeding your estrogen dominant you heavy bleeding that's in effect energy magnesium manganese B vitamins lipoic acid magnesium B vitamins B vitamins tyrosine phenylalanine aspartate, glycine, histidine, arginine, proline. Glycine, valine methionine, right? These are all amino acids over here. So, we need amino acids to run these systems. We need B vitamins. We need magnesium and then of course, once we pump these things around, here's our NADH and then our FADH should be there somewhere as well. So here NADH, it may not. They may just be oversimplifying it not showing it. But we have NADH here. We should have an FADH2 coming in. This all goes right into. Guess what? This is the electron transport chain and base. Yeah, fatty acid oxidation right there, right? This is now now hydroxymethyl Glutarate. This is Co Q10. This is where Co Q10 comes in and this is where it runs through the electron transport chain and burning fat for fuel and we generate our 36 to 38 ATP from all these three sources 1-2 and three and so that's what's happening in your mitochondria. So just to kind of highlight macro nutrients, fats, protein, carbs, very important two, don't junk it up with all the toxins that you mentioned. And then of course, making sure we. Can breakdown protein. Make sure we're getting enough iron making. Sure, we're not. Anemic right? All of those things kind of flow into allowing all these pathways to to work optimally.
Evan Brand: That's amazing, I love the breakdown to that. The visual super helpful. So just to clarify a little bit. So for women out there, you're saying that if having heavy ministration, they have low iron. It's not just the the low iron that we assume is creating like a low oxygenation, you're you're showing here. The low iron is literally creating a mitochondrial deficit.
Dr. Justin Marchegiani: Correct. You're not getting the oxygen in right? If we go back to here, right? Mitochondria, what do we need to get into the mitochondria? Oxygen, what's one of the big carrying capacities for oxygen in the body? Hemoglobin and then iron affects hemoglobin in red blood cells, right? Hemoglobin is part of the red blood cell carrying capacity and we need the iron to really keep the hemoglobin levels up so we can carry enough oxygen.
Evan Brand: Wow, so there's why you're tired.
Dr. Justin Marchegiani: Could be. Yet, one and then of course all of the other nutrients play a role. Not enough of the amino acids. The only issue with this graph, any biochemists that are looking on? I think the only thing that's missing is really the FADH2, so it should. So, all these things, they're just reducing compounds. Really, the whole goal of this Kreb cycle to run is just grabbing hydrogens. And then once we grab these hydrogens, Uhm, these things get cleaved off, and then it generates ATP. What's happening there? And all these things like hydroxymethyl iterate. These are right. These are all driven through Co, Q10, right? We need Co Q10 to make that happen.
Evan Brand: Now for people like supplementing ketones, if you go back up to the top there, you can basically kind of inject your own spark plug into the cycle, I guess right? If you're taking exogenous ketones, what is that doing in relationship to this whole cycle?
Dr. Justin Marchegiani: It's giving you more beta hydroxybutyrate. The problem is your body is going to primarily want to use that when insulin levels are lower, so you have to keep your insulin levels and check. If not, you're not setting your Physiology up to want to burn that. If you're probably, gonna pee it out more like more than likely versus burn it. Cause typically, your body has an enzyme called hormone sensitive light pace where it wants to break down fat and convert more of these ketones. Hormone-sensitive light base is inverse with insulin. So hire your hormone-sensitive light pace is you need lower insulin to make that happen.
Evan Brand: So the lady who eats the donut and then goes to the store and buys her exogenous ketones, she's wasting her.
Dr. Justin Marchegiani: Probably not as good. There may be some mild benefits that you get cognitively just 'cause your brain has some additional fuel to run on. If people brains are insulin resistant, they may have a lot of sugar from that doughnut, but the cells in their brain maybe so numb. To it that they may not be able to access it so some ketones could be helpful, but in the end, you want to fix the insulin resistance if you're going to do it. Try doing both. Don't just do the ketones. Try to do both that you can.
Evan Brand: And you can make your own ketones too. For free.
Dr. Justin Marchegiani: Yeah, yeah, that's how you're doing that you keep in your insulin in check. And you're going to start. Making your own. 100%.
Evan Brand: Yeah, cool.
Dr. Justin Marchegiani: Cool, that was awesome. Very cool guys. I hope you guys enjoyed today's podcast. We're trying to be a little bit more visual; you know. Go into some hard hard science Y stuff, but you know just kind of zoom out. Like what's the take home right? The take home is don't put junkie toxins and that screw up your mitochondria right? Antibiotics, I mean antibiotics? You know if if you have an acute infection that's not resolving, you know you gotta do what you gotta do, right? You have an acute pneumonia. You gotta do what you gotta do. Talk to your doctor about it. Just don't go to antibiotics all the time as your first line defense. Try to do some. More natural things to fix it #2 you know, try to be aware of mold in your environment. Make sure you're not. Getting exposed to pesticides. Chemicals heavy metals. Make sure you're doing your best to hydrate right. We need water to make this whole thing work too. I would say after that make sure you have your macronutrient style, then good quality protein fats and carbohydrates. Organic sources dial in your carbs so you're not insulin resistant and make sure your inflammation is good. Inflammation helps with oxygenation and blood flow. Then after that we can look at using supplemental nutrients in my line and Evans line we have mito supports products mine is mito synergy. Evans is my toe. Boots will put links down below. Those products have a lot of these nutrients. It's going to have the ribose to creatine the carnitine, the B vitamin. Since it's going to have the Co Q10, it's going to have actually Kreb cycle intermediary compounds like fumarate malate, succinate. All those different nutrients or run those pathways better. Of course, that all sits on top of a solid diet. Don't take supplements if you're going to eat crap, eat really great and then say OK now I'm going to work on enhancing it. And again, we can run testing on organic. Message to look at some of these intermediary nutrients, like citrate to connotate succinate bloomer, a mallet we can actually test them, which is pretty cool.
Evan Brand: Yeah, the testing is the best part because you you know if you actually need it. I can tell you the average person has mitochondrial problem, so in general, could you just take this? I kind of call it a multi for the mitochondria. Could you just take that test? You know like a guess and check you could, but we like to see the data and obviously my biggest thing is looking for mold colonization. Candida overgrowth clostridia. Some of these gut infections and how that affects your brain chemistry too. So when you do the oh, you really are getting the best bang for your buck in terms of testing. Like if you could only do one test out there, I think the oh it would. Probably be the number one most.
Dr. Justin Marchegiani: Important 110%. Anything else you want to say?
Evan Brand: If people need help, they can reach out to you worldwide or me worldwide. Doctor J at justinhealthcom me Evan at evanbrand.com and we would love to chat with you about your symptoms, your goals and we'll tell you for your good fit for care, so please feel free to reach out. Look forward to helping you.
Dr. Justin Marchegiani: Foot and get adjusted. Help calm here and then you guys have any questions, comments or concerns. Put him down below. Let us know. Kind of what you're doing. What's working that really helps us out as well. Very cool. Alright guys, well you guys have a phenomenal day here and we'll. Be in touch. Take care of y'all.
Evan Brand: Sounds good.
Dr. Justin Marchegiani: Alright Bye bye.
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