Transcript 

Talking Mitochondria, Glutathione & Glyphosate with J Gulinello, FNTP

 

Michelle Shapiro [00:00:00]:

So, you know, as a podcast host, right. It is my job to prepare outlines, prepare questions for guests, kind of set the pace for how it goes. What you do, Jay, in your extensive research and preparation, is come in with a 15 page outline to each episode.

 

J Gulinello [00:06:36]:

I do.

 

Michelle Shapiro [00:06:37]:

And it's a problem for who you are. It's a problem. And you know what? Let's air our dirty laundry here. It's, you know, it is something that we. It is a problem here. You know what I mean? Because you're taking all the work off of me. First of all, you do this with every damn podcast you go on. You do all the prep work for the guests, for the host.

 

Michelle Shapiro [00:06:54]:

We become the guests on our own podcast. And I love it, you know, thank you.

 

J Gulinello [00:06:58]:

It's a little bit worrisome from my end because I actually start to think that maybe sometimes, anyway, I think, like, is the audience even going to. You know, I really try hard to make sure that the audience has a reason for listening, and I don't want it to just be, hey, why don't you come to biochemistry class? Because who the hell wants to do that? But I think that I put too much pressure on myself for all of these. All of these podcasts. You're right. It doesn't matter who I'm doing this with. If it's somebody like you and it's going to be a much higher level conversation, then, yeah, then I put even more pressure on myself.

 

Michelle Shapiro [00:07:31]:

So I know it's not good. The way that we live our lives, Jay, is not what other people would call enjoyable. It's not fun. And the combination of us together is. It's not gonna be a good time on this episode. Okay? And I need people to understand that coming into it, we're not having a fun chit chat. All right, we're getting to work on this episode, as per usual with you, and I am obviously joking when I say all of this because it is such a delight to have you on, because you are such a well prepared guest. You care so deeply, and the way your brain works is such a delight for all of us.

 

Michelle Shapiro [00:08:04]:

So I am so overjoyed to have you back. You know, the second I started bringing recurrent guests back, you were the first person on my list, because when we did the cholesterol episode in season one, the reception was so profound. Because, Jay, you have this really amazing way of laying out the high level and then going deep into the nitty gritty. And I am beyond grateful for the prep work you do and beyond grateful for how much care you put into every single thing that you do.

 

J Gulinello [00:08:30]:

Well, thank you for that.

 

Meet J Gulinello

Michelle Shapiro [00:08:32]:

Last time you came on the podcast, you did an incredible episode on. By the way, Phil, you can use Phil's. My editor is going to come on. You can use the original part of what I said because I think it was more whatever. You don't have to do this part, but I need Jay to hear this part so we can respond to it. The last time you came on the podcast and he did an episode on Cholesterol, it was so well received because you do this beautiful thing where you can weave in the high level and then kind of get into that nitty gritty. And for that reason, I am so excited to have you here. So excited to have you back.

 

J Gulinello [00:09:02]:

I'm super excited to be here, and that really means a lot from coming from you. And also, if that's the feedback that you got from your audience, that I'm able to take complex topics, sort of talk about them high level, but then also break them down into the nitty gritty, because I want people to not listen to anything that I do and think of it as just an academic exercise. I want someone to be able to take away something they can use in their life to improve their health. I mean, that's why we do what we do. So as far as that goes, I'm very excited. I'm ready to roll. I have way too much information here, so you're going to have to be my guide, my sherpa, and let's get rolling.

 

Michelle Shapiro [00:09:40]:

You know what I'll do? I'll kind of host this thing. I'll host this thing, and I'll host us through it, and we're going to make it through. I want everyone to know, listening, that there was extreme anxiety on both of our ends to make sure that we covered these complex topics for you, and there will be a lot of care associated with that, but that we are going to get through as much of these topics as we can in a way that we promise will be tangible and real. Because when it comes to mitochondria, when it comes to glutathione, and when it comes to glyphosate, which are all three very different things, by the way, but why those three we bundled together, we'll talk about, too, I think I've never seen more misinformation and misunderstanding about topics than these. So all over the social space, all I see is boost your mitochondria, and either glyphosate is going to kill you in an instant, or it's completely something that's non harmful. And we need to really be able to understand what we're talking about. And what I love that Jay does and what you do is that you're such a storyteller. So I know that we'll kind of lay this visual for people so that they can really understand what are we even talking about? I am so sick of health information not even being, quote unquote wrong.

 

Michelle Shapiro [00:10:49]:

I'm not nervous about it being wrong as much as I'm nervous about it being not useful. So I want to make this information understandable and useful. So, Jay, to kick us off, highest level, and we will break it down. Take a deep breath, Jay. We're going to make it through this. Okay? We're going to get through all the information. We're going to get through. I see concern on his face.

 

Michelle Shapiro [00:11:07]:

We're going to get through the 15 page outline. What are our mitochondria?

 

What are our mitochondria?

J Gulinello [00:11:13]:

Okay, so if we were to think back from high school biology, people probably remember that name, mitochondria. I think it's, oh, it's the powerhouse of the cell, right? But it only, it doesn't just produce energy. So it's also extremely important in fat metabolism, in carbohydrate metabolism, in heme synthesis, in cellular death, apoptosis. It is a central player in many things. And the reason that I think it's important to talk about mitochondria is that, well, every disease that I've ever looked up at some point had some degree of mitochondrial dysfunction in the ideology of the disease. And so this isn't just an academic exercise. This is something that, if anything, that is a net negative for the mitochondria, I think is a net negative for the person. And anything that is a net positive for the mitochondria is a net positive for the person.

 

J Gulinello [00:12:01]:

So I hope the people listening will take that away. That's why we're talking about this mitochondria, because it does play a role in your health, even if you don't necessarily know that you're feeling it. I promise you that even something like fatigue can be directly related to mitochondria because it's producing your energy. So it really is relevant to people. And I think if we keep it from that high level, that's a pretty good place to start so people understand what we're talking about.

 

Michelle Shapiro [00:12:24]:

Absolutely. And this vision of it being a powerhouse of the cell, I think if we can just go back to a visual of it almost being like a factory for energy, like, I almost, I think of the liver as being like a factory for repackaging toxins and sending them out. The mitochondria is a component of the cell that is, would you agree, like, a place where energy is generated. And of course, there's many steps for that energy generation that happens within the mitochondria. But when we say powerhouse the cell, we mean this is the site of. Of energy production.

 

J Gulinello [00:12:57]:

Mm hmm. Yeah. And you can think of, if I use this analogy, if you think of a house and you think of the mitochondria would be a room inside that house. And every room in your house has a different function. Right. The kitchen is where you make food. The bathroom is where you take a shower. Right.

 

J Gulinello [00:13:12]:

So the mitochondria is just, it's an organelle, which is just another room inside that house. Technically, it's got its own membrane, so it's walled off from the rest of the cell because it has its own function. But that's just an easy way to sort of think about it in terms of what it is in the cell, but. Absolutely. And energy production is probably, it's famous for that. And it's the most important thing we're going to talk about today, because a diminished energy production, I think, is what leads to disease in the end. So even though it does a bunch of other things that are incredibly important, energy production is certainly high on the list.

 

Michelle Shapiro [00:13:44]:

When you say energy production, I think people are hearing energy, like, in the context of I'm jumping up and down, in the context of, I feel like have low energy, I have fatigue. What do you mean when you say energy in this kind of academic context? What do you mean when you say energy?

 

J Gulinello [00:14:03]:

Yeah. I mean, energy is really everything, right? Every cellular process in the body requires energy. So even transporters on the membrane of a cell to sometimes to exchange molecules or to exchange sodium and potassium, right. ATP, which is the energy currency of the body that's required to do everything. So yes, from the high level, you are talking about jumping up and down physical performance, sports performance, things like that, but you're also talking about even every single metabolic process or not every single. But anyone that requires energy is going to be using ATP to do that. So energy really is a catch all term, but it relates to the bigger picture, energy movement, but it also relates to metabolic processes. So that's all energy.

 

Michelle Shapiro [00:14:47]:

It's a great question when your body is lacking processes to create generate ATP. The insinuation I'm hearing and where we're going is that lacking capacity to generate energy can lead to illnesses of all kinds. Tell me a little bit about what that process looks like.

 

What does the process to create and generate ATP look like?

J Gulinello [00:15:11]:

Well, so I do this sort of high level thing where I say, so the mitochondria is a subcellular organelle, so it's inside the cell, right. When that goes dysfunctional, that spreads to the cell. The cell can become dysfunctional. When the cell becomes dysfunctional, then the organ can become dysfunctional. And when the organ becomes dysfunctional, you move up to the tissue level, then you move up to the organ systems, then you move up to the organism. I guess, again, that's just another way to wrap people's minds around this. Why we're talking about something that's, we're not even talking cellular level, we're talking subcellular level. But it's so important up the kinetic chain that it causes dysfunction.

 

J Gulinello [00:15:51]:

And it can cause something like in a type two diabetic, it can cause disruptions in insulin secretion, it can cause in the brain, it can cause neurons to misfire. And thats why I say any disease that ive looked up, if you control f. Mitochondria, you will find it somewhere in that paper where they are explaining how energy is produced and how this lack of energy production or some kind of disruption in mitochondrial function leads to the things that we call symptoms. But that can be a variety of things. So thats why its hard to narrow down. But as you look at disease, I always try to work backwards. And as I go backwards, eventually I get to a place where I'm looking at the mitochondria every time. And so that's become the obsession of mine, is that if we can convince people that they should be taking care of their mitochondria, then by proxy, they're taking care of all the things that they would label as a symptom.

 

J Gulinello [00:16:46]:

Rather than just put a drug which just masks the symptom. I want to try to get to the underlying cause, which is usually mitochondrial dysfunction.

 

Michelle Shapiro [00:16:52]:

I've made a joke that the root cause of all illness is either mold or trauma. I think you're adding a third layer to that. It's mitochondria, mold, or trauma at the root of all root causes.

 

J Gulinello [00:17:05]:

Well, you know, so I have this little mitochondrial fact sheet, which is super cool, because I think people will get a kick out of, like, just how massive the mitochondria are. So most cells have about 80 to 2000 mitochondria in each cell, but some neurons can have a million to 2 million mitochondria in one single cell. Okay? ATP is produced, and that's adenosine triphosphate. That's the energy currency that we use to do everything. It's produced every second of every day. And a resting cortical neuron consumes 4.7 billion ATP molecules every second. So, again, just to give people the scale of this, it is about. Mitochondria are about 10% of your body weight.

 

J Gulinello [00:17:47]:

So if you weigh 150 pounds, you pick up a 15 pound dumbbell, that's the weight of your mitochondria. And yet a billion of them can fit inside a grain of sand. So they're that small, but they're that powerful, and they also have their own DNA. And that might be something that we could talk about or not. But just so that people understand this, how we got our mitochondria is a whole other discussion. It's such a fascinating theory, but separate from our nuclear DNA, when we talk about our own DNA, the mitochondria has its own DNA that's separate from us, and they work together with our nuclear DNA to help create the proteins that make energy. So it's this beautiful symbiotic relationship. But I wanted to give people that high level understanding.

 

J Gulinello [00:18:27]:

Again, we're not just talking about one single organelle in a cell. In some cases, we're talking about millions of mitochondria to the point where it's 10% of your body weight. So it's no small thing that we're talking about. And that's why dysfunction can lead to disease.

 

Michelle Shapiro [00:18:40]:

I'm asking you a question that I authentically don't know. If you are putting interventions in place to affect mitochondrial function, does that affect all mitochondria in all cells of the body? Or are the interventions usually site specific, or the mitochondria that needs more support. Is all mitochondria on the same pace and do all interventions affect all mitochondria?

 

Do interventions affect all mitochondria in all cells of the body or are they site specific?

J Gulinello [00:19:06]:

Thats a great question. I dont know for sure, but I can tell you that, that mitochondria are all sort of, they're very dynamic and they're constantly turning over. Right. Mitophagy is a term that we use. Many people know the term autophagy, which is cellular turnover. Mitophagy is the mitochondrial version, mitochondrial fusion and fission. So very often they're breaking down old parts, they're fusing together or they're breaking apart. And that's a very dynamic process.

 

J Gulinello [00:19:35]:

So I think that generally speaking, when you have the nutrients to support mitochondrial function, the mitochondria will basically turn over the ones that are damaged and then the ones that are working properly will sort of take over the burden. So I think that, again, I think that giving the body what it needs does impact all the mitochondria at the same time. But generally speaking, all the mitochondria are at different places in their health Spanish. And so that's why supporting them is incredibly important. That's why a lot of the things that I do lifestyle wise, to improve mitochondrial function, I'm thinking of that turnover and that ability to remove old mitochondria that maybe are damaged and not working well and improve the function and supply the nutrients for the mitochondria that are working well.

 

Michelle Shapiro [00:20:20]:

Absolutely. And then also, I mean, we're talking about, again, mitochondrial turnover, we're talking about cellular function. What I know people are going to be asking in their head is, is there any way to, like measure this? Is there any way for me to know if the mitochondrial issues are present? And I think I know what your answer is going to be, but I'm going to ask you the question anyway.

 

How can we measure whether mitochondrial issues are present?

J Gulinello [00:20:47]:

Yeah, I mean, it's really hard, and I would love to get to the place where we have these fantastic tests. There are proxy tests like citrate synthase, and there are all these different lab markers that you're not going to get from a regular doctor. Those are like research laboratory markers. But generally speaking, when people ask about a healthy microbiome, I remember I was talking with a PhD student and she said to me, a healthy microbiome is the microbiome you have when you're healthy. When it comes to mitochondria, I think if you're generally speaking, free of symptoms, you have plenty of energy, you sleep well, you don't have any of the exterior signs of premature aging, and you don't have any of the internal blood markers that correlate with metabolic dysfunction, then generally speaking, I think your mitochondria are doing pretty well. But it's a great question, and I really wish there were specific lab markers that we could use, but they're all just kind of in the research world, and you'll never find any of those markers on a standard quest to lab result. So I think at some point we'll probably have that. But right now we kind of have to go with our, with the way we feel.

 

Michelle Shapiro [00:21:50]:

I was reading about this recently that they're like, actually like known to be an ancient bacteria. Tell us about that, if you know anything about it. It's interesting.

 

J Gulinello [00:22:00]:

I mean, I think it's. The theory is that at some point in our very, very, very early history, a symbiotic relationship was established. And so these, we provide them a safe place. We provide them with nutrients that they can't otherwise ascertain, and then they provide us with all those other functions, like energy and all the other things that the mitochondria does. So it's this amazingly beautiful relationship. And again, once upon a time, the theory is that there were separate creatures and they came together to say, hey, you know, we're better off together than apart to survive in this really harsh early earth environment. And now we have what we know as the mitochondria, which is, again, why they carry their own DNA signature still from that time period. So it's a little bit creepy when you think about it.

 

Michelle Shapiro [00:22:46]:

I know, but I'm like, down to their function, but I'm like, don't be in here. Don't be in here. Millions and trillions of you.

 

J Gulinello [00:22:53]:

As long as you're in control, Michelle, as long as you maintain control, we're fine.

 

Michelle Shapiro [00:22:56]:

Jay, do you think. I think I'm in control of the mitochondria. I'm not in control of my mitochondria. They're completely in control of me. I don't feel that way at all, by the way. But. Okay, so I think, again, when we kind of look at conventional medicine, we're looking at how do medications affect potentially disease, but more so how are they affecting symptoms? Right. So that's going to be on like a very organ level and a very even higher level than that.

 

Michelle Shapiro [00:23:26]:

It's our perceived experience of what's going on inside of our body. Mitochondria is almost like further, as far down the line as you can go in ways of narrowing in, like you're saying, because it's subcellular it's so much deeper. And there's something so holistic in the conversation of talking about them because they're so like ubiquitous throughout our body. They're so essential to these functions. And then there's also something that feels so frivolous. And I will tell you about talking about it because it's like, can we really make a difference if this is like this kind of world that's existing within a world within our body?

 

J Gulinello [00:24:08]:

That's such a great question. I mean, I think so. I look at something like antibiotics, for instance, right? We didn't really get into the weeds of energy production. And that may help people understand this. Again, the lecture that I created was, the first half of it is 15 minutes. And it's all about the actual process of how food becomes energy, because I want people to understand that. It also removes. Michelle, the reason, I'm sorry to go a little side tangent here, but the reason I think this is important also is that it removes a lot of the feeling when it comes to health and nutrition.

 

How can antibiotics directly impact the mitochondria?

J Gulinello [00:24:42]:

Like in our space, a lot of people who have really deep felt beliefs about the diet or the nutrition that they adhere to. And I try, and I have my own biases, we all do. But what I try to do is break it down to this biochemical level because it just removes a lot of the emotion. So when I talk about food, and I say the macronutrients, protein, fat and carbohydrate, I explain how each of those, so your steak, your potatoes and your olive oil, how those become energy, literally reducing it down to hydrogen, protons and electrons, so that people stop thinking about it as food. I mean, I don't want to take the joy out of food, but I do want to remove a little bit of the dogmatic thinking about food because that's always where I get my answers from. And so in the process of energy production. So let me go through that, because I want to explain to you then why something like how antibiotics can directly impact the mitochondria. Again, we, we don't ever want to live in a world without antibiotics.

 

J Gulinello [00:25:37]:

They save lives, but they don't, but they're not without a price. And I think that's really important for people to understand. Like you said, any medication can have an impact on the body, positive or negative. And I think we just need to weigh those in some kind of a cost benefit analysis before we just start pill pumping antibiotics every time we have a sniffle. Okay, so let me see if it's going to be a little bit more difficult without visual aids. But I think that I can basically give you the highlights of energy production. So your food, your fat, your carbohydrate, and your proteins, they get broken down through digestive processes into something called acetyl CoA. Now, I am, like, really high leveling this.

 

J Gulinello [00:26:18]:

Like, we're not going to go through how all that happens, but your food.

 

Michelle Shapiro [00:26:21]:

There'S energy, chemical processes, there's so many for each type of food. And each type of food also goes through different stages of digestion, and different organs act on that and different mechanical, again, and chemical and biological processes. So let's just say we're at the acetyl CoA part of it after digestion. Yes.

 

J Gulinello [00:26:42]:

Right. Because, and you're right, the stomach, the intestines, the enzymes, all that stuff, and that's all critically important. But, but essentially the goal of eating that food is to break all the food down into a molecule called acetylcholine. Now, for the most part, proteins are structural. You can derive energy from proteins, but you don't really want to do that because, like, in starvation, your body will start stripping away muscle and will use those amino acids to generate energy, but it's not efficient, and we don't really want that. Our primary energy source is fats and carbohydrates, but they all become acetyl CoA. And they enter something that you probably are going to have flashbacks from high school biology. They enter something called the Krebs cycle.

 

Michelle Shapiro [00:27:18]:

Which is, by the way, I just need you to know this, Jay. You got a little bit different of a nutrition degree than me as an RD. The Krebs cycle slash TCA cycle is about 75% of the education we get. I can still tell you all the substrates. It's just, it's just a majority. But the word mitochondria is very rarely used. It's just really about the substrates in the TCA cycle. But that is a, isn't that part of the dietitian degree?

 

J Gulinello [00:27:43]:

Isn't that interesting? Now, I had to memorize all of these steps in the TCA cycle. It's also called the citric acid cycle. I don't know why they do that. I call it the Krebs cycle, but, but it's interesting to me that they wouldn't mention the mitochondria because this is happening in the matrix of the mitochondria. So the mitochondria, for people who don't know, is a double membrane structure. So think of it like a doughnut, right? You got the outer membrane, you've got the inner membrane and the matrix would be like the hole in the doughnut. So that's where this whole sit. So your food, again, gets broken down through a variety of processes to make acetyl coa enter the Krebs cycle.

 

J Gulinello [00:28:13]:

And the whole point of the krebs cycle, it does generate a little bit of atPdeze, but really, the point of the krebs cycle is to generate two more molecules that will go on to the next phase of energy production. And those two molecules are NaDH and Fadh two. Those are. They have long names, but just. But that's what the point of the Krebs cycle is. So again, your food becomes acetyl CoA. Acetyl CoA goes into the Krebs cycle. This variety of chemical processes with enzymes to create this other substrate, or these two substrates, NADH and FADH two, they're going to move on to the next phase of energy production, which is called electron transport.

 

J Gulinello [00:28:52]:

This is, again, a little bit more complicated without visuals, but essentially, the electron transport chain is a series of protein complexes that sit in the inner mitochondrial membrane. They're just sitting there. They're waiting to receive these molecules, NADH and FADH two, from the Krebs cycle, complex 1234. And then there's a complex five. And that is called, also, it's called ATP synthase. That's where ATP energy is generated. They all have names. We're just going to call them complex one, two, three and four.

 

J Gulinello [00:29:23]:

So NaDh and Fadh two, they are picked up by complex one and two. Okay? And essentially, it's like a game of hot potato. They take the electrons from these two molecules and they pass them down the chain, complex 1234. And at the end of that complex four, there's a final electron acceptor, which is oxygen. That's why we breathe. When we breathe in, that oxygen combines with those electrons and they make molecular water. So that's pretty cool. So your food has now become molecular water.

 

J Gulinello [00:29:53]:

But you may ask, why are we playing this game of hot potato? What's the point? How do we create energy? Those molecules, NADH and FADH two, when they are passed to complex one and two in the electron transport chain, hydrogen protons are also pumped through that membrane into the intermembrane space. So that's the membrane space between the outer membrane and the inner membrane. I know this is getting a little bit confusing. So complex one, three and four, they all pump protons. Every time those electrons are passed down the chain, that causes a conformational change in the protein, and that allows hydrogen protons to sneak from the matrix up through the complexes into the intermembrane space. And what we're doing there is we're creating an electrochemical gradient. So you have a lot of hydrogen protons in the inner membrane space. You have less in the matrix separated by a membrane.

 

The analogy between the mitochondria and a battery

J Gulinello [00:30:42]:

And nature always wants to create equilibrium. So those hydrogen protons, they really want to come back into the membrane, into the matrix to create equilibrium, but the membrane does not allow them to do that. They have to pass through ATP synthase, that's that complex five, that final step. That's how energy is actually created. Those hydrogen protons are separated. It's also separated by a charge. So if you can think of something in your regular life, these opposite charges separated by a membrane, something in your everyday life that you use, can you think of what that might be? I'm just curious if I know. The audience obviously can't answer, but do you know what I'm talking about, Michelle?

 

Michelle Shapiro [00:31:22]:

Are you talking about like a battery? What are you talking about?

 

J Gulinello [00:31:24]:

Yes. So how cool is that? Your mitochondria is a potential store of energy. It is a battery. And I like to make that analogy because now you can think of your mitochondria as a little, a little store of energy in the form of a battery in your cell. So it's now all those. All those hydrogen protons are now going through ATP synthase. They go back to the matrix and then they're exported out to the cell to do work, to do energy. So that's energy production.

 

J Gulinello [00:31:52]:

It's food to acetyl CoA through the Krebs cycle to create these reducing equivalents of NADH and FADH two. They go into the electron transport chain. Those electrons pass down the chain, they pump hydrogen protons to create a gradient to work against. And then ATP synthase allows those hydrogen protons to come back into the matrix at the expense of creating an ATP molecule. So it's actually a beautiful system and that's how food becomes energy. And you can really start to understand now why I said it really removes a lot of the dogma when it comes to food, because any food that provides nutrients. And when I go through this presentation at the end, I show you that red meat actually has all of the nutrients that the mitochondria need in the form that they need, which is funny. So when people tell you red meat is bad for you, I go down to the mitochondria and say, show me how red meat is bad for you.

 

What nutrients are required for energy production?

J Gulinello [00:32:40]:

Because it provides everything that the mitochondria needs. So there you go. Thats energy production in a nutshell.

 

Michelle Shapiro [00:32:46]:

Yeah, I mean that's, that was a beautiful nutshell. And also, you know, it makes me constantly also think recently in the biohacking world, there's a lot of talk of hydrogen water taking hydrogen pills. Is that is the goal usually from your perspective, to help facilitate energy metabolism. Is that why this has become so popular recently?

 

J Gulinello [00:33:08]:

I think so. And it's funny, somebody else just mentioned this to me the other day and I actually have to do more research into it. I've only. Ive only recently began to look into it, but I believe thats the idea, providing that hydrogen substrate for energy production. But I do want to look more into that. Its actually a really good question.

 

Michelle Shapiro [00:33:23]:

So red meat, like youre saying, and what happened at the end of your presentation, but we dont have the visuals up. Red meat has a higher energy and mitochondrial production potential than what other foods were you mentioning in your discussion?

 

J Gulinello [00:33:38]:

No, I think it really was just to highlight the silliness of claiming red meat somehow is bad for you when it contains coq ten, which is a part of the electron transport chain, when it contains carnitine, which shuttles fatty acids into the mitochondria for energy production, creatine, which can increase mitochondrial density and membrane potential riboflavin, which is part of the TCA cycle, and complex one and two. So it has all the nutrients that are required for energy production. So I wasn't comparing it to another food. I was just trying to say, isn't it interesting how we say blanket statements like red meat is bad for you, but I'm literally showing you on a biochemical level what red meat provides, and just trying to provoke some thought experiment in people to think maybe some of the things I've been told, they're not exactly accurate. And when I understand the nitty gritty, it's a little bit clearer, I think.

 

Michelle Shapiro [00:34:29]:

So there's a really important point in what you're saying that I want to emphasize, which is that for even the Krebs cycle to happen, nutrients are required because energy production is still nutrient expensive, right? So we need those nutrients like detoxification. I've said a million times in this podcast, is energy and nutrient expensive. The production of energy in the first place is also nutrient expensive. What nutrients are required for energy production?

 

J Gulinello [00:35:00]:

Well, I mean, I would say the three or the four that I listed. There are some of the major ones, you know, coq ten works in the electron transport chain at complex two, and it's helping to shuttle electrons down the electron transport chain. Carnitine is really important, especially for fatty acid energy metabolism because it actually brings long chain fatty acids into the mitochondria where energy production happens to. So your point, I love the point you're making that we need to understand what foods provide in terms of micronutrients. I think it's even more important than macronutrients. Don't get me wrong, I do think macronutrients matter. And obviously, people that have impaired glucose metabolism, which generally ends up manifesting eventually as hyperinsulinemia and type two diabetes, they have a problem with carbohydrate metabolism. It doesn't mean that carbohydrates are bad.

 

J Gulinello [00:35:51]:

It means for that person at that time that they have an issue with metabolizing carbohydrates. But I think we need to start thinking of foods. The way you're mentioning it, like the individual constituents that they are and what they provide to the body, omega three is the same thing. It's just omega six omega three ratio that's critical for inflammation, and they share enzymes. So when you eat too much omega six, like in the form of a seed oil, you're impairing the ability of omega three s to fully elongate into anti inflammatory mediators. I don't know. I love looking at food this way. I know it's not very romantic because it totally, when your birthday rolls around and people want to give you cake and you're thinking of what that cake is going to do to your mitochondria, it's a little bit less romantic.

 

J Gulinello [00:36:35]:

But I think it's really important when we're trying to get down to the nitty gritty of health and disease.

 

Michelle Shapiro [00:36:38]:

Absolutely. Which is what we, as nutritionists, that is what we're slated to do, actually, and get to the bottom of this, so to speak, when it comes to, let's just talk about detoxification and let's talk about liver detoxification, because mitochondria also play a huge role in that. I've always found it really interesting and fascinating, and I'm going to segue us, as I'm saying this, that glutathione is so essential in phase one and phase two of liver detox, and I've often suspected it's also because it's affecting the mitochondria, and the mitochondria are essential for detoxification, too. So tell us a little bit, if you can, about the role between mitochondria and detoxification in the body. As well.

 

What is the role between mitochondria and detoxification in the body?

J Gulinello [00:37:20]:

Yeah. And let me go back real quick, just because this was something that you had said before, before we went into energy production, but how medications or something like that can interact with the body. But now that you understand the high level of energy production, antibiotics are very interesting. Again, they're life saving, but they also. So remember we got that electron transport chain. Antibiotics have been shown to decrease complex one activity by roughly 16% to 25% and complex three activity by 30% to 40%. And remember I told you that complex one, three and four are the hydrogen pumping complexes, so you're diminishing the efficiency of two of those protein complexes. So again, antibiotics are life saving, but they're not without a price.

 

J Gulinello [00:38:07]:

They can also elevate things like eight ohDg, which is a marker for DNA damage. Now, if we want to transition into something like glutathione, what's super interesting is that supplementing with something like n acetylcysteine, which is the precursor to glutathione, and I'll explain that in a minute, that can actually reduce the reactive oxygen species created by the diminished energy production and can also alleviate the DNA damage. So you take Nac before a round of antibiotics, and you're going to support the mitochondria. So again, it's all about supporting the mitochondria through everything that you do in life. So if you have to take an antibiotic, one of the best things you can do. This paper was really cool. It just kind of laid that whole thing out, that this is what happens when you take antibiotics. This is how you can rescue that process.

 

J Gulinello [00:38:54]:

So I just want to let people know. That's a big part of what we do here, is trying to understand how every intervention comes at a cost, especially when you're talking about pharmaceuticals. They're unnatural to the human body, but again, they can save a life in a precarious situation. So I just think it's really important to understand that.

 

Michelle Shapiro [00:39:12]:

I think it's really important, too. Yeah.

 

What is glutathione?

J Gulinello [00:39:14]:

Okay, so let's go to glutathione. Glutathione is really interesting, and I found out some really cool information. We'll see if, see if you, if you're aware of this. I wasn't aware of it, so I'm not sure I'm not going to be.

 

Michelle Shapiro [00:39:26]:

And I'm ready to learn. Literally define glutathione first.

 

J Gulinello [00:39:30]:

Sure. So it's a, it's what's known as a tripeptide, and it's a combination of the amino acid cysteine glycine and glutamate. So it's a tripeptide and it's actually found in really high levels in the cells. I was reading a paper that compared it to the levels of cholesterol, potassium and glucose in the cell. That's what high level it's found in. Yeah. Pretty amazing. What's really cool is that it's also produced exclusively in the cytosol of the cell.

 

J Gulinello [00:40:00]:

So when we mentioned the mitochondria as a room in the house, the cytosol is sort of like the common area. Right. Of the cell, if you will. I was trying to think of an analogy last night. I couldn't come up with a good one, but I just think, like, the common area, I guess, is the best I could come up with. And what's cool, this is the part I was curious if you knew about. They've recently identified the transporter. So mitochondria actually transport glutathione into the mitochondria from the cytosol.

 

J Gulinello [00:40:25]:

And the transporter is SLC 25 A 39. What a wonderfully. Just rolls right off the tongue. But what's cool about that transporter is that it's not only a transporter, but it also seems to be a sensor for glutathione availability. And when they did, they had animal studies where they did, they created knockout mice where they knocked out that particular transporter and the mice didn't survive. That tells you how important it is, and we don't quite yet know. And also, if you knock out that transporter, glutathione in the rest of the cell seems to remain intact. It's just mitochondrial glutathione that is impacted.

 

J Gulinello [00:41:06]:

So that's really interesting. Just to understand that dynamic. It seems like the mitochondria use that transporter, which is also a sensor, to call glutathione, into the mitochondria.

 

Michelle Shapiro [00:41:17]:

Because the mitochondria uses its own glutathione, the rest of the body can use glutathione as well. But the mitochondria uses its own. It's its own once it's inside of the mitochondria.

 

J Gulinello [00:41:28]:

Yes. And also just to let people know, I should have mentioned this during energy.

 

Michelle Shapiro [00:41:32]:

Production, also like bringing up this bigger question of how energy related itself, mortality and lifespan are to our ability to have glutathione within the mitochondria. So the transport is essential. And the presence of glutathione as a compound is essential, obviously, to the rest of the body. But that could be the most essential to literally being alive. That's really interesting.

 

J Gulinello [00:41:56]:

Absolutely. And so glutathione protects from oxidative stress. It even protects from mercury and other toxic metals. It protects from alcohol, persistent organic pollutants. So it does a lot. And I should also have mentioned this, but when I was talking about energy production, mitochondria also, during that process of energy production, some of those electrons that are passed down the electron transport chain, they can leak out. And essentially what that is doing is it's creating something that most people are familiar with called reactive oxygen species. And so that's what glutathione is particularly useful for.

 

J Gulinello [00:42:29]:

Right. Ros. And that's a normal part of energy metabolism. So, you know, some, we had that theory of aging that was antioxidant driven, that we need to, you know, destroy all reactive oxygen species. But we found out that that's actually not accurate, that reactive oxygen species can actually be secondary signaling molecules. So they actually serve a purpose in the cell. But when they get out of control and they exceed the body's ability to be able to handle them, that's when they can become problematic. So glutathione is imported to the mitochondria to handle that.

 

J Gulinello [00:42:58]:

And the mitochondria also, just as a side note, has another endogenous found in the matrix, an endogenous antioxidant called manganese superoxide dismutase. That's the mitochondria's own special antioxidants. So between that and glutathione, generally speaking, you're handling those reactive oxygen species, and what's so cool, it's totally off topic, but, like, the excess of reactive oxygen species can do a lot of things in the body. But one of the things I found was that it could be the potential premature graying of hair could be due to a, an overabundance of reactive oxygen species and has to do with hydrogen peroxide. But. But that's just to show you that.

 

Michelle Shapiro [00:43:35]:

Like everyone, very closely now, Jay, everyone heard graying hair, and they all started listening to you now, right.

 

J Gulinello [00:43:43]:

It seems to be that this overabundance of or an inability to remove hydrogen peroxide may be at play here. So I'm going to do a little bit more digging on that. I just, like recently, and also, like.

 

Michelle Shapiro [00:43:56]:

I would think, like, bleaching from hydrogen peroxide, that's really, really interesting because then your hair is, like, bleached. Also, there's a copper component to this, too, because copper deficiency is well known to be a root cause of premature graying of hair as well. And I'm wondering, because copper is obviously involved in energy metabolism too, where these two meet. Now I'm interested in putting these two together.

 

J Gulinello [00:44:19]:

I am as well. And also, and so copper and zinc superoxide dismutase, those are the antioxidant systems in the cytosol of the cell. So you've got those, you've got manganese superoxide dismutase in the matrix of the mitochondria. And you've got glutathione. That kind of is known as the master antioxidant. It kind of travels in between and kind of handles everything. You've got redundancies, because, again, reactive oxygen species aren't inherently dangerous on their own when they're controlled. It's when they get out of control that they may become problematic.

 

J Gulinello [00:44:48]:

So, yeah, something I thought that was.

 

How is glutathione related to the regeneration of vitamin C and vitamin E?

Michelle Shapiro [00:44:51]:

Okay, this is a very. This is like a twisty, turny question, but roll with me. When people are sick, they take vitamin C to boost immune function. We know that vitamin C has antioxidant capacity. Okay, everyone, hold that thought. Who's listening? Hold that thought for a second. Glutathione is known, like you said, it's this master antioxidant because it's used in many different parts of the body, well, every single part of the body, and has great capacity and power. Is the issue with mitochondria causing disease that you don't have the energy to run your normal body processes? Or is it that the byproducts of energy metabolism, like you're saying, are not being handled properly and those are wreaking havoc on your body, whereby again, the vitamin C.

 

Michelle Shapiro [00:45:43]:

Everyone's thinking you boost your immune function in this very simplistic way of doing it. My idea of what glutathione helps the body to do when it comes to mitochondria and the rest of the body is it really helps the body to either remove things that are potentially dangerous, and in addition to that, do the vitamin C thing, which is actually just enable your body to function properly. So the question is, is the root of disease that we have a buildup of the bad stuff or not enough energy to do the good stuff?

 

J Gulinello [00:46:12]:

Man. Now you're getting into terrain theory, and I love that because I don't know the answer, but what I can tell you is that. Yeah, it's what an interesting question. So what I can tell you is that glutathione also participates in the regeneration of vitamin C and vitamin e. So theres the potential there that taking vitamin C frees up glutathione to be able to handle other issues, and that may be why. So I think theres multiple factors at play here. Yeah, its just, its so interesting and I dont know the answer because the first step towards improving glutathione function in one of the fantastic paper I read by Joseph Pizorno, who wrote one of my textbooks, one of my functional medicine textbooks in college. Yeah.

 

J Gulinello [00:46:55]:

Here are this amazing sort of paper on glutathione. And he said the first thing that you need to do is remove the things that are causing this upregulation of glutathione. Right. So remove the stressor is always the first thing, whether it's a chemical, physical or emotional stress. You got to remove that stress first. So I think it's a combination of the two, to be honest.

 

Michelle Shapiro [00:47:17]:

It's fascinating. Yeah. Are you at the, you know, you're a believer that the balance of omega six fats, omega three fats is one of the root causes of a lot of the dysfunction that we see. Are you feeling and what, from what you're researching, coming to the conclusion that glutathione, I don't want to call it deficiency imbalance or something because it's hard to call it a deficiency or mitochondrial dysfunction, are root causes of the chronic illness rise that we're seeing today. Is that a belief that you have?

 

J Gulinello [00:47:52]:

Yeah, I do. Yeah. Really? I think, and there are salvage pathways, even for glutathione. I think it's the gamma glutamyl cycle, I think, that regenerates. I remember this from grad school because we used to look at organic acid tests on patients, and there's a specific organic acid called pyroglutamate that was a sign that there was glutathione wasting, which means there's so much need. Glutathione is being pushed into the salvage pathway and regenerated. And by the way, cysteine, the amino acid cysteine is sort of the rate limiting step in glutathione synthesis. So it was just interesting to see on certain people's labs that had a heavy oxidative burden, oxidative stress burden that they would, generally speaking, be peeing out more pyroglutamate, which told me that the gamma glutamyl cycle was in high gear trying to recycle glutathione as quickly as possible.

 

J Gulinello [00:48:45]:

And of course, since we're also magnesium deficient, it took three magnesium molecules to help recycle glutathione. So this is really interesting that I just remember this extra salvage pathway that seems to kick in when things are really kind of going haywire in terms of the toxic load that a person is experiencing.

 

The role of protein

Michelle Shapiro [00:49:07]:

If you studied cancer patients or terminally ill patients, that you would see a lot of what you like. I like the phrase that you salvage pathways, again, on this very high level, Jay, what I'm seeing is, and from this conversation, I always get insights, even in our conversations, texting conversations, I even get insights from you. But the body acts in a certain way when it has all of the information, all of the resources that it needs, and then it starts acting in compensatory ways when it doesn't have those nutrients and resources. Something I need to highlight in saying this is that what we're talking about? Glutathione, this master antioxidant, is composed of three amino acids. It is a protein structure, right? These are made of the smallest part of a protein, which is the amino acid, the most base structure of a protein, that are then linked together to create longer proteins. So someone listening to this might say again, well, where does protein fit in in ways of my overall health? Where does protein fit in in ways of weight loss? And have these conversations. And then I know someone who might be consuming a very low protein diet is saying, well, I consume a low protein diet, and I'm fine, right? I'm okay. But the question is, do we know if we're okay at that protein level? No, we don't really know.

 

Michelle Shapiro [00:50:31]:

And then also how essential protein is outside of what we always talk about in addition to, of course, just like, very simple things, like it's satiating, and then things that I talk about all the time, it being the basis of neurotransmitters, it being the basis of our immune system, our antibodies, the structural glue that holds our entire bodies together. Especially in hypermobile bodies like mine, we really need as much extra connective tissue and protein as we can get. It just brings me again back to this thought of, where is someone's body operating from? Is it operating from a place of compensation because it hasn't had the protein it needs for so long that the body just starts operating on a different level and that eventually, again, turns into disease. So this just brings up that thought process I always have is, yes, you might be, like, alive and you might be functioning, but without the right amount of protein for your body to do these deeply complicated and very energy intensive processes, it just accumulates over time. So that was more of a thought. But another question.

 

J Gulinello [00:51:37]:

No, I think of things like triage theory, and unfortunately, we don't know because the human body is so good at making excuses for a suboptimal diet. Right. And so that is the question. When are we functioning optimally? I mean, I think I have an idea, but I think a lot of it is subjective in terms of how you feel. And I know a lot of people who will even. I know a lot of people who don't feel well, but continue on the same path, whatever it is, whether that be like a vegan diet or something, even to the detriment of how they feel because of an ideology, which is exactly. Which goes back to the original thought that I just really want people to break this down into a dispassionate biochemical lens so that we can figure out what we need to do. And, and that's.

 

J Gulinello [00:52:21]:

And I, and I. So I totally understand what you're saying. And I agree with your point that, you know, we don't really know, but I think that, you know, for instance, glutathione, right. Practitioners of meditation have been found to have 20% higher levels of glutathione. So what is that? What is that telling us? That's telling us that somehow we are reducing some sort of oxidative stress burden, even just through a parasympathetic shift, potentially. And that is allowing glutathione to be saved. Right. It's not being used on a per second basis to deal with all of those reactive oxygen species that we're generating through either poor lifestyle or poor nutrition.

 

J Gulinello [00:52:58]:

So if you can see something like meditation, improving glutathione levels, I mean, I think that tells us a lot about how the body will compensate for certain things and if we treat it well, how much better it will perform.

 

How do you get glutathione measures levels measured?

Michelle Shapiro [00:53:11]:

Totally. And also, you can measure glutathione levels. So tell us, how do you get glutathione measures levels measured?

 

J Gulinello [00:53:19]:

So, actually, I'm only looking at it through labs, but, yeah, I mean, I think you can get it in serum, correct?

 

Michelle Shapiro [00:53:30]:

Yeah.

 

J Gulinello [00:53:31]:

And I mean, in a lot of the, you know, and just so that if people are wondering, people ask me all the time, what kind of glutathione do you use? And I know we kind of talked about this a little bit offline. I actually don't supplement with glutathione. So I take this approach. I reduce the toxic load. And then I actually, when I do decide to supplement with something, it would be Nac n acetylcysteine, which is the precursor to glutathione, because I kind of am a firm believer that I need to let the body decide how it's going to use, whatever it's going to use and what it's going to need. I just have this strange thought about dumping in high levels of an antioxidant because I just don't know what the body's going to do with that. And then there's also the argument that glutathione doesn't even make its way through the digestive tract. And I've read quite a few papers that talk about potential transdermal liposomal glutathione being effective.

 

J Gulinello [00:54:27]:

But the research is still new. But I always err on the side of ill give the body the precursors. So I eat a high protein diet and I use NaC whenever necessary. And then I think that just kind of like I let the body take over because I trust it. It knows way more through millions of years, it knows way more than we do about what we should do to improve health. So thats just my thought about supplementing with glutathione in case people are, because im sure people are going to wonder.

 

Michelle Shapiro [00:54:50]:

Yeah, because you're Jay. Also, I have to mention that it's like this very funny view the humans have had with the body where we're like, if you eat cholesterol, cholesterol high in blood, we have this very caveman view of it with the same thing as glutathione, which is like we take glutathione equals higher glutathione and it's like, do you know the amount of processing is your body has to go through for it to create the internal glutathione versus the external. I almost have people, I'll often give people amino acid supplements to help boost glutathione just so that they have the actual components of it.

 

J Gulinello [00:55:24]:

Absolutely. So, you know what's interesting is that glutathione production from something like, if you have ever looked at, I have this diagram from grad school memorized in my head. But the methylation pathway and then the transulfation pathway, b six, is required for homocysteine to become cysteine. So I know b six is part of that. And then that eventually can become glutathione. So those are all those we know.

 

Michelle Shapiro [00:55:45]:

Because we measure homocysteine, um, which we look at as a measure of either B vitamin deficiency, b twelve, or we're looking at orfolate and we're also looking at it from the perspective of potential inflammation in the body, too, because, which is the, that's a different, a different day. Mthfr, we're talking mthfr a different day. And I will have you back to talk that, because it's really fun. So, um, I do, I will just say on a note, I have used NAC with clients. I've used glutathione with clients, I've used, um, iv's with glutathione in them. You know, Jay, the reason why this is a bigger conversation, because I want to do glyphosate too, but this became very important and controversial and interesting during COVID also. I mean, I know that the conversation of mitochondria has been around for, you know, since the beginning of science. Like, I'm sure, you know, this has been a conversation for a long time, the focus of mitochondria being the center of longevity.

 

Where do you believe NAc and glutathione play into COVID and immunity?

Michelle Shapiro [00:56:42]:

Where do you see glutathione Nac? Because NAc also was a supplement that the government was like during COVID Like, ooh, I kind of want to have this instead of you guys having this from individual suppliers.

So where do you believe that nac and glutathione play into immunity and Covid? Why was this coming up so much during COVID Was there interesting data that came out? What happened.

 

J Gulinello [00:57:19]:

On the outer mitochondrial membrane? Right, the outer membrane that faces the rest of the cell, and the cytosol. There are mitochondrial antiviral signaling proteins. So the mitochondria actually also participates in immunity as well. And so I was just interested in the fact that the mitochondria was never mentioned during COVID But I knew doctors that were using things like Nac, that were using iv vitamin C, that were using a lot of things, and that were having massive success. And this is in March of 2020, before anybody knew anything. And so my large big picture perspective was always this. You cant tell me from one perspective that you dont know whats going on, but by the same token, you can tell me, you know, what's not going to work. So that was my biggest thing.

 

J Gulinello [00:58:08]:

So Nac, I'm sure, had, if you look it up, you'll see a lot that has to do with COVID And I remember that they were trying to remove that as a supplement over the counter, which was just shocking to me, given what an important role it plays. My whole thing during COVID was, why is nobody mentioning metabolic health? Because we knew that was a severe risk factor. Why was nobody mentioning mitochondrial health? Because, again, antiviral signaling proteins on the outer mitochondrial membrane. It just kind of drove me crazy.

 

Michelle Shapiro [00:58:35]:

You know, that a lot of the work I do is around mast cells, histamines, pot, everything like that. Like, I think that there was unique issues with COVID specifically. Maybe the vaccine, combinator, whatever, something, the virus itself or the combination and everything together, where there was challenges on two fronts. I think there were challenges to the mast cells because Covid attaches directly to mast cells. And I think there were challenges to the mitochondria. And I think, like, looking back, if we look at what long Covid was and is a grossly underprepared population, including myself, I'm not. I'm not saying we. It's all of us together who had poor mitochondrial function, probably low glutathione, I don't know, levels.

 

Michelle Shapiro [00:59:19]:

I don't know what to call it, but. And at the same time, we were primed from a nervous system perspective, from a mast cell perspective, for our bodies to react really strongly to this. I think it was actually like we were a perfect population. Because I think, as I'm putting the pieces together, after years and years of working with clients on this and now seeing it's been four years of looking at this, in my own experience, I put it in those two buckets, I think the mast cells were critical, and I think the mitochondria were critical. When it comes to long Covid, well.

 

J Gulinello [00:59:50]:

We tend to, and we tend to as a population, we don't address things until they've occurred. So we don't work on, like, we talk about preventative medicine in the field. We do preventative medicine, but most doctors don't do preventative medicine. They wait until symptoms arise, because that's the algorithm. I mean, I hate to say this, but I worked in a hospital, and I talked to many doctors who don't know what to do with the human body unless there's a marker out of place that needs to be nudged with a medication or some symptom that needs to be treated. They have no idea about mitochondrial function. They have no idea about just metabolic health in general. They have a very limited scope, and that's just the way they're trained.

 

J Gulinello [01:00:25]:

And many of them admitted that to me when they were in my office, candidly, they said, you know, we didn't study any of this. Or if we did, it was at the first semester and I forgot it all. And that's. I think you're right. I think the population and I think, honestly, going forward, we would be in the same position. Because we have certainly not improved our metabolic health or a mitochondrial health over the past four years. So that's why shows like this, I think, are very empowering for people that can at least have that idea put in their head that, hey, this may be a downstream issue of metabolic consequences. And maybe Covid or anything else wouldn't be as bad.

 

Michelle Shapiro [01:00:58]:

And I think we found out what is not health during this time. Because people who, again, had no symptoms, it was so devastating to see that people who probably would have been fine for another 30 years. Fine is the word I'm going to use. It doesn't mean that they felt exceptional, but without extreme symptoms, had overnight extreme symptoms. I have a lot of philosophy around that and why that was so challenging from a psychological perspective for people too, like myself. I've been chronically ill since I was a kid. I've had different stuff come up much of my life. So I have a very high resilience, to be honest with you, for uncomfortable symptoms, because I'm used to them now.

 

Michelle Shapiro [01:01:35]:

I'm the healthiest I've ever been, thank God, I'm so happy to say. But it was. It took me really progressing to a point and not understanding my health and getting to that point for me to start lifting myself up. But it was slow for me, for other people who feel totally fine, have no stomach symptoms, no anxiety to overnight, hit that point. It was scary to watch. And I'm so glad I was able to go through it first because I was really having, like, all this kind of stuff happening before. But it was disastrous, and I do believe, again, mitochondria, mast cells, there's some interplay there that was between the two of them. Quick question before we do a little glyphosate.

 

Michelle Shapiro [01:02:11]:

People take NADH supplements. What do you think about taking the actual substrate? Tell me what you think. And IV's. People take IV's of that, too.

 

J Gulinello [01:02:20]:

Yeah, I just don't think we have enough research to support that yet. I mean, I can understand it, but again, I'm all about providing the body with the nutrients that it needs to do what it wants. I just have a. I have issues, or I have concerns about forcing molecules into the body that are going to create a response right away. And I just. I don't know. I've read a lot of research on it because I've been very curious about it. And people have asked me, but nothing seems to be super convincing yet.

 

J Gulinello [01:02:49]:

And then of course, there's the question of which version is more absorbable and which one is more bioavailable. So I don't know. I think the journey is still out on that. I think there's a lot of research, and I know a lot of people have said that they have positive results, but I'm. I remain skeptical in terms of NAD for now. I just want to read more research on it.

 

Michelle Shapiro [01:03:08]:

That's how I feel too. But I feel pretty strongly about NEC, and I feel pretty. I actually think there's some. I haven't seen as many positive results from taking glutathione directly, even liposomal. And like, trust me, I was a biohacker. I was in. I was like, I'm totally bought in. I actually have seen better results with NaC.

 

Michelle Shapiro [01:03:26]:

Again, this is nothing from. I haven't conducted a formal study. I'm just sharing what I've seen. And I actually, I tend. We've seen the same patterns, honestly. So it's interesting to reflect upon. So we know also, just to put a bow on our glutathione part of the conversation, we know what affects glutathione production and ultimately then mitochondrial function. Outside of food and eating the right nutrients, what else can affect your mitochondrial function? What else can affect your glutathione production?

 

Outside of food and eating the right nutrients, what else can affect your mitochondrial function and glutathione production?

J Gulinello [01:03:56]:

Well, I would say. I mean, I would say in general lifestyle, I think about things like, I was having this conversation with somebody recently that after exercise, you could imagine with a ramped up energy production that you would also have an increase in reactive oxygen species. Something interesting that I've been trying lately, and it seems to be working, is after intense exercise or a run or something like that, I'll take off my shoes and actually go ground stand on the earth and do a little exchange situation. Yes. And that is an antioxidant in many ways. And I've noticed, I have some right knee issues and I've noticed significantly less inflammation when practicing that. Once upon a time, I thought that stuff was really out there, and I was not super interested in that. I just thought it was woo woo.

 

J Gulinello [01:04:44]:

But then I started to read the science and I remained open minded, and so I found some really fantastic results. So it's really just. It's sleep, it's the three pillars. It's sleep, it's proper nutrition, and it's movement, you know, and it doesn't have to be anything crazy when it comes to movement, doesn't have to be a crossfit gym. It just has to be, your body is meant to move. Body's in motion, stay in motion. So I think, you know, the more, and the people that have been active their whole life, they tend to stay active. And they, you know, they're the 80 year olds that you see out there that are still working in the yard and have no real aches and pains.

 

J Gulinello [01:05:18]:

And I love to see people doing that kind of stuff. So start when you're young. But, yeah, those are the things. I think also, you know, sleep is very underrated. You know, we live in a culture where people say, oh, I'll sleep when I'm dead. I think that's a huge problem because, you know, we don't have an opportunity for the brain to do its work unless we're really in that deep parasympathetic state and getting some deep sleep. So, so sleep, nutrition, and movement are my, are my three keys for all of that. Again, remember, removing that toxic load for glutathione status, removing that toxic load is a big thing.

 

J Gulinello [01:05:51]:

So if you've got heavy metal poisonings or you're living above a, you know, I don't know, living above a machine shop and there's diesel fumes and things, you know, you have to really consider your environment where you're living. I had to have that conversation with people. Say, you know, you might want to.

 

Michelle Shapiro [01:06:05]:

Consider moving to Jay.

 

J Gulinello [01:06:07]:

Yes. You might want to consider moving because you're just. Yeah, yeah. So it's, it's, that's the big, those are the big things. Those are the, your controllables, your lifestyle, your nutrition, and your sleep. So control them as best you can.

 

Michelle Shapiro [01:06:20]:

And I'm in the sleep category. I'm going to add light as well, because I think the research is. Explain. That's a great one on light and mitochondria and glutathione. It's really, really fascinating. And Doctor Alexis Cowen did an episode of the podcast who's kind of like the Light Queen. Now, to be honest with you, if you need resources on understanding light and energy and how it influences our overall health, was talking specifically about how it affects our mitochondria. And again, there's that something about it being this ancient bacteria, like with the rhythms of earth and interfacing.

 

Michelle Shapiro [01:06:52]:

There's something very spiritual about the mitochondria, too, and the way that they're begging us to be human again, I always say this, on every single podcast episode, you have to be a human first. And that really does influence glutathione I would say function production, even more than just taking an NAC supplement. Those things are so important.

 

J Gulinello [01:07:12]:

Complex four. When I talked about energy production, light has a direct. It's a photo acceptor complex for cytochrome C oxidase. That is a. It's stimulated by light. So, yes, light at specific nanometers does directly impact your mitochondria. So I love red light therapy.

 

Michelle Shapiro [01:07:27]:

Yeah, it's unbelievable. Yeah. And even again, people just orienting themselves to natural light at the right time versus using your phone. That's why all these annoying biohacking people, you see them being obsessed with the lights and everything. I don't know that all of them know why they're doing it, but there is a reason they're doing it, by the way, whether they know it or not. It's valid. It's actually valid. The obsession with the light thing is real.

 

Michelle Shapiro [01:07:50]:

So, you know, let's do a little glyphosate, Jay, because I can't steal your whole day, even though, damn, I'd love to. There has been extreme controversy around glyphosate, specifically recently. I needed to bring you on to talk about it because I was devastated about the bonza situation, which we're going to talk about. What is glyphosate? Why is glyphosate? Start me somewhere.

 

What is glyphosate?

J Gulinello [01:08:16]:

Yeah. So glyphosate is the most widely used herbicide in the world, in agriculture. And it's essentially, which is interesting because it actually shares something in common with glutathione. It's essentially a glycine molecule with a methyl phosphonyl group bound to the nitrogen atom. So it's very similar structurally to glycine. And that becomes really important because of how it interacts biochemically. But what's super interesting is that the United States, after 2014, really stopped reporting glyphosate usage, which is kind of scary, because you really don't even know how much we're using. And that was according to a 2021 paper in foods.

 

J Gulinello [01:08:49]:

They had no existing data on glyphosate usage after 2014. It went off patent in 2000. So most of it is made in China. Now, it was originally used as a descaling agent. And for people who don't know, descaling agents effectively bind to metals. It was used in pipes to pull out things like calcium and magnesium. And so it's a chelator of anything that's a plus two cation. So you're talking about manganese, magnesium, calcium, iron, in certain states, just things that.

 

Michelle Shapiro [01:09:19]:

Provide the energy and electricity for our bodies. Okay, got it.

 

J Gulinello [01:09:22]:

Absolutely. Absolutely. That's, you know, and I see people all the time and these people drive me crazy. And it's, you know, that's why I love doing shows with you, because you're a dietitian who has really studied this stuff. But I just find. So I just recently somebody last night, I think, sent me like, you know, just a reel on somebody, some dietitian, making fun of people being concerned about glyphosate. And that just blows me away because the only evidence that she had was appeal to authority, saying, like, well, it's been approved for use, you know, blah, blah, blah. And so it's nothing.

 

J Gulinello [01:09:52]:

It's, you know, according to whoever, it's perfectly safe. Now, the World Health Organization puts it in a class of carcinogens similar to red meat, which tells you everything you need to know about the World Health Organization's classification of carcinogenic material.

 

Michelle Shapiro [01:10:08]:

I thought you were going to use the World Health Organization as an example to say it puts it as a carcinogen. I'm like, but don't they also put meat in the same category? So I'm glad you said that.

 

J Gulinello [01:10:15]:

Yeah, exactly.

 

Michelle Shapiro [01:10:16]:

Yeah.

 

J Gulinello [01:10:16]:

I mean, so it's just the appeal to authority thing is a little silly, if you ask me. And so I've got so much material on this, and this could be its own episode, but it has been shown. And remember when we were talking about antioxidants in the mitochondria and I mentioned manganese superoxide dismutase? That's a matrix side mitochondrial antioxidant. There's a paper in 2013, the Journal of Environmental and Analytical Toxicology, they found that Roundup ready did create deficiencies in manganese and cobalt. And if you know anything about cobalt, cobalt is the center of the b twelve molecule. So you could see b twelve deficiencies. You could see. Now if manganese superoxide dismutase is impacted, that's going to, that's going to disable one of the endogenous mitochondrial protections against reactive oxygen species.

 

J Gulinello [01:11:07]:

What that also does is that damage is one of the enzymes. You said you memorized all your, your Krebs cycle enzymes. So that damages an enzyme called econotase, which is the enzyme that turns citrate into isocitrate in the Krebs cycle. So now you've got energy production being damaged potentially on the TCA cycle end, and you've got a disabling of some of the mitochondrial antioxidant defenses. And that's just one paper and I have seven pages of information on this because again, what am I trying to do? Michelle, im always trying to say, listen, my approach is the precautionary principle. Im not telling you, I know for sure that glyphosate certainly its not going to kill you instantly, but its this long term exposure that we, again, I just told you that we have no idea how much were even using. So when they tell you, well, this much was found in a pasta, but it would take 20 pounds of that pasta to cause problems. My answer to that is, well, how much other food are you consuming that is doused in glyphosate? And the answer is, nobody knows.

 

Why have other countries banned glyphosate?

J Gulinello [01:12:07]:

So when people say the dose makes the toxin or the dose makes the poison, like with fluoride in the water, I say, sure, but how are you controlling the dose? Nobody has any idea what the dose is. So now I break it down to those biochemical principles and the mitochondrial impact. And I say, absolutely stay away from glyphosate because everything is safe until it isn't.

 

Michelle Shapiro [01:12:26]:

Totally. And I mean, my question is, why have other countries banned glyphosate?

 

J Gulinello [01:12:32]:

It's a great question.

 

Michelle Shapiro [01:12:33]:

Yeah.

 

J Gulinello [01:12:33]:

Based on what?

 

Michelle Shapiro [01:12:34]:

Yeah, well, that. Do we actually know the answer? Why have they banned it? Like, there's, there's many countries who have banned use of roundup and glyphosate being sprayed on foods. I am assuming it's because they have linked it to health outcomes.

 

J Gulinello [01:12:47]:

No, I believe so. And I'll also tell you this, that Monsanto in this country, well, until it was bought by Bayer, was very active in sort of obfuscating the truth. So the International Journal of Risk and Safety in medicine in 2018 put out a report on a set of 141 declassified Monsanto documents made public during the whole roundup litigation. And I want to just read this quote. The document revealed Monsanto sponsored ghost writing of articles published in toxicology journals and the lay media interfered in the peer review process, behind the scenes influence on retraction, and created and the creation of a so called academic website as a front for the defense of Monsanto products. So Monsanto themselves, if they had a product that was so fantastic, why would they need to engage in all this obfuscation of the truth? And so again, as a person who doesn't want to be, you know, those commercials, you see, Michelle, that, you know, if you were a loved one, had been injured by, you know, whatever product that's always 20 years down the road, you don't want to be the person that needs a settlement because you've been injured by something like glyphosate. In my opinion, it's best to stay away from it because we have enough mechanistic data to say it's probably dangerous and it's also impacting things like honeybees, so it's not good for the environment. Why are you using it?

 

Michelle Shapiro [01:14:01]:

Other concern, by the way, but the mono cropping combined with the spraying of the roundup. Olivia talks organic. Olivia. Olivia Matrono talks a lot about this too, and has for ten years because of the. How much it affects the diversity of the other animals, plants, everything in the area. So, Jay, in addition to these tiny mechanisms that we're talking about on the electron transport chain, is there known, any known glyphosate issues with digestion, progression of cancer, like cancer, any other disease? Are there studies that link it to those?

 

Are there any studies that link glyphosate issues with other diseases?

J Gulinello [01:14:37]:

There's a ton. There was a recent study that came out that showed that for the first time, that glyphosate can actually cross the blood brain barrier and increase tnf alpha. So there's now potential disruption of brain metabolism and research that's connecting it to Alzheimer's. So again, cancer. There's a ton of that. So let me see, what did I find for cancer? Yeah. The EPA, March 1985, classified glyphosate is a class c carcinogenous. But then.

 

J Gulinello [01:15:07]:

So here's some other interesting information. Let me read this to you. So, Doctor George Levinkas, director of the environmental assessment and toxicology, there was an internal memo that found senior management at the APA reviewing these proposals to classify glyphosate as a class c, probably carcinogen because of these kidney adenomas in mice. A Monsanto doctor, Doctor Marvin Kushner, they said that he'll review the kidney section and present his evaluation of them to the EPA in an effort to, and I quote, persuade the agency that the observed tumors are not related to glyphosate. So, I mean, I don't know, Michelle.

 

Michelle Shapiro [01:15:47]:

Oh, go ahead. Yeah, yeah.

 

J Gulinello [01:15:48]:

No, no, I'm just gonna say, when I think of science, this is not what I think of. I don't think of backroom deals and I don't think of, you know, internal people. It's like the fox investigating the hen house 100%.

 

Michelle Shapiro [01:15:58]:

It just, you know, so I think it's just so hard with the dietitians on social media. I love you all. I'm a dietitian. We know. I love you so. I love you guys so much. But what I feel frustrated about is that we have pretty reasonable and understandable mechanistic evidence, but that is not going to translate into pubmed journal research. It's kind of the same thing with the seed oil fight that you have every day of your life, Jay, which is just like.

 

Michelle Shapiro [01:16:29]:

You're like, yes, if you have too many omega six fats, it's going to take the enzyme needed in order to have the active form of omega three that you need for the body. Like that is, it's just the mechanism. So I find with the glyphosate conversation, it's really hard to explain mechanism, even on social media. And also, you're not going to find. It's just not. No one's funding that and no one's allowing that research to come out. I think, like, evidence from other countries banning it is substantial. I would like to know each country why they would have made that decision.

 

Michelle Shapiro [01:17:01]:

To be honest with you, Jay, the bigger, harder question I have about all of this is because forget about trying to prove people of anything. I don't really care. We're just going to give people the information we have and let people make their own empowered decisions. Like, since we don't know what's being sprayed with glyphosate and we don't have quantifiable values for it, how do we even start the process of trying to avoid foods that have it? How do we know what it's in and how do we get that information?

 

How can we start the process of trying to avoid foods that have glyphosate?

J Gulinello [01:17:27]:

I mean, you can look at certain environmental working group and other groups that do that, but the real answer is you need to test yourself. You need to go as organic as you can. But glyphosate is in the water, it's in the air, it's on grass. You play in the park, it could be on the grass there. So the best thing you can do is test yourself. A cheap urine test can get you an idea of your glyphosate load. And then you need to engage in some of the things like chlorella, activated charcoal, sauerkraut, Quercetin, Nac, some of those things that can really help you avoid. And honestly, there was a paper published a couple of years ago that showed that meat and meat products, milk, dairy, meat, did not bio accumulate in ruminant animals, which is interesting.

 

J Gulinello [01:18:09]:

So it might have something to do with their metabolism, which is another reason why I say animal based diet is a really great place to start. So if you're trying to avoid it, meat seems to be a safe place to be. But the truth is, you've got to test yourself and then you've got to engage in some of the mitigation principles, because you're right. There's really no way for sure to know what your exposure level is because it's even been found in tap water. So are there.

 

Michelle Shapiro [01:18:32]:

Are there certain foods that are guaranteed to almost have higher levels? I mean, like, GMO corn probably will. I think chickpeas are actually very heavily sprayed as well. Like, there's. Are there certain foods, you know, are usually sprayed and that you would say, maybe go organic? Does going organic health? Those are my two questions.

 

J Gulinello [01:18:50]:

Yeah, absolutely. The EPA, in 2015, they had a list of foods there like almonds, soybeans, cotton, corn, figs, grapes, lemons, oranges, pistachios, sugar beets, sunflowers and walnuts. Um, and then again, you know, hummus is another big one that one sense. Every time somebody does an investigation into hummus, they tend to find high levels of. Of. Of glyphosate. Um, pizza, like, 90% of pizza samples. Uh, wheat flour, crackers, fresh pasta.

 

J Gulinello [01:19:15]:

So, I mean, you know, a lot of those foods I tend to avoid anyway, but, yeah, yeah, but so, yeah, grains are really important to go organic. Um, I mean, go organic as much as you can, but you technically should.

 

Michelle Shapiro [01:19:27]:

Not have herbicide sprayed on organic foods. Right? Shouldn't that limit it should be. No pesticides, herbicides. That's the point. Yeah.

 

J Gulinello [01:19:36]:

Except the fact that, you know, you could have an organic field that's right next to a. A non organic field, and they have this concept called genetic drift. So, you know, the. The glyphosate still, you know, we just don't live in that kind of a bubble. But, you know, I get a lot of my stuff from an amish farm in. In Pennsylvania, which is really nice because they. There's, you know, there's nothing around them. And so.

 

J Gulinello [01:19:54]:

But, you know, I've. I want to test my own glyphosate levels, and I actually just. I just purchased the urine test because I wanted to test just to see, you know, given my lifestyle, I should be pretty low. But if I wasn't, it was going to be really something interesting to investigate. So I highly recommend it for people if they're concerned about that, if they see any of the, you know, the side effects, which, again, could become, you know, mitochondrial dysfunction. It's good to know what your toxic load is.

 

Michelle Shapiro [01:20:19]:

And that's what your concern with glyphosate is, mostly mitochondrial dysfunction. Or is it, like, I know, gut lining attacks are a big concern for people. Are those your main concerns? When it comes to glyphosate, absolutely.

 

J Gulinello [01:20:31]:

Yeah. Upregulations in zonulin, which control tight junctions in the gut epithelial cells, that's another thing. So, yeah, I mean, everything from gut to even loss of blood sugar control has been found. I mean, like I said, I got seven pages of research on what it could potentially do. And so even if a percentage of those are accurate, when it comes to humans, I mean, what's the downside of avoiding it? And I just find it funny when people actually advocate for it. Like, I wonder about these dietitians who do these reels, and I think about their poor kids. Are you just dumping cereals and grains with just glyphosate on top of glyphosate? And then if something happens, are you gonna pretend that it has nothing to do with glyphosate?

 

Michelle Shapiro [01:21:09]:

Yes.

 

J Gulinello [01:21:10]:

I just wonder about the idea of. Yeah, I mean. I mean, why not avoid it? That's my point of view. Again, that's my bias, but at least I let you know.

 

Michelle Shapiro [01:21:19]:

So my sister, my nephew, every morning he was eating bonza chickpea waffles. And then there was this huge mom's group who actually investigated, and they tested, and they found that there was the highest level of glyphosate of any food they've ever tested in the group before. And unfortunately, my nephew now walks around with the bonze box screaming waffoo. Every morning. He's like, one and a half. And we're like, so what my sister's been doing is making organic waffles in her waffle maker and then putting it in the bonza box now so that he doesn't know we've been doing it. But, you know, it's so interesting because a lot of people were like, you know, my sister even was going back and forth with me a little bit, and she asked me to ask you these questions because she was like, yeah, but still, like you said you'd still need, like, 20 times the dose for it to cause potential harm. I'm looking at something from, like, you are from, like, a harm reduction standpoint, right.

 

Michelle Shapiro [01:22:13]:

That's what I'm really looking at, is how much can I mitigate potential inputs when it comes to glyphosate or when it comes to other pesticides and things like that? Because also, like, everything we eats in plastic, like, we're going to get toxic exposure a lot and all the time. So I think we can just do the best we can. And something like this, I definitely jumped and I'm still, like, he's not eating those anymore. I'm going to be honest with you. I'm like, I'm definitely not doing that. I'm glad. And then it kind of made me start thinking about, you know, chickpeas are very commonly sprayed, but those are supposed to be organic also. So that is, I think, part of the problem and something that I have to think about and we all have to think about it doesn't make me go crazy, but it makes me jump into action.

 

Michelle Shapiro [01:22:57]:

And I'm going to say, you know what? Even if it's not, this one dose makes the poison. How many doses, like you're saying are you getting? It's the dose makes the poison. And in what little tiny one year old body is it going into?

 

J Gulinello [01:23:08]:

Right. And that's a developing child. So, yeah, I have concerns about that. I won't lie. And again, you don't want to be one of those people that's in the end filing those lawsuits because something happened to you because you thought it was safe, because influencers told you it was safe, because the government told you it was safe. And then all of a sudden one day it wasn't safe because there are plenty of drugs that have been on the market that later on were recalled because they weren't safe. So it's not like this is unprecedented.

 

Michelle Shapiro [01:23:34]:

Yeah, and it will be, and I'm sure it will be known in our lifetime, but it might already be known because other countries ban it, so it might already be known. I like when you said that phrase, because influencers told you it was safe. That is not how I'm going to be making health decisions, by the way, because influencers are telling me something is safe. I'm also not going to make health decisions based on if this amazing moms group who studied the bonza pasta, if they told me it wasn't safe, I then have to do my own investigations. And that's where I did some reflections, Jay. And I was like, you know what? I kind of, like, have to be conscious of even chickpeas is something that I want to be really conscious of eating organic if I'm eating them, you know, like, it's just something that to think about. And in these processed foods, there's intense amounts of chickpeas or if it's like an almond flour, like it's a lot of different products and things like that. You have to think about the, you know, I, well, I have to think about those things.

 

Michelle Shapiro [01:24:28]:

No one, no one listening has to think about them. I'm just letting you know, what I'm thinking about and what I'm considering when I see that information. It doesn't. Seeing something online doesn't prompt me into action. It prompts me into speculation, curiosity and suspicion, and that might ultimately lead to action in many situations.

 

J Gulinello [01:24:44]:

Agreed? Agreed.

 

Michelle Shapiro [01:24:45]:

Yeah. Did we miss anything on our. Okay, so I guess the one, one sum up question is, anything that helps to support your glutathione will help support your mitochondria. Anything you do to help reduce glyphosate intake or increase glyphosate excretion will also help your glutathione, which will ultimately help your mitochondria agree or disagree. And anything you want to add onto that.

 

J Gulinello [01:25:14]:

No, I think I totally agree. Again, we go back to this conversation about terrain theory, and the best thing you can do is remove. That's the first r, and the four or five hour protocol is remove whatever offending agent is. And that allows your body to, you know, that's often, you see people get sick when they go on vacation. And I think that's not a, that's not a coincidence. I think a lot of times people go on vacation and then their stress burden, you know, decreases, and then the body is able to engage in all these maintenance things, and that's when you end up feeling the symptoms of being sick. Same kind of thing. You just want to be able to remove as much of those toxins as possible, get adequate sleep.

 

J Gulinello [01:25:48]:

That's going to really help you detoxify. And then again, like Michelle, you were just saying, buy the highest quality food you can afford, do the best you can. It's not a judgment if you can trust me, I've been in that position in my life before, and it sucks. But you need to do the best you can, because as far as I know, you only get one body. And I just want to be here to, again, just provide people with information. What they do with it is up to them. But in the end, I think as long as you're doing the best you can and you're being conscious, like, I just. I just want people to be conscious consumers of health information instead of just like, by osmosis receiving information, because there's a lot of it is conflicting, a lot of it is confusing.

 

J Gulinello [01:26:28]:

And hopefully what we do is try to help you parse through some of that stuff in a way that makes sense to you. If something I'm saying doesn't make sense to you, then you probably should go look it up for yourself. But if. But if you get through listening to this conversation, and you think that makes a lot of sense. Okay, great. Then you're. Then you're at your first step of making some changes in your life that are going to benefit you in the long run, 100%.

 

Michelle Shapiro [01:26:50]:

I also just want to comment on you saying you think we only have one body. I'm a firm believer in reincarnation, by the way. And sometimes I'm kind of like, I don't know if this was my best round when it comes to the body. I might have taken some stuff from some other lives, and I think I accumulated a little bit too much from the past lives. I think I'm carrying some stuff on this one that's fair now, you know?

 

J Gulinello [01:27:14]:

So hopefully, you can take everything you've learned in this one into your next one, and then you're going to be like, primo.

 

Michelle Shapiro [01:27:18]:

But you know what? You're taking the trauma with you, too, okay? And we already know that, all right? And we take it intergenerationally, potentially, through life. I always have the best freaking time learning from you. And I mean learning from you. I learn from you in every single Instagram post you make. I learn from you every joking dm we send a, and I am always learning from you. And that is one of my greatest appreciations of a friendship. So I thank you so much for being such a teacher, such a lifelong learner. I just.

 

How can people find, connect, and work with J Gulinello?

Michelle Shapiro [01:27:48]:

I appreciate you so deeply. Tell me, Jay, how can people work with you? Find you? I'm going to put links, of course, below, but tell us, how can we engage and learn more from you?

 

J Gulinello [01:27:57]:

Yeah, well, again, I really appreciate the time. I enjoy the conversations and enjoy learning if the feeling is mutual. These are my favorite kinds of conversations, so if people want to find me. Instagram is certainly something that I've been active on for a long time, although lately not getting much traction there. So I'm branching out into videos. So you can find me on rumble at perpetual health. You can find me on substack at perpetual health. I'll give you all the links, but those are the places I try to put up different content in different places.

 

J Gulinello [01:28:24]:

So if you want to watch a visual, representative representation of what I do, you can go to rumble. If you want to read about it, you can go to substack, or you can go to Instagram. And the website is perpetualhealth co.