164 | Miracle Molecules - Glutathione (Part 2)

Unlock the secrets to the body's second "miracle molecule," glutathione, in this eye-opening episode of Inflammation Nation. Ever wondered how antioxidants can help protect your cells from inflammation and oxidative stress? We promise you’ll leave understanding the sophisticated system your body uses to produce and recycle glutathione, and the pivotal roles amino acids like cysteine and glycine play. If you're a vegan or vegetarian, find out why meeting your protein needs is essential and how you can overcome the unique challenges of plant-based diets.

We'll demystify the complex relationship between oxidative stress, glutathione, and the integrity of your gut and brain barriers. Learn how maintaining optimal intracellular glutathione levels can prevent barrier breakdowns that lead to chronic conditions and autoimmunities. We cover vital lab tests such as Cyrix Labs Array 2 and Vibrant Labs Neural Zoomer, which can identify potential issues like leaky gut and leaky brain. Furthermore, discover the importance of immune system balance, especially the role of regulatory T cells and how their function relies on both glutathione and vitamin D. You'll also get practical advice on monitoring your glutathione status through GGT levels in blood tests.

Ready to boost your glutathione levels? We'll guide you through the most effective methods, from direct supplementation with acetylated and liposomal forms to the benefits of whey protein, N-acetylcysteine, glycine, and high-dose omega-3 fish oil. But that’s not all—personalized healthcare is key, and we delve into the importance of tailored lab tests and coaching programs. Explore how diet and lifestyle modifications can naturally support your health and wellness. Tune in for actionable insights and personalized strategies to elevate your health journey!

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Transcript

Speaker 1 0:02

Hey everyone, welcome to the Inflammation Nation podcast. I'm your host, Dr Steve Noseberg.

Speaker 2 0:08

One of the greatest obstacles to crafting health and wellness is identifying and controlling inflammation. It's at the core of all complex and chronic diseases and it's the driving mechanism that underlies the most common symptoms that people like you struggle to overcome. Join us as we explore cutting edge science and research to give you the information and tools you need to create the quality of life you want and deserve. And now here is the host of Inflammation Nation, dr Stephen Nosworthy.

Speaker 1 0:36

Hey guys, welcome back to the podcast. This is part two of our talk about glutathione as another miracle molecule. In that last episode we just did, I introduced glutathione as my second miracle molecule and I shared that this is a tripeptide molecule made up of cysteine, glutamine and glycine, all complex together, and we talked about the primary role that glutathione plays in your body, which is, as your major antioxidant, the thing that protects your cells from inflammation and from oxidative stress, also mentioned that your liver makes and stores most of the glutathione in your body and there's a balance between the levels and storage what's in circulation and what's inside of your cells. And I also shared how not only can we make glutathione as needed, we also have a way to recycle glutathione that has already been used so that, essentially, we can reconstitute it and use it over and over again. And the process of making and recycling glutathione is governed by the activity of a set of different enzymes, which themselves are governed by the level of oxidative stress that we have, and this is all part of the intelligent design of the human body. And how amazing is it that we have a system designed to sense when we have increased oxidative stress or when that gets too high and responds to that by increasing the production and the recycling of glutathione, and that's pretty amazing, at least I think so. I also mentioned one specific enzyme last time, and that is GGT. And again, it's usually only ordered on blood labs by your medical doctor when they suspect that you have gallbladder disease, perhaps if they think you're an alcoholic. But the medical literature shows many different studies where we can use GGT levels as a potential marker for low glutathione and hence the need to support that.

Speaker 1 2:36

Now one more thing about the amino acids that make up glutathione, before we talk about some of the other roles that it plays outside of controlling oxidative stress. If you remember, in the episodes on nitric oxide, our first miracle molecule, I talked about this thing called BH4 or tetrahydrobiopterin as the rate limiter for nitric oxide production. And this idea of a rate limiter is not unique to nitric oxide. Pretty much every other system in the human body has some kind of a rate limiter is not unique to nitric oxide. Pretty much every other system in the human body has some kind of a rate limiter, Otherwise function would get out of control.

Speaker 1 3:11

And for glutathione it turns out that the levels and availability of predominantly cysteine, but also glycine, two of the three different amino acids that make up glutathione. Those levels determine how much glutathione you make. And where do those rate-limiting amino acids come from? They come from the protein in your diet. So low protein intake in general can reduce the availability of these raw materials cysteine and glycine that you can pull from to make more glutathione, and if that happens, then you won't be able to neutralize even the typical oxidative stress of just simply being alive and being metabolically active, let alone the increased oxidative stress that comes from having various health issues.

Speaker 1 3:58

Now, I've talked a lot about diet in this podcast. I've talked about the pros and cons of different diet approaches, and you know I make no secret of the fact that I'm not a huge fan of vegan diets and I've gone through my arguments about that in other episodes. But one thing that we can add to the list is that since plant-based protein sources are inherently low in both cysteine and glycine inherently low in both cysteine and glycine then as a general rule, vegans and vegetarians or even omnivores on a low protein intake they by default tend to have low capacity to make glutathione if we compare them to people who eat plenty of animal proteins. And that's just the fact, and this has been demonstrated in multiple studies. So, as a quick reminder, optimal protein intake is based on your muscle mass, the type of activity you engage in. So the more muscle you have and the harder you use them, the more protein you need. And since we're all different in size and activities, the optimal range of protein intake it's not a single number. And activities the optimal range of protein intake it's not a single number. It's somewhere between 0.6 and 1.0 grams of protein per pound of body weight. And, as a general rule, if you have more than 30 pounds of excess body weight that you want to lose, it's best to calculate your protein intake needs not off your current weight, but off the weight that you feel like you should be, like your ideal body weight.

Speaker 1 5:24

Now the good news is that taking both glycine and cysteine, either separately or together, can increase your chance of making glutathione enough glutathione to offset your oxidative stress. So, again, as a general rule, number one, you need to be eating adequate protein throughout the day, every day, to make sure that you optimize many health and longevity factors, including your ability to make glutathione to serve in its many roles, and in some cases you may want or perhaps need to supplement. But here's a caveat Before you start supplementing, make sure you're eating enough protein. That's probably the easiest and actually the most cost-effective thing to do. Remember that supplements are supplements. They are added to or in addition to your base strategy of eating well and moving well. Those should be your two priorities eat well and move well.

Speaker 1 6:20

So, having said all that, what are the other rules of glutathione? Well, let's take them one by one. This is not going to be exhausted. I'm just going to hit some points of the most common roles that glutathione serves. So, first of all, glutathione plays an integral role in two different aspects of detoxification, or what might be more technically termed as biotransformation, but I'm just going to use the word detox because that's the word everyone use. So the first role in detoxification is actually in what we call the second phase, or phase two, of liver detox. Now, I've gone through this again before in other episodes and I actually even have a self-paced learning course on my website that you can find called 3D Detox. I call it the new science of detox and I go through this in great detail. I'll go ahead and I'll put a link to that in the episode description if you have any interest in going through that learning module.

Speaker 1 7:19

But when people talk about detox, you know they're usually talking about the liver and the built-in system the liver has for processing toxins and helping us to eliminate them. Now we can get rid of toxins in many ways. We can get rid of it through sweat, through the kidneys and urine. But our greatest strength in handling toxins is through a four-phase detox system that starts in the liver. Now, very quickly, when a toxin has to be cleared, the liver first has to use enzymes to convert it from a fat-soluble form to a water-soluble form and that lets it mix with the liquid portion of bile from the liver so that we can export it into the small intestines. But once we're past that phase one enzyme, once that enzyme system does its job, we need to do one more thing to that toxin in what's referred to as phase two conjugation. So it goes phase one, then to phase two and then on to phase three and four, and this word conjugation refers to attaching another molecule to the toxins that have passed through the enzyme system of phase one, so that the toxin now becomes larger and heavier and can be mixed with bile that is again made by your liver and once the toxin passes through phases one and two, it mixes with bile in phase three and that gets exported into the gut where it gets eliminated in phase four, which technically would be just simply having a bowel movement.

Speaker 1 8:55

But in this phase two conjugation your liver has several options to choose from. To make the toxins coming out of phase one larger and heavier, it can add different chemical groups to the original compound. So, for example, it can add a methyl group, and the process of methylation again involved in many different things, but this is how we process and metabolize estrogens and testosterone, for example. Or we can add acetyl groups or a sulfur group.

Speaker 1 9:28

But one of the most active aspects of phase two conjugation, this process of adding something to the toxin to make it bigger and heavier, is what we call glutathione conjugation. So a toxin comes out of phase one and has a glutathione molecule attached to it which not only makes it mixable with bile but also neutralizes it so that it now becomes non-reactive. So a toxin that has glutathione to it attached to it generally is considered non-reactive and can't really cause many problems, as opposed to a toxin that is free-floating, so to speak. It doesn't have glutathione or any other conjugate group added to it. That is going to cause a lot more problems in terms of oxidative stress and potentially changing your physiology and damaging your cells. So, going back to this idea of glutathione conjugation as being a critical part of phase two detox, meaning that you know just like again, we talked about this before glutathione attaches to nitric oxide and deactivates it so that we can prolong its half-life and let it circulate to other tissues.

Speaker 1 10:33

Glutathione attaches to these phase one intermediates in the liver, neutralizes them, so they can't cause problems as they are escorted hard to say that word, escorted out of the body through the gut. Now, all of this happens in the context and the confines of the liver and the GI system, but we know that glutathione lives not just in the liver, but it's also in the bloodstream and it's also in your cells and in those places glutathione does the same thing. But instead of calling glutathione a phase two conjugate, which is really referring to what it does inside the liver, when we talk about glutathione and how it interacts with toxins in the bloodstream or in the cells, we call it a chelator. You've heard of chelation before cells. We call it a chelator, you've heard of chelation before.

Speaker 1 11:23

And so, as glutathione floats around your blood and gets transported inside your cells, it can latch onto things like heavy metals or mold toxins. Environmental chemicals can bind them, can neutralize them and then helps us excrete them or get them out of the body. And so glutathione actually does double duty when it comes to detox it works inside the liver and it works in the rest of the body to clean up toxic junk so that we can get rid of it. So you can imagine then backing up if we have a low protein diet and we can't supply enough cysteine or glycine in adequate amounts to keep our glutathione levels where they need to be, or if we have a problem with an increased toxic load that depletes our glutathione. Not only do we lose cell protection, our toxin load accumulates over time. That depletes glutathione to the point where it starts to affect other systems and functions, and it can create other problems, things that we're all concerned about, and that would be things like leaky gut and even leaky brain. And that brings in the concept of barrier systems. And another critical role that glutathione plays in health and function is that it protects our barrier systems. So let's talk about that for a second.

Speaker 1 12:34

What is a barrier? Well, a barrier is designed to do one thing it's designed to keep two spaces separate from each other and to control or prevent things from one space from getting into another. And that's why your house or your apartment or your condo has a front door and it has windows, and the door has a lock on it, because you get to control who comes into your house. You don't want random strangers off the street walking into your house uninvited, and so you put a barrier there that we call a door and a lock. And so the truth is the world that we all live in it's full of toxins and pathogens that just they want to get inside us and infect us or poison us. We live in and interact with a toxic and pathogen-laden world, and the average person has heavy metals, they have environmental chemicals, they have potential pathogens already in their body all the time, and our barriers protect us by controlling what gets into our bloodstream and how we react to that, and it does that through specialized cells that make up our skin, that are part of the lining of our intestinal system or the gut, or the lining of the lungs and even the lining of the blood vessels that bring blood into your brain tissue.

Speaker 1 13:49

Now, by comparison, there's far more research on leaky gut than, say, a leaky brain. Or, to say it a different way, there's far more research on the structure and function of the gut barrier as opposed to the brain barrier. So we'll just stick to that for this episode. But what research tells us is that, with all the things that can break our barriers down, we don't lose integrity in those barriers until the intracellular levels of glutathione in that tissue is depleted to the point where it can't handle the oxidative stress that causes damage to the cells that make up the barrier themselves. And when that tissue breaks down, we lose the integrity and the function of the barrier system. So if you've ever been tested for leaky gut or for leaky brain, one thing that you can conclude is that at least those tissues have an imbalance. If you tested positive, I should say at least those tissues have an imbalance between the oxidative stress attacking them and how much glutathione they need to defend themselves. Now, on that note, you can you know testing related. You can check out my lab shop. You'll see their tests for leaky gut from a lab called Cyrix Labs. That's called array number two, and there's a leaky brain test which I tend to get from another lab called Vibrant Labs as part of a bigger test on neurological function, and that's called the neural zoomer test. So an array two from Cyrix Labs or the neural zoomer test from Vibrant Labs will allow you to test for leaky gut and or leaky brain.

Speaker 1 15:23

Now, fixing a leaky gut and brain is about more than just simply taking glutathione. In the bigger picture, you have to find and fix the things that caused it to begin with and then use glutathione strategies combined with other approaches based on the entire picture. Right, there are specific supplements designed to help heal the broken barriers in the gut, in the brain, et cetera. But it's more than just simply taking extra glutathione. One of the key things when your barrier systems are not working and when you're dealing with toxic or pathogen loads is to make sure your immune system is balanced and controlled. And now we get a chance to talk about glutathione as part of the system that helps us to control that. And that's because glutathione is a potent trigger or supporter of what we call regulatory T cell function.

Speaker 1 16:15

Now, these regulatory T cells I might refer to them as Treg cells. These are unique immune cells that really they don't kill infections, nor do they label them with antibodies. Those functions come from different types of cells, but these Treg cells are essentially conductors of your immune response that directs other parts of the immune system so that they do the right job in the right place at the right time. So think of the Treg cells as the conductor, as the manager, if you will, as the executive that tells all the other parts of the immune system what to do, how to do it and where and when to do it.

Speaker 1 16:53

And it's very common in chronic conditions, especially autoimmunities, even things like mold toxicity or Lyme disease, very common for these Treg cells to be deficient. For these Treg cells to be deficient and when they are deficient and you lose control of your immune response, which typically results in one of several possible outcomes. Number one an inability or a decreased ability to mount an efficient immune response that can lead to things like persistent or recurrent infections. You might have an inability or decreased ability to calm down an immune response which tends to lead to ongoing and increasing inflammation over time. And finally, you can have lack of control of any autoimmune reactions that might be going on within your tissues, within your systems. And then you know. Obviously none of these outcomes are good.

Speaker 1 17:45

But on the good side, we do now have some solid lab testing where we can get a handle on Treg cell function, and this is called a lymphocyte map. And lymphocytes are certain types of white blood cell and I use this anytime I'm dealing with complex and chronic illness, particularly autoimmunities, for example, hashimoto's disease. I use it in most cases where I'm working with someone who has Lyme disease or co-infections like Bartonella, or if I'm dealing with someone who has mycotoxin or mold toxin illness or problems with environmental chemicals and there's a picture of immune dysfunction and dysregulation as well. And again, this is called the lymphocyte map. But here's the connection. These regulatory T cells are loaded with receptors not just for glutathione but also for vitamin D, so in the case of a glutathione deficiency, we can expect your Treg cells to be less capable and less functioning. So optimal glutathione is often a strategy that we use clinically to balance the immune system and to improve control of autoimmunity as well as the inflammatory state.

Speaker 1 18:57

All right, so I hope that's enough to convince you that glutathione is indeed a miracle molecule, and as I close out this episode, I want to give you some options for testing and some things you can think about for increasing glutathione levels. So let's talk about testing first. So the first thing to remember is that when you run regular blood tests, you should ask your doctor to check your GGT levels Again. That's not part of routine labs for most docs it is for me, but I've just learned a lot over the years, right, and so the higher your GGT level is, even within the normal reference range, the more likely it is that you have a problem with glutathione. The optimal value we would certainly we want to see GGT in the lower one-third of the lab range, probably preferably in the lower one-quarter. So if you take the lab range, divide it into four segments, it should be towards the lower end.

Speaker 1 19:50

Now we can also run a blood test for glutathione. There's only a few labs that supply this. You can get a total glutathione done at the big national labs like LabCorp, for example, but the problem is that when you test only the total glutathione levels, you can't tell the difference between the glutathione that has been used already and which is ready to be retrieved and recycled. Remember that there is this recycling process which, if it's not working effectively, allows the total glutathione to remain the same, but it changes the ratio between what's been used and what's ready to go. So, in essence, the total glutathione is really kind of only half the picture, and that's why I like to use a test called the Advanced Oxidative Stress Test, from a lab called Precision Point Diagnostics. It gives me the total glutathione level in the blood plus the amount that has been used, so that I can understand whether or not my client is recycling glutathione appropriately. Plus, it also gives me three additional markers of oxidative stress. There's more than three, but usually that's enough for us to get a handle on things. It tells me, number one, what is their oxidative stress level. Number two, what is their total glutathione levels in relation to their oxidative stress? And number three do they have a good recycling capacity? And that's a pretty robust understanding of somebody's glutathione systems. And again, this advanced oxidative stress test you can check it out in my lab shop. You can order it on your own. You don't need a prescription for that. Results will come to you directly.

Speaker 1 21:28

Now, finally, as we close, let's talk about ways to increase glutathione. Number one you can take glutathione directly. Many different companies make a glutathione product. There's different versions, many different types. There's different ways to deliver it.

Speaker 1 21:46

The most effective way to increase your glutathione directly through a pill or a capsule is using what's called an acetylated form, and you can get that in a liquid. Even a liposomal form would be better for absorbability, and so what we call AC glutathione or acetylated glutathione, especially in the liposomal form, by far has the best absorption rate and the best probability of increasing the level of glutathione inside your cells, better than anything else. So if you're looking at these products, look for acetylated glutathione, look for liposomal forms. Those are your best performers. Acetylated glutathione, look for liposomal forms. Those are your best performers.

Speaker 1 22:27

Now that doesn't mean that old school forms, what we call reduced glutathione, won't help. We've used those for decades before these more advanced formulas came around. It's just that now we have better tools Doesn't mean the old tools are bad. They're just not as good as what we have now. And in research, dosing these different forms of glutathione ranges anywhere from 500 to 1,000 milligrams per day over a period of several months to correct deficiencies and imbalances. And that's assuming that you're finding and fixing the sources of your oxidative stress. Right. If all you're doing is taking glutathione but you're not finding the problem that's causing the oxidative stress, that's, in the long run, it's a losing battle. You're just kind of patching things up Now.

Speaker 1 23:10

If you don't want to or need to take glutathione directly, there are some other ways to increase glutathione that are pretty tried and true. Number one is to use a whey protein supplement. We have many years of research where different studies have looked at different daily doses of whey protein and found that the amount of glutathione that comes out of it is actually dose-dependent, meaning that if you're going to take 10 grams of whey protein a day, you're going to get a little bit of glutathione. But if you eat, for example, 45 grams of whey protein per day, that can increase glutathione levels by, say, up to 25%. So lower whey protein intake has less of an impact. Higher has more of an impact. But if you start getting more than 45 grams per day of whey protein intake, it doesn't necessarily mean that more is better, but a little more is better than a little less. So whey protein intake is one, and that's assuming you're okay with dairy at least the whey protein intake is one, and that's assuming you're okay with dairy at least the whey protein fraction of that.

Speaker 1 24:09

Another way to increase your glutathione levels is through supplementing with N-acetylcysteine and or glycine. Right, research is a little bit more variable here, showing that different people respond differently to even the same dose or the same type of supplement. Even some organ systems in the same person responds differently. So if I take, you know, n-acetylcysteine, for example, maybe I get increased glutathione in my liver, but not in my respiratory system or my lungs. So we all have different responses.

Speaker 1 24:42

It's not uniform, but as a rough guideline, taking somewhere between three to five grams of N-acetylcysteine sometimes you will hear people call it NAC, n-a-c so three to five grams of N-acetylcysteine and glycine combined can be effective for some people in some conditions, and you would want to split that up over the day. You don't really want to take all of that at the same time. You can do that, you know split it between two different daily doses. And finally, just to give you one more thing to think about, we have some research that says fish oil shows some promise here too, where high doses of omega-3 in the range of 4,000 milligrams or four grams per day yields some statistically significant increases in glutathione.

Speaker 1 25:27

Now, one of the problems with people taking fish oil is number one they don't take good quality fish oil. And number two usually their dose is way too low. So we're talking when I say 4,000 milligrams per day to increase your glutathione levels. That's not of the fish oil in its total. That's the active ingredients, which we call EPA and DHA, and I generally recommend to people at least 2,400 milligrams of EPA plus DHA per day. Now you can get this easily by eating sardines or mackerel, anchovies, salmon, what we call the SMASH fish, and SMASH is an acronym. Let me go through that Salmon, mackerel, anchovies, sardines and herring. These are the fish varieties that will maximize your omega-3 fatty acid intake and minimize things like mercury and other heavy metals that become a concern when we start talking about eating different fish varieties. Now, if you tool around the internet, you're going to find references to all kinds of strategies to increase glutathione, from consuming more vitamin C to milk thistle to even exercise and sleep strategies. But from a clinical standpoint, here's what I think is best.

Speaker 1 26:43

Number one make sure you have adequate protein in your diet. Make sure you have adequate stomach acid to break down, digest and absorb the protein and give you the amino acid you need. Some people are eating enough protein, but their hydrochloric acid status is not appropriate. They can't break down their proteins the way that we want. It just kind of sits in their gut and causes maldigestion.

Speaker 1 27:06

If you need to get your glutathione levels up quickly, take a direct form of glutathione for several months and that would be your acetylated glutathione, or even a reduced glutathione, but make sure it's in a liposomal form, a liquid form. But if you don't have an acute need to raise your levels quickly and you just want to protect yourself from an antioxidant perspective, from an immune balance and controls perspective, you can add a couple of scoops of a good quality whey protein to your daily protein intake. You can take some supplemental N-acetylcysteine and or glycine and make sure you either eat some fatty fish or take several grams of fish oil per day, like on the days you eat sardines, for example, or mackerel. You don't need to take fish oil because you're already getting it from your food, but on the days you're not eating fish, make sure you take good quality fish oil. All right, let's call that a wrap for this episode.

Speaker 1 28:01

Don't forget to check out the Lab Shop for direct lab pricing on tests that I use in my personal coaching practice. And if you feel like you need personalized touch, like a personalized program, reach out to me. Use the link in the description or find the contact information on my main website, which is simply wwwdrnoseworthycom. That's drnoseworthycom. There's a contact form there that you can reach out to me and that comes directly to my email. All right guys, we'll be back again to talk about the next miracle molecule right here on the Inflammation Nation.

Speaker 1 28:36

This podcast is for general informational and educational purposes only and does not constitute the practice of medicine in any form or capacity. No doctor-patient relationship is formed. The use of the information in this podcast or any materials associated with or linked to the podcast is at the listener's own risk. The content of this podcast is not intended to be a substitute for professional and personalized medical advice, diagnosis or treatment, and listeners should not disregard or delay obtaining proper medical advice when a health condition exists and warrants that. And finally, functional medicine is not intended or designed to treat disease, but rather is a natural approach to support restoring health and wellness. The use of diet and lifestyle modifications and nutritional supplementation is supportive for adjunctive care.