Written by Christopher Kelly
Nov. 10, 2017
Christopher: Hello and welcome to the Nourish Balance Thrive Podcast. My name is Christopher Kelly and today I'm joined again by Dr. Bryan Walsh. Hi, Bryan.
Christopher: I am delighted to have you. Do you remember it was almost two years ago, Bryan, that we recorded our last podcast on social isolation and, I think, that has to be the most impactful podcast that I have ever recorded. Do you believe it's almost two years?
Bryan: I was just reflecting on that while you're doing the intro and how honestly you sound a lot more seasoned. You sound a lot more confident that you'd been doing this for a while and interviewing so many people. Yeah, as you're doing the intro, I thought I was like, "Man, this guy has really come a long way."
Christopher: Thank you.
Bryan: A big congrats to you that you're still around two years later and going stronger than ever.
Christopher: Thank you. I appreciate that. I have now published 205 episodes of this podcast, 189 of which have been transcribed, and that is a total of 1.7 million words. So, the kind people over at Cabbage Tree have transcribed 1.7 million words of my podcast and I checked this morning and your name, Bryan, appears 25 times in 25 episodes of this podcast. That gives you an idea of how impactful your work has been to us at Nourish Balance Thrive. So, thank you.
Bryan: I appreciate that. I'll try to keep succinct this time so maybe they don't have to transcribe so many.
Christopher: So many words. For people who don't know Bryan, and I don't think that will be very many people by this point, Bryan is a teacher. He's a critical thinker. He is a biochemist. And, I think, your unique superpower, you would agree with me on this Bryan, is your ability to bridge the gap between conventional allopathic and naturopathic or natural medicine. You seem to have your foot in both of these worlds and you do a fantastic job of bringing the best of both to health and fitness professionals.
Bryan: It's nice to hear you say that. That's my goal. I don't know how well I accomplish that. I certainly wouldn't call it a super power. I think my super power is being able to construct rational thoughts despite the fact that I'm sleep deprived with all my kids. But no, that's my goal. And as I said before, western medicine has -- We owe so much to western medicine. On the other hand, there's these thousands of years of nutritional medicine and things that people had been doing.
The thing that I've seen that lacked the most is just what you said, the bridge, something that connect the two because we're not two distinct organizations or industries. We're trying to achieve the same things but we're doing it separately. I think that we need to have more conversations together to see what the other is doing because we're both doing really good work. I just think that we could probably accomplish a lot more if we had some of the bridges get across.
Christopher: I'm really interested to know what people listening to this podcast think actually. I'm at a point now where I'm ready to move on and call conventional medicine conventional medicine, let it do what it does best, which is treat acute and episodic illness. So, the next time I crash my mountain bike which might be this afternoon, please call an ambulance.
But for everything else, I'm going to need something else. I think a really good term is sustained health engineering, designing and building lifestyles that are conducive to health and probably more importantly health span, longevity. I don't think medicine is broken. I don't think it wants for anything. It's doing exactly what we designed it to and that maybe we need to do something completely different. But I don't know what you think about that.
Bryan: I think that that's valid. I mean, you said conventional medicine. I usually use the term western science because when you read the research -- Now, granted it's all not conventional medicine that's doing this research but we really owe a lot of our understanding of the body and these pathways and the mechanisms to western science in the first place. I think conventional medicine reads some of the papers and some of the science with their bias and then they interpret it the way that they want to.
I like how you said that though. I think that that's good. You're right. Chronic disease, they generally, I don't say they're failing at it but there's a lot of room for improvement. In fact, I will say this. I was thinking about this call just a little bit ago and one of the things that I think we need to keep in mind, and this speaks to a little bit about what you're saying, was that we've been wrong so many times before. We'll just say in this particular place.
I do believe that history does have a tendency to repeat itself. The problem is that in the nutritional world, for some reason, we feel like we're immune to that. And one doesn't have to look far to see how history may be repeating itself. For example, days gone past, the disease pellagra. It was a well known fact that it was caused by a bite from a black fly. It was published. It was written about. And then it turns out it was just a simple nutrient deficiency. Well, is there anything today that we're absolutely irrefutably blaming on a particular infection of some kind that we may turn out to be wrong?
Like Lyme disease, for example. We blamed cholesterol for heart disease. That turned out to be wrong. In the 18th century, people were willingly, knowingly, intentionally ingesting mercury pills because they thought there were some therapeutic benefits to it. And I look at things like the rampant use of vitamin D and wonder if in a hundred -- Just as we look back then and we say, "Man, they sure were stupid. I mean, what were they thinking by doing this?"
At that time, they had the same attitude that we do now. They looked in the past and said, "Well, that was dumb but now we know and this is what we're going to do." We're no different. We're giving all this vitamin D or curcumin or whatever it might be, we may be just as wrong as they did but we don't think that we're necessarily wrong, if that makes sense. Actually, I read about this. Do you know where the phrase blowing smoke up one's arse comes from?
Christopher: No, but I hope you could tell me.
Bryan: Holy crap. This is fantastic. This just tells you. I mean, we're no different than our ancestors were 100 years ago, really. I mean, we have a certain amount of information at our disposal, which is true for us now, we make decisions based on that information, and then when we find out that maybe we're wrong we usually change our mind about things and maybe make some alterations.
It was also around the late 1700s that there was this supposition that if somebody was half dead, or usually drowning, if they had drowned and maybe were unconscious, that you could literally take a billow, the things that people use to blow air on their fire, and blow smoke up somebody's anus. And the thought was that that would stimulate respiration and get the heart going again to the point that, and I was reading about this, on the River Thames, there were on the boats, instead of life jackets, they actually billows on these boats so that if somebody fell in the water and started to drown and were unconscious you quickly could blow smoke up their anus.
Christopher: That's absolutely brilliant.
Bryan: And we look at that and we laugh but I honestly say, well, what in a hundred years are we doing now? And there's plenty of things that people are going to look back at and say, "Wow, they were idiots." I mean, about glucose regulation. Are they going to look back and say, "You guys were injecting insulin? That's the stupidest idea I've ever heard." Or, "You thought insulin regulated glucose? Well, that's dumb."
Who's to say that what we're thinking now and what we're doing is that much superior to what we've done in the past when really we have a certain amount of information that we're using and dealing with and they did too. So, I wanted to say that because, I think, that gives context for any and all of this stuff that if we question, you question, I question, is what we're doing currently, could it possibly be wrong? I think the answer is, obviously, yes. It could also be right. But you don't know until time say.
Christopher: To your point sustained health engineering would be all evidence based so I'd always be able to send you a study for anything that I recommend or at least some data of some sort. But then it would also follow that principle of first do no harm. You talked about vitamin D. This morning I got some vitamin D. I hope, maybe it's a little bit too late in the year now, even in Northern California, but I went outside with my dog and I went for a walk and trained my circadian rhythm.
This is all very evidence-driven. But at the same time what's the worst that could happen here? If we look back on this in 50 year's time and say, "The guy went out for a walk with his dog first thing and attempted and trained his circadian rhythm," it's not like taking vitamin D in a pill, right? What's the worst that could happen? You just went for a walk.
Bryan: I think evidence based plus first do no harm. That's phenomenal.
Christopher: Let's talk about blood glucose. There's so many things that we could talk about yet today we're going to talk about blood glucose regulation. We've talked about this topic many times in the podcast. At this point, I feel like I might have got it dialed. I understand this. I pricked my finger this morning and I got a number back and it seemed pretty good. I figured out the foods that maybe affecting my blood glucose. As a practitioner or as a super user, I feel like I may have got this sorted now. Why should we still care about blood glucose?
Bryan: For reason that I just said, maybe we don't know everything there is to know about it in the first place. I think one thing that's fairly clear is that if glucose is not regulated well whether it goes through extreme fluctuations or there's period of extreme low glucose or if it's elevated, it does cause some significant physiological disruption. I think you could pretty much name a system and if glucose is not being regulated properly, whether it's the nervous system or the immune system or the endocrine system, that there's going to be some negative repercussions to the point that--
And the body's one large integrated unit, for course. But glucose dysregulation, personally, this is where I live right, is one of the most fundamental things that somebody needs to consider before addressing some other issues. For example, if a man or a woman has some kind of hormone symptoms whether it's infertility or libido issues, is to first consider glucose dysregulation because if glucose is not working well, the hormones will probably not work as well either.
If somebody has a mood dysfunction of any kind -- I really hate talking about these terms, depression, anxiety. Just say somebody's brain is not functioning the way that it should optimally, that to first, before jumping to neurotransmitter substrates, things like tryptophan or something that might impact some of the neurotransmitter levels, to first take a really critical look at glucose dysregulation.
The second point of what you're saying is I don't think we're looking critically enough at it. It hasn't been that long that A1c was not even really run that often. And now a lot of doctors are looking at serum glucose and usually hemoglobin A1c but that's about it. And there's a much bigger story to glucose dysregulation that, I think, is being completely missed if we don't take a harder look using some of the great novel markers and thinking about it physiologically, is to take a much better look at somebody's ability to regulate their glucose.
Christopher: I wanted you to talk a little bit about jumping to the next shiny new object before you fully mastered the basics because, I think, that might be an important point for people like me and other health and fitness professionals. Example, we've seen MTHFR, we've heard about mTOR and Nrf2, all these fancy pathways, that everything is the next new shiny object that we need to worry about. Can we speak to the importance of mastering the basics? I appreciate, that's a bit of a leading question and I may have already answered it.
Bryan: No, I love that you said that. I would not have covered that. So the first thing is it's really not our fault. I think it's our society quite honestly. That's just what we do with everything. We have this sort of ADD where if something new and better comes along then that gets most of our attention. And it's not that we incorporate it into what else we were doing but typically we forget about some of these other things.
I'm no different than anybody else as a practitioner in that I learned what I learned in school and get distracted by some of these cool things. But then if we don't go back and take a critical look, five years or a decade, there's been a lot that's been learned and a lot that's been published about that topic that really isn't getting the attention that it deserves.
We're talking about western science. It keeps happening. We do this too. But it keeps happening that it wasn't that long ago that when they talk about mapping the human genome, the excitement around that was, "This is finally going to bring us the answers that we've been looking for for so long." And was it a cool project? Absolutely. Did it come up with some cool findings? Definitely. But did it give us the answers we were looking for? No.
And so now it's the big one. Well, the genome, we thought it was going to be it but it wasn't. Let's look at the microbiome. That now is going to be thing. And again, history does repeat itself. I have a strong suspicion that some really awesome things are going to come out of the microbiome project and the other future projects. But it's never going to be that final answer. A blood chemistry quite -- Well, let's just a multivitamin is not sexy. Nobody talks about multivitamins. It's always green tea extract or nowadays curcumin or vitamin D.
But on a fundamental level, I would rather have a multivitamin than the fanciest new supplement that came out that did something to my body because the basic biochemical pathways are going to run off that multivitamin and not run off goji berries, for example. And then when it comes to glucose, the thing is, you said it, I feel like I have this thing so I'm going to go ahead and look at something else. But is it possible that we're wrong on something? Is it possible that we don't have a topic really as understood as we possibly can?
There was one paper, in fact, that was talking about this a little bit. I forget the exact title but it was something like -- No, I forget it. But talking about the low hanging fruit found in just a basic blood chemistry. Not even a basic blood chemistry, the CBC, however much that cost at cash now. it's like $10 or something like that. But saying that in this post -- That's what it was, the post genomic era, are we missing the low hanging fruit?
This guy wrote this paper that basically said the genome product didn't really turn out the way we had hoped. Are we so enamored by the next greatest biggest best sexiest thing that we're missing really critical crucial information in tried and tested and true basic CBC? So, he was talking about something else that we're not really talking about now. But I feel like that he was onto something. Saying like let's stop looking for that smoking gun or the golden chalice and just really focus with what we have.
Just to take it a step further. But we do this all the time. We do this in our marriages and our relationships. We go to read these books and go to these seminars on how to improve your marriage or your parenting skills and all these things but you might be sitting on the very tools that you already have. You just haven't used them well enough. You haven't tried hard enough.
And we don't need all these peripheral extraneous expensive stuff. Again, I say that because it's not our fault. But it happens all the time and, I think, that we're sitting on these acres of diamonds, basic markers that just we don't really talk much about anymore.
Christopher: Talk about the importance of blood glucose variability and long term health.
Bryan: Yes. There's a perfect example. I don't want to give myself any credit but prior to -- I know that you attended a couple of things. But I had never learned about glucose variability. In any of the seminars, in anything that I've done, I'd never really heard anything about this. All I'd heard about is glucose fluctuations with regards to things like hypoglycemia.
But it turns out that this term, this concept of glycemic variability, may be, at least that I've read and I believe, more critical to finding, first of all in people, than is chronically elevated glucose. Critically elevated glucose, elevated A1c, that gets all the attention. It's associated with a number of different chronic diseases and degeneration. But glycemic variability is actually more damaging to the body than is chronically elevated glucose which just by itself -- There's people who are like, "That's not possible."
Actually, it is. And the research is pretty clear on this, that this glucose excursions, excessive glucose excursions, typically after eating, is more damaging to the body, causes more oxidative stress, is associated with just as many things in terms of cardiovascular risks and risks of stroke and neurodegenerative diseases, obesity. There's even some paper showing that increased glycemic variability is associated with lower quality of life, certain mood disorders, far more than just chronically elevated glucose.
Essentially what it is, I don't know how deeply you want to get into this, you can ask as many questions you want, but it has to do with the first-phase insulin response.
Christopher: Yes. Let's get into the first-phase insulin response. That's a very interesting topic.
Bryan: And I will say that glycemic variability is one of the earliest predictors of insulin resistance, metabolic syndrome, type II diabetes far, far before fasting glucose is abnormal and/or A1c is abnormal. That's huge. Because that's what the doctors are typically looking for. But this glycemic variability, it comes first. And so, essentially what happens is -- You have the pancreas, the beta cells. It pre-forms and stores a little bit of insulin right and ready for when somebody is to consume some sort of food.
The pancreas can either, it makes a little bit of insulin already in the beta cells, ready to go, and then it can also make it on demand. I always say it's like McDonald's. It has few of the burgers under the warmers that are ready if there's a lunch rush but they can also continue to keep making the burgers as long as they keep having customers. That's the beta cell.
Essentially what happens, which is really fascinating, is two minutes after, and it's the ingestion of food, it's not the absorption of food, not the swallowing of food, it's the two minutes after your first few bites, insulin is released. That's really interesting to me because the food that you've ingested, in two minutes it's not going to be absorbed. Depending on what it was, probably much of it is going to leave your stomach in two minutes quite honestly.
But within the first two minutes, insulin is released, and what's called a first-phase insulin response. It usually lasts supposedly around five to ten, 15 minutes long, and then that's all the pre-formed insulin that was made. But then as the food starts to digest and starts to absorb then the pancreas goes through the second phase insulin response and that's insulin on demand. So, depending on the macronutrient contents of the food or the meal, depending on how much food is actually consumed and how quickly or slowly it's absorbed, insulin in the second phase insulin response can last for hours theoretically and just keep pumping out insulin on demand as needed based on the glucose that's entering into the bloodstream.
Now, what's interesting is, and it's hard without a visual, but if somebody lacks the first-phase insulin response -- Insulin goes up before glucose even comes in out of the gastrointestinal tract and into the bloodstream. And it's thought that it's kind of like -- Well, it makes sense. There's these sensors in the gastrointestinal tract for carbohydrates essentially and that the gastrointestinal tract, and I'm taking a little creative license with it, because the "body knows" that glucose can cause issues if it gets too crazy, the gastrointestinal tract, in the presence of food or the presence of carbohydrates or probably some amino acids as well, sends the message to the pancreas and says, "Hey listen, I'm digesting some stuff right now that I'm going to be throwing out your way in a little while. I just thought I should let you know so that you can release some of the insulin stored up so that glucose won't get too high."
And so the pancreas does it. It releases this pre-formed insulin. And then what's really interesting -- And again, this is the part where if there's visuals it would be easier. If you imagine two people that just consumed the exact same amount of food and it tracks their postprandial glucose levels two hours after the consumption of this meal, the person that has the first-phase insulin response has a very normal sort of blunted postprandial glucose response. It's a nice curve, doesn't get that high.
The person without the first-phase insulin response, because insulin wasn't there to prime the system for this glucose that was going to be coming, goes incredibly high. It goes much higher than it would have if somebody does have a first-phase insulin response no matter how much insulin is being made during the second phase insulin response. And the problem with this is if somebody can have normal fasting glucose levels but then they have this exaggerated postprandial glucose response, and hemoglobin A1c isn't necessarily going to pick that up because that's an average of total serum glucose levels over a period of a few months or whatever.
What this person has is this sort of extremes that glucose goes really high after meal because they're lacking that first-phase insulin response but then it comes back down eventually. And so hemoglobin A1c won't catch this. Fasting glucose, they might have totally normal fasting glucose. But yet that first-phase insulin response is, according to the research, considered to be one of the earliest predictors of type II diabetes.
I'll say that again in case anybody misses that. A blunted or muted or dysfunctional first-phase insulin response, in the science that we have right now, is considered to be one of the earliest predictors of eventual type II diabetes. And so then the question is, well, why aren't we evaluating this? Why aren't we looking into this a little bit more? If we're really truly talking about preventative medicine, shouldn't we be trying to catch type II diabetes 20 years before it happens and do we have the technology to do that?
Christopher: Talk about GlycoMark. I want to know how I can detect my blunted first-phase insulin response.
Bryan: So, GlycoMark is the trademark name. The actual analyte is called 1,5-anhydroglucitol. Molecularly, it's a hydroxyl group away from being glucose. It's a 6-carbon sugar, it's ubiquitous, it's found in a variety of different foods. It's not metabolically utilized which is kind of awesome as a marker now because glucose is metabolized but that extra hydroxyl group, the body doesn't really use it.
So, this GlycMark is I thought a new marker. A new marker is something for me that just came out maybe a year or two ago. But in the world of biomarkers, it is considered fairly new. Meaning that there's quite a few practitioners that may not be aware of it. It has its own trademark. It's been validated. It's a heck of a marker. I think someone over in Japan might have discovered it originally.
But essentially what it is -- The short version is GlycoMark measures somebody's glycemic variability. Because, I'll put it another way, is it evaluates postprandial after eating glucose levels two weeks prior to taking that test. So, you go in and you get your GlycoMark run at LabCorp, Quest, it's looking at your postprandial glucose levels for two weeks before you had your blood drawn.
And the way it works is basically this, so that 1,5-anhydroglucitol and glucose -- The kidney does, when it comes to filtering, the kidneys filter the blood. That means that stuff leaves the blood and actually goes into the kidney tubules, the convoluted tubule. But then a lot of things are reabsorbed. And then other things that don't reabsorbed get excreted and that shows up as urine. So, both glucose and this 1,5-anhydroglucitol both get filtered. Meaning, they leave the blood and they go into the kidney tubules.
Under normal circumstances, they both get reabsorbed back into the bloodstream and, therefore, aren't excreted. But then what happens is when serum glucose levels go too high, and the magic number that they use is above 180 milligrams per deciliter, which is pretty much only going to happen after a meal, when glucose levels get too high, they both get filtered into the kidney tubules but then glucose wins for reabsorption.
There's something called the Tmax, the transport maximum. Glucose wins for reabsorption and the 1,5-anhydroglucitol loses so you end up urinating it out. What that does, if you're urinating out all this 1,5-anhydroglucitol, your serum level goes down. So, a low 1,5-anhydroglucitol or low GlycoMark is actually indicating that your glucose levels are going too high after meals. Again, the magic number is above 180, which is arguably too high after any meal regardless of what somebody ate, and is looking therefore at glycemic variability.
And it's also, and I don't know why more papers aren't written about it, there's a couple of them, which is technically looking at first-phase insulin response. The question is why would somebody's blood glucose go above 180 after a meal? Well, just what I said. If somebody lacks the first-phase insulin response then it's going to go high. If somebody has an adequate first-phase insulin response then it's probably never going to go that high.
There's other variables, of course. But generally speaking, GlycoMark, if below 15, is too low. That's indicating that somebody doesn't have it in the blood because they're urinating it out because when it came to the reabsorption glucose won and 1,5-anhydroglucitol lost so your serum levels end up low. It's a validated great marker looking at glycemic variability. And the way I look at it is not just glycemic variability but, in fact, first-phase insulin response.
Christopher: And does that predict anything else about your metabolic health?
Bryan: So, one of the biggest problems it seems with excess glycemic variability is oxidative stress and that's where a lot of the damage and all other problems come from initially. I don't like to make too many assumptions about somebody unless there's some kind of lab data to justify it to some degree but if excess glycemic variability accompanies excess oxidative stress and if a low GlycoMark indicates glycemic variability then, yes, I would assume, it's an assumption but it's a strong assumption, that if somebody had low GlycoMark and, therefore, excess glycemic variability and damaged first-phase insulin response, that they also were suffering some degree of too much oxidative stress.
Christopher: How does GlycoMark compare to glycated proteins like fructosamine?
Bryan: That's an interesting question and that's -- Well, okay. So, things like fructosamne, and there's also glycated albumin, and from what I understand and have read is that they're different. Fructosamine can look at globin, for example, or globulin, sorry, looking at glycated proteins. But glycated albumin is a separate marker and it's said that glycated albumin may be a better marker of short term glucose levels than is fructosamine, first of all.
What's interesting then is whether you're talking about fructosamine or glycated albumin, that those -- The reason why hemoglobin A1c is a marker of about three months of glucose regulation is because what you're looking at is the glycation of hemoglobin. Hemoglobin is part heme part globin and globin is a protein and glycation, as you already know, is basically glucose plus protein.
Because red blood cells have, and therefore hemoglobin have a lifespan of about three months, hemoglobin A1c, when they look at the amount of glycation of hemoglobin then they're looking at what they think is about three months of glucose regulation. Now, proteins like albumin and some of these other proteins that they're using only have lifespan of about two to three weeks. And so they're looking at the level of glycation over a two to three week period.
Now, that doesn't look at glycemic variability per se. It's just looking at how much glycation is taking place. There are some interesting papers that are looking at things like glycated albumin compared to something like hemoglobin A1c and suggesting that there may be a way of looking at glycemic variability that way. It's interesting. I'll just say this. With some of this new information that's been found about glycemic variability, there's a lot of effort that's going into trying to identify the best ways of actually looking at this glycemic variability.
GlycoMark, it's a very inexpensive one. Like I said, it's a validated marker. It's mostly accurate. But there are other ways. I've learned, I think, in the UK maybe they don't have GlycoMark available. I created this glucose program which we may talk about at some point. But I'm going to add another video that talks about some of these other ancillary ways of testing for glycemic variability using things like glycated albumin or fructosamine and hemoglobin A1c ratio.
Christopher: GlycoMark is on our NBT panel now. But before you mentioned it, I'd never heard of it. I just wonder, do you know, is it just cultural thing? Are primary care doctors in Japan, for example, running GlycoMark on everyone?
Bryan: It's a good question and I have no idea. What I do know is it takes a long time for something to make its way. I call it the nutritional grapevine or you could say the medical grapevine, that someone tells someone else and they tell someone else. But I lecture to health practitioners and there was one talk I gave where one woman in the audience said that she was running it routinely. Most of the people hadn't heard of it yet.
Christopher: Wow. Good information. Talk about your reference ranges for fasting blood glucose because when I attended your blood chemistry seminar in Denver earlier this year, you were the first person to give me references for the reference ranges. Everybody always talk about how optimal fasting blood glucose might be around 85 milligrams per deciliter but no one before you could ever really present any references to support that. So, talk about some of the research that you did that led to citing those papers.
Bryan: Yes. I'm going to start by saying I don't think I'm anything particularly special when it comes to this stuff. I mean, I question things. I think that's what I do. And so I learned the same reference ranges that you've learned because -- I'm not going to get into the history it unless you really want me to.
There are some people call them optimal reference ranges for blood chemistry markers, there's functional reference ranges, some people call them nutritional reference ranges, there's a variety of different ways to saying the same thing. But most of the time -- There's a couple of people that taught this sort of functional blood chemistry. I know where the references come from. And I learned those and I use those because that's what I was taught.
But my issue was I needed to know why because if I had a patient that was in the medical profession, maybe a nurse or a doctor, and I started talking about functional reference ranges, they'd be like, "There's no such thing." And you can say, "Well, it's plus or minus one standard deviation," or, "We're trying to look at things before it becomes a pathology of some kind of disease." But that didn't sit well with me. I wanted more.
And so I initially, quite honestly, this is the reason why I do anything, I have questions that I need answered for for myself. I don't care about anybody else. I want to find the answers. And so I start digging and I start looking at the published literature for reference range for glucose. To throw out anything that I heard or even believed, being open to whatever I found, and just to go and then take a look. Inevitably, it takes a long time unfortunately, to find different papers that are suggestive of a reference range that I feel far more comfortable using that's backed up by these papers which--
And here's the thing. You and I could look at the exact same papers and come up with a slightly different fasting glucose reference range based on that. And I say that at the presentation. What I'm comfortable with is between 80 and 90. Someone else might look at those same papers and say, "Well, maybe 81 to 89 is better." That's totally cool. One thing that I did turn up that you probably remember is there's a lot of papers that suggest that 85 is the happy spot for the body, that when serum glucose is 85 milligrams per deciliter that there's no insulin that's produced, there's also no glucagon that's produced, and it seems to be a nice hovering spot.
And it turns out there's some papers where at around, when it started to go up above 85, and it wasn't a lot of problems but that's when some problems started to go up. That's when the hazard ratio for some different things went up. And so based on that, yeah, I think 80 to 90. I'm really comfortable with the reference range of 80 to 90 myself. I think once it starts to go above 90, that's too high and there's already some issues that are taking place. As a standalone marker. Of course, you have to look at a number of other things.
And if it goes down below 80, and I've even seen -- You have started asking about hypoglycemic tendencies or symptoms but I've seen people that have glucose of 83 and that starts to look like it's a little bit low and they have hypoglycemic symptoms. The thing with the reference, you have to cut it off. Your reference range can't be 85. Meaning, if someone is 86, they're too high. If they're 84, they're too low. You can't have that. I use 81 to 90, to 89. It might be a little tighter.
I mean, I don't know if you want to go to the references themselves. I have to try to pull those up. But that's the process, questioning what we're doing, questioning what I've been taught, taking a look at what the literature says, eventually finding some things and that's what I feel comfortable with for fasting glucose.
Christopher: Do you think you can go too low? Did you see anything in the epidemiological data that suggested there was a lower limit below which some bad things might be happening?
Bryan: Yeah, I forgot about that. The paper, I think, was called -- Oh, no, I forget what it was called.
Christopher: How low should it go?
Bryan: Yeah, it was fasting plasma glucose, how low should it go? What they did was they looked at, I think it was cholesterol and hypertension and a variety of different things and, yeah, it was around that point. I mean, 85 was the sweet spot in that one paper when they graphed it all out. People, when their fasting glucose started to go above 85 they had an increased risk for high triglyceride levels and cholesterol and hypertension.
But also, below 85 tended to go up as well. That's why 85 seems to be this sort of magic number where that's a pretty darn good fasting glucose, all things considered, of course, looking at other markers. But, yeah, low glucose is riddled with just as many issues as high glucose, absolutely. I mean, there's a paper looking at heart rate variability and same thing, when glucose starts to dip down too low, it makes sense because there might be a sympathetic response, then heart rate variability gets a little bit wonky.
And I'll tell you that we've done a lot of work with PCOS, polycystic ovary syndrome in women and that's a whole major segment of those women that is not talked about. It is in the literature a little bit, fortunately, that don't have insulin resistance or chronically elevated glucose, have completely normal A1Cs but they suffer from what appears to be periods of low glucose.
Christopher: Interesting. I want to move on and talk about the action of insulin and the causes of insulin resistance. But before we do, I realized I missed a question.
You talked about the incretins in the first-phase insulin response. Can you speculate or maybe even answer definitively as to what causes the loss of theat incretin release?
Bryan: The loss of the incretin release? That's a good question. It's not something I looked into too much. You might be able to speak to it. These incretins or these peptides or gut hormones like GLP-1 or glucagon-like peptide-1, those are these -- They're enteroendocrine hormones released from the entroendocrine cells that line the gastrointestinal tracts, the simple columnar cells.
I don't know, I haven't looked into it too deeply, one of my suspicions is just dysfunctional gastrointestinal tract. If there's any kind of dysbiosis or I would say any kind of microbial imbalance of any kind, if there's an infection, I would suspect that possibly if there's inflammation in the gastrointestinal tract maybe from foods, maybe from stress, maybe from infections I mentioned before, if there's any kind of dysfunction in those simple columnar cells that line the gastrointestinal tract then my suspicion is the enteroendocrine cells that are making these incretins probably would work as well on their own.
Then the other question is what's going on in the beta cells that it seems that the GLP-1 -- And actually, I didn't really talk about that too much, but that's a big piece, man. I love, at least right now I'm in love with GLP-1 and what it does and there's some really, really interesting research coming out not just on its effects with things like beta cells and glucagon suppression and insulin release but as an immunological molecule as well. It's really fascinating. I mean, that does so many things. It's cardio protective. It's neuroprotective. It helps increase glucose disposal in skeletal muscle. I mean, it's pretty incredible.
Anyhow, yeah, I don't know. I haven't looked in that too much. Well, I looked a little bit. I didn't find a whole lot. But it does seem that lack of incretin release for whatever reason is related very much to this first-phase insulin response. But then so too is dysfunctional beta cells. If they have issues with making that pre-formed insulin in the first place then that will also blunt the first-phase insulin response.
Christopher: I can add something here with the help of Tommy and then also Gabor [Phonetic] from the lower insulin Facebook group who has been citing some really interesting papers that says at least partly to do with the disassociation of macronutrients from the normal hormonal effects through processing and also the effect of food on the gut microbiome. So, maybe refined carbohydrates are ruining or getting rid of your incretins.
Bryan: Yeah, that's fascinating. That's interesting.
Christopher: Let's talk about insulin, the action of insulin and the causes of insulin resistance. Perhaps first it will be a good idea to talk about the action of insulin. What is the primary action of insulin?
Bryan: Well, it's a long story. I'll just give you the quick answer. It seems that its primary role is, within the pancreas itself, is to suppress glucagon. That's pretty much it. If you want to get a quick answer. As far as I can tell, what's called intra-islets. In the pancreas, they have these what are called the islet cells. It's these pockets of these endocrine cells. You have the beta cells and alpha cells. But these intra-islets, so within these little islands of cells. I picture this kind of like Hawaii where there's a bunch of islands that are close to each other.
One island releases a hormone to tell the next island to stop doing what it's doing, basically. Before it even goes systemic, just within the pancreas, that the release of insulin, and there's also a concomitant release of GABA at the same time, and it's those two things that when the alpha cells, when insulin binds on the insulin receptor of alpha cell that there's sort of a GABA channel that becomes available in that alpha cell, that GABA which was released in the beta cell goes into the alpha cell is responsible for hyper polarization of the alpha cells which really in English just means it suppresses glucagon. That seems to be, as far as I can tell and what I've read, unless I can read or hear something else more compelling, insulin's primary job is to suppress glucagon.
Christopher: What then is insulin resistance? What's it for? Where does it happen?
Bryan: That's interesting. I can honestly say I don't think anybody knows. I think there's a lot of really interesting theories that are going around. One of the things, when I also spoke about questioning things, if what we're doing today is going to be wrong even a little bit of a lot or bit in the future, is also considering, and this is a big one, is considering the evolutionary benefit possibly to a thing going on in the body. You could say this, "Well, it started with low vitamin D." Is there an evolutionary benefit to low vitamin D? Meaning, is the body intentionally keeping vitamin D low for a reason?
You could talk about that with low cortisol. Is there an evolutionary benefit to low cortisol? I mentioned PCOS. Is there an evolutionary benefit to PCOS? And most people will say, "Well, no, because we need cortisol, we need vitamin D. And no, we need to be fertile so we don't need PCOS." But I feel that that's kind of a myopic view in that maybe there was a benefit and it turns out nobody really knows but there's some really interesting theories about that and there's some theories that insulin resistance was of evolutionary benefit.
Which is also to say you and I might be here today because our ancestors were able to be insulin resistant and there's people that aren't around today because their ancestors weren't very good at being insulin resistant during times of stress. And perhaps they needed glucose more for brain function during periods of stress so that the body didn't dispose of glucose as much.
One of the really interesting theories that I like, and there's some really very compelling research papers on this, is intracellular metabolic disarray. We'll just call it that. And this makes a world of sense to me. There are some cells that are good repository for glucose when glucose is elevated, things like adipocytes and skeletal muscle cells. There's some evidence that glucose can get into them anyhow at basal level. But that these cells that have these four transporters that can allow a considerable amount of glucose and when serum glucose levels go up -- This just makes a lot of sense.
Let's say you're having a party at your house and it's gotten really out of hand. I mean, people are drinking at keg stands and I don't know what kind of parties do you have but people are ruining your furniture and spray painting your walls. And more people arrive to the party. You feel like, "Listen, no, nobody else can come into my house until I deal with what's going on inside here." Well, the cells aren't any different.
If there's metabolic stress inside of a cell, if the mitochondria aren't working well, if there's already too much glucose in there, if there's too much oxidative stress because the mitochondria is trying to utilize all these glucose and pyruvate, if there's accumulation of ceramides or fatty acid accumulation inside of a cell, then it would make sense that that cell close up its doors to any more glucose coming in until it can deal with this metabolic havoc that's occurring on the inside.
And so there's some evidence that, I think this is phenomenal, that cells are intentionally insulin resistant to protect themselves from further damage. If you consider that, our primary goal as humans is survival when it really comes down to it and we're really just a bunch of cells that each cell's goal ultimately is survival, that to have a cell that its survival is threatened for some reason, intentionally walling itself off, not allowing more glucose in. Insulin may knock on the door but it's not opening the door because it knows that that's more glucose and then it's going to cause more cellular dysfunction.
Those are a couple of them but there's some -- Like I said, the evolutionary part is really interesting that nowadays we're more a brain-based society than we are a skeletal muscle based society and that maybe because of all of this brain power that we're using, publishing and listening to podcasts, for example, all day long.
Christopher: I'm standing right now, I promise.
Bryan: No, no. But also, I will say, but we could be standing and moving around but there's some serious, a lot of brain power. Our jobs are almost brain-based and thinking and creating and doing and listening and reading and sensory experience. Anyhow, there's some really interesting evidence that from an evolutionary perspective -- And, I will add to this also, this gets a little bit further out, but in terms of population control.
So that from an evolutionary perspective, a species, any species will replicate rapidly if there's essentially no competition and there's the abundance of resources and if there's really no threat to the survival of the offspring. And so species can essentially become insulin resistant in essence to stop making as many babies and to put more effort into the babies that you do have which could be called gestational diabetes.
A woman that has gestational diabetes has a larger -- Some people say they're too heavy but it's the moms putting more for biochemical and physiological resources into that baby so that there's a greater chance for survival and perhaps having less babies so that if resources are scarce, if there's too much competition, that on almost a subconscious level that it's actually beneficial to have less babies and just put more of your attention and resources into that one.
There's a ton of different theories about it. I don't know if that's enough for you. But it certainly lends some really interesting conversations and thought process. The one thing I will say too, is then it really changes how we approach this therapeutically.
Christopher: Right. I was going to say if insulin resistance has a purpose, does it make any sense to be using insulin sensitizers, insulin secretagogues, insulin mimetics? Can you talk about that?
Bryan: Well, I think one of the stronger theories is that whole cellular metabolic havoc or stress that's going on inside of the cell. And I love this. There are some papers where researchers are saying, "Listen, maybe injectable insulin isn't the best idea." I mean, if we just take a big step back, more insulin will lower serum glucose. But maybe we're chasing the wrong thing. Maybe serum glucose isn't what we should be using as our biomarker.
Insulin will lower. And in the botanical world, in the natural medicine world, there are a lot of really potent botanicals out there that will lower your glucose, period, so much so that they even are considered hypoglycemic agents. But then the question is how are they actually doing this? And a couple of papers that I'm thinking of, they're saying is aggressive insulin treatments. And there's plenty of papers showing that that's not a good thing. Trying to lower glucose or A1c rapidly does not bode well. They've had to cancel some trials based on that.
But they're saying that if the cell is rejecting glucose in the first place by intentionally becoming insulin resistant, should we be injecting insulin or, like you said, giving insulin mimetics or secretagogues? Anything that basically looks or smells or acts like insulin in the body or has it make more insulin, is that just making that problem worse? Is it forcing more glucose into a cell that already has too much to deal with in the first place?
And going back to the house party, that'd be like somebody opening the door, forcing the doors open and allowing more people in. It's going to ruin your house even more. And so we look at conventional medicine and what they do is wrong. But in our medicine, we're doing the same thing. When you look at the mechanism of action of some of these botanicals that we're using, some of these are insulin secretagogues. Some of them molecularly look like insulin. Some of them stimulate insulin receptors.
And so I ask, and I don't know that I have the answer, but are we doing that much better by focusing on glucose and A1c and giving things that essentially are looking like or acting like insulin? This is a big deal to me because there are people that greatly benefit from some of those botanicals. And in my humble opinion, I think that there are people that are actually making people worse by giving a natural version of insulin if you will.
Christopher: It's somewhat of an arbitrary classification whether this is an over the counter thing or a prescription drug. It differs from country to county which tells you something about how arbitrary it is.
Christopher: Okay. So, let's move on and talk about what to do. Let's say I've measured my fasting glucose and it's elevated and then I better give you some more information because there's lots of reasons why that might be true. My hemoglobin A1c is normal but my GlycoMark is low and it looks like I might have lost my first-phase insulin response. How would you go about tackling that sort of problem?
Bryan: In that specific case, I wouldn't worry so much about the fasting glucose. There are a lot of things that can impact that and your A1c is normal. It seems that that wouldn't be my focus. I would rerun your fasting glucose after a period of weeks just to see if it came down on its own but I wouldn't be overly concerned about that. The bigger the concern would be the low GlycoMark.
For me, low GlycoMark, if we go backwards again, if GLP-1 and these incretins stimulate the first-phase insulin response or are responsible for the first-phase insulin response and you are apparently not having a first-phase insulin response but are otherwise healthy -- I would also encourage you to have your C-peptide run just to get a--
Christopher: Of course, you mentioned C-peptide.
Bryan: More complete picture. Here's the deal with that really quickly. You can't fully evaluate something if you don't have all the pieces of story. And so A1c is good, GlycoMark is good, fasting glucose is good, but one of my questions will be what is the insulin doing? Is it high? Is it low? Is it normal? I think it's the best part of the story too because, and this would be a little bit weird, but let's say you had a low C-peptide or low insulin levels, you'd suspect you'd have a higher A1c but maybe that had something to do with your GlycoMark in the first place, is that you weren't even making a whole lot of insulin.
Anyways, I would suggest that. But the focus for you would be to try to maximize GLP-1 as much as possible. And the nice thing about GlycoMark is it's one of the fastest markers to show an improvement. And not that you would want to go get your blood drawn. You might. But the average normal person might not. You can go get your blood drawn in a couple of weeks and start to see progress, if somebody is making progress with regards to that. You quickly know if your protocol was essentially right. Then the question is what can increase GLP-1?
One of the first things, and, yes, there's actually a paper on this, is chewing your food thoroughly. In this paper, they looked at things like cholecystokinin, but they also looked at GLP-1. And people that chewed their food 40 times had a greater GLP-1 response than those that chewed their food 15 times. And there's people out there that say chew your food until it's liquid, chew your food 100 times. But going back to what you're saying, in terms of the evidence, 40 chews of every bite of food seems to better for stimulating digestion and some of these incretins.
And then there's just a number of other things. [0:50:33] [Indiscernible] has been shown to increase that, P-protein in high amount might do that as well, Bio-essence, Berberine does that. I wouldn't take it for that. But fish oil or EPA and DHA can do that. And then some of the digestion resistant starches are actually fairly potent at stimulating GLP-1 as are sweeteners, things like sugar alcohols or xylitol, sorbitol. And, I believe, although I won't recommend it for people, but I believe things like aspartame and some of the chemical sweeteners also increase GLP-1.
But that would be the goal. It's just to try to give you a GLP-1 stimulating protocol. And what I would do, in fact, since you asked, I would -- There's no such product that exists currently, and I don't want to be giving anything away here, but it would be to take some of these things about ten to 15 minutes before meal, try to stimulate GLP-1, try to stimulate the first-phase insulin response sort of right before the first bite of food would have come in. And then retest your GlycoMark in two weeks and see if that helped.
Christopher: I would love to get into some more of the different cases that may arise but perhaps the better thing to do would be to redirect people who are interested in learning more to the new training course that you've just produced and I have done recently and very much enjoyed. Can you talk about the training course?
Bryan: Yeah, sure. I called it Everything You Want to Know About Glucose Regulation because I felt like that's what it was, quite honestly. I didn't have a title for it. After I put the whole thing together I thought this pretty much covers, at least that we know right now in the science, A to Z when it comes to glucose regulation.
So, it starts out. You know me at this point. You can't have a conversation about a thing unless you know what the thing is you're talking about. Currently, it's a five-video course. I forget, it's like seven hours of videos. I will be adding another one, like I said, about some of these glycemic variability markers in somebody who doesn't have access to GlycoMark. These courses are fairly dynamic. I will add to them as I see fit.
The first part is how does it work? What is basically the anatomy and physiology of glucose regulation in the first place? Because you can't talk about defect unless you know how it's supposed to work in the first place. Part one is -- And I love this stuff because, in my experience, people don't go into the detail of talking about how this stuff really works. After video one, people will know first-phase insulin response and how it works and what it looks like and the pancreas and the different cells and the role of insulin and glucagon.
It's like glucose regulation 101. I personally think it's great. Then I go into, well, if that's how it works, what happens when things go bad? And so then we start to critically look at what is insulin resistance conventionally but then start to critically evaluate, well, maybe there's some areas in our way of thinking when it comes to glucose. And again, you know me, I like to tell stories and so I tell this story of here's how it's supposed to work, here's what we're taught, but then I always start to dismantle this a little bit. I'll start to dissect this and see if based on the literature what we're saying about insulin and glucose is right or wrong or if we can elaborate on this.
And then I start to go into some of these theories about what insulin resistance might actually be which ultimately somebody really wants to know what do I do about it, right? You can't tell them what to do if you don't know what can go wrong? And so we learn about what can go wrong and what goes wrong, that can help inform some of what we do. But then the story, of course, isn't over because, skip video three for a second, but then in video four I talked about the biomarkers.
So, you say, okay, here's how it's supposed to work, here's what happens when it goes wrong, here's some really, really fascinating new-ish papers suggesting what's actually happening. Then the big question that people should have in their mind is, well, how do I test it? And so that's what I do in video four as I talked about all the different biomarkers, evidence-based reference ranges, looking at the different studies that went into those optimal reference ranges.
And then video five is what to do. At that point, I got some really great feedback from a colleague friend of mine that when I went over a bunch of different cases towards the end, he said, "I was with you the whole time. I know exactly what you're" -- Because of the story that I had told up to that point he said, "I knew it. I knew the answers before you actually said that." Again, just being totally humble and honest, that's what I want for people. I don't want people to believe me. I want people to see the information, to learn the information, and to be able to go and do this on their own.
And I don't want them to parrot back things that someone says. I want them to learn the information. And then the only other thing, video three was kind of a tangent. One thing that's greatly misunderstood, I don't know how you felt about the hypoglycemic video, but is this thing of hypoglycemia. I was taught about it, reactive hypoglycemia, what is it, what causes it. There's really nobody having strong conversations about this thing that a lot of people suffer from.
So, I did a whole what I thought was a pretty awesome video on hypoglycemia, what it is, what does the evidence say about low glucose, are these people that experience these symptoms, do they really have low glucose? Is it something else? What are the causes? And then, of course, what are some things that people can do?
Christopher: Yeah. I absolutely love the course. People ask me all the time what education do you have? What did you do? Did you go to medical school? And the answer is no. I just watch a bunch of videos on the Khan Academy and I did all of Bryan's training. That's basically what got me to where I am today. That's certainly the most valuable training. Now, I'm not financially affiliated with your courses in any way but I am a true fan. A true fan is to find someone that will buy anything you produce. A diehard fan will drive 200 miles to see you sing. Does that sound like me, Bryan, driving to see you in Denver?
Bryan: Yeah. You showed up in Colorado.
Christopher: Yeah. They will buy the hard back and paper back and audible versions of your book. They will purchase your next figurine sight unseen and they'll buy your best of DVD even though everything is for free on YouTube. That definitely describes me. And every time you publish one of these things you send me that via email, the link to the landing page and there's all these sales copy which just gets in my way. I'm just looking for the ad to cut button. I know it's somewhere on that page. Because I've just had such a great experience with everything else that you've done in the past.
Bryan: That really means a lot to me because I told you in full disclosure the way that's happened, it starts out as a question in my mind. And then I start researching it. When I get blown away by something, it's twofold. One is I read something, like this is the coolest piece of information that I've come across in a while, and also this sort of frustration of why the heck did I never learn this from anybody? I've never heard some of the stuff. Why is nobody talking about that?
When those two things happen -- I mean, cool information is fine. But that doesn't mean I need to make a course about it. But when it's really cool information and then I'm like why did I need to find this on my own? People need to hear about that. That's when I make the course. I don't even know if it's going to be well received, quite honestly. These things just come from me wishing I had this course when I was a practitioner earlier on.
And so to hear you say what you did about it means a lot because I don't know if you're going to like stuff. I don't know if anybody finds it valuable as I do. And so to hear that feedback actually, it means a lot to me. I appreciate that.
Christopher: It's my pleasure. Where's the best place for people to go to find the training course?
Bryan: Well, I guess, two. The easier one to remember is just drwalsh.com. I haven't been there myself for a while but I think there's links to just about everything there. Regarding this course, it's metabolicfitnesspro.com. There's a few courses. I'm going to be adding quite a few in the coming probably year. The glucose course that I just refer to is specifically on that site.
Christopher: Awesome. Is there anything else you want people to know about?
Christopher: That means I did a good job?
Bryan: Yeah. Regarding this, no. I think my parting words are, above and beyond all this stuff, a lot of people are chasing after health thinking that it's going to bring them happiness. But I think that one of the things beyond glucose, beyond any awesome conversation we could have biochemically or pathway related, is we have to love ourselves. That's the thing that I see missing the most out there. People searching for happiness but happiness is on the inside of you already and all you need to do is just access it. It's not about finding it outside of yourself. It's already there. And so, anyhow, that's my final parting words above all that.
Christopher: And I should refer people to the End of Three Fitness betterhumanoloy Podcast by Jerred Moon. I just listened to that on my afternoon walk yesterday and there was a fantastic discussion where you went into much, much more detail there. I should refer people to that podcast. I'll link to it in the show notes for this episode. You can always come to nourishbalancethrive.com/podcast, drill down to a particular show and then to a particular episode you'll find the time map that I'm going to produce for this episode. You will find all the references and everything else that Bryan talked about.
Bryan, always a pleasure. Thank you so much. I hope it's not another two years before you're back on the podcast. I'm sure it won't be.
Bryan: Hopefully not. No, it won't. I always enjoy it, Chris. Thank you so much for your time and for doing this.
Christopher: Thank you.
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