The Dr. Hyman Show - How Men's Health Is Affected By Stress & Blood Sugar Imbalance

Episode Date: May 6, 2022

This episode is brought to you by Athletic Greens and Rupa Health.   Many of us are living our lives out of balance and are stressed from the time we wake up until the time our heads hit the pillow. The problem is that chronic stress causes inflammation and is behind many of the health conditions that affect men specifically. Stress can drive low testosterone, for instance, which is a common problem for men that drives many other health issues.    In today’s episode, I talk with Dr. George Papanicolaou, Dr. Louis Ignarro, and Jessie Inchauspé about low testosterone and its effects on men, the heart-protective molecule nitric oxide, the importance of minimizing blood sugar spikes, and much more.    Dr. George Papanicolaou is a graduate of the Philadelphia College of Osteopathic Medicine and is board certified in Family Medicine from Abington Memorial Hospital. He is also an Institute for Functional Medicine practitioner. Upon graduation from his residency he joined the Indian Health Service. He worked on the Navajo reservation for four years at the Chinle Comprehensive Medical Facility, where he served as the Outpatient Department Coordinator. In 2000, he founded Cornerstone Family Practice in Rowley, MA. He began training in Functional Medicine through the Institute of Functional Medicine. In 2015, he established Cornerstone Personal Health, a practice dedicated entirely to Functional Medicine. Dr. Papanicolaou joined The UltraWellness Center in 2017. Dr. Louis Ignarro is a medical research scientist who was awarded the Nobel Prize in Medicine for his breakthrough discovery of how nitric oxide positively impacts health and longevity. His groundbreaking research on nitric oxide paved the way for—among other innovations—Viagra. He is an award-winning Distinguished Professor Emeritus of Molecular & Medical Pharmacology at the University of California, Los Angeles, and has his PhD in pharmacology, with over 35 years of experience teaching. Jessie Inchauspé holds a bachelor’s degree in mathematics from King's College London and a master’s degree in biochemistry from Georgetown University. Her work at a genetic analysis start-up in Silicon Valley made her realize that, as the key to good health, food habits beat genetics. In her first book, Glucose Revolution, Jessie shares her startling discovery about the essential role of blood sugar in every aspect of our lives, from cravings to fertility, and the surprising hacks to optimize it while still eating the foods we love.   This episode is brought to you by Athletic Greens and Rupa Health. Right now, when you purchase AG1 from Athletic Greens, you will receive 10 FREE travel packs with your first purchase by visiting athleticgreens.com/hyman. Rupa Health is a place where Functional Medicine practitioners can access more than 2,000 specialty lab tests from over 20 labs like DUTCH, Vibrant America, Genova, and Great Plains. You can check out a free, live demo with a Q&A or create an account at RupaHealth.com. Full-length episodes of these interviews can be found here: Dr. George Papanicolaou Dr. Louis Ignarro Jessie Inchauspé

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Hi, this is Lauren Fee and one of the producers of The Doctor's Pharmacy podcast. Stress is something we all experience, including many men who are living life out of balance, taking on too much, sleeping and moving too little, and eating an inflammatory diet. Stress from these unhealthy lifestyle patterns can contribute to issues such as declining testosterone levels, sexual dysfunction, low sex drive, fatigue, mental fogginess, and bone loss. The good news is that making changes to your diet and lifestyle can improve hormonal balance, heart health, and so much more. In today's episode, we feature three conversations from

the doctor's pharmacy about topics that intimately affect men's health in their everyday lives. Dr. Hyman speaks with Dr. George Papanikolaou about why men have low testosterone and how to increase it, with Dr. Louis Ignaro on the anti-inflammatory benefits of the miracle molecule nitric oxide, and with Jesse and Chauspie about tips and tricks to minimize blood sugar spikes. Let's jump in. What are the drivers of dropping testosterone in guys from a lifestyle perspective, and what do you do to address those stress nutrition lack of exercise poor sleep too much alcohol too much pot bad relationships the usual suspects yeah so so you said stress lowers testosterone yeah my favorite study was this study where they they looked at guys who went to football games

and they measured their testosterone before and after the game. I know this study. And the guys whose team won, their testosterone levels went up. The guys whose teams lost, their testosterone levels went down. Particularly the ones that had been gambling. Oh, the ones that had been gambling. I didn't really get that far.

That was in the fine print of the methods of the study. I didn't get that. But that is striking when you think about that. So your mental state has a huge effect on your hormones. Yeah. So you mentioned also nutrition. Talk about that because I think that's something people understand. How does food affect your hormone levels, particularly testosterone?

Well, food is fundamental. It's the building blocks for everything that we need. So hormones require certain food macronutrients. Like you need really good healthy fats so you can have cholesterol in your system. So you can make, because cholesterol is the building block for testosterone. So diet provides us the macronutrients we need to be the building blocks for creating hormones. Cholesterol is a building block. So cholesterol is what actually testosterone is made from. Yes. Right. So what about people

taking statins? They could potentially, statins can lead to low testosterone because you're going to drop your cholesterol levels. And if you get them too low, you're not going to have that building block. And if you're under lots of stress and if you're not sleeping well both of those are going to drive down your to start you know are going to really create we'll get to this later an imbalance where you're going to actually produce too much cortisol which is going to demand the use of cholesterol because cortisol is also made from cholesterol so you have this this you have this this sink of cholesterol and it needs to be used to make your hormones.

And if you're using it primarily to make cortisol... Like the cortisol steals it away. It steals it away from being able to make testosterone. So, getting back to the nutrition piece, we do need those building blocks that come from eating fatty fish,

taking a fish oil capsule if you don't, and then making sure you have all the other nutrients that are required to make testosterone. It's very important. And what about what causes it to go down? Because that's what causes it to go up. In fact, saturated fats can help it go up. Right.

Exactly. So what causes it to go down? Yeah. You know, sugar plays a big role in creating inflammation. Sugar also will drive insulin up, and that can have an impact on your testosterone levels as well. So having a diet that's going to be rich in whole foods, low in sugars, processed foods, will definitely be beneficial. So essentially what you're saying is that our diet plays a huge role in regulating our hormones. So good fats are good for you. And even a little

saturated fat is necessary to produce cholesterol. And our starchy sugary diet, which is about a pound a day per person in America of starch and sugar, which basically are the same interchangeable, flour and sugar, drives your testosterone down. Absolutely. And when you get high insulin levels from eating too much starch and sugar, that causes the deposition of belly fat. So what you see is it's this amazing phenomenon of these guys. They get these big bellies.

Their testosterone goes down. They lose hair on their body, and they actually get man boobs. So why does that happen? Dr. Yeah, because what's happening is that when you have that excess belly fat, it's basically too much estrogen. And estrogen, and we're going to, when I talk about my case, we're going to talk about this, when you have too much estrogen, then estrogen drives something called sex binding, sex hormone

binding globulin. So this is a, it's a protein that carries your testosterone throughout your body. But the active testosterone is free. It's not bound. So when you drive your estrogen levels up, then you're going, you know, by being overweight, you're going to store excess estrogen in that belly fat. Then what's going to happen is that you're going to then drive down, drive up your sex hormone binding globulin. You're going to bind that free testosterone. And now you're going to start to experience the effects of low testosterone. Yeah. And also, testosterone gets converted to estrogen.

Right. And there's ways to block that conversion. There are. But the key is, it's so diet-related. So maybe getting your sexual function back has to do with getting your belly to go down. Absolutely. Do you want something else to go up? Yeah.

And it's so true. What happens to men in our society is that they're working too hard, they're stressed out, they don't sleep well, then they eat in such a way that they're going to gain weight. And all of those things are impacting their testosterone levels. But there's this combination too, where cortisol, as we talked about, is going to steal. You'll lose your testosterone there. But also, you begin to have other hormones that are involved.

So if you're, again, we're going to talk about this in the case. If your thyroid isn't functioning well, there are some studies that show, and it wasn't really clear to me as I looked at the studies, and I don't think that they delineated it, but when you have hypothyroidism, you can also have low testosterone. So, you have to look at all, you have to look at all the formats. Yeah, low sexual desire is one of the symptoms of low thyroid. Yeah.

So, you have to look at, when you think about testosterone in men, where they come in saying, hey, I think my testosterone's low, or I'm having erectile function issues, or I can't build muscle mass in the gym. I think about testosterone, but I think about balancing all the other hormones. I start to look at the entire lifestyle package. Well, they're all connected, right? It's like a big chicken wire. We learn about insulin, sex hormones, cortisol. they're all interchangeable. They're all interchangeable. They're all separated by a few different molecules that are regulated by different

enzymes and it's like a pinball machine. Which ones are going to go down, you don't know. And if you're just looking at testosterone alone, then you're going to potentially miss the root cause of the problem. And so, just replacing testosterone is never a good idea. And alcohol is another huge factor. When you see guys who drink and have, you know, quote, beer bellies, what happens to their bodies?

They get this big belly. They get breast enlargement. They lose all the hair on their body, so they look more like women. And it's because the alcohol increases estrogen production in the body. That's why alcohol increases the risk of breast cancer. But it has that effect in men as well. And when you help them cut out the alcohol, cut out the starch and sugar, increase the good fats, increase fiber, increase plant-rich diet, these guys see dramatic improvements

in their hormone levels without actually using medication. So that's always the first step is addressing these lifestyle factors, sleep, stress, exercise, diet, and sugar, alcohol. And the other thing that is fascinating is muscle. It plays a huge role. And one of the ways to boost testosterone is to exercise and build muscle.

Yeah, strength training literally will build your muscle. And will build your testosterone levels. Yeah. So when I'm talking about patients with low testosterone, it's always lifestyle first. And managing all of that. So the first things I'm going to do with my patients are the things that we've already discussed.

And it's going to be get them exercising again, get them meditating to reduce their stress and their cortisol levels, get them to avoid alcohol as much. And you know what? That's not what they come in for. They don't come in for me to tell them to do that. They want the magic. And they want a testosterone injection or a testosterone gel. And that's not where I start. And in the end, for a majority of the men I work with,

they're much happier because by changing all their lifestyle factors, they're much more satisfied and they're much healthier. There's a lot of beneficial side effects. Huge side effects to improving all of those things. They get weight loss, increase energy, better sleep, happier, all that stuff. Oh, just by getting them to meditate. You know, I very much believe in the benefits, you know, the data on meditation and its impact on your body, your overall health is huge.

So I've probably, every male patient that comes into my practice has that conversation with me. And they're just like, they're just shocked that we're talking about meditation when they come in for all the issues they come in with. And I identify stress as a major issue. And I tell them about meditation that will drive their cortisol down and that will help them improve the testosterone levels in and of itself. So, so tell us about this patient you had who came in with, you know, fatigue and he was overweight. What was the story with this patient and how did you approach him? Because functional medicine is a very different approach. You know, like you said, it's not just here, take the

testosterone. It's looking at all the variables that could be impacting a patient and affecting their hormones, whether it's toxins, whether it's their gut, whether it's nutritional deficiencies, whether it's their diet, stress,'s nutritional deficiencies, whether it's their diet, stress, all these factors we look at comprehensively in functional medicine. That's what we do at the Ultra-Vulnerable Center. That's why you have so much success because we're not just a knee-jerk, oh, you have low testosterone, give testosterone. It's a comprehensive approach that deals with all these variables.

Right. So, this gentleman came in, he was experiencing fatigue. He, as you described already, he was having adiposity around his waist and also in his breast tissue. And he had been working out. And he'd already been to a physician who had given him testosterone and it wasn't, he was not getting the clinical benefit that he wanted. So when they, when a patient like that comes in, we begin to go through everything. We go through the lifestyle, we begin to go through everything. We go through the lifestyle, we go through previous treatments, and we go around our matrix, which is that tool that we use that identifies the way we think about overall

health in a patient. And we don't treat the symptoms, we treat the systems. So in this particular patient, I immediately identified that he was a busy executive, 52 years old, he was under stress, he was a little bit overweight, and he had been on testosterone, and he brought me some lab values, and his testosterone had gone up,

but his free testosterone was really low. That's the active testosterone. That's the active testosterone. That's the active testosterone. So I started to think. So in other words, what you're saying is a guy could have a normal level, if the doctor says, let's see your check, the normal is let's say 300 to 1,000.

Yeah, he was about 550. So it's 550, which seems pretty good, but if you don't check the level of active free hormone, you're not really knowing what's going on. And if you don't check these other tests you're gonna talk about, you don't really know what's going on. And if you don't check these other tests you're going to talk about, you don't really know what's going on. So tell us about how that works.

Yeah. So when you see that, you're like, well, that's interesting. So the tests that I do included something called a Dutch profile. A Dutch profile just doesn't tell me about the total amount of testosterone. It also tells us how you metabolize your testosterone. And as you mentioned earlier, Mark, that you convert your testosterone to estrogen. And there are some men that naturally convert their testosterone very efficiently, too efficiently into estrogen. And so they're over-aromatizing. And you can see that on the Dutch profile.

You can see that the results show you that pattern. He was an over-aromatizer. And so when he was being given testosterone, he was converting a lot of it into estrogen. So he was actually taking testosterone. Yeah, at the time. He came in with testosterone. He was taking testosterone when he came in and he actually gained more gain more visceral fat while he was taking. So it sort of backfired. Yeah it backfired totally.

He was supposed to build muscle. This is very interesting. This is why I brought up this case. This is a great case because you know if you just go to a regular traditional doctor even when you get testosterone they'll just give you testosterone they won't look at all these other variables and like well I don't know why you're losing muscle and gaining fat and growing boobs and losing hair on your body right so it was an interesting case because what hadn't been tested was his sex you know uh hormone binding globulin hadn't been tested and his estrogen had not been tested and he had been on the testosterone for almost nine months. And he saw these differences. So on the basic labs that anybody can get, I checked his estradiol level.

I checked his sex hormone binding globulin. And his estradiol level relative to his testosterone was elevated. His sex hormone binding globulin was also elevated. And that's what was binding the free testosterone. And then when I looked at his Dutch profile, it all made sense. He was an over-aromatizer. So this Dutch profile is a test we do here at the Ultra Wellness Center. It's quite different.

It looks at how all these hormones interact, how they're metabolized, what's getting converted to what, where the imbalances are. This is not something you get where there's a traditional hormone test that you go to the lab and get. Right, exactly.

It's a saliva test. It's a saliva test. And so, and it's very, it's a very test it's a saliva test and so uh and and it's very it's a very effective test and uh it made sense when i saw that picture so so that's the that's the difference now he had some other things going on um and that included the sleep apnea but the the main thing was is that all we needed to do was address this hormone imbalance. And to do that, we needed to account for the fact that he didn't aromatize really well. So you add in something, an aromatase inhibitor called an anastrozole.

So I added an anastrozole to his treatment plan. And that, you know, was going to make a difference. Now that was going to block his body's natural ability to so readily turn testosterone into estrogen. And because of his age and the urgency, because he was getting a lot of emotional stress over this, I added in a peptide. So I added in something called CJC-1297, and that actually helps you, along with Ipramoralin, that combination will help you lose fat and gain muscle. So we added that in for a three-month cycle, and he did extraordinarily well. He lost all that visceral adiposity around his waist.

Also, the man boobs went away and he was feeling great, gaining muscle mass, and he was extraordinarily pleased with the outcome. Amazing. So, you know, you talk about anastrozole, which is a medication. It's used often in cancer treatment for women, for breast cancer, because it blocks estrogen production by the body. There are also natural ways to inhibit aromatase and to help with the excess estrogen. One of the ways that we deal with hormone imbalances is using foods and using even ingredients that are in foods that are powerful regulators of hormones. One of the most important things is a compound found in the broccoli family, the brassica family.

Right. It's called diendylmethane or DIM. Right. And that can be used in patients who are taking testosterone to help affect the hormone metabolism into estrogen and limit that. Absolutely. You can also use biotin. Right. And so there's a lot of other things that can be taken.

Yeah. Along with the hormone replacement to help mitigate. And I will commonly use DIM and calcium deglucurate because they both increase the metabolism of estrogen. I use them in women, but I also use them in men, particularly gentlemen like this, that would have been an option. I chose to do something that would be a more aggressive approach. Yeah, this is definitely going know, this is definitely gonna work. Yeah faster I mean, I mean what about the the method of testosterone replacement? Can you talk about the options for men about what kinds of available? Testosterone placements there are and what is the point at which you would initiate that?

What's your decision on these patients of okay? This is now the time to start right? So the first thing I do is as I I said before, is we balance out everything else. We do lifestyle factors and we make sure that that's all in place. If after six months or so of lifestyle factor intervention, they're not improving, that's when we'll start talking about testosterone replacement. And testosterone replacement, you can do topicals, you can do injectables. And I tend to use the injectables because they're very effective and very efficient. So how does that work? How do you do an injection?

So injectables can be given IM, but recently- In the muscle. Which is in the muscle. And the research has shown that the sub-Q injection, meaning you just pinch the little fat around your waist, you inject right into that little piece of tissue that you have there, that's called a sub-Q injection. You can get absorption and elevation of testosterone just as effectively as I am. So it's a very, very simple approach. And that's an easier procedure.

Oh, it's very simple. And you use compounded hormones, you just get them at the regular pharmacy. Where do you get them? So they can be, you can get them in a regular pharmacy and you can get them compounded. Most of the time, the raw ingredient of testosterone is going to be very similar. It's the carrier molecule that might be different. So some pharmacies use grape seed oil. I mean, some compounding pharmacies use grape seed oil because there's some theoretic advantage of absorption. So when they compound it, it's going to be the same raw material.

It's going to be the carrier that might be different. And so I use compounded when that's appropriate. Sometimes patients don't want compounded. It's a little more expensive. So we'll go with a pharmaceutical grade from the local pharmacy. And then we'll do sub-Q injections. And what about the topicals? Can you talk about when you would decide to use topicals or why? I don't use topicals that often. And the reason being is that they're just sloppy.

I'll just say you need to use large quantities of them to get the concentration that you need. You need to be sure to wash your hands after you've used it because you can actually, by touching your child or touching your wife, they can actually absorb effects of elevated testosterone because they're coming in contact with their husband's testosterone on their shoulder on, you know, or what other location you may have placed it or if he didn't wash his hands appropriately and they're in intimate contact. So I don't use gels that often because you can do sub-Q injections. I primarily will use the sub-Q injectable form of testosterone. And there's other forms, right? Pellets. Can you talk about that?

Oh, you can do pellets. So now, again, pellets. What is that? How do you do it? So they have to be placed on your skin, and they're usually placed for up to six months. They get replaced. The issue, well, there's no issue with pellets.

They work fine, but you don't have the ability to make any alterations in the testosterone concentrations. So if it's not enough, they're not experiencing it, you have to remove them. You have to put new pellets in. I find that using testosterone injectable is just, it's very flexible and it's very, very simple and easy. And it doesn't involve the placing of pellets

in the skin. I want to get into the exact reasons why nitric oxide is so important in our biology and all the different things it does, everything from heart health to sexual health. Yes. But what's fascinating to me is that nitric oxide is this very quickly formed and eliminated molecule, but it's so important. Well, what really struck me was when I started research about the effect of statin drugs, which is the number one selling drugs in the world for lowering cholesterol. And I began looking at the research on cholesterol. It didn't really seem that the cholesterol-lowering effect

of the statins was the real reason that it had all the benefit. That you could look at people who had high LDL, but if they didn't have inflammation and they had these other issues, they'd be fine. And one of the mechanisms of action of statins is it increases something called nitric oxide synthase, which is a enzyme that makes nitric oxide. So I'm wondering what you think about that theory, that maybe it's the effect of nitric oxide

and not the cholesterol-lowering issue around heart attack. To me, it just seems like a no-brainer. Well, I'm so happy that you understand that because a lot of people don't. Most physicians don't. I'm a little weird. All this time, I thought that the statins work by altering cholesterol metabolism and on and on. But then there were

a couple of abstracts. I remember a couple of papers that came out, publications, and I heard something speak at a meeting showing exactly what you said that some of these statins can upregulate the enzyme that is create more enzyme no synthase and that's the enzyme that makes nitric oxide so if you have more no synthase you have more no and um and people reproduce that work and i remember that i that I met Joe Goldstein at a meeting. He was one of the guys who shared the Nobel Prize for discovering cholesterol metabolism and their work led to the statins. And I said, you know, you realize that, of course, the bottom line is really nitric oxide. And what did he say? He laughed and said, get out of here, you know, and he walked away. But I think that one of the major effects of the statin drugs is to boost nitric oxide

because nitric oxide prevents inflammation of the arterial wall. That will prevent certain blood cells from coming in to deposit cholesterol plaques and develop atherosclerosis. And that is why our arteries make nitric oxide. We make nitric oxide in order to protect us against hypertension and protect our arteries against inflammation and prevent unwanted blood clotting, nitric oxide, very potent that way. So if you prevent unwanted blood clotting, you can prevent a stroke. If you prevent inflammation of the arteries, that certainly will go a long way to preventing the development of coronary artery disease, right,

which causes myocardial infarction or heart attack. Yeah, absolutely. And I think what's striking is, you know, statins have what we call pleiotropic effects. They have multiple effects. They lower cholesterol, they increase nitric oxide, they decrease inflammation through other mechanisms and lower C-reactive protein. That may be the real way they work. But what's really fascinating to me is this link between nitric oxide and inflammation. Because anybody who's listened to my podcast or understands my work around the role of food as medicine is that inflammation is the driver of almost all the major chronic diseases we see today. Heart disease, cancer, diabetes, Alzheimer's, autoimmune disease, all these diseases are driven by inflammation. So

it seems like nitric oxide could play a big role in modulating these diseases or influencing diseases. That's exactly correct. Nitric oxide has pretty powerful anti-inflammatory effects. And the reason is that nitric oxide is a free radical, believe it or not. It is a free radical, but it's a fairly safe free radical. And what free radicals like to do is to interact and find other free radicals so that they can react covalently and take them out. And that's what nitric oxide does. It is an anti-inflammatory because it goes after other radicals, whether it's oxygen radicals like superoxide or fatty acid radicals, for example, that hang around in membranes. Like rancid fat in your arteries, right?

Exactly. And by neutralizing those free radicals, then by definition, nitric oxide is anti-inflammatory. Actually, we can say that NO is antioxidant. You know, in many cases, believe me, after all the years of research I've been involved with, antioxidant and anti-inflammatory are very similar phrases. It's almost the same thing. Absolutely. It's incredible.

So let's talk about some of the mechanisms because what was going on with Viagra was fascinating because it was designed to be a blood pressure drug. And it didn't really work that great, but it had this side effect that people complained about, or maybe they were celebrating. I don't know. And that's what happened. And then there's this blockbuster category of drugs, which are these drugs that actually increase nitric oxide. And tell us about this sort of relationship between blood vessel health,

blood pressure, blood organ flow, because really where blood goes is where health goes, right? Of course, of course. Well, I can tell you a little bit more about Viagra and the development, if you like. I mean, as you said, so when Viagra was first being developed, it was actually tested to see if it could lower the blood pressure in humans. And they found that if they raise the concentration high enough, it was still very safe and could lower the blood pressure. But unfortunately, or fortunately, depending upon how you look at it, a side effect was produced. And that is all the male volunteers who were in this study developed an erection, whether they wanted to or not. And appropriately, this was noticed by the nurses who were running the study.

I didn't want to hear about that. I was on the advisory, scientific advisory board Pfizer for a long time before, a while back. And so what happened was that Pfizer did not want to deal with this. They had no concept then that this could be a useful drug to treat erectile dysfunction. But because of the side effect, they said, listen, we're not going to mess with this. So they stopped developing the drug. They put the drug on the shelf. Then I published my work in 1992 in the New England Journal of Medicine

that nitric oxide, because we had shown for the first time, the neurotransmitter released from the nerves that causes penile erection was not known. That's why no drugs could be developed to treat ED. You didn't know what the neurotransmitter was. How can you develop a drug? So we discovered that the neurotransmitter was our good friend, nitric oxide, which makes good sense, right?

It's a vasodilator. And so they read my work and they realized, oh my goodness, our drug works by increasing nitric oxide. So they filed a new drug application. They took the drug off the shelf. They developed it. The FDA fast-tracked it. And in six years, it was marketed as sildenafil or the trade name Viagra. And what's interesting is that Pfizer invited me six months later because it was just after the Nobel Prize, invited me to their to their pharmaceutical company in England where the work was done and showed me the laboratory where this was done. And you could see all my reprints pasted on a wall and in the laboratory notebooks. It was really great to see this. And from that point on, I'm not sure if you're aware of this, but from that point on, I was given the acronym of the father of Viagra. Which is an acronym I don't mind at all, but my mother was alive at the time, and she used to get very upset whenever she heard that.

And she would tell me, why don't you tell them to stop that already? Well, I imagine they probably didn't have trouble getting volunteers for that study. So that's incredible. So you call it a neurotransmitter, as well as an antioxidant, anti-inflammatory. So it has all these different effects, right? It's really amazing. When it's released from the nerves, it functions as a neurotransmitter in the erectile tissue of men and women, by the way, but it's also a neurotransmitter in the brain where it's released in certain areas of the brain that promote memory, learning, and information recall.

Many scientists believe that dementia, especially Alzheimer's disease, may be attributed to a deficiency of nitric oxide neurotransmitter in the brain. And what I tell all my young scientists when I was teaching, I would tell my graduate students that remember this the brain has 10 times more nitric oxide than does any other organ in the body and we don't know why so go after that problem i mean that's a good problem to go after that's amazing so let's just kind of review and then i want to get into the question everybody's thinking about, which is how do I get more of this stuff in my system? So let's see. It dilates your blood vessels and lowers your blood pressure and improves blood flow in your organs.

It prevents clotting, you mentioned, and prevents blockage in the arteries. It's an anti-inflammatory, so it helps keep the healthy arteries. It promotes learning, memory, and information recall. It helps regulate erectile function in men and rousal in women. And other things, including affecting, protecting your skin from the sun and skin cancer. And you also mentioned in your work that it promotes digestion by helping the movement of digested foods and regulating digestive enzymes and hormones. So, it's like an incredible molecule that is doing all these things that no one even knew about until you came on the planet. Isn't that something? I mean, it took somebody to discover that nitric oxide, which had long

been known to be a pollutant in the Earth's atmosphere, it took someone to show that our bodies could actually produce it. And once that was identified, everyone jumped on the bandwagon and so many different people discovered so many different effects of NF. But what's miraculous is that one single molecule can exist ubiquitously throughout the body and produce all of these effects. And, you know, we've mentioned only half of them. So to me, as a scientist, I find that remarkable. But if you have a chemistry background, which I do, and you look at NO, it's perfectly suited for its job. Why have 25 different chemical molecules in the body, each doing something, when you can have one nitric oxide, but it has to be regulated because, you know, you don't want to increase blood flow to your legs

at the same time that you're creating a penile erection. You know, I mean, in one place it works, another place it doesn't. So it's highly regulated so that it's not working everywhere at the same time. It's incredible. So how do you know if you're low in nitric oxide as a person walking around the street? Well, let me tell you something, sir. If I did not retire and I still had my laboratory, I would invite you to my laboratory to try to work out that problem because no, it's such a difficult problem. It's impossible to measure nitric oxide real time because it's an unstable gas. It has a half-life of about two or three seconds. That's it. As soon as it's made in the body, it works within a second or two,

and then it's gone. And that's what you want from a signaling molecule. You know, you don't want the molecule to hang around forever. You just want it to hang around just for a little bit. But luckily, we're continuously making nitric oxide. If we have healthy arteries, they are continuously making nitric oxide. Unfortunately, we can't measure it. We can measure byproducts. In other words, we can measure nitrite, NO2 minus, and nitrate, NO3 minus, because NO is oxidized.

That's how it's broken up. It's oxidized to nitrite and nitrate. So you can measure that. It's good in laboratory animals, but not in humans. Not great for going to your doctor and having it checked out. Well, because nitrites and nitrates are present in all the foods we eat. If you like beets and spinach and Brussels sprouts, and you like to eat bacon and so on, all those foods are loaded with nitrite nitrate. So you'll have a very, very high background level.

And although it's been attempted, you cannot measure changes in nitric oxide production that way. But symptomatically, there's ways people can know, right? I mean. Sure. Oh, absolutely. Well, what would be the kind of symptoms people might have? What we have tied, we meaning the scientific community, not I, but anyone with hypertension that's been examined clinically using invasive methods to measure NO, it's been shown that NO

production by the arterial endothelial cells is diminished. People who are obese have absolutely low levels of nitric oxide produced by endothelial cells. People who lead a sedentary lifestyle, the same. People have been subjected to physical activity, just even minor physical activity, walking fast, riding a stationary bike, and there's ways to measure indirectly nitric oxide production. I can tell you about that in a second. And that NO goes up. And the way you measure NO indirectly is you put something like a blood pressure cuff on your finger, and it's made tight. And then the blood flow in your arm is stopped just for a few seconds. And then the blood flow in your arm is stopped just for a few seconds. And then the tourniquet is released.

That will cause blood flow to go through the finger. And there's something called flow, blood flow dependent vasodilation. In other words, when you release that cuff and you allow the blood to flow through the hand, the blood flow, because it creates a force against the arteries, that's called shear stress, that stimulates the arteries to make enormous amounts of nitric oxide. That's good because you want to dilate all the blood vessels there that have just been constricted. So NO is released to dilate the blood vessels and allow blood flow. That's what happens during exercise in all of your skeletal muscle, by the way. But you can measure that flow-dependent vasodilation, and that's a pretty darn good measure of your capacity to make nitric oxide. So if you run that test, which is expensive, you usually have to go to a clinic, whatever,

for now anyway, you can determine how much NO you can make. And what we know is that people who lead an unhealthy lifestyle, if I just leave it at that, make substantially less nitric oxide. That's been borne out every time. What happens to men when they eat too much sugar and starch is they actually produce, because they produce way more fat cells, and the fat cells have a compound called aromatase which converts testosterone into estrogen. And so the men get man boobs and they get soft skin and they lose the hair on their bodies so they become

more like women. So basically, men become more like women, women become more like men. It creates this massive chaos in the hormones. And I just want to reinforce what you're saying because you say glucose. And most people, when they think of glucose, they think of sugar. But you should think of bread or sugar or cornflakes in exactly the same way. In fact, bread is the gold standard for measuring glycemic index. And it's worse than sugar. The score for bread is 100. The score for sugar is 80. So actually, you're better off having

the sugar than the bread. I would disagree, Mark, because in the sugar, there's also fructose and all the things we talked about, you know, the aging, the inflammation, fructose does it at an even higher rate than glucose alone. That's true. I would argue that if you have a choice between something starchy and something sweet, I would go for the starchy thing, but better even have some vegetables first, then some protein and fat, and then have the starchy thing. And maybe you won't even want to have the sugary thing at the end. Yeah, I think that's fair. But I also say if you're going to have starch, have starch that's in forms that are coming

in a good package. So for example, I have a Japanese purple sweet potato at night. I love that, which is starch, but it's got full of phytochemicals and fiber and vitamins and minerals. And I eat the skin. So it's really actually a very healthy food. And it's quite different than eating white bread, which is also a starch. So starch is a starch is a starch. It really depends on where it's coming from and how it's metabolized. Even oatmeal versus steel coat oats, profoundly different. Absolutely. And this is, so what I've been doing in my work is testing all these things on my own

body and using a continuous glucose monitor, showing people the different spikes that happen. So I tested steel cut oats versus regular oatmeal and the steel cut has a smaller spike and same for bread. So white bread is far worse than something like sourdough, for example, which is worse than something like very dark pumpernickel bread that's all gooey and feels almost like a cake because it's so rich of fiber. Yeah, from Germany. So it's always a spectrum, right? You have to think within a category.

There's different types of bread, different types of potatoes, different types of starch, and you can always make a choice that's a bit better. And you can always add some fiber to it and some vinegar and go for a walk after. So basically, throw some Metamucil and some vinegar on your food and you're good, right? Pretty much, yeah. Sounds delicious. So tell us some of the surprising things, Jesse, that you learned about your own body and in researching this about what you thought was okay to eat,

but actually wasn't, or what you thought wasn't okay to eat, but actually maybe was okay. Well, as I mentioned, you know, I used to have donuts for breakfast. So I really got a cold shower in terms of nothing sweet first thing in the morning, because first thing in the morning, when your body is completely fasted, your glucose levels will respond incredibly fast to anything that you ingest so I realized that if I wanted to eat something sweet for example a donut I should never ever ever eat it on an empty stomach I should always eat it after a meal yeah then in terms of other surprising things I mean oatmeal was a big one because they even say oatmeal is for diabetics. I mean, there's all this information that's very confusing. Yeah. Rice cakes. Oh my God. It's not a health food. No, it's not rice cakes. This is crazy. Brown

rice cakes. How could they be bad? I tested brown rice versus white rice. Literally no difference. Well, what if you put like a nut butter on top then it's perfect that sounds really gross but it probably works i love that's my favorite thing i get the rice cakes and i put like on the rice cake i thought you meant put the nut butter on actual rice like warm rice i need a rice cake and you put on the the nut butter and it's it's kind of good yeah i think i think so so so all the breakfast things are really in this country so geared toward extremely high levels of starch and sugar.

And in fact- Fruit juice? Yeah, fruit juice is terrible, right? And I think people need to realize that the most important thing they need to do when they eat in the morning, eat plenty of protein, fat and fiber. Yes.

Because those are the magic tricks to actually keep your blood sugar normal protein fat and fiber and you have to learn what foods have protein fat and fiber it's it's a little bit of an education because you know as people may not know but it actually it actually is the key to success and you're basically saying eat protein fat and fiber before you eat any starch or sugar and that will mitigate all the results exactly something else that was very surprising was oat milk creates a big glucose spike because it's no more oatmeal lattes the oat milk lattes no no way huh people got really sad when i posted that test i was like i'm sorry i know you guys love your oat milk but it's just it's just a big bowl of glucose it's dessert have it as dessert don't have it first thing in the morning on an empty stomach and then um fruit was actually quite surprising to me mark because i learned that fruit have been

bred for centuries to be extra sweet and extra juicy and contain lots of glucose and fructose so especially grapes yeah grapes are the worst you eat eat 20 grapes, super big glucose spike. So I learned that anytime I have fruit, always put clothes on it. I'm French, so grapes and cheese. I actually just posted that test yesterday on my Instagram, glucose goddess, if anybody wants to see it. If you add cheese to the grapes, the glucose spike is smaller because you're adding this fat. But it's still there.

It's still there. But it's still there. Yeah, so have it as dessert. Yeah, pineapple, bananas, definitely always put some clothes on those. And I've really completely changed the way I ate, Mark. I mean, now for breakfast, I have leftovers. This morning, I have leftover green beans and cauliflower and two eggs. I don't have cravings anymore.

So dinner for breakfast. Dinner for breakfast. Dinner for breakfast. I feel better than I ever have. And I'm older than I ever have. I feel so good. I don't have any cravings. I have energy throughout the day. I don't even drink coffee anymore because I have so much energy just naturally. I mean, I sleep amazingly. It's very powerful. That's amazing. So you basically have learned how to hack. Now,

what other foods you thought were bad for you that actually weren't so bad well there was this whole thing about fat is bad for you you know fat makes you fat fat's not good and i learned that actually that's not the case you know what drives heart disease the most is fructose in your liver creating low density ldl and that fat is actually your friend and so i started putting way more avocado and avocado oils and olive oil and good fats like that, eating more fish. And that really helped stabilize my glucose levels. Other foods that I thought were bad that were actually good. Hmm. I think it was mostly the other way around. It was lots of foods I thought were good that were actually bad. What about yourself? What did you discover? Yeah. Fruit, yeah right yeah i think fruit fruit has you have to be

careful with fruit because it depends on the fruit depends on how uh you know sweet it is how is bread the kind of fruit you know like when you when you go kind of get a wild fruit they're very sweet but they're very very small you know and i think you know oh dried fruit is another big one oh dried fruit's terrible yeah dried fruit's like candy you know it is like candy and now what i do you know when i want something fruity i'll have one of your shakes um the you know the berries with nut butter and lots of nuts in them chia seeds almond milk like that kind of stuff and that makes for a very satisfying fruity a little snack but that contains all this extra protein and fat and fiber to minimize the spike yeah yeah that's one of my

favorite things i call it a fat shake so you basically take you know nuts of any kind throw in a bunch of nuts like almonds walnuts uh you can take pumpkin seeds chia seeds flax seeds hemp seeds and then throw throw in some berries and frozen berries i put in cranberries in there maybe throw some lemon in maybe i'll throw a couple of tablespoons of nut butter sometimes to make it creamier and you put in some non-sweetened macadamia milk i hope macadamia milk's not bad because i i use that a lot. I got to check that out. Because you were telling me that's like oat milk. I'm like, oh boy.

It comes from nuts, so it's fine. That's good. Okay. And you blend it up and you can throw in greens in there. You can throw an avocado in there. I throw, you can throw in- Put some cacao nibs on top. Oh yeah, cacao nibs are good. So you can make a really yummy smoothie

that's basically not from processed powders but actually from whole foods i have that recipe in my book ultra simple diet i'm sorry the 10-day detox diet which has that recipe in it and i can add some protein powder too you can add some protein powder and i think you know particularly in terms of muscle mass it's really important and the science is so clear on this that that we need high-quality protein in the morning, particularly to load up, build muscle synthesis, we need about 30 grams. And it has to be high-quality protein, which has to include amino acids that are found primarily in meat or animal products. Now, if you're a vegan, you have to figure out how to get those extra amino acids. You have to supply amino acid powders and add them in because if you don't have leucine,

which is very low in plant proteins, you can't trigger protein synthesis. In other words, building muscle is critical. And you look at, I mean, not judgmentally here, but if you look at most vegans, they tend to lose a lot of muscle mass. And the longer they've been on a vegan diet, the worse their muscle loss is. And, oh, they're thin, they look good, their weight's great. But no, they're actually, can be metabolically unhealthy. In fact, they can get what we call a toffee, which is thin on the outside, fat on the inside, or metabolically obese normal weight, we call it, or otherwise called skinny fat. Most commonly known as skinny fat.

Yeah, you look skinny, but you're really fat. And that actually is just as dangerous as actually being overweight in terms of risk for heart attacks, diabetes, strokes, all the same risk factor. So I think people need to understand that you've got to look under the hood.. You got to look at what's going on. So maybe you're, you're a vegan and you, you're like, okay, well, how am I going to get protein

in the morning? I don't want to eat meat or I have a whey protein shake, but what can I do? Well, you kind of have to look at your own biology. And I encourage people to look at their continuous glucose monitoring. I encourage people to measure fasting insulin, even measuring a two-hour post-meal insulin level, which most doctors will not order, but you can try to get them to order it. If not, you can just maybe order it yourself. There are now companies where you can order stuff yourself. But I think it's really important. You can go to IHOP and have breakfast.

Yeah, you said that in your podcast with Casey or your Instagram Live. You said, just eat something that has a bunch of glucose in it. Eat a bunch of rice and then two hours later, go get your insulin and your glucose listed and you'll know. Yeah. Yeah. So that's really important. So the tips you gave are so important. The sequencing of food. I mean, even if you have a glass of wine and I mean, the worst thing in restaurants, right? Because what do they do? You want to drink? Here's a bread basket. You know, it's like the worst possible thing you could actually do for your health.

If you think about it, if you're a restaurant owner and you want people to order a bunch of stuff at your restaurant. Of course. That's what you do because you give them bread. They eat the bread first, big glucose spike. 90 minutes later, they're crashing. So they're super hungry and they want to order dessert. I mean, it's brilliant. Of course. It's brilliant. Of course. Exactly.

Exactly. And I wonder if they know that or it's just sort of a habit, but it definitely, it's a sure way to get people to order more food. Absolutely. And I think drinking wine, the timing of the food, when you eat what matters. It's not just about time-restricted eating, but it's even the sequence of eating in a meal. It's actually the combinations of the food that you eat. Like you said, don't eat naked carbs. That's a really important concept. The vinegar thing is a very cool hack. The walking after eating is really important. Getting your muscles to work and suck up the glucose, super important. Were there any other surprises or things you learned as part of your investigations, your scientific sort of diving into your own biology? Maybe we can talk a little bit about alcohol because I think this is one of the places where context is very important to think about the fact that glucose is not everything. If you just have a glucose monitor and you drink two bottles of wine, your glucose levels will stay steady.

And they might even decrease, actually, because the alcohol is interfering with your liver's job to release glucose into the bloodstream. But the issue is you might think, oh, well, my glucose levels are steady. This must mean that this food is good for me. And on the completely opposite end of that spectrum, I discovered that when I exercised, I sometimes saw a glucose spike. So if I was just looking at everything from the glucose lens, I would think, okay, wine, good for me, exercise, bad for me. Totally a great plan. How do I get on that health plan? Let's see, a bottle of wine and skip the exercise. Okay.

No? Perfect. Well, then you'll have steady glucose levels, but you're going to get severely sick. And I realized, okay, there's some instances in which it's important to look beyond glucose. So in the case of alcohol, yes, it keeps your glucose level steady because it's hurting your liver. That's not a reason to drink alcohol. Similarly, when you exercise, you might see a glucose spike because your liver is releasing all this glucose so that your mitochondria can make energy. reason to drink alcohol. Similarly, when you exercise, you might see a glucose spike because your liver is releasing all this glucose so that your mitochondria can make energy. But the downsides of the glucose spikes, so the toasting, the inflammation, et cetera, are actually counteracted by all the positive sides of exercise. So in the balance,

it's a positive effect on the body. So I learned about nuance. I became very important. And it's very interesting when you start diving into it, but you definitely need context if you wear a glucose monitor for the first time. You need to have some information to make sure you understand these pitfalls. It's interesting. I had the same experience. I had a good protein shake. My blood sugar, I had my continuous glucose monitor on. It was like maybe went up to 90 after my protein shake in the morning. I thought, I'm going to go play tennis. And I really worked out hard. I had a great tennis game.

And then I checked my glucose. I'm like, that's going to be really good. I checked it. And I was like, holy crap, it's 145. And I texted Casey. I was like, what's up with this? He's like, yeah, yeah, well, that's normal. Because when you exercise, you increase cortisol, you increase your blood sugar, increase adrenaline, you actually release glycogen from your muscles. So yes, when you're

running from the tiger, you want to release a lot of glucose so you can fuel your muscles. But the body doesn't really know that there's tennis. It just knows that you're running because you're chasing a tiger or you're being chased by a tiger. Yeah, on the topic of being chased by a tiger, I also saw a massive glucose spike after I gave a presentation to the whole company when I was working in Silicon Valley. And I was quite stressed out. And after the presentation, I checked my glucose levels,

and just huge spike to 200, but very short and rapid spike. And that was because my body was preparing for me to run far away and fast from the tiger. So released all this glucose into my bloodstream. And it was really cool to just be able to see what was happening and to understand inner workings. And of course it got me just incredibly curious. And that's how this whole journey started. Well, that's an important point you're making, that stress alone causes you to have imbalanced blood sugar. And stress alone will release cortisol, which then causes you to increase your glucose levels

and to become diabetic and to become more insulin resistant. So short-term spikes of cortisol are great. You need them to wake up in the morning, go deal with any kind of urgently stressful situation, but it's the chronic low-level stress and unmitigated, unremitting stress that actually causes us to have these metabolic problems down the road. So stress actually makes you gain weight. Yeah. And poor sleep as well, Mark. So I discovered, I used to have a cappuccino every morning and I discovered that on the days where I was rested, the cappuccino wouldn't create a big spike. But then on the days where I was tired, the cappuccino would create a much bigger spike in my body. So I did the

research and I found out that when you're not rested, your body has a harder time dealing with any influx of glucose into your system. So what I found out is that the days when I'm feeling tired, to put all the chances on my side to not create a big glucose rollercoaster, always savory breakfast, like non-negotiable. And then I try to get in 10 minutes of high intensity exercise, very soon after I wake up. So jumping jacks, whatever, put on a YouTube video,

like 10 minute HIIT class. And this helps my body become more insulin sensitive. And so I don't create this big spike from that cappuccino. Because what's so awful and so vicious is that when you're tired, you really crave sugar even more because you're feeling like it's going to give you energy. But the problem is that same sugar that you're going to eat will create a bigger spike than usual, putting you on the cravings roller coaster. and then you're going to crave even more sugar. I hope you enjoyed today's episode. One of the best ways you can support this podcast

is by leaving us a rating and review below. Until next time, thanks for tuning in. Hey, everybody. It's Dr. Hyman. Thanks for tuning into The Doctor's Pharmacy. I hope you're loving this podcast. It's one of my favorite things to do and introducing you all the experts that I know and I love and that I've learned so much from. And I want to tell you about something else I'm doing, which is called Mark's Picks. It's my weekly newsletter.

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