The Dr. Hyman Show - Daily Steps To Prevent Heart Disease

Episode Date: June 24, 2022

This episode is brought to you by Gut Food, ButcherBox, and Paleovalley. Heart disease is the number-one killer in the world, and it is often thought of as a cholesterol problem. When you take a closer look, however, there are other factors that drive this chronic disease that can’t be fixed by the most commonly prescribed medication: statin drugs. The way you eat, how much you exercise, how you manage stress, and more all contribute to heart disease. In this episode, I talk with Dr. Aseem Malhotra, Dr. Stanley Hazen, and Dr. Cindy Geyer about why heart disease is easier to prevent than to reverse, why statins are not the answer in most cases, and how the gut microbiome is connected to heart health.   Dr. Aseem Malhotra is an NHS-trained consultant, cardiologist, and visiting professor of Evidence-Based Medicine at the Bahiana School of Medicine and Public Health in Salvador, Brazil. He is a pioneer of the lifestyle medicine movement in the UK and in 2018 was ranked by software company Onalytica as the number-one doctor in the world influencing obesity thinking. He is the author of, The Pioppi Diet, coauthored with Donal O'Neill, The 21-Day Immunity Plan, and, A Statin-Free Life. Dr. Stanley Hazen is both the chair of the Department of Cellular & Molecular Medicine at the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation at the Heart and Vascular Institute of the Cleveland Clinic. He’s published more than 400 peer-reviewed articles and has over 50 patents from his pioneering discoveries in atherosclerosis and inflammatory disease. Dr. Hazen made the seminal discovery linking microbial pathways to the pathogenesis of cardiovascular disease. Dr. Cindy Geyer received her Bachelor of Science and her Doctor of Medicine degrees, with honors, from the Ohio State University. She completed her residency in internal medicine at Strong Memorial Hospital in Rochester, NY, and is triple board certified in internal medicine, integrative medicine, and lifestyle medicine. She joined The Ultrawellness Center in 2021 after practicing and serving as the medical director at Canyon Ranch for 23 years.   This episode is brought to you by Gut Food, ButcherBox, and Paleovalley. Gut Food uses the power of three critical gut-supporting components—prebiotics, probiotics, and polyphenols—and five ingredients at clinically validated dosages to help reduce inflammation, support the growth of beneficial gut bacteria, improve digestion and bloating, and support mood & energy. Check it out at gutfood.com. If you sign up today, ButcherBox will give you two ribeye steaks for free in your first box—just go to butcherbox.com/farmacy. Paleovalley is offering my listeners 15% off their entire first order. Just go to paleovalley.com/hyman. Full-length episodes of these interviews can be found here: Dr. Aseem Malhotra Dr. Stanley Hazen Dr. Cindy Geyer

Coming up on this episode of The Doctor's Pharmacy. Avoid ultra-processed foods. If it comes out of a packet and has five or more ingredients, it's the ultra-processed avoidant, and that includes even packaged bread. In my practice, I always look at the gut first. When someone's gut is messed up, it can impact their overall health,

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I talked to S-Burson Gut Health, read a ton of new research on the microbiome, and figured out a way to heal my body using three critical things, prebiotics, probiotics, and polyphenols. I created a multivitamin for the gut and you can't keep that information yourself. So I put it all together into a simple daily product that anyone can take and it's called Gut Food. This product uses five powerful ingredients at clinically validated dosages to help reduce inflammation, support the growth of beneficial

gut bacteria, improve digestion and bloating, and support mood and energy. I really believe this is the next frontier of gut health. Just like we take a multivitamin and mineral to give our bodies the nutrients we need, our gut also requires specific ingredients to thrive. You can learn more about gut food and check it out at gutfood.com. This episode is sponsored by ButcherBox. You probably heard me talk about ButcherBox before You probably heard me talk about ButcherBox before because they've revolutionized the process of buying high quality meat and seafood. I love to cook and I have a super busy schedule. So whenever I can spend some time in the kitchen, I want to have all my favorite ingredients right at my fingertips. I'm also

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That's 200% grass-fed ribeyes by going to butcherbox.com forward slash pharmacy. Now, I'm all about using health tools that have stood the test of time as part of different medical traditions. So I was really excited to learn about Paleo Valley's apple cider vinegar complex. Apple cider vinegar has actually been around for millennia, used both for cooking and wellness. I mean, Hippocrates was even known to prescribe it for different ailments. So it's easy to see why it stuck with us for so long. And we found benefits in using it for things like blood sugar regulation, supporting a healthy weight, and improved digestion. It might sound surprising that many of us lack sufficient stomach acid, which is pretty key for extracting nutrients from food. Apple cider vinegar counteracts that problem and supports the right environment on our stomachs for optimal nutrient absorption. Considering that more than

90% of us are nutrient deficient, it's a good thing to think about. But drinking vinegar doesn't appeal to most people, and I get it. And it can actually even damage the enamel of our teeth. And that's where Paleo Valley's Apple Cider Vinegar Complex comes in, a convenient capsule that combines apple cider vinegar with other health-supporting ingredients like lemon, cinnamon, ginger, and turmeric, all of my favorites. Right now, Paleo Valley is offering my listeners 15% off their entire first order. Just go to paleovalley.com forward slash hymen to check out all their clean Paleo products and take advantage of this deal. That's paleo valley p a l e o v a l l e y.com slash hyman. Now let's get back to this week's

episode of the doctor's pharmacy. Hi, this is Lauren Fee and one of the producers of the doctor's pharmacy podcast. Heart disease is still the number one killer in the world. Yet most people don't actually understand what markers most drive risk. And while statins have become the panacea for treating heart disease, most people and even many doctors aren't fully informed about the risks versus the benefits of this drug, nor are they aware of other treatment options for heart disease. In today's episode, we feature three conversations from the doctor's pharmacy on a comprehensive approach to preventing and treating heart disease. Dr. Hyman speaks with

Dr. Asim Malhotra on why lifestyle changes are key to preventing heart disease, with Dr. Stanley Hazen on the role of the gut microbiome as it relates to heart health, and with Dr. Cindy Geyer on functional lab work that looks at inflammation and cholesterol particle size. Let's dive in. As a cardiologist, what really is the best predictor of heart disease if it's not LDL? And what can we do lifestyle-wise to both prevent, treat, and reverse the risk and even the status of actually having heart disease. Yeah. So, Mark, so I think, again, I would come back to keeping the basics, stuff that relatively simple to measure, inexpensive. Okay. So, you know, the things I always go through with my patients, like, so let's go through these five markers. What's your blood pressure? You want your blood pressure ideally to be less than 120 over 80 now the diagnosis is if

it's more than one between 120 and 140 systolic um or between uh you know um 80 and 90 diastolic then you have pre-hypertension and that that doubles your risk of stroke and also contributes to heart disease so you want to look at the blood pressure hba1c should be less than 5.7 percent between five and different i know different countries have different ranges, but essentially between 5.7% and 6.4% is pre-diabetic and 6.5% and above is type 2 diabetic. So you want your HbA1c to be less than 5.7% ideally. You want your waist circumference for a Caucasian man

to be less than 102 centimeters measured around the belly button and less than 90 centimeters if you're a female. And then your triglycerides should be ideally less than one millimole per liter, which the equivalent, I think, in the US is I think 150 milligrams per deciliter. Mark, you would probably correct me on that if I'm wrong. I think that's the range. It should be less than 150. The HDR to be similar, so when you're above 150, so greater than 1 millimole per liter. If you have those all in range, which as you said earlier on, actually having all those markers in normal range for the average American adult is only about 12% of adults. 88% of adults in the US don't have those in the normal range, which which is very troubling right and this isn't just older people only one in four adults aged between 20 and 40 mark in the us have those in the normal range and this is what we're dealing with but the good news is again those are really indirect markers of insulin resistance if you want to do more slightly

more expensive tests and people get this in the us more easier than the uk is uh you do a fasting insulin level and there's a different units i won different units. I won't get it wrong, but there'll be a normal range. I think it should be less than six international units, I think, if I'm not wrong, in terms of insulin, fasting insulin, right? So that's another marker that you can use. So once any of those are out of the normal range, then you've got some degree of insulin resistance. So the question is, what can you do about it? And then it's, well, let's just go back to very basic principles. I keep it simple. So avoid ultra-processed foods.

What are ultra-processed foods? Well, the data now, and I know you've been a big advocate for this, Mark, in recent years as well, and writing about this, is that more than 50% of the UK diet, more than 60% of the US diet is now coming in terms of calories from ultra processed foods i think here's 67 67 is that right it's unbelievable right this is food that comes out of a packet that usually has five or more ingredients a combination of of sugar starch unhealthy oils okay usually with additives and preservatives and that's a

very simple rule of thumb so i tell my patients if it comes out of a packet and has five or more ingredients, it's the ultra-processed sub-void, and that includes even packaged bread, right? So these are the things to cut out. And then low-quality carbohydrates. So minimize sugar and low-quality carbs. So these are refined carbohydrates and lack fiber. Your white breads, your pastas, your rice, your potatoes. Now, it doesn't mean you have to completely eliminate it.

It depends where you're starting from. So a lot of people have also metabolic health already who are generally doing this stuff, right. 80% of the time, probably don't need to be as strict, but if you're starting from a position where you're type two diabetic and all your markers are off, then you have to be more extreme to see the bigger benefits. Right. So, um, what, you know, I, I, I, I, I, like, I have my insulin levels are like less than five, pretty much about two. I have a 6% body fat. Yes. I'm bragging, but I I'm pretty metabolic healthy exercise a lot. I eat really healthy. And I went to Sardinia last summer and I'm like, you know, here I am for a week. I'm just going to like eat whatever. And I'm going to eat the pasta,

the bread, the drink, the wine. And I went, I, you know, I was treated well and had a very, you know, abundant diet and I gained like five pounds and I got the belly fat and, you know, it was, so even if you are extremely healthy, if you start to eat more of that stuff, you're going to start accumulating that. And it's really, you know, unless you're just like doing a marathon every day, it's really tough to keep up with that carbohydrate load that we have. Sure. Well, that's a really important point. Yeah. I think we have to be aware of that. Again, we become, and different people are more sensitive to these carbohydrates as well, right? So I think,

you know, one of the, there's a quote in the book from Dean Ornish, I quoted him, just to give people a concept to understand a bit of nuance with this management, Mark, is that it takes more to reverse disease than it does to prevent it. Well, I think he was borrowing from Benjamin Franklin, which says an ounce of prevention is worth a pound of cure. Absolutely right. Absolutely. But the bigger picture for most adults in Europe, Americans, around the world, the big issue is ultra-processed food, low-quality carbs, as you said. I think if you get that out of the diet, that it's about patient preference and the values. I'm an advocate for the traditional Mediterranean diet, but minus the way we're living now, the ultra-processed, obviously the starchy stuff. Because there is, as you know, we've talked about gut microbiome as well. The positive side comes from with the best available evidence we have and things evolve

seem to be that there is antioxidants, anti-inflammatory components with, with whole fruit and vegetables, um, you know, extra virgin olive oil, nuts and seeds. Um, you want to be getting obviously enough protein. You want to get all your nutritional requirements as well. So you think about, okay, how am I going to get all my nutritional requirements? So I minimize the need for supplements. I mean, I know supplements have a role, but minimize the need for supplements, right? And also reduce the chances of me developing insulin resistance from the diet. And if you focus on that, that's what I do with my patients. Then as long as you get the base of the diet right, other things here or there, it doesn't

matter so much. So get the base right, cut out the crappy stuff, pardon my language, right? And then it's about preference advantage, different cultures, right? Different types of foods, Indian food, Chinese food, whatever. There's going to be obviously some big differences in a lot of the food that people eat. Yeah, I think that's right. I think the lifestyle stuff is so huge. And you talked about the Piappi diet. I talked I think that's right. And I think, I think the, the, um, the lifestyle stuff is so huge. And, and, you know, you talked about the Piappi diet. I talked about the Pagan diet.

It's essentially focusing on quality. So whatever you're eating, the key concept is it should be high quality, meaning nutrient dense, unprocessed, whole real food. And you can kind of go up the chain, you know, eating a feedlot steak is better than eating, for example, you know, a bunch of bread, right? But it's not as good as eating wild elk or eating a grass-fed steak. So you can keep going deeper in the quality chain. The second is to really understand that food is medicine and that everything you're eating is regulating your biology in real time. And three, it's personal. Everybody's biologically different. And some people may be more carbohydrate tolerant than others. Some people

may be more fat intolerant than others. And there are ways to figure that out, which is really important. Absolutely. So that really covers a lot of the diet side of stuff. And then obviously, from a heart disease perspective, exercise, I think we've somehow over-ended the most important message is keep moving do what you enjoy be careful of overdoing it a lot of people get injuries they overdo it there's a you know um especially if you're stressed out and you're doing more than say 60 minutes of moderate to vigorous exercise a day more vigorous side that can actually worsen your stress so the data really says that you know 30 minutes of moderate activity a day um And you can do different things. You do Pilates, you do yoga, you do cycling.

You know, I'm not a particular big, I used to be a runner. I've kind of shifted more to cycling now because, you know, running on the road generally is not particularly good for your knees. I mean, I do sprints once a week. I do hits. Right. So all these things are there, but do enough, but don't overdo it. Right. With the exercise.

And then the big thing mark um something i've discovered in the last few years which certainly has a big impact in my patients is stress psychological stress chronic psychological stress which in its own right and i write about in this book is the equivalent of another risk factor like high blood pressure or type 2 diabetes in terms of its cardiovascular risk but a lot of people aren't managing that not realizing how important it is and of course it links to inflammation um there's a lot of people aren't managing that not realizing how important it is and of course it links to inflammation um there's a lot of emerging data there's this stuff related to clotting problems increasing fibrin in the blood which is involved in as a clotting factor um and what i do with all my heart patients is i ask them you know i do a very simple

questionnaire kind of on them and i ask them in you know naught to ten in the last few years you know these are people come we've already got diagnosed heart disease, some people who've had scans done, they've got some furring of the arteries. And I say to them, you know, where is your stress levels in the last two or three years? I know it's obviously been pandemic time, so it's a bit skewed, but in general, most of them say, you know, that their stress levels are kind of eight, nine out of ten, right, for the last few years and they've not done anything about it. And then I write about in the book, you know, we need better quality data more data but what's fascinating that the largest study

on heart disease reversal which was done in india um by uh a cardio interventional cardiovascular to call the mount abu healthy uh heart trial yeah Basically, it took patients with significant coronary disease, so well over 100 patients, moderate to severe, so at least 50% to 70% blockage in their arteries. These are people that didn't want

to have a bypass operation, didn't want to have stents. And he put them through his healthy lifestyle plan. Now, in India, there's a lot of vegetarians, so it was a very high-fiber vegetarian diet.

There was some starch in there, but it was a very high-f diet. There was some starch in there, but it was very high fiber vegetarian diet. It was moderate exercise. So two 30 minute brisk walks a day. Okay. And then it was something called Raj Yoga meditation, which also wasn't just about meditating. It was like, there was a bit of counseling. It was about reconnecting with your family and your friends and the social aspect, trying to reduce stress levels. Long story short, the end of the, you know, after two years of the trial, then followed up for five years, they found that in the people that adhered to the lifestyle program, there was a 20% reduction on average in the stenosis of the arteries, which is unheard of, right?

You mean the plaque, the clogged arteries got better? Yeah, they got better. They reduced from, say, 70%, 50%, 50%, 30%. I mean, extraordinary, right? And this is no statin. No statin. This is pre-statins, no statins. And then when they tried to look into what was the most important factor by far of all the lifestyle factors that contribute to the reversal, it was 40 minutes of meditation a day. Wow. Right. So this is a big missing area, I think. And, and I think the other thing about the stress reduction, which links to chronic inflammation,

that's the mechanism is that we think now heart disease, these plaques that develop these blockages, the dynamic processes. So you get some inflammation, you get a plaque formation, it then progresses. You can potentially, it seems that you can potentially reverse those blockages or reduce them. But the biggest factor so far, I think that's been ignored is stress reduction through meditation. And as you know, as well, if people incorporate that, then they're also more likely to sustain the lifestyle, the other lifestyle factors in terms of their adherence to the diet. But their mental health is better, Mark. So it's quality of life. It's not just about something potentially being helped

within the long term. Within a few weeks when people do this, and some people need more help. You know, I find it difficult to meditate just from using an app. I have a Pilates teacher that I started seeing a few months ago that comes to see me once a week. I need to probably do more.

It was fascinating. Within an hour, even that session of Pilates, one hour, which is also, you know, it's a great exercise, but it's meditative as well. You feed your stress levels. You just feel like a different person. Yeah. Yeah. It's true. I mean, I think that, you know, the mechanisms are interesting when you look at stress, what it does is a number of things. One, as you mentioned, increases inflammation. Two, it increases cortisol, which is a hormone that your body makes that actually causes your blood sugar to go up,

your blood pressure to go up, causes your lipids to get worse. If you look at a race car drivers before and after a race, their cholesterol goes up a hundred points just from the stress. And not only that, but it actually, it actually causes your fat cells to store more fat. So if you eat under stress, there's nerve endings that innervate your fat cells and the stress response communicates through your nerves and your autonomic nervous system to your fat cells and tells them to store the fat. So it's kind of a big deal. And I agree with you. I think we are under such a barrage of stressors in our lives, whether it's work, family stresses, financial stresses, COVID stresses, climate change.

I mean, I don't watch the news anymore. It's just too stressful for me. And yet it's so simple. It's free, it's accessible. And I've been practicing meditation for years and it's such a key thing to help regulate your life and your biology in so many ways. It improves the stem cell production, it reduces inflammation, improves neuroplasticity,

brain connectivity. The data is just so powerful in this. And if anybody's really interested, you can listen to the podcast I did with Daniel Goleman about his book, Altered Traits, which studied advanced meditators using very advanced imaging technology, looking at their brain function and their, and their brain waves and see what happens when you have somebody who's been meditating for a long time, but it really doesn't, you don't have to be a professional meditator where you're living in a cave for nine years, just 20 minutes a day or 20 minutes, twice a day is very powerful. And I personally use a technique. It's called Ziva meditation, Z I V A meditation. You can look it up online. You can take an online course to learn how to do it.

It's super easy. And you don't need any special equipment except, you know, sit on the floor or a chair. And through that technique, you're going to have all kinds of benefits, not just heart disease, but all kinds of benefits. So I encourage you to take heart to what you're saying, because I think it is one of those neglected factors. So diet, exercise, stress reduction, sleep. I think the data you presented on the reversal is quite interesting because most of us don't

think we can unless you take aggressive high-dose statin. You know, Dean Orr's work showed that there may be possibility through lifestyle interventions to change the course and actually reverse the trajectory. And Mark, anecdotally, I'm getting patients, and I will be writing about this soon, and hopefully I'll be able to even fund a trial to try and get a bit more definitive in terms of the answers. But I'm seeing patients, many of my patients coming back, who have either halted the progression of heart disease, so, you know, from imaging, and some have even had some reversal. One patient recently contacted me, and I'd forgotten, you know, I was in the set, you know, Dr. Marger, I saw you in 2019. She'd suffered a TIA, a mini stroke.

She'd had a blockage in one of her blood vessels of 75%. And she emailed me back saying, I've followed your lifestyle protocol. And I was shocked, Mark, to receive this. I had to read it again. And she said, I've repeated the imaging. And now the reduction has gone to less than 50% within two years. I mean, and I'm just doing what the data, you know, I'm saying the very least that's reduce your risk.

I don't give people promises and say, you know, there is some potential here, but your quality of life is going to improve. We're going to improve your risk factors. And hopefully, you know, there may be some reversal, but at least we can help stop progression at the very least, you know, according to what would happen normally. And the feedback is extraordinary once people follow it. So we need to try and get this more data, of course, but we need to get this more inculcated into medical practice as well across the board. and behavior change. So the power of community and the power of group support or medically,

you know, medical group appointments or shared medical appointments can be very, very effective. And we've seen this at even getting people to change their lifestyle is, and the outcomes are almost three times better using groups than actually one-on-one doctor visits. We've done that at Cleveland Clinic. It's really quite interesting data to see. We've done a lot of things to mess up our gut. We've eaten foods that are processed. We're not eating as much plant foods. We're having less fiber.

We're taking antibiotics. We're born by C-sections. We're taking other drugs and mess up our gut like acid blockers and anti-inflammatories. All these things are driving this ecosystem to be out of balance and that seems to be leading to more obesity more disease more chronic illness across the spectrum that's one way to put it i think it's hard i don't like characterizing the gut is out of

balance or good or bad because it's never so easy as a single switch on and off. Good, bad. Each particular pathway you look at is everything is different shades of gray. But yes, the shift is happening and it's undeniable. And one of the things that is the most astounding is, as you mentioned, you can take an obese mouse or even human and harvest microbes from the intestine, that's the feces, and transplant it into a recipient and show that you literally transmit the susceptibility for things like changes in blood pressure, changes in susceptibility for clotting risk and atherosclerosis and changes in obesity. Amazing. So let me try to understand this because you're a preventive cardiologist, you're focused on the heart. How the heck did you kind of even come up with the idea that you should be looking south?

That's a good way to put it. Well, we weren't looking for this. My background also, as you mentioned, was in chemistry. And we were looking for chemical signals in the blood that actually tracked with and predicted the future development of disease. So we had collected samples of blood from a large number of subjects who agreed to be followed over time. And at the time we collected them, they did not have a disease, but in the ensuing three-year period, half had developed a heart attack stroke or death and the other half had not and so we asked what chemical signatures in their blood predicted the future event and then

basically a large number of those chemical signatures could only have been made by bacteria and that led they weren't human molecules well they are human molecules we didn't realize they were there the vast majority of the compounds in our plasma we're still trying to figure out what the structure is believe it or not yeah and um so when we finally figured out that these compounds in the blood could only be made by at least some point in the lifetime of bacteria to help make that compound then we put two and two together and said well the the majority of the bacteria in our bodies are actually in our intestines and then there was kind of a eureka moment where we said well wow everything we eat goes through that filter yeah and and we're able

to show that both in animals and in humans if you gave a cocktail of like poorly absorbed antibiotics that really aren't normally given orally are only given intravenously, but we could show we would virtually almost sterilize the gut. And then the level of all these compounds in the plasma just plummet and go to near zero. And that's when we really knew that we were onto something that these compounds that predicted so strongly a person's risk, for example, a heart attack could only be made by gut bacteria that's so fascinating so the idea that that uh you discovered that the gut and the heart are connected was a total serendipitous discovery right it wasn't like you were looking for it we weren't looking for it we just saw the we were looking for compounds that tracked with risk we just had no idea to think that they would

involve being made by bacteria so now let's talk about that compound which you're famous for and have won many awards for discovering tmao or trimethylamine n-oxide and this is a fancy word but tmao is easy to remember and it's produced by bacteria apparently in response to certain nutrients in the diet, specifically choline and carnitine, which are high in animal products. That's true. And fish and meat and eggs and dairy. And so you kind of went down this pathway to look at how this is working and how do

you change diets? And you did some early studies comparing how diets of vegans affected their microbes in the TMAO versus meat eaters. And so can you talk about some of that early research and what you found? Sure. So in general, the precursors that give rise to this compound TMAO are more abundant in animal products. And in particular, one of the compounds, this thing called carnitine, is almost exclusively found in red meat. Carni. That's where the word comes from. Carnitine. Yeah, carnivore.

Carnivore, right. Yeah. And in fact, carnitine, when it was first identified, it was named that because of the connection to red meat. But I will point out that choline is in all of us and we all synthesize plenty and it's actually found in bile. And when we eat even a cucumber, our gallbladder squeezes, dumps a lot of bile in the intestine and actually on a molar basis, choline is more abundant than bile acids. So even the vegan and vegetarian is constantly feeding

their gut choline. And so what you do see is that there's a basal amount of TMAO that gets made in everybody. And that has to do with choline constantly being fed to the gut microbes. And there are many different microbes that do this reaction with choline however for people who eat a lot of red meat in their diet what we have seen is that there can be a very dramatic increase in tmao level coming from the other nutrient called carnitine yeah and in fact the more recent studies looking at what's the impact of diet on TMAO level that were done in very carefully controlled circumstances where every meal was provided to the individual over the course of virtually half a year. And they switched from a red meat diet to a white meat diet to a plant-based or non-meat

containing protein source. And what we see is there's about a threefold increase in TMAO in virtually everybody when they're on a red meat containing diet. But where they started in that factor of three can be highly variable. And some of the individuals, you know, even when they eat a fairly good starting diet can have a very high TMAO level. And it's just because of the different microbial community they have. So just like in the same wayial community they have so just like in

the same way you have different susceptibility for developing diabetes and having an elevated glucose level we see even vegetarian and vegans can have a high tmao level but in general it's lower because they're having less of the nutrient but you did say to me before we got on the on the show that vegans have high levels of tmao so So that was confusing to me. They in general do not. But the highest levels of TMAO we have actually ever seen happened to have been in a vegan woman. And we were trying to understand what was going on. And finally, I mean, her level was so high.

We didn't understand. Had to hide in that closet and eat steak or what? Finally, we found out that she would on a weekly basis do a bowel cleanse with a lecithin enema. Oh, fantastic. And so she was putting choline into her body, but from the other side. Oh. And, but the bottom line is, is the gut microbes don't care where it comes from, whether it's

from food. Isn't lecithin from soy, which is. It is. And soy is a so if you're a vegan you're eating a lot of soy is that a source of choline it is a source of choline but we can't get away from it it's an essential nutrient also so you can't like and so it's carnitine right no carnitine we do not need to ingest carnitine at all our body makes all that we need um people who have end-stage renal disease who are on hemodialysis are

constantly having carnitine sucked out of their system with dialysis. And so they will get carnitine back in during dialysis. It used to be that they got it orally, but now most of the time, I think perhaps in response to our research, it's given intravenously and bypasses the whole gut during the dialysis procedure. Yeah, fantastic. So the TMAO does a few things. It actually seems to increase the stickiness of platelets and making them more likely to clot and increase the sort of likelihood of having heart attacks.

Talk about some of the mechanisms of how this works and why you think it's linked to heart disease. Because it's not just the idea that you've seen it in the blood, you actually understand some of the mechanistic ways in which it actually does its damage. So there are two major pathways where we think it's involved. One involves cholesterol, deposits in tissues. And the other, as you mentioned, changes your susceptibility for clotting by changing platelet function. With regard to the cholesterol, the way to think of it is it's like the rheostat on a light switch. Cholesterol is to atherosclerosis what electricity is to turning on a light bulb. You can't have plaque development. You can't have atherosclerosis without cholesterol.

But your susceptibility to the cholesterol level and how bright a light you get, how much atherosclerosis you get can be just like a rheostat switch. And TMAO, when the level is high, you're more susceptible to cholesterol. There's an enhanced propensity to deposit the cholesterol in the artery wall, both going in, in terms of the cells that collect the cholesterol deposits the receptors that are involved in that are upregulated and less ability to move cholesterol out of the artery wall that pathway is inhibited on the other hand we do know that at the platelet side and i mean you can live with cholesterol or atherosclerosis but you die from clotting events like a heart attack or stroke.

And what we do see is that TMAO directly interacts with platelets and makes them more prone to clot. And at a higher TMAO, it's in the normal range, but people's blood will clot faster. And also, if you look at a large scale at the population-based level, over thousands and thousands of people, you see TMAO tracks with risk for heart attack, stroke, and death quite strongly, independent of traditional risk factors. And we think it's through this mechanism. Fascinating.

So going back to the diet part, if you look at some of the vegetables like broccoli or the cruciferous vegetables, quinoa, these often, these often have higher high levels of TMAO too, right? No, they don't have TMAO. They can have choline. Oh, choline is what I mean. They promote. Yeah. But the level per gram of food is much lower than the level of the nutrient precursors of what you find in animal products. So we have to choose something

to eat. I like to tell my patients, we're not air ferns. We need to eat something. So it's always a choice. And what we do see is that eating plant related products is a better choice, perhaps a healthier choice most of the time than animal related products. Although I like to emphasize with my patients that diet is a personal choice. And if they're not really interested in becoming vegetarian to try and emphasize, well, maybe just start with one day a week, you'll do a vegetarian diet. And then over time you say, well, what about two days a week? And the other thing is is you can actually look at your tma level and see

do you need to be more aggressive or not uh you can measure it now it's a commercial test you've developed it is and it's available though broadly across the country uh as a as a blood test and it's yet another way to help personalize dietary choices. Just like we can target cholesterol or triglycerides or glucose, this is now another facet of that. Well, it's fascinating because the dietary implications are massive. And people might be hearing, well, I have to cut out meat and eat only vegetables. But it's fascinating, in one of your original studies, you had vegans who never ate meat versus meat eaters who were eating regularly eating meat. And I'm not sure what the rest of their diet was. And the meat eaters had higher TMAO.

But the vegetarians or the vegans had low TMAO. But when you fed them a steak, their TMAO didn't really go up because their gut bacteria were the kind that didn't produce a lot of TMAO. Right? So what if you ate a diet that was plant rich with a little bit of grass fed meat? Is that a bad thing? I don't think it's a bad thing, but I think that the thing to do is to, to test in the individual, do they have a high level or not? And if they do, then they might try parsing it down in terms of the amount the frequency the portion size um alternatively um if the level now that's not to say that all that tmo is the whole story this is just the tip

of the iceberg it's the first of many many many pathways that we now are recognizing gut microbes are linking to various aspects of our health, mostly in cardiovascular and metabolic is where this has been done. But actually what's interesting is beyond that, even in cognition and behavior, there are connections to microbes. And what's astounding is you can transplant the microbes and show a difference in how fast a mouse can solve a maze

or whether or not it wants to bury marbles and save them for a rainy day. That kind of behavior, it's fascinating, has been linked to microbial transplants and showing shifts in behavior. That's fascinating. You just change the poop out in people and you can give them brain damage or heart damage

or autoimmune disease. So what are the implications for medicine? Because all of a sudden, all the silos are breaking down, all the barriers between what we thought was true. I mean, cardiologists never learn about gut microbiology in cardiology fellowship, but maybe they need to now. And same thing for neurocognitive diseases or immune diseases. And what are the implications for how you have to rethink healthcare and medicine and education? What are your thoughts about that? Well, I think one of the major consequences of this is it really has opened people's eyes to how important, as you mentioned, food is as a medicine, if you will,

and to our health, because that is the clearest, most obvious direct connection that we can impact in terms of chronic dietary patterns shift the composition of the microbes in our intestine. And so that is actually the single biggest influence initially that we can do. But I would say beyond that, we will be developing targeted therapies that actually go after microbial pathways and try to curb them or inhibit them much in the same way you inhibit like cholesterol synthesis with a drug called a statin as you know we're now in the process of developing drugs that instead target the bacterial enzyme pathways and have shown at least in animal models we haven't transitioned it to humans yet that we have drugs that can block the formation of tma and tmao

and therefore inhibit have shown inhibition in diet dependent atherosclerosis and diet influenced thrombotic event rates in animal models so you can have your steak and eat it too actually my favorite study you did i want to know if this is really valid or not was that if you have red wine and olive extra virgin olive oil and balsamic vinegar you can mitigate the effects of tmo so if you have your steak with a glass of red wine a nice salad with olive oil and vinegar does that work it's hard to say but what we what we did see you published it didn't yeah well what we thought what we saw is that we we developed the first drug that we developed for this pathway to block it turned out also because of its structure we thought it was a natural product and so we

screened in our pantries and then were surprised to find that this natural product was actually didn't realize it was a natural product but found it in extra virgin olive oil and balsamic vinegar and grapeseed oil and and so again there's another aha moment and you say oh maybe some of the benefits of a mediterranean diet may might be derived from these kind of compounds that are in these you know in a mediterranean diet at higher level one of the things that's interesting is the compound that we initially were working on uh it's not very potent you need to take it in large amounts so you need a lot of extra virgin olive oil but in uh the mediterranean countries they do it's a lot like a tablespoon tape like four to eight tablespoons a

day a day but that's actually approximately what they do consume. And the other thing we found is that if you cooked the olive oil, you lost the compound because like alcohol, it was a small alcohol, it was cooked out. And what's interesting is here in the United States, we often try, have this obsession with heating our oil and putting things in it and frying. And so actually using the extra virgin olive oil after the cooking is done and drizzling it on top, I preserved the compound in it. So a typical doctor might measure a glucose and an A1C to look at their blood sugar status, and they would do a standard cholesterol profile, which, interestingly enough, calculates your LDL

cholesterol, the one we usually think of as being the lousy cholesterol, from a formula. Doesn't even really measure it. And base most of the decisions on that. If they have symptoms, they might send them to a cardiologist for a stress test. If they have chest pain. If they have chest pain, right. Or shortness of breath on exercise. It's already kind of down the road. Right. But most doctors don't measure C-reactive protein because as I mentioned before, it's like, well, what do we do with it?

What do I do with it? What do I do with it? Oh, statin and aspirin. And then they're probably going to treat them with, if they are pre-diabetic or diabetic, they're going to give them metformin or medications to lower blood sugar and probably a statin to control the cholesterol. How often do they actually talk to them about those root causes such as diet and stress and sleep?

Maybe not. Yeah, they're talking about this poly pill as a treatment, which is this combo pill of an aspirin, a statin, and a blood pressure drug. Yes, put it in the water. Just like give it to everybody. It'll prevent heart disease. I'm like, yeah, okay. Well, why do we have high blood pressure drug. Yes. Put it in the water. Just like give it to everybody. It'll prevent heart disease. I'm like, yeah, okay.

Well, why do we have high blood pressure? Why do we have a need for aspirin inflammation? Why is our cholesterol all screwed up? And you know, it's really interesting. Believe it or not, there's a potential behavioral component for patients who go on a statin and their cholesterol is now normal. It's good. Oh, yeah. I can eat my cheeseburger. I can eat my cheeseburger. Or my fried chicken. a statin and their cholesterol is now normal. It's good. Oh, yeah.

I can eat my cheeseburger. I can eat my cheeseburger. My fried chicken. Isn't that interesting that people change their diet in an unhealthy way when their number's better? One of the worst things I ever read was there was a bunch of cardiologists advocating for selling statins over the counter at McDonald's and fast food restaurants. Oh, my gosh. I think they do sell even statins over the counter.

And it's like those commercials for the acid blockers like take some pepsi because don't worry daddy you can eat your peppers and sausage just take it and i'm like no don't eat the peppers and sausage so you know you kind of mentioned they do it sort of a cholesterol profile, but there was a hint of a subtext in that sentence where they really weren't measuring the right thing. So we tend to look at things that we're used to looking at that are easy to test and measure. But, you know, one of the things that I think people forget, and I think doctors honestly forget, is we get trained in this panel of tests and it's your blood count your metabolic profile and your cholesterol and we measure like a few things maybe it's 30 40 things maybe if like it's a super fancy doctor they'll measure 100 things like and they think they're kind of checking everything. Oh, your tests are fine. Everything's great. You look good.

And the truth is that they're missing a huge amount. There are literally tens of thousands of different molecules in your body all doing things all the time, every minute, every second. And we ignore most of them. And in fact, we may ignore some of the most important ones. And when it comes to cholesterol, we've covered this on the podcast with Dr. Bohm. We went really deep into this. We should just do a quick refresher.

Because the test that most people get, not the one we get here at the Ultra Wellness Network, but the test that most people get is like an antiquated cholesterol test that doesn't really tell you a whole lot. And I have a patient yesterday who was a classic example of that. So tell us about, and I'll tell you about his testimony, but tell us about the new kind of testing that we're doing. It's not so new because we've been doing it for 20 years, but it's like, and the discovery that allowed for the testing was 50 years ago. Yeah. So the focus has been on amount of cholesterol, but we want to know the quality of the cholesterol. So we focus has been on amount of cholesterol, but we want to know the

quality of the cholesterol. So we know, for example, LDL, that's typically labeled the lousy cholesterol. There's big, fluffy, puffy pattern A LDL cholesterol, which is less easily made into a plaque in the artery, less prone to inflammation and oxidative stress and rupture. So it's a less risky LDL, whereas somebody could have small dense pattern B LDL, and that's the really risky LDL. So quality matters. And if you have two people with a calculated LDL of 130, one of them could all have pattern A low risk LDL, and they're actually fine. Somebody else could have lots of those dense particles that's not captured by the calculated LDL of 130. So the quality matters.

The same is true for HDL. We've historically thought of HDL as being the good healthy cholesterol, but size matters there too. Small HDL doesn't seem to be as able to cart out the bad LDL and get rid of it. So we want to know the quality and the size of both the HDL and the LDL. And we want to know what other remnant particles are floating around, like very low density lipoprotein and intermediate density lipoprotein. And those don't show up on a typical panel. Yeah. So practically what you see is people come in with what looks like a normal cholesterol.

Like this guy yesterday has early dementia. His i think was 160 something sounds good yeah his lbl was i think under 100 his triglycerides weren't bad his hdl was 39 which is kind of low um but we looked at his particle number even though his lbl like if your regular dog oh that's a great 160 that's a great cholesterol they missed the boat because his particle number was was like 1500 it should be under a thousand wow and his small particles which should be like zero or less than 300 is you know you can live with but anything over that is high his was 900 wow he was like, and he was a skinny older guy, was 84 years old and had, you know, lost muscle, belly fat, you know, underweight, over fat. And he was pre-diabetic and that was driving some of his dementia. But they were, oh,

your cholesterol is fine, not an issue. And we also look at a lot of other things besides that. And by the way, you know, in 2021, no one should get the regular cholesterol panel. I mean, you got to insist from your doctor. You can get it from LabCorp Quest. It's called NMR or CardioIQ. It's so important to do. And I guess, you know, the problem is most doctors won't know what to do with it once they find it. There's no drug for it.

Like, oh, your LDL is high, we'll give you a statin. It's like we treat what we can easily test and find, not necessarily what the right thing is. And so with heart disease, you know, it really is a metabolic issue. It's, you know, they shouldn't be called cardiologists, they should be called cardio-endo-immunologists. Right. Because it's all about the hormones, including insulin, and all about the inflammation, the immune system. And you mentioned earlier that study by Paul Ritker and Libby,

in which it was sort of the beginning of the conversation. A lot of the follow-up studies, like the Jupiter trial, they found that if patients had a high LDL, but they didn't have a high CRP, their risk of heart disease was negligible. But if they had a high LDL and a high CRP, that was the problem. So independent of inflammation may not be an issue. And also, you can get falsely confused by cholesterol tests. You've seen these patients who were, and I don't mean to stereotype people, but it was this kind of cohort of women who were probably in their 70s and 80s who were thin, who were fit. The ladies we see at Kenya Ranch who like exercise, eat well, don't smoke,

normal blood pressure, no diabetes, and their cholesterol is 300. And their HDL is 100. And their LDL is like, I don't know, maybe 150 or something. And they have no small particles. And they have all these large fluffy things. And they're in really no risk for heart disease. And they don't need a statin, right? I even asked Peter Libby, who's the chair of cardiology at Harvard,

like, do these women need a statin? And they're like, no, they don't. We don't have any data to say that they do. And I'm like, oh, that's interesting. So we kind of have to be really personalized in our approach. And that's the other feature of functional medicine. Not like one size fits all. Everybody gets the polypill. Everybody gets the statin aspirin and blood pressure pill. Like, no, we have to start to think about what's the cause. And the heart disease is a symptom. It's a syndrome. There are many, many causes. So let's talk about this whole

idea of metabolic health because, you know, we were chatting a little earlier and it's staggering to me as a physician just how poor our metabolic health is. So how healthy are Americans metabolically? Yeah, not very. So a recent study was looking at the Haynes data from 2009 to 2016. Government surveys. Government surveys. All of our blood tests and health records and everything, right? A recent study was looking at the NAHANES data from 2009 to 2016. It's a government survey. Government survey. All of our blood tests and health records and everything, right? And trying to say, well, how many people are what we would call metabolically healthy?

And if you're not familiar with it, for people who may not be familiar with that term, it's sort of meeting the optimal numbers for a blood pressure less than 120 over 80, HDL levels being in the high range, a good range, greater than 40 for men and 50 for women, having triglycerides that are low, having a glucose that's less than 100. And they found that 12.12% of Americans- 12.2%. 12.2%. Thank you. 12.2% of Americans were metabolically healthy. Which kind of means that almost 88% of Americans are metabolically unhealthy.

And since 75% of people are overweight, there's another 13% there. Yes. It's like, what's going on with the skinny people? Well, and that's the interesting piece. Fewer than one third of so-called normal weight people were metabolically healthy. So that's another really important message. Wait, wait, wait, wait. Did you just say that two thirds of skinny people are metabolically unhealthy and have prediabetes like syndrome? Yes. Two thirds. That's mind boggling to me. Okay. So that means that what, like 95% of Americans are metabolic?

No, no, no. It's still the 88%. But we're looking at how strongly it correlated with weight. That's so terrible. So just having a body mass index that's less than 25 is not a guarantee that you're metabolically healthy. So if you're a skinny sugar and bagel eater, don't think it's fine because you're skinny. Exactly. It's basically the bottom line. Exactly.

Because foods have other impacts besides just what they do with cholesterol anyway. Foods directly impact the elasticity of the arteries, for example, which is another key player. You mean food is more than calories, Cindy? Food is information, Mark. You said that for years. It talks to our genes. It talks to our systems. Yeah. Wow. So you're talking about how the food impacts our metabolic health. And we're not really good at diagnosing metabolic dysfunction. I mean, 90%... I mean, okay, one out of two Americans has prediabetes or type 2 diabetes.

And if you look at this new study, I would argue that nine out of ten Americans have some degree of prediabetes or type 2 diabetes. Like 90% of Americans. So when you look at that data and you also look at the parallel data that 90% of Americans with prediabetes are not diagnosed by their doctor, that's terrifying, especially because this is a 100% reversible, preventable, treatable condition. And it gets worse and worse over time. And people just don't even know they have it. And doctors miss it because there's no pill to take. Oh, tecmetformin. Well, that's not going to help, right?

It's like, and so what are the kinds of ways that we look at these patients differently? What are the tests that we do? What are the things that we really focus on? When someone comes in with a risk of heart disease and they're concerned about heart disease, you know, what's our approach? It's not just looking at the typical cholesterol and even CRP. Yeah. So we would look at those, of course. We would also want to know what is somebody's insulin. Most doctors measure glucose, but not insulin. I personally like to look at somebody's glucose trends over time. Because if you think about something that's preventable,

you don't want to wait till they cross that threshold to pre-diabetes or diabetes. So even in the range of so-called normal glucose mark, you know this, somebody who's fasting glucose runs less than 85 is in a very different metabolic place than somebody who's fasting glucose is 95 to 99, even though they're both technically normal, that it's a spectrum of risk. And the farther along you march that spectrum, the higher the risk of heart disease and diabetes. So if somebody's glucose used to be 85, and then it was 91, and now it's 98, we're going to talk to that person right off the bat about all the things they need to put into place to prevent it from progressing, because they're already on that spectrum.

We also want to know insulin levels, not just a fasting insulin, but sometimes the insulin response to food. Because the other thing that's emerged is insulin is a player. And way before somebody's blood glucose goes up, they might be pumping out tons of insulin to try to keep it in a good place. And insulin by itself contributes to inflammation and more weight gain around the middle, that visceral adipose tissue. So we want to know their insulin, both fasting and in response to a challenge. So wait, wait, wait.

Are you saying that sugar, not fat, that's causing heart disease? And sugar, the thing that's driving the insulin? Because fat doesn't cause insulin spikes. Well, there is some, I mean, fat is a player. Fat by itself. Fat by itself is a player. If you eat fat with other food, it will.

Yeah. Yeah. And I would say that quality of fat does matter. And we can talk some more about that, but I think fat plays a role with artery elasticity, which is another component of vascular risk. Yeah. So fried foods, trans fats, refined oils, those are nasty. Absolutely.

But fat itself, if it's made from whole food sources and nuts and seeds and avocados and olive oil. Might actually be beneficial. Actually beneficial, yeah. So what you're talking about is a set of diagnostic tests that are so important but mostly ignored. So the particle size and number number which nobody's doing and the second is not just measuring your blood sugar a1c which may be perfect and you may be in really bad trouble but measuring also insulin in response to drinking like a couple of cokes right i i have a patient cindy that i remember who was a super high risk

for heart disease and she had I mean she looked like the Tasmanian devil and she was just like a round apple ball like this and her belly was like this big thing and I'm like this woman is in big trouble and she's inflamed she's high risk for heart disease high blood pressure diabetes and I'm like let's check her glucose tolerance test with insulin and this is you know this is like 20 plus years ago and no one was like looking at this even today no one's looking at this it's like so hard I mean it took 50 years from the time the guy said hey we should wash our hands before surgery for us to wash our hands you know McKinley died President McKinley because he

got shot in the belly and the doctor McBurney stuck his finger in the wound to check it out without washing his hands you know know, that's like crazy. It took 50 years from the time the guy said, let's do a stethoscope so we don't get lice jumping into the doctor's hair to start using the stethoscope because the doctor used to put their head on the patient. So it takes forever and we've been doing this. Anyway, this woman, I did this test. I gave her this drink and it was the most shocking thing I'd ever seen.

And it taught me so much about what we miss in medicine. Her blood sugar was perfect. did this test i gave her this drink and it was the most shocking thing i'd ever seen uh and it taught me so much about what we miss in medicine her blood sugar was perfect like 80 like and and she took the sugar drink and it was like perfect like like it never went over 110 after taking like the equivalent of two coca-colas you know she's fine her a1c was perfect her insulin normally should be under five fasting and under like 25 or 30 after a drink her insulin was like 50 fasting wow and like 250 after a drink so her body was just pumping out insulin which was making her hungry slowing her tablets putting fat in her belly cells which which were basically inflammation factories, and leading to this perpetual cycle. And she was able to lose 50 pounds like that when we cut out

sugar. And I just feel like, you know, that showed me so much because you can even do a normal glucose tolerance test. And that looks perfect. And if you were super hyperinsulinemic, you're going to miss that patient's real problem. And you know are super hyperinsulinemic, you're going to miss that patient's real problem. And it's interesting, Mark, because that scenario is also associated with that cholesterol profile we talked about with the small dense LDL and low HDL and the sequelae that we usually link to diabetes, fatty liver, peripheral neuropathy, all these other organs that are affected. And it can happen with the high insulins alone before the sugars go up yeah it's a metabolic imbalance yeah so that's really the take-home here is that in

heart disease is really a hormonal issue or on insulin and insulin resistance and inflammation issue unless you address those two things not with aspirin and statins which will work to some degree or statins, which will work to some degree, or metformin, which will work to some degree. And by the way, high blood pressure, which just goes along with all this stuff, they're all seen as separate. High blood pressure, cholesterol, diabetes, they're seen as separate. They're the same condition. They're manifestations of the same underlying biology of insulin resistance. And unless you really know how to look at the metabolic pathways in the right way, like we talked about insulin testing or the cholesterol or the cause of inflammation,

because like you said, insulin in resistance is probably the biggest cause. So probably the biggest cause of inflammation is diabetes, prediabetes, and the starch and sugar that we about a pound of each every day in America. That's the problem. But there are other factors that also contribute that people don't think so much about, especially cardiologists. So those are the big ones. And of course, you know, exercise, sleep, stress, all those. We've covered those on other podcasts.

Relationships, connection, community, really important. But there's some other factors that are a little unusual that we look at in functional medicine that I'd love to dive into that have a big impact. So can you just share some of some other factors that are a little unusual that we look at in functional medicine that I'd love to dive into that have a big impact. So can you just share some of the other factors that could drive inflammation? Well, yet another example where the gut microbiome seems to play a role. and look at these microbial patterns, there's a so-called microbial signature that strongly predicts insulin resistance, diabetes, and cardiovascular disease. And a couple of general scenarios you see is there's a loss of overall microbial diversity

in the gut. There's a loss of a couple of signature species. One are the phyla that produce this signaling molecule called butyrate. Butyrate plays a role as fuel for colon cells to help them replenish and be healthy. And it's also an anti-inflammatory molecule. And another species called Acromantia mucinophila. And you can kind of tell from the Latin mucin base that it's a mucus loving bacteria. So that pattern of low diversity, loss of butyrate and loss of acromantia

correlates with loss of integrity of the gut lining, more absorption of unwanted things into the bloodstream, more calories, and more inflammation that in turn exacerbates insulin resistance. So the question is, is it chicken or the egg? Because we know that pattern also shows up in response to diet, of course.. You mentioned metformin earlier, right? And we used to think that metformin helped our cells respond to insulin better, but it also has a microbiome effect. Interestingly enough, there was a study that found that people who took metformin, you saw a rebound of microbial diversity, a rebound of acromantia, and a rebound of those butyrate species. With metformin. With metformin, which I think is fascinating, right?

The way we think drugs are working may actually be completely different. We call those side effects. We call those side effects, right? But we also know in functional and integrative medicine that we can achieve the same thing when we encourage people to eat a diverse array of plant-based colorful plant-based foods and foods that are really good for rebound of acromantia, like polyphenolic foods, berries, deeply pigmented berries and greens and garlic and onions and cranberries. Right. So of course people want a pill,

but there are other things that can potentially achieve the same thing. 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. I hope you enjoyed this episode of The Doctor's Pharmacy. Make sure to check out Gut Food and learn more at gutfood.com. And I want to tell you about something else I'm doing, which is called Mark's Picks. It's my weekly newsletter. And in it, I share my favorite stuff from foods to supplements to gadgets to tools to

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