 Okay, I'd like to get started now. Everybody, the next speaker, the next speaker is Dr. Linda Frosetto from UCSF. The talk is Paleo Diets and Blood Pressure Control. How do we think it works? Yay. Thank you all for being here. Hasn't it been really great so far? I have to say, I feel like I've learned an awful lot. Like, I'm not going to say a word about statistics, period. And as a kidney doctor, I actually really appreciated Chris Masterjohn's talk on calcium and vitamin D, because that's something that we do all the time. So really, I'm really glad and thank you all for being here. So two years ago, I gave a talk on paleo diets and diabetes, because as a kidney doctor, we really deal with high blood pressure, diabetes, and people who are overweight. So it's something that I'm really interested in. And so today, I'm going to talk just a very little bit about how does your body control your blood pressure. And then I'm going to talk a little bit about where does the idea of salt sensitivity come in? Like, how do we decide who is salt sensitive? And what does that mean? And then finally, the last three things on this list. So the various chemicals that make up the diet, the importance of weight loss, and damage to the blood vessels. This is where I think, these are sort of my ideas about where I think paleo diets have an effect and where I think it's important to, in terms of the pathophysiology and the mechanisms behind blood pressure control. So first off, how many here in the audience know what your blood pressure is? Yeah, not too bad. So we'll be a test on this after the quiz. So in the background of all of this is genetics. So this is a very complicated system. And for all of these various things, there are genetic differences so that it's one of the reasons why it's been so hard for us to do blood pressure control and try to decide how to get people's blood pressures really well controlled, because there's lots of different systems that you can use. But generally, when you need to raise your blood pressure right away, your brain sends signals to the nerves in the body that cause the blood vessels to constrict. And then it sends signals, chemical signals, that help the blood vessels constrict. And it sends signals to the heart to make your heartbeat faster. And so that helps raise your blood pressure. The blood vessels are thinner, the heart is beating more, the blood pressure goes up. And then if you need to have your blood pressure up for a long time, and it's good to have good blood pressure is because that way you get blood to your brain and that's important. And if you need to keep your blood pressure up for a long time, then the signals, the nerve signals and the chemical signals tell your kidneys that you need to retain sodium. So when we talk about salt and blood pressure, one of the main reasons that we do that is because kidney retention of sodium is such an important part of raising your blood pressure, increasing the sodium that's reabsorbed into the body causes you to reabsorb more water. You have more fluid in the system and just having more fluid in the system raises the pressure inside the pipes, which are the blood vessels. And in a sodium poor environment, that's great. That's exactly what you want. But that's not what we have. And so in a sodium rich environment, you find sodium literally in everything. So you find it in bread products, you find it in dairy products, you find it in processed foods over here. And I didn't know this, but you find it in poultry products too. When we did one of our studies, we send our diets out for chemical composition and we got one of them back and it was really high in sodium. And it turned out that that was the turkey roll because they put the turkeys and brine in order to make them juicier. And so it turned out that unexpectedly, like the turkey roll had all the sodium that we were trying to put in the entire diet. So I didn't realize that they did that. And despite many, many years of people telling you that you need to eat more salt, in general that never happens. And in general, this is from N. Haines, people tend to eat the same amount of salt all the time, no matter what. And it tends to be in the medium and high category. And so this is, this over here is 100 millimoles and then this over here is, up here is about 200 millimoles and that would be considered to be an extremely high sodium diet. I'm going to, excuse me, my slides are going to switch back and forth from milligrams to millimoles. So just so you have an idea of what's what. But in paleo diets where, you know, back many, many, I'm going to say, hundreds of thousands of years ago, when the salt was not something that was added to all the food that we eat, the sodium and therefore the chloride content of our diet, so the sodium, and therefore the chloride content of our diet was really low, and the potassium was much higher. And in a lot of foods, potassium is also linked to alkaline salts, especially in fruits and vegetables. So if you're getting a lot of your food from plant sources, you're going to be eating a lot of potassium alkali. So in the old days, you had a lot of potassium alkali and very little sodium chloride, and that's not what we have now. And I got into this because we started, we were looking at what are the, what are the acid base effects of eating a high acid versus a low acid diet, and I'm going to talk about that just a little bit in a few minutes. Okay. And these slides are from staff in Lindeberg. So he looked at these people that live in the middle of the Pacific Ocean, a couple hundred miles east of Papua New Guinea on this little, tiny island called Kitava. And the people in Kitava eat basically a plant-based diet with fish. And you can see here, this is data from the InterSalt study, so this is systolic and diastolic blood pressure. And this is about where the Kitavans fall. And so they don't eat a lot of salt. Okay. And they do eat a lot of plant-based products. And it turns out that even if you eat a lot of salt, okay, like over here, okay, if you also eat a lot of potassium at exactly the same time, it actually makes your blood pressure go down. And that's because potassium is what we call a direct arterial vasodilator, which means that if you have a piece of aorta and you put potassium on it, it'll cause the aorta to dilate. So potassium directly causes the blood vessels to open up and that causes the blood pressure to fall. And it doesn't really matter whether you give potassium to young people who tend to have high blood pressure or to old ladies who don't have high blood pressure. Potassium makes the blood pressure drop. So that, and this has been known for many years. And this is, this was one of the reasons why they put the DASH diet together because they wanted to look at things like this. And here is the DASH diet. So the DASH diet was a really amazing diet study where they actually had all these people and they gave them the foods for, they actually made them, made the foods and then they gave it to them for four weeks of time. And they did two separate things. So one thing that they did was they lowered the amount of salt in the diet from high to medium and medium to low. But then the other thing that they did was they also put them on a much higher fruit and vegetable diet. So this is a high potassium diet. And you can see here just like I showed before that just adding potassium to the diet was enough to make the blood pressure drop and actually drop a fair amount. And then lowering the sodium in the diet caused the blood pressure to drop even more. And so when you talk about blood pressure it's not just the salt in the diet. There are other things that also affect blood pressure and if you eat enough of them they can really make a difference. But then the other thing that the DASH diet showed us was that it doesn't affect everybody the same. So people are not all the same, the genetics are not the same and there are so many different things that control blood pressure and each individual person is going to have some mixture of these various things that control blood pressure. And so, and we know that if you have a family history of high blood pressure the chances are you're going to have high blood pressure. There are some people who have very specific mutations in their kidneys that cause them to have high blood pressure. So we know that there's a genetic component. And so you can see here that some people like black people with hypertension anybody with hypertension tended to have more of an effect when they put them on the diet than the people who didn't have high blood pressure. Okay? So here are the people on the DASH diet who had normal blood pressure. Here are the people who had hypertension and here these are middle aged women who tended to be overweight in this study. So you can see that some people responded more than other people. And so when you're treating people with diet and you want to try to get their blood pressure down and ask yourself, you know, I mean, if it doesn't work, it may not work very much because they may not have that much of an effect from doing this. So everybody is different. You know, they recently changed the blood pressure rules. So just about, I don't know, maybe four or five months ago now the new commission came out with the new rules for what blood pressures are. And so it used to be that we were trying to get everybody's blood pressures to like 125 over 75. And the new rules now say 140 over 90. And I listened to somebody give a talk about this and they said, yeah, but, you know, that's just sort of like a generalization. So what you have to do is you have to look at the individual person and say, you know, what works for this person? So I'm a big fan of like knowing what the rules are but then being able to actually say, and how about for you? You know, what should you have? Okay, so now let's talk about salt sensitivity, which is one of the reasons why not everybody responds to the same diet. And salt sensitivity means that if you eat a lot of salt, your blood pressure will go up. And the more factors you have for metabolic syndrome, so the more likely you are to be overweight, hyperglycemic, hyperlipidemic, not just overweight, but have truncal obesity as opposed to all over obesity. So the more likely you are to have these things, the more likely you are to be salt sensitive. And so what that means is even if you have, you know, even if you don't have high blood pressure, you know, if you end up being fat, okay, you end up having high lipid levels and you end up being hyperglycemic, chances are you're also going to have high blood pressure. And as a kidney doctor, this is what I see. And so you can see here this is, these are done in normo-tensive blacks, some of whom were salt sensitive and some of whom were salt resistant. And they come, this study was done on the research center where I work. So they come in and they're fed a very specific diet. And this is a very low sodium diet. And then they go to a very high sodium diet. And in the salt sensitive people, you can see that their blood pressure just goes up and up. But in the salt resistant people, I mean, essentially there's no change at all. And the younger you are, okay, the more likely you are to be in this group over here, the younger and healthier you are, the more likely you are to be in that group. And we think that one of the reasons that people are salt sensitive is because they don't make enough nitric oxide. So nitric oxide is another one of those things that makes your blood vessels dilate. And this is a balance. So on the one arm is nitric oxide and on the other arm is endothelin. So as the nitric oxide levels go down, the relative balance of endothelin to nitric oxide goes up. And so your chances of having your blood vessels constrict go up. So people who are salt sensitive actually lower their nitric oxide levels as compared to the people who are salt resistant, who markedly increase their nitric oxide levels. So as you feed them more and more salt, their blood vessels dilate more and more, which allows them to keep their blood pressure normal. Whereas in the people who are salt sensitive, they lower their nitric oxide levels. This causes their blood vessels to constrict, and so therefore their blood pressure goes up. And we have just very recently found some of the transporters, which are in the kidney, which we think may be actually partially responsible for you being salt sensitive. So there's a genetic component to this and there's an environmental component to this. And one of my colleagues, Curtis Morris, believes that some people are sodium sensitive, some people are potassium sensitive, some people are chloride sensitive, and some people are bicarbonate sensitive. And so if you have really bad luck, then you have all the bad factors, and if you have really good luck, you have all the good factors. Each of these is important in and of itself, and in rats that are specially bred to develop high blood pressure, the more chloride you give them, the more their blood pressure goes up. And chloride is another one of those things which is in a balance. So the higher your chloride levels are, the lower your bicarbonate levels are, and vice versa. So if you feed people more chloride, then you lower their bicarbonate levels. And in fact, you increase the acid in the body, so their acid balance actually goes up. And so acid indirectly affects lots and lots of things, including the insulin receptors in the cells, as well as activating the osteoclasts in the bone. So you start to break down your muscles. That is in order to be able to send glutamine to the kidneys so you can get rid of the extra acid. And you start to break down your bones in order to release the alkaline matrix, which is trapped in the bones, in order to, again, balance the amount of acid in your body. Your body really hates having extra acid in it. And so in our studies, when we put people on, and this just shows what I just told you, which is that the more chloride you have in your body, the higher your hydrogen ion levels are and the lower your bicarbonate levels are. So you have more of a metabolic acidosis. And in our recently completed study, where we had type 2 diabetics that we put on either a paleo diet or an ADA diet, we expected that there would be no change in acid levels in the ADA diet. On the other hand, our paleo diet, which is about 40 to 45% calories from carbs, which come from fruits and vegetables, 25% calories from protein and the rest from fat. Then in this diet, what you see is that the acid levels from the paleo diet went way down. And in the salt sensitive people, what you see is that as the urine pH increases, which means that the acid levels are going down, their blood pressures tended to drop the most, whereas there was no relationship at all in the people who were salt resistant. So really, again, something about being salt sensitive that makes you particularly seem to respond to a paleo diet. And just in case you don't know, high blood pressure is bad for you. And really, it's because it damages the blood vessels. High blood pressure and diabetes is a blood vessel disease. And so it damages the blood vessels in the brain and in the eyes and in the heart and in the kidneys and in the periphery. And so when you have people who have, when you have people, for example, who are on dialysis, it's not just the kidneys that don't work. Nothing works because the blood vessels are completely shot. So talk a little bit about dying from high blood pressure and how much salt. How much salt is bad for you? You know, this has been argued for, you know, what, 50 years, 70 years, something like that. The Institute of Medicine has never really wanted to come out with sodium guidelines because of the various studies that, you know, show one thing or another. This is the most recent meta-analysis that I could find. I said I wasn't going to talk about statistics. But I do think that it shows that when you're talking about really high sodium levels, so that's where the more than 5,000 milligrams comes from. Chances are you're more likely to die because your blood pressure is high if you're eating that much sodium. And I think I'll skip this slide over here, no statistics. What about the other end? You know, like how little sodium do you need to eat in order to be able to be okay? And here I think that, you know, really, the answer is it's a little hard to decide because, you know, maybe you can't tell from these kinds of studies. Or maybe, and this is what the author said, maybe it's a U-shaped curve. And in medicine and in clinical medicine, they talk a lot about U-shaped curves because too high is bad and too low is bad. So you want it to kind of be there in the middle. It's just a question of where do you set the limits of what's too high and what's too low. And I'm not sure that we have an answer to that yet. And I'm not sure that you can look at this and population studies like this because I really think that here you have to individualize it. But this is what the literature shows. Okay, so another thing I said that high blood pressure causes kidney disease. So that's, and presumably, high sodium chloride causes kidney disease. But if you add bicarbonate to people's diets, and this was done by somebody who works in Texas, Donald Wesson, what he was able to show is that just adding bicarbonate to people's diets over time slowed the damage that they were having because of their high blood pressure to the kidney so that after five years, the people who are on the bicarbonate had better kidney function than the people who are on either sodium chloride or on placebo. And he was able to show that what was happening was that the people who are on the bicarbonate had lower levels of endothelan. And remember, endothelan is one of those vasoconstrictors. So that meant that it would raise your blood pressure. So these people had lower levels of endothelan and lower levels of aldosterone. And so this is from the Renan angiotensin-aldosterone axis, one of the well-known accesses to raise your blood pressure. So two separate accesses where you had lower levels in the group that got the bicarbonate compared to the group that got the sodium chloride or the group that got the placebo. So maybe, okay, just like you can use potassium in order to be able to neutralize the effect of the sodium, maybe you can use bicarbonate to neutralize the effects of the chloride and age. So interestingly, in these people who live in, let's say, the rural areas of, let's say, Africa and the Solomon Islands and New Guinea and whatnot, ones who tend to eat a very low sodium diet, their blood pressure doesn't go up with age. But in any study that you look at done in Western cultures, blood pressures go up with age. Okay, that's extremely common and it was actually thought to be normal many years ago. In addition to that, as you increase your sodium intake, if you happen to be salt sensitive, it also increases your insulin levels. So now you tend to have high insulin levels. And I'm not going to talk about insulin resistance today, but insulin resistance is another thing that would make you even more salt sensitive. On the other hand, when you looked at people who were put on paleolithic diets, and this is from the Swedish group again, where they had people who had atherosclerosis and then they put them either on a paleolithic diet in the white circles or their diabetes diet in the black circles, these people tended to have lower blood pressure when they were on the paleolithic diet. And they also tended to lose more weight. And it turns out that weight loss in and of itself helps people's blood pressures. So over here, this was a study done in about a thousand older people. And so people who were randomized to the weight loss group, just like people who were randomized to the sodium group, they both had a lower incidence of this is free of end points. So these are, this is cardiovascular events. So they either had a heart attack or they had a stroke or they had an anginal episode that put them in the hospital or they developed heart failure. So both weight loss and salt reduction tended to decrease their chances of having these bad things happen to them. And when they put them both together, it worked even better. So not only do you have to lower your sodium intake, but you need to lose weight too. And if you look at the people on Kitava who have essentially zero incidence of heart attacks or strokes or diabetes or high blood pressure, they also tend to be much thinner than their Swedish counterpoints in this study. And as they get older, their blood pressure doesn't go up. So over here is the average blood pressure of the Swedish people as they got older, eating their 3.4 gram sodium diet. And over here are the Kitavan people who are eating their less than 1 gram sodium diet. So you see, not only didn't their blood pressure go up, they are significantly thinner than their Swedish counterpoints. So again, you know, they're not eating the same diet. They're eating a lot more potassium. They weigh a lot less. And in fact, and this is in our study, done with couch potatoes after two weeks, if you put them on a treadmill test, they can do the same amount of exercise, but they do it at a lower blood pressure with a lower heart rate. And so, really, this kind of diet is really good for your exercise parameters too. So finally, I want to talk a little bit about damage to the blood vessels, because if the blood vessels are shot, then you're going to have trouble trying to lower your blood pressure. So over here, this is a nice, clean aorta, so full of nice, great elastic tissue that can contract and can relax. And over here is an atherosclerotic, obviously grubby-looking aorta. And over here, this is an x-ray. So this is a plain x-ray of somebody. And see over here? See these little white things over here? These are his calcified blood vessels. There is no way you should be able to see these on an x-ray. So see that they're almost as white as the bone over here? So just imagine if this was your plumbing, what your pipes would look like if they had this on the inside, and then they were turned into solid rock because of the calcification. These blood vessels can't respond at all. So when you see this kind of thing, then you can expect people would have higher blood pressure. And I'm going to skip this slide. So let's talk a little bit about atherosclerosis. So one of the reasons that the Cochrane, that the Institute of Medicine never wanted to say anything about sodium intake was because on extremely low sodium diets, people's lipid levels actually increased. And so they were afraid that if they told people not to eat a lot of salt, that that would actually make it atherosclerosis worse. However, on the Danish diet, they never were able to show that there were any changes in lipids, either because of the diet or because of lowering the salt. So then people began to think, well, maybe changing it to this range of sodium. So this is about 50 millimoles, which would be about 1,500, 1,200 milligrams a day. But we were able to show, and again, this is in our Type II Diabetics, is that some people really improved their lipid profiles, and some people didn't so much. So the people who were salt sensitive, even if they were on the control diet, tended to have more decrease in their lipid profiles than the people who were salt resistant and blue who are on the paleo diet. And they also tended to have better glucose control. So, you know, again, maybe a paleo diet works for everybody. Maybe it particularly works for some people, but it may actually affect the amount of atherosclerosis that's damaging the blood vessels. And if you look at cardiovascular risk factors in the ketavins, you can see that their blood pressures are low, their glucoses are low, their lipid profiles are low, their insulin levels are low. This occurs in both men and women. Basically, all the things that are bad are really low. So, I mean, is it any surprise that the ketavins, okay, don't have high blood pressure compared to, excuse me, the typical western person? You know, really, I would be amazed if, like if they all had high blood pressure, you'd have to ask why, you know? And so, when you look at blood pressure control, remember that it's multifactorial, okay, that there's a genetic component, that there's an environmental component. That salt does make a difference, but it particularly makes a difference to some people. And the more likely you are to have metabolic syndrome, the more important it is. I think that weight loss can improve blood pressure control. And I think that on a paleo diet, if, you know, generally, people tend to lose weight. And so, really, I think a paleo diet would help with that. Furthermore, most paleo diets tend to be lower in salt and higher in potassium and alkali than western diets, which, you know, again, may be both directly and indirectly affecting blood pressure control. And then, you know, if you're lowering the amount, if you're improving the blood sugar control, you're improving the lipid control, and didn't talk about this, but you're probably also lowering the calcium intake, then you may be getting less damage to the blood vessels. And so this combination of factors may be important for trying to get people's blood pressures better. It's not just one thing, but a paleo diet does more than one thing. It actually probably does a whole bunch of different things. And so, you know, that's when, so if you're going to say, you know, what can you do and, you know, what's important, I mean, really, I think it's a bunch of different factors. And I want to acknowledge my mentors, Tony Sebastian and Curtis Morris, my team from UCSF, Ashley Mason and Jenny Chen, who helped me do some of the statistics. Staff in Lindeberg and his students, who gave me some of their slides, and our research centers at UCSF, who were the ones who actually did a lot of the diabetes and healthy volunteer studies that I've shown the data on. And finally, just, we're time for questions. I just have one thing I want to say. So we are doing another study, and we're going to be doing it in people who are insulin resistant, because we think that insulin resistant people respond really well to paleo diets. And this time we're going to use PCOS, and we are crowdfunding this. And we're using the money to pay for the labs and to pay for the materials for the studies and to draw the blood and process it and freeze it. We're not being paid anything, so we're all volunteering our time. And we need your support, so we need you to go to this website over here and give us some money. But even if you don't, talk to other people about this, because I think it is really important for us, excuse me, us the paleo community, to prove that we can prove that paleo diets are good. I mean, people now, you know, it's so tiring to hear that there's no data to back this up. Well, really, support the research that does the studies. So really, let me just put my plug in for that. Okay, now I'll take questions. Three minutes. Yes? I can't hear a thing. Sorry, the fans are in the way. How did the Texas Group accomplish the high bicarbonate diet? What did they add? What did they add? They added potassium alkali or sodium alkali. I mean, they actually gave it in pill format. This is more an anecdotal observation than anything else, but blood pressure control is the one thing that I can point to personally that was measurable, a measurable change in myself. And this was 12 years ago when paleo went even on the map. And seriously, I was looking at this as a performance enhancement diet. And I had elevated blood pressure for the longest time, could not figure out what the deal was. Was a healthy person, healthy, you know, 12 years ago, thought I ate a healthy diet. And I really didn't need a lot of sweets or anything at that time. It was a, you know, people here would consider, yeah, that's pretty healthy with some rice and pasta. That's the type of diet I was eating. One thing that I can point to that changed, as soon as I changed to a straight-on paleo diet, my blood pressure normalized from what was generally 140 over 90-ish to 120 over 80 or 70 now. And I mean, it was immediate. So whatever the change was, it was immediate. When I say immediate within a couple of weeks. And it's never been, it's never been otherwise now. So that's just one observation. I have to say that in our studies, you know, in our research center, we see the blood pressures drop right away. So, yeah. Other questions? Nope. Thank you very much.