Dr. Bredesen, Dr. Rao, and Julie Gregory discuss the paradox of fasting to prevent and reverse Alzheimer’s disease. While Alzheimer’s disease arises from insufficient support for our brains, it seems counterintuitive to recommend fasting, which is essentially taking something away. It helps to understand that this lack of support for our brains is often born of excess. Safely learning to adopt a long daily fast can promote multiple mechanisms, including autophagy (cellular housekeeping), and help create insulin sensitivity which is critical for supplying fuel to our brains.

We’ve included a complete recording of the session and a full transcript below for your convenience.

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Dr. Bredesen: Hi, everyone. I hope everyone is staying safe and just to say today if I’m a little bit slow or appear a little bit ill or get a little bit hoarse, I have COVID-19. So my wife and I recently went on a trip, quote post pandemic trip after full vaccination, with full precautions, etc. Unfortunately, both developed probably the Delta virus. We have a sequence pending, but it looks like it’ll probably be the Delta, which is now 83% of the isolates in the United States. So incredibly common. And so please, everybody out there please stay safe.

Dr. Bredesen: This is a tough time and have to say the fatigue with this virus is a real pain and of course, loss of sense of smell and things like that. But the fatigue has really been the tough part. And of course it affects voice and things like that. My coughing is getting a little better, which is good. But again, if I’m a little slow today, it’s because I’m fighting COVID-19. But we really wanted to get this, Julie, Ram and I, and Lance all thought it would be a good idea to talk about perhaps the most common issue. And it’s something that I think really is a bit of a paradox and misunderstood. What our research showed us over 30 years is that what we call Alzheimer’s disease is fundamental, is at its very heart, is an insufficiency. Instead of being an insufficiency of like vitamin C or something simple like that, it is a complex insufficiency. So you have a plasticity network within your brain and when things are good, you’re making and keeping new connections of course, which we do for our whole lives. And when things are bad on the other hand, when we are under assault, when we have pathogens and toxins and ongoing inflammation and reduced energy and reduced trophic support, you go into a protective mode and you can literally trace the molecular pathways that show that this is what’s going on. And at the center of this sits amyloid precursor protein, which we studied for many years in the laboratory. So when you, therefore, when you’re dealing with this, we’re talking about things like fasting. Well, here’s a situation where we don’t have enough support for this complex neural network. And yet we’re saying, well, we’re going to now take something away. So there’s a paradox there. And here’s the problem. This deficiency is in many cases, born of excess. That is the paradox here. We’re developing the insulin resistance because of our diet that’s high in simple carbohydrates, because of the processed food and things like that, because of the way we eat, because of the eating late at night and short fasting periods. So this is why it’s tricky. We want to balance. Now what’s interesting is this is such a common contributor to cognitive change. Extremely common and there are over 80 million Americans who have metabolic syndrome, for example. And so what happens is when you have glycol toxicity and insulin resistance, in fact it actually hits all of the four major groups that contribute to cognitive decline. So it does give you some inflammation because you get this non-enzymatic glycation, literally like remoras on a shark, the molecules stick, the sugar molecules stick to proteins and they alter both their structure and their function. So you get an inflammation from that. On the other hand, you also get some toxicity. You make things like glyoxal cells that are inappropriate products. Thirdly, you actually reduce your energetic support because you don’t have a normal metabolism. And because you also begin to develop some vascular disease and then fourth, you actually have a reduction in trophic support because insulin is a critical trophic factor for the brain. And you lose that beautiful effect of insulin as a growth factor for your neurons and synapses. So this is a huge issue and there are things where, for example, people with very low BMI will go into too much fasting and hurt themselves. And on the other hand, people who have a very high BMI and may have a lot of insulin resistance, won’t get rid of that insulin resistance because of what they’re eating. So it’s critical. You have to kind of get that passed through the eye of the needle to make yourself both insulin sensitive. You’ve got to get that ketosis in, you’ve got to make it so this whole system is working together and it’s really the first and most important step toward reversing cognitive decline. And of course also very important in the prevention of cognitive decline. So we thought it was really important to, for so many people to talk about this paradox and how we can address it. So, Julie, let’s start with you and talk a little bit about your own experience with this paradox.

Julie Gregory: It’s kind of interesting because I’ve sort of experienced it on both sides of the spectrum. When I began my journey, I was insulin resistant. And so if I would try to fast for any period, I would become hypoglycemic and sometimes acutely so. I once had to call the paramedics. I tested my blood sugar and it stopped reading and just said low, low, it was very frightening. I was starting to lose consciousness. So when the body has been burning glucose exclusively for a number of years, it has a very difficult time mobilizing fat stores. And for that reason, we have people extend the fast especially those that are insulin resistant very slowly. On the other hand, I’m a small woman and my BMI can sometimes drop too low. And when my BMI is low, I have to be careful. I mean, at that point I eat basically two, three times a day until I get to a weight stable, strong place. And that’s what we want for everyone. We want everyone to begin the program at a weight stable, optimal weight. And ideally we want you to have strong muscles and to feel energetically stable before you begin fasting. And if you’re not there, you might need to gain some weight before you start a long, extended fast. Or if you’re insulin resistant, you may need to start very slowly, increase that fast by five minutes a day. You can’t go from fasting four hours a day or six hours a day to suddenly doing 12. It’s something you have to work your way into.

Dr. Bredesen: It’s a great point. And I know that this is one of the reasons that I always suggest people just start with some exogenous ketones, because remember we’re dealing with a couple of things at once. We want to get you into being insulin sensitive because it’s such an important part of the reversal process and the prevention process and metabolically flexible. On the other hand, you’ve got this gap, you’re trying to bridge an energy gap when you begin, if you have symptoms and again, we’ve talked about this. This can be since your late twenties, if you’re positive. So you need to bridge that gap. And as Dr. Stephen Cunnane has taught all of us, you can bridge that gap with ketones. You’ve now got two energy sources. Well, as Julie has pointed out at the beginning, you’re not particularly keto adaptive. So it takes a little time, but so start with that and then ease into it. The other thing Julie mentioned, the hypoglycemia that is a problem in and of itself. People are typically doing this. They’re getting hyperglycemic, which is a problem for your brain. Then they’re getting hypoglycemic, especially when you sleep at night, which is another problem for your brain. We want to smooth things out and your brain will do much, much better. Now it can use ketones, it can use glucose. It’s not seeing the spikes. It’s not seeing the dips; it’s getting appropriate amount of insulin. And most importantly, your insulin receptors and your signaling downstream with IRS one and other signaling molecules is coming back to normal. So I think this is really critical. Ease into it. Take some time, make sure your ketones are there, make sure you’re getting into some insulin sensitivity, energetics from one of the most important parts of this. Let’s take a minute. Ram, could you talk a little bit about how Ayurveda deals with this and how you’ve dealt with your Ayurvedic patients with respect to glycotoxicity and insulin resistance?

Dr. Rao:  Yeah. It’s very interesting, Dale because Ayurveda as well, we have this concept of, talk about the term ketosis, they talk about microbiome, but what they mentioned is they said everyone, everyone should have what they call the term they use is sama agni. If you translate that term, sama agni, I would like to call it as metabolic flexibility. It’s beautiful, it’s just what we want. So they use the term sama agni metabolic flexibility and they said everyone should try to achieve that metabolic flexibility in order, not just for the body alone. They said for the brain and for the mind as well, for the emotions as well. So they knew that there’s a link between digestion, the brain and the emotions. Now here’s what they’ve said. In order to maintain that metabolic flexibility, they said it is always good to have a properly timed meal. Okay. So they said have a big meal when the sun is at its peak. So, which is we know data, the big midday lunch. And then what they said, try to have a light supper or dinner before the sunset. So in those days they didn’t have a clock but they use the sun’s axis and they said before the sun set. So, you know, give and take around 6, 6:30, and then they said, make sure that you leave at least three to four hours gap between the time you had your last meal and your sleep. So now we know they’re talking about a three hour gap between your supper and your dinner. And then interestingly, what they said is in the morning, when you wake up before rushing to the kitchen to eat or to drink, they said, first of all, they said, try to wake up before the sun rises. And now we know somewhere around 3:30 or four or 4:30, somewhere in that ballpark, depending on where you live.

Dr. Bredesen: Wow.

Dr. Rao: So if you’re at four and five in the morning, that’s when, you know, before the sun rises, they said, you wake up and then, you know what they said? They said, instead of rushing to the kitchen, they said, do your mental activities. And they talk about what are the specific mental activity? They said, reading or writing, or, you know, learning scriptural passages, something so that you’re activating your brain. Now, remember you are having a 12 hour fast and then you’re doing a mental training exercise which means you’re breaking up whatever glucose is leftover. Or even if there’s no glucose, now we are trying to break down the fats. And then they said, following a mental training exercise, start a physical exercise. So they will say by then the sun would rise, right? Then they said sun salutations and yoga. So they said 30 to 45 minutes of stretches, physical exercise. And then they say, you can break your fast. Now, interestingly, they said, so this was the, this was the day-to-day pattern, Dale. So anybody can do this. Now, in addition to that, they also said, in order to encourage fasting, you want to get in proper ketosis, get in proper acid. They said, it’s always good to fast. And then they provided a means to do that. They said, you know, in order for people to remember, they said on Mondays so that it becomes easy for people to know. They said on Mondays, try not to have a dinner, just have a lunch. So, which means that it was one meal a day. And then they said on Saturdays, try to have one meal but make sure that it’s only vegetables and fruit. So now they’re trying to move you away from the entire picture of nutrition, into a small aspect of nutrition, which is fruits and vegetables. So people automatically, they said Monday fast, we knew that, they were doing a lunch and they’re not doing anything else. If they said Saturday fast, we knew they were doing only fruits and vegetables. So if at all, they went home to somebody else’s home or they paid a social visit, they would say, I’m observing a Saturday fast. So then they would be fed either fruits of vegetables. Now, in addition to that, they said, okay, now they did all this. And they said, do this. Now, if you’re not able to do a Monday fast, or if you’re not able to do a Friday fast, they provided two days in a month for sure they said this coincides with the new moon and then the full moon. The new moon is a dark phase. And the full moon is the actual, you know, when the moon is at its full.

Dr. Bredesen: Right.

Dr. Rao: For some reason they said it has an influence on digestion. They said, probably we did not know what the scientific merit was, but they said it has its effects on digestion. So they said on those two days, please remember not to indulge in a large or too many frequencies of food. Just try to limit yourself to either one meal or no meal at all. So that gave people a tool. It was like a place holder. They knew either a Monday or they Friday, or if they missed that, they said, okay, twice in a month, one week before the moon rose and the one week when the moon is full you can do your fasting. So this was the way they encouraged that. And now we know the benefits of that. We know the benefits of why they said that, even though they didn’t mention that, they said, it’s very good for your brain, very good for your body and very good for emotions. Now, it’s all built in. We bring in the scientific evidence and we now know why it is so.

Dr. Bredesen: Yeah, we’ve talked about this before that there’ve been so many accurate observations of the Ayurvedic physicians from thousands of years ago. And of course also from the traditional Chinese physicians. And now in the 21st century, we can begin to understand at the molecular level, what these things are all about, why it is that those observations have proven to be correct. So, Julie, let’s come back to you for a minute. If you could talk a little about what you would recommend, if someone’s got a very low BMI and they’re trying to do the best they can for their cognitive change. How should they get started?

Julie Gregory: Right. I think if you have a very low BMI, first of all, we have to say that low BMI alone can increase your risk for cognitive decline.

Dr. Bredesen: Good point.

Julie Gregory: Because it increases the risk of sarcopenia, loss of muscle and osteopenia, loss bone. So that alone is a risk factor.

Dr. Bredesen: And high BMIs.

Julie Gregory: Well and high BMI, but for now, let’s talk about the low, low end of things. So if someone has a low BMI, I am very concerned about a long daily fast. I think the most important thing at that point is to get to a healthy weight, make sure you have enough protein, make sure you’re doing strength training to get the muscles strong. But I understand the brain needs energetics. So at that point exogenous ketones, and also playing around with your macronutrient ratios can be helpful. So these folks can eat up to 70% of their total calories in fat, which sounds like a lot, but it really isn’t. That’s equivalent to about four to five tablespoons of olive oil that you can put on top of all your non-starchy vegetables, a handful of nuts and an avocado. It’s very easy to incorporate high amounts of fat into a healthy diet. So these folks need to get weight stable. They need to get strong. If they change their macronutrient ratios, that’s going to push them towards ketosis as well as using isogenic sources of ketones.

Dr. Bredesen: Yeah. It’s interesting how many times, again and again we see the very things that make you healthy actually have this anti-Alzheimer effect that to some extent there’s a lot of overlap between the ill health of sarcopenia and insulin resistance and sleep apnea and hypoglycemia and metabolic syndrome. I mean the epidemiologists show us that all of these things are associated. So no question, you know, this is a disease that is ultimately a disease of ill health, but the good news is we can now dissect the molecular pathways and say, okay, here are the ones that are actually driving this for each person and really get a very good handle on addressing those.

Dr. Bredesen: So, we have a number of excellent questions here. Let’s talk about some of these. So Leanna is asking, I had a CT of the brain done. They said I have calcifications in the brain. Is that the same thing as amyloid plaques? So good question. They are different. So the amyloid plaques are often not calcified. Calcifications can mean a number of different things. There is a syndrome called FAHR Syndrome, FAHR which is calcifications all over the brain in association sometimes with some degree of degeneration, but that’s very severe. So calcifications in general will indicate that there has been some minor damage there. It can also indicate an imbalance. So for example, if you have a lot of vitamin D, but you don’t have the K2, you can end up putting some calcifications in the vessels, which is why we always recommend when you take your D please don’t forget to take a hundred micrograms of K2. And in fact, there are some ongoing trials where people are trying higher levels of K2 to see if they can reverse some of the calcifications that are vascular calcifications. So you might consider looking at taking slightly higher doses, anything from 150 up to 600 micrograms, or talk to your practitioner about that and ask a little bit about what are these calcifications coming from?

Samantha says slow and steady wins the race. Absolutely important. And I think one of the things that we’re seeing again and again, is that people will skip in their interest in being rapid they’ll skip the fact that, oh, wait a minute, I am getting hypoglycemic. I am getting hyperglycemic, oh, wait, I am having some nocturnal hypoxia and this hasn’t been addressed or I’m not getting into very good ketosis. Like kind of tweaking all these things one at a time to get that optimum, to support your brain is absolutely critical. So I agree with you, slow and steady wins the race and people who are jumping into these severe diets can definitely get hurt by them. I have certainly a personal experience with that. So you want to ease into these and I couldn’t agree with you more. Not only slow and steady, but the steady part, keep once you get on there, keep doing it. And I think Julia is a fantastic example as is Ram. They’ve been doing these these practices for years and they continue to tweak them, continue to optimize them and continue to get , continue to get better and better outcomes.

Let’s see here. And then Liana says, makes sense. Pre-diabetic, cardiovascular disease, some brain shrinkage, memory testing normal range, but tested after I started the recommended supplements post COVID with pneumonia. I feel for you, I hear you. Post COVID tough, pneumonia was when cognition took a dive. And so, yeah, let’s talk about that for a minute. We have a number of people now they will be doing well. They will be doing improved, they’re on the right track. And then they have a major stressor, a kidney stone, pneumonia, a viral infection, COVID-19, head trauma, went on a trip and stayed up all night repeatedly, a tremendous stress in their lives from some event in their family, on and on and on these things will cause you to take a step back. So you now gotta just, gather yourself, keep up and I know Julie, you’ve had multiple of these issues as you were first starting out. You’ve had, you know, everything from anaphylaxis at times to motor vehicle accidents, to, you know, issue, I mean, on and on and on. So you have continued to stick with it. And I certainly agree that keeping with this and continuing to optimize it, as she said, slow and steady wins the race, huge issue. So yeah, so Leanna, I feel for you, I certainly agree. I’m dealing with this myself right now. And my wife is noting some brain fog, dealing with brain fog with COVID-19. So please stick with it, it’s more important than ever. It doesn’t mean that this is not working. It means that you have been working. But now this is basically changing the equation that we always talk about.

And then Wendy says, at what BMI should you not be fasting? What is considered healthy BMI? So we usually recommend a BMI between 19 and 25. Some people would say up to 24, 25, right in that range. If you’re up at 30, you’re likely to have some insulin resistance. If you’re down at 17 or 18, which we see a lot, then you’ve got to be very careful. You may not have the fat to burn. And so you want to be careful. And again, if you’re on the low side, I would start with the exogenous and start with, you getting your weight up just as Julie said, before you launch into this. And then let’s see here, Brian says, what’s the best way to test ketone level and what’s the target? So we usually recommend you can go one of two directions, you can go with BHB, the beta hydroxybutyrate, and you want to do blood, a finger stick, and 1.0 to 4.0 millimolar for BHB. If you go with a breathalyzer like BIOSENSE, they’ve got a nice job with looking at the ability to do this through the breath. They don’t match up perfectly. You’re measuring something different. Now you’re measuring acetone and you’d really like to get up, you know, up there in the kind of 10 to 20 range, it’s typically about a 10 ACEs to 1.0mM BHB. So you can see that you want to get up above 10 and that what you can do is do it multiple times. That makes it easier to do it many times during the day, and you can get a curve and you really want to be sitting up there, you know, above 180 close to 200 or even more on the overall curve, which simply means that your level is going to be something like, you know, over 1.0mM per day. So that’s the sort of, if you’re, you know, if you’re 1.0mM all day and you have a 10 ACEs to 1.0mM BHB, and that’s going to give you a 240 for the end of the day score, so you want to be somewhere kind of in that range. Now, there is a difference in the half-life. If you come out of ketosis, the half-life on the breathalyzer is about eight hours, the half-life in the blood is more like two hours. So you’ll see it doesn’t fall as quickly once you bump it up. All right and then Brian says low BMI does not suggest the insulin resistance of the metabolic syndrome, yeah. We didn’t suggest that it does. Typically insulin resistance is associated with a high BMI. The concern is if you have both, if you have a low BMI and you have some insulin resistance it’s just that much tougher because you have to be so careful.

Tim says my amyloid has been diagnosed with aspirin allergy and glucose metabolism deregulation. And yes, as you can see, there are so many contributors to this amyloid. The amyloid is nothing but telling you you’ve had an insult, you’re not making the supply, meet the demand. And therefore we’re putting you in a protective downsizing mode. It can be from your metabolic syndrome or pathogens or toxins, all the things we’ve talked about. So therefore it’s critical to identify those.

And then Di asks BMI 18, 5’7″, 118 pounds. Hard to gain weight is it okay if it’s been like this consistently? Hard to fast greater than 12 hours. So great point, and you would be a perfect candidate for exogenous ketones if you’re positive. Maybe consider some ketone salts or esters. If you’re negative may consider some MCT oil or things like that. So, Julie, what would you recommend for Di?

Julie Gregory: Well, so I’m going to link a BMI calculator that takes into account gender and frame size. Because I have a very small frame. So my BMI is on the low side as well, but I’m very weight stable at this point. And I’m very strong. So without knowing, Di I don’t know where she falls on that spectrum. But by taking measurements of your wrist and looking at your height and weight and looking at your overall muscle mass, you can sort of determine whether or not your weight is healthy. But certainly I would encourage Di to shift her macronutrient ratios, to being more fat, less carbohydrate, adequate protein. If there’s not enough protein in the diet, your body will cannibalize your muscles, which is something we do not want. And then as you’ve mentioned, exogenous ketones are very helpful until she can get to a weight stable point if she isn’t there already.

Dr. Bredesen: Absolutely. And then Donald asked, does it make sense to take exogenous ketones to extend a fast, or can, should they be consumed at any time during the day, even after breaking fast? Absolutely. So first of all, that’s a great point because when you take them, you are by definition breaking a fast, however, you are still in ketosis, absolutely. In fact, you’re now in more ketosis. So in that sense, you’re doing both, you’re getting ketosis and you are breaking a fast, but not in a way that is giving you simple carbs, which is fantastic. So absolutely you can do that. And then absolutely during the day you want to, you know, your brain is looking for that energy. And in the perfect world, when you get finished with optimizing things, you’re going to have a situation where you’ll use carbs at times, you’ll use fat at times and ketones, you’ll use carbs, you’ll use ketones, you go back and forth. That is by definition, metabolic flexibility, and you’ll be able to burn both of them. And then of course you have to have adequate mitochondrial function to do the burning. You have to have adequate vascular function to supply the substrates. You’ve got to have adequate oxygenation to burn the substrates. So as you can begin to see this all works like a beautiful concert, it’s all working together. And then Ina says, did a few things you suggested in your book and have been doing much better in terms of memory and focus. Always so great to hear that. And the new book coming out actually in a few weeks on August 17th is called, “The First Survivors of Alzheimer’s”, seven wonderful stories of how to do it. And we have a separate chapter there for enhancing normal cognition. So this is huge. Most of us could absolutely do better with our cognition.

And then the next one here is from Liana, who says, since I started your protocol about six weeks before the memory testing, could it have improved my cognition enough to push me into the low normal range? Is that effected that quickly? So we’ve seen in general, it takes a couple of months. The very first person who started, patient zero, who is in this new book, took one month. She noticed clear changes in one month. We have had a person who noticed even after four days, that’s the exception. We’ve have people where it takes six months. You remember, you know, we’re changing a chemistry, we’re changing the fundamental nature of your brain from a protective, downsizing mode. You’re feeling stressed, you’re feeling threat. You’re feeling these pathogens, etc., to now a growth and maintenance mode. It’s very much like our country, coming out of a recession where everyone’s trying to cut back and now we’re going into growth once again. So there are going to be some hiccups. You’re going to have to tweak things one at a time. And this is why it’s helpful to work with a health coach or a practitioner and things like that. So yes, absolutely, it can be effected that quickly.

Luiz asks, how do you know if you have insulin resistance? And so, Julie, maybe you can talk a little bit about that?

Julie Gregory: Well, one easy way of knowing is belly fat. Other ways we know we can look at biomarkers, your HbA1C we want to be below 5.3. Your fasting insulin we like to be below 5.5 and your fasting glucose we want to see that below 90. So when you look at all of those things together including your  waist measurement. And also if you’re experiencing the highs and lows of insulin resistance, I was on that roller coaster where you felt great right after eating, and then you’d get a drop with hypoglycemia. That often accompanies insulin resistance.

Dr. Bredesen: This is a good point. And it’s something, because you’re trying to do the right thing and unfortunately, you’re hurting yourself. This is the paradox. This is the very reason we wanted to talk about this because people will just jump into this and actually hurt themselves and get themselves into recurrent hypoglycemia, get themselves into again, keto flu, all of these sorts of issues. So absolutely.

Oji says I did a three-day water fast and felt sick afterwards. Yeah this is an issue. Again, too much, too soon. Please, you know, ease into it. More muscle twitching, that concerns me because, you know, your twitching can be for a number of reasons, but you know, this is saying something bad is happening to your muscles. Either there’s some degree of denervation, which causes twitching, or you’re actually getting some sarcopenia and some muscle damage. So yeah, please don’t jump in so quickly. Extreme weakness, yeah, body shaking, yeah. So you, when you feel that weakness, what it’s saying is you don’t have either. You’re not dealing with the ketones, you’re not dealing with the glucose. So you need to feed that and get yourself back. Lost a lot of fluid, also a problem. And I had problems with that myself, trying to get into ketosis. So please ease into it, please be careful. And Ram what do you recommend when patients come to you and they kind of overdo it at the beginning and have these additional health problems, because they’re being a bit over-exuberant with trying to get into fasting?

Dr. Rao: Oh, Dale, we are very clear. We tell them to stop everything that they’re doing. And then we tell them, you know, just once again, a metabolic flexibility or sama agni, we emphasize on the digestive part. We say, you know, the only way you can improve, the only way you can lose whatever problems you have, if you want to heal on that, make sure that you go very slowly. And so, you know, we put up proper diet for them, whether it’s ketosis diet or whether it’s non-ketosis diet, but we make sure that they’re following the diet properly. We’ll tell them to, you know, bring in exercise again, both physical and mental exercise. And then we tell them to do the sleep part because a lot of people think for some reason they don’t want to, sleep has been, at least in my experience, sleep has been one factor where I noticed time and again, with people they say, no, they’re not doing very well. And finally, Dale, it’s only after a lot of questions that they tell you that they’re not having proper sleep. So sleep is something which I tell them to address again. So I tell them to go very slow. And then once they are there, Dale you know, it’s interesting because what happens is a lot of people, once they are maintain that, and they see the changes, they think everything is fine and they’ll go back to whatever they’re doing before.

Dr. Bredesen: Right.

Dr. Rao: So I tell them very clearly if you see the changes and the beneficial changes, please live in that. Don’t.

Dr. Bredesen: Yeah, please keep optimal.

Dr. Rao: Yeah keep on that because you have to sustain those changes.

Dr. Bredesen: Absolutely. So Candace says my BMI is 17 but cholesterol is very high, and this is, you know, a common combination. I just got my Keto- Mojo, doctor has me on vitamin C. I feel the EVOO may be bad for this, what can I do? I’m not sure what you mean by bad for this bad for this. Bad for what? I guess you’re talking about for your cholesterol. And I think Julie would point out that with appropriate good fats, you’re not going to have lipid problems. And in fact, your triglyceride to HDL ratio which is much more important than your cholesterol itself tends to be very good. And Julie, maybe you can say a little bit about your own lipid numbers given the fact that you do have a high, good fats intake.

Julie Gregory: Right. I am an APOE 4/4 and we tend to hyper-absorb dietary fat. And my LDL-P, my particle number is always under 1000. And my HDL is typically higher than my LDL and my triglycerides are quite low, so it’s possible to have optimal lipids with lots of EVOO. But sometimes when you are eating the healthy fats and you still have this elevated cholesterol, something else is at play. It could be a virus; it could be thyroid function isn’t optimized. It could be leaky gut. There are other avenues that she may want to explore with a good functional medicine practitioner.

Dr. Bredesen: Absolutely. So then let’s see, Candice, let’s see. Okay, here we go. Di asks can blood-brain barrier be healed and how long? It’s a great question. And we don’t have perfect ways to measure your blood brain barrier. We can get some indirect knowledge about this through things like . In general, there seems to be a fairly good correlation, leaky gut, leaky blood brain barrier. So we’re typically talking about a month or so. And for some people more, it depends on your status with prebiotics and with probiotics and your status with sensitivity to grains and things like that. So all of these things are critical. And typically you want to think about at least a month to give yourself some time to heal. But you know, continue to do the right things and you should heal this up. And this is certainly an important thing because one of the early changes in Alzheimer’s and pre Alzheimer’s are changes in the blood brain barrier.

Donna says, my A1C is 6.1. Got it down just by stopping prednisone, took many months. Yeah so please remember, we’re changing fundamental physiology here and pathophysiology. So it’s going to take a little time to change these things, change you to an insulin sensitive state, change you to a state in which you have metabolic flexibility, change you to a state in which you are detoxing, change you from a state where you’re perceiving stress and threat to one where you’re actually happy. This is why, you know, joy and appropriate interactions and social networks actually so important. And of course, why depression and suicides went up during the pandemic. So these are all critical things. We are making the system work and making the system get feedback. It’s getting feedback to itself that, hey, I’m on the right path, things are going well. Which you get as you start to improve your cognition. So yeah, you’d like to see your A1C even lower. You’d like to see it down around the, you know, 5.0, 5.2, somewhere in there, but this is, it sounds like you’ve come from higher one and this is a good start. And yes, prednisone definitely will bump it up. It is often associated with pushing people into some degree of type two diabetes.

Luiz asked is fruit bad? Absolutely love fruits, especially mangoes. Great point. And Julie, maybe you can talk a little bit about this because you wrote about it extensively in the second book.

Julie Gregory: Right. No fruit overall isn’t bad. Mangoes, especially under-ripe mangoes are very healthy. They have digestive enzymes that are very helpful. You know, we encourage people to avoid high glycemic fruit. And we also like people to eat fruit in season. Berries in particular have been shown to have neuroprotective properties. So enjoy fruit within moderation.

Dr. Bredesen: Yeah, great. And then Jackie says, my A1C is 5.3, okay. Cholesterol, 289, HDL 68, BMI 24.5. Does this indicate metabolic syndrome? No. Metabolic syndrome is a combination of your insulin resistance, you have hyperlipidemia, typically hyperglycemia with that. So your A1C is typically much higher. You also have increased waist circumference, typically hypertension associated with this as well. So this alone, no, the A1C is okay there. And the HDL of 68 is certainly good. Your BMI of 24.5 is fine. And the cholesterol of 289 may or may not be an issue. We worry about total cholesterol when it’s down below 160 or 150. These ones that are pushed down by statins 100, 110, these are dangerously low. So it would be helpful to know both your triglyceride to HDL ratio, which we don’t have here. And of course, as Julie mentioned, a minute ago, your LDL particle number. So you, you know, just the 289 by itself, doesn’t say something negative and you should be able to address this and get it down and get up the appropriate lipids by diet, exercise, sleep, stress that, you know, the basics.

Melissa is asking, how do you adapt this for severe coronary artery disease with stents? This is a great point. And certainly this is we’ve talked before about calcium scores, about making sure that you don’t have cardiovascular disease. But people do better with their cardiovascular disease with optimal diets. But again, there are all sorts of work arounds. And Julia wrote about this extensively in the second book, please work with your cardiologist. And I would work specifically with a cardiologist who is understanding about integrative and functional medicine. And there are more and more who are, who can help you to do the right things to minimize this. And certainly this goes back to Dean Ornish 35 years ago, using diet. Now he has a slightly different take on the type of diet to use, but he was using diet at the time and proving very clearly a reduction in coronary artery disease. You know, you may want to think about more on the vegan side of things, but again, that doesn’t stop you from getting optimal brain health.

And then Brian’s asking which supplements help insulin resistance? And there’s a whole set of them. And we talk about that in the end of Alzheimer’s program. And, you know, there are things, everything from you know, cinnamon to berberine, to, you know, on and on. But the idea is not to jump in with a supplement. Supplements are supplementary. And so for the vast majority of people, you should be able to achieve insulin sensitivity without any supplementation. And by the way, without pharmaceuticals as well. The good news is now you have an arsenal. So you start with the diet, exercise, sleep, stress piece of it, and then you can layer on as you need them additional supplements. And there’s again, you know, a whole list that we can go through. And so we’re running out of time here. So maybe we’ll end here and we’ll be happy to take further questions online. Thank you so much, Julie, thank you Ram for your insights and for your experience and look forward to seeing everyone next time. Please, everyone, especially with the Delta variant out there, please, everyone stay safe.

Julie Gregory: Bye.

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