Apollo Health’s Chief Science Officer, Dr. Dale Bredesen, and Chief Health Liaison Julie Gregory discuss the importance of ketosis for cognition. Ketosis plays several roles in the healing process. It provides a readily accessible fuel source when the brain is struggling to effectively use glucose. When achieved endogenously (through diet + fasting + exercise) it can help to optimize metabolic health, restoring metabolic flexibility — the ability to use either glucose or ketones as fuel.

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

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Dale Bredesen: Hi, everyone, and welcome. I’m here with Julie G. as always. Julie, welcome.

Julie Gregory: Thank you. Happy to be here.

Dale Bredesen: I hope everybody is staying safe. And we wanted to talk today, Julia and I, about a concept and about a part of the overall protocol for optimal cognition that is often missed that is extremely important. If you take the big picture and you look at the four major areas that impact cognition, and that are important for cognitive decline, they are energetics, probably the most important of all, inflammation, toxins, and trophic activity. So, we want to optimize those four things to get optimal cognition on a day-to-day basis, and to prevent cognitive decline.

So, when you think about energetics, we include in there cerebral blood flow, so you’ve got to get the blood to the brain. We include oxygenation, and this is why people who have, for example, sleep apnea have problems and increased risk for cognitive decline, mitochondrial function, and then of course, you’ve got to have a fuel for your mitochondria to burn.

And the human brain is very much like a Prius, it runs on two different things. Just as a Prius can cycle back and forth between gasoline and electricity, same idea with the human brain, you basically have the option to burn two different things, you have the option to burn glucose or to burn ketones.

But the issue is what’s so important is, as we’re developing cognitive decline, we lose both of those abilities. So, literally, our brains are starving for energy. We lose the ability to burn glucose because we develop insulin resistance. And so, now, in fact, you do a PET scan, what do you see? In pre-Alzheimer’s and Alzheimer’s, you see a reduction in the utilization of glucose in the temporal and parietal regions.

And on the other hand, when the insulin is high as it is with insulin resistance, we’re unable to make the ketones and we tend not to be keto adapted. So, when someone comes in with the beginning of cognitive decline and even pre-cognitive decline, you’re really saying that you’re in a state of starvation. And so, part of the protocol, and something that Julie has written about so beautifully, is to get both of those back. We want to get the ketosis back, but you also want to become insulin sensitive.

And ultimately, you want to be able to cycle, just as a Prius does, between those two, you want to be able to cycle back and forth, so that you have metabolic flexibility. And Julie, I know you’ve written beautifully about your own story. And talk a little bit about how you came to this and your own story of insulin resistance.

Julie Gregory: Right. So, when I first learned I was an APOE-4 homozygote, I was insulin resistant. But I didn’t know it. None of my doctors had mentioned that term before. And I was experiencing hypoglycemia throughout the day. And when I would visit my physicians to try to figure out why this was happening or what I could do, they would tell me to eat more carbohydrates or to drink fruit juice, which is the exact opposite of what my body needed at that point.

So, I know firsthand what it is to experience cognitive decline, partially due to my inability to provide fuel to my brain. And because I was having hypoglycemia throughout the day, I was eating very often to keep that blood sugar up, which was making me more insulin resistant. So, I’ve lived this and I really know how dramatically it can impact your brain function. I’ve also lived with healing it.

And now that I’m bio energetically stable, it is amazing, absolutely amazing. I mean, I went from having these blood sugar highs and lows to now I’m steady throughout the day. The best part is that I’m steady throughout the day without eating all day, which is wonderful.

Dale Bredesen: Yeah, and of course smoothing this out is huge because as we find out, unfortunately, it’s damaging to your brain to have the glucose go up too high. You now start to glycated proteins and lipids and things like that and damage them. On the other hand, it is damaging to your brain to drop too low.

And we hear this all the time as people start to do continuous glucose monitoring. They can actually see these spikes in the valleys and the peaks and the valleys. And so, what happens, they wake up in the middle of the night and their blood glucose is 45. Well, that’s damaging. Again, you are now not getting enough support for your brain.

On the other hand, when you have the right diet, which is why we use this KetoFLEX 12/3 that Julie has written about so extensively, then now you have a much more smooth curve. You go to bed, you go through the night, you do very, very well.

And so, one of the most common things, one of the reasons we want to talk about this is we hear this all the time from someone who says, “I’m not doing that well or my spouse isn’t doing that well.” They’ve been on this program for three months. They don’t seem to be responding. So, we started looking at, okay, what’s the troubleshooting? Step one, when you record your ketones what are you seeing? Oh, we don’t do that. or we don’t worry about that, or we’ve skipped that part.

Well, again, now you’re keeping your brain, unfortunately, in a state of starvation. We need to get those. Now, there are another all sorts of critical pieces to this. When you start to get into ketosis, you have to be careful because you’re not yet adapted. So, it takes a couple of weeks typically, take it slowly, don’t do a starvation.

Here’s an example. A number of people who are very thin don’t have a lot of fat to burn to make the ketones and they don’t take exogenous ketones at the beginning, which is what we recommend; just start with some exogenous ketones. Help yourself to get going here. But what they’ll do is they’ll go on this crash fasting period.

And of course, they’ll actually get worse, because now they’ve taken what little energy they’re getting to their brain with the glucose, and they’re now even taking that away. So, instead of getting better, they actually get worse. So, again, we’ve got to build this back. We’ve got to build back the insulin sensitivity. We got to build back the keto-adaptation.

When I tried it once in a crash way to get into ketosis, it actually was harmful to me after a couple of days, because I tried to do it too quickly, was not adapted. And in fact, one of the things that happens is you lose fluid and electrolytes. And that can be a problem. So, take it slowly. Move yourself into this. Start with some exogenous ketones. And, Julie, maybe you could talk a little bit about what are your favorite exogenous ketones?

Julie Gregory: It’s funny you should mention that. I don’t really use them. And at the time that I needed them, I didn’t know very much about them. I have experimented though with MCT. And I’ve also experimented with ketone salts. I think those are in the LifeSeasons Morning Blend.

Dale Bredesen (07:27): Yeah.

Julie Gregory: And they both work very, very well. The one thing I will say about MCT oil is, oh, my goodness, go slowly. Because the first time I tried it, I took a full tablespoon, and it was awful. I began trembling and sweating and I had so much energy. I literally had to go outside and start running until I felt normal again. So, please go slowly.

And for folks who do find they need the ketone, exogenous ketone supplements, It’s important to understand this is something that you have to repeat throughout the day. The effect is short-lived. And so, you need to take them typically about three times a day in divided doses, until you can endogenously create your own ketones. And that really is our goal. The prefix “endo” means coming from inside the body. This is a natural way of creating ketones.

And I think Lance is going to share a diagram in the chat, because I want to kind of give the basic instructions for how to achieve ketosis. And we do that by using our diet, the KetoFLEX 12/3 diet that we talk about so much. I think Lance is also going to share a link to that. We combine that with a long daily fast. And we want folks to fast for a minimum of 12 hours with at least three hours before bed.

And we also want people to engage in daily exercise, try to work up to at least a 30-minute aerobics session, maybe with an outdoor walk. Try to mix walking and running and do strength training at least three to four times a week. Exercise wakes up your mitochondria. And these are the basic instructions: are diet, the long daily fast and exercise. And when you put the three together, you naturally achieve a state of ketosis that will lead you to once again become metabolically flexible.

Dale Bredesen: Yeah, that’s a great point. And of course, as Dr. Mary Newport has taught all of us, coconut oil is another way to go. So, we always suggest that look, look at your LDL particle number. We’d like to see it between 800 to 1200. If you’re way up at 1600, 1800, 2000, stay away from MCT oil and coconut oil and go with the ketone salts or esters or the combinations where you have both ketone salt and esters, so that’s fine.

But if you are in the 800 to 1200, no problem. You probably don’t have major vascular problems, your lipid panel looks good, then go ahead and you can use MCT oil or coconut oil. So, you really have your choice there. That’s kind of step one. So, we’re now bringing back at least some form of energy. Then, as Julie said, we want to over about a month or two slowly get you into the endogenous ketosis.

Now, if you have very little fat to burn, okay, as long as you’re having a high fat diet, you’re going to be able to get the ketones from that fat. The good news, if you do have fat to burn, if you’ve got a few extra pounds, those are going to burn off. So, you’re actually going to get a really nice reduction and you’re going to get a much more stable weight and healthy weight.

This is why often we see people as they begin to get on the program, guess what, they’re no longer hypertensive. They no longer are prediabetic or type 2 diabetic either, and they are no longer needing their statins. They can slowly get off these things because they’re actually doing the right thing. And you can certainly save a lot there.

Then so, we want to get you first to get into ketosis and get you ultimately into endogenous ketosis. And we also want to make you insulin sensitive. That combination, now your brain gets both of its sources. You have so much more energy. And you’ve often, just as Julie has pointed out, you feel the energy. You feel more energetic. You can do more things. You can do more cerebral work during the day. And in fact, your performance at work or with whatever you’re doing cognitively will be improved.

Now, that doesn’t mean that every single person is going to reverse their cognitive decline. Because remember, there are other issues. There are immune related, we talked about inflammation. We talked about toxins. We talked about trophic activity. So, now we have to fix the other three. But now, you’ve really fixed the first big one. And of course, we want to make sure that you have appropriate blood flow, which is very much helped by the exercise. So, those are the kind of the steps.

Now, one of the things that comes up is how often. Many people will ask, should I be cycling in and out of ketosis. And Julie, talk a little bit about cycling in and out and what’s helpful and what’s not helpful about that.

Julie Gregory: I cycle in and out of ketosis every single day. So, I’ve settled on eating one large meal, which is really an extended meal that lasts several hours. So, I basically have a fasting window of about 20 to 22 hours a day. And then I eat one meal a day. So, throughout the day, because I have the long daily fast and the exercise, I’m in ketosis. And once I began eating, I’m sure that I knock out of ketosis, even though I’m using the KetoFLEX 12/3 approach.

Julie Gregory: I cycle in and out of ketosis every single day. So, I’ve settled on eating one large meal, which is really an extended meal that lasts several hours. So, I basically have a fasting window of about 20 to 22 hours a day. And then I eat one meal a day. So, throughout the day, because I have the long daily fast and the exercise, I’m in ketosis. And once I began eating, I’m sure that I knock out of ketosis, even though I’m using the KetoFLEX 12/3 approach.

So, on a daily basis, I’m going in and out of ketosis. And for my state of healing, my cognition is fine with that approach. Some people find that they need to be in high states of ketosis on a pretty regular basis. So, they need to pretty dramatically restrict carbs and increase fat, especially at the beginning when they’re healing from insulin resistance. And these folks may need to do weekly carb refeeds, where they go ahead and enjoy approved KetoFLEX 12/3 carbs in a more liberal way, because we need to remind the body that it can burn glucose as well as fat.

Dale Bredesen: Exactly.

Julie Gregory: I think that’s a great question. And you know Dale, it’s really individualized. I think people need to keep a journal and see how they feel at different levels of ketosis and do whatever works for them.

Dale Bredesen: It’s a great point. And as you’ve mentioned, some people will find that when they really cycle out of ketosis, they don’t have quite as good cognition as when they’re in. Other people actually like the idea of cycling in and out and actually will do quite well in both cases. And of course, it really suggests that they have that flexibility, the metabolic flexibility. The ones who are having trouble when they cycle out probably are not having as much metabolic flexibility as we’d like to see them have.

So, again try it, but the key is how to be able to do this, how to be able to get yourself. And let’s talk for a minute about people who happened to have some vascular disease and they may know ahead of time. They may have found this out, for example, with looking at carotid minimal thickness, so, they may have found this because of having some history of ischemia or a poor lipid profile or what have you.

Dale Bredesen: They’ll often say, “Well, wait a minute, you’re telling me to eat a high good fats, low carbohydrate diet, but aren’t the fats going to get me into trouble with my cholesterol.” So, maybe Julie, you could talk a little bit about your own situation where you’ve had a very high fat diet, 70, 75% of your calories are something from good fats. And your lipid profile is fabulous.

Julie Gregory: It’s fabulous and my coronary calcium score is zero. And I’m an APOE-4 homozygote who hyper-absorbs dietary fat. So, it’s absolutely possible to care for your heart and your brain at the same time. But if people come to the program with known vascular disease, if you’ve had a (low radiation) heart scan, you know you have a positive calcium score, or you’ve got thickness in the carotid arteries, you have to practice this much more carefully.

We want you to work with a cardiologist that endorses a low carb approach. We also want you to start by focusing on glycemic markers before you start increasing healthy fat. It’s very important for these folks to give up all forms of sugar, to give up all simple carbs, even to give up all grains and conventional dairy, because not only are these high glycemic, but they’re also highly inflammatory.

And the last thing we want is for people to increase even good fat with these high inflammatory, high glucose foods on board. So, this needs to be done in a stepwise fashion. So, give up those foods, work on getting the glycemic markers in order. We pretty much find that insulin resistance tends to be a part of heart disease and that most folks with vascular disease have some degree of insulin resistance.

And these people can really benefit from using continuous glucose monitoring, so they can actually see in real time and one and two hours after eating a meal how certain food is affecting your glucose. And once you do start adding those healthy fats, once you’ve gotten things in order, it’s really important to focus on poly and monounsaturated fats, so heart healthy fats, as opposed to the fats that are high in saturated fat. So, we’re talking about high polyphenol extra virgin olive oil, avocados, nuts, seeds, fatty fish, things like that. Our diet can be very heart healthy. But if you come to the protocol with vascular disease, please work with a cardiologist that endorses this approach.

Dale Bredesen: Yeah, absolutely. And one of the common things that we hear is, “Well, what if I just keep eating the way I’m eating, but then I just add a bunch of fats, is that good enough?” And as you pointed out in the second book, that actually can be harmful to you. So, imagine you’ve got these things in your gut things like lipopolysaccharide, LPS, highly inflammatory, this can actually interact with the fats.

And now if your gut is not healed, it actually get into your bloodstream better. So, you actually can harm yourself if you just add fats to a diet that’s already high in carbs and already is giving you metabolic syndrome, already is giving you inflammation and leakiness of your gut. So, you really have to kind of bring these together. Again, this all works as an orchestra. The symphony has to work together to get the best results and healing the gut is a critical part of that.

And so, what about people who say, “Well, you’re telling me to have some MCT or coconut oil, but how do I switch over ultimately, and get myself into endogenous ketosis?”

Julie Gregory: So, I love that you recommend your people transitionally start with exogenous ketones. If you’re experiencing cognitive decline, there is a neural fuel insufficiency. So, exogenous ketones will help. But at the same time, you’re taking those, please follow the basic instructions, use the KetoFLEX 12/3 diet. Engage in that long daily fast and also engage in daily exercise. The goal is to no longer need those exogenous ketones and to be able to endogenously naturally create ketosis.

Dale Bredesen: Right. Okay, great. So, we’ve got lots of good questions here. Let’s come to some of the questions here. Matthew asks, is the glucose itself so bad or is the body’s mismanagement of glucose, is that the issue? He says, “I do great on high carbs in every respect. Less carbs seem to be very stressful.” I’m so glad you asked that, Matthew. I think that’s an excellent question. And the answer is both.

So, the glucose for example, as your glucose goes up, it will non enzymatically placate your protein. So, think of a shark with remorse stick to it. That’s what happens with these molecules. And you actually You get damaged. And so, you change these various proteins and lipids, they become more proinflammatory. And actually, they don’t function as well. And of course, we measure this as hemoglobin a1c, you can get a general idea, but this is happening throughout your body. So, the glucose itself, if you’re sitting up there at 100, 105, 110, or above all the time, that is a concern.

On the other hand, yes, the mismanagement comes up because you now develop insulin resistance. And we see that again, you can do a PET scan, and you what you see in the brains of Alzheimer’s patients is poor utilization of glucose in a classical pattern, which is this temporal parietal pattern that we’ve talked about so many times. So, it really is both.

Now, when you say you do great on high carbs, I think the main thing is just check to see what is your HOMA-IR. Check your fasting glucose and check your fasting insulin, you simply multiply those two and divide by 405. You can see very quickly what your HOMA-IR is. If it’s above about 1.2, 1.3, you’re heading up for insulin … If you’re up at two or three, you are very insulin resistant.

So, some people definitely do better because of what Julie talked about a few minutes ago, which is continually dipping into hypoglycemia. So, you keep kind of chasing that hypoglycemia with carbs. But look, if you’re having carbs that are carbs that are complex carbs, you may do very well. In fact, one of the blue zones is people who eat a lot of complex carbs, lots of roots and things like that, then that’s fine.

Again, we’re focusing on what is best for your cognition. And time and time again, what comes out is this ability to have metabolic flexibility to have fuel from both sides. Because we are dealing with a problem that is fundamentally an insufficiency of a network. Lots and lots of things. We talked about blood flow and immune status and all this, but ultimately, it is not feeding that network. So, I would simply say to Matthew, please, please check your HOMA-IR. Maria is asking … Go ahead, please.

Julie Gregory: Can I say one other thing? And Matthew, you may want to see how easily you can fast.

Dale Bredesen: Yeah.

Julie Gregory: How do you feel after a 12-hour fast or 14 or 16 or? So, if you feel like you’re a little shaky, a little hypoglycemic, you may very well have the early stages of insulin resistance. So, if you’re metabolically flexible, which Matthew may be, this diet may be working for him as long as he’s not over-indulging and he’s exercising every day.

Dale Bredesen: Yeah. And using complex carbs, you may be doing very well. Maria is asking, can you talk more about ketone esters. Great point, Maria. So, again, as Julie has said, ketone salts, ketone esters, both, and then of course MCT oil or coconut oil.

So, the ketone esters tend to be the ones that get you up to the highest ketone. It’s just why athletes use them. They also tend to be things that tastes horrible, which is why many people don’t use them. That’s why I kind of liked this idea of combining the two, you get the best of both worlds in some ways. But if you are trying to do 100-mile bike ride or something, many athletes will use things including things like carnitine, creatine, and things like that, but also these ketone esters because they give you that burnable substrate.

So, absolutely ketone esters are fine. Check them out. Some people say just swallow it and then do a chaser with some sparkling water. I’ve tried them before. And I found that helpful to do with chaser. So, absolutely, they’re fine. And now also remember, one of the issues with the salts is you’re going to be losing salt at the beginning when you first start into endogenous ketosis. So, some people like the ketone salts, because it’s helping you to replenish those salts that you’re losing. But again, experiment, don’t push it too quickly.

Dale Bredesen: And then Julie, have you tried ketone esters? And do you like them?

Julie Gregory: No, I never have.

Dale Bredesen: Yeah. Melissa says, “It’s so nice to not have to eat all the time and no more “hangry” episodes. I couldn’t agree more. It’s fantastic. And to have the energy, I mean, that’s the other thing. That’s really fantastic. So, no question, it is the way to go. And of course, it is the ancestral way that people worked.

And then Maria says, “I have sporadic fatal insomnia.” I’m very sorry to hear that. She says, “I’m still alive after four years. I’ve been doing the Wahls protocol and taking doxycycline” All right, fantastic. And again, one of the big questions right now is, can we take these same sorts of approaches? Of course, Terry Wahls, who I just talked to recently, has done a wonderful job with multiple sclerosis and she’s looking at can we adapt this to other things.

We’ve worked more on the cognitive decline side. But that’s the same sort of thing. We’re trying to now look at, what if we modify this for things like Lewy body where we’ve already seen good results, Parkinson’s, frontotemporal dementia, ALS. And right now, we have the first few patients with macular degeneration. Again, it’s a modification. Each one of these has its own unique biochemistry and genetics. We need to address those differently for each one.

But one of the things that’s unknown right now is what about things like familial, what’s typically called fatal familial insomnia. As you pointed out, Maria, in your case, it’s not familial, it’s sporadic. But it’s the same idea. It is a rare neurodegenerative disease. Nobody knows whether these specific things are things that are going to be helpful. And so, I’m so happy to hear. It sounds like you’re doing well after four years. I hope this will go for many, many, many years. We’re dealing with a few people right now who have familial Alzheimer’s, the rare, rare APP mutations. And looking at can we see improvements in those particular people?

And one person in particular has done well for many years now. And I hope it will be many years to come. But this is all new territory. So, Maria, I’m very glad to hear that you’ve done well with the Wahls protocol and the doxycycline. And doxycycline and those sorts of approaches have been used. This came out of a screen years ago, looking at things that would have impact on the activation of proteases that were involved with programmed cell death. So, glad that you’re doing that.

And then Maria says, “What are some of the major signs of insulin resistance?” So, and I know, Julie, you live this. So, maybe talk a little bit about what were the things that really keyed you in to having insulin resistance.

I have been very thin my whole life. And when I was insulin resistant, I had a lot of abdominal belly fat for the first time in my life. My blood pressure had been very low all of my life.

And suddenly, I was getting readings like 140 over 90. I’ve never seen anything like that before. I didn’t know to be testing my blood glucose, so I wasn’t doing that. But that’s something that folks can do. And we’d like to see your fasting morning glucose between 70 and 90. We like fasting insulin to be below 4.5. We want hemoglobin A1c to be below 5.3. And as you mentioned, HOMA-IR to be below 1.2. So, those are all things that you can be looking at.

Dale Bredesen: Yeah, great point. And as you said, the typical thing is you begin to see some belly fat that you didn’t have before. Your blood pressure goes up. You also have cravings. And you start to realize, “Oh, my gosh, I really want some more carbs. I really need these.” You often will go through these cycles that Julie mentioned earlier.

So, you go to bed and then you wake up in the middle of the night, you may be sweating, your heart may be pounding. Your body is actually making adrenaline, trying to get you get that glucose back up because you’ve dropped. And of course, one of the things that can happen is beginning to have some confusion and some cognitive decline. All of these things are related. And so, great point to address.

Of course, visceral fat is another one. And this is, again, what correlates with vascular disease. So, I think a lot of people would say many of the ills of the chronic illnesses that we associate with the 21st century and the late 20th century really are insulin resistant-related diseases. It’s kind of a typical metabolic syndrome type of problem. And then let’s see here, Lisa is saying, “How common is keto flu. I’m beginning the program and what should people do?” That’s a great point.

And this is again, why we say don’t just jump into it immediately. You may have this diuresis. You may be losing too much in terms of fluid and electrolytes, and that may hurt you. So, Julie, maybe you could talk a little bit about easing people into the KetoFLEX 12/3.

Julie Gregory: Right. It can create this perfect storm. You’ve just give up processed and refined foods that are very high in sodium. At the same time, you begin this low-carb diet. And when you begin to deplete your glycogen stores, it creates a lot of water that we lose through urination. So, it’s very important that during the time you’re trying to get into ketosis and during the entire time you’re using ketosis that you stay very well hydrated and you liberally use good high quality sea salt.

We get lots of other electrolytes from our high-plant diet. So, you don’t need to worry about adding additional potassium or anything like that. We’re getting all of that from the diet already. So, stay well hydrated and use lots of good quality sea salt.

Dale Bredesen: Yeah, great point. And then Maria says, “My metabolic sensitivity has suffered since menopause, working with BHRT.” Fantastic, very helpful, but she says, “But ketosis is much harder to achieve.” So, you might consider some things like fat bombs. And again, if you’re not achieving ketosis, and we’re focusing on cognition, add some exogenous ketones.

Over time, you may be able to get off those. Some people, though, will continue to use them when they need them. And I know, Julie, you went through a period where you would take small amounts of MCT just when you needed it, and it became less and less common for you to need that. So, what would you recommend for Maria, who’s having a little harder time getting into ketosis?

Julie Gregory: Right. So, I’m guessing the way she’s experiencing that is that it’s harder for her to go long periods of time without food, because she feels more hungry. And I think small amounts of MCT oil or other exogenous ketones are a great way of getting over that hump, until you can extend the fast a little bit longer and get into endogenous ketosis. But certainly, all the hormonal craziness that happened with perimenopause and menopause definitely makes it more difficult, but it’s certainly possible.

And we should also mention, Dale, that even for people that do have a fairly easy time getting into ketosis, there’s a period of time where you’re uncomfortable

Dale Bredesen: Yeah.

Julie Gregory: You feel hungry. Though I’m very well keto-adapted, I may have 10 or 30 minutes throughout the day where I feel pretty uncomfortable. I feel hungry. If you’re experiencing the hunger plus, you’ve got the shakiness and the sweating, and you think you may be hypoglycemic, by all means check your blood sugar. And if it’s below 70 milligrams per deciliter with symptoms, end the fast and go ahead and eat something. We don’t want you to become ill.

But if you have low blood glucose and you don’t have those symptoms, which is something that I regularly experience, you’re fine, and you can just wait it out. And 30 minutes later, you’re into ketosis, and that uncomfortable feeling goes away.

Dale Bredesen: Yeah, that’s a good point. And then Jihane says, “Hi, everyone. I used to follow a keto diet. I’m now more paleo.” Certainly, these are absolutely compatible, “And absolutely love the way it made me feel. What do you guys struggle with when trying to get on keto?” So, as you’ve indicated some of the things already, people will have cravings, people will get keto flu. I think the number one thing is people have trouble changing their diet.

They say, “Hey, I like to have pizza and Coke. I don’t want to stop having pizza and Coke.” And so, it takes some time, get rid of those carbs, get rid of the simple carbs, and slowly get yourself … What happens, you start getting positive feedback. You start getting that feeling of, wow, I’m sharper, I’ve got more energy, I can do more. And you just start feeling better. And that actually gives you that positive feedback that helps you.

But I do think part of it is just where do I shop? What do I buy? I’m so used to having the processed foods. I’m so used to going out to eat and then how do I find the right things when I’m going out to eat? Maybe we talk about that for just a moment or two. So, Julie, when you and Bruce are out to dinner somewhere, how do you find yourself a keto-friendly diet?

Julie Gregory: It’s challenging, and we find that we don’t eat out as often. But when we do, it’s a real treat. And we can very well with farm-to-table restaurants. They have wild caught seafood or grass fed meat like a burger or something (without a bun.) And I also bring high polyphenol extra virgin olive oil in my purse with me. So, what I typically do is order a big salad, lots of vegetables. And then, if I am also having protein, I’ll do a piece of wild caught salmon or something with it.

I never use salad dressing from a restaurant. I always use my own olive oil that I put on the salad and it’s fabulous. And you can totally stay on track with the diet. When you eat out, you just have to be careful about selecting the restaurant. Check the menu out ahead of time to make sure there’s something that you can eat.

Dale Bredesen: Yeah. And if worse comes to worse, you may cycle out for one meal. And so, yes, it does happen, and people do that. The other thing I think it’s important to point out, some people don’t do well with high-fat diets. And one of the common causes is they just don’t have the enzymes. So, taking some digestive enzymes for those of us who are over 40 or way, way over 40 in my case, so, okay, maybe you may have to take some digestive enzymes.

I notice I do better if I have a high protein meal if I take some digestive enzymes. I think many people find the same thing. So, that’s another one that can be helpful to many people. Then Christina is saying, “Do you focus on supplementing D3 and K2 as well?” And so, absolutely depends on your levels. If you’re up above 80, no, you don’t need supplementation. But we’d like to see people typically in the 50 to 80 range with vitamin D3.

And yes, you want to make sure to take some K2, 100 micrograms of K2 or above, that’s fine. So, check your level. If it’s below that, we want to get you into that range, again, for optimal cognition and performance. If you’re already above that, then I wouldn’t be supplementing. And then so actually, Julie, how much D3 do you typically take?

Julie Gregory: I take a really high amount. And my level is only 55.

Dale Bredesen: Great.

Julie Gregory: So, it’s really surprising. I take the 6000 IU a day.

Dale Bredesen: Yeah.

Julie G: So, I need that higher amount. So, even though I’m outside every day. Maybe because I live in a northern climate, I’m just not getting enough sun on my skin.

Dale Bredesen: Yeah. And then Jihane asked, “Did I miss the part that’s more about cognition.” Yeah. “What’s the link between keto and brain power?” Absolutely. This is what we started with. So, the critical piece here again was we talked about earlier, your brain is like a Prius. You basically got two ways to go, you got the electricity, you got the gas. In the case of the brain, you’ve got the ketones, you’ve got the glucose. And yes, they’re both important. And in a perfect situation, you’re able to cycle back and forth, you’ve got that metabolic flexibility.

As I mentioned, PET scans show it. You are not metabolizing that glucose. And unfortunately, for most of us, as we get into some cognitive decline, what’s happening? We lose both. So, we truly have a starvation. It’s amazing to me that brains function as well as they do for as long as they do when you have the combination of inability to use glucose because of the insulin resistance and inability to use ketones because you’re not keto adapted and your high insulin is preventing you from making ketones. It’s amazing.

But what your brain does, it says, “Okay, I’ll do it the best I can. I will involute. I will shrink.” It’s just like saying your car has got very little gas, the engine is not working very well, there’s not much charge in it. But we can go 20 miles an hour. Okay. So, that’s what your brain is doing. It’s going 20 miles an hour. And when you’re now doing the right things, you’re actually going to be able to make it go over 100 once again.

And then Mike says, “Thank you for this info. I’ve changed my lifestyle because of information about APOE-4.” He say, “I’m APOE-4, have zero calcium score.” Fantastic. “Went on a carnivore diet, love it, should I be concerned of minimal veggies and fruits?” Yeah, this is a great point. And there was this question just recently and it had been suggested that we actually have a debate. Well, I said, look, there’s nothing to debate at this point. There’s not a single article on a carnivorous diet improving cognition. Whereas there are many articles on KetoFLEX 12/3 and on the MIND Diet and things like that.

Now my hope is in the long run, people will begin to publish things. I would love to know, we only have one goal here, we’re agnostic, we want the best outcomes. So far, what seems to be best for cognition again, and again and again, is to have this combination. Now, that includes some meat. It includes some grass-fed. It includes organ meats. It includes fish. All those things if you want to do it, great.

On the other hand, if you want to be vegan, fine. Be careful about those things. As Julie has written about very nicely in the second book, be careful about things like your homocysteine and your vitamin D3 and your B12 and things like that, but it’s fine. So, the key here is get the combination because, yes, you’re going to get better fiber, you’re going to get prebiotics better, even probiotics if you’re eating some fermented foods. You’re going to get better detox. You’re going to get better glycemic load. You’re going to get better lipid profile, all of those things from the plant rich diet. But again, you combine these things.

And as far as Mike said, I just stopped dairy. Good idea. For many people that is inflammatory. And then Tanya says, “What about hypothyroidism in this situation?” And, Julie, have you had any issues? Certainly, there’s an issue about thyroid sensitivity versus true hypothyroidism.

Julie Gregory: Right. So, I think that our approach does tend to reduce thyroid function a bit. And I don’t know that it’s necessarily a bad thing. When you’re running the engine very efficiently, you just don’t know need as much thyroid support. That being said, I do take a little bit of thyroid medication, a very, very small dose every day, just to optimize my trophic factors. But yeah, it’s a really great question. It’s something that some people do experience in more significant ways, but many of us just have slightly reduced thyroid function.

Dale Bredesen: Yeah, and again, you have to remember the difference between thyroid measurement and the thyroid function. So, what you may see is that your free T3 may drop down below three. So, you may be down to 2.5 or something like that, which is slightly suboptimal. We’d like to see it more low three. But check your TSH. If your TSH is below two, you’re probably doing well. If your TSH is up at 5 or 10 or something, yes, you’re working overtime.

But then your symptoms, how well is this actually happening? Again, we get insulin sensitivity. There’s a strong suggestion that there’s also thyroid sensitivity. And by the way, cortisol sensitivity. So, if you’re doing that, if you are feeling fine in a normal temperature room, you’re probably fine. If you’re beginning to have the symptoms of hypothyroidism, that’s a different story.

And then if you want the room 10 degrees warmer than everybody else, if you’re beginning to lose hair, if you’re beginning to have problems with cold, sleeping too long, having trouble getting up, things like that, then yes, you should really think about getting small amounts of thyroid to balance that out. But a very, very good point.

And then the next one, Lisa says, she meant to ask about keto rash, not keto flu. And Julie, have you seen anyone developing a keto rash?

Julie Gregory: No, I’ve actually never heard of that. Have you?

Dale Bredesen: Yes. So, I’ve heard about this before. But as I understand it, it is evanescent. And so, my assumption is if you just ease into it slowly, this should not be a major issue. Yes, of course, we are changing and optimizing the immune function. And so, yeah, I mean, again, it depends on what you’re taking. Usually what we recommend is, look at the things you’re taking for supplements when you have a rash, get rid of all of them, and then reintroduce one at a time.

One of the common ones that I’ve seen is with NAC. So, this may not be keto per se. It might be part of something else. But it’s a good point. And we’d love to hear more. Lisa, if you’ve developed a keto rash, please let us know more about that. And then Christine asks, “Do you monitor both fasting glucose and insulin levels while doing a glucose tolerance test?” Great point. “And depending on the level of insulin resistance, you may have.” Yeah.

So, if you look at the various sensitivities, it kind of the least sensitive but the easiest thing to check is just your glucose level. And then you go into okay, you can look at hemoglobin A1c, because that gives you where things went, then you can look at the fasting insulin and HOMA-IR, which tends to be even more sensitive. And the most sensitive all, of course, looking at continuous glucose monitoring, very helpful.

But the most sensitive is to do that glucose tolerance test. Because some people, although they’ll keep their glucose within the normal range, it’s because they’re just pushing out massive amounts of insulin. Of course, that is very stressful to your beta cells and your pancreas. So, we want to make it so that you have that sensitivity, which is why we look at HOMA-IR. So, we usually don’t do it with the OGTT. But for those few people where you’re not seeing that and you’re really suspicious that there is some degree of insulin resistance, you may want to do that. Again, as you get to do the right things, you’re going to see it improve.

So, you mentioned here are found to be a hyper insulin secretor. Yes, that is a concern. And of course, it’s a concern because those people are also subject to these real valleys, where they have tremendous hypoglycemia at times. And then Knox asks, “My oxygen drops a lot during the day, 89 to 94. But it’s not from lungs, but brain. Have you heard of oxygen desaturation from brain problems?” So, yeah, this is essentially related to central sleep apnea.

The other thing, there’s something called Pickwick syndrome, where people can have changes in their oxygenation during the day. They literally just don’t quite breathe enough. And it is often associated with some insulin resistance and also with some degree of obesity in some cases. So, you can check that out.

And yeah, now, 89 and 94 is not horrible. If you’re telling me it’s 85, 80, I worry about especially with COVID-19, we worry about your lung status. We worry about whether history of smoking, whether you have some degree of emphysema or bronchitis, but if it’s truly just from the brain, then this is more related to what’s been called Pickwick syndrome.

Maria says, “Cauliflower crust pizza is a great cheat.” So, do you ever have cauliflower crust pizza?

Julie Gregory: Absolutely. Yeah, we just did it recently. It’s a great treat for us.

Dale Bredesen: Yup.

Julie Gregory: It doesn’t taste the same, but it’s still delicious.

Dale Bredesen: Yeah, I had some two days ago. I love it. It’s great stuff. Okay, Jihane asked, “Do people who work with a health coach adapt faster and find it easier?” Yes, Jihane, I’m so glad you asked that. Often, we find health coaches can be so helpful. And so many people, that’s one of the other common things we ask when people aren’t doing well, okay, what’s your ketone level? What’s your HOMA-IR? What’s the sleep status? Have you checked your oxygenation, all these sorts of things? And then, we say “Do you have a health coach?” Because the health coach can absolutely help you.

And so, yes, we do find that we don’t want to adapt so quickly that we are getting people again, to have too much keto flu and things like that. But yes, we do find especially the right health coaches, well trained, really good health coaches. And Julie, have you ever worked with … I know you have a lot to teach health coaches. When you are going through this early on, did you ever work with a health coach?

Julie Gregory: When I was going through this early on, there was no such thing as a Bredesen protocol. There was no blueprint for healing anything that I was going through, so I never did. But I recently did a, I think it was a six-week program with a health coach, because I wanted to go through that process and to see what it’s like.

And I would highly recommend it for anyone who’s trying to adopt the protocol. I mean, this is someone who walks with you and is there to support you every step of the way. So, for anyone who’s struggling with all of these strategies, please consider using a highly-trained health coach. And we like health coaches that have the ReCODE 2.0 training that is the most current and up-to-date training.

Dale Bredesen: Great point. Then Christine says, “I’ve started practicing a TCM approach called B-I-G-U, Bigu fasting. I learned exercises, which assist the body to detox toxins specific to each organ, promote blood circulation and lymphatic drainage.” Yeah, if we’ve talked about before, traditional Chinese medicine treated the whole body together, but didn’t know anything about DNA, RNA, things like that. Modern medicine, very good with mechanistics, DNA, RNA, things like that. But we have these hyper specialists who just focus on one neuron in the brain, that sort of thing, or they just focus on one part of the heart.

So, the new 21st century medicine is bringing these together, and all of these things, and yes, lymphatic drainage is huge. And by the way, as we’ve written about and Julie has written about beautifully in the second book, if you are detoxing, you may need a little higher protein load. You may need more protein during that detox time. And again, this is why the phytonutrients, this is why the plant, this is why plant-rich diets tend to be so helpful. We have so much that can be done for detox. Everything, from the basics of filtered water, and saunas, and nontoxic soaps and things like this, we all have.

And again, exercise, just getting out there breathing harder, moving the blood around, so, so helpful. And Julie, are you familiar with Bigu fasting? Have you ever used this approach?

Julie Gregory: I’m not, but it sounds fascinating. Yes.

Dale Bredesen: Yeah. And then Knox says, “Where do you stand on carbs? How many carbs do you recommend for keto?” And Julie, I know, again, you wrote about this in the second book. Could you talk a little bit about kind of the basic macronutrient breakdown, or, for example, just the one that you like to use for yourself?

Julie Gregory: Right. The amount of carbs you’re able to tolerate and use is going to shift depending where you are in the program. If you’re insulin resistant and you’re trying to get into ketosis, you may need to drop your carb intake more dramatically than when you’re healed later on in the program. So, I think in the book, we did a macronutrient ratio breakdown of a woman who was, I think, 130 pounds, and she ended up with, I think, a fat intake, maybe around 70%. I’m doing this from memory. I think carbs were around 15, maybe. Protein was around 15%. It’s going to vary a little bit.

But in the book, The End of Alzheimer’s Program, we give you the formula so you can figure it out for yourself, your best macronutrient ratio breakdown. And of course, you don’t know what macronutrient ratio is going to get you into ketosis unless you check your ketone levels. So, please check them to see. And once you’ve been very well keto-adapted like I am, I eat a pretty high amount of carbs every day. And I’m still very easily able to get into ketosis. So, the amount you need will shift over time.

Dale Bredesen: Yeah. The next one here is from Britta, says, “You talk a lot about insulin resistance, high fasting insulin level.” Yeah, Britta, I’m so glad you brought this up. Britta says, “What about a very low-fasting insulin? Mine came back as less than 0.1.” That’s unusually low. “My fasting glucose is 80.” Wow. “C-peptide 0.8, hemoglobin A1c 5.1. We’ll have to worry about diabetes type 1 or adjust to keto flex.”

So, okay, first of all, let’s take this in two pieces. The first thing is, absolutely, what we find in general is it’s easier for the people who make too much insulin, because as they do the right thing, they’re able to make that insulin comes down, no problem. I worry more about the people whose fasting glucose is 105 and their fasting insulin is one. They’re not able. They need to make more insulin, but they just can’t make it.

However, in your case, you have the third piece here, which is that you are sensitive. Look, you’re fasting glucose is 80. Now, you’re a great candidate for continuous glucose monitoring. Because are you going through periods that are higher? Well, it’s unlikely that you’re going through too many high periods, because your hemoglobin A1c is 5.1, which is again, why we want all these different pieces. We can construct a story here that understands the different pieces.

In your case, it doesn’t sound like you’re having major spikes, or at least not a lot of them. Now, are you having some periods of hypoglycemia? I don’t know. But you would be from what you’ve told us so far, you are a highly insulin sensitive person, which is fine. Now, you might want to check at some point to see with a glucose tolerance, can you make the insulin when you need to? But so far, you seem to be doing very, very well.

Are you at risk for type 1 diabetes? Well, if you can’t make insulin when you need to, you might be down the line. But so far, you’re doing very, very well. You have excellent numbers throughout. Now, of course, that brings up the last piece. What are your symptoms? Are you having symptoms of hypoglycemia ever? Are you having issues with hyperglycemia? And Julie, I know you’re fasting insulin tends to run on the low side, but in a good way. You’re very sensitive to it. Have you dealt with other people that had these extremely low fasting insulins?

Julie Gregory: No, mine’s always around 1.5 or 2. This sounds extraordinarily low. So, I love the idea of having her do continuous glucose monitoring to see what’s going on or to do a challenge to see if she can create the insulin when she needs to.

Dale Bredesen: Yeah. And then I thought we were getting late in the hour here. So, let me just take one more here that Janie is asking about. Janie says, “No, no. Dr. Bredesen, it’s not about the TSH.” So, agree here. But here’s the point, for each of these, we want to have multiple factors so that we can understand what’s the response, what’s the basic biochemistry. We’d like to have the genetics as well. So, again, when we talk about glucose, we want the HOMA-IR. We want the fasting glucose. We want the hemoglobin A1c. Yeah, we want to the fasting insulin.

We may want a CGM so that we kind of get an overall look at what’s happening. Human bodies are complicated organisms and optimizing your cognition, you’re dealing with the most complicated organ as you’re trying to get everything to work correctly. So, you’re absolutely right. Many doctors will only check TSH, which is a horrible idea. This is why we look at free T3. We look at free T4. We look at the ratio. We want to look at your reverse T3. We want to look at your free T3 to reverse T3 ratio. That’s also telling in and of itself. And some people would argue that’s one of the best ways to go.

If we can get it, then we’d also like to look at symptoms and we’d like to look at a Thyroflex test so you can actually look at the rapidity of the response of the reflex. And you can get a very good idea about whether you’ve got some symptoms. Unfortunately, most offices don’t have a Thyroflex. So, therefore, you can look at symptoms. Is someone having symptoms of hypothyroidism or hyperthyroidism? So, I completely agree with you Janie. It’s not just about the TSH, but we want that as well as these other things.

So, I know we’re getting a little bit late here. So, Julie, let me thank you so much and thank everybody for the great questions. And let’s take the rest of these questions. I know there are many more here. Let’s take these online. And Julie, look forward to seeing you next time.

Julie Gregory: Thank you so much.

Dale Bredesen: All right, everyone stay safe. Thank you. Bye-bye.

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