Rhonda: Yeah, I wanted to ask you about this because, so a colleague of yours, Dr. Eric Verdin at the Buck Institute, I spoke with him a few months back on a very interesting paper he had published, I believe was [the journal] Cell Metabolism, where he had given animals a cyclic ketogenic diet, and there was just, you know, improvement in health span in general but what was really, really robust was the improvements in cognitive function and brain aging and it was just, you know, hands down like clear that that diet really helped delay brain aging. And so, you know, of course, those weren't ApoE4 positive mice but...

Dale: But this is the exact same thing we're seeing with people, and especially people with early cognitive decline. Now, as you go later and later, it's more and more difficult, but we have seen people even with MoCA scores of zero show improvement. So, yes, I think the work that you quoted supports that notion, that in fact, having ketones is actually quite helpful for cognition.

Rhonda: Beneficial. Do you think, and here's a couple of questions related to that, and that is, you know, is that...you know, probably multiple things, but one, because you're obviously going to have improved insulin sensitivity, you're not going to have high blood glucose levels and all the inflammatory processes associated with that. Also the ketones, as you mentioned, are used by the brain quite nicely. And interestingly, it actually spares...are you familiar with the glucose sparing, what happens with the...yeah, so glucose gets spared to make NADPH, a precursor for glutathione so that helps repair damage.

But I'm wondering if people like myself, I don't really practice a ketogenic diet but I also don't...I eat a very healthy diet. I definitely try to make sure I don't eat anything refined, no refined carbohydrates or processed food or things like that. But the thing is, is that my...so my fasting insulin's really good and my blood glucose and all that's really good. So, for me going on a ketogenic diet, do you think there would still be more benefit even though the whole, you know, insulin sensitivity thing...maybe it would still improve, I'm not sure.

Dale: Well, I think the only way you're going to know is to try it.

Rhonda: To try it, yeah.

Dale: And you know, you can even do so all sorts of online evaluations for your own cognitive ability. And I do think that many of us are sub-optimal in our metabolism, and we know this. One of the problems, of course, is that there have been a lot of assumptions made during the 20th century. Yes, it's fine to have processed foods, it's just as good, you know, it's fine to have more sugar, on and on and on, which just simply have turned out to be wrong. And it has to do with sleep, it has to do with exercise, all sorts of things. We were built, as human creatures, to do certain things well and to do other things we weren't built for. If we all were jumping out of third-story windows as something to do that would be fun that would not go over well for us. And to some extent, we're doing the same thing with the way we're living.

So, obviously, you've managed to stay fit and to have good fasting insulin and all these sorts of things. However, a little bit will depend on what you're actually doing, for example, where is your hemoglobin A1C? For example, is there some inflammation there or not? The bottom line is that we were not made as human organisms to consume the amount of simple carbs that we typically are exposed to. So to some extent, just as we're being exposed to all these other toxins, of course, sugar is one of them. And whether you try to be exposed to it or not often we are exposed to it from all sorts of different foods and things like that.

Rhonda: Going out to eat, you never know.

Dale: Going out to eat...there's also the whole issue of leaky gut. So many people...and this wasn't even known as a problem when I was in medical school but it's become very clear that it's very common. It does contribute to chronic inflammatory conditions like arthritis and like cognitive decline. So, I think that having a high-fat diet has been helpful for many people, but what you can suggest is, look, if you ever have any cognitive decline get in as early as possible and then consider this. In your case, of course, as you indicated, you're interested in prevention because you already know that you're ApoE4 positive, so it might be worth trying it just to see, but you know, obviously, you're doing a lot of other things right currently.

Rhonda: And measuring a lot of different...you know, other cardiovascular-rated biomarkers is also good so you're going to measure things like LDL particles, number and size, and triglycerides, and all those things as well to make sure that the changes you're making are actually going to be good for you. I think that's very important.