Rhonda: Well, in contrast to that, getting to the same place, in my mind, in my opinion, one of the reasons I am so drawn in addition to the time efficiency aspect of high intensity interval training is the brain effects. And there's no doubt that exercise in general has global effects on the brain. I mean, there are improvements, you do any type of exercise, you look at any observational study, exercisers, non-exercisers, definitely, you know, brain benefits, lower risk of, you know, age-related diseases, neurodegenerative diseases, excuse me.

So, you know, not that there's not, you know, a role for any type of just getting your blood flow higher. However, I'm increasingly convinced when it comes to intensity of exercise, there may be very unique benefits on the brain, and that is where I think, you know, high-intensity interval training or any type of high-intensity training has a special role.

Some of that has to do with actually wanting to increase your lactate levels. So instead of this lactate threshold training that we were talking about, the zone 2 sort of going, you know, right below the lactate threshold, which I guess is defined various, you know, ways depending on what you're reading or who is doing it.

But the lactate shuttle theory, George Brooks proposed this, you know, it's not a theory anymore, so it kind of...the name kind of...it's a little out of date. But can you talk just kind of briefly about the lactate shuttle theory and maybe, like, where the brain comes in to that?

Dr. Gibala: Sure. So, you know, the lactate shuttle theory or lactate, you know, many of us, if you look back at your textbooks, you'll learn that lactate was this metabolic waste product, end product, and it's just a metabolite like anything else. And it can be an extremely valuable fuel. And we know that...and there's elegant studies, including from Dr. Brooks and others, to show that, you know, first of all, skeletal muscle can produce lactate under fully aerobic conditions. So there's always some lactate production happening. And certainly, during more intensive exercise where we produce lactate inside the muscles, it can be released from active skeletal muscle, it can circulate to other places like the heart, like the liver, like the brain, but certainly in heart.

Heart can be a big consumer of lactate, and so it takes up that lactate, can convert it back to glucose, and then utilize it during exercise. And so this is the idea of cell-to-cell or inter-organ lactate exchange, and I think that's very well established now. Like you, and you would be far ahead of me, but I'm following this area with immense interest.

I have some colleagues at McMaster who are, you know, both from a cognitive psychology standpoint and also more a hardcore, you know, neurophysiology standpoint, we’re engaged in some collaborative research with them. But generally looking at this question of physical activity and brain health and probing the role of intensity there.

So you know, my understanding is mainly based on talking to my colleagues, trying to read reviews of some of this research, and my sense is, you know, very well established potential mechanisms now from some of the animal studies. And the human data is certainly intriguing, but you know, that link between lactate, BDNF, absolutely there appears to be a role for intensity there in terms of higher intensities, the better in terms of, you know, potential BDNF bathing the brain, some of these outcomes associated with neurogenesis.

Rhonda: Yeah. The lactate, and we can talk about measuring it, but it's interesting because I do measure mine. I do the finger prick, and my workouts, I'm like trying to go higher for my lactate. You know, and I've read a lot of study... For me, I'm very interested in neurodegenerative disease. On both sides of my family, Alzheimer's and Parkinson's.

So to me, I'm like, I need to really focus on brain health. And so looking at the studies on lactate and, you know, even infusing lactate into humans, it increases BDNF, just infusing it. And I'm like, oh, I get these levels from my really all-out hard workouts. Like this is great. But also, I feel really good.

So I start my day with, including today, most days, you know, at least five days a week, I'm doing a...and I wanna talk about protocols, but I'm doing like a 10-minute, you know, Tabata. So I'm doing two back-to-back Tabatas, actually. It's two back-to-back Tabatas. And then I have...there's some, you know, a minute warm-up and a minute cool-down. I actually don't... I use them more for...I'm actually still going hard, like half the time, and then I, like, cool down after that minute. So I, like, at the end, I go an all-out minute after my two back-to-back Tabatas, and then I'm like...and then I cool down. But, you know, I do this for my brain. I feel amazing.

And there's actually science showing that executive function is improved, and it totally correlates, and this is in humans, with lactate after high-intensity exercise. And it doesn't correlate with anything else, you know, glucose, like nothing. It's specific to the lactate. And like you said, it's a growing area of research.

I'm particularly interested in it. Like, I, for sure, notice a difference in terms of, like, if I go hard, like, I feel better, I feel smarter, I'm, like, more on task, you know? So for me, it's a very important part of my protocol. And I do think there's a lot of benefits for the brain. So I'll have to be in touch with some of your colleagues at McMaster because I love sharing studies and stuff that I find and learning what, you know, what other people are doing as well.

Dr. Gibala: And so the...and maybe there's data out there on this, but, you know, the scientist in me is innately curious around things like, I, you know, maybe now there's really, really good dose-response stuff in terms of exercise dose and BDNF increase and some of these other measures. So, you know, so for example, is short, sharp, large changes in lactate better than prolonged moderate levels of lactate?

Rhonda: Right. And I'll tell you something. It's not lactate that I've looked into, but I've looked into blood flow and shear force. And I think this is a very...I think it's an emerging field looking at the effects of shear force. And that is where, I mean, we're talking about a flash flood coming through if you're talking about high intensity versus just, you know, a little trickling.

And the shear force itself, at least at the blood-brain barrier, and this kind of...when you were talking about muscle capillary, I was thinking about the shear force. In and of itself, in a dose-dependent manner is responsible for increasing VEGF and BDNF at the blood-brain barrier. Again, dose-dependent, all on the shear force effects.

These mechanoreceptors that are on cell surfaces and stuff, like these are all sensing things, and it's also very important. So I think it's another...so there's the lactate part of it where you're increasing the lactate, and it's a quick sort of...and it is. Like I've measured my lactate spikes up, you know.

I don't get up to the levels that my husband did. I'm more like a 7, 8 millimolar, and he gets up to like 14. But after 20 minutes, I'm back down to 1 millimolar, to my baseline, basically. So is there something with that lactate going intensely up, but also the shear force, I think. There's another interesting component to that that I think needs to be calculated into this equation because I'm seeing increasing data on that, not just with respect to brain health, but also people that have cancer.

So there's a lot of work from Justin Brown, he's at...I think it's Tulane in New Orleans. But the shear force and how it's affecting the circulating tumor cells. So basically people that have been diagnosed with cancer, you'll have a tumor cell that escapes the primary tumor site, goes into circulation, and that's the potential to metastasize, right?

So then goes, you know, is able to travel to another organ and take up camp there or whatever. So there's evidence that exercise, in general exercise, is involved in basically anything that gets your blood flow up. Basically those cancer cells die because they're so like disrupted and sensitive to the mechanical forces, whereas normal cells are fine.

But it seems to also, again, be a dose-dependent effect, where the more intense the exercise, the more blood flow that's going quicker, the more intense the effect. And also blood flow to the brain too, right? I mean, just getting that shear force as well. So I think there is a lot of interest there with the brain.

It to me is a differentiating factor from more continuous moderate exercise, even longer duration. Obviously, there's a lot of compensation probably that can happen metabolically when you're going for a longer duration, you know, period of time. But I do see something unique and I'm, you know, looking... I'm reading the literature, I'm trying to follow it as much and, you know, I mean, it's emerging, right? I mean, we don't really know.