How Lactate Links Vigorous Exercise to Brain Health

Thomas DeLauer: Do you think that lactate levels are a contributing factor to the improvements in cardiovascular disease risk and things like that?

Dr. Rhonda Patrick: The lactate question is an interesting one because I sometimes measure my lactate after an intense workout and it's funny because most of the time, when people are trying to stay in that zone two level, they're trying to keep their lactate low and I'm the opposite. I'm trying to raise it as high as I can, right? So, lactate is a lot of times thought about as a metabolic waste molecule when we're forcing our muscles to work really hard our body is using glucose without the mitochondria and it's metabolizing glucose and then lactate's made as a byproduct. It's like, oh, this is a waste product.

Actually it's not a waste product. It's actually getting reused by muscle, by mitochondria for energy because it's easily used as energy by mitochondria. But it's also getting released into circulation. And in circulation, it's getting transported to tissues like the heart and it's used again as energy in the heart.

It's transported to the brain. And this is my biggest interest because of the effects on the brain. Lactate's being consumed at high quantities by the brain. This has been shown in a variety of animal studies, in human studies, radiolabeling studies have shown that lactate does get consumed by the brain during exercise and it's essentially not only an energetically favorable type of fuel.

So, what I mean by that is like your neurons like to use it because it takes less energy to use that than it does glucose. But it's also a signaling molecule. It's a way for your muscles to communicate with your brain, hey, I have a lot of stress being put on the body. We got to respond to the stress.

It's a stressful situation, right? And so it's a direct form of your muscles to communicate with your brain because you got to be mentally like on top of your game if you're like working out really hard. Like your body has these systems in play, right? And so it increases things like norepinephrine.

That's been shown as well. So, lactate increases norepinephrine and this actually fuels your brain activity during intense exercise. And it's funny because fMRI studies have shown this and you really like norepinephrine supports focus and attention. Your brain also is working harder when you're exercising hard just like your muscles and your heart and it's important.

You need your brain to work hard, too, right? And that lactate is what's essential for that. The lactate's doing it. The other thing lactate's doing is it's signaling to increase what's called brain-derived neurotrophic factor, BDNF.

And that is happening in your vascular system. It's also increasing at the blood-brain barrier and it's increasing in the brain. And what it does in the brain is it's very important for the growth of new neurons. So, this happens in certain regions of the brain like the hippocampus, which is involved in learning and memory.

In fact, there's a study from I think it was like Dean Ornish's group many years ago that showed like a couple of months of aerobic exercise increased hippocampal volume in like older individuals and it was like, oh, wow, you can actually increase your brain volume after exercise, right? So, BDNF plays a role in that. It also plays a role in learning and strengthening connections between neurons and memory. It plays a role in neuroplasticity.

So, this is the ability of your brain to change and adapt to a changing environment. So, this is very important for not only just cognition, but also just plays a role in depression as well. So, people that are depressed have decreased neuroplasticity. So, in other words, they have a problem.

Their brains aren't able to adapt to changing environments as well and that's part of what sort of instigates the depressive feelings when you can't adapt to your environment. It's like what do I do? I can't like what I don't know what to do. It's like so it plays a role in depression as well.

So, increasing brain-derived neurotrophic factor improves cognition, staves off brain aging, plays an important role staving off neurodegenerative disease. In fact, there've been studies in animals done exercise-induced BDNF. If you give an animal a drug that blocks that they don't experience any of the cognition benefits from exercise.

Thomas DeLauer: Short-term and long-term?

Dr. Rhonda Patrick: I don't know how long-term the studies went out. I mean, that's a good question. I don't, because then it's like you get, well, what about taking that drug long-term? What's that doing?

But certainly short-term. So, like the cognition boosts and stuff that happened immediately. Also neurogenesis and stuff isn't increasing as well, but like the battery of cognitive tests they subject these animals to, they didn't have the improvements that they did when they had the exercise without the BDNF blocking drug.

Thomas DeLauer: Interesting. Do you think that some of the mental benefits we have chalked up to endorphins are actually an acute response to lactate?

Dr. Rhonda Patrick: I do. Yeah. I think there are a lot of things changing with exercise.

I mean Mike Snyder's group showed something like 500 molecules in the blood are like changing. Five hundred. So, there's a lot of changes that are occurring. Lactate is one of them, and it is very acute.

So, you can go from a baseline steady-state level. Most people have about 1 millimole per liter of lactate. When you start to do your high-intensity training, depending on how intense we're talking about, let's say you go anywhere between 7 to 20 millimoles per liter. That'll go down pretty quick.

After about 20 minutes, you're back to 1 millimole per liter. And that is largely because other organs are consuming it fast. The brain is one of the biggest consumers of lactate. Again, it fuels brain activity, so when your brain is working harder, lactate is fueling it.

So, right now, our brains are working hard. We're having a very intellectual discussion. The question is, if we had just made a bunch of lactate from exercise, would that help fuel our brains? I think so.

I think so because lactate is increasing norepinephrine, serotonin, and brain-derived neurotrophic factor. But it's also helping our brain use energy efficiently.

So, lactate gets transported across the blood-brain barrier through the same transporter as beta-hydroxybutyrate, called an MCT, the ketone-body transporter that everyone talks about in the context of ketosis. It gets into the brain and neurons use it for energy much like they do beta-hydroxybutyrate. So, it's converted into pyruvate and easily used as energy. Very easy.

Much easier than actually having to convert glucose into energy. In fact, most people don't realize that many neurons use lactate for energy. Astrocytes, our brain-supporting cells, make lactate, and neurons take it up from the astrocytes and use it for energy. In addition to increasing brain-derived neurotrophic factor and neurotransmitters, making extra lactate also increases mitochondrial biogenesis. Animal studies show that lactate increases PGC-1 alpha, one of the main regulators of mitochondrial biogenesis.

Animal studies have found that exercise-induced lactate gets into the brain. That increases PGC-1 alpha and mitochondrial biogenesis specifically in neurons. I haven't seen any human studies. I don't know that we ever will.

I mean, to do that would require tools that we don't have yet. But there's no reason why that mechanism wouldn't be conserved in humans. I think lactate probably increases mitochondrial biogenesis in human neurons as well. That has yet to be empirically shown in humans.

That's another important aspect because mitochondrial health is hugely important for cognition, for staving off brain aging, when we're talking specifically about the brain. And then lactate is also allowing glucose to be spared from neurons. In other words, neurons then don't have to consume glucose. They do not have to use the energy required to be able to use glucose as an energy source.

So, they're not having to work as hard and that glucose is now allowed to be used for other things. There is a term in the literature called glucose sparing. The glucose sparing effect and specifically in neurons what happens is glucose can then be used in other biochemical pathways. And one of the main pathways is the pentose phosphate pathway to make precursors for glutathione, NADPH being the main one.

It has been shown that lactate can allow glucose sparing and thereby increase glutathione synthesis, because glucose is not being used for energy. It can be used to make this other important antioxidant, which is the major antioxidant in the brain. My personal take is that the repeated doses of lactate from high-intensity exercise probably have cumulative effects on glutathione synthesis and brain-derived neurotrophic factor.

But also just going to the traumatic brain injury model, which I think is a very interesting way to look at brain aging in real time because brain aging is this sort of insidious damage that happens over time. It accumulates and you have inflammation, reactive oxygen species, dysfunctional mitochondria, autophagy going down, protein aggregates. You get the point, right? Like this stuff is accumulating over decades, right?

And it's part of the aging process. Traumatic brain injury is almost like Alzheimer's disease in real time.

Thomas DeLauer: Accelerated.

Dr. Rhonda Patrick: Yeah. In fact, TBIs increase the risk of Alzheimer's disease depending on how many TBIs have occurred, anywhere from two-fold to like 15-fold. Like they have the same effect of having the well-known genetic APOE4 allele or it's almost like having two of them. So, with traumatic brain injury, a lot of damage is happening.

It's almost like the whole aging process, but like instead of over 30 years, it's like 24 hours, right? So, there's been studies with looking at traumatic brain injury and lactate. So, George Brooks, the father of the lactate shuttle, the one who was originally responsible for showing lactate gets shuttled from muscle into the brain, into the heart, and it's beneficial in acting as a signaling molecule. He's done a lot of work collaborating with UCLA and traumatic brain injury patients.

For example, people with a gunshot wound to the head come into the ER. Infusing patients with sodium lactate improves their TBI scores and their outcomes. Like they do better. And so, like why is that?

Well, it's probably a lot of reasons, but glucose sparing could be one, the BDNF, mitochondrial biogenesis. Speculation on that. All these are sort of the mechanisms are sort of speculation, but there's a lot of possibilities and biologically plausible reasons why sodium lactate is improving TBI outcomes compared to just saline, right? So, I personally think the more vigorous the exercise, you're getting that lactate, and it's having such beneficial effects in the brain that it's really important for staving off brain aging.

I have a high risk for neurodegenerative diseases. They're in my family. And so, I'm very focused on the brain. And when I am exercising, it's very much like I don't want to get Parkinson's.

I don't want to get Alzheimer's disease. And this is where, I think exercise intensity shines and why I'm so focused on trying to get my heart rate up to make sure to make my lactate higher. I don't always measure lactate after every workout. I have measured it quite a few times, but that, trying to get my lactate higher, like it's important to me because I think that it's just so beneficial and I think that there's cumulative effects of it as well.