Evolutionary Biologist: Our Hunter-Gatherer Past and the Exercise-Brain Health Link

Regular physical activity can improve cardiovascular and brain health, especially for those worried about Alzheimer’s risk. And for people who may already be living with dementia, forms of exercise like dance and yoga have shown cognitive benefits. Understanding this relationship could help us understand how to protect our brains from neurodegenerative disease… and some scientists are looking to humans’ evolutionary history to understand it. Biological anthropologist David Raichlen at the University of Southern California is one such scientist. His research probes how humanity’s hunter-gatherer could may shed light on the reasons that physical exercise seems to protect brain health.

As a professor of evolutionary biology in the Department of Biological Sciences at USC, Raichlen’s research focuses on the connection between human evolution, physical activity, and health across the lifespan. Currently, he’s focused on understanding how and why exercise and physical activity benefit brain structure and cognitive function, especially as we age.

Raichlen joined Being Patient founder Deborah Kan in conversation to share insights on this research. Read or watch the full conversation below. 

Being Patient: What do we know about exercise and the brain from our hunter-gatherer ancestors?

David Raichlen: To me, this is really the critical context for understanding how and why exercise and physical activity are beneficial across our physiological systems today, including brain health. Beginning around two million years ago, the best we can reconstruct, we see a shift in patterns of physical activity from more ape-like activity levels earlier on in our evolutionary history to the adoption of a hunting and gathering lifestyle, which was linked to much higher levels of physical activity. 

We can see that in changes in the human skeleton beginning about two million years ago. We see lots of adaptations throughout the body that seem to support higher levels of activity. Then, in our work with living hunter-gatherers today, we can work with people who lived this lifestyle, and get a window into what physical activity levels are like in this lifestyle. We just see profoundly high levels of activity, especially compared to humans living in more industrialized societies today.

Being Patient: What does a lot of physical activity look like?

Raichlen: For hunter-gatherers today, we see activity levels. There are a couple of different ways that we can think about it— probably people are really familiar with tracking your step counts, like how many steps per day you take. For modern hunter-gatherers, we see step counts of up to about 18 to 20 thousand steps per day. That’s quite a lot, considering most people in industrialized societies get around six to eight thousand steps per day.

We can also think about activity levels in terms of what’s called moderate to vigorous intensity physical activity. This is the type of physical activity that’s thought to be the most health-enhancing. Our government recommends that we get about 150 minutes per week of moderate to vigorous physical activity to maintain health. The hunter-gatherers that we work with meet those guidelines in one day. They generally get over 150 minutes per day of moderate to vigorous physical activity, so really high levels.

“For modern hunter-gatherers,
we see step counts of up to about
18 to 20 thousand steps per day.”

Being Patient: What’s the difference between then and now, in terms of consistency and the amount of exercise that we’re getting?

Raichlen: It’s really important to talk about what we mean when we think about using our evolutionary history as context. One of the things that we want to guard against is saying, “Well, that was what was happening in our evolutionary history, so that is the prescription for health today.” We know that’s not necessarily true. 

One key part of evolutionary biology is that evolution, and these processes don’t actually care about your health as you age. Evolutionary processes care about how you reproduce [and] how many offspring you have. The kinds of activity levels that we see in hunter-gatherers are not necessarily the best for aging, but they are the best for allowing those individuals to get enough food to survive and reproduce. 

I think that’s really critical because you don’t necessarily want to use 20,000 steps a day, for example, as the marker for what is healthy. The reason I think about it as context is that these kinds of studies tell us that our bodies evolved within the context of very high levels of activity, and that helps us understand why activity is so important to us. 

Now, what is optimal for brain health is an entirely other kind of concept. That’s something that we need to measure mostly in humans living in the context we’re living in today. I’m sure we’ll talk more about this, but just sort of as my guideline is that more is better than less in terms of what we see. Wherever someone is right now, adding a little bit of physical activity to their day is likely to generate benefits. As you get stronger and more fit, adding more will likely lead to more benefits.

“Wherever someone is right now,
adding a little bit of physical activity to
their day is likely to generate benefits.”

Being Patient: Hunter-gatherers had a certain dietary pattern. As it has been explained to me, they would hunt, feed, rest, get hungry again, and go back out and hunt. That pattern is also what a lot of people refer to when they talk about fasting and certain diets. Do we know if that’s actually a better dietary pattern for the brain?

Raichlen: I think that, in many ways, the idea of hunter-gatherers being incredibly food-stressed and having an enforced fast is not entirely accurate. Living hunter-gatherers have a really strong sexual division of labor. 

It is true that meat is not readily available at all times, because that’s a much harder resource to gain access to, but half of the population on a daily basis is going out and foraging for plant foods. That makes up a huge portion of their diet.

Especially when I’ve been out living with hunter-gatherer groups, there’s consistent food coming into camp every day. You’re not having difficulty getting access to food; it’s just not always meat. I think that’s sort of a critical aspect of their lives.

There’s been a lot of discussion in the literature about the Paleo diet. Again, it’s like trying to use the evolutionary prism as a prescription. One of the things that we’ve learned by working with hunter-gatherers around the world and looking at ethnographies from the recent past, is that humans are not adapted to a single style of diet or a single way of eating. 

Humans are adapted to variety. The human story is really a story of being able to accommodate new environments, new food resources, [and] new patterns of living. That’s how we’ve succeeded in spreading out across the globe. We’re flexible, and we eat a variety of diets in a sort of subsistence-level community. I think the Paleo diet is really being adaptable in my mind.

“The human story is really a
story of being able to accommodate new
environments, new food resources, [and]
new patterns of living.”

Being Patient: When you exercise 20 to 30 minutes per day, what are the benefits to the human brain?

Raichlen: We see widespread benefits associated with [exercise], especially meeting those physical activity guidelines. There are two types of studies that we want to be talking about when we’re thinking about these kinds of brain benefits. One is our cohort studies, where people are able to follow groups of people, track their physical activity, and then take measurements of brain volume in different regions. Those are association studies, so we can’t make causal links from those studies, but we can look at associations. 

Then, there are randomized controlled trials, where people are randomly assigned to groups that are either going to exercise or not. Over time, we can look at what happens in the group that was randomly assigned

to exercise. That tells us something more causal. There is evidence from randomized control trials that hippocampal volume in humans does increase, especially in older adults, if they’re randomly assigned to an exercise group. 

What we were talking about before we went live was: what is that volumetric increase? That’s where it gets a little tricky in humans because we don’t know if that’s new neurons or increased blood flow or what’s going on there that’s driving the volumetric increase. We know that the volume is increasing, and there have been studies that have shown that those volumetric increases are actually linked to improvements in memory in those randomly assigned exercise groups. 

Those studies are really hard to do and so there are not as many of them that are really high quality. There are a lot more of these association studies, which, if you think about them working in concert with randomized control trials, end up bolstering the evidence. 

Those association studies do show links between physical activity, brain size, and regional brain volumes. [This is] not only in the hippocampus but in frontal regions as well, [which] are associated with both memory and then with executive function. Decision making, planning, multitasking, [and] things like that. Again, we can’t causally link those from association studies. But it’s important to know that in large samples, we do see links between being physically active, having larger brain volumes, and better cognition.

Being Patient: If we exercise, can the risk to brain health from comorbidities like diabetes decrease? What do we know about the relationship between other diseases that can be helped with exercise?

Raichlen: We do know that people with diabetes who are physically active have a lower risk, or that’s associated with a lower risk of developing dementia later in life. Same with heart disease. This sort of whole cardiometabolic spectrum of diseases that do seem to have impacts on brain health, those impacts, or at least the risk of having those impacts, can be reduced by engaging in physical activity. 

What are the mechanisms linking physical activity in the brain? Some of those mechanisms might actually be minimizing these comorbidities, especially diabetes and cardiovascular disease. 

We see brain effects in terms of white matter hyperintensities, which is a vascular problem that can happen in the brain. When you exercise, you get a reduction in those hyperintensities. Those reductions may be telling us that we’re seeing vascular benefits from exercise that are having brain-associated benefits.

“We do know that people with diabetes
who are physically active have a lower risk, or
that’s associated with a lower risk of
developing dementia later in life.”

Being Patient: I wrote about this in my newsletter. I got a full-body preventative care scan done by a company, and one of the things I found is one of those white hyperintensity areas in my brain scan. It can be attributed to normal aging, and I was told to keep an eye on it. I’ve had two of those scans within four years, and it hasn’t gotten bigger. It’s about the same. I emailed a neurologist friend, and he told me to just keep exercising. For areas that appear on a brain scan, how much control do we have over those with exercise?

Raichlen: This is a ripe area for research, looking at the links between these white matter lesions and exercise and then future health impacts. White matter hyperintensities are an imaging feature that’s associated with these white matter lesions that are linked to the higher risk of stroke and a higher risk of Alzheimer’s disease and other related dementias. They do appear to be associated with vascular problems in the brain. They are a part of normal aging as well. 

I’m not a neurologist, so I don’t want to give out health advice, but from what my colleagues have told me, just finding white matter lesions in the brain on MRI is not something to be terribly concerned about, but they are associated with these risks. We do know that physical activity can play a role in minimizing white matter lesion loads. 

That is one area. We have a few lifestyle behaviors that we can control. In my mind, if we see links between a behavior and a disease outcome or some intermediate outcome that may be linked to disease, we have some control over whether we can engage in more or less of that behavior. 

That’s on us [and] we should really try to try to modify our behaviors. This is a really good example of that. [If] you find something on imaging that may be concerning, it hopefully is even more motivation to keep engaging in these behaviors that can minimize those.

Being Patient: What are the direct mechanisms happening in the brain when we exercise?

Raichlen: I think of a few different mechanisms, and we’ve kind of touched on two of them already. One is exercise and physical activity is just great for all the other physiological systems that are linked to the brain. [The] cardiovascular system [and] metabolic systems. 

Reducing cardiovascular disease, diabetes, and other comorbidities is one mechanism that actually allows physical activity to be associated with good brain health [and] vascular improvements. We know that physical activity is one of the most powerful things you can do for your vascular system. That improved vasculature brings more blood flow and more nutrients to the brain, which can be incredibly beneficial. 

Then, the third mechanism that we [consider] when we think about exercise and the brain is the increased neurotrophic levels. One in particular that we think about is a neurotrophin called brain-derived neurotrophic factor, or BDNF. BDNF, we know from animal studies, is strongly associated with the birth and survival of new neurons, especially in the hippocampus. 

This is sort of what we were talking about earlier. In animal studies, there have been direct links between physical activity upregulation of BDNF and the growth and survival of new neurons in the hippocampus. That is linked to cognitive improvements and reduced risk of cognitive decline. 

We can’t directly measure those new neurons in the human hippocampus, but what we can do is measure changes in BDNF associated with exercise. We can see these imaging increases in BDNF in hippocampal volume, and perhaps those two are related. Those are sort of the three mechanisms: improving comorbidity risk, improving vasculature and blood flow to the brain, and then neurotrophic upregulation that’s associated with neuronal health.

Being Patient: Can we supplement anything to boost that BDNF?

Raichlen: I mean, I have some ideas, but there’s not a lot that’s been tested specifically. There are some genetic polymorphisms [where] some people may be lucky and [have] an increased BDNF upregulation with exercise. Whether there is some kind of exogenous substance we can take in that can then improve that remains to be seen. 

If you can develop that, I can guarantee you will be a very happy and wealthy person down the road, right? Prevention, in my mind, is probably our best bet against Alzheimer’s disease and dementia. If we can find ways to boost these neurotrophins that may be beneficial to preventing disease, I think we really could make a big dent in disease incidence.

“If we can find ways to boost these
neurotrophins that may be beneficial to
preventing disease, I think we really could
make a big dent in disease incidence.”

Being Patient: What do we know about different types of exercise and brain health?

Raichlen: Great question. There really have not been direct head-to-head studies [with] a different exercise regime. We don’t have the kind of head-to-head studies you would need to answer that question. I can give you a little bit of the context that we can use to think about what might be best. There’s also been less work on resistance exercise, I’ll say that. 

Most of the work in this area has been focused on cardiovascular exercise. Sometimes, I think that’s because it’s easier to do that with animal models. So, the translations are easier because getting mice and rats to weightlift is not easy. There are ways to model that, but it’s complicated. 

From my evolutionary perspective, one of the pieces we’ve worked on is trying to understand why exercise is linked to the brain. We have developed a hypothesis that exercise or physical activity in the brain is likely linked because that’s what you need to do when you’re foraging. When you’re foraging for food, you are physically active, but you’re also cognitively active. 

You’re using spatial navigation and memory and making decisions, and really engaging in a lot of complex cognitive activity while you’re physically active. There, we’ve done some work showing, and others have shown that that activity that combines physical activity and cognitive activity may actually be some of the best exercises you can do. 

This brings us back to: what’s the best exercise? We think about the kinds of standard things that we do. Yes, dance might be really beneficial, because it’s such a combination of physical and mental activity. I tend to think that exercising in a gym, like getting on an elliptical or something, is great exercise. But maybe including some outdoor activity where you’re having to navigate, and you’re having to really pay attention to your surroundings might give you a little bit extra. That has not been directly studied, so I want to be careful. We don’t have an answer, but that’s the sort of context that I think about what could be the most beneficial?

“When you’re foraging for food,
you are physically active, but
you’re also cognitively active.”

Being Patient: Tell me a little bit about your own exercise routine. What do you do?

Raichlen: As I said, I’m a runner. That’s my main form of exercise. It is my therapy. If I don’t start my day with a run, then I feel kind of sluggish and not well all day. My wife knows when I haven’t run that day. I also stress [that] the reason that I do this is because I love it. If I didn’t love it, I wouldn’t do it. 

When we think about what kind of exercise [we] should do, I can tell people the best is the one that you enjoy and will do on a consistent basis. Because I know plenty of people who hate running, and they’re never going to do it. That it’s not something they’re gonna do day in and day out for the rest of their life. I happen to love it. 

It sounds like you do as well, and I can’t imagine my life without it. There are people out there [where] it’s pickleball, and they can’t imagine their life without that. There are people out there who just take a brisk walk after dinner with a friend or partner. That’s fantastic, right? That is exactly what I encourage; whatever you love and you can’t imagine your life without, that’s the one that you should focus on.

Being Patient: What do we know about the chemicals in our brain when we run and exercise? I find that when I run, I’m more focused and can think clearly. Are we stimulating our neurons when we exercise?

Raichlen: No, I don’t think so. I think there’s really good evidence for the sort of neurochemical changes that are associated with that feeling that you get after a workout. I’ve done work early on in my time in this field on endocannabinoids, which are the body’s endogenous form of the active ingredient in marijuana. 

Then there’s obviously a lot of work on endorphins, which activate opioid receptors and brain reward regions. Both of those work together actually in concert, during and after exercise bouts, and they seem to be responsible for those feelings of well being. The reason that you feel good for hours after a workout is because of these chemical changes in the brain. 

I always think about it from an evolutionary perspective. So I think about why these things evolved. And so, you know, we think about these compounds as being analgesics. They actually are pain relievers, which you can imagine being very beneficial for being physically active to have a little bit of pain relief, and also motivators. 

When you feel good, it motivates you to do this activity again. [It’s] motivating you to do something that is, in an evolutionary sense, what you needed to do to find food. I think we can kind of hijack these evolved mechanisms to find the behavior that makes you feel good, and that’s the one that you’re going to want to keep doing. 

One of the cool things I think about the endocannabinoid system, at least from animal studies [is], that the mechanisms is not really well understood, but that if you remove that endocannabinoid signaling from rodent models, you can knock out cannabinoid receptors, that exercise does not lead to the same kind of neurogenic activity or the birth of new neurons as if you have those cannabinoid receptors active. 

There seems to be a link between some of these molecules that are making you feel good, and the brain benefits, the neuronal benefits of exercise. Again, if you like doing something, it’s probably not just going to be beneficial to your mood, it’s probably going to be beneficial to other aspects of your health.

“If you like doing something, it’s
probably not just going to be beneficial
to your mood, it’s probably going to be
beneficial to other aspects of your health.”

Being Patient: What are you researching right now, and what do you hope to discover?

Raichlen: I’m interested in sedentary behavior right now. It’s not necessarily the flip side of physical activity, but the time we spend sitting is really interesting to me because it is our most common waking behavior. It’s what we do. Most people do it for most of the day. I don’t want to say everyone, but most of us sit for long periods of time. 

When you walk into a room, you can start looking around. You’ll notice that we structure our entire inner space in our homes, offices, and in public spaces around where you can sit. It’s a really common thing. What we’ve started to notice is that the time people spend sitting is linked with brain health in really interesting ways, not necessarily in a linear way. 

We published a paper last year showing that the time people spend sitting is linked with the risk of incident dementia in a nonlinear way. Up to about nine to nine and a half hours per day of sitting, there’s no change in the risk of developing dementia down the road. After that, ten-plus hours a day, the risks start to go up exponentially. You see really high risks that 12 to 14 hours a day of sitting, which is a lot of sitting admittedly. 

I’ve been really interested in this because, when we think about motivating people to be physically active, who out there doesn’t know that being active is beneficial to their health? But that doesn’t necessarily translate into lots more people engaging in physical activity. If there’s another modifiable behavior like sitting, that’s something that we can maybe tweak a little easier. 

We can sit less. You can find ways to get up and break up your long stretches of sitting. That may translate to some brain benefits. My research right now and going forward is kind of incorporating this sedentary behavior angle so that we can maybe think about ways to tweak that part of our behavior to improve brain health.

“What we’ve started to notice is
that the time people spend sitting is
linked with brain health in really
interesting ways, not necessarily
in a linear way.”

Being Patient: If I go for an hour-long run and then sit at my computer for 10 hours, will sitting so long negate the exercise, or does it not work like that?

Raichlen: We’re not sure if it works that way. It’s complicated. We know from some work on cardiovascular health that yes exercise can rescue long periods of sitting. From our brain health studies, we’ve done one very detailed look at that question and found that it did not matter how much exercise you got; sitting for long periods of time, especially watching television, was associated with increased dementia risk. Sitting and doing cognitively active things seem to be associated with benefits. So, it gets really interesting and nuanced. 

The accelerometer-based study where we were actually objectively tracking the amount of time people spent sitting, we did not find much evidence that physical activity was going to rescue that risk. I think that’s really that’s sort of a major area for us to understand: how to mitigate the risk of sitting. 

We can’t eliminate sitting and we don’t want to. Again, taking our evolutionary perspective, when we worked with hunter-gatherers, they sat for about nine or 10 hours a day. Our evolutionary history likely involved a lot of rest. There’s a reason why it feels so good. There’s a reason we gravitate towards sitting. It feels great, right? It is the most comfortable we can be, and we don’t need to eliminate it. We just need to minimize some of our long bouts of sitting.

Katy Koop is a writer and theater artist based in Raleigh, NC.