Newsletter #292

One of the most compelling findings in the sphere of lifestyle medicine is the impact of physical activity not just on the body, but also on the health and performance of the brain. This is driven by an array of mechanisms, which have been further elucidated fairly recently through research in animal models.

For one thing, exercise promotes the release of neurotrophins, proteins that stimulate growth of nerve cells and formation of synapses. Most notably, exercise boosts levels of brain-derived neurotrophic factor (BDNF), a protein that helps brain cells grow and connect to one another, and that is essential for learning and long-term memory. Levels of BDNF rise transiently, as much as ~3-fold, in response to acute exercise, then returning to baseline shortly thereafter. These relatively short-lived “bursts” of BDNF, as well as some other factors, are correlated with exercise-induced cognitive improvements.

Human interventions have shown that greater intensity often leads to significantly greater levels of BDNF, even compared to a much greater duration and volume of lighter physical activity. For instance, just six minutes of cycling intervals dramatically increases BDNF (from 396 pg/L to 1170 pg/L) — 4-5 times more than when subjects perform 90 minutes of light cycling!

That increase was correlated with a 6-fold rise in lactate, and that might be an important clue as to why intensity matters. Lactate is responsible for the “burn” you feel in your muscles when you’re working really hard. But it is far more than just a waste product of anaerobic metabolism. We have previously discussed here how lactate, generated during exercise, may rejuvenate T-cells, making them better at fighting cancer, and could facilitate weight regulation through its appetite-suppressing effects.

It has been suggested that lactate may play a role in the cognitive benefits of exercise, and this could have important implications for the right intensity needed to elicit maximal levels of BDNF, and other humoral factors that modulate cognition. If indeed lactate is a key mediating factor, then you would probably need to train hard enough to recruit your fast twitch muscle fibers. In other words, just walking or jogging might not cut it. And how do these biochemical changes translate into improvements in memory and other useful cognitive functions?

Exercise intensity seems to be a key regulator of "exerkines," or factors released into circulation in response to exercise. However, the optimal intensity remains unclear. Furthermore, other factors outside of BDNF may affect cognitive processes, either independently or in concert with BDNF. For instance, cathepsin B is a recently discovered factor secreted by muscles in response to exercise, and which appears to cross the blood-brain barrier and influence cognition by inducing BDNF.

To narrow down just how intense exercise needs to be to maximally trigger these factors, researchers affiliated with Incheon National University in South Korea recruited nine young men, and had them visit the lab to test their cardiorespiratory fitness (VO2max) and take other baseline clinical measurements.

Then, the men went through four different experimental exercise sessions, each separated by 1-week intervals:

To measure BDNF and cathepsin B, as well as other biomarkers, blood samples were collected at four separate intervals:

Levels of lactate were far higher following the HIIE, and remained elevated even 90 minutes post-exercise, compared to all other sessions. This was accompanied by higher levels of BDNF and cathepsin B. Furthermore, increases in blood lactate were positively correlated with changes in the exerkines.

This makes sense. For one thing, lactate can cross the blood-brain barrier and lactate uptake in the brain increases by more than two-fold during exercise. And this may be driven by its interactions with BDNF. Studies that use blood lactate to monitor exercise intensity have shown that higher lactate concentrations are correlated to increased levels of BDNF, and when researchers administered IV infusions of lactate to resting human participants, BDNF levels rose significantly.

Prior research on the effects of acute exercise on memory have produced conflicting results, which seem to hinge upon the intensity of the exercise bout. As shown above, this may be due to differences in humoral responses to harder physical activity, including the aforementioned neurotrophic factors. Additionally, the stress of intense exercise tends to elicit greater increases in adrenal hormones, or catecholamines, which are thought to potentially influence memory performance.

To examine how exercise intensity, and associated hormonal changes, can affect learning and memory, researchers at the University of Münster recruited 27 young male students, and put them through progressive exercise tests to determine each individual's physical fitness.

Then, they had the guys visit the lab on three different occasions. During these sessions, they went through the following conditions, using the exercise tests and blood lactate testing to carefully modulate the intensity of the activities for each subject:

Fifteen minutes after every intervention, subjects learned vocabulary words in an artificial language, with a different version of the novel vocabulary offered for each condition. They were tested on their ability to translate these words immediately after the training session, then at retention sessions which occurred one week later and 8 months thereafter.

So what happened?

After the aerobic exercise, no improvements in learning and memory were observed. But after sprinting, the subjects learned vocabulary 20% faster, compared to when they either rested or jogged.

As expected, the sprinting also resulted in elevations in catecholamines, as well as BDNF. Higher sustained BDNF levels while studying were linked to better short-term learning, and higher levels of catecholamines (suggesting greater arousal) were associated with better long-term retention of vocabulary in subsequent testing.

Solid line = sprint, dashed line = moderate, dotted line = relaxed control

One key thing that I think is worth noting here is that the total volume of exercise here was very modest. Two 3-minute sprints is tough, but it's not an utterly exhausting exercise load, and it probably wouldn't result in a whole lot of sweating. I point this out because research does show that strenuous exercise which results in fatigue or dehydration is counterproductive with respect to cognition. So if you're going to try to take advantage of this phenomenon, especially when working or studying, you will want to rein in the volume.

🐁 Mice in the wild will use an exercise wheel if it’s left outside for them.

A lot of the research that examines the benefits of exercise for cognitive function, as well as other domains of health, use wheel running to facilitate physical activity. This is obviously necessary for lab animals living in cages, plus it’s a little easier to measure and control levels of exercise this way. But is wheel running a “natural” behavior, or is it a pathological activity that rodents develop in the captive environment?

To answer this question, some Dutch researchers installed running wheels in open areas where feral mice were known to roam, and set up cameras to record. Sure enough, wild mice happily used the wheels year round.

But not just mice — the researchers captured wheel running in other species, including rats, shews, frogs, slugs, and snails!

Obviously, one drawback to training hard enough to generate substantial amounts of lactate is that it’s really freaking hard. This is where LactiGo can help.

When you exercise hard, lactic acid is generated, which is subsequently broken down into lactate and hydrogen ions. This causes cellular pH to drop, producing the well-known burning sensation and making it hard to maintain force production. Carnosine has long been known to act as a pH buffer, and higher levels of carnosine in muscle can help prevent accumulation of hydrogen ions during high-intensity exercise. This increases the power you can produce during a workout, and potentially aiding recovery, while still enabling you to reap the benefits of lactate-generating activity.

To learn more about how it works, and how it could enhance your own training, check out our past interview with Brad Dieter, LactiGo’s lead scientist.

In this course, we review:

🧠 Effects of exercise on the brain

💡 How physical activity within the day can improve your thinking

🏋️ Strategies to integrate more movement into your day

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