Greetings!

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

Exercise burns energy. Food replaces it. And if too little energy remains after training, the body starts cutting costs. And when athletes under-fuel, we tend to treat the problem as a simple “calorie shortage.”

That basic idea is captured by a concept known as energy availability. It is the energy you consume minus the energy you expend during exercise, divided by your fat-free mass:

Energy availability = (energy intake − exercise energy expenditure) ÷ fat-free mass

Imagine a runner with 60 kilograms of fat-free mass who eats 2,500 calories and burns 1,000 calories during training. That leaves an energy availability of 25 calories per kilogram of fat-free mass per day. That’s a level low enough to trigger physiological changes within a matter of days.

What does that look like? Well, the body responds to this shortage by becoming more selective about where it spends energy. Processes essential to immediate survival take priority. Processes related to growth, reproduction, bone remodeling, and other longer-term investments may receive less. This is the physiology underlying low energy availability, the Female Athlete Triad, and Relative Energy Deficiency in Sport, also known as REDs.

But there is one huge complication…

That creates a difficult question: how much of the body’s response is caused by the energy shortage itself, and how much is caused by having too little carbohydrate available? Because they are not necessarily the same thing!

Two athletes can have identical energy availability while finishing the day with very different amounts of carbohydrate left after training. Researchers call this carbohydrate availability:

Carbohydrate availability = carbohydrate intake − carbohydrate oxidized during exercise

One athlete might replace most of the carbohydrate burned during a long workout. Another might consume the same number of calories but replace those calories largely with fat or protein. Their energy budgets are identical. Their carbohydrate budgets are not. And carbs are much more than just fuel. They influence IGF-1 (a hormone important for growth and tissue repair), testosterone, thyroid hormones, appetite hormones, and more.

Many of these reliably fall during short periods of low energy availability. So the question is whether some of that decline reflects low carbohydrate availability layered on top of the calorie deficit.

A new randomized crossover study tried to separate the two.1

Researchers recruited 16 young, recreationally active adults—nine women and seven men—and put each participant through two four-day periods of low energy availability.

That brings up an important point. Low energy availability does not always mean someone is eating very little. A high training load can create the same shortage even when food intake looks substantial on paper. In fact, I think there’s good reason to assume that a calorie deficit achieved via eating less is NOT the same as the same deficit achieved by exercising more. But I digress…

The two conditions differed in how their calories were distributed:

• During the low-carbohydrate-availability condition, participants consumed 4.2 grams of carbohydrate per kilogram of body mass per day. After subtracting the carbohydrate used during exercise, their carbohydrate availability was about 1.4 grams per kilogram per day.

• During the high-carbohydrate-availability condition, participants consumed 6.7 grams per kilogram per day, leaving about 3.7 grams per kilogram per day available after exercise, or roughly twice that of the low-carbohydrate group.

Even the “low” condition included what might look like a respectable daily carbohydrate intake. It became low only in the context of nearly two hours of cycling every day.

Energy intake and protein intake were nearly identical between conditions. To make room for more carbohydrate without adding calories, the researchers reduced fat. Carbohydrate supplied 46% of calories in the low condition and 73% in the high condition; fat supplied 37% and 11%, respectively; protein was matched at 15% of total daily calories.

Before and after each condition, the researchers measured body composition, resting metabolism, fasting hormones, fuel use at rest and during exercise, blood lactate, peak oxygen uptake, and maximal cycling power.

What happened?

Both conditions produced almost identical weight loss: about 2.2 pounds or roughly 1 kilogram in four days. Resting metabolic rate did not change. So the calorie deficit was doing what calorie deficits do, regardless of where the calories came from.

The hormonal response was a bit more interesting.

IGF-1 fell in both conditions, but the decline was roughly cut in half when carbohydrate availability was high.

IGF-1 declined by 20.2% during low carbohydrate availability and by 9.4% during high carbohydrate availability.

The higher-carbohydrate diet did not prevent endocrine suppression. But it meaningfully attenuated one of its clearest signals.

Insulin and testosterone both declined significantly during low carbohydrate availability but not during high carbohydrate availability. Leptin (sometimes referred to as the “hunger hormone” also appeared to fall less in women when more carbohydrate was available.

But this is where the statistics matter. When the researchers tested that difference directly, changes in insulin, testosterone, leptin, and T3 were not significant. In other words, they didn’t change. IGF-1 was the only measured hormone for which the evidence clearly showed a different response between the two diets.

Now onto the exercise data.

Maximal blood lactate during the max exercise test fell by 1.2 mmol/L after the low-carbohydrate condition and was essentially unchanged after the high-carbohydrate condition. The lactate curve also shifted to the right only when carbohydrate availability was low.

Odd, right? A given lactate concentration at a higher percentage of peak oxygen uptake might look like an improved lactate threshold. But after four days of under-fueling, that is probably not what happened. Rather, the decline in maximal lactate suggests that low carbohydrate availability reduced the ability to rapidly break down carbohydrate and produce lactate during hard exercise!

Keeping carbohydrate availability high appeared to preserve more of that glycolytic capacity.

That did not translate into a measurable performance difference. Peak oxygen uptake and maximal cycling power were unchanged in both conditions.

At rest and during exercise, low energy availability shifted the participants toward greater fat use, but higher carbohydrate availability did not clearly prevent that shift. Men generally showed larger increases in maximal fat oxidation and larger decreases in carbohydrate oxidation during submaximal exercise.

In other words, the calorie deficit still shifted resting and exercise metabolism in a meaningful way, even when carbohydrate intake was high.

So, is low energy availability partly a carbohydrate problem?

It appears to be—at least for some acute responses.

This study makes a strong case that the macronutrients inside a calorie deficit are not interchangeable. Two diets can produce the same energy availability while creating different hormonal and energy-use signals. Preserving carbohydrate availability cut the short-term IGF-1 decline roughly in half and prevented the reduction in maximal blood lactate. But otherwise, all else looked mostly the same after this four-day intervention.

Carbohydrate softened part of the response but did not make under-fueling physiologically harmless.

I think that this study cannot tell us a lot of things, but that doesn’t mean it isn’t practical. It doesn’t tell us that a change in fasting IGF-1 over four days leads to a noticeable health or performance outcome, nor does it tell us whether more carbohydrate prevents the long-term outcomes associated with REDs such as menstrual disturbances, impaired bone health, recurrent injury, or declining performance. Those questions require longer studies in athletes.

Here’s the use case.

If you’re temporarily entering an energy deficit, knowingly or unknowingly, such as might happen during a high-volume training block, a weight-making phase, or simply a few days when food intake isn’t keeping pace with your training… protect your carbohydrate intake!

In practice, that may mean really focusing on carbohydrate across high-demand training days and, at the micro level, optimizing the timing of carb intake around workouts (though this study did not test nutrient timing).

Eat enough to support the work you’re doing. Carbohydrates aren’t a shield against chronic under-fueling. But if you can’t restore a deficit immediately, the type of calories you preserve probably matter. The body appears to respond not only to how much energy remains, but also to which fuel remains available.

The best solution to low energy availability is still to restore energy availability.

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Last week, I appeared on The Neuro Experience podcast with Louisa Nicola, a neuroscientist and one of my absolute favorite people in the health and wellness space right now.

We talked about some of the latest science on what running a marathon does to your brain, the best types of training to improve VO₂ max, exercise non-responders, and much more.

I’ve included the YouTube video below.

You can also find the podcast on Spotify and Apple Podcasts.

Greetings!

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

Exercise is generally accepted as a great way to lose weight, maintain weight, or prevent weight regain.

And that’s because we tend to view metabolism as a math equation.

The number of calories we burn in a day—our total energy expenditure, or TEE—is ultimately determined by three things:

• Resting energy expenditure (REE), which reflects how many calories your body uses to support normal physiological processes.

• Activity energy expenditure (AEE), which reflects how many calories you burn through exercise and other physical activity.

• Diet-induced thermogenesis (DIT), which reflects the energy required to digest and process food… think “meat sweats.”

Researchers call this the additive model of energy expenditure. It assumes resting and activity energy expenditure are independent: one does not meaningfully reduce the other.

Over the past decade or so, the additive model has been challenged by another theory known as the constrained model.

Researchers observed that among highly active people, activity energy expenditure tended to be high, but total daily energy expenditure was not always much greater than it was in less-active people. In some studies, when people undertook huge amounts of exercise, their total daily energy expenditure rose less than their activity level would predict—or sometimes not at all.

This discrepancy was attributed to something called metabolic compensation. It’s the idea that doing more activity somehow causes the body to reduce energy allocation elsewhere, lowering resting energy expenditure and keeping total daily energy expenditure relatively constant. I go on that same 10-mile run, burn 800 calories, but my body “offsets” that by investing less energy in other stuff my body has to do.

That compensation might come from lower hormone production, fewer resources devoted to reproduction, or what researchers call behavioral compensation, where people simply engage in less non-exercise activity, such as fidgeting, pacing, or spontaneous movement throughout the day. I’ll admit that I spend a bit more time on the couch after a long run… that’s behavioral compensation in action.

The constrained model is often used to explain why exercise is not a particularly powerful tool for weight loss: the body “adapts,” and eventually calorie burn becomes something like a zero-sum game.

It’s a highly controversial idea—and according to a new study, this particular version of it is not well supported by the evidence.1

• • •

To test whether energy expenditure is truly additive or constrained, researchers used two complementary approaches.

First, they conducted a tightly controlled experiment in 12 adults. Each person completed two separate 10-day periods—a high-activity and a low-activity period—separated by a washout period:

• During the high-activity period, participants added 135 MET-minutes of physical activity per day. A MET is a unit of activity intensity: 1 MET is the rate of energy expenditure at rest. 35 MET-minutes is roughly equivalent to 30–45 minutes of moderate-intensity activity or a few hours of brisk walking. Not elite-athlete levels, but well above their usual baseline.

• During the low-activity period, they were essentially told to be “as lazy as possible” (my wording, not theirs).

During the high-activity phase, activity energy expenditure rose by about 28%, or roughly 250 calories per day.

What happened to total energy expenditure?

It rose by about 272 calories per day—a 10% increase—while resting energy expenditure, adjusted for body size and composition, did not fall (neither body weight nor body composition changed meaningfully in either group during each 10-day period).

In other words, the extra activity these participants were doing added almost one-for-one to their total energy expenditure, without measurable compensation through a suppressed resting metabolism—exactly what the additive model predicts.

Case closed, right?

Somewhat.

This was a short-term study, and one argument for the constrained model is that there may be a time lag between increases in activity and metabolic compensation. Ten days might not be enough for that compensation to emerge.

So the researchers complemented the experiment with observational data from 268 adults living under normal, free-living conditions.

If long-term physical activity really causes resting metabolism to drop, you would expect to see that relationship across a diverse group ranging from sedentary to highly active.

As a final sanity check, the researchers also compared the human data with metabolic scaling patterns across other mammals. The same basic relationship held: resting and activity energy expenditure behaved independently. Their findings in the large group of adults did not appear to be some unique quirk of human biology.

• • •

Most of us do not exercise simply to burn calories. Nor are the benefits of exercise limited to losing or maintaining weight.

But it is nice to know that, within the range of activity most people are likely to perform, our energy budget appears to be more additive than constrained. The more you exercise, the more energy you burn.

That does not mean you should take the calorie number on your fitness tracker literally. This study supports the direction of the equation, not the precision of a wrist-worn estimate.

The body is not a perfectly predictable math equation. Energy expenditure on any given day fluctuates with activity, body composition, diet, sleep, and a host of other factors we cannot fully account for.

I also don’t think this study proves once and for all that the constrained model of energy expenditure has been debunked. I’m not even sure science can ever do that with a single model. But I think anecdotal experience alone is enough to convince most of us that the additive model makes intuitive sense.

Anybody who has done a block of intense exercise training—preparing for a marathon or triathlon, for example, or simply increasing activity for the fun of it—has probably noticed that unless they stay on top of their eating, weight tends to drop. When I run more, I lose weight. If I eat more to offset that running, my weight stays stable.

On the opposite end of the spectrum, there is even some evidence that energy expenditure may remain elevated after strenuous exercise through a phenomenon known as excess post-exercise oxygen consumption, or EPOC.

I’ll end with one final nuance that I don’t think much of this research has fully addressed. Even the high-activity condition in today’s study involved a fairly moderate amount of daily exercise. There is still a chance that some metabolic compensation occurs at the extreme upper end of exercise—what you might see in Tour de France cyclists, Ironman triathletes, or ultramarathon runners.

I’m open to the possibility that there is some kind of cap on sustained human energy expenditure (in fact, it’s an idea that has been proposed in the literature). Once you approach that cap—which very few people ever do—the body may begin diverting resources away from physiological maintenance. That is probably part of what we see in athletes who lose their menstrual cycle when high training loads are combined with inadequate energy intake.

Whether metabolism is constrained probably does not change how you or I are going to train. Regardless of which model is ultimately closest to the truth, it probably shouldn’t.

But I’m curious: would it change anything for you?

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Greetings!

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

"Those who think they have not time for bodily exercise will sooner or later have to find time for illness." — Edward Stanley, 19th century British Politician

In science and medicine, exercise is usually treated as the intervention—the unusual thing we add to someone’s life to see whether it improves their health.

But physical activity is not the intervention. It is the biological norm. Being inactive is the intervention, at least in modern times.

Our physiology evolved under conditions of regular movement (exercise, by contrast, is a relatively modern invention… and quite weird if you think about it).

As the authors of a new paper (the subject of today’s newsletter) put it, physical activity is a “canonical characteristic” of humans. Yet we’ve normalized its absence so completely that we now view exercise as a special behavior.

You can see this play out in medical and exercise research, where “healthy sedentary” people are often used as the control group. But Inigo San-Millan and his colleagues argue that the concept of a healthy sedentary person may be biologically inconsistent. Sedentarism may not represent a neutral baseline at all, but rather, an early stage of “bioenergetic dysfunction”—a state in which the machinery responsible for producing energy has already begun to downshift, even before someone develops a disease.

And if we know anything, it is that mitochondrial dysfunction is the root of all evil (I am only slightly being tongue-in-cheek here).

This new study by Dr. San-Millan’s group asked whether the way someone burns fuel—and the point at which lactate begins to rise during exercise—may serve as a window into what is happening inside their mitochondria.1

The answer appears to be yes. In sedentary people, what looked like “low fitness” from the outside was accompanied by a distinct bioenergetic phenotype underneath it.

You’re going to want to sit down (or perhaps, stand up and run around) for this one…

The study included 19 otherwise healthy men who were around 42 years old on average. Nine did no regular exercise (ever!), while ten performed at least 150 minutes of aerobic exercise per week for six months or longer. These are referred to as the “sedentary/inactive” and “active” groups, respectively.

One thing to keep in mind is that these groups were not perfectly matched. The sedentary participants had a higher average BMI (28.3 versus 23.8 in the active group), which could have contributed to some of the metabolic differences. They also had a VO₂ max that was nearly 40% lower than the active group.

The first big difference was that the muscles of the sedentary people had a smaller aerobic engine.

Compared with the active participants, the sedentary group had 26–36% lower capacity to produce energy across the entire mitochondrial electron transport chain (this is the “battery” that turns electron flow into ATP inside the mitochondria). For every milligram of muscle tested, the sedentary participants had roughly one-third less capacity to use oxygen and produce energy through their mitochondria.

The biggest difference involved a protein called mitochondrial pyruvate carrier 1, or MPC1.

When we break down glucose, we produce pyruvate. That pyruvate then has two main options: it can enter the mitochondria and be oxidized for energy, or it can be converted into lactate. MPC1 is part of the transport system that moves pyruvate into the mitochondrial matrix. You can think of it as one of the doorways connecting the breakdown of glucose outside the mitochondria (glycolysis) to aerobic energy production inside the mitochondria.

In the sedentary participants, MPC1 abundance was 49% lower! This was the largest difference among the major proteins measured in the study, and it was accompanied by a 37% reduction in the muscle’s ability to use pyruvate to produce energy.

Interestingly, the groups had similar amounts of GLUT4, the transporter that helps move glucose into skeletal muscle cells, and similar amounts of two proteins involved in converting pyruvate and lactate back and forth. So it doesn’t appear that the groups differed in their ability to bring glucose into the muscle cell—the difference was downstream at the step where pyruvate (from glucose breakdown) enters the mitochondria.

(I get that some of this stuff sounds complex. But it’s so cool! So bear with me).

A simple way to think about this is that glucose could still reach the muscle, but the doorway into the mitochondria appeared to be narrower. This was confirmed by showing that two breakdown products of lactate (citrate and malate) were also less capable of making their way into the mitochondria in sedentary muscle compared to active muscle (about a 35–40% reduction).

Every result we’ve just talked about relates to glucose (carbohydrate) metabolism. So sedentary people might just be worse “carb burners” and make up for it by being better “fat burners.” Wrong.

In sedentary people, activity of CPT1—the enzyme that helps move fatty acids into the mitochondria—was 51% lower, and fatty-acid oxidation inside the mitochondria was 32–25% lower.

Sedentary people had a generalized reduction in the amount of oxidative machinery available within the muscle. They were worse at transporting/burning carbs and fat for energy.

And their mitochondrial membranes looked different too.

The researchers also measured reactive oxygen species, or ROS.

At first glance, the active participants actually produced more ROS in absolute terms. But they also had more metabolic activity, and when this was accounted for, the sedentary participants generated more ROS relative to how much oxygen they were consuming—which could mean less efficient energy production or even worse antioxidant capacity.

Another big difference is what we’ll refer to as a “metabolic traffic jam” upstream of the mitochondria. Sedentary muscle appeared to accumulate more breakdown products of carbohydrates while having less capacity to move those fuels into and through the mitochondria.

Meanwhile, the active profile was more consistent with greater use of fatty acids and more activity within the energy-producing systems in the mitochondria.

What happened when they exercised?

All of the differences the researchers observed between the muscles of active and sedentary participants were reflected during exercise.

The active participants had:

• 31% higher absolute VO₂ max

• 38% higher VO₂ max relative to body mass

• 35% higher maximal power output

• 42% higher power output relative to body mass

None of that should be particularly surprising. The more interesting result was how the two groups produced energy as exercise intensity increased.

• In the active group, fat oxidation rose throughout low-to-moderate exercise and peaked at around 0.35 to 0.40 grams per minute near 150 watts.

• Lactate remained below approximately 1 mM across much of this range, and only as the workload became harder did fat oxidation begin to decline while carbohydrate use and blood lactate rose.

• At easier workloads, the active participants could rely heavily on fat. As exercise became more demanding, they gradually shifted toward greater carbohydrate use.

This is metabolic flexibility in action, and it’s the “classic” response to increasing exercise intensity (and it’s quite beautiful, if you ask me).

The sedentary group followed a very different pattern.

• Their fat oxidation peaked at only around 0.15 to 0.20 grams per minute, roughly half of what was observed in the active group. It also began falling much earlier as workload increased.

• At the same time, carbohydrate use became dominant earlier and lactate began rising from the first few stages of exercise (in addition to being higher at rest, before they even started pedaling the bike).

• At 125 and 150 watts, blood lactate was more than 60% higher in the sedentary participants. They reached the limits of their oxidative metabolism (“fat burning”) much earlier. They had to rely more heavily on glycolysis, resulting in earlier and greater lactate accumulation.

Now let’s get to what I think is the most practically useful part of the study.

The researchers did not just find differences between the two groups. They also found that the measurements taken from resting muscle were strongly related to what happened during exercise.

People whose muscle had a greater capacity to use fat at rest also burned more fat on the bike.

Blood lactate showed the opposite pattern. People with lower mitochondrial capacity at rest tended to accumulate more lactate during exercise. And participants with more MPC1 (the pyruvate transporter we talked about earlier) tended to burn more fat and accumulate less lactate during exercise.

Having a higher VO₂ max was also associated with better mitochondrial energy production.

All of this suggests that the lactate and fat-oxidation responses observed during an exercise test may provide some insight into what is happening inside the muscle.

The authors even propose that measuring fat oxidation and lactate during a submaximal exercise test could provide a noninvasive window into mitochondrial health.

They specifically suggest that the combination of:

• Blood lactate above 2.5 millimoles per liter

• Fat oxidation below 0.4 grams per minute

During exercise at approximately 50% to 60% of VO₂ max may “

“... define a noninvasive physiological signature of mitochondrial function, directly linking systemic exercise responses to underlying cellular bioenergetics.”

I would treat that threshold as a hypothesis, not a diagnostic rule. The study did not show that people who crossed this threshold went on to develop diabetes, cardiovascular disease, or any other clinical outcome. But I see this as potentially being the next thing these researchers investigate to validate their thresholds, and the broader concept is intriguing.

Rather than using VO₂ max alone, an exercise test could potentially assess how much fat someone burns, how quickly lactate rises, and where the body shifts toward greater carbohydrate reliance, which could provide a more detailed picture of metabolic flexibility than VO₂ max by itself.

For nearly all of human history, regular movement was built into daily life. Sedentarism is the newer experiment. And if this study tells us anything, it’s that skeletal muscle appears to build—and maintain—only as much capacity as it is regularly asked to use. It’s literally “use it or lose it” in action.

In that sense, the lower mitochondrial capacity in sedentary people is less a mysterious malfunction and more of a predictable adaptation to an environment that no longer requires much physical work. And it explains why it’s estimated that only about 12% of people are “metabolically healthy.”

How I think we should think about this is that exercise is not some optional “health intervention” layered on top of normal human biology. To quote the authors:

That flips the usual framing not only for personal health philosophy, but for how we think about exercise science and medicine. We often assume that a person who does not exercise is starting from a neutral baseline and that training pushes physiology above normal. This paper suggests the opposite may be true—regular physical activity maintains the metabolic machinery our bodies expect to need, while inactivity allows that machinery to gradually atrophy.

The sedentary men in this study were not sick. Yet their muscles already show signs of metabolic dysfunction, which may be some of the earliest detectable steps on the path from inactivity to metabolic disease, long before a diagnosis ever appears.

None of this is to moralize exercise or physical activity. That happens too often on social media. But we can’t deny the major reality of biology.

Movement is not something we do to improve our physiology. It’s our default state.

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Believe it or not, one of the most frequently asked questions I get about running isn’t even about running. It’s about how I use cycling to run better.

Indeed, cycling has become a huge part of my overall training in recent years, partly out of necessity and partly out of utility. I wanted to find a way to train more without putting myself at risk of inj…

Read more

Almost every time I read a new scientific study, and especially every time I sit down to write about one, I find myself returning to the same basic question: 

What the heck can I actually do with this?

In the world of exercise science, nutrition science, and medical science, much of the work is ultimately pointed toward application. We study the body beca…

Read more

Greetings!

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

“It’s tough to make predictions. Especially about the future.” – Yogi Berra

Most of us take our workouts for granted.

When we embark on a marathon training plan or progressive overload regimen in the gym, we expect that it’ll lead to the desired result—a faster time or bigger, stronger muscles.

That’s especially true if we’ve performed the same training before with reasonable success. We responded well the first time, so we should respond in a similar way the next, right?

Let’s refer to this idea as “reproducibility of training adaptation.” The basic idea is that if I put you through 12 weeks of high-intensity intervals, tempo runs, and a hefty amount of zone 2 training, you might improve your VO₂ max by 5–10%.

If I let you take some time off to eat some ice cream and enjoy a few drinks by the beach (the more scientific word for this is “detraining”), and then put you through the exact same training again, we’d expect your VO₂ max to improve by that same 5–10%, assuming you started at the same baseline.

Once a responder, always a responder.

A new study suggests our assumptions about this are wrong.

Exercise science might have a reproducibility problem.

The study—aptly titled “Limited reproducibility of individual physiological adaptations to repeated endurance exercise training”—used a design that is surprisingly rare in exercise science: the same people completed the same endurance training program… twice.1

Rather than comparing one group of people to another, the researchers essentially asked what happens if we put the same individuals through the same training stimulus, under carefully controlled conditions. Do they adapt the same way both times?

The study was built to directly test the idea that people have somewhat consistent “trainability”—someone who improves a lot from one endurance block should also improve a lot when exposed to a similar block again.

Participants completed two separate eight-week endurance training periods, with an eight-week detraining period between them. Each training block included 24 supervised cycling interval sessions, lasting 45 minutes each, performed at intensities ranging from moderate to maximal effort. Every session was supervised, the workouts were prescribed, and the same individuals repeated the same training program twice.

Before and after each eight-week training period, participants completed two submaximal cycling tests, a VO₂ max test to exhaustion, and a 15-minute maximal performance test.

This gave the researchers several layers of information:

1. How participants responded at lower fixed workloads.

2. How their maximal oxygen uptake changed.

3. How their actual cycling performance changed in a sustained maximal effort.

They even had participants perform a familiarization session one week before the first baseline testing period to reduce learning effects, and a rest day was scheduled before each testing block so fatigue from recent exercise would be less likely to distort the results.

The study also went well beyond performance testing to include whole-body DXA scans to assess body composition, leg muscle biopsies, blood samples, total hemoglobin mass measurements, and questionnaires. If it’s relevant to performance, they measured it.

When the researchers zoomed out and looked at the average response (what’s typical in exercise science research), the endurance training intervention was effective and remarkably reproducible.

But when they zoomed in and asked whether the same person responded the same way to the same training program, the answer was mostly no.

That distinction is the entire study.

First, the basics: participants actually did the training. Adherence was nearly perfect, and participants entered the two training periods in a highly comparable state. Baseline VO₂ max, 15-minute cycling power, maximal power, hemoglobin mass, blood volume, body mass, and lean mass were all very reproducible before the first and second training blocks. That means the eight-week detraining period was largely successful, and people were not simply carrying the adaptations from the first block into the second. The study had essentially “reset the clock” well enough to ask the main question.

Here’s what happened at the group level:

• The first eight-week training block increased 15-minute maximal power output from 137 to 154 watts, a gain of 17 watts or about a 15% improvement. The second block increased it from 142 to 164 watts, a gain of 22 watts or about a 16% improvement.

• VO₂ max increased by 3.3 mL/kg/min in the first block and 3.4 mL/kg/min in the second (a 9.4% vs. a 9.8% increase).

• Maximal power output during the final minute of the VO₂ max test increased by 24 watts in the first block and 30 watts in the second.

But then we look at the individual data…

The researchers asked whether the people who improved the most in the first training period were also the people who improved the most in the second. If “trainability” were a stable personal trait, you would expect a fairly strong relationship. That is not what happened.

Individual changes in VO₂ max showed poor reproducibility between the two training periods. The same was true for 15-minute cycling performance, maximal power, submaximal performance, hemoglobin mass, blood volume, red blood cell volume, plasma volume, muscle fiber size, mitochondrial enzyme activity, and capillarization outcomes. Almost everything that mattered physiologically showed weak within-person agreement from one training block to the next.

This is the key result: the group average was stable, but the individual rankings were not.

A person could gain a lot of VO₂ max in the first block and much less in the second. Another person could look like a modest responder the first time and then adapt more strongly the second time (if you look at the right panel in the figure below, which depicts individual responses, this is clear to see).

We see the same story when we look at the muscle level.

• Citrate synthase activity, a marker of mitochondrial oxidative capacity, increased in both training periods: by about 47.7% in the first block and 38.4% in the second.

• Another enzyme involved in fat metabolism increased more in the second training period than in the first.

• Capillary density increased more in the first training period than in the second, and the number of capillaries per muscle fiber (a marker of capillary density) showed a larger numerical increase in the first block as well.

• Hemoglobin mass, blood volume, red blood cell volume, and plasma volume increased more in the first training period than in the second, while hemoglobin concentration changed more in the second. But many of these differences were small (close to the expected measurement error for some blood-volume assessments).

The broader point is not simply whether capillaries or hemoglobin mass increased more in one block than the other.

Because VO₂ max is driven by improvements in oxygen delivery and extraction (i.e., hemoglobin mass, mitochondrial function, and capillarization), we might expect variability in these measures to explain a large portion of the variability in VO₂ max or performance. But they didn’t.

Hemoglobin mass variability explained only a small portion of the maximal power changes. Capillary density explained a modest portion of 15-minute performance and VO₂ max changes. But most of the tested relationships were weak—there was no single obvious mechanism that explained why someone responded differently the second time.

In other words, the “instability” of training response was not simply because hemoglobin or mitochondria changed differently. The adaptive response appeared to be distributed across systems, and the variability probably emerges from the interaction of many moving parts… and maybe even some random biological noise!

The researchers also found no clear evidence that the relationship between the first and second training response differed by sex or age.

Why might the same training program produce different responses in the same person?

I don’t think “noise” fully captures what is happening here.

To me, two explanations stand out. The first is that the body remembers. The second is that life is never the same twice.

Let’s start with muscle memory, or, more broadly, biological memory. The researchers did an impressive job trying to reset participants before the second training period. But “returning to baseline” on a few measurable outcomes does not mean the body has returned to the exact same biological state.

In that case, the second training block may have been applied to a subtly different biological organism, one that had already experienced eight weeks of structured endurance training. This is especially true since these participants were initially “untrained” and had never really performed formal exercise training. That point should be underscored.

“Muscle memory” probably isn’t one clean mechanism, though. It may be a collection of partially retained adaptations—structural, metabolic, vascular, neural, and molecular—that influence the starting state for the next block of training.

The second explanation is one that we’re all familiar with—lifestyle variables are never the same.

Even in a tightly controlled study, people are not lab animals. We sleep differently from week to week. We eat differently. We experience stress, illness, travel, family obligations, work demands, mood changes, changes in motivation, subtle changes in daily activity, and countless other fluctuations that are hard to measure and impossible to fully control.

Training adaptation is a result of the workout interacting with the body’s current state. A 45-minute interval session performed after a good night of sleep, adequate carbohydrate intake, low stress, and a normal week of activity is not the same biological stimulus as the same interval session performed after poor sleep, under-fueling, elevated stress, or the tail end of a mild illness.

That context includes stable factors like genetics, sex, age, and baseline fitness, but it also includes ever-changing factors like recovery, sleep, energy availability, stress, inflammation, illness, glycogen stores, and prior training history. Some of these variables may shift enough that they never show up in a standard baseline test, yet still meaningfully influence the adaptive response.

So if we really think about it, the “messiness” of the study might actually be its most realistic feature. The researchers controlled everything they could, yet individual responses still varied widely. It makes the findings reflective of real life. None of us ever repeats the same training block under identical conditions.

Here’s the question we should all be asking when starting any training program (or even a workout): “What state am I in right now, and what does my body need in order to respond?”

When I initially read this paper, it seemed like the nail in the coffin for exercise science research. After all, if we can’t even get reliably consistent results in the same exact person, then everything we know about how to prescribe training is wrong. And what to make of the hundreds, if not thousands, of studies we’ve used to base our training, nutrition, and even sleep recommendations on for decades? Should we just throw them out the window and concede that none of it matters if we can’t predict whether they’ll work or not?

After some reflection, I don’t think we’ve hit crisis mode quite yet. Exercise science doesn’t have a “reproducibility problem.”

Exercise science has a human problem.

We’re all unique. So we should take what we can from training studies, apply it to our unique selves, and adapt and respond accordingly. That’s the real takeaway here.

And I think it’s a real paradigm shift for how we think about exercise.

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Several months ago, Daren Lake (from the YouTube channel ‘The 1% Better Runner’ approached me with the idea of recording a “masterclass” on VO2 max. I said yes without hesitation. Below, you can find the video and show notes (both of which were published to Daren’s blog and YouTube channel).

Enjoy! And give Daren a follow… he creates some incr…

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Greetings!

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

Carbs are the hottest and most divisive topic in endurance.

That’s odd, because carbs aren’t new… a century of research tells us that carbohydrate availability influences endurance performance.

But endurance sport has changed. Athletes (myself included) are practicing nutrition more deliberately.

At the elite end, we are seeing cyclists, marathoners, triathletes, and ultra-endurance athletes experimenting with carbohydrate intakes approaching 120 grams per hour or more. Those are levels that would have seemed absurd a few decades ago (and still do to some people). They’re amounts that would give any low-carb advocate an aneurysm.

Though we know a lot about how carbs work and why, there’s still a lot of conflicting info and, really, a lack of guidance on what athletes really need and how they should fuel.

That’s why I wanted to cover a timely review article titled: From Metabolism to Medals: Contemporary Perspectives and Revisiting Carbohydrate Guidelines for Fueling Endurance Athletes during Exercise.1

It’s probably the best and most nuanced view of carbs and endurance performance I’ve read, and it also provides some incredibly practical guidelines.

Why carbs remain central to endurance performance

Carbohydrates (carbs, as we like to call them) and fat are the two major fuels used during exercise, but they are not interchangeable, nor is one automatically “better.”

Fat is abundant and essential, especially for long-duration performance. A well-trained endurance athlete needs a high capacity for fat oxidation, particularly during moderate-intensity exercise and in events lasting many hours.

But carbohydrate is the higher-performance fuel. It can support higher rates of ATP production and is generally more oxygen-efficient, meaning we can produce more work for a given oxygen cost.

Carbohydrate intake during exercise helps performance through several overlapping mechanisms:

It maintains blood glucose availability.

It delays or reduces liver glycogen depletion.

It helps sustain high rates of whole-body carbohydrate oxidation.

It may modestly spare muscle glycogen in some contexts.

It suppresses fat oxidation as carbohydrate remains available.

It may help preserve economy, efficiency, and durability late in prolonged exercise.

The problem is that, while the human body can store carbohydrates as glycogen in the liver and muscle, those stores are finite. Muscle glycogen supports local muscular work. Liver glycogen helps maintain blood glucose. During prolonged moderate-to-high intensity exercise, both become increasingly important.

Without carbohydrate intake from outside sources (termed “exogenous carbohydrates”), blood glucose can eventually fall because liver glucose output can’t keep up with the muscles’ demand for glucose. Hypoglycemia (low blood sugar) can develop around the 3-hour mark if you’re not taking in carbs, largely because liver glycogen availability drops.

Carbohydrate feeding changes this equation. Even relatively modest intakes of 20–30 grams per hour can reduce the body’s reliance on endogenous glucose production. Higher intakes, particularly around 90–120 grams per hour, may further suppress liver glucose output/help preserve liver glycogen.

The bigger point is that carbohydrate intake helps maintain carbohydrate availability across the whole system. It keeps blood glucose stable, supports exogenous carbohydrate oxidation, and allows the body to continue relying on carbohydrate as a major fuel source.

Delaying the drift toward fat

One of my favorite concepts in this area is something called the “crossover point.”

During prolonged endurance exercise, the body often shifts gradually from carbohydrate-dominant metabolism toward greater fat oxidation as glycogen stores deplete. This is not inherently bad. In fact, the ability to oxidize fat at high rates is a hallmark of elite endurance physiology. But if you’re trying to sustain a high pace or power output, a forced shift away from carbohydrate can reduce performance. Fat is valuable, but it cannot fully replace carbohydrates.

In studies cited by the review, carbohydrate intake delayed this crossover point during prolonged cycling. At 45 and 90 grams per hour, the shift from carbohydrate toward fat is delayed. At 120 grams per hour, carbohydrate remains the predominant fuel source (in other words, the “crossover” never occurs).

Reconsidering the 90-gram “ceiling”

The 2016 sports nutrition guidelines recommend 30–60 grams of carbohydrate per hour for endurance exercise lasting 1–2.5 hours, and up to 90 grams per hour for events longer than 2.5–3 hours.

That 90 g/h recommendation was grounded in the evidence available at the time. But newer studies suggest that trained athletes can oxidize more carbohydrate than previously assumed, especially when using glucose-fructose or maltodextrin-fructose mixtures (combining multiple carb sources allows you to utilize different sugar transporters in the body and absorb more of what you’re eating. More on that below).

Now, this says nothing about the performance implications of such high intakes. Just because you can use more carbs doesn’t automatically mean you’ll run or bike faster. We don’t yet have hard performance outcomes for ultra-high-carb consumption… only anecdotes (which aren’t useless).

In that case, 90 grams per hour should probably no longer be considered the absolute upper limit. For trained athletes, 90–120 grams per hour appears to be a more contemporary evidence-based upper range. Intakes beyond that are being explored in the field, especially in cycling, but the scientific evidence is not yet strong enough to recommend them across the board. This is where I think some people in the endurance space are putting the cart before the horse. Are carbs good? Yes. But the idea that everyone should be fueling with 90+ grams per hour for every session lacks support.

Carb type matters

At lower carbohydrate intakes, the type of carbohydrate matters less. You can consume 30–60 grams of glucose or maltodextrin alone, and it’ll work out fine.

But as intake rises, the source matters more.

Glucose and maltodextrin rely primarily on a transporter in the intestine known as SGLT1.

Fructose uses a different transporter, GLUT5. When you consume only glucose-based carbohydrates, absorption eventually plateaus because that single transport pathway becomes saturated. But when glucose or maltodextrin is combined with fructose, you can use multiple transporters, increasing total carbohydrate absorption and oxidation.

The ratio also matters. The authors discuss evidence suggesting that a fructose-to-glucose ratio between about 0.6 and 1.0 may optimize exogenous carbohydrate oxidation. In practice, this includes common formulations such as 2:1 glucose-to-fructose, 1:0.8, or even 1:1 blends. And that’s what many modern-day fueling products deliver (if you have an energy gel handy, take a look at the package and you’ll probably see one of these numbers).

The gut is adaptable

During strenuous endurance exercise, the GI tract is under stress. When carbohydrate intake exceeds absorption capacity, unabsorbed sugar can pull water into the intestine and contribute to bloating, cramping, nausea, and diarrhea. No fun…

But repeated exposure to carbohydrates during exercise can reduce symptoms. This is the idea of gut training, and the evidence for it is well-established.

Across gut-training interventions using 30–90 grams per hour, athletes generally report less GI discomfort over time. The evidence is not yet clear that gut training dramatically increases exogenous carbohydrate oxidation, but it does appear to improve tolerance and reduce issues with absorption. Maybe you can’t train the gut to use more carbs, but you can train it to handle more without issues.

But when you add in environmental stress, things get more complex.

In heat, carbohydrate demands may increase because exercising at a given intensity becomes more physiologically stressful. Heat can increase glycogen use and reliance on carbohydrate. At the same time, heat appears to reduce exogenous carbohydrate oxidation by roughly 20–30%. That creates a difficult scenario where carb needs rise, but our ability to tolerate and use them effectively drops.

At altitude, especially high altitude above around 4,000 meters, exogenous carbohydrate oxidation appears to be reduced. Cold exposure is less likely to impair exogenous carbohydrate oxidation.

Carb intake should probably be modified not only according to the demands of the exercise you’re doing, but also the environment in which you’re doing it.

Updated carbohydrate targets

The review proposes a more nuanced model that considers both exercise duration and intensity. Let’s translate that into some practical targets:

Exercise less than 60 minutes

Carbohydrate during exercise is usually unnecessary, unless the session is very intense, you’re starting with low carbohydrate availability, or the event involves repeated high-intensity efforts. I emphasized usually here because, of course, what’s needed and what’s optimal don’t always overlap.

Typical range:

• 0–30 g/h

1–2.5 hours

Carbohydrate becomes more relevant, especially as intensity rises.

Typical range:

• 30–60 g/h

• Single-source carbs may be sufficient at the lower end.

• Dual-source carbohydrates may be useful as intake rises closer to 60 g/h

2.5–4 hours

Typical range:

• 60–90 g/h for many athletes

• 90–120 g/h for well-trained athletes with practiced gut tolerance

• Multiple-transportable carbohydrates are strongly recommended at higher intakes.

More than 4–6 hours

Typical range:

• 60–90 g/h as a practical baseline for many athletes

• 90–120 g/h for competitive athletes who tolerate it

• Mixed-format fueling becomes increasingly useful.

Beyond 120 g/h

This is where the science becomes less certain. Some elite athletes are experimenting with intakes far above 120 g/h, but the review makes clear that efficacy is not yet well established. For now, these strategies should be considered experimental and highly individualized.

A subtle but important point in the review is that high-carbohydrate fueling during competition does not mean athletes should consume maximal carbohydrate in every training session. I feel like that goes without saying, but some of the discussions in the endurance world lack this crucial nuance.

This is where the idea of carb periodization, sometimes summarized as “fuel for the work required,” comes in.

While I have become increasingly intentional about fueling my workouts and races, I still intuitively use this “fueling the work” approach. There are several times per week when I’ll run or ride fasted for 60–90 minutes simply because the session intensity is low, and practically, it’s just more feasible not to eat before a 5:30 AM workout. I do not think this compromises my performance in any way, but I’m still wary of too much fasted training due to the risks of low energy availability.

That being said, I fuel when the session requires it, often using many of the same guidelines provided in this review.

A major limitation in this field is the lack of female-specific research. Much of the carbohydrate fueling literature has been conducted in male athletes, and female-only studies are rare.

However, the existing evidence does not suggest that female athletes cannot benefit from carbohydrates. They clearly can. But it remains uncertain whether absolute intake targets should be identical across male and female athletes, especially at very high carbohydrate intakes. I’m aware of at least a few ongoing or completed studies that are conducted specifically in female athletes. So that’s promising.

Some coaches and athletes think that all exercise should be fueled maximally all the time. I disagree with that sentiment, especially because most people exercising at a recreational level aren’t “under-fueling” in any respect. I said it at the start of this post, and I’ll say it again: Carbs are not a magic bullet.

And I don’t even think they are the main reason we are seeing an explosion in endurance performances (it’s the shoes).

But they are one of the most reliable performance tools endurance athletes have. They allow harder and healthier training. Which means better performance across the board. In this sense, adequate fueling can be revolutionary for many athletes. Carbs are still king when it comes to endurance sports.

If anyone tells you differently, they’re wrong.

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Greetings!

It’s been a while since I’ve posted a training log/training update… but that’s been intentional.

I got injured last year during my build-up to the California International Marathon. I was obviously devastated. It was my first injury in nearly 2 years. And it occurred when I was in some of the best running shape of my life.

It was also an “opport…

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I’m incredibly excited to share this video with you for this week’s edition of the newsletter.

I sat down with Dr. Latt Mansor of Ketone-IQ to dive deep into a brand-new study in cyclists showing that taking ketones after exercise enhances beneficial blood vessel responses and increases EPO production during recovery.1 I’ve provided the study abstract and summary below, but we get into all the details in the video.

What excites me so much about this study is that they used Ketone-IQ (rather than ketone esters, which have dominated the research to date). It’s the ketone supplement I’ve been using for my own training, so seeing these effects validated in the research is huge.

Full disclosure… I’m part of the science advisory board at Ketone-IQ, and I’m an affiliate for their products, but it’s for a good reason. They have become the brand I trust, and their team is dedicated to advancing the science of ketones.

Try some for yourself: Unlock sharper focus and support long-term brain health and exercise recovery with Ketone-IQ — Get 30% off your subscription.

My training is built around consistency. Most days, that means running. But the equipment in this garage lets me add low-impact aerobic work, strength training, uphill treadmill sessions, easy spins, warm-ups, and recovery workouts without needing to leave the house.

A few of the main pieces I cover in this video include:

• FEIERDUN DB1 adjustable dumbbells

• YOSUDA EM1 long-stride magnetic elliptical

• Feier TM1 fully folding treadmill

• Concept2 RowErg

• Zwift Ride Smart Frame paired with a Wahoo KICKR CORE trainer

Huge shoutout to Jason Rodriguez for filming this content and creating an incredible video. You can find Jason on Instagram @ctxsmedia.

Equipment featured

FEIERDUN DB1 Quick Adjustable Dumbbells

Find them here: https://www.fedfitness.com/products/quick-adjustable-dumbbell-52-5lbs

These have probably been my favorite addition to the gym. As a distance runner, upper-body strength is something I can easily neglect, and having adjustable dumbbells makes it much easier to get in quick, consistent strength work.

The DB1 dumbbells go up to 52.5 pounds each and adjust in 2.5-pound increments, which gives me plenty of flexibility for curls, presses, push-ups, accessory work, and short strength sessions throughout the day. The big advantage is convenience: instead of needing a full rack of dumbbells, I can quickly adjust the weight and move from one exercise to the next.

YOSUDA EM1 Long-Stride Magnetic Elliptical

Find it here: https://www.fedfitness.com/products/long-stride-magnetic-elliptical-machine

I’ve never been a huge elliptical person, but this one has become a useful tool for low-impact cardio days. It’s smooth, compact, and easy to use when I want aerobic work without adding more running impact.

I’ve been using it about once a week, especially when I want something different from the bike. It has multiple resistance levels, Bluetooth/app connectivity, and a compact footprint, which makes it a good fit for a garage gym or smaller home gym setup.

Feier TM1 Fully Folding Treadmill

Find it here: https://www.fedfitness.com/products/fully-folding-treadmill

The treadmill has become a daily-use tool for me. I use it for uphill strides, controlled intervals, easy runs, shakeout runs, and bad-weather training days.

It goes up to 11.2 mph and 12% incline, which gives it a wide enough range for many of the treadmill sessions I like to do. One of my favorite uses is putting on a weighted vest, cranking up the incline, and doing uphill walking when I want a harder low-impact session. I’ve also been impressed by the softness of the ride, the traction of the belt, and the fact that it folds up when not in use.

Concept2 RowErg

The Concept2 rower is one of my daily warm-up tools. I often use it for 90 seconds to three minutes before a run to get the upper body, lower body, and cardiovascular system moving before I head out the door.

It’s simple, durable, and effective, and for me, it’s less about doing long rowing workouts and more about using it as a quick full-body primer before training.

Zwift Ride Smart Frame + Wahoo KICKR CORE

Get it here: https://us.zwift.com/products/zwift-ride-kickr-core-2

The Zwift setup is probably the biggest overall game-changer for my training as a runner. I use it almost every day, sometimes twice per day, mostly for easy aerobic riding and additional low-impact training volume.

Cross-training has become a major part of how I build fitness while staying healthy. The bike lets me add five to ten extra hours of aerobic work per week without the impact of running. Most of my rides are easy spins, but I’ll also use it for intervals about once a week.

The electronic shifting, Zwift integration, and TV setup make the experience much more enjoyable. I’m not just staring at a wall—I can ride Zwift, watch something, listen to a podcast, or use it as an easy way to loosen up after a hard run.

Why I built a home gym

The biggest reason I built this setup is convenience. I’m using something in this gym almost every day. Some days it’s the treadmill. Some days it’s the bike. Some days it’s the dumbbells. Some days it’s just a short row before a run.

I think the key pieces for anyone are equipment that supports what you already do: strength training, low-impact aerobic work, controlled treadmill running, and recovery-friendly movement. You don’t need everything at once, but it helps to think about what would let you train consistently even when the weather is bad, life is busy, or you don’t feel like driving to the gym.

For me, the essentials are:

• A way to strength train

• A treadmill for controlled running

• A low-impact cross-training option

• A space that feels enjoyable enough to actually use every day

The next step for this garage gym is making it feel a little more homey, and eventually, I’d love to add a sauna. But for now, this setup gives me almost everything I need for marathon training, strength, longevity, and general fitness.

Disclosure: FED Fitness sent me several of the products featured in this video to test and review.

Greetings!

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

If you want to perform well in any endurance sport (whether you run, ride, swim, row, ski, hike, race triathlons… or simply train for health and longevity), you need a big aerobic engine, the ability to hold a high fraction of that engine, and the efficiency to turn oxygen into forward motion.

These are more commonly referred to as VO2 max, fractional utilization, and movement economy. And for a long time, they’ve made up the “holy trinity” of endurance sports.

But this classic endurance model isn’t perfect.

Two athletes can have similar lab values and look nearly identical early in a workout or race. Then, somewhere after an hour or so of hard effort, repeated surges, heat, hills, fueling mistakes, muscle damage, or plain old accumulated fatigue start to separate them. One athlete keeps rolling. The other starts fading (in physiology, morale, or both).

That difference is what sports scientists are increasingly trying to describe with a new set of terms: durability, fatigability, repeatability, and resilience.

They sound similar, but they’re not, and this week’s study by Benedikt Meixner, Michael Joyner, and Billy Sperlich does a great job at defining them and laying out what they mean for endurance sports (I’ll try to do the same as it applies to everyday athletes, too).1

It’s not a traditional experiment. It’s a viewpoint article, which means the authors are not testing a new training intervention or reporting a new dataset. Instead, they are trying to clean up the language around these emerging concepts. And honestly, it matters a lot. Because a lot of people are using words like durability, fatigue resistance, resilience, and repeatability almost interchangeably. Coaches use them. Researchers use them. Athletes use them. I’ve probably done it too. But these terms do not all mean the same thing. And if we want to measure them, train them, and actually apply them to performance, we need to be more precise.

That is the central idea of this paper. The classic endurance model is still foundational, but it may be incomplete unless we also account for how athletes respond when exercise gets long and unpredictable.

Durability

Durability is probably one of the most important concepts for anyone doing endurance exercise.

A durable athlete does not just have a good lactate threshold in the lab. They still have a strong threshold after 90 or 120 minutes of exercise, their heart rate does not drift wildly upward at the same pace or power, their mechanics do not collapse, and their fuel use does not become inefficient.

Durability captures the idea that your fitness on paper is not always the same as your fitness after you have already done a lot of work (it’s why I often recommend people give some extra thought to their “predicted marathon pace”).

The authors point to several mechanisms that may contribute to durability, including cardiovascular drift, neuromuscular fatigue, metabolic shifts, carbohydrate depletion, and changes in economy or critical power. They also note that durability can be assessed by looking at physiological drift during prolonged exercise or by testing performance markers before and after a long endurance effort.

I think durability is one of the missing links between being fit and being able to execute the event or workout you trained for.

Fatigability

Fatigability is related to durability, but it is not the same.

This concept is especially obvious in cycling, where athletes may need to respond to surges, climbs, attacks, and stochastic power demands. But it applies across endurance sports too, and even Hyrox competition is probably a fantastic example where “fatigability” emerges as an important attribute.

An athlete with high fatigability might look great early but lose output rapidly as the session or race continues. Their power, pace, mechanics, coordination, or perceived effort starts to deteriorate quickly. An athlete with low fatigability can absorb the work and keep producing.

The key difference from durability is that fatigability often involves variable or repeated intensity while recovery is limited. Durability is more about preserving physiological function over prolonged steady or semi-steady exercise. Fatigability is more about how quickly someone cracks as the workload accumulates.

Repeatability

Repeatability is the ability to recover and reproduce high-intensity performance across multiple bouts, stages, heats, or efforts.

An athlete can be durable but not very repeatable. They may grind well for a long, steady effort but struggle when asked to produce repeated surges or high-intensity bouts. Another athlete may have excellent repeatability in short efforts but lack the durability to hold performance deep into a long event.

Repeatability depends on recovery kinetics. That’s how quickly heart rate, lactate, neuromuscular function, metabolic processes, and fuel availability rebound between efforts. The paper notes that this trait appears trainable and may improve with maturation and accumulated training experience. Training consistently over time fixes everything. Well, not everything… but it fixes a lot.

Resilience

Resilience is the broadest and perhaps most slippery concept.

A resilient athlete can adapt when the day gets ugly. They can manage heat, adjust pacing, fuel when the gut is unhappy, and absorb mental fatigue without a total performance collapse.

This trait matters for almost everyone who trains. A hot day, a missed water bottle, poor sleep, travel stress, a chaotic schedule, or an unusually demanding load at work or family life can expose whether fitness is robust or fragile.

This is not just a psychological trait either. Resilience has physiological roots, including our ability to regulate body temperature, hydration, sleep, cognition, and neuromuscular function.

That is important because I think many of us often moralize fatigue. When we fall apart, we assume we were weak or “soft.” Sometimes effort and mindset matter, of course. But often the body is dealing with a complex set of stressors that were not prepared for.

Resilience can be trained, but it requires specificity. Heat acclimation helps with heat. Long sessions help with prolonged fatigue. Fueling practice helps with gut tolerance. Strength training may help protect mechanics and muscular function. Sleep and recovery help preserve the systems that keep you adaptable.

Although I’d like to think there is some “cross-adaptation” that happens, too.

It’s important to note that the paper argues that these constructs should not be treated as interchangeable names for “good at not getting tired.” They are different capacities, with different mechanisms and different relevance depending on the event or goal.

That might be hard to see at first (I had to re-read these definitions several times), but physiologically speaking, the concepts become intuitive when you place them in the context of your own athletic domain. That exercise can also be useful for identifying your weaknesses (we all have one or two) and training them accordingly.

I’ll volunteer mine:

I am extremely durable. I can run forever. And if you tested me before and after a 2-hour run, I could likely produce similar values on a VO2 max or lactate threshold test. I’m also very repeatable—my efforts often get better as a workout goes on (if I get sufficient recovery), not worse.

But I am NOT resilient. Throw a wrench in my plans and introduce an unexpected variable, and I’m likely to psych myself out or crumble a bit under the unpredictability. So that’s something to work on…

None of this means we throw out VO2 max, lactate threshold, or economy. Those are still the foundation of a well-rounded performer.

But I think the next frontier in endurance performance may be understanding not just how high your ceiling is, but how much of that ceiling you can still access when the going gets tough.

That is what durability, fatigability, repeatability, and resilience are trying to describe.

The lesson for us all is simple: don’t just train to be strong when fresh. Train to remain yourself when tired. And that, I think, applies to much more than just athletics!

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Greetings!

Welcome to the Physiology Friday newsletter.

Here’s my “favorite social post of the week". Maybe it’s the fact that the algorithm is feeding me more of this guy’s content, but Dr. Sean OMara seems to one-up himself every day with a more ridiculous take on health. Here, he claims that “fruit ages you” despite mounds of evidence that it probably does exactly the opposite (it’s loaded with nutrients, fiber, and other stuff that’s beneficial for health).

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

The world of comparative physiology has always fascinated me. How do humans stack up against other animals when it comes to our ability to function and adapt at the cellular or structural level?

One of my favorite examples is the heart.

A shrew’s heart can beat more than 1,000 times per minute. At that rate, the entire cardiac cycle (the squeeze, the relaxation, the refill, and the next squeeze) happens in about 60 milliseconds.

A blue whale lives at the other end of mammalian physiology. Its heart rate can drop to just 2 to 8 beats per minute, giving each heartbeat somewhere between 7.5 and 30 seconds to unfold.

This incredible contrast reveals one of the most important constraints in cardiovascular physiology: the heart is always racing against time. Let me explain.

Every beat has to accomplish two things. First, the heart has to fill with blood. Then, it has to eject that blood into circulation. When heart rate is low, there is plenty of time for both. When heart rate rises during exercise, the cardiac cycle shortens. The body needs more blood flow, so the heart beats faster. But the faster it beats, the less time it has to fill.

That presents somewhat of a paradox. To exercise harder, our heart has to pump more blood per minute. But to pump more blood per minute, it often has to beat faster. And the faster it beats, the less time it has to fill the ventricles (our heart’s largest chambers) before the next contraction.

This is where the endurance athlete’s heart becomes so interesting.

Elite endurance athletes are often bradycardic, meaning they have unusually low resting heart rates. In my case, my overnight resting heart rate is often around 33 beats per minute, which is deep in the “athlete’s heart” range.

“Athlete’s heart” refers to the structural and functional remodeling that occurs in response to long-term endurance training. It is not a disease. It is usually a physiological adaptation to repeated exposure to high cardiac output demands (e.g., chronic endurance training).

During endurance exercise, cardiac output can increase dramatically. Cardiac output is the amount of blood the heart pumps per minute, and it is determined by two things: heart rate (how often the heart beats) × stroke volume (how much blood the heart ejects per beat).

Most people think about exercise intensity through the lens of heart rate. But endurance performance is not just about beating faster. In fact, endurance athletes often have lower heart rates at rest, lower heart rates at the same absolute workload, and sometimes slightly lower maximal heart rates than non-athletes.

Their major advantage is stroke volume.

With chronic endurance training, the heart adapts to move more blood per beat. The left ventricle often becomes larger and more compliant, meaning it can accommodate more blood. The heart also becomes better at relaxing quickly between beats, a property called lusitropy.

This matters because diastole (the filling phase) is not passive in the simplistic sense. The heart does not just flop open and wait for blood. It actively relaxes. That relaxation creates a pressure gradient that helps pull blood into the ventricle. Then, late in the relaxation phase, the atrium contributes an additional push.

So for an endurance athlete, the heart is not simply bigger. It is better timed. It can fill more and eject more. And during exercise, when the cardiac cycle is getting squeezed into smaller and smaller windows of time, it can preserve performance by moving blood faster through each phase of the heartbeat.

That brings us to the central question of a new study: how do endurance athletes maintain larger stroke volumes during exercise when rising heart rate progressively steals away the time available for the heart to fill with blood?1

The results show us that a low resting heart rate may not just be a marker of fitness. It may represent a built-in timing advantage. A slower heart rate gives the ventricle more time to fill. And in endurance athletes, that extra time is paired with a bigger, more compliant, more powerful pump.

The researchers studied 32 people: 21 endurance athletes and 11 controls.

The athlete group included cyclists and runners primarily, with a few athletes from other endurance or highly trained sporting backgrounds. The control group exercised less than three hours per week and had no long-term history of competitive endurance sport. The groups were similar in age, sex distribution, and resting blood pressure. But as expected, they were very different physiologically. The athletes had a VO₂ peak of 56.2 mL/kg/min compared with 33.1 mL/kg/min in controls. They also produced much higher peak power on the exercise test: 394 watts versus 251 watts. So we’re definitely looking at two “levels” of performers here (important).

Participants exercised on a cycle ergometer at 20%, 40%, and 60% of their peak power output (representing light, moderate, and high-intensity exercise, respectively) while researchers measured heart rate, stroke volume, cardiac output, left ventricular ejection time, diastolic filling time, and something called the systolic-to-diastolic duration ratio.

That last variable is important, so let’s break it down. Systole is the ejection phase, when the left ventricle contracts and sends blood into the aorta. Diastole is the filling phase, when the ventricle relaxes and refills before the next beat.

At low heart rates, diastole takes up most of the cardiac cycle. This is good for filling. But as heart rate rises, diastole shortens much more dramatically than systole. Eventually, the heart starts “running out” of filling time.

The researchers also calculated systolic and diastolic flow rates. Plainly speaking, what we’re looking at here is how fast the athlete’s heart can empty, and how fast it can refill.

At rest, the athletes showed the classic features of athlete’s heart.

• Their resting heart rate was much lower than controls: 44 vs. 68 beats per minute.

• Their left ventricular end-diastolic volume index was much larger: 98 vs. 65 mL/m².

• Their left atrial volume index was also larger: 47 vs. 31 mL/m².

That means the athletes had bigger filling chambers.

But the heart was not just bigger. It also showed signs of enhanced diastolic filling and appeared to “front-load” filling. The ventricle relaxes well, fills efficiently early in diastole, and does not need to depend as heavily on a forceful atrial push at rest. The athletes also had a longer cardiac cycle, a longer diastolic (filling) period, and a longer ejection time compared to controls. In other words, the athlete’s heart had more time for everything. More time to fill. More time to eject. More time to operate.

That is the benefit of a low resting heart rate!

The problem during exercise

In both athletes and controls, exercise dramatically shortened the cardiac cycle. But the athletes handled the timing constraint differently.

At high-intensity exercise, the athletes were working at a much higher absolute workload: 226 watts compared with 145 watts in controls. Despite this, their heart rate was lower: 133 vs. 147 beats per minute.

That lower exercise heart rate gave the athletes slightly more time per beat—they had a longer total cardiac cycle, a longer filling phase, but a similar ejection time. By high-intensity exercise, the difference between athletes and controls was mainly on the filling side. The athletes preserved a little more diastolic time while also moving a much larger stroke volume.

The systolic-to-diastolic (S/D) ratio gives us a way to visualize the shifting balance between ejection time and filling time.

At rest, both groups spent more time in diastole (filling) than systole (ejection). During exercise, the S/D ratio increased in both groups. This is expected. As heart rate rises, diastole shortens disproportionately, so systole occupies a larger fraction of the cardiac cycle. But at high-intensity exercise, the athletes maintained a lower S/D ratio than controls: 0.82 vs. 1.00.

That means the controls had reached a point where systolic time and diastolic time were roughly equal. The athletes, despite doing more mechanical work, still preserved a more favorable balance toward diastolic filling. This may be one reason endurance athletes can sustain high stroke volumes at high heart rates. They are not simply forcing the heart to beat faster. They are preserving enough filling time while also increasing the velocity of filling and ejection.

But the new insight from this study was how athletes maintained those stroke volumes under severe timing constraints.

At rest, systolic and diastolic flow rates were similar between athletes and controls. But during exercise, the athletes pulled away. At high-intensity exercise, systolic flow rate was significantly higher in athletes. Diastolic flow rate was also higher during moderate exercise, though by the highest exercise stage, the groups were closer together. From rest to high-intensity exercise, systolic flow rate increased by 89% in athletes compared with 63% in controls. Diastolic flow rate increased even more dramatically: 400% in athletes and 370% in controls.

That last number is wild. During exercise, the heart has to fill with approximately the same volume it ejects, but it has to do it in a dramatically shorter time window. The only way to make that work is to increase filling velocity. This is where the athlete’s heart appears to excel. It has a larger ventricle, better filling characteristics, and the ability to generate high flow rates to fill the ventricle with more blood before the next ejection phase (don’t you just love physiology?)

Stroke volume and cardiac output

The athletes had higher stroke volume indexes at every stage (rest and low-, moderate-, and high-intensity exercise). That higher stroke volume translated into higher cardiac output during exercise.

At rest, cardiac output was identical between groups: 5.8 L/min in both athletes and controls. This is one of the elegant features of endurance adaptation. The athlete’s resting cardiac output is not necessarily higher because the low heart rate offsets the larger stroke volume. Fewer beats, more blood per beat, similar flow per minute.

But during high-intensity exercise, the athlete advantage became obvious. Cardiac output reached 17.3 L/min in athletes compared with 14.4 L/min in controls. The athletes were pumping more blood per minute, producing more power, and sustaining larger stroke volumes despite having less and less time to fill the heart with each beat.

This is one of the central physiological advantages of endurance training.

Why do athletes have lower maximal heart rates?

One interesting observation was that athletes had a slightly lower maximal heart rate than controls: 171 vs. 179 beats per minute, which is consistent with prior research suggesting endurance training can slightly reduce maximal heart rate.

Why would an endurance athlete benefit from a lower peak heart rate? The answer may be that heart rate is only helpful as long as filling is preserved.

At some point, increasing heart rate further may not increase cardiac output because the ventricle has too little time to fill. For a highly trained endurance athlete with a large ventricle and high stroke volume, the constraint may not be whether the heart can beat faster. The constraint may be whether the heart can fill fast enough. A slightly lower maximal heart rate may preserve diastolic filling time just enough to maintain a large stroke volume. In that model, the athlete’s heart is not underperforming by beating slightly slower. It may actually be optimizing the balance between rate and filling.

Thoughts on overtraining and suppressed heart rate

The most intriguing application for athletes may be overtraining, overreaching, and the sometimes confusing observation that heart rate can become suppressed when an athlete is fatigued.

Many endurance athletes (myself included) have experienced this. You go out for a workout expecting to hit a normal high-end heart rate, but your body will not get there. The usual explanation is autonomic fatigue, altered sympathetic drive, or reduced cardiac responsiveness. Those explanations may still be true. But this study adds another possible layer.

If the fatigued heart has impaired relaxation, it may not be able to fill as quickly. If filling rate is compromised, then pushing heart rate higher could further reduce diastolic filling time and threaten stroke volume. In that situation, a suppressed heart rate response might be “protective.” The system may be limiting heart rate to preserve enough time for the ventricle to fill.

That idea is speculative, but it makes sense, physiologically speaking.

During normal training adaptation, the athlete’s heart becomes better at filling quickly and ejecting powerfully. During excessive fatigue, the opposite may occur temporarily: filling dynamics may be impaired, stroke volume may be harder to maintain, and the heart may avoid higher rates because the time cost is too great.

So, while a low resting heart rate can be a sign of endurance adaptation, a suppressed exercise heart rate during a workout can be a sign of fatigue.

This study paints an awesome picture of how every heartbeat is a negotiation between filling and ejection. Between the need to move more blood and the need to allow enough time for the ventricle to refill.

The athlete’s heart wins that race not by ignoring the clock, but by adapting to it.

Hopefully, you found this exploration interesting, even though the usual “practical applications” aren’t there. When a study like this catches my eye, I can’t help but write about it. Because even if there’s not a clear takeaway, I think that when we learn the physiology of how our bodies work, we can intuit more about our own health and performance. Which is perhaps the biggest practical application of them all.

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Greetings!

Welcome to the Physiology Friday newsletter.

This week, I wanted to share some of my favorite studies from the endurance sports world that I’ve been excited about. All of these summaries were published in my other newsletter, ‘Run Long, Run Healthy’, where I explore the science of running (mostly) and summarize the latest research in the world of endurance.

I promise you’ll find these studies useful whether you’re a runner or not! Here’s what you’ll learn:

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

Do Super Shoes Make You Faster While Increasing Injury Risk?

Super shoes have become one of the strangest training decisions in running. On the one hand, they are clearly fast. The combination of highly resilient foam, tall midsoles, and stiff embedded plates can improve running economy and make race pace feel just a little more forgiving. On the other hand, almost every runner now has a story: the friend who started doing workouts in plated shoes and suddenly had calf issues, foot pain, or a bone stress injury that seemed to come out of nowhere.

That does not mean super shoes are dangerous. But it does raise the question of when these shoes do change how we run, where does that stress go?

A new study looked at exactly that question in elite distance runners. The researchers had 23 healthy elite runners, 11 women and 12 men, run in three different shoe conditions: a neutral shoe, a lightweight responsive foam shoe, and an advanced footwear technology shoe with highly cushioned foam and a stiff embedded plate. The runners tested each shoe in randomized order at three self-selected speeds: training effort, tempo effort, and 5K race pace. During each condition, the researchers measured movement and force patterns that have previously been associated with bone stress injuries.

In the advanced footwear condition, runners showed a lower cadence, meaning they took fewer steps per minute. Lower cadence often goes along with longer strides or slight overstriding, which can increase loading demands on the body over time. The researchers also found more inward collapse of the arch/rearfoot compared with the neutral shoe, another mechanical pattern that has been linked with bone stress injury risk. These changes were described as small, but small changes repeated thousands of times per run can matter when an athlete is stacking workouts, long runs, and high weekly mileage.

But there was also a potentially protective signal. In the super shoes, runners pushed off less with their ankles. That suggests the shoe may reduce demand on the ankle plantarflexors, including the calf-Achilles complex, during propulsion.

This is the part that makes the interpretation more complicated. Super shoes may not simply increase or decrease injury risk; they may redistribute load. Less ankle demand could be helpful for some runners, while altered cadence and greater rearfoot motion could shift stress elsewhere, including toward the bones of the foot or lower leg.

What this means

If you race in plated shoes, you probably need some exposure to them in training so race day does not become a brand-new mechanical stimulus. But I would be cautious about making them your everyday trainer, especially during high-volume blocks or when returning from injury.

Rotate shoes, introduce plated models gradually, and pay attention to early warning signs in the foot, shin, calf, and Achilles. The key idea is that super shoes may help you run faster by changing how load is distributed, but your bones, tendons, and muscles still need time to adapt to that new loading pattern.

Female Runners are More Durable than Males

Most runners think about fitness in terms of what they can do when they’re fresh. What’s your VO2 max? What’s your threshold pace? What can you run for a 5K, half-marathon, or uphill time trial when the legs are ready to go?

But racing rarely asks that question. Racing asks a much more interesting one—what can you still do after two or three hours of accumulated fatigue?

That’s the idea behind “durability” (a.k.a “physiological resilience”), one of the more useful concepts in endurance performance right now. It’s not just how strong your engine is at the start. It’s how much of that engine you can keep using after glycogen drops, muscles get beat up, stride mechanics shift, and perceived effort starts climbing. A new study asked whether male and female runners differ in that quality.

Researchers studied 11 highly trained female trail runners and 11 highly trained male trail runners who were matched by performance level using International Trail Running Association rankings. The runners completed three lab visits: a graded exercise test, a fresh 12-minute uphill time trial, and then a 3-hour treadmill run at moderate intensity with another 12-minute uphill time trial inserted every 60 minutes. During the prolonged run, the athletes consumed 90 grams of carbohydrate per hour and drank water as desired, while the researchers measured physiology, biomechanics, perceived exertion, and the strength of muscles in the thigh and surrounding the knee.

The women held up better. After three hours, female runners had only a 1.1% decline in uphill time-trial speed, while male runners slowed by 9.9%. That is a massive difference in durability. This was not because the women were working less hard in the time trials; heart rate, perceived effort, and peak oxygen uptake during the time trials were broadly similar in how they responded across the protocol. Instead, the difference seemed to come from greater metabolic and neuromuscular resilience.

During the 3-hour steady-state run, both groups shifted toward greater fat use over time, but the shift was much larger in men. By three hours, carbohydrate oxidation had dropped by 29% in male runners versus only 9% in female runners. Respiratory exchange ratio also fell more in men, suggesting a bigger move away from carbohydrate metabolism. During the repeated uphill time trials, the same pattern showed up again: men had larger drops in carbohydrate oxidation, larger increases in fat oxidation, and bigger reductions in peak blood lactate.

That lactate finding is important. In a hard uphill effort, peak lactate is partly a sign that the runner can still access high-intensity carbohydrate-driven energy production. By the final time trial, male runners showed a 53% drop in peak lactate, compared with a 27% drop in females. That suggests the men were losing some ability to hit the same high-intensity metabolic gear as fatigue accumulated.

Muscle strength also declined more in men, with males showing an 18% reduction after two hours, while females were essentially unchanged at that time point. Meanwhile, running economy worsened similarly between sexes, and both groups made fatigue-related biomechanical adjustments: longer ground contact time, reduced stride length, and lower leg stiffness. In other words, the durability advantage in women did not seem to come from some radically different stride pattern. It looked more like better preservation of the metabolic and muscular systems that support performance late in a long effort.

There is one big caveat: the study matched runners by duration, not distance. Because the men ran faster, they covered more total distance during the protocol: about 26 miles versus 22 miles for women. They also expended more energy relative to body mass. The researchers tried to account for this statistically, and the findings largely held up, but this still matters. If the study had matched distance instead of time, the gap might have been smaller.

What this means

The practical takeaway is that durability deserves more attention than fresh fitness.

A runner with a great threshold test or fast standalone workout may not be the runner who performs best after two or three hours, especially on hilly terrain. For everyone, one of the best ways to assess durability may be to place short, controlled hard efforts late in long runs and see how much performance, form, and perceived effort deteriorate. The race is not decided by what your physiology looks like when you’re fresh; it’s decided by what’s still available when the easy miles are behind you.

Does a Post-Run Cold Plunge Block Training Benefits?

Ice baths have one of the best reputations in endurance sports and one of the messiest evidence bases. They feel like recovery. They look like recovery. But there’s always been a bigger question of whether they’re actually helping adaptation, or just making you feel like you’re recovering better?

To answer this question, a new study looked at what is happening inside the muscle after five weeks of interval training plus regular cold-water immersion.

The researchers recruited 16 healthy young men and split them into two groups. Both groups completed the same five-week high-intensity interval training (HIIT) program on a treadmill: three sessions per week of 2-minute intervals at 95% of the runner’s speed at VO2 max, progressing from 5 to 8 reps before tapering down at the end. One group did 11 minutes of cold-water immersion at about 52℉/11°C immediately after each session, while the control group just sat passively at room temperature. Before training, after week 4, and again after week 5, the researchers measured VO2 max, maximal aerobic speed, and time to exhaustion in a run at a constant speed. They also took samples of the runners’ muscles to look at satellite cells, markers of mitochondrial growth, and inflammatory markers.

The main finding was that the ice baths did not meaningfully change anything that mattered. Both groups improved over time, and they improved to a similar extent.

• VO2 max went up.

• Speed at VO2 max went up.

• Time to exhaustion improved.

On the muscle side, satellite cell content increased, and a marker of mitochondrial growth known as PGC-1α also rose, which is what you’d hope to see with a solid block of interval training. But none of those changes were different between the cold-water immersion group and the control group. The inflammatory markers in muscle also did not meaningfully shift with cold-water immersion. The training worked, and the post-workout ice baths neither boosted nor blunted the main endurance adaptations they measured.

What this means

If you use cold-water immersion after hard workouts because it helps you feel fresher, less sore, or more mentally ready for the next session, this study suggests that habit probably is not harming your endurance adaptations.

But it also probably is not giving you a secret fitness edge. That makes ice baths more of a recovery management tool than a performance-enhancing one. I would view them as optional, context-dependent, and most useful during heavy training blocks, races with short turnarounds, or periods where soreness is interfering with consistency.

The bigger levers are still the obvious ones: good training, enough easy running, enough fuel, enough sleep, and recovery practices you can actually stick with.

What Elite Ethiopian Runners Can Teach Us About Training Blocks

There’s always something fascinating about studies on elite East African runners, partly because we’re trying to understand athletes who are already operating near the ceiling of human endurance performance.

A new study asked what happens when elite distance runners move through sequential blocks of endurance, strength, and speed training?

Instead of treating these training types as competing philosophies, the researchers looked at how each block contributed to different pieces of performance. Twenty elite Ethiopian male middle- and long-distance runners completed three six-week training blocks in a fixed order: endurance training first, then strength training, then speed training. There were two-week periods of normal mixed training between blocks. Testing was done before and after each phase, including estimated VO₂max, resting heart rate, running economy, blood markers like hemoglobin and hematocrit, 400-meter speed, a 5,.000-meter time trial, and a 12-minute Cooper test. The athletes trained and tested at altitude, roughly 2,400–2,700 meters (which reflects their normal environment).

The endurance block looked like classic aerobic development: high-volume continuous running, progressing toward about 75 miles/120 kilometers per week, mostly at moderate aerobic intensity. This phase produced the biggest aerobic and hematological changes.

• Estimated VO₂max increased by about 6.2 ml/kg/min

• Resting heart rate dropped by nearly 4 beats per minute

• Hematocrit increased by 4.35 percentage points

• Red blood cell count rose

• Hemoglobin increased modestly.

• Performance improved too: the Cooper test increased by 236 meters, and 5,000-meter time improved by about 18 seconds.

The strength block included circuit-style bodyweight strength work and hill sprints, which makes it more specific to running than a generic resistance program.

• This block produced the largest improvement in running economy, with oxygen cost falling by 4.2%.

• It also improved 400-meter speed by 1.21 seconds and shaved another 6 seconds from the 5,000-meter time trial.

• VO₂max and most hematological markers did not change much during this phase, suggesting the main benefit was neuromuscular: better force production, better coordination, and possibly improved stiffness or elastic return.

The speed block used long intervals from 1,000 to 1,600 meters and shorter intervals from 200 to 800 meters, with intensity ranging from about 95% to 110% of estimated VO₂max.

• This phase improved 400-meter speed by another second and 5,000-meter time by 9 seconds, with only a small increase in estimated VO₂max.

What this means for runners

Runners should stop thinking of endurance, strength, and speed as separate camps and start thinking about how they fit together across a training cycle.

For most runners, the sequence makes intuitive sense: use an endurance-focused phase to build aerobic capacity and durability, add strength and hills to improve economy and force production, then layer in faster intervals to sharpen race-specific speed. The biggest mistake would be copying the exact training of 13-minute 5K runners; the better lesson is the structure. Even elite athletes improved when training stress became more targeted and sequential. For recreational and competitive runners, that might mean spending several weeks emphasizing aerobic volume, then keeping the mileage stable while adding strength and hill work, and finally shifting toward faster intervals as race day approaches.

Why “Feelings” Outperform Complex Training Load Metrics

Runners are drowning in load metrics right now. Training load, recovery score, acute load, chronic load, biomechanical stress, heart-rate strain. The promise is that if you track enough of them, you’ll finally understand what your training is really costing you. But a new paper asks whether these metrics even agree with each other in the first place?

Researchers took 12 experienced recreational runners and had them complete three different outdoor runs: a 45-minute steady endurance run, a 5k submaximal effort, and a 5 x 1000-meter interval session with 2 minutes of rest between reps. The runners wore heart-rate monitors and special units that could measure their biomechanics on the pelvis and lower legs, and they also gave a rating of perceived exertion (RPE) after each workout. From that, the researchers calculated three different load measures: session RPE, heart-rate-based training impulse (TRIMP), and a biomechanical load score based on estimated peak ground reaction forces summed across the run. The biomechanical metric was not just counting steps or distance. It was trying to estimate how much cumulative loading the body experienced by weighing higher-impact steps more heavily (no pun intended).

Session RPE clearly separated the workouts in a way that makes intuitive sense. The endurance run felt easier, while the 5k and interval sessions felt harder. Average session RPE was about 112 for the endurance run, 188 for the interval session, and 194 for the 5k effort.

But TRIMP did not significantly distinguish the sessions. Neither did the biomechanical load metric. That is the heart of the paper. The runners felt a clear difference between session types, but the objective metrics did not really reflect that difference, at least not in a clean way. TRIMP averaged about 85 for the endurance run, 95 for intervals, and 94 for the 5k. Weighted cumulative load was also fairly similar across sessions. So, depending on which metric you looked at, these workouts either looked meaningfully different or basically the same.

The correlations tell a similar story. Session RPE and TRIMP had a moderate relationship (heart rate and perceived effort lined up somewhat), but biomechanical load seemed to be capturing something else entirely, or maybe not capturing load very well in this setup.

What this means

You should be very cautious about handing too much authority to any single load number on your watch.

Heart-rate load, biomechanical load, and perceived effort are not the same thing, and this study suggests they may diverge quite a bit depending on the session. I think that is a strong argument for keeping subjective feedback in the loop, even if you love data. How hard the run felt still matters. In practice, the best monitoring system is probably a simple combination of session type, duration, pace, heart rate, and (honest) session RPE, rather than chasing one supposedly all-knowing metric. The body is more complicated than that, and your training log should reflect it.

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Greetings!

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

Endurance performance comes down to three things: VO₂ max, threshold, and economy.

VO₂ max is your aerobic ceiling. Threshold is how much of that ceiling you can use and sustain. Economy is how much oxygen it costs you to produce a given pace or power output.

This framework is often associated with Dr. Michael Joyner’s classic 1991 model of marathon performance, which estimated the limits of human endurance based on these three physiological determinants. Since then, the model has become one of the foundational ways scientists, coaches, and endurance geeks like me think about performance across sports like running, cycling, triathlon, cross-country skiing, and other long-duration events.

The “problem” with the model is that it’s never been used to answer this question: if you take a large group of real endurance athletes, ranging from recreationally trained people to world-class performers, how much does each factor actually matter? What separates “good” from “great”?

A new study in Sports Medicine tried to answer that question with a huge dataset of 888 endurance athletes, including 495 runners and 393 cyclists. The researchers examined how VO₂ max, exercise economy, and fractional utilization of VO₂ max related to endurance performance.1

They wanted to know which physiological traits best explain why some athletes can sustain faster speeds or higher power outputs than others.

The answer? VO₂ max still matters a lot. Economy matters a lot too. But fractional utilization, the percentage of VO₂ max you can sustain at threshold, may not be as useful for separating higher- and lower-performing athletes as we often assume.

The classic endurance model

Dr. Michael Joyner’s model is elegant because it reduces endurance performance to three big pieces (I like to think of them as “pillars” of endurance performance).

First, there is VO₂ max, the maximum amount of oxygen your body can take in, deliver, and use during intense exercise. A bigger aerobic engine gives you more room to work with. This matters not only for performance, but also for health, because VO₂ max reflects the integrated function of the heart, lungs, blood, blood vessels, mitochondria, and working muscles.

Second, there is fractional utilization of VO₂ max. This is the percentage of your VO₂ max you can sustain at a key threshold. Two athletes might both have a VO₂ max of 60 ml/kg/min, but if one can sustain work near threshold at 85% of VO₂ max and the other can only sustain 75%, that changes the performance equation.

Third, there is exercise economy. For running, this is the oxygen cost of running at a given speed. For cycling, it is the oxygen cost of producing a given power output. More broadly, economy is how much energy it costs your body to perform a specific endurance task. A more economical athlete uses less oxygen at the same pace or power (they’re more efficient).

Together, these three factors can be used to estimate the speed or power an athlete can sustain at lactate threshold or lactate turnpoint—an intensity that’s close to “marathon pace.” Lactate threshold was defined in this study as the first rise in blood lactate above baseline, while lactate turnpoint represented a more rapid and sustained increase in lactate. The researchers used speed at these points for runners and power at these points for cyclists as performance proxies.

So this study did not directly test race outcomes, finishing times, or real-world competition results. It tested physiological markers that are strongly related to endurance performance.

The study included 495 runners (105 of whom were female) and 393 cyclists (42 of whom were female). The participants ranged widely in ability, from recreational athletes to world-class performers.

Everyone completed lab-based incremental exercise testing. For runners, the test was performed on a treadmill. They ran in four-minute stages, with short rests for blood lactate sampling, while researchers measured oxygen uptake and ventilation. After the submaximal test, participants rested for 15–20 minutes and then completed a separate test to exhaustion to determine VO₂ max.

For cyclists, the protocol was similar but performed on a smart trainer or cycle ergometer. They completed four-minute stages with increasing power, blood lactate sampling, and gas exchange measurements, followed by a ramp test to exhaustion.

From these tests, the researchers calculated VO₂ max, exercise economy, fractional utilization at lactate threshold and lactate turnpoint, and speed or power at those thresholds.

They then asked two big questions.

First, how strongly does each physiological trait relate to threshold speed or power (our “performance proxy”)?

Second, how much does each trait contribute to the overall prediction of these performance proxies?

VO₂ max is still the heavyweight

VO₂ max was the strongest predictor of performance proxies in both runners and cyclists.

That means when you look across a broad range of endurance athletes, the people with bigger aerobic engines tend to perform better. There are exceptions, of course, and exceptions are often the most interesting cases. But at the population level, VO₂ max remains the physiological variable that most clearly separates lower-performing from higher-performing endurance athletes.

VO₂ max is not destiny, but it is still one of the biggest determinants of endurance potential.

The key nuance is that VO₂ max becomes less useful when you compare athletes who are already very similar. If you take a group of elite endurance athletes with VO₂ max values clustered in a narrow range, economy, durability, fueling, biomechanics, tactics, heat tolerance, and threshold characteristics may explain more of the difference. But if you compare recreational athletes, competitive amateurs, sub-elites, and elites together, VO₂ max is going to do a lot of explanatory work, and that’s exactly what happened here.

The second big contributor was exercise economy.

Lastly, fractional utilization of VO₂ max—the percentage of VO₂ max used at lactate threshold or lactate turnpoint—contributed far less to performance differences than VO₂ max or economy.

That does not mean threshold does not matter. It absolutely does.

But it does suggest that when you look across a broad range of endurance athletes, fractional utilization is not very good at distinguishing who is better. A recreational athlete with a relatively low VO₂ max might operate at a high percentage of that VO₂ max at threshold. Meanwhile, a better-trained athlete with a much higher VO₂ max might have a similar or even lower fractional utilization but still produce a much higher absolute output because the engine is so much larger.

Here’s a simple way to think about it.

Athlete A has a VO₂ max of 45 and can sustain 85% of it.

Athlete B has a VO₂ max of 65 and can sustain 78% of it.

Athlete A may look better if you only focus on fractional utilization. But Athlete B is almost certainly producing more work because 78% of a much larger engine is still a bigger absolute output.

Similar performance can come from different physiological profiles

If we could accurately predict who wins a race by just looking at, say, VO₂ max, then it wouldn’t be much fun, would it?

Not every endurance athlete needs the same physiology. In fact, similar performances can be achieved with very different combinations of VO₂ max, economy, and fractional utilization.

This is one of the reasons endurance performance is so fascinating. There is not one perfect physiological profile. Some athletes are engine monsters. Some are economy freaks. Some have exceptional threshold characteristics. Some are durable and barely fade. Some are biomechanically gifted. Some are unusually efficient in a specific sport. Some are just really, really good at doing the work for a very long time.

The Joyner model gives us the major ingredients, but athletes can combine those ingredients in different ways.

The paper gives a great historical example of this idea using Frank Shorter and Steve Prefontaine (two legendary American distance runners).

On paper, their race performances over 5,000 and 10,000 meters were remarkably similar. Shorter ran 13:26.6 for 5K and 27:45.9 for 10K, while Prefontaine ran 13:21.9 and 27:43.6. That’s essentially the same performance neighborhood. But physiologically, they were not identical athletes. Prefontaine reportedly had a much higher VO₂ max (84.4 ml/kg/min) compared with Shorter’s 71.3 ml/kg/min.

That difference is enormous. If we only looked at VO₂ max, we might assume Prefontaine should have been far superior. But the stopwatch says otherwise. Shorter was able to arrive at almost the same performance outcome with a smaller aerobic engine, which implies that other factors (likely economy, fractional utilization, durability, pacing skill, biomechanics, and race execution) helped close the gap. Pre just had a monster engine.

This is also a useful reminder for everyday athletes. You may never know your exact VO₂ max, economy, or lactate profile, and you probably don’t need to obsess over any single number. It’s better to ask: “What is my current limiter?”

Some athletes need to build the engine. Others need to become more economical. Others need to improve fatigue resistance, fueling, or race execution.

This is an incredibly foundational study, in my opinion. And its biggest strength is the sample size.

A lot of endurance physiology studies include 10, 15, or 20 participants. This study included 888 athletes.

The study also included both runners and cyclists, both males and females, and athletes ranging from recreational to world-class. That makes the findings more useful than studies limited to a tiny group of homogeneous athletes.

The main limitation is that this study did not directly measure race performance. It used speed or power at lactate threshold and lactate turnpoint as performance proxies.

Those are meaningful proxies, but real-world performance is messier. Competition is not just a lab test stretched over a longer time period. Actual endurance performance includes pacing, fueling, heat, terrain, equipment, tactics, muscle damage, psychology, and durability.

Durability may actually be the biggest missing piece here.

The classic Joyner model focuses on VO₂ max, fractional utilization, and economy, but endurance performance is increasingly being understood through a fourth lens: how well these variables hold up under fatigue. An athlete’s economy when fresh is useful. Their economy two, three, or four hours into an event may be more important (for more on durability, see my previous post on it).

Two athletes may have identical VO₂ max, threshold, and economy in the lab, but one may maintain those traits after prolonged work while the other deteriorates. That is performance durability, and it may help explain why some athletes are much better competitors than their lab values suggest. And honestly, I think it’s the variable that still gives much of endurance sports its mystique.

How should we apply this paper to training and health?

Let’s stop treating VO₂ max, threshold, and economy as competing explanations and start seeing them as interacting pieces of the same performance and health puzzle.

If you are newer to endurance training or still developing aerobically, raising VO₂ max and building a bigger aerobic engine probably matters a lot, which means consistent training volume, aerobic development, intervals, long sessions, and long-term exposure are foundational.

As you become more trained, economy, threshold, and durability likely become increasingly important. They are what’s going to move you from “good” to “great” within your current performance capabilities.

The best endurance programs probably touch all three determinants across a season: build the engine, make the engine more efficient, and then teach the body to sustain a high output when fatigue sets in.

This study is a nice reminder that endurance performance is both simple and complicated.

The simple version is that better endurance athletes usually have a bigger aerobic engine and better economy. That was true 35 years ago, and it is still true now. Dr. Joyner’s model still holds up.

The complicated version is that athletes can arrive at similar performances through different physiological routes, and the best athletes often have several of these traits stacked together, but the combination is not identical for everyone.

For anyone interested in improving their endurance performance, the art is figuring out which part of the puzzle needs the most attention right now.

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Greetings!

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

“The best time to exercise is the time that works for you.”

At the most basic level, I agree with this statement. Exercise is good for you, no matter when you do it.

But if we look a little deeper into the biology of it, theoretically, there should be a time of day—one that’s unique to each of us—that produces the most robust response to a workout, and therefore the greatest health, fitness, or performance benefit.

It all has to do with circadian biology.

Much of this is determined by your chronotype—the biological predisposition to be a “morning person” or a “night person.” This isn’t just about when you like to go to bed or wake up. Your chronotype literally influences when you prefer to engage in physical activity, your motivation to do so, and, perhaps more importantly, when you perform your best.

This suggests that personalizing exercise to one’s chronotype could optimize its benefits, whether by improving blood pressure, glucose regulation, or VO₂ max. It also suggests that, unfortunately, “night owls” forced to exercise in the morning (or “early birds” forced into a late-night workout) due to work schedules and society’s structure might be blunting their physiological adaptations.

There is biological plausibility here. The concept is clean and easy to understand. And according to a new study, there may be some genuine merit to the idea that exercise works better when it’s aligned with your internal biological rhythm.1

The study included 134 adults who had at least one cardiovascular risk factor, such as high blood pressure, overweight or obesity, impaired fasting glucose, low physical activity, or a family history of cardiovascular disease. So they were at risk for cardiovascular disease, but didn’t actually have a clinical diagnosis of it.

The participants were classified using a validated questionnaire as either a morning or an evening chronotype. Then they were assigned to one of two groups:

• A chronotype-aligned group that trained at their preferred biological time—morning types trained in the morning, and evening types trained in the evening.

• A chronotype-misaligned group that trained at the opposite time—morning types exercised in the evening, and evening types exercised in the morning.

Everyone performed the same training: 40 minutes of moderate-intensity aerobic exercise, at 60–70% of max heart rate, five times per week for 12 weeks.

Both groups improved, as you would expect, but the participants in the chronotype-aligned exercise group improved more… much more in fact. For most outcomes, the improvements were roughly twice as large in the group that exercised at a time aligned with their chronotype:

• Their systolic and diastolic blood pressure dropped by 11 mmHg and 7 mmHg, respectively, versus drops of about 6 mmHg and 3 mmHg in the misaligned group.

• Their estimated VO₂ peak increased by 4.4 mL/kg/min, versus a 2.3 mL/kg/min improvement in the misaligned group, and they also lasted longer on a treadmill test: +4.3 minutes versus +1.5 minutes.

• Their HRV improved by 12.7 ms, versus a 5.8 ms improvement in the misaligned group.

• Their LDL cholesterol dropped by 13.7 mg/dL, versus a 7.6 mg/dL drop in the misaligned group.

• Their fasting glucose decreased by 6.6 mg/dL, versus a 3.2 mg/dL drop in the misaligned group.

• Their body weight decreased by about 1.6 kg, versus a 0.8-kg drop in the misaligned group.

• Their sleep quality improved by 3.4 points, versus a 1.2-point improvement in the misaligned group.

There was one finding (though exploratory) that I found interesting. All of the participants—regardless of whether they were a morning or evening chronotype—experienced improvements in blood pressure, HRV, aerobic fitness, and other risk factors. However, the magnitude of improvement generally appeared to be larger in morning chronotypes compared to evening chronotypes, regardless of whether they were in the aligned or misaligned group. What that implies, I’m not quite sure.

I have probably read and/or written about dozens of studies at this point investigating whether the time of day at which exercise is performed is important. The results of most of these studies have been pretty unequivocal—it doesn’t matter. Exercising in the morning or evening generally produces similar health and performance outcomes.

But after reading this study, I realize that the research has been asking the wrong question.

It’s not “night vs. day.” It’s biological alignment versus not.

Many of these studies failed to account for chronotype. In other words, they were isolating time of day as a variable without taking into account individual biological variation.

When we do that, it turns out that timing does make a difference.

Does this mean you should reorganize your workout routine to sync with your biological clock?

Most likely, you’re already doing this out of pragmatism. With at least some control over our daily schedules, most of us have chosen to work out when it’s most enjoyable. For some, that means early in the morning before the workday. For others, that means late-afternoon exercise after leaving the office.

The good news from this study is that even when exercise isn’t performed at our biological “sweet spot,” it’s still beneficial.

On the other hand, I think there is a strong case that if you do have the freedom to choose when to exercise, doing so at a time that aligns with your chronotype is smart. Chronotype-aligned exercise produced roughly twice the improvement as misaligned exercise in this study. That meant larger gains in aerobic fitness, larger reductions in blood pressure and other cardiovascular risk factors, and even a greater reduction in body weight. And that was when participants did the exact same exercise. If you told me I could get twice the benefit from my workout just by shifting when I performed it, I’d take that deal.

These findings can also apply more broadly. All of us should probably be thinking about when we schedule our tasks and obligations during the day so that they align with when our alertness, mood, and performance peak. I know myself well enough to never plan on doing deep or creative work after about 4 PM. And if I want to be at my best for a podcast, I know that scheduling it for late morning, immediately after my workout, is when I’m giving the best performance.

Circadian biology has been one of my favorite topics for a while. I think that’s because it takes health and makes it more granular.

It’s not just about what we do, but when we do it. Biology thrives when we’re aligned.

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Initially, I figured it would be a good rehab tool and a bridge between walking and returning to run. But now, even though I’m back to running full force, I don’t go a day without walking with either the 20- or 30- lb plate on my back. Why not?

Much of this was inspired by Michael Easter, author of the amazing Substack Two Percent and too many other awesome books to name. So… I decided to pick his brain on whether “rucking” or walking with weight could have benefits for runners and athletes (the answer is yes, but you’ll need to listen to learn why and how).

I really enjoyed this one. You will too.

Newsletter partners you should check out…

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

  

Greetings!

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

I’ve run a few marathons in my life (4 to be exact). One thing that’s consistent after each one is the debilitating muscle soreness that often lingers for up to a week.

Another is that my brain typically feels like mush for a few days. I get the “runner’s high” like anyone else (especially after a personal best), but when it comes to any high-level thinking… consider me useless.

There’s probably a good explanation for that.

A few months ago, I wrote about a study showing temporary reductions in brain myelin content after marathon running. Myelin is the fat-rich insulation around axons in the brain that helps neural signals travel efficiently. So if you hear “myelin reduction,” your mind may immediately go to neurological disease or damage. But the prior study suggested that this reflected a reversible change after extreme endurance exercise, with recovery over time (levels normalized after about a month). What I found most interesting about the study was the mechanism.

During prolonged endurance exercise, the body (and brain) gradually shifts toward greater reliance on fat as carbohydrate availability becomes more constrained. We understand that shift reasonably well in skeletal muscle. We understand it less well in the brain, which is usually thought of as a glucose-hungry organ, but it is not metabolically static. Under certain conditions, it can use alternative fuels, and the support cells around neurons may play an important role in helping neural circuits keep functioning when energy demand is high. The possibility raised by this line of research is that myelin is more metabolically flexible than we used to assume.

When the brain runs low on glucose in the latter stages of a marathon, myelin might provide energy-rich lipids as an “alternative” fuel source. Hence, myelin levels dropped post-race in the group of runners.

Well, the authors of that study just published a follow-up paper that asks (at least I think) a more interesting question: If myelin changes after a marathon, does brain function change too?1

The answer is not as simple as “yes” or “no.” The researchers found that basic neural signal transmission appeared preserved, while some higher-order cognitive functions showed temporary changes after the race. Let’s take a deeper look.

The study focused on two main questions.

First, the researchers wanted to know whether neural signal transmission was preserved after marathon running. Since myelin helps determine how quickly signals travel through the nervous system, the most direct concern would be slower conduction. If a marathon meaningfully disrupted myelin function, you might expect motor, sensory, visual, or auditory pathways to show impairments.

Second, the researchers wanted to know whether cognitive performance changed after the race. They tested specific domains, including processing speed, interference control, visuomotor speed, attention, and executive flexibility.

I like this design because it separates basic neural transmission from higher-order cognition. Those are related, but they are not the same. The nervous system can preserve basic signaling while still showing temporary changes in more demanding cognitive tasks.

It turns out that distinction ends up being central to the study!

The participants were healthy adults divided into a marathon-running group and a non-running control group. The runners were recruited from official marathon or ultramarathon events and regularly engaged in endurance training. The control group came from the same general population, was matched as closely as possible for age and sex, and did not complete endurance events during the study period. Overall, the cognitive testing sample included 43 marathon runners and 29 controls. The neurophysiology portion (measuring conduction speeds) was much smaller, with only three runners, so I would treat that part as preliminary and proof-of-concept rather than definitive.

Participants were tested before the race, within 48 hours after finishing, and again one month later. Controls were tested at similar time intervals. This is important because cognitive testing has practice effects. If you repeat the same test multiple times, you often improve simply because you understand the task better. Having a control group allowed the researchers to compare post-race changes against normal learning effects.

The most reassuring result (if you’re a marathon runner) was that neural signal transmission appeared stable after marathon running. The researchers also looked at response amplitudes, which can reflect the strength or excitability of the brain’s response to stimuli. These were stable as well, with no consistent post-marathon reductions.

This suggests that even if MRI markers of myelin content change after extreme endurance exercise (as shown in the prior study), the basic timing of neural communication may be preserved. The nervous system may have enough redundancy or “buffering capacity” that short-term myelin remodeling does not translate into obvious deficits in neuron signaling.

On the cognitive tests, the pattern was not that runners became broadly impaired after the marathon, but that certain higher-order functions looked temporarily less efficient. In a processing speed test, controls improved across repeated sessions (as you would expect from practice), while runners showed a smaller immediate post-race improvement before catching up by one month. On a test known as the Stroop Test, controls again improved with repetition, but runners showed a temporary increase in interference after the race, suggesting it was briefly harder to suppress an automatic response and stay focused on the correct one. By one month, that effect had normalized, too.

On the other hand, basic visual/motor, attention, and executive tasks were preserved after the marathon. Runners and the control group improved over time on tests of these measures, with runners showing no clear post-race impairment.

To me, this is the key result. The marathon seemed to selectively affect more demanding cognitive processes while sparing more basic mental tasks. They didn’t broadly experience “marathon brain.”

The way I read this paper is that the marathon brain is not damaged. It is metabolically stressed and temporarily adapting. I’ll insert one of my favorite quotes from the paper here:

A marathon places the body in a state of prolonged energetic demand, and we need to think about how that affects the brain as much as it does the muscles, heart, and other organs. The brain has to help regulate movement, effort, pain, motivation, temperature, autonomic function, and decision-making throughout the event. In fact, it would be surprising if the brain looked exactly the same afterward, especially in the first 48 hours.

At the same time, the brain appears to protect its most essential signaling systems, and the authors connect this to other stress states where higher-order cognition is more vulnerable than basic sensory or motor function. Under fatigue, low-oxygen conditions, or acute physiological stress, the brain “sacrifices” higher-order thinking but keeps basic processes online. That’s how evolution wired us, after all.

Most of us can understand this intuitively, even if we have not thought of it as neuroscience. After a major race or hard competition, the body is not the only thing that feels a little off. The brain can feel slightly foggy, and study gives a “why” and a “how” to that experience.

The practical takeaway is not that marathons are dangerous for the brain (maybe just your mental health).

The more useful takeaway is that the brain should be included in how we think about recovery from extreme endurance exercise.

It’s normal for athletes to think about muscle repair, glycogen restoration, hydration, and sleep. But cognitive recovery matters. The day or two after a major endurance event is probably not the best time to schedule your most cognitively demanding work, make major decisions, or expect yourself to be mentally sharp for hours (it’s perhaps ironic that most marathon races occur on a Sunday).

What does that recovery look like? Probably not much different than how we think about bodily recovery. Sleep, adequate carbohydrate intake, enough total energy, hydration, and reducing stress levels. The study did not test recovery strategies, so we cannot say that any one intervention speeds cognitive normalization. But from a physiology perspective, it is reasonable to assume that restoring energy availability and sleep would support brain recovery and are probably the strategies with the biggest return on investment.

Honestly, what makes endurance exercise such a fascinating model for human physiology is that it’s not just a test of the legs or the cardiovascular system. It is a test of the entire human being, including the brain’s ability to maintain function under stress.

The brain after a marathon may not be “worse.” It may be doing exactly what a resilient biological system is supposed to do. It protects what matters most, adjusts what can temporarily be adjusted, and recovers when the stress has passed.

A good metaphor for running… and for life.

Thanks for reading. See you next Friday.

~Brady~

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).

Welcome to the Physiology Friday newsletter.

Details about the sponsors of this newsletter and deals on products I love, including Ketone-IQ, Create creatine, Equip Foods, and ProBio Nutrition can be found at the end of the post.

This week, I’m sharing the video of my recent appearance on the Down to Health podcast, where I talked about VO2 max, wearables, cardio myths, and other topics related to training, fitness, and longevity.

This was by far one of the most fun podcasts I’ve ever been a part of, and I think you’ll love it. Be sure to give the guys at DTH a subscribe if you enjoy their show!

Ketone-IQ is high-performance energy in a bottle. I use it for post-exercise recovery along with enhancing focus, mood, and cognition. Take 30% off your order.

Create is the first “modern creatine” brand. They sell a wide range of creatine monohydrate gummies, and just launched a new creatine + electrolyte mix product plus travel-size packets of creatine gummies. They’re giving my audience 20% off their order.

ProBio Nutrition—the all-in-one supplement that I use every single day—is offering 20% off. My preference is the tangy orange flavor, but they also sell an unflavored “smoothie booster” that’s great in a shake, smoothie, or juice.

• Equip Foods makes some of the cleanest, best-tasting protein products around. I am absolutely obsessed with their Prime grass-fed protein bars (the peanut butter ones are to die for, but they also just released a new chocolate peanut butter flavor).