Brady Holmer on VO2 Max, Marathon Brain, and Training That Reverses Aging
Exercise physiologist Brady Holmer joins Louisa Nicola to explain why a marathon can briefly fog the brain, what VO2 max really measures, and how to train for a longer, sharper life. They cover the oxygen cascade, the strive for 50 at 50 target, finding your training bottleneck, and simple protocols like the Norwegian 4x4, sauna heat, and one long weekly session.
Overview
On The Neuro Experience, host Louisa Nicola sits down with exercise physiologist and endurance writer Brady Holmer to unpack what actually makes the body and brain younger. They begin with marathon brain, a small study showing that a marathon can temporarily cut brain myelin by about 20% and dull higher-order thinking for roughly a month before recovering.
Brady explains the leading theory: as glycogen runs low, the brain may burn fatty acids from its own myelin for fuel, which is why smart fueling and omega-3s may help. The conversation then turns to VO2 max, reframed as a whole-body oxygen cascade spanning the lungs, heart, blood vessels, capillaries, and mitochondria. Brady lays out why VO2 max is such a strong predictor of longevity, the roughly 15 to 20 ml/kg/min floor for independent living, and his strive for 50 at 50 target.
He describes how the brain itself licenses fitness gains through myokines like BDNF, and how to tell whether your bottleneck is central or peripheral using a simple lactate test. Practical protocols follow, from the Norwegian 4x4 and its two-to-eight-minute sweet spot to sauna heat, post-exercise ketones, and iron status. He closes with a single framework for the decade ahead: consistent sleep timing and one long, easy 60-to-90-minute session each week, ideally outdoors.
Key quotes
5Your brain is temporarily damaged after a marathon, but a month or two after that, you recover.
Everything you do requires energy and therefore requires oxygen, so your ability to use oxygen is fundamental to life.
Strive for 50 at 50 - that's a really, really good goal to shoot for.
What's good for the heart is good for the brain, because it's all connected.
At least once a week, do a workout that is between 60 and 90 minutes - longer than you might typically do.
Key ideas
8Marathon brain is real but temporary
A small MRI study found roughly a 20% drop in brain myelin after a marathon, with mildly impaired higher-order cognition for about a month. Levels and function recovered within one to two months, so it is a transient effect, not lasting damage.
Why the brain may burn its own myelin
As glycogen runs low late in a marathon, the brain may metabolize fatty acids from myelin for energy. It is an adaptive, fuel-seeking response, which is why adequate fueling may blunt it.
VO2 max is a whole-body oxygen cascade
VO2 max is the maximum rate at which the body takes in oxygen and uses it to make ATP. It depends on the lungs, heart, blood vessels, capillaries, and muscle mitochondria all working together, not just heart and lungs.
A VO2 max floor for independent living
Basic daily activities require roughly 15 to 20 ml/kg/min. Dip below that and ordinary tasks feel like maximal efforts, which is how frailty sets in with age.
Aim for 50 at 50
A common target is a VO2 max of about 50 for men around 50, with roughly 40 for women, who tend to run about 10 ml/kg/min lower. VO2 max declines with age, so building a high baseline early pays off later.
The brain licenses fitness gains
Exercising muscles release signaling molecules called myokines, including lactate and BDNF, that tell the brain to adapt. In mice, blocking specific brain signals abolished the endurance-training benefit.
Find your bottleneck: central or peripheral
In young, trained people the limiter is usually cardiac output; in older or untrained people it may be muscle oxygen extraction and mitochondria. Knowing which one guides how you train.
Non-responders don't really exist
Some people show little VO2 max change after a training block, but something in the body always adapts. With enough dose and the right stimulus, essentially everyone eventually responds.
Practical takeaways
7- 1
Fuel your long efforts 13:00
Going into and during long endurance sessions, take in adequate carbohydrate so the brain is not forced to seek alternative fuel. Loading omega-3s beforehand may also support recovery.
- 2
Guard the post-workout window 42:00
The one to two hours after training appears key for adaptation. Avoid jumping straight into cognitively demanding tasks or stimulating screens, and let yourself downshift for 30 to 45 minutes.
- 3
A DIY check for your limiter 48:00
At a low, easy intensity, spiking lactate on a simple finger-prick test can signal poor mitochondrial fat-burning. Sitting above roughly 2 mmol at a leisurely pace is one clue your limiter is peripheral.
- 4
Hit the VO2 sweet spot 51:00
Intervals of two to eight minutes near 90% of max, like the Norwegian 4x4, keep you pushing against your ceiling longer than very short sprints. Repeat four to eight times.
- 5
Use heat as an amplifier 56:00
Sauna or a hot bath after exercise mimics an altitude-like stimulus and can boost hemoglobin, blood volume, and VO2 max beyond training alone. It costs time, but adds a little extra return.
- 6
Consistency beats duration in sleep 59:00
Going to bed and especially waking at the same time helps synchronize circadian rhythms. Regular timing can offset some effects of imperfect sleep length.
- 7
Do one long, easy session weekly 1:00:00
A 60 to 90 minute low-intensity session, ideally outdoors in nature, supports fat metabolism, mitochondria, and prolonged brain oxygenation. It is the one habit to add for the decade ahead.
Topics & chapters
14The marathon brain question
Louisa opens by asking whether running a marathon really damages the brain.
Inside the myelin study
The MRI findings of a roughly 20% myelin drop after a marathon and what they mean.
Cognition and the fuel mechanism
About a month of mild cognitive impairment and the theory that the brain burns myelin for energy.
Fueling and protecting the brain
Carbohydrate, ketones, and omega-3s to support recovery after long efforts.
VO2 max and the oxygen cascade
A refresher on what VO2 max really measures across the whole body.
Why VO2 max predicts longevity
Oxygen use, daily function, and the threshold below which frailty begins.
Targets by age and sex
Average numbers, the 50-at-50 goal, and the VO2 max bank account.
The brain mediates fitness
Myokines, BDNF, and the immediate recovery window for adaptation.
Finding your bottleneck
Central cardiac output versus peripheral muscle and mitochondria.
A simple lactate test
Using a submaximal effort and a lactate meter to spot mitochondrial limits.
Training each link
Respiratory muscle work, iron status, and heat for hemoglobin.
Responders and non-responders
Trainability, molecular signatures, and why everyone can adapt.
Amplifying your training
Post-exercise heat and ketones to get more from each session.
Sleep and the weekly long session
Consistent sleep timing and one long, easy session as the core framework.