Why Normal Labs Miss Your Fitness Decline
Brooks Leitner of VO Health on estimating VO2 max from blood, and why a clean lab panel can still hide falling cardiorespiratory fitness.
Normal labs are a low bar. Your glucose can be flat, your lipids clean, your blood pressure fine — and you can still be losing reserve, the capacity to absorb a flight of stairs, a surgery, an infection, or a brutal year. Almost every test you can order at Quest or LabCorp was designed to detect disease, which means it can tell you whether you are sick but not what healthy looks like. Brooks Leitner makes the case that cardiorespiratory fitness is the missing vital sign, and that the population data is moving the wrong way: average VO2 max in the FRIEND registry has been trending down for three decades.
We spend most of the hour on the physiology rather than the pitch. Why one number can integrate heart, lungs, blood, muscle, mitochondria, and brain through the oxygen cascade. Why the mortality curves keep showing a dose response with no obvious ceiling. Why endurance training and VO2 max training are not the same thing, why METs and training zones are fuzzier than the internet suggests, and what VO2 max misses entirely — starting with strength and grip.
The last stretch covers VO Health's blood-based proteomic estimate of VO2 max. It is a genuinely interesting approach and it is early-stage: an estimate anchored to real CPET data, not a replacement for the test, and not a validated clinical tool. We press on where the error lives on both sides, including the reproducibility of the gold standard itself. This conversation is education, not medical advice.
Before you watch
- A clean panel does not rule out declining reserve. Standard labs are built to detect disease, not to characterize how much stress your physiology can absorb before something breaks.
- VO2 max is powerful because it is integrative. The oxygen cascade requires lungs, blood, heart, vessels, skeletal muscle, mitochondria, and the brain to work together, so one number carries information no single biomarker does.
- The mortality association is dose-responsive with no clear upper limit. In the Kokkinos VA analysis of roughly 750,000 adults, moving from the bottom fitness quintile to the next was associated with meaningfully lower all-cause mortality, and the pattern holds across sexes, races, and age bands into the 80s.
- Training for VO2 max is not the same as training for endurance. A VO2 max test is an 8–12 minute maximal effort, so intervals in that neighborhood (the Norwegian 4x4, a 2k row) drive it — while Ironman-style volume trains a different capacity.
- VO2 max misses strength almost entirely. The highest VO2 max athletes are often cyclists and triathletes with very little upper-body mass, and grip strength carries its own independent longevity signal.
- Blood-protein estimates of VO2 max are an early research direction, not a validated clinical tool. Brooks is explicit that the anchor is real CPET data and the goal is a screening signal, not a diagnosis.
- Fitness is worth tracking on its own terms. It does not cancel ApoB, blood pressure, or glucose, and those still need their own attention.
Chapters
Why normal labs miss the mark
Normal is a low bar. Clean labs can coexist with falling reserve, and medicine barely measures reserve at all.
What routine blood work gets wrong about health
Nearly every commercial lab test was designed to detect disease, so it can define abnormal but not healthy.
Defining true resilience and hormesis
Resilience as the buffer you can absorb before daily function breaks, and hormesis as stress you adapt to rather than break under.
The shocking decline in population fitness
Average VO2 max in the FRIEND registry has trended down for 30 years, and what sedentary work and urban design have to do with it.
Cardiorespiratory fitness: the missing vital sign
The AHA argued in 2016, and again in 2024, that CRF belongs alongside blood pressure. Why primary care still does not measure it.
The oxygen cascade: how VO2 max actually works
Oxygen from air to mitochondria, and why that chain makes a single number an integrative measure rather than a synthesized score.
The surprising data linking VO2 max to mortality
The Kokkinos VA dataset, the quintile-by-quintile pattern, and why there is no obvious ceiling on the benefit.
Improving VO2 max: is it possible?
Levine's heart-failure work and the Hickson protocol — 10 weeks, six hard sessions a week, a 44% improvement, and why nobody programs that way now.
Weight loss, muscle mass, and gaming your VO2 max
Body weight sits in the denominator, so is losing weight cheating? Why the metric rewards fat loss but punishes muscle loss.
Heart rate training zones and the problem with METs
A MET is just 3.5 ml/kg/min wearing a costume. Brooks on why METs travel badly from epidemiology to individuals.
Why endurance training won't maximize your VO2 max
A VO2 max test is 8–12 minutes by design, so the training that raises it looks different from Ironman volume.
What VO2 max completely misses (strength and grip)
Strength is essentially absent from the metric, and grip strength has independent implications for functional capacity.
Sauna, altitude, and drugs for VO2 max
Heat and altitude can passively shift blood volume and red cell mass. Why most drugs cannot generate a real adaptive stimulus, and the DNP cautionary tale.
Proteomics: estimating your VO2 max from a blood test
Profiling ~1,000 proteins down to a ~50-protein composite anchored to true VO2 max tests, plus state vs. trait proteins.
Wearables and their accuracy in measuring fitness
What happens when the blood estimate and the treadmill disagree, why sleep and alcohol may explain some of it, and the 4–8% reproducibility of the gold standard itself.
The ultimate zero-equipment hack to build VO2 max
Find the steepest hill near you and walk up it as fast as you can. It scales to almost any starting fitness level.
Questions
Can a blood test replace a VO2 max test?
No. A blood-based proteomic score is an estimate anchored to cardiopulmonary exercise testing (CPET), which remains the reference standard for measuring cardiorespiratory fitness. VO Health's test is early-stage and not a validated clinical tool. An estimate may tell you it is worth getting properly tested; it does not stand in for the test.
Does a high VO2 max cancel out high ApoB, blood pressure, or glucose?
No. Fitness is an independent axis of risk, not an offset. High cardiorespiratory fitness is associated with lower all-cause mortality, but it does not neutralize lipid, blood pressure, or metabolic risk. Those need their own measurement and management with your clinician.
Is Zone 2 or interval training better for VO2 max?
They train different things. Because a VO2 max test is an 8–12 minute maximal effort, intervals in that range — the Norwegian 4x4, for example — map most directly onto raising the number. Lower-intensity aerobic work builds the base that supports it. Neither is a universal prescription, and what is appropriate depends on your health status and training history.
What is the simplest way to start improving cardiorespiratory fitness?
Brooks's answer: find the steepest hill in your neighborhood and walk up it as fast as you can. No equipment, works from almost any starting point, and it scales as you get fitter. Check with your clinician first if you have cardiac symptoms or known heart disease.
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