Can a Proteomic Test Actually Predict VO2 Max?

This article covers what the proteomic cardiorespiratory fitness score research has shown so far, specifically how it relates to measured or estimated VO2 max and mortality risk. It does not cover consumer availability, cost, or whether such a test is offered clinically.

A large multi-cohort study built a blood protein score that tracked with cardiorespiratory fitness and predicted all-cause mortality risk independent of traditional risk factors, and the score also shifted in people who completed a structured exercise training program, tracking with how much their fitness changed. That is a real, specific finding. It is not the same as saying a blood draw currently replaces a treadmill test or a wearable's VO2 max estimate for an individual person.

Why a blood test for fitness sounds almost too convenient

There's a particular kind of skepticism that shows up whenever a lab test promises to stand in for something you'd normally have to earn through sweat and a stopwatch. Fitness numbers on a wrist or a treadmill printout feel effortful, physical, real. A proteomic score, built from a blood draw, feels like it's skipping a step somehow. So the natural question isn't just 'does it work' but 'work compared to what, and for whom.'

The tension gets sharper because cardiorespiratory fitness already has a credibility problem of its own making: everyone agrees it matters, but almost nobody gets it measured directly. Estimating it, whether from a questionnaire, a wearable, or now a protein panel, has always been a workaround for that gap. Which workaround holds up is the real question.

What the proteomic score is actually measuring

The study behind this idea didn't set out to replace a treadmill test with a needle prick for its own sake. It set out to solve a specific, practical problem: cardiorespiratory fitness is one of the more reliable health markers researchers have, but measuring it directly, with a maximal exercise test, is hard to do at scale. So the researchers linked blood protein profiles to fitness data across four cohorts, and built a score from that relationship.

What makes this different from, say, a questionnaire-based estimate or a smartwatch reading is the mortality link baked directly into the same analysis. The score wasn't just correlated with fitness in a side-by-side comparison. In a UK Biobank sample, higher scores tracked with a markedly lower risk of dying from any cause over the follow-up period, and the association held up even after accounting for standard clinical risk factors. It also appeared to shift when people's actual fitness changed through a structured exercise training program. I find that detail meaningful: a static biomarker that never moves wouldn't be much use for tracking anything.

None of this happens in isolation from the rest of the fitness literature. Fitness measured the conventional way, through maximal or symptom-limited treadmill testing, has one of the strongest track records of any single health marker, with large studies linking it to mortality risk reductions across quintiles of fitness and describing it as a candidate vital sign in clinical guidance. The proteomic score is being proposed as a new way to get at that same underlying signal, not a competing definition of what fitness is. Readers curious about how that underlying number is defined and tested in the first place can find the conventional methods this proteomic approach is being compared against laid out in how VO2 max is actually calculated.

How this compares to the estimate already on your wrist

It's worth placing the proteomic score next to the tool most people already have access to: the wearable's own VO2 max estimate. A validation study comparing Apple Watch's VO2 max readings against indirect calorimetry, the gold-standard laboratory method, found the watch consistently underestimated fitness, with a meaningful average gap between the two methods and real variability in how far off any individual reading could be. That's a useful reference point, it shows even a widely used, algorithm-driven estimate has known error margins against direct measurement. The proteomic score hasn't been tested against wearable estimates in the same head-to-head way described in the evidence here, so it's not possible to say which is closer to a true lab measurement for a given person. Readers who want the mechanics of how a wearable arrives at its number in the first place might find how consumer wearables model VO2 max from heart rate and pace useful background.

The broader estimated-fitness literature, covering things like non-exercise questionnaires, adds another layer of context. Across large meta-analyses, estimated and objectively measured fitness have both shown associations with mortality risk, though the strength and consistency of that association can differ by estimation method. The proteomic score sits within that same family of tools: an estimate standing in for a direct measurement, evaluated on how well it tracks the outcome that matters. Not on whether it feels like a shortcut.

Where the fitness-mortality link comes from in the first place

None of this proteomic work exists without decades of prior evidence that fitness itself, however it's measured, predicts how long people live. An early study of over 13,000 men and women found mortality rates dropped sharply across rising fitness quintiles, a pattern that held after adjusting for smoking, cholesterol, blood pressure, and blood sugar. A later meta-analysis of cohort data quantified that relationship in metabolic equivalents. A scientific statement went further, calling fitness a candidate vital sign and arguing it adds predictive value beyond standard risk factors like smoking or high cholesterol. A more recent overview of meta-analyses, covering nearly 21 million observations across almost 200 cohort studies, found fitness had the strongest association with reduced all-cause mortality when comparing high versus low fitness groups, with heart failure showing one of the largest risk reductions of any single outcome examined.

That deep, consistent literature is the reason a proteomic shortcut to fitness is worth taking seriously at all. If fitness weren't already this well established as a mortality predictor, a blood-based proxy for it would be a much smaller story, a footnote rather than a finding. For a fuller accounting of that mortality relationship on its own terms, VO2 max and longevity: what the evidence actually establishes covers it in more depth, and the heart failure-specific findings are explored further in VO2 max and heart failure mortality.

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