The short version
- Among 122,007 adults given treadmill tests at the Cleveland Clinic, the least-fit group had an adjusted all-cause mortality hazard ratio of 5.04 against the elite group, larger than the hazard associated with smoking (1.41), diabetes (1.40) or coronary artery disease (1.29) in the same model.
- Pooling 33 cohort studies covering 102,980 people, each 1-MET increase in maximal aerobic capacity was associated with a relative risk of all-cause mortality of 0.87.
- In the PURE study of 139,691 people across 17 countries, every 5kg of lower grip strength carried a 16% higher hazard of all-cause mortality, and grip predicted mortality better than systolic blood pressure did.
- UK Biobank data on 502,293 adults found hazard ratios per 5kg lower grip strength of 1.20 in women and 1.16 in men, but adding grip to an office-based risk score improved discrimination by a C-index change of only 0.013.
- No supplement in the LUVO catalogue has been tested against all-cause mortality, because trials powered for that outcome cost tens of millions of dollars and the supplement industry does not run them.
Between 1991 and 2014, the Cleveland Clinic put 122,007 consecutive adults on a treadmill for a symptom-limited exercise test, then watched what happened to them over 1.1 million person-years. Thirteen thousand six hundred and thirty-seven of them died.
When Mandsager and colleagues stratified everyone by age- and sex-matched cardiorespiratory fitness, risk-adjusted all-cause mortality fell in a straight line as fitness rose. The bottom group against the top: adjusted hazard ratio 5.04.
The comparison in the same model is what makes it land. Coronary artery disease carried an adjusted hazard ratio of 1.29. Smoking, 1.41. Diabetes, 1.40. Being in the least-fit group was associated with a larger adjusted hazard than any of them. And there was no ceiling — the elite group still beat the merely high group (HR 0.77), including in patients over 70.
Be honest about the design: this is an observational cohort of people referred for a treadmill test, so illness that had not yet declared itself can push people into both the low-fitness group and the mortality column. It is not a randomised trial and it cannot be. Which is why the next study matters.
The same finding, in a unit you can actually train
Kodama and colleagues pooled 33 cohort studies in JAMA — 102,980 participants and 6,910 deaths for the mortality analysis. Their result comes in a usable dose-response: for every 1-MET higher maximal aerobic capacity, which is roughly one kilometre per hour of extra running speed, the relative risk of all-cause mortality was 0.87, and of coronary or cardiovascular events, 0.85.
Below 7.9 METs is their low-fitness band. People in it had a relative risk of all-cause mortality of 1.70 against the high-fitness group, and 1.40 even against the middling group. One MET is a realistic training target for most people over a few months. That is the whole appeal of this number: it moves, and it moves with work.
The test that costs nothing
The PURE study measured grip strength with a hand dynamometer in 139,691 people across 17 countries and followed them a median of four years. Per 5kg of lower grip strength, the hazard ratio was 1.16 for all-cause mortality, 1.17 for cardiovascular mortality and 1.17 for non-cardiovascular mortality. The association held across low-, middle- and high-income countries.
And the line that gets quoted for good reason: grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure was.
UK Biobank replicated it at scale — 502,293 participants aged 40 to 69, 13,322 deaths over a mean 7.1 years, hazard ratios per 5kg lower grip of 1.20 in women and 1.16 in men.
Now the deflation, which the same paper supplies. Adding grip strength to an established office-based risk score improved its discrimination by a C-index change of 0.013 for all-cause mortality. That is a real improvement and a small one. Grip is a superb cheap marker of how your whole system is doing; it is not a crystal ball, and in PURE it showed no significant association with incident diabetes, falls or fractures.
Muscle mass, with its asterisk
Srikanthan and Karlamangla followed 3,659 adults from NHANES III who were 55 or older, measuring skeletal muscle by bioelectrical impedance and excluding anyone underweight or who died within the first two years. Adjusted for central obesity and other covariates, the top quartile of muscle mass index had an all-cause mortality hazard ratio of 0.80 against the bottom quartile.
Bioimpedance is a rough instrument and this is observational, so hold it more loosely than the grip data. The direction is consistent with everything else here: what you carry matters more than what you weigh.
The part where we argue against our own shelf
Not one of the numbers above came from a supplement. There is no capsule in our catalogue — or anyone else's — with all-cause mortality data behind it, and the reason is unglamorous: a trial powered for mortality costs tens of millions of dollars and runs for a decade, and the supplement industry does not run them. When a brand implies otherwise, it is borrowing the credibility of studies like these without having done anything comparable.
Creatine is the one product of ours that belongs anywhere near this conversation, and its role is narrow and worth stating precisely: it is an adjunct to resistance training, not a replacement for it. The muscle in the study above was built by using it. We have written separately about what creatine's own evidence supports. It has never been tested against mortality, and we are not going to let the adjacency in this article imply that it has.
What we'd actually tell you
Get the two numbers. A graded exercise test through your doctor gives you a real fitness estimate and a baseline that means something; a hand dynamometer costs less than a month of most supplement stacks and takes ten seconds. Write both down. Retest in six months.
Then train them, in the two ways that are unfashionable because they are obvious: enough easy aerobic work each week that a MET gain is plausible within a year, and enough resistance training that your grip and your muscle mass are going up rather than quietly down.
Buy a supplement after that, if you still want one, and know exactly what you are buying it for. The order matters. A capsule taken instead of the training is the most expensive thing in this article.
Good questions
Is VO2 max really a better predictor than smoking or diabetes?
In the Cleveland Clinic cohort of 122,007 people, yes — low fitness carried a larger adjusted hazard than smoking, diabetes or coronary artery disease did in the same model. One caveat worth keeping: it is an observational study of people referred for treadmill testing, so undetected illness can influence both fitness and outcome.
How do I measure my grip strength at home?
A hand dynamometer costs less than a month of most supplement stacks. Squeeze at maximum effort, take the best of three per hand, and write the date next to it. The useful information is not one reading but the direction of travel when you retest in six months.
Can any supplement improve VO2 max or grip strength?
Nothing on our shelf will do it on its own. These are outcomes of training, and the supplements that have any role at all — creatine being the main one — work as adjuncts to the work rather than substitutes for it. If a product implies otherwise, it is borrowing credibility from studies it had no part in.
Is creatine worth taking for longevity?
Not on longevity grounds, no. Creatine has never been tested against mortality and we are not going to suggest it has been. Its honest role is supporting the resistance training that builds and maintains the muscle mass these cohort studies track. Buy it for the training, not for the lifespan.
How much do I need to improve to matter?
One MET is the useful unit — roughly one kilometre per hour of extra running speed — and it was associated with a 13% lower relative risk of all-cause mortality across 33 cohort studies. That is a realistic target over months rather than years, which is what makes fitness a more actionable marker than most.
Should I still bother with supplements at all?
Only after you know what you are buying them for. A specific gap, a specific product, a specific window to judge it in. What none of them will do is substitute for the two numbers in this article, and a supplement bought instead of the training is the single most expensive purchase discussed here.
Sources
- Mandsager K, Harb S, Cremer P, Phelan D, Nissen SE, Jaber W. Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Netw Open, 2018. View study
- Kodama S, Saito K, Tanaka S, et al. Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA, 2009. View study
- Leong DP, Teo KK, Rangarajan S, et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. Lancet, 2015. View study
- Celis-Morales CA, Welsh P, Lyall DM, et al. Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants. BMJ, 2018. View study
- Srikanthan P, Karlamangla AS. Muscle mass index as a predictor of longevity in older adults. Am J Med, 2014. View study
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
