Greetings! Welcome to the Physiology Friday newsletter. ICYMI Check out my guest appearance on The Neuro Experience podcast with Louisa Nicola, where we talk about the science of V̇O2 max. On Wednesday, I published a post about some of the most common myths about coffee and caffeine. Details about the sponsors of this newsletter including Examine.com and my book “VO2 Max Essentials” can be found at the end of the post! Physiologically Speaking is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. If you can fill the unforgiving minute With sixty seconds’ worth of distance run, Yours is the Earth and everything that’s in it, And—which is more—you’ll be a Man, my son! — Rudyard Kipling, If— In my book “VO2 Max Essentials”, I make the case for why cardiorespiratory fitness should be considered the most important vital sign. Among all risk factors, V̇O2 max is the only one that’s a composite of multiple physiological systems, rather than a snapshot of health at one point in time or a single biomarker measured via a blood test. Your maximal oxygen utilization capacity (V̇O2 max) represents the maximum integrated capacity of the pulmonary, cardiovascular, and muscular systems to uptake, transport, and utilize oxygen during whole-body, dynamic exercise. The function of your autonomic nervous system, your heart and blood vessels, your lungs, your muscles, and your mitochondria all influence your maximal aerobic capacity. It’s not just a strong heart that gives someone a high V̇O2 max. A strong body is a prerequisite. This is, in my opinion, why a high V̇O2 max is so often associated with beneficial health outcomes. You won’t find someone with a high V̇O2 max who is in poor health, and often people with an extremely low V̇O2 max are in poor health. Though it’s not routinely measured in clinical practice (yet), V̇O2 max has recently appeared on the radar of many healthcare professionals. People are becoming aware of the predictive power of cardiorespiratory fitness and are increasingly interested in how (and why) to improve it. Over the last 20 years, evidence has emerged linking higher cardiorespiratory fitness to lower risks of all-cause mortality and other diseases. Thus, it’s about time we had a scoping review of the evidence, which brings us to today’s study. The study, published in the British Journal of Sports Medicine was an overview of all previously published systematic reviews and meta-analyses on the relationship between V̇O2 max and an array of health outcomes. The studies were eligible if they included adults with or without health conditions and measured cardiorespiratory fitness using a maximal graded exercise test, a maximal or submaximal exercise test with a prediction equation (i.e., without direct measures of gas exchange), or a non-exercise prediction equation. When pooling the data and examining the outcomes, the authors compared the groups with the highest cardiorespiratory fitness to those with the lowest cardiorespiratory fitness. Overall, a total of 26 studies with over 20.9 million participants from 199 different cohorts were included in the review.  Eight of the included studies examined the association between V̇O2 max and death (mortality) from all causes, cardiovascular disease, sudden cardiac events, all cancers, and lung cancer.  Compared to low cardiorespiratory fitness, having high cardiorespiratory fitness was associated with a 41% to 53% lower risk for premature mortality. Furthermore, each 1 metabolic equivalent (MET) increase in cardiorespiratory fitness (1 MET is equal to an increase in V̇O2 max of 3.5 mL/kg/min) reduced the risk of premature mortality by 7% (all cancers) to 51% (sudden cardiac mortality). A notable limitation for mortality outcomes was the large disparity in male vs. female participants — more than 1.8 million male participants were included in th