Dr Bill Evans holds a PhD in exercise physiology, has published more than 20 peer-reviewed papers, and now researches applied training science, including double threshold training, at Elon University in North Carolina. We asked him to break down two of the biggest questions in endurance training: what actually causes fatigue, and what's really happening in your body when fitness improves, or disappears.
What actually causes fatigue
Fatigue splits broadly into two categories: central and peripheral.
Central fatigue mostly refers to your central nervous system, your brain and motor neurons, not your heart and lungs. Your heart, notably, essentially doesn't fatigue in any meaningful way during exercise; it's extremely efficient at consuming oxygen and using lactate, and just keeps beating. Your lungs, too, are rarely the limiting factor unless you have a pre-existing condition like asthma or COPD.
Peripheral fatigue is about the muscles themselves: metabolic fatigue, mechanical breakdown of contractile proteins, ionic imbalances in calcium handling, and, perhaps most importantly, your body's ability (or inability) to keep oxygen delivery up with demand.
The central governor theory
One of the more compelling explanations for why we slow down is the central governor theory, popularised by physiologist Tim Noakes. The idea: your brain actively limits your muscles to prevent damage, well before your muscles are actually incapable of producing force.
The classic supporting study is almost comical in retrospect: researchers had a subject repeatedly contract a finger until voluntary force output dropped to zero, seemingly complete exhaustion. Then they applied electrical stimulation directly to the muscle. Force production shot straight back up to baseline. If the muscle itself could still produce full force, something further upstream, the brain, was the actual limiter.
Stress as a training metric
Because of the central governor's role, subjective stress becomes a genuinely useful thing to track, not just a soft, feel-good metric. A simple 1-10 self-rating (how stressed do you feel right now, accounting for muscle soreness, headspace, sleep, everything) correlates reasonably well with objective markers like cortisol.
There's a sweet spot, similar to how caffeine works: too little arousal and your nervous system isn't primed to perform; too much and you're already burning resources just to function, before you've even started training or racing. Managing that isn't complicated in principle, box breathing, reframing, visualisation, but it starts with actually taking the self-inventory in the first place, something most runners skip entirely.
One particularly useful application: race anxiety responds well to repeated exposure. Racing more often, even when it goes badly, trains your nervous system to stop treating the start line as a threat. It's the same principle behind exposure therapy for phobias, and it works partly because performance genuinely improves with familiarity alone. VO2 max testing shows this directly: repeat the same test a few days later on someone with no test experience, and their number improves, not from new fitness, but purely from learning how to execute the test itself.
What's actually adapting when you get fitter
There's a fairly well-established sequence of physiological changes that occur as fitness improves, starting with the fastest-adapting systems and working down to the slowest.
1. Plasma volume (fastest to gain, fastest to lose)
This is the first adaptation to occur, and also the first thing lost when you stop training. More plasma volume increases the fluid your heart can pump, driving up cardiac output and, in turn, oxygen consumption.
2. Mitochondrial enzymes
Rather than becoming more efficient individually, your body simply makes more mitochondria. They exist not as isolated "jelly beans" but as an interconnected network (a reticulum), and their structure and positioning around capillaries directly shapes how well they function.
3. Cardiac remodelling
The heart's left ventricle thickens and grows outward (not inward) in response to the eccentric loading that comes from pushing more fluid volume through it during training. This increases stroke volume, the amount of blood pumped per beat, which further drives up oxygen consumption capacity.
4. Capillary density
Your muscle fibres develop more of the tiny, single-cell-thick blood vessels that deliver oxygen directly to working tissue, while the fibres themselves shrink slightly, shortening the distance oxygen has to travel to reach the mitochondria.
5. Tendon stiffness and neural coordination
Improved motor unit coordination contributes directly to running economy, meaning you use less oxygen at any given pace. Strength and plyometric training in particular increase tendon stiffness, adding elasticity and "bounce" that runners don't get from running volume alone. We go deeper on exactly how this works in how strength training improves running economy.
6. Lactate threshold
An increase in specific transport proteins (monocarboxylate transporters) improves your muscles' ability to shuttle lactate out and convert it into usable fuel. Contrary to popular belief, lactate itself doesn't cause fatigue, it's actually a valuable fuel source once your body gets efficient at processing it.
Why easy running has a ceiling
All of the above can be triggered by easy running alone, and there's more room for improvement through easy running than most people realise. But eventually, genuine intensity becomes necessary to keep progressing.
The trigger for further capillary growth is hypoxia, low oxygen concentration in working tissue, which activates a signalling molecule (HIF-1a) that drives new blood vessel formation. Similarly, mitochondrial growth is triggered partly by free radicals produced during harder efforts, which stimulate the master regulator of mitochondrial density (PGC-1a).
As a rough guideline, once weekly volume reaches somewhere around 50-70km, that's roughly where it becomes worth deliberately introducing higher-intensity training to keep driving these adaptations further.
Why the order of training matters
A landmark study looking at VO2 max, lactate threshold and running economy (the three key determinants of endurance performance) found something important about sequencing:
- Easy running improves running economy.
- Threshold training improves running economy and lactate threshold.
- VO2 max training improves all three: economy, threshold, and VO2 max.
It's tempting to conclude VO2 max training is simply the best use of your time since it touches everything. But VO2 max adaptations are also the least sustainable, and if you front-load them, you risk detraining that specific adaptation by the time you circle back to lower-intensity work later in your plan. This is essentially why periodisation exists: you have to build the underlying machinery in the right order, then peak at the right time, rather than chasing the biggest stimulus first and hoping it holds.
Why you can't sustain intensity year-round
Faster running means significantly higher vertical ground reaction forces, and tissue tolerance for that kind of repeated loading has real limits, particularly as you age. Push too hard, too consistently, and you move from productive overreaching into genuine overtraining, where performance actually declines. In female athletes specifically, sustained high intensity can also disrupt menstrual health.
What happens when you stop, and how fast you get it back
De-training research paints a striking picture. In classic astronaut bed-rest studies, complete inactivity for around 60 days produced VO2 max declines comparable to roughly 40 years of aging, and losses of 20-30% of VO2 max in that window.
The encouraging part: those same individuals, once put through 8-12 weeks of intense retraining, returned to their previous VO2 max levels. Adaptation tends to follow a roughly three-week cycle, three weeks of measurable progress, then a plateau week, before the next round of improvement.
One reassuring detail for anyone who's had extended time off through injury or life circumstances: some of the deeper structural changes, like the additional muscle nuclei associated with hypertrophy, tend to stick around even when other markers fade. The "machinery" doesn't fully disappear, which is part of why returning athletes often rebuild faster than complete beginners.
Cross-training during time off
For athletes managing injury, particularly those with a history of low bone density, cross-training can maintain the vast majority of these physiological adaptations, enzyme activity, capillary density, cardiac changes, without the impact loading of running. The elliptical is a particularly good substitute for maintaining running-specific fitness, since your body position more closely resembles running than cycling does (where a more horizontal position changes the pressure dynamics your heart is working against). If you're navigating a bone stress injury specifically, Beau Tyrrell's account of his own tibial stress fracture covers exactly this kind of return-to-training decision-making.
A useful mindset for the early stages of any return-to-training block: work is work. You don't need training to be running-specific until you're roughly 8 weeks out from a real goal. Getting specific too early tends to produce very fast fitness gains that aren't sustainable, and increases injury risk before your tissue has had time to catch up with your cardiovascular system's rapid rate of adaptation.