What is Fatigue? Part I: Causes of Fatigue

What even is fatigue?

Before establishing what causes fatigue, we should first determine what fatigue is.

At its essence fatigue at any time point, in any event, is the inability to maintain or continue generating power from the neuromuscular system, given power is determined by strength x speed the root cause of a drop in power can be either; a limitation in speed (of the sliding filaments or enzymes breaking down or cleaning up different substances in the muscle) or strength (typically a failing of the nervous system).

This can seem a little simplistic, and it is, but from long distance and endurance type events all the way to Olympic Lifting an inability to maintain the right combination of strength and speed is the ultimate physiological cause of reduced performance. 

The actual processes causing that fatigue are a complex and almost always occur simultaneously, so trying to blame one component or physiological factor is unfair and far too simplistic, but let's try anyway...

Marathons/half-marathons/race walking (80-240minutes)

Beyond the psychological side of having the grit and motivation to attempt these gruelling types of distances, the real limit to power will be running out of intramuscular glycogen. The body has many fuel sources, but it's favourite, and most potent of these is glycogen pre-stored in the muscle. Glycogen is our favourite because it's just so damn easy to use, sitting right there in the muscle ready to be broken down through glycolysis, feeding the mitochondria as pyruvate and giving us ATP for contraction. 

We also have glycogen stored in our liver and glucose (glycogen is just the collective noun for glucose, they are essentially the same thing) floating around in the bloodstream, these are handy fuel sources but when it comes to glucose and glycogen it's all about location, location, location.

Transporting glucose into the muscle from the liver or the blood stream into the muscle takes a transporter protein called GLUT4, a hormonal state of rest and digest, and energy. Three things a muscle under huge levels of stress is not overly interested in diverting attention too. That's not to say your half-time or mid-race sugar is useless, a bit of top-up glucose will certainly help but it really only trickles into the muscle, which is why strategies like carb loading and picking the perfect pre-game meal are so important.

The third alternative fuel our body can access for exercise is fat. Fat is a great dense fuel source and athletes can manipulate their diets and training (it's called fat adaptation) to improve their fat oxidation capacity and efficiency but fat is still ultimately an inefficient secondary substitute to muscle glycogen (especially for anaerobic events like team sports).

The first time I studied this graph I was shocked - glycogen is such a finite resource, and it runs out really fast

The first time I studied this graph I was shocked - glycogen is such a finite resource, and it runs out really fast

400m - 10km (45sec - 30minutes)

With training in this territory, as long as your pre-event nutrition is OK glycogen should no longer be an issue, the biggest threats to power output now are your ability to consume and process oxygen, so VO2 max (sometimes called maximum aerobic speed - MAS), and lactate threshold (sometimes called anaerobic threshold) the ability to buffer and handle metabolite build up.

There isn’t a clear-cut line between energy systems. They're all inter-playing all the time. If you start working above the point of VO2 max, your body starts demanding and using more energy than you can produce aerobically, which means the byproducts of glycolysis and the phosphocreatine system (hydrogen ions (H+), inorganic phosphates (Pi), free calcium (Ca2+, ADP & AMP, and lactic acid) are produced at a rate faster than the muscles can deal with and utilise them.

Glycolysis: The process of turning glucose and glycogen into lactic acid (without oxygen) or pyruvic acid for use by the mitochondria. Note the byproducts along the way including the 2 ATP molecules - these are the ATP we get from the anaerobic (lactic acid) energy systems. NADH is another compound that is used in the mitochondria later on for aerobic metabolism.

Glycolysis: The process of turning glucose and glycogen into lactic acid (without oxygen) or pyruvic acid for use by the mitochondria. Note the byproducts along the way including the 2 ATP molecules - these are the ATP we get from the anaerobic (lactic acid) energy systems. NADH is another compound that is used in the mitochondria later on for aerobic metabolism.

Science seems to be telling us that lactic acid (or lactate) is not the true cause of fatigue, and in fact, fitter athletes produce more of it faster, instead, you can probably pin the blame for why 400s are so damn tough on hydrogen ions and inorganic phosphate.

Hydrogen ions (or H+) are produced in the same pathway that turns glycogen into pyruvic acid. Under aerobic conditions, H+ are good for us, but in the absence of enough oxygen, they cannot be processed in the mitochondria fast enough and instead begin building up in the muscle cell, creating an acidic environment which blocks the speed of contraction in the muscles.

The ATP production process within the mitochondria, the pyruvate produced at the end of aerobic glycolysis is converted to acetyl CoA and enters the Krebs (citric acid) cycle. The real energetic power house of the mitorchondria is the electron transport chain which takes Hydrogen ions, NADH and FADH and pumps out huge amonuts of ATP.

The ATP production process within the mitochondria, the pyruvate produced at the end of aerobic glycolysis is converted to acetyl CoA and enters the Krebs (citric acid) cycle. The real energetic power house of the mitorchondria is the electron transport chain which takes Hydrogen ions, NADH and FADH and pumps out huge amonuts of ATP.

The other is Inorganic phosphate (or Pi). As we break down ATP into ADP, Pi is released. This inorganic phosphate loves calcium, but we will talk about that soon...

200m - 50m (30s - 6s)

In these more explosive distances, strength and the ability of the nervous system to drive contraction is now playing a massive role (not to say endurance athletes don't need strength). From an energy system standpoint, phosphocreatine stores are more valuable than gold.

ATP is the end product of all the energy producing pathways, the fastest way to replace and create new ATP is a compound called phosphocreatine (or PC or PCr, or CP. My favourite is PCr).

That phosphocreatine (PCr) donates one of its phosphate molecules back to the ADP to recreate ATP. Our muscles have enough PCr for about four to eight seconds of high-intensity work (that number is heavily disputed and varies for everyone). Once it runs out, our body has to rely on anaerobic glycolysis, which is a much slower and less efficient form of energy production.

So why is this zone as far out as 30s even though we only have 8s worth of PCr?

Well, for elite sprinters a 200m is 18-21 seconds and given their training histories and probable use of Creatine supplementation they are probably creeping out to the 12-15 second range for PCr stores, which is now well above 50% of the race time. Remember: There is always an interplay of the energy systems, for the average human 200s will be an anaerobic glycolysis limitation while for Bolt Thompson and co, PCr stores and strength are going to holding them back.

40m - 10m (5s - 2s)

With something like a single 20-minute sprint, there isn’t really anything energetically causing fatigue. The biggest limits to performance are going to be technical factors, strength, and genetic factors such as muscle fibre type.

Repeat Sprints (Multiple efforts of 2 - 10s)

With repeat sprints, do enough of them or have short enough rest periods between each rep and any one of the above factors will come into play (20 x 20m on 20s rest anyone?). But one of the biggest overarching factor at play is the sarcoplasmic reticulum’s ability to reabsorb and recycle calcium.

This is where things get really nerdy (if they hadn't already?), but bear with me.

Our brain sends a signal down the motor neuron's axon to the muscle cell, that signal then travels down a structure called the T-tubule, which in turn releases calcium (Ca2+) from this structure called the sarcoplasmic reticulum (or SR) which sits just inside the muscle cell. That calcium then acts on your actin and myosin allowing contraction to work via the sliding filaments,

So, remember before, how I mentioned inorganic phosphate loves calcium? Well, inside the muscle cell they cling to each other tight. While they are stuck together, that calcium can’t be reabsorbed (re-sequestered as the textbooks call it) back into the SR, which means we can't repeat and recycle that contraction process.

In the video I diagram out this Calcium process:

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