The Hungry Pharmacist

You’re probably thinking, What kind of silly question is that? I asked myself the same thing after the thought crossed my mind during a workout, when I felt tired after just five kilometers of running. Of course, I would feel tired—especially since I’m not particularly well-trained at the moment. But I asked myself why that is, given that I currently carry at least ten kilograms of excess body fat—which is likely enough energy for several marathons.

One kilogram of fat contains about 7,700 calories, which means I have at least 80,000 surplus calories, if not more. A single marathon burns around 2,600 calories, assuming an average of 100 calories per mile. So, in theory, I have enough energy stored as fat to run about 40 marathons. And yet, I struggle with just five kilometers. Why doesn’t my body use this potential energy? In fact, the heavier we are, the harder it becomes to even jog, let alone run long distances or perform any demanding physical task.

Why do we get tired even after a busy week, counting down the minutes until the weekend or the end of the day just to “recharge our batteries”? Fatigue is a defense mechanism of the body, a response to physical, mental, or emotional strain. If fatigue didn’t exist, we would likely suffer more frequent illnesses, infections, or even cancer due to excessive wear and tear on the body.

Highly trained athletes often feel less fatigue, and I’ll explain why—but they still experience it, sometimes at an even greater intensity. In his book “Can’t Hurt Me”, former Navy SEAL David Goggins describes the effects of fatigue after his first ultramarathon. Warning: his descriptions are not for the faint of heart—from intense diarrhea to near kidney failure. At one point, his dehydration was so severe that his urine turned brown.

So if this defense mechanism (much like pain) didn’t exist, it could lead to disastrous consequences. That’s why different systems in the body work together to create the feeling of fatigue:

1. Cellular Energy Imbalance

The primary fuel in our body is ATP (adenosine triphosphate), mainly produced from carbohydrates, then fats, and only to a small extent from proteins. If you eat an energy bar 30 minutes before a workout, it can provide enough fuel. If you don’t, the body seeks energy elsewhere. Carbohydrates are stored in the body as glycogen in the liver and muscles—about 1% of our body mass, meaning they can be depleted quickly.

The body prefers glycogen because it can rapidly convert it into energy. During running or swimming, muscles need a lot of energy fast. To create ATP, cells require oxygen for aerobic respiration, the process that produces the most ATP from glucose. The problem is that under strain, the body can’t deliver enough oxygen to the cells, prompting us to breathe faster and deeper.

Eventually, oxygen delivery via blood can’t keep up, and the body switches to anaerobic respiration, which doesn’t require oxygen—but it’s less efficient. It produces less ATP and leads to the accumulation of lactate (lactic acid) in the muscles, lowering pH (making the environment more acidic), which causes burning, pain, and muscle contractions. That’s usually the point when people give up.

So why not use fat instead?
Because converting fat into ATP takes longer—it’s a slower process called beta-oxidation. During intense activity, the body simply doesn’t have time for it. However, low-intensity activities like walking or light jogging do burn fat. I’ve previously written about this in my post on Zone 2 training. That’s why lighter activities are recommended for fat loss and endurance building (at around 60–70% of your max heart rate).

2. Accumulation of Byproducts

As mentioned, lactate is a byproduct of energy production without oxygen. When you’re biking uphill and pedaling hard, you start breathing shallow and fast. Soon after, your calves and quads begin to hurt and cramp.

Mitochondria (the power plants of our cells) produce ATP and send signals to the brain that they need more oxygen. The brain tells the lungs, and breathing speeds up—requiring even more energy. When you can’t breathe any faster or pump more blood, the body shifts to anaerobic energy production. Lactate builds up, acidity increases, muscle pain starts, and enzyme function decreases—leading to fatigue.

Luckily, lactate is eventually converted back into glucose, and about 30 minutes later, your muscles can resume activity.

3. Neurotransmitter Imbalance

In my dopamine article, I mentioned neurotransmitters. Besides dopamine, our brains also use serotonin and norepinephrine.

Dopamine, often called the “happinness hormone”, is actually a neurotransmitter released as a reward when achieving a goal or experiencing pleasure. Low dopamine levels reduce motivation—whether for training, work, eating, or studying. That’s why managing dopamine is crucial.

Serotonin regulates mood and sleep. Too much can cause drowsiness, while too little leads to poor focus and alertness. A neurotransmitter imbalance, which fatigue can cause, leads to decreased motivation, mental fatigue, and reduced psychological endurance.

Example: You’re on a long run—say, 10 km. After a few kilometers, your brain plays tricks on you: “Why are you doing this?” “Give up—it’s not worth it,” “Wouldn’t you rather be on the couch?” Those inner voices are signs of neurotransmitter imbalance—the brain’s way of trying to escape fatigue and convince you to stop.

4. Inflammation and Cytokine Release

Cytokines are small molecules produced during tissue damage, physical stress, or infection, as part of the immune response. They signal the brain when there’s injury or fatigue. The most important fatigue-related cytokines are IL-6 (interleukin 6), TNF-alpha, and IL-1.

Their effects include reduced strength, the urge to rest, and sometimes even a mild fever.

5. Hormonal Imbalances

Fatigue—especially chronic fatigue—affects hormone production:

• Cortisol – the stress hormone. Initially helpful in managing stress and reducing inflammation, but chronically high levels (due to overtraining or stress) lead to chronic fatigue and hinder recovery.
• Melatonin – the sleep hormone. Physical stress disrupts its normal rhythm, leading to poor sleep.
• Testosterone – in men especially, low levels reduce recovery ability and increase stress.

How to Overcome Fatigue?

Training increases mitochondrial capacity and VO2 max (lung/oxygen capacity). This improves oxygen delivery to cells during physical activity, enabling more aerobic energy production and reducing lactate buildup and muscle pain.

A combination of HIIT (High-Intensity Interval Training) and Zone 2 training is ideal for improving VO2 max.

Avoid constant dopamine stimulation from social media, food, and entertainment. Instead, shift toward natural stimuli like nature and meditation. This helps prevent dopamine crashes and motivation drops.

A strong immune system minimizes overproduction of cytokines. Proper nutrition with adequate macro and micronutrients, fiber, hydration, and training is key. So are sun exposure, time outdoors, and fresh air—for immunity, focus, and stress reduction.

All these—training, nutrition, sunlight, nature, meditation, avoiding social media—also contribute to hormonal balance. For example, waking up at 6 or 7 AM raises cortisol to help us wake up, and daily stress is more manageable. Regular sleep maintains melatonin production and a healthy biological rhythm.

Conclusion

If our body were a simple machine, it would tap into fat stores anytime we needed energy. But the body saves fat for hard times—like days or weeks without food. Luckily, most of us never experience this, and we carry those reserves our whole lives.

So to better manage fatigue, we need to activate fat stores through training and optimal nutrition—and increase the number of energy-producing units in the body.