Reading Time: 10–12 Minutes
Summary
-
The immune system is one of the body’s biggest energy consumers – every activation costs an enormous amount of ATP.
-
If the immune system remains permanently overactive, chronic inflammation ensues: energy production collapses, increasing fatigue and exhaustion.
-
The study by Che et al. (2025) shows how immune hyperactivity drains energy in ME/CFS – with important implications for healthy individuals too.
Overview
- Why Immune Activity Costs So Much Energy
- The New Study by Che et al. (2025)
- Results: When the Immune System Overreacts
- Transferability to Healthy Individuals
- Everyday Tips for a Balanced Immune System
- Conclusion – What We Can Learn from the Research
- Original Publication
Why Immune Activity Costs So Much Energy
The immune system is one of the most energy-intensive systems in our body. Every immune response is hard work at a molecular level: immune cells must proliferate rapidly, signalling substances (cytokines) are released in large quantities, and specialised cells like macrophages or killer cells actively confront intruders. These processes require not just proteins, enzymes, and messengers, but above all, enormous amounts of ATP, the universal energy currency of cells.
Under normal circumstances, an immune response is temporary. Following an infection or injury, the defence processes are shut down, inflammatory messengers subside, and the body returns to an energetic equilibrium. This balance is precisely what is crucial: it ensures the immune system fulfils its task without consuming unnecessary energy or attacking healthy structures.
However, the reality can sometimes be different. If the immune system doesn't switch off but remains in a state of **permanent readiness**, a condition arises that researchers call low-grade chronic inflammation. Immune messengers remain permanently elevated, metabolic pathways go awry, and the mitochondria – our cellular powerhouses – switch to an inefficient emergency mode. The result: increased susceptibility to exhaustion, limited energy production, and, in extreme cases, chronic fatigue.
A recent, compelling study by **Che et al. (2025)** investigated exactly this mechanism. The researchers were able to show that in people with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome), the immune system exhibits heightened activity – even in response to minor stimuli. This involves the production of unusually high amounts of cytokines, metabolic pathways such as the citric acid cycle or fat burning fall out of balance, and metabolic products are created that can explain fatigue, cognitive problems, and persistent exhaustion.
The New Study by Che et al. (2025)
To illuminate these mechanisms in detail, the research team conducted a comprehensive study involving **56 patients with ME/CFS** and **52 healthy control subjects**. Crucially, both groups were carefully matched for age, sex, and other health parameters – ensuring that differences in the results could actually be attributed to the illness and not to random confounding factors.
All participants subsequently completed a **standardised cycle ergometry test**. This type of stress test is frequently used in medicine to measure the influence of physical activity on cardiovascular and metabolic functions. In the case of ME/CFS, it serves as a targeted trigger for a known symptom: post-exertional malaise (PEM) – a drastic worsening of well-being after even mild physical or mental exertion.
The study design, which captured the temporal dynamics rather than just snapshots, was particularly insightful: **Blood samples were taken both before the exercise and 24 hours afterwards.** This allowed researchers to precisely track how the immune system and energy metabolism react to stress – and whether the reactions in ME/CFS patients differed from those in healthy individuals.
For the analysis, the team used a modern **Multi-Omics approach**. This involves examining various biological levels simultaneously (more on this in the excursion below).
One can imagine this approach as a large puzzle: each "omics" piece provides information individually, but only together do they create a holistic picture of how the immune and energy metabolisms intertwine – and why massive disruptions occur in ME/CFS.
Excursion: Multi-Omics Explained
The term **“Multi-Omics”** describes the simultaneous analysis of different biological levels that are often studied separately. This involves looking at the **genome** (genetic information), the **proteome** (currently formed proteins, including immune messengers), and the **metabolome** (small metabolic products like sugars, fats, or amino acids) together.
The advantage: This creates a comprehensive picture that shows which processes are currently active – not just what would theoretically be possible. Especially in diseases like ME/CFS, this clarifies how immune responses disrupt energy metabolism and why mitochondria work less efficiently under stress. This approach can be imagined as the difference between a single instrument and the sound of the entire orchestra.
Results: When the Immune System Overreacts
The analysis provided clear findings:
- **Cytokine Overproduction:** Even at rest, the immune cells of ME/CFS patients released unusually high levels of inflammatory messengers (e.g., IL-6, TNF-α). After exertion, this release even increased – instead of calming down as in healthy individuals.
- **Disrupted Energy Metabolism:** Key pathways for energy generation did not run smoothly. Sugars, fats, and proteins could not be efficiently utilised. Instead of producing energy (ATP), intermediate products like citrates or blood fats accumulated – a sign of blockages in the “energy flow.”
- **Mitochondrial Stress:** The mitochondria – the cells' powerhouses – no longer worked efficiently. They produced less energy and, at the same time, more "waste products" in the form of oxidative stress, which additionally burden the body.
- **Tryptophan Metabolism:** Instead of the important messenger substance serotonin, more breakdown products were formed that can irritate the nervous system. This could explain typical complaints such as low mood, sleep problems, or "brain fog."
- **Gut Barrier:** There were signs of a more permeable gut lining ("Leaky Gut") and an altered microbiome. This allows tiny components of bacteria to enter the bloodstream and further inflame the immune system.
Excursion: Cytokines – Small Molecules, Big Impact
Cytokines are tiny messenger substances that immune cells use to communicate with each other. They ensure that the correct defence cell becomes active at the right time and place. Without cytokines, a coordinated immune response would be impossible. However, if they are permanently elevated, chronic inflammation ensues. This consumes enormous energy – and causes mitochondria to switch to an emergency mode.
The problem arises when these signals are permanently "on loud." This creates chronic inflammation, which no longer specifically fights intruders but burdens the entire organism. This consumes enormous energy and forces the mitochondria into an emergency mode: they produce less ATP but more oxidative stress. Over time, an actually useful signal can become an energy drainer.
Transferability to Healthy Individuals
The mechanisms described are not only observed in ME/CFS. Healthy individuals can also fall into similar patterns if the immune system remains permanently on alert:
- **Chronic Stress**: Hormonal fluctuations, especially in cortisol, disrupt immune balance.
- **Sleep Deprivation**: Even a few nights of poor sleep measurably increase inflammatory markers in the blood.
- **Unhealthy Diet**: Lots of sugar, trans fats, or alcohol promote "silent" inflammation, which secretly drains energy.
- **Infections & Long COVID**: After infections, the immune system often remains active for weeks – even when the acute illness is long gone.
Excursion: Mitochondria as a Central Switch
Mitochondria are far more than just the "powerhouses" of our cells. They react very sensitively to signals from the immune system and act like small control centres: if the body enters an inflammatory state, the mitochondria change their mode of operation.
Instead of efficiently producing energy in the form of ATP, their performance drops – at the same time, more free radicals (reactive oxygen species) are created. These, in turn, intensify inflammation and further stress the cells. This creates a vicious cycle: less energy is available while immune activity continues to be fuelled.
Everyday Tips for a Balanced Immune System
Even though we cannot directly "switch on or off" the immune system, there are many adjustable levers in everyday life that help keep it in balance – thus avoiding energy loss through silent inflammation:
- **Sleep:** A consistent 7–8 hours per night demonstrably lowers inflammatory markers and gives the immune system time to regenerate.
- **Diet:** Plenty of vegetables, Omega-3 fatty acids from fish or flaxseed, and polyphenols from berries and green tea act as natural anti-inflammatories.
- **Exercise:** Moderate activity – such as walks, cycling, or light strength training – strengthens the immune system without overburdening it.
- **Stress Management:** Breathing exercises, meditation, or conscious breaks stabilise cortisol levels, thus protecting against chronic immune system overload.
- **Micronutrients:** Vitamins, zinc, magnesium, and selected secondary plant compounds contribute to promoting immune balance and curbing oxidative processes.
Conclusion – What We Can Learn from the Research
The study by **Che et al. (2025)** makes it very clear: an immune system that remains permanently on alert is a genuine energy drainer. In patients with ME/CFS, this leads to massive exhaustion, concentration problems, and physical weakness. However, the underlying mechanisms – excessive cytokine production, disrupted energy metabolism, and overloaded mitochondria – can also occur in healthy individuals. The triggers are often everyday factors such as **chronic stress, too little sleep, or recurring infections**.
The good news: our body has strong self-regulation mechanisms. A **balanced immune system** is created when we provide it with the right conditions. This includes sufficient sleep, a **varied diet with anti-inflammatory foods**, regular exercise at moderate intensity, and conscious breaks for stress reduction. Certain micronutrients and secondary plant compounds can also help ensure that the immune response does not "overheat."
In this way, we protect not only our immune defences but also our **mitochondria** – and thus the basis of our energy production. Those who keep their immune system in balance maintain more vitality, concentration, and quality of life in everyday life.
