Chronic Fatigue Syndrome (CFS, Myalgic Encephalomyelitis)
Chronic Fatigue Syndrome (CFS, or Myalgic Encephalomyelitis) is a complex disorder in which a person experiences constant or recurring debilitating fatigue that does not resolve with rest and significantly reduces quality of life. Its exact causes are not fully understood, but today several factors and biological processes are identified as influencing the development and course of this syndrome.
Main factors and conditions influencing CFS
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Immune system dysfunction
Patients often show chronic activation of the immune system (elevated cytokines — IL-6, TNF-α).
The condition resembles a “prolonged post-viral reaction,” where the body remains in a constant state of readiness to fight infection.
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Viral and bacterial infections
CFS often develops after infections (Epstein–Barr virus, cytomegalovirus, herpesviruses, COVID-19).
It is believed that viruses can trigger cascades of immune and neuroinflammatory processes.
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Neuroendocrine dysfunction
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.
Patients often have reduced cortisol secretion — the main stress hormone, leading to rapid fatigue, decreased stress resistance, and a persistent sense of exhaustion.
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Mitochondrial dysfunction
Mitochondria — the cell’s “power plants.” Many CFS patients show impaired mitochondrial function and reduced ATP synthesis.
This results in energy deficiency even with minimal exertion.
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Nervous system dysfunction
Decreased activity of neurotransmitters (serotonin, dopamine, norepinephrine).
Increased central sensitization (the brain processes normal signals as excessive), manifesting not only as fatigue but also as musculoskeletal pain, sleep disturbances, and cognitive issues (“brain fog”).
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Chronic stress and psycho-emotional factors
Prolonged stress depletes regulatory systems, increases inflammation, and leads to neuroendocrine disruption.
CFS is not just “psychological fatigue,” but psycho-emotional factors can worsen the condition.
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Sleep disturbances
Deficiency of deep sleep phases leads to impaired recovery.
Even with adequate sleep duration, patients wake up feeling “unrefreshed.”
What happens in the body with CFS
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Immune system: chronic “low-grade inflammation,” constant cytokine release → fever-like sensations, pain, loss of strength.
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Endocrine system: reduced cortisol secretion and stress hormone imbalance → poor adaptation to stress and activity.
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Mitochondria and energy metabolism: impaired ATP synthesis, cells experience “energy starvation.”
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Nervous system: neurotransmitter imbalance and hyperactivity of brain fatigue/pain centers → persistent weakness, cognitive dysfunction.
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Metabolism: many patients have insulin resistance and nutrient deficiencies (vitamin D, B vitamins, magnesium), aggravating fatigue.
Summary
Chronic Fatigue Syndrome is not simply “stress-related fatigue,” but a complex disorder where the immune, nervous, endocrine systems, and energy metabolism are simultaneously affected. This is why a person feels constant fatigue even after sleep and rest: their cells do not produce enough energy, the brain misprocesses signals, and the body remains in a state of chronic inflammation.
Therapy with Active Mitochondria
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What happens at the mitochondrial level in CFS
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Reduced activity of the mitochondrial respiratory chain (complexes I–IV), impaired electron transport.
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Decreased ATP levels, leading to cellular “energy starvation.”
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Increased production of reactive oxygen species (ROS), enhancing oxidative stress and inflammation.
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Disturbed NAD⁺/NADH balance, limiting glucose and fatty acid metabolism.
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Mitochondrial DNA damage and reduced biogenesis of new mitochondria.
How the introduction of active mitochondria works
Modern studies (mitochondrial transplantation, introduction of purified mitochondria, or stimulation of their biogenesis) show:
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Increase in ATP production
Donor mitochondria integrate into target cells (muscle, neuronal, immune).
Respiratory chain function is restored, ATP output increases.
Patients feel more energy, reduced sense of “energy collapse.”
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Reduction of oxidative stress
Healthy mitochondria utilize oxygen more efficiently and reduce free radical formation.
Lower ROS → less protein, lipid, and DNA damage.
This leads to reduced inflammation.
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Restoration of NAD⁺/NADH balance
New mitochondria restore normal function of dehydrogenases and Krebs cycle enzymes.
Higher NAD⁺ levels improve sirtuin (SIRT1, SIRT3) function → anti-aging, restored cellular metabolism.
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Activation of mitochondrial biogenesis
Donor mitochondria release signaling molecules and factors (mtDNA, mitochondrial proteins) that activate PGC-1α — the key regulator of mitochondrial biogenesis.
In response, the body produces new mitochondria.
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Immunomodulation
Improved mitochondrial function in immune cells reduces chronic inflammation (lower IL-6, TNF-α).
This reduces neuroinflammation and fatigue.
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Neuroprotection and cognitive improvement
In neurons, new mitochondria restore glutamate and calcium balance.
Signal transmission improves, reducing “brain fog.”
Biochemical improvements experienced by patients

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↑ ATP production → more energy in muscles and brain.
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↓ ROS and oxidative stress → less inflammation and pain.
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↑ NAD⁺ → improved function of metabolic enzymes, antioxidant systems, DNA repair.
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↑ Mitochondrial biogenesis → long-term sustained effect.
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↑ Neurotransmitter balance (dopamine, serotonin) → better mood and cognition.
Conclusion: Therapy with active mitochondria acts as a “reset of cellular energetics”: it restores normal energy metabolism, reduces inflammation and oxidative stress, and stimulates regeneration. For CFS patients, this may mean a shift from constant exhaustion to gradual recovery of functionality, mental clarity, and physical endurance.
Neural Induced Stem Cells (iPSC-derived NSC/NPC) in CFS Therapy

How neural iPSC cells may help
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Restoration of neurotransmitter balance
iPSCs can differentiate into dopaminergic, serotonergic, or GABAergic neurons.
This replenishes neurotransmitter deficits → improved mood, reduced fatigue, enhanced cognition.
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Strengthening inhibitory pathways
Introduction of GABAergic interneurons can increase inhibition in the spinal cord and brainstem, reducing sensory hyperactivity and central sensitization.
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Neuromodulation and trophic effects
Neural progenitors secrete neurotrophic factors (BDNF, GDNF, NGF).
These improve survival of existing neurons, normalize synaptic plasticity, and reduce pathological hyperactivation.
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Regulation of glutamate metabolism
Some iPSCs can differentiate into astrocytes → they regulate glutamate levels, preventing its excessive accumulation.
This reduces excitotoxicity and hyperexcitability.
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Reduction of CNS inflammation
Neural stem cells can modulate microglia, lowering IL-6 and TNF-α release.
This reduces neuroinflammation associated with chronic fatigue and “brain fog.”
Potential patient benefits
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Improved sleep and cognition (via increased serotonin and dopamine).
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Reduced chronic pain and fatigue (via central sensitization suppression).
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Improved mood and reduced anxiety.
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Restoration of normal neural network plasticity.
Conclusion: Neural iPSC-derived cells may represent a promising direction in CFS therapy, as they target two key mechanisms: normalizing neurotransmitter levels and reducing central sensitization.
It is important to understand the nature of chronic fatigue, establish the correct diagnosis, and, based on the existing imbalance, select precise medical intervention tools.
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