Understanding ME/CFS
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition that
can make even simple daily activities feel exhausting. Scientists are discovering that it’s not just
about feeling tired, real biological changes are happening in the body. Key players include your
brain’s neuroglia, your mitochondria (the energy factories in your cells), your immune system, cardiovascular system and your autonomic nervous system (ANS), which regulates your body’s “fight or flight” and
“rest and digest” responses.
Neuroglia and Stress
Neuroglia, including astrocytes and microglia, support and protect neurons in your brain. In
ME/CFS, these cells can develop a “stress memory,” staying overactive and hypersensitive to
even minor stressors (Renz-Polster et al., 2022). This helps explain why activities that seem
small can trigger post-exertional malaise (PEM) the flare-up of fatigue, pain, or brain fog after
exertion.
Being in the loop of fear, activated emotions and chronic stress worsens this by disrupting the
immune system, mitochondria, blood vessels, and nervous system, creating a cycle that can
intensify symptoms. It’s like multiple systems in your body are stuck in a loop of reacting as if
your body is in danger when the danger is long gone. Neuroglia also play a role in central
sensitization, where the nervous system becomes more sensitive to pain. Combined with
dysfunction in the hypothalamic–pituitary–adrenal (HPA) axis, this can reduce cortisol’s ability
to dampen pain signaling, amplifying fatigue and cognitive symptoms (Nijs et al., 2011).
Mitochondria: Your Cellular Powerhouses
Mitochondria produce the energy your cells need to function. Chronic stress can overload them,
creating “mitochondrial allostatic load,” which reduces energy efficiency and increases oxidative
stress (Smith, 2020). Overactive sympathetic nervous system activity further impairs
mitochondrial function across multiple tissues, leading to fatigue, inflammation, and cellular
stress (Kullmann et al., 2019). Something important to note is that while the mitochondira can
become dysfunctional or even damaged, these activities can promote biogenesis of new
mitochondria and support moving them toward more function.
On the flip side, relaxation and mind-body practices reduce mitochondrial stress, allowing cells
to use energy more efficiently (Karrasch et al., 2023). Gentle exercise, when tolerated, also
promotes mitochondrial growth and improves energy production (Picard & McEwen, 2018).
Immune System and Inflammation
Chronic stress can suppress protective immune responses while promoting harmful
inflammation. Mind-body interventions such as yoga, meditation, and hypnosis can lower pro-
inflammatory molecules and enhance antiviral defenses (Lee et al., 2025; Lemmy Schakel et al.,
2019; Thibodeaux & Rossano, 2018).
Genetics and ME/CFS
The DecodeME study, the largest genetic investigation into ME/CFS, has identified eight genetic
signals linked to immune and nervous system function. These findings confirm that ME/CFS has
a biological basis, with genes that can be switched “on” or “off” by environmental factors like
stress. This process, called epigenetics, changes gene activity without altering the DNA
sequence. Stress can activate genes that worsen symptoms, while stress reduction may help turn
them off, offering a pathway to better symptom management (Solve M.E., 2025; PMC, 2017).
The Autonomic Nervous System (ANS)
The ANS controls involuntary functions like heart rate, digestion, and blood pressure. In
ME/CFS, the sympathetic nervous system (“fight or flight”) can stay overactive long after
exertion, keeping the body in a heightened stress state and worsening fatigue, pain, and cognitive
issues (Wyller et al., 2009; Nelson et al., 2021).
Why Mind-Body Work Matters
One of the most effective ways to support mitochondria, immune function, and cardiovascular
health is through mind-body practices that regulate the nervous system. Meditation, yoga, deep
breathing, guided relaxation, challenging thoughts that cause more stress, shifting the way we respond to symptoms and hypnosis shift the body from chronic sympathetic arousal to
parasympathetic activation (“rest and digest”), lowering stress hormones and calming overactive
neuroglia (Karrasch et al., 2023; Thibodeaux & Rossano, 2018).
By supporting the nervous system, you create a ripple effect across the body: reducing
inflammation, improving energy metabolism, enhancing blood flow, and strengthening immune
function.
Gentle Strategies to Support Your Body
Movement: Walking, stretching, or gentle yoga can support mitochondria and circulation
without triggering PEM (Picard & McEwen, 2018). This needs to be done with proper pacing!
Mind-Body Practices: Meditation, guided relaxation, hypnosis, or yoga nidra reduce stress
hormones and calm the nervous system (Karrasch et al., 2023; Thibodeaux & Rossano, 2018).
Nutrition and Supplements: Anti-inflammatory foods like berries, turmeric, green tea, and
omega-3s help reduce oxidative stress. Supplements such as CoQ10, alpha-lipoic acid, L-
carnitine, and NAC support energy production and antioxidant defenses (Morris & Maes, 2014).
Sleep and Circadian Rhythm: Good sleep allows mitochondria to repair and restores nervous
system balance. Keeping consistent sleep times and using relaxation techniques can improve
sleep quality (Karrasch et al., 2023).
Heart and Circulation: Gentle movement, omega-3s, L-arginine, and relaxation practices
improve blood flow and endothelial function (Toda & Nakanishi-Toda, 2011).
*Always consult with a doctor or pharmacist before trying new supplements
Takeaway
ME/CFS affects multiple interconnected systems that can be worsened by stress but the reverse
is also true. Gentle, individualized strategies targeting stress reduction, shifting our responses and reactions to symptoms, mitochondrial support,
immune balance, and ANS regulation can help manage symptoms and improve overall
resilience. Small steps, like a few minutes of deep breathing, a gentle stretch, or gently affirming safety can have meaningful benefits for your body.
References
Andrés-Rodríguez, L., Borràs, X., Feliu-Soler, A., Pérez-Aranda, A., Rozadilla-Sacanell, A.,
Montero-Marin, J., ... & Luciano, J. V. (2019). Immune-inflammatory pathways and clinical
changes in fibromyalgia patients treated with Mindfulness-Based Stress Reduction (MBSR): A
randomized, controlled clinical trial. Brain, Behavior, and Immunity, 80, 109–119.
https://doi.org/10.1016/j.bbi.2019.03.011
Dhabhar, F. S. (2014). Effects of stress on immune function: The good, the bad, and the
beautiful. Immunological Research, 58(2–3), 193–210. https://doi.org/10.1007/s12026-014-
8517-0
Gautam, S., Saxena, R., Dada, T., & Dada, R. (2021). Yoga—impact on mitochondrial health:
Clinical consequences. Annals of Neurosciences, 28(3–4), 114–116.
https://doi.org/10.1159/000511134
Karrasch, S., Mavioğlu, R. N., Matits, L., Gumpp, A. M., Mack, M., Behnke, A., ... & Kolassa, I.
T. (2023). Randomized controlled trial investigating potential effects of relaxation on
mitochondrial function in immune cells: A pilot experiment. Biological Psychology, 183,
108656. https://doi.org/10.1016/j.biopsycho.2023.108656
Kullmann, F. A., McDonnell, B. M., Wolf-Johnston, A. S., Kanai, A. J., Shiva, S., Chelimsky,
T., Rodriguez, L., & Birder, L. A. (2019). Stress-induced autonomic dysregulation of
mitochondrial function in the rat urothelium. Neurourology and Urodynamics, 38(2), 572–581.
https://doi.org/10.1002/nau.23876
Lee, S.-C., Tsai, P.-H., Yu, K.-H., & Chan, T.-M. (2025). Effects of Mind–Body Interventions
on immune and neuroendocrine functions: A systematic review and meta-analysis of randomized
controlled trials. Healthcare, 13(8), 952. https://doi.org/10.3390/healthcare13080952
Lemmy Schakel, D. S. V., Crompvoets, P. I., Bosch, J. A., Cohen, S., van Middendorp, H.,
Joosten, S. A., ... & Evers, A. W. M. (2019). Effectiveness of stress-reducing interventions on
the response to challenges to the immune system: A meta-analytic review. Psychotherapy and
Psychosomatics, 88(5), 274–286. https://doi.org/10.1159/000501645
Morris, G., & Maes, M. (2014). Mitochondrial dysfunctions in myalgic
encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory,
oxidative and nitrosative stress pathways. Metabolic Brain Disease, 29(1), 19–36.
https://doi.org/10.1007/s11011-013-9435-x
Nelson, M. J., Buckley, J. D., Thomson, R. L., Bellenger, C. R., & Davison, K. (2021). Markers
of cardiac autonomic function during consecutive day peak exercise tests in people with myalgic
encephalomyelitis/chronic fatigue syndrome. Frontiers in Physiology, 12, 771899.
https://doi.org/10.3389/fphys.2021.771899
Nijs, J., Meeus, M., Van Oosterwijck, J., Ickmans, K., Moorkens, G., Hans, G., & De Clerck, L.
S. (2011). In the mind or in the brain? Scientific evidence for central sensitisation in chronic
fatigue syndrome. Journal of Internal Medicine, 269(5), 498–518.
https://doi.org/10.1111/j.1365-2362.2011.02575.x
Picard, M., & McEwen, B. S. (2018). Psychological stress and mitochondria: A systematic
review. Psychosomatic Medicine, 80(2), 141–153.
https://doi.org/10.1097/PSY.0000000000000545
Renz-Polster, H., Tremblay, M. E., Bienzle, D., & Fischer, J. E. (2022). The pathobiology of
myalgic encephalomyelitis/chronic fatigue syndrome: The case for neuroglial failure. Frontiers
in Cellular Neuroscience, 16, 888232. https://doi.org/10.3389/fncel.2022.888232
Smith, E. F. (2020). Mitochondrial allostatic load: The impact of chronic stress on mitochondrial
health. Nature Reviews Endocrinology, 16(10), 555–568. https://doi.org/10.1038/s41574-020-
0363-6
Solve M.E. (2025). First DNA results from DecodeME study offer new insights into ME/CFS.
Solve M.E. https://solvecfs.org/first-dna-results-from-decodeme-study-offer-new-insights-into-
me-cfs
Thibodeaux, N., & Rossano, M. J. (2018). Meditation and immune function: The impact of stress
management on the immune system. OBM Integrative and Complementary Medicine, 3(4), 1–23.
https://doi.org/10.21926/obm.icm.1804010
Toda, N., & Nakanishi-Toda, M. (2011). How mental stress affects endothelial function.
Pflügers Archiv-European Journal of Physiology, 462(6), 779–794.
https://doi.org/10.1007/s00424-011-0969-5
Wyller, V. B., Eriksen, H. R., & Malterud, K. (2009). Can sustained arousal explain the chronic
fatigue syndrome? Behavioral and Brain Functions, 5(10), 10. https://doi.org/10.1186/1744-
9081-5-10
