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The role of oxidative stress in ME/CFS and Long Covid

  • Writer: Isabel Hemmings
    Isabel Hemmings
  • May 29
  • 4 min read

Updated: Jun 2


Oxidative stress is increasingly recognised as a key contributor to the symptoms experienced in ME/CFS and Long Covid. These conditions, both marked by chronic fatigue, cognitive difficulties, and a range of systemic symptoms, are thought to involve widespread cellular dysfunction. One mechanism central to this dysfunction is oxidative stress.

 

Diagram illustrating oxidative stress effects, featuring spindle errors, DNA damage, mitochondria deterioration, and declining ATP levels.



What is Oxidative Stress?


Oxidative stress is a state where the body’s balance between harmful free radicals and protective antioxidants is disturbed.


Oxidative stress occurs when reactive oxygen species (ROS), also called free radicals, are produced in the body at levels beyond what our antioxidant systems can neutralise. While ROS are a natural by-product of cellular metabolism and even play some beneficial roles in immune response,  too many ROS can damage critical structures within cells, including proteins, fats, mitochondria, and DNA, as shown in the diagram below:


Diagram showing a cell creating ATP and ROS from oxygen and glucose. Free radicals cause protein, mitochondrial, DNA, and membrane damage.


What symptoms arise with oxidative stress ?


A range of symptoms can arise when oxidative stress is present, including:


  • Fatigue

  • Brain fog

  • Musculo-skeletal problems

  • Pain

  • Sleep disturbance


Silhouette of a head with an outlined brain inside, in blue and white. Simple design, no text, evokes a sense of intelligence and thought.


Oxidative stress and energy production in ME/CFS and Long Covid


In people with ME/CFS or Long Covid, high ROS levels can interfere with energy production, increase inflammation, and worsen fatigue, brain fog, and musculoskeletal pain.


Mitochondrial damage caused by oxidative stress is particularly concerning as mitochondria are responsible for making energy in the body. When mitochondria become dysfunctional, energy production falters, contributing to the profound fatigue and post-exertional malaise characteristic of both conditions.


Woman asleep at desk beside laptop and mug, in a sunlit room. She appears exhausted. Green plant visible in the background.

Numerous studies support the role of oxidative stress in ME/CFS. For example, a 2020 systematic review found consistent evidence of increased markers of oxidative damage in people with ME/CFS, including elevated lipid peroxidation and reduced levels of key antioxidants such as glutathione (Jammes, 2005).


Similar patterns have been observed in people with Long Covid, with increased oxidative stress markers and mitochondrial dysfunction (Stufano, 2023). Oxidative stress may not just a by-product of chronic illness but may be a potential driver of ongoing symptoms and energy deficits.

 

What causes oxidative stress?


There are several causes of oxidative stress relevant to ME/CFS and Long Covid. These include:


  • chronic viral infections

  • immune dysregulation

  • poor sleep quality

  • stress

  • nutritional deficiencies

  • disrupted circadian rhythms


    Environmental toxins, ultra-processed foods, and sedentary lifestyles can further aggravate oxidative imbalance.


Diagram showing some of the factors that can contribute to oxidative stress

Flowchart illustrating factors like diet, stress, and sleep deprivation contributing to oxidative stress. Arrows point to a central "Oxidative stress" circle.

 

How can oxidative stress be reduced?


There are many dietary and lifestyle strategies that can help to reduce oxidative stress and support cellular health.


Antioxidant foods


Foods high in antioxidants, such as berries, dark leafy greens, nuts, seeds, olive oil, and oily fish, can help neutralise ROS and support mitochondrial function.


Wooden spoon with blueberries and raspberries on a wooden board. Bright colors and fresh fruits create a vibrant, appetizing mood.

Specific nutrients


Specific nutrients that are known to be helpful in reducing oxidative stress include include vitamins C and E, selenium, zinc, and plant-based compounds like polyphenols and flavonoids.


Glutathione


Glutathione, often referred to as the “master antioxidant,” plays a central role in neutralising ROS. While direct supplementation may not always be effective due to poor absorption, dietary precursors such as cysteine (found in poultry and eggs), glycine (found in collagen-rich foods), and glutamine (present in meats and dairy) can help the body synthesise glutathione naturally.

Grilled salmon on a black plate with spinach and spiralized vegetables, garnished with a lime wedge and placed beside a fork on a dark surface.

 

Circadian rhythms


Another important but often overlooked factor is the circadian rhythm—the internal biological clock that regulates our sleep, metabolism, and immune responses. Disruption of circadian rhythms can impair the body’s ability to detoxify, repair cellular damage, and regulate inflammation. Inconsistent sleep, irregular eating patterns, and lack of daylight exposure can all worsen oxidative stress and inflammation.

 

“Almost every aspect of eating, from craving food or feeling hungry to digestion and elimination, occurs according to strong circadian timing.

What’s more, we also know that eating the wrong foods at the wrong time not only disrupts the digestive clock but creates disease and chronic illness.”

 

Dr Satchin Panda, The Circadian Code

Resetting and supporting circadian rhythms can improve energy regulation and cognitive clarity. Simple strategies include:


  • waking and sleeping at the same time each day,

  • getting natural light exposure in the morning,

  • avoiding screens before bedtime,

  • fasting for at least 12 hours overnight

  • eating meals at regular times.


This consistent routine helps align hormonal signals, optimise mitochondrial repair, and reduce systemic oxidative stress.

 

 

Practical ways to reduce oxidative stress


In practical terms, people with ME/CFS and Long Covid can benefit from taking a gentle, structured approach to reducing oxidative stress. This includes:


  • choosing nutrient-dense, whole foods

  • avoiding sugar, ultra-processed snacks

  • avoiding inflammatory seed oils

  • building in regular but manageable routines for sleep and meals

  • incorporating light movement, mindfulness, and rest

 


Conclusion


While more research is needed to establish targeted antioxidant therapies, current evidence strongly supports the inclusion of anti-inflammatory and antioxidant-supportive nutrition and lifestyle strategies as part of a holistic management plan for ME/CFS and Long Covid.

 


References:


  1. Jammes Y, et al. Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med. 2005 Mar;257(3):299-310. doi: 10.1111/j.1365-2796.2005.01452.x. PMID: 15715687.


  2. Stufano A et al. Oxidative Damage and Post-COVID Syndrome: A Cross-Sectional Study in a Cohort of Italian Workers. Int J Mol Sci. 2023 Apr 18;24(8):7445. doi: 10.3390/ijms24087445. PMID: 37108606; PMCID: PMC10139201.

  3. 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


  4. Panda, S. (2018). The Circadian Code. Rodale Books.


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