Oxidative Stress in ME/CFS & Long COVID and why nutrition is important

People living with ME/CFS and Long COVID commonly experience profound fatigue, post-exertional symptoms, brain fog and reduced ability to tolerate physical or mental activity. Increasingly research suggests that these symptoms may involve disturbances in the way cells produce and use energy, a mechanism which may be underpinned by oxidative stress

Here we describe details of an interesting study published in 2025 which found evidence of increased oxidative stress in immune cells from people with both ME/CFS and Long COVID. We describe how diet, particularly a Mediterranean diet, can reduce the impact of oxidative stress.

What is oxidative stress?

Our cells constantly produce molecules called reactive oxygen species (ROS). These are sometimes described as "free radicals". They are not necessarily harmful—in controlled amounts they have important roles in cell signalling and immune function.

The body has sophisticated antioxidant systems to keep ROS under control, including:

• glutathione

• superoxide dismutase

• glutathione peroxidase

• catalase

• other antioxidant enzymes.

Oxidative stress occurs when the production of reactive molecules exceeds the body's ability to control or repair the resulting damage.

This is particularly relevant to mitochondria, the structures within our cells responsible for producing ATP—the energy currency of the body.

Oxidative stress in ME/CFS and Long COVID

In 2025 new research was published by Shankar and colleagues entitled 'Oxidative stress is a shared characteristic of ME/CFS and Long COVID'

Researchers studied the immune cells from:

• 25 healthy controls

• 27 people with ME/CFS

• 20 people with Long COVID

They found evidence of increased oxidative stress in immune cells in both conditions. There were also changes in the systems normally responsible for controlling oxidative damage.

Importantly, the researchers found lower mitochondrial ATP (energy) levels in immune cells from both groups. On average, ATP levels were approximately 1.6-fold lower in ME/CFS cells and 2.8-fold lower in Long COVID cells compared with controls.

This is interesting because ATP is fundamental to cellular energy production.

However, the researchers were studying immune cells in the laboratory, rather than measuring energy production throughout the whole body. Therefore, the findings do not prove that oxidative stress causes fatigue in ME/CFS or Long COVID.

How might oxidative stress contribute to symptoms?

One possibility is that oxidative stress, mitochondrial dysfunction and immune activation may interact. Mitochondria produce energy, but they can also generate ROS. ROS can influence immune-cell behaviour and inflammatory signalling. Conversely, persistent immune activation increases the energy requirements of immune cells.

The researchers point out that immune cells can use a considerable amount of the body's energy, particularly when activated.

The study also found evidence of lipid oxidative damage and alterations in antioxidant pathways, including superoxide dismutase and glutathione-related pathways. This provides a possible link between:

oxidative stress → mitochondrial dysfunction → altered immune activity → increased energy demand

However, this remains a proposed mechanism rather than an established explanation for ME/CFS or Long COVID.

How nutrition may help reduce oxidative stress

At the current time there is not enough evidence to recommend a particular antioxidant supplement to support either condition. The best nutritional approach is therefore likely to be a nutrient-dense dietary pattern rather than taking large doses of individual antioxidants.

Here we outline some of the best dietary ways to reduce oxidative stress:

1. Consider a Mediterranean-style dietary pattern

One of the most evidence-supported approaches for reducing oxidative stress is to adopt a Mediterranean-style diet. A recent systematic review and meta-analysis of 20 randomised trials involving 2,208 participants found that Mediterranean diets increased overall antioxidant capacity and reduced several markers of oxidative damage. Whilst this research did not involve people with ME/CFS or Long Covid, it showed how Mediterranean-type diets reduced oxidative stress, and therefore may be helpful in these conditions.

A Mediterranean diet is one which includes:

• dairy, eggs and poultry

• vegetables and fruit

• beans and lentils

• whole grains

• nuts and seeds

• extra-virgin olive oil

• fish and seafood

• relatively little ultra-processed food.

2. Eat a wide variety of colourful vegetables and fruit

Vegetables and fruit provide a wide range of:

• vitamin C

• carotenoids

• polyphenols

• flavonoids

• folate

• potassium

• magnesium

• other compounds involved in antioxidant and cellular defence systems.

Aim for variety rather than concentrating on one "superfood".

Different plant foods contain different antioxidant compounds, so eating a range of colours is a good way to include a range of these important compounds.

Examples include:

• berries

• broccoli and other cruciferous vegetables

• tomatoes

• carrots and sweet potatoes

• leafy green vegetables

• peppers

• citrus fruits

3. Include nuts and seeds

Nuts and seeds provide:

• vitamin E

• magnesium

• selenium (particularly Brazil nuts)

• polyphenols

• unsaturated fats.

They can therefore contribute several nutrients involved in antioxidant protection and normal cellular function.

A small handful of mixed nuts can be an easy addition to meals or snacks.

4. Include sources of omega-3 fats

Oily fish contain essential fatty acids, EPA and DHA. Oily fish include fish such as:

• salmon

• sardines and pilchards

• herrings

• mackerel

• trout

• anchovies

Omega-3 fatty acids are antioxidants, but they are involved in regulating inflammatory processes and may therefore be relevant to the wider relationship between inflammation and oxidative stress.

The best source of omega 3 fatty acids for vegetarians and vegans is algae oil as it provides the active form of omega-3 that the body needs.

5. Make use of polyphenol-rich foods

Polyphenols are naturally occurring compounds found in many plant foods.

Good sources include:

• fresh berries and currants eg blueberries, blackcurrants, blackberries, plums

• extra-virgin olive oil

• cocoa/dark chocolate

• tea, black and green,

• coffee

• herbs and spices, e.g cloves, peppermint, star anise, oregano and rosemary

• colourful vegetables - red onions, red cabbage, garlic, leeks, tomatoes

• apples, with peel

• Nuts and seeds - eg walnuts, flaxseeds, almonds,pecans

Their biological effects are more complicated than simply "neutralising free radicals". They can also influence cellular signalling and endogenous antioxidant pathways.

This is one reason why whole foods are preferable to relying on isolated antioxidant supplements.

6. Support the body's own glutathione system

Glutathione is one of the body's major intracellular antioxidant systems.

The body makes glutathione itself from amino acids, particularly:

• cysteine

• glycine

• glutamate.

Adequate protein therefore matters.

Useful food sources include:

• eggs

• fish

• poultry

• dairy

• meat

• tofu

• beans and lentils

• nuts and seeds.

This Photo by Unknown Author is licensed under CC BY-NC-ND

The 2025 ME/CFS/Long COVID study found alterations in glutathione-related pathways in both conditions, although these changes were complex and differed between groups and sexes.

This does not mean that everyone with ME/CFS or Long COVID needs glutathione or NAC supplements. However, it reinforces the importance of ensuring adequate intake of the nutrients required to maintain normal antioxidant systems.

7. Don't neglect micronutrients

Several vitamins and minerals are required for normal antioxidant and mitochondrial function.

These are shown below:

Should people take antioxidant supplements?

This is an area where caution is important. It can be tempting to think that If oxidative stress is involved, more antioxidants must be better. But biology is more complicated.

ROS have useful physiological functions, particularly in immune signalling and cellular adaptation. Very high doses of antioxidant supplements can potentially interfere with normal signalling pathways.

Instead it is better to consider food first and to identify any specific deficiencies and to supplement where there is a good reason.

Practical steps for people with ME/CFS and Long COVID

Nutrition should support the body's ability to cope with physiological stress, rather than become another source of stress.

For people with ME/CFS, Long COVID or significant gastrointestinal/autonomic symptoms, eating a "perfect" diet may be unrealistic.

Practical priorities might therefore be:

1. Eat enough

2. Get sufficient protein

3. Avoid unnecessary dietary restriction

4. Eat a variety of plant foods as tolerated

5. Correct confirmed nutritional deficiencies

6. Stay adequately hydrated

7. Choose minimally processed foods where practical

What does this research mean overall?

The 2025 study provides interesting new evidence that oxidative stress and altered mitochondrial function are biological features shared by ME/CFS and Long COVID, particularly within immune cells.

But it does not yet demonstrate that oxidative stress causes the illnesses, nor does it demonstrate that antioxidant treatment will improve symptoms.

The most evidence-based nutritional response at present is therefore not a high-dose antioxidant programme, but a nutrient-dense, varied dietary pattern that supplies the raw materials required for the body's own antioxidant and mitochondrial systems.

A Mediterranean-style dietary pattern is particularly attractive because clinical trials show improvements in several markers of oxidative stress, while it also provides good-quality protein, fibre, unsaturated fats, vitamins, minerals and polyphenols.

References

• Shankar V et al. Oxidative stress is a shared characteristic of ME/CFS and Long COVID. PNAS, 2025.https://doi.org/10.1073/pnas.2426564122

• Dorczok MC et al. Dietary Supplementation for Fatigue Symptoms in ME/CFS – A Systematic Review. Nutrients, 2025. (PubMed)

• Nutritional Support During Long COVID: A Systematic Scoping Review, 2023. (PubMed)

• Ilari S et al. Dietary Patterns, Oxidative Stress, and Early Inflammation: A Systematic Review and Meta-Analysis, Nutrients, 2025. (PubMed)

• Effects of the Mediterranean diet on oxidative stress: a systematic review and meta-analysis of randomized clinical trials, 2026. (PubMed)

• Updates on Mediterranean diet and health status: active ingredients and pharmacological mechanisms, 2026. (PubMed)