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Oxidative stress and inflammation are two of the most frequent findings in patients with chronic fatigue syndrome.


Oxidative stress is essentially an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralisation by antioxidants. A balance between free radicals and antioxidants is necessary for proper physiological function.

While the nutrition industry and the media have pushed the benefit of antioxidant supplementation to counteract the negative effects of oxidative stress, we have to focus on our food first. In fact some research has shown supplementation with antioxidants to be detrimental in certain cases.

For example some research demonstrates that certain cellular processes may be blunted by high doses of antioxidants:

An emerging theme supports the view that because Nrf2 is activated by a mild pro-oxidant signal, high doses of antioxidant supplements may blunt signals required to activate endogenous defences.

It is for reasons such as this, among others (many studies being done on animals rather than humans for example), that some argue that we should focus more on polyphenols and other phytochemicals [molecules found in foods like fruit and vegetables] as a way of modulating oxidative stress and supporting endogenous defence mechanisms.

Have we become more reliant on multivitamins and antioxidant supplementation than on the vast range of food derived molecules that come from our food? The below quote certainly gets us thinking:

“It has been estimated that there are more than 5000 different phytochemicals present in food and our current knowledge is limited to a reasonable understanding of the function of just a few….The realization that food-derived molecules are in constant conversation with complex intracellular control systems via signalling pathways has unveiled the role of food as so much more than a source of micro- and macronutrients….What becomes immediately apparent in this model is that no multi-nutrient supplement can substitute for the enormous diversity in phytochemicals present in a balanced human diet.”

Enter Nrf2!

Nrf2 as “Master Regulator” of Cell Defense

NRf2 is a key transcription factor regulating several anti-oxidant and anti-inflammatory genes. NRf2 also induces the synthesis of proteins with roles in detoxification pathways.

There are three benefits in regards to NRf2 that are worth highlighting:

  1. Antioxidant Effects of Nrf2: NRf2 influences over two dozen genes that increase antioxidant activities.
  2. Glutathione Production: There are three genes related to enzymes that are required for the production of glutathione, and they are all activated by Nrf2. Glutathione, a powerful antioxidant, is often found to be depleted in patients with CFS (see our article “CFS – A Th2 dominant condition?”).
  3. Anti-inflammatory effects: Nrf2 stimulation produces several anti- inflammatory effects.

Foods that stimulate NRf2 include:


Green tea, curcumin, ginger, broccoli, cabbage, broccoli, Brussel sprouts, turnip, collard greens, pomegranate seeds, rosemary, red grapes, cinnamon, lycopene (found in tomatoes), olive oil, sage, garlic, zinc and selenium

The benefit of phytochemicals may lie in the fact that they act hermetically (see our article on ‘key concepts‘ we use at Conquering fatigue Successfully), and emerging evidence suggests that polyphenols or their metabolites exert their systemic intracellular effects not as direct “antioxidants” per se but as modulators of signaling pathways.

While research is limited in this area at this stage, I don’t think anyone would argue with the recommendation to regularly consume the above listed foods, unless a health condition dictates otherwise.

Sulforaphane from broccoli seems to be the most researched from a Nrf2 perspective – so do what your mum told you to do – eat your greens!


Houghton et al., (2015) Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician’s Expectation Be Matched by the Reality? Oxidative Medicine and Cellular Longevity