Why Do We Feel Fine, Until We Don't?

By Dr. Pascale Ricci, Head of Precision Nutrition 

Oxidative stress is a state of imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defence mechanisms. This imbalance occurs when ROS levels exceed the capacity of antioxidant systems to neutralize them, leading to oxidative damage to proteins, lipids, and DNA, as well as other macromolecules.

ROS are generated from both endogenous and exogenous sources (for example, cigarette smoking, radiation and pollution.) Under normal physiological conditions, low to moderate levels of ROS serve as signalling molecules in processes like cell growth and immune defence, however, when ROS production becomes excessive, it transitions to harmful oxidative stress that disrupts cellular homeostasis.

Oxidative stress is largely imperceptible because it begins at the molecular and cellular level, causing gradual, cumulative damage that cells can initially compensate for, through antioxidant defences and repair systems, and therefore does not immediately produce noticeable symptoms. The damage accumulates slowly over time before manifesting as clinical disease.

The silent progression explains why oxidative stress contributes to numerous chronic diseases, including cardiovascular disease, neurodegenerative disorders (Alzheimer's and Parkinson's disease), cancer and diabetes, to name a few, that develop insidiously over extended periods. Substantial oxidative damage has already occurred when symptoms appear, making early detection, through biomarkers, essential for prevention. 

Multiple modern lifestyle factors significantly increase oxidative stress including, inadequate sleep, poor diet, cigarette smoking, alcohol consumption, lack of physical activity, psychological stress, and air pollution exposure. 

Vitamin C is a water-soluble antioxidant that is a cornerstone of the body’s antioxidant defence network. It exerts multiple mechanisms of action:

a) acts as a direct free radical scavenger,         

b) has synergistic interactions with other antioxidants, which amplify vitamin C’s protective effects,       

c) regenerates other antioxidants, and             

d) activates endogenous antioxidant defence systems. 

Measurable changes in several categories of biochemical markers provide the earliest indication of antioxidant defence strain. 

Decreased levels of glutathione, vitamins C and E, uric acid, and beta-carotene indicate that non-enzymatic antioxidants are being consumed faster than they can be replenished. Routine laboratory markers can provide clues too, including uric acid, ferritin, and gamma-glutamyltransferase (GGT) levels. These biomarkers correlate with oxidative stress status and can be informative in predicting oxidative burden.

Lipid peroxidation markers such as F2-isoprostanes, are particularly valuable markers as they are stable, specific products that can be measured in both plasma and urine. 

DNA damage markers, particularly 8-hydroxy-2'-deoxyguanosine (8-OHdG), indicate genomic instability. Elevated urinary 8-OHdG levels correlate with age, ferritin levels, drinking habits, and vitamin E status, suggestive of chronic oxidative stress. 

When ROS production exceeds the body’s antioxidant defences, it leads to oxidative distress, damaging lipids, proteins, and DNA. This damage impairs critical cellular processes including energy metabolism, gene expression, and signalling pathways, which all lead to loss of function and progression towards cell death. 

Mitochondria play a central role in this process, as they are both major sources and targets of oxidative stress. Mitochondrial dysfunction creates a vicious cycle – damaged mitochondria produce more ROS while becoming less efficient at energy production, further compromising cellular function. 

In the immune system and tissue repair, ROS also have a dual role. They are necessary for pathogen killing, immune cell signalling, and wound healing processes like angiogenesis and tissue remodelling. But chronic or excessive oxidative stress impairs immune balance, weakens antioxidant systems, and promotes persistent inflammation and autoimmune dysfunction. Similarly, while controlled ROS levels support healing, excessive oxidative stress disrupts repair processes, delays wound closure, and contributes to chronic wounds, especially in conditions like diabetes or aging.

Overall, maintaining a balance between ROS production and antioxidant capacity is crucial for preserving cellular function, effective immunity, and optimal recovery. Clinical patterns that may suggest chronic oxidative stress include nonspecific findings such as fatigue, reduced physical performance, increased susceptibility to infections (reflecting immune dysfunction), and accelerated manifestations of chronic diseases. However, these are late manifestations rather than early warning signs.