FREE RADICALS: THE POSITIVE & NEGATIVE EFFECTS ON HEALTH

ROS PRODUCTION

Reactive oxygen species (ROS) are biological products ofmetabolism that exert both positive and negative effects on the body.  ROSinclude free radicals like the hydroxyl radical (OH ?·), superoxide anionradical (O2–), nitric oxide (NO·), etc. as well as other oxidants (e.g. hydrogen peroxide (H2O2), peroxynitrite (ONOO-) singlet oxygen (1O2),etc.).The primary source of ROS formation occurs via the membrane bound NADPH oxidase enzyme complex and the electrontransport chain (primarily complex 1 and 3) of the mitochondria duringaerobic metabolism.

 NEGATIVE EFFECTS OF ROS

Numerous articles discuss the negativeconsequences of ROS and their implications on virtually every disease: Immunedisorders, such as diabetes mellitus,multiple sclerosis,asthma, rheumatoidarthritis,chronic inflammation, and other fatal diseases such ascardiovascular disease, cancer,neurodegenerative diseases such asAlzheimer’s diseaseand Parkinson’s disease as well as aging (perhapsdue to telomere shortening).

A more recent understanding of ROS demonstratesthat although they may have negative side effects at high levels, they are alsoimportant biological signaling molecules that exert therapeutic and protectiveeffects against diseases, and play a pivotal role in mediating the benefits ofexercise. The above figure illustrates ROS production in the mitochondriaand its involvement in cell signal transduction.

PROTECTIVE MECHANISM OF THE BODY

Because high levels of ROS are stronglyimplicated in the progression and pathogenesis of disease, our bodies have the ability to scavenge these ROS after they exert their beneficialsignaling effects.  For example, the mitochondrial-produced superoxide isdismutated to hydrogen peroxide by superoxide dismutase, which is subsequentlyreduced to water via the glutathione peroxidase/reductases/NADPH system. Thebody also uses catalase, glutathione, vitamins A, C, E, etc. to help protectagainst ROS-induced damage.

 REDUCTIVE STRESS AND OXIDATIVE STRESS

There are two opposing forces in biologicalsystems: oxidative stress and reductive stress. Reductive stress is achievedwhen the concentrations of reducing agents exceeds that of oxidizing agents.This is seen under the metabolism of ethanol (i.e. high ratios of NADH/NAD+ &NADPH/NADP+). Reductive stress may also partly explain why high doses ofconventional antioxidants may increase cardiovasculardisease, cancer and absolute mortality . Aging has recently been linked to a loss of oxidizingpotential of the ER, which impairs protein folding; whereas, the cytosolbecomes more oxidizing. Thus, it is possible to have reductive stress inone system, and oxidative stress in another.

Oxidative stress is defined as when the formationand concentration of ROS exceeds the clearance and scavenging activity of thebody’s endogenous antioxidant self-defense system. Oxidative stress iscorrelated with aging and the standard American diet.  Interestingly,exercise drastically increases the levels of ROS and consequent oxidativestress. Therefore, one may conclude that exercise has negative sideeffects to health; however, it is well known that exercise exerts potenttherapeutic and protective effects. Research has demonstrated that one ofthe reasons why regular exercise exerts these therapeutic effects is because itupregulates the body’s endogenous antioxidant activity, which reduces theabsolute risk of cellular injury by oxidative stress.

 ANTIOXIDANTS MAY NEGATE EXERCISE BENEFITS

 Furthermore, exercise-induced ROS formationenhances insulin sensitivity via ROS-dependent transcriptional coactivatorsPGC1α and PGC1β, and the transcription factor PPARγ, which are linked todiabetes. However, the pathway is blocked by ingestion of high amounts ofconventional antioxidants vitamin C and E. The ROS-related induction of PPARγ,PGC1α, and PGC1β lead to an increased expression of the ROS-detoxifyingenzymes, including SOD1, SOD2, and GPx1 thus offering anincreased protection against various diseases that arise from oxidative stress.

 HOW MUCH EXERCISE IS NEEDED?

It is unclear the frequency, duration orintensity of exercise needed to up-regulate the expression of these endogenousantioxidant enzymes to such a degree that will offer protective effects againstoxidative insult.  The literature, however, does shed some light into theeffects of a single bout of exercise versus regular exercise.

A single bout of exercise increases the levels ofROS and reactive nitrogen species.This increase leads to acute oxidativedamage and a lower resistance to oxidative stress. Physiologicalfunction also decreases;however, the activity of endogenous antioxidant enzymesincrease,  with a possible increase in oxidative repair mechanisms.

In contrast, regular exercise is associated withan absolute decrease in ROS and reactive nitrogen species, as well aslower oxidative damage. Moreover, physiological function, resistanceto oxidative stress , oxidative repair mechanisms and activity ofendogenous antioxidants ,  all increase with regular exercise.

 CONCLUSION AND RECOMMENDATION

In order to experience the positive therapeuticeffects of exercise-induced upregulation of the endogenous antioxidantself-defense system, regular exercise is needed.

Exercise regularly

Be cautious about ingesting high amounts ofconventional “pill” antioxidants

Consume molecular hydrogen (H2), as H2 onlyneutralizes the cytotoxic non-signaling ROS