Dr. McClane Duncan, ND

This post was originally published on Naturalpath.net.

If you’re like me, you have a few antioxidant supplements in your medicine cabinet.  This is probably because you’ve been trained to think that oxidation in the body is bad, leading to rapid aginginflammation, and increased all-cause mortality.  Is this actually true?  Is oxidation killing us and does supplementing with antioxidants or other supplements for that matter actually improve our health?

I would assume that many of us are overusing antioxidants, misguided by our understanding of conventional toxicological drug models and fueled by our human tendencies to think that more must be better.

Widespread use of supplemental antioxidants began in the 1950’s.  Dr. Denham Harman MD, PhD, an anti-aging practitioner and major proponent for antioxidants usage, hypothesized that antioxidants quench the formation of Reactive Oxygen Species (ROS), responsible for accelerating the aging process.  Dr. Denham’s work and antioxidant research on the detrimental health effects caused by free radicals popularized indiscriminate antioxidant use among the general population. Moreover, nutraceutical companies, health associations, and health practitioners have driven the use of antioxidants through prescriptions on the assumption they prevent or treat diseases commonly associated with inflammation.

As a Naturopathic Physician, I practice medicine from a Vitalistic perspective, where I strive to stimulate the body to bring about healing and wellness.  As a result, I utilize restorative medical therapies, one of which is Ozone.  Through my Ozone practice, I quickly realized that the ROS were actually the agent responsible for instigating the healing process.  Yet, this was counterintuitive and in direct conflict with what I had come to believe about free radicals.  My realization spawned further research into oxidative healing mechanisms where I found more evidence supporting my conclusion that the body reacts positively to small amounts of oxidative stress.  Surprisingly, I also found a handful of research articles suggesting that antioxidant supplementation actually attenuates the health benefits of exercise, decreases insulin sensitivity, and increases the rates of all-cause mortality.

This study found that a high dose of vitamin E, a fat-soluble antioxidant increased rates of mortality:

“When all of the trial results were analysed together, vitamin E supplementation did not affect all-cause mortality. However, in 9 of the 11 trials testing high-dosage vitamin E (greater than 400 IU/day), a significantly increased risk for all-cause mortality in comparisons of vitamin E versus control was observed. The pooled all-cause mortality risk difference in the high-dosage vitamin E trials was 39 additional deaths per 10,000 persons. For the low-dosage trials, there were no statistically significant risk differences between the participants receiving vitamin E and those receiving placebo. Overall, the meta-analysis showed a statistically significant relationship between vitamin E dosage and all-cause mortality, with increased risk at dosages greater than 150 IU/day.”

Through my Ozone Therapy practice, I’ve found that in most cases a little oxidative stress is obligatory in triggering the body’s innate healing response.  This can be attributed to the oxidative stress, prompting in vitro antioxidant production, improved mitochondrial function, enhanced cellular detoxification, and activation of vitagenes responsible for healthy cellular stress responses.

Ozone, or oxidative therapy, can be explained as follows:

“Ozone is a safe, inexpensive, and effective clinical tool with a wide range of therapeutic applications. Pain management is an area where ozone excels, and many studies have been done to demonstrate its analgesic properties. Ozone was first discovered by Christain Schonbein in 1840, and the first US ozone generator was developed by Nikola Tesla in 1896. In 1902, an article on the use of ozone to treat middle ear deafness was published in The Lancet, and ozone therapy was used with success to treat infections during World War I. Since then, numerous clinical trials and basic research studies have been conducted to investigate the effects and mechanisms of action of ozone therapy. From the literature, ozone as a medicinal substance has been shown to be beneficial for a wide range of conditions, including pain, cardiovascular disease, mitochondrial dysfunction, infection, and non-healing skin lesions. Clinical practice has also shown benefit in neurological disorders, autoimmunity, cancer, fatigue, and others.”

A New Toxicological Model to Consider

The Biphasic Dose Response model, aka, the Hormesis Dose Response model explains the effects that low dose applications of an agent have on biological systems.  The Hormesis model can in part explain the ROS healing phenomenon.  Hormesis research is showing us that dose is really the determining factor influencing physiologic responses to therapeutic applications of chemotherapeutic agents, ranging from bioflavonoids to nuclear radiation.  Exposing individuals to high levels of antioxidants suppresses the body’s own healing response.  Exposure to low levels of oxidants, even toxins, stimulates a stress reaction in the body akin to an athlete training to achieve better performance.  A little stress encourages the body to become stronger and more resilient, improving overall health and longevity.

Dr. Paul Kalnins, a professor at NCNM in Portland OR, and an expert in hormesis, suggests that some of the benefits we derive from our herbs, fruits, and vegetables are due to the fact that they’re poisoning us.  The medicinal compounds are irritating us just enough to trigger a healing reaction, resulting in stronger immune function.  Dr. Kalnins goes on to strengthen his position by reporting on epidemiological findings where those exposed to low levels of Radon gas are at lower risk for developing lung cancer.

This study explains how the dose of ozone therapy is crucial:

“The therapeutic efficacy of ozone therapy may be partly due the controlled and moderate oxidative stress produced by the reactions of ozone with several biological components. The line between effectiveness and toxicity of ozone may be dependent on the strength of the oxidative stress. As with exercise, it is well known that moderate exercise is good for health, whereas excessive exercise is not.”

The pharmacokinetics of low doses as described by hormesis dose-response models goes a long way in validating the Vitalistic approach to medicine.  Health practitioners who understand hormesis can begin to take comfort in knowing that homeopathyherbal medicine, drainage, and cell salt therapies can have a big impact on a person’s health. These modalities are influencing the body to be stronger and more resilient.

Practitioners can begin to let go of the toxicological linear dose model that begs for higher doses, let go of the notion that all oxidative stress is pathological, and embrace the stimulatory effects of low doses.


  1. Thompson, Richard E. Epidemiological Evidence for Possible Radiation Hormesis From Radon Exposure:  A Case-Control Study Conducted In Worcester, MA. Dose-Response, 9;59-75, 20ll.  http://dos.sagepub.com/content/9/1/dose-response.10-026.Thompson.full.pdf+html
  2. K Zarse et al. Impaired Insulin/IGF-1 Signaling Extends Life Span by Promoting Mitochondrial L-proline Catabolism to Induce a Transient ROS Signal. Cell Metabolism. 2012 15(4): 451-465
  3. Miller, ER 3rd et al. (2005) Metanalysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. Annals of Internal Medicine142(1): 37-46.
  4. Sagai M, Bocci V. Mechanisms of Action Involved in Ozone Therapy: Is Healing Induced via a Mild Oxidative Stress?  Medical Gas Research. 2011;1:29.
  5. Costanzo M, Cisterna B, Vella A, et al. Low Ozone Concentrations Stimulate Cytoskeletal Organization, Mitochondrail Activity and Nuclear Transcription. European Journal of Histochemistry: EJH. 2015;59(2):2515.
  6. C. Cornelius et al., Stress Responses, Vitagenes and Hormesis as Critical Determinants in Aging and Longevity, Immune Aging. 2013; 10(15)
  7.  Kalnins, Paul, ND. Why Dosage Matters: Exploring the Concept of Hormesis in Medicine. OANP 2015.
  8. Thompson, Richard E. Epidemiological Evidence for Possible Radiation Hormesis From Radon Exposure:  A Case-Control Study Conducted In Worcester, MA. Dose-Response, 9;59-75, 20ll.  http://dos.sagepub.com/content/9/1/dose-response.10-026.Thompson.full.pdf+html