Naviaux on Oxidative Stress vs Shielding.

[Remy]

I haven't read this in any detail yet but figured we might want to become more familiar with Dr Naviaux's previous work.

As always, emphasis is mine.

http://jpet.aspetjournals.org/content/342/3/608.long

In this review I report evidence that the mainstream field of oxidative damage biology has been running fast in the wrong direction for more than 50 years. Reactive oxygen species (ROS) and chronic oxidative changes in membrane lipids and proteins found in many chronic diseases are not the result of accidental damage. Instead, these changes are the result of a highly evolved, stereotyped, and protein-catalyzed “oxidative shielding” response that all eukaryotes adopt when placed in a chemically or microbially hostile environment.

The machinery of oxidative shielding evolved from pathways of innate immunity designed to protect the cell from attack and limit the spread of infection. Both oxidative and reductive stress trigger oxidative shielding. In the cases in which it has been studied explicitly, functional and metabolic defects occur in the cell before the increase in ROS and oxidative changes.

ROS are the response to disease, not the cause. Therefore, it is not the oxidative changes that should be targeted for therapy, but rather the metabolic conditions that create them.

This fresh perspective is relevant to diseases that range from autism, type 1 diabetes, type 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer disease. Research efforts need to be redirected. Oxidative shielding is protective and is a misguided target for therapy. Identification of the causal chemistry and environmental factors that trigger innate immunity and metabolic memory that initiate and sustain oxidative shielding is paramount for human health.

 

[Cort]

I haven't read this in any detail yet but figured we might want to become more familiar with Dr Naviaux's previous work.

As always, emphasis is mine.

http://jpet.aspetjournals.org/content/342/3/608.long

I think this is great. I've questioned whether antioxidants can do the trick with oxidative stress. I'm sure that they help but not to the degree to which we would like. Naviaux is obviously more interested in getting at the cause.

How interesting that oxidative shielding evolved from innate immune system pathways as the innate immune system appears to be messed up in ME/CFS.

Time will tell but Naviaux looks like a great addition to the ME/CFS research universe.

 

[Cort]

Treatment of oxidative changes in chronic disease with antioxidants is similar to treating a fever with aspirin instead of treating the pneumonia. Naviaux​

He believes cells actually produce free radicals to protect themselves by producing a more impervious cell membrane...

....cells might choose to defend themselves from harm by intentionally making reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, and by stiffening the cell membrane to make it less permeable and less vulnerable to attack, we need to start at the beginnings of life on our planet.
What Triggers the Production of Superoxide, Hydrogen Peroxide, and Other ROS?

Hostile, damaging, or unhealthy conditions surrounding the cell trigger the production of superoxide, hydrogen peroxide, and other ROS. Both stress and shielding schools agree with this answer.
What Is the Function or Purpose of ROS?

The shielding school holds that the function of ROS is, first, to protect the cell if possible, both as signaling molecules and by physically decreasing the cellular uptake, release, and exchange of potentially toxic pathogens or chemicals from and with the environment; and second, to actively kill the cell by apoptosis or necrosis when the local environmental conditions threaten to spread to neighboring cells and jeopardize the survival of host. ROS are an effect of disease, not the prime cause.
What Is the Target of Effective Therapy in Diseases Associated with Increased ROS and ROS-Related Damage?

The shielding school holds that because the prime cause of disease can ultimately be traced back to toxic exposure, microbial pathogen, unhealthy nutritional practices, nutrient loading, or unhealthy patterns of exercise and activity therapy should be directed at eliminating these causal factors. ROS production will naturally fall back to normal levels when physiologic balance is restored.

Catalogs of the many forms of oxidative changes that are found in 100 chronic diseases provide no insight into the underlying pathogenesis of disease. Treatment of oxidative changes in chronic disease with antioxidants is similar to treating a fever with aspirin instead of treating the pneumonia.

New methods of targeted and untargeted metabolomics will help decode the language of metabolism in disease (Tautenhahn et al., 2011; Yanes et al., 2011) and assist physicians in providing personalized medical treatment. NextGen treatments will need to restore the normal “ecology” of metabolism.

It's metabolomics study that Naviaux is involved in with ME/CFS...He's definitely an interesting guy...

 

[weyland]

I've questioned whether antioxidants can do the trick with oxidative stress. I'm sure that they help but not to the degree to which we would like.

The question isn't can they affect oxidative stress. The question is should we affect oxidative stress. Naviaux says no we shouldn't. Others have been asking the same question.

The antioxidants dilemma: are they potentially immunosuppressants and carcinogens?

 

[Cort]

Good point! I remember some studies which found that antioxidants had negative effects. I had completely forgotten about those. I remember thinking how strange that way and thinking that I'd better not mess with them too much.

It's a strange world when oxidative stress becomes part of a protective response....

The question isn't can they affect oxidative stress. The question is should we affect oxidative stress. Naviaux says no we shouldn't. Others have been asking the same question.

The antioxidants dilemma: are they potentially immunosuppressants and carcinogens?