Antioxidant / Pro-oxidant

This is prompted by something Live2day wrote:

"When first diagnosed, I had an Amazon bill of perhaps $100/month taking anti-oxidants that had been linked in pre-clinical studies or just website chat, e.g. pomegranate, garlic, oregano, etc. Doing Provenge 6 months ago, I was asked to stop all this. During radiation 4 years ago, I got the same request. The theory is that anti-oxidants might actually be helping cancer cells. Nobody really knows. I complied and now I'm off anti-oxidants, except through healthy diet."

I have read countless studies that used polyphenols (common antioxidants), which showed benefit against PCa - at least in cells &/or rodents. A subset of the papers contain wording along these lines:

1] {Capsaicin comes from cayenne.}

"Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death."

2] {WZ35 is a curcumin analog.}

"Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis, ER stress activation, and cell cycle arrest, indicating an upstream role of ROS generation in mediating the anti-cancer effect of WZ35."

3] {Phenethyl isothiocyanate (PEITC) comes from watercress}

"an antioxidant reagent, N-acetyl-L-cysteine (NAC) which suppresses reactive oxygen species (ROS) generation, reversed the early inhibitory effects of PEITC on cell proliferation"

When men are diagnosed with PCa, a common reaction is to migrate to a "healthier" diet, assuming it to be a somewhat therapeutic diet. The diet might be rich in brightly colored vegetables & fruits. We discover, perhaps, that the pigments are polyphenols & all have an antioxidant effect.

If a particular polyphenol has value against PCa, what is the optimum dose? Invariably, an effective dose is often higher than a realistic dietary intake. And the reason why the polyphenol is effective, is that it induces the generation of Reactive Oxygen Species [ROS]. The antioxidant has become pro-oxidant.

& the proof is to introduce NAC into the study. NAC is a pure antioxidant (generally), & it can reverse the effect of pro-oxidants. If the agent used in the study induces cell death except in the presence of NAC, the assumption is that ROS must be involved.

There is a philosophic issue here which some have a problem with. The back-to-Eden healthy-lifestyle approach conflicts with the idea of inducing oxidation to kill the cancer. Some simply refuse to take supplements.

Unfortunately, there is little proof that physiological doses are beneficial - except to normal cells. Pharmaceutical doses tend to be more toxic to cancer cells than to normal cells. Sometimes, normal prostate cells are unaffected in these studies.

I mentioned that I had radiation on a solitary bone met last year. The subject of antioxidants came up. I told the radiologist that I was using some polyphenols that inhibit radio-resistance in studies, & that while they would be antioxidant in the diet, were pro-oxidant at the doses I was using. He confirmed that radiation-induced oxidative damage was essential to the treatment.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/266...

[2] ncbi.nlm.nih.gov/pubmed/265...

[3] ncbi.nlm.nih.gov/pubmed/194...

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  • Enhancing radioresistance may be more of a problem with electron beam than proton beam since proton beam (and IMRT) use way higher doses.

    I asked a proton beam radiotherapist if I should stop antioxidants before beginning therapy & the answer was no

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