All RTx relies on oxygen to transduce the physical energy into biochemical changes. Without oxygen, the radiation damage is repaired in 1/100,000th of a second. The potent radiolytic products of water, the hydroxyl radical OH* and bare protons H+ react with molecular oxygen and other reactive oxygen species ROS to form stable enough radicals to generate lipid peroxidation. Polyunsaturated fats combined with oxygen-stabilized hydroxyl radicals are the most potent bio-killers from radiation therapies. Radiation activates sphingomyelinase or ceramide synthetase which hydrolyzes the cell membrane lipid sphingomyelin, increasing ceramides, resulting in apoptosis – the cell dies.
Given the crucial role of reactive oxygen species (ROS) or free radicals of oxygen, it is readily apparent that anti-oxidants (AOx) could in theory blunt the impact of RTx. In fact, this is easily demonstrated. However, there are exceptions to this rule, and these exceptions are of great clinical significance. Radiation oncologists have used carbogen and pentoxyphylline in radiation care, despite their antioxidant properties. Naturopathic oncologists use curcumin and melatonin in radiation therapy, despite their known AOx properties. Research clearly shows a net benefit to humans undergoing RTx who use these medicines, due to their many redeeming properties. While the AOx effects are probably negative, it is a case of two or three steps forward and one step back, one is still clearly ahead.
We know some antioxidants can flip and become pro-oxidative under some conditions. For example, vitamin C by mouth is antioxidant but in high intravenous doses is clearly pro-oxidative. Curcumin radio-sensitizes cancer cells by increasing ROS, and markedly increasing MAP kinases, leading to reduced oncogene MDM2 expression. Yet in healthy cells it is radio-protective by reducing lipid peroxidation. So, there is an increase in killing of cancer cells, while inflicting less harm to the patients. Brilliant!
Melatonin has many complex actions, several of which interact with RTx, including modulation of the immune system, interleukins IL-6 and IL-2, tumour necrosis factor TNF, fatty acid metabolism and lipoxygenase. Presumably, the major impact on RTx is melatonin inhibition of corticotrophin-releasing factor, reducing cortisol levels and that of other adrenal corticosteroids, which protect cancer cells from radiation injury. Over fifty years of quality research published in leading journals, including several meta-analyses which Level One evidence are, show increased responses, longer survival, and less adverse effects in humans using melatonin during RTx.
Therefore, there is no hard rule against AOx in RTx. We clearly want to avoid vitamin C by mouth in large doses, grapeseed extract, vitamin E and many other antioxidants during RTx. However, if an antioxidant has good human research indicating a net benefit, the antioxidant properties can be safely ignored. Slavishly following the anti-oxidant theory can rob cancer patients of significant clinical benefits. The most important situation to use AOx in RTx is in head and neck cancers, where the radiation adverse effects can be extreme, and protectants make huge impacts on tolerance of the therapy, without loss of efficacy.
After radiation therapy has ended, the major long-term adverse effect is a progressive fibrosis or scarring of the delicate endothelium lining the blood vessels, and other tissues. This fibrosis can be minimized using the anti-fibrotic properties of curcumin, vitamin A and alpha lipoic acid. Grapeseed extract also reduces inflammation and heals the lining of blood vessels.
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