1. Excess Peroxynitrite Vicious Cycle
Nitric oxide forms a tissue damaging free radical known as peroxynitrite.5 8 9 10 This then forms even more nitric oxide. Peroxynitrite can also form hydroxyl free radicals,3 which also cause damage. Peroxynitrite is a highly potent free radical that damages proteins3 (including enzymes), lipids (brain and cell walls, mitochondrial (energy producing) membranes, ribosomal (protein making) membranes and genetic (DNA) membranes.11
Antioxidants such as natural Vitamin E (tocopherols) and related substances called tocotrienols (act like vitamin E in brain and lipid membranes), vitamin C (ascorbic acid), and glutathione help protect against these effects.11 The body needs selenium and vitamin B2 to help glutathione function well to help heal damage.11
This vicious cycle with increased nitric oxide and peroxynitrite can cause brain cell death andneurodegenerative disease.3 5 10 12 13 14 15 Peroxynitrite also weakens the blood-brain barrier, allowing chemicals to enter the brain more readily.16 Nitric oxide also damages the first detoxification step,17 allowing chemicals (and many drugs) to build up more in the body. This further increases inflammation.
Exhaled nitric oxide is a medically accepted marker of airway inflammation.18 Excess nitric oxide impairs the body’s energy capacity3 and can increase death of energy structures.3 This can lead to chronic fatigue.
2. Excess Superoxide Vicious Cycle
Superoxide free radical reacts with nitric oxide, which then increases peroxynitrite. Superoxide is a damaging free radical that also causes the damages discussed above for peroxynitrite. Superoxide is reduced by the body’s protective enzyme, SOD (superoxide dismutase). SOD needs minerals zinc, copper and manganese (in proper ratio) to function.
3. Damage to Mitochondria/Energy Structures, which increase NMDA which further increases Nitric Oxide
Peroxynitrite depletes energy ATP,3 19 20 which then further increases the sensitization of NMDA.15 21 Increased peroxynitrite forms excess hydroxyl radical, which in turn damages energy-making.22
Mitochondria are structures in body cells that generate energy by producing ATP. Mitochondriadamage has been documented in the vast majority of patients with chronic illness from chemicalinjury.23 This is a major cause of their fatigue.
When nitric oxide is increased too much, there can be a decrease in body defense antioxidants such as SOD (superoxide dismutase), catalase and glutathione peroxidase.24 Healing substances are needed to help these body protections function better.
Neural sensitization thus involves self-perpetuating excess brain/nerve cell (neuroexcitation) response to further chemical exposure.25 26 Since nerve cells communicate with all body organs, increased inflammation can involve many organs. This can cause hyperactivity in children and a feeling of being “wired” in all ages, despite fatigue.
