Mitochondrial nutrients: Reducing mitochondrial decay to delay or treat cognitive dysfunction, alzheimer’s disease, and parkinson’s disease

Mitochondria are the source of energy and also the source and target of oxidants. Mitochondrial decay due to oxidative damage and nutrient deficiencies is a major contributor to brain aging and age-related neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson’s disease (PD). Therefore, protecting mitochondria from oxidative damage is essential for delaying brain aging and preventing/treating age-related neurodegenerative diseases. We define mitochondrial nutrients (mt-nutrients) as those which protect mitochondria from oxidative damage and improve mitochondrial function, including those that can (1) inhibit or prevent oxidant production in mitochondria; (2) scavenge and inactivate free radicals and reactive oxygen species; (3) repair mitochondrial damage or induce phase-2 enzymes to enhance antioxidant defenses, and (4) act as cofactors/substrates to protect mitochondrial enzymes and/or stimulate enzyme activity. The cofactor/substrate protection is based on the idea that oxidatively modified enzymes lose activity and have reduced binding affinity for substrates and cofactors, and the loss of binding affinity may be overcome by providing high doses of enzyme substrates and cofactors similar to that of high dose B vitamins remedy for some genetic diseases. We discuss the relationships among mt-nutrient deficiency, mitochondrial decay, and cognitive dysfunction, and summarize available evidence suggesting an effect of mt-nutrient supplementation on AD and PD. It appears that longer term administration of combinations of a number of mt-nutrients is more effective in delaying and protecting mitochondrial decay. Thus, optimal doses of combinations of mt-nutrients to delay and repair mitochondrial decay could be a strategy for delaying and treating neurodegenerative diseases, including AD and PD.