A systematic review of the impact of Ozonated fish oil on Mitochondrial function in pyramidal neurons under stress from intensive physical training

Background: Enforced exercise training results in extreme neurometabolic stress, especially on pyramidal neuron mitochondrial function. Ozonated fish oil has shown promise as a neuroprotective agent because of its improved bioavailability and antioxidant effect. Objective: The present systematic review critically discusses the existing evidence regarding the effect of ozonated fish oil on pyramidal neuron mitochondrial function under extreme physical training stress. Methods: Systematic Web of Science, Scopus, PubMed, and Cochrane database searching from 2014 - 2025 was performed. Inclusion was based on studies that had examined ozonated fish oil supplementation and mitochondrial function in neuronal tissue under exercise stress. Results: Seventeen studies were found to meet inclusion criteria, for which there was moderate evidence in support of the protective role of ozonated fish oil in mitochondrial respiratory function capacity, ATP yield, and oxidative markers in pyramidal neurons. Conclusion: Preliminary signs are that ozonated fish oil could be useful to maintain mitochondrial activity in pyramidal neurons with intense training, but further randomized controlled trials must be carried out to confirm fixed treatment protocols. Keywords: Ozonated Fish Oil, Mitochondrial Function, Pyramidal Neurons, Exercise Stress, Neuroprotection.