Advanced glycation end products (AGEs) are reactive compounds formed through non-enzymatic glycation in a process known as the Maillard reaction. While humans produce AGEs endogenously, these compounds can also enter the body through dietary sources, food preparation methods, and exposure to agricultural and food-related chemicals. AGEs can accumulate within cells and impair cellular function. In addition, when AGEs bind to receptors for advanced glycation end products (RAGE), they activate intracellular signaling pathways that promote the generation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation. Sustained AGE-RAGE signaling drives chronic inflammation contributing to the development of various ailments, including neurodegenerative diseases. This review examines AGE formation, metabolism, and accumulation, with an emphasis on dietary sources as modifiable contributors to AGE-RAGE mediated pathology. We highlight the need for further research on dietary AGE restriction as a potential strategy to prevent or slow the progression of neurodegenerative and neuroinflammatory disorders.

Importance: The Defense and Veterans Brain Injury Center reported 358,088 mild traumatic brain injury (mTBI) among U.S. service members worldwide between the years 2000 and 2020. Veterans with mTBI have higher rates of Post-Traumatic Stress Disorder (PTSD), depressive disorder, substance use disorder, anxiety disorder, and suicide than their healthy counterparts. Currently, there is no effective treatment for mTBI. Objective: To assess the efficacy of hyperbaric oxygen therapy (HBOT) as a treatment option for mTBI. Design, Setting, Participants: This is a case series of 39 U.S. Veterans diagnosed with mTBI and treated with HBOT. Of these participants, 36 were men and 3 women, and their ages ranged between 28 and 69. The treatment was administered by The 22 Project (a veteran-centered nonprofit organization) using monoplace hyperbaric chambers located in Delray Beach, Florida. Neuroimaging using Single Photon Emission Computer Tomography (SPECT) brain scans performed pre- and post-HBOT were made available for secondary analysis. Nilearn Python Library was utilized to visualize the corresponding neuroimaging data. A two-sided paired t-test in R was used to compare the pre- and post-treatment results. Intervention: A full treatment of HBOT involved 40 sessions. Each session consisted of the administration of 100% oxygen at 1.5 atmospheres for 90 min, twice a day, for 20 days, Mondays to Fridays only. Main Outcome and Measure: Perfusion in the brain’s Brodmann Areas (BA) comparing pre- and post-HBOT using NeuroGam software analysis from brain SPECT scan neuroimaging and multi-symptom self-reports. Results: A comparison between the pre- and post-HBOT brain scans showed significant improvement in the brain perfusion, and the difference was statistically significant (p < 0.001). Separately, participants reported reduced pain, improved mood, and better sleep, an outcome that translated into an average of about 46.6% improvement in the measured symptoms. Conclusions and Relevance: This series demonstrated that HBOT could be a useful treatment for mTBI in U.S. veterans. The participants in the study showed marked improvement in both brain perfusion measured on SPECT scan imaging and measured mTBI symptoms. This is the first study to use brain SPECT scans with quantitative numerical measurements to demonstrate improvement in brain perfusion in veterans with mild TBI treated with HBOT and measured mTBI symptoms. Future research studies are currently being done to validate these important findings.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating, multi-system disease characterized by profound fatigue, post-exertional malaise (PEM), and a constellation of immune, neurological, and autonomic symptoms. Despite its global prevalence, the pathophysiology of ME/CFS remains elusive, and there are no FDA-approved treatments targeting the underlying mechanisms. Symptom-based pharmacologic management is often complicated by hypersensitivity reactions and mitochondrial toxicity. Non-pharmacologic interventions, such as energy conservation, autonomic regulation, and nutritional strategies, are frequently employed to mitigate symptom burden. Emerging research points to mitochondrial dysfunction as a core contributor to ME/CFS pathology, marked by impaired ATP production, oxidative stress, and bioenergetic failure. Mitochondrial-derived peptides (MDPs), particularly MOTS-c, offer a novel therapeutic avenue by enhancing mitochondrial biogenesis, reducing oxidative damage, and modulating inflammatory responses through AMPK and NRF2 activation. Preclinical evidence suggests that MOTS-c improves glucose metabolism, increases mitochondrial density, and enhances fatigue resistance. However, safety and efficacy data in humans are lacking. Future investigations are needed to evaluate MOTS-c's potential as a disease-modifying therapy in ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition marked by severe, long-lasting fatigue and exhaustion that does not improve with rest. ME/CFS is reported in individuals of all ages and various racial, socioeconomic, and ethnic groups. This condition lacks standard treatment. Nutritional supplements and dietary interventions are often used to manage symptoms, but the efficacy of these interventions remains scarce in the current literature. This systematic review aims to evaluate and summarize recent evidence on nutrient supplementation and diet-based interventions in patients with ME/CFS sourced from clinical trial registries and article databases. Registries improve the quality, integrity, and transparency of clinical trials by providing a standardized platform for reporting study design and results and, thus, reducing the biases related to selective reporting practices. Systematic reviews using these registries, therefore, are an efficient pathway to acquire current medical evidence for use in clinical decision-making and the development of practice guidance in various fields. ClinicalTrials.gov, Medline, PubMed, Cochrane, and Web of Science were systematically searched for interventional studies in which patients suffering from ME/CFS supplemented or altered their diet. The results of this review showed several supplements that suggest improvement in patients’ symptomatology, including nicotinamide adenine dinucleotide (NADH), coenzyme Q10 (CoQ10), wasabi, and probiotics. However, many of these registered clinical trials did not employ the U.S. National Institutes of Health (NIH)’s National Institute of Neurological Disorders and Stroke (NINDS) suggested common data elements (CDEs). These standardized outcome-measuring tools allow the generalization and true comparison of the patient-reported outcomes.