Clinical Bioenergetics

Background: Chronic rhinosinusitis (CRS) affects nearly 9% of the global population with a rising incidence over recent decades. Neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease pose significant global burden, and emerging evidence suggests pathophysiological links through shared bioenergetic dysfunction, peripheral-to-central inflammatory signaling, and altered nasal microbiota. This review evaluates the evidence for CRS as a potentially modifiable peripheral contributor to neurodegenerative disease progression. Methods: A systematic review was conducted using PubMed, Cochrane, Web of Science, Embase, and CENTRAL from January 2000 to July 2025. Search terms included “Chronic Rhinosinusitis,” “Neurodegeneration,” “Mild Cognitive Impairment,” “Alzheimer’s Disease,” “Parkinson’s Disease,” “Bioenergetics,” and “Microbiome.” Clinical and experimental studies exploring epidemiological links, mechanistic pathways, biomarkers, and therapeutic targets were included. Results: Twenty-one studies involving over 100,000 participants met the inclusion criteria. Existing meta-analytic evidence demonstrated significant associations between CRS and cognitive impairment, with patients scoring approximately 9% lower on global cognitive measures than controls. However, other large-scale cohort studies did not pinpoint an increased dementia incidence, suggesting CRS may contribute to early, potentially reversible cognitive decline without directly driving dementia onset. Neuroimaging studies revealed altered frontoparietal connectivity and orbitofrontal hyperactivity in CRS patients. Mechanistic studies support peripheral inflammatory cytokines disrupting the blood–brain barrier, autonomic dysfunction impairing mucociliary clearance, microbiome-driven amyloid cross-seeding, and compromised cerebrospinal fluid clearance via olfactory–cribriform pathways. Discussion: Evidence supports complex, bidirectional relationships between CRS and neurodegeneration characterized by convergent inflammatory, autonomic, and bioenergetic pathways. Therapeutic strategies targeting sinonasal inflammation, microbiome dysbiosis, and mitochondrial dysfunction represent promising intervention avenues. Recognizing CRS as a treatable factor in neurodegenerative risk stratification may enable earlier diagnosis and prevention strategies.

Nicotinamide adenine dinucleotide (NAD+) is an important coenzyme essential for metabolism, energy production, gene regulation, and cellular communication. With aging, NAD+ levels decrease, which may be partly responsible for age-related disease and impaired function. While certain lifestyle practices may help to maintain NAD+, such as intermittent fasting, exercise, and reduced alcohol consumption, these activities do not appear to support optimal NAD+ levels. For this reason, numerous dietary supplements have emerged, with the claim of increasing NAD+ levels and resulting in improved health and, possibly, increased longevity. Such agents include NAD+, as well as the NAD+ precursors niacin, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). This article discusses the scientific rationale and evidence for using such supplements, with a particular emphasis on human oral ingestion and associated health outcomes. The current literature has been reviewed, and practical applications are presented.

Traditionally, referred to as the “Powerhouse of the Eukaryotic Cell”, mitochondria are essential for host defense in addition to producing ATP. Through processes like mitochondrial antiviral signaling (MAVS), the generation of reactive oxygen species (ROS), and the modification of inflammatory pathways, they respond to bacterial, fungal, viral, and parasitic infections while coordinating immune signaling, controlling cell death, and detecting pathogens. Pathogens, on the other hand, have developed ways to interfere with or harm mitochondrial function, which results in oxidative stress, cell death, altered metabolism, and compromised immune signaling. This type of mitochondrial dysfunction impairs the removal of infections and is linked to tissue damage, chronic inflammation, and long-term health issues. The dual roles of mitochondria in infection are highlighted in this review, which looks at both their defense mechanisms and the ways in which pathogens use them to increase their chances of survival.