Nicotinamide and Pyruvate as Potential Therapeutic Interventions for Metabolic Dysfunction in Primary Open-Angle Glaucoma-A Narrative Review.

Mitochondrial dysfunction and oxidative stress have been suggested as potential contributors to the initiation and progression of primary open-angle glaucoma (POAG). Nicotinamide and pyruvate are important in the human body for maintaining metabolic function and preserving cytoskeletal structures. Both substances show an age-dependent decline in humans which may contribute to metabolic dysfunction and POAG vulnerability. Pilot works suggest their consumption may help prevent retinal ganglion cell deterioration under elevated intraocular pressure (IOP) and oxidative stress. Currently, there are no approved POAG treatments to mitigate risks from non-IOP drivers of disease, including oxidative stress. The purpose of this review is to summarize and critically evaluate interventional studies that have investigated nicotinamide and pyruvate supplementation in attempts to treat metabolic dysfunction in POAG patients. A review of the relevant literature from October 1979 to November 2025 was performed using related search terminologies through PubMed, ClinicalTrials.gov, and Google Scholar, and by reference cross-matching of all related articles. Current pilot data suggests that supplementation with nicotinamide and pyruvate demonstrates certain aspects of retinal neuroprotection and produces short-term improvements in visual function. However, much of the existing work has been conducted in animal models, and human study data are severely limited in scope and duration. Several clinical trials are registered as being in progress that aim to determine the chronic effects of nicotinamide and pyruvate in humans. Long-term longitudinal investigations with significantly larger and diverse sample sizes tied to functional and structural outcomes are needed for the safety and potential clinical utility of nicotinamide and pyruvate for POAG.