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# Nicotinamide and Mitochondrial Rescue: Can Metabolic Therapy Restore Function? Glaucoma is a leading cause of irreversible vision loss, often progressing even when intraocular pressure (IOP) is controlled. A growing body of evidence highlights that **retinal ganglion cells (RGCs)** are particularly vulnerable to metabolic stress, notably from chronic depletion of nicotinamide adenine dinucleotide (**NAD+**), a coenzyme essential for mitochondrial energy production ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12609723/#:~:text=Glaucoma%20continues%20to%20be%20a,demonstrating%20enhanced%20preservation%20of%20RGC)). Nicotinamide (NAM), a form of vitamin B3 and an NAD+ precursor, has therefore emerged as a promising neuroprotective therapy. In animal models and early human studies, NAM supplementation has shown significant preservation of RGC integrity and function ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12609723/#:~:text=Glaucoma%20continues%20to%20be%20a,demonstrating%20enhanced%20preservation%20of%20RGC)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC11352092/#:~:text=and%20potential%20adverse%20effects,regulation%2C%20and%20neuroinflammatory%20pathways%20were)). This article reviews recent randomized clinical trials of high-dose NAM (with or without pyruvate) and discusses how NAD+ repletion might “rescue” stressed but viable RGCs. It also covers dosing considerations, safety, heterogeneity of responses, patient selection, and ongoing research. ## Metabolic Basis of Glaucoma and NAD+ Repletion RGCs have extremely high metabolic demands and rely on robust mitochondrial function. In glaucoma, aging and chronic stress trigger progressive NAD+ depletion in RGCs. NAD+ is a key cofactor in oxidative phosphorylation and in pathways (like sirtuins and DNA repair) that support cell survival ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12609723/#:~:text=Glaucoma%20continues%20to%20be%20a,demonstrating%20enhanced%20preservation%20of%20RGC)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12428967/#:~:text=Nicotinamide%20and%20its%20precursor%20nicotinamide,combined%20to%20address%20multiple%20targets)). When NAD+ levels fall, RGCs experience bioenergetic failure, elevated oxidative stress, and susceptibility to apoptosis. Nicotinamide supplementation can replenish NAD+ via the NAD+ salvage pathway. This helps maintain mitochondrial ATP production and activates survival enzymes (e.g. SIRT1) while preventing over-activation of PARP1 (a DNA repair enzyme that can otherwise deplete NAD+) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603231/#:~:text=visual%20field%20locations%20after%20trabeculectomy,edge%20of%20scotomata%2C%20which%20are)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12428967/#:~:text=Nicotinamide%20and%20its%20precursor%20nicotinamide,combined%20to%20address%20multiple%20targets)). In short, restor

Nicotinamide and Mitochondrial Rescue: Can Metabolic Therapy Restore Function?

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