Can High-Dose Vitamin B3 Protect the Optic Nerve? A New Glaucoma Trial Will Test 3 Grams a Day

This audio article is from VisualFieldTest.com.Read the full article here: https://visualfieldtest.com/en/can-high-dose-vitamin-b3-protect-the-optic-nerve-a-new-glaucoma-trial-will-test-3-grams-a-dayTest your visual field online: https://visualfieldtest.comSupport the show so new episodes keep coming: https://www.buzzsprout.com/2563091/supportExcerpt:Can High-Dose Vitamin B3 Protect the Optic Nerve? A New Glaucoma Trial Will Test 3 Grams a Day Research updated September 13, 2026 Introduction Glaucoma treatment has traditionally focused on one target: lowering intraocular pressure. That strategy clearly helps, but it does not eliminate risk. Some patients continue to lose retinal ganglion cells and visual-field sensitivity even when their eye pressure appears well controlled. The NADIR trial—NCT07808333—is designed to test a different strategy. It will add high-dose oral nicotinamide, the non-flushing form of vitamin B3, to standard glaucoma treatment and measure whether the inner retinal layers thin more slowly. The central biological idea is straightforward: > Retinal ganglion cells may become metabolically fragile before they die. If nicotinamide raises cellular nicotinamide adenine dinucleotide availability, it might help stressed but living cells withstand glaucoma-related injury. That hypothesis is supported by striking animal research, early human electrophysiology studies, and a plausible link between aging, mitochondrial dysfunction, impaired axonal transport, and retinal ganglion-cell degeneration. But the human evidence remains preliminary—and 3 grams daily is a pharmacological dose, not an ordinary nutritional supplement dose. My overall assessment is that nicotinamide is one of the most credible current candidates for pressure-independent glaucoma neuroprotection, but it is not yet proven to slow glaucoma progression in humans. --- The NADIR Trial: What Is Actually Being Tested? As of September 13, 2026, NADIR is listed as not yet recruiting. It is a single-center University of Chicago study expected to begin enrollment in June 2027. The registry describes it as a Phase 2 study, while the protocol title calls it a Phase 2a trial. () Trial summary For the full table, please open this article on visualfieldtest.com. The trial is important because it is not asking whether nicotinamide lowers eye pressure. It is asking whether it protects retinal tissue despite ongoing standard pressure-lowering treatment. Who can participate? NADIR is designed for adults with mild to moderate primary open-angle glaucoma, not advanced disease. Key inclusion requirements include: Age 40 to 80 years Primary open-angle glaucoma in at least one eye Study-eye visual-field mean deviation between −2.0 and −12.0 decibels At least one reliable Humphrey 24-2 visual-field test Fixation losses of 33% or less False-positive responses of 15% or less Best-corrected visual acuity of 20/40 or better Structural damage on optical coherence tomography and/or a reproducible glaucomatous visual-field defect Macular ganglion cell-inner plexiform layer and retinal nerve fiber layer thickness above the device’s measurement floor Stable pressure-lowering therapy for at least four months Screening intraocular pressure of 21 millimeters of mercury or less The visual-field range is strategically chosen. Patients with mean deviation between −2 and −12 decibels still have enough surviving retinal tissue for a protective treatment to be measurable, but they have established disease rather than merely being glaucoma suspects. () Who is excluded? The important exclusions include: Advanced glaucoma with mean deviation worse than −12 decibels Best-corrected visual acuity worse than 20/40 Significant retinal disease, including advanced age-related macular degeneration or more than mild diabetic retinopathy Non-glaucomatous optic neuropathy Recent eye surgery Liver dysfunction, including alanine aminotransferase or aspartate aminotransferase greater than twice the upper limit of normal Total bilirubin greater than 1.5 times the upper limit of normal Estimated glomerular filtration rate below 30 milliliters per minute per 1.73 square meters Poorly controlled diabetes, defined as hemoglobin A1c greater than 9% Current use of nicotinamide, high-dose vitamin B3, nicotinamide adenine dinucleotide supplements, gingko biloba, coenzyme Q10, or certain drugs that could complicate safety interpretation Pregnancy or breastfeeding Active ocular inflammation Media opacity that prevents reliable imaging Patients with untreated normal-tension glaucoma are also excluded. NADIR is therefore testing an adjunctive treatment in patients whose glaucoma is being treated conventionally, not a therapy for every glaucoma subtype. () Nicotinamide dosing: Why 1.5 grams, then 3 grams? Participants assigned to the treatment arm will take: Weeks 1–6: 500 milligrams three times daily, totaling 1.5 grams daily Week 7 through month 12: 1,500 milligrams twice daily, totaling 3 grams daily The tablets are taken with meals. Advancement to the full dose requires an early safety review confirming acceptable gastrointestinal tolerance and no significant hepatic adverse event. () What is the basis for the escalation? The publicly available record does not describe a formal human exposure-response pharmacokinetic model. The dose appears to come from three sources: The earlier Australian human glaucoma study, which used 1.5 grams daily for six weeks followed by 3 grams daily for six weeks. Mouse glaucoma studies, in which relatively high nicotinamide exposure produced the strongest protection. A mechanistic assumption that substantial nicotinamide availability may be needed to overcome age-related or disease-related limitations in the nicotinamide adenine dinucleotide salvage pathway. The 3-gram dose was not selected because it is a standard nutritional requirement. The recommended daily amount of vitamin B3 is roughly 14–16 milligrams in adults, making 3 grams approximately 150 to 200 times the usual nutritional intake. Animal investigators have described 3 grams daily as the lowest human-equivalent dose likely to reproduce the effective exposure seen in their mouse model. A later rat study used doses equivalent to approximately 2.1 grams and 6.3 grams daily in a 70-kilogram adult, with the higher dose needed for some intervention settings. This is body-surface-area extrapolation, not proof that humans require the same exposure. () NADIR’s endpoints Primary endpoint The primary outcome is the annualized rate of macular ganglion cell-inner plexiform layer thinning. Measurements will occur at: Baseline Month 3 Month 6 Month 12 The statistical analysis will use a linear mixed-effects model with: A participant-level random intercept Repeated measurements over time A treatment-arm-by-time interaction The key question is whether the nicotinamide group has a less negative slope than the standard-care group. Secondary structural and functional endpoints The secondary outcomes include: Annualized rate of peripapillary retinal nerve fiber layer thinning Visual-field mean deviation slope Grade 2 or higher hepatic and gastrointestinal adverse events Nicotinamide adherence Study retention Additional exploratory measures include: Macular superficial capillary plexus perfusion density by optical coherence tomography angiography Peripapillary radial capillary plexus perfusion density The registry specifies that optical coherence tomography and visual-field readers will be masked to treatment assignment through de-identified participant identifiers, even though participants and investigators will know which treatment is being given. () Statistical strengths and weaknesses Strengths Randomized 1:1 allocation Active standard-care control Stratification by mild versus moderate disease Stratification by race and ethnicity Masked structural and visual-field reading Repeated optical coherence tomography measurements A structural primary endpoint that may be more sensitive than visual-field change over only one year Weaknesses The trial is open-label There is no placebo Only 96 participants are planned It is being conducted at one center Twelve months is short for proving long-term visual-field preservation The public registry does not provide a detailed power calculation or a prespecified minimum clinically important difference A positive NADIR result would therefore be important, but it would probably be considered proof of biological activity, not definitive proof that nicotinamide should immediately become routine treatment. --- Why Might NAD Matter in Glaucoma? Nicotinamide adenine dinucleotide is an energy and repair molecule Nicotinamide adenine dinucleotide is needed for: Mitochondrial energy production Transfer of electrons during cellular respiration Maintenance of redox balance DNA repair Regulation of protein acetylation through sirtuin enzymes Calcium handling Axonal transport Cellular responses to oxidative stress Retinal ganglion cells are unusually vulnerable to energy failure. They have long axons, high electrical activity, substantial transport demands, and a portion of their axons that remain unmyelinated inside the retina. Their energy supply must remain reliable even when pressure-related mechanical stress affects the optic nerve head. Mitochondrial dysfunction may occur before obvious cell loss In the DBA/2J mouse model of glaucoma, abnormal mitochondrial gene expression, mitochondrial cristae disruption, oxidative phosphorylation changes, synapse loss, and pattern electroretinogram abnormalitSupport the show