Can oral nicotinamide supplementation assist in preventing or treating glaucoma?

Oral Nicotinamide for Glaucoma Prevention and Treatment

Oral nicotinamide supplementation shows promise as an adjunctive neuroprotective therapy for glaucoma based on emerging clinical trial evidence, though it is not yet established as standard care and should be considered investigational.

Current Evidence Status

Clinical Trial Results

The most recent and highest quality evidence comes from a 2025 randomized, double-masked, placebo-controlled crossover trial in normal-tension glaucoma (NTG) patients 1. This study demonstrated:

• Significant functional improvement in retinal ganglion cell function measured by photopic negative response amplitude (PhNRPT increased by 3.121±3.968 μV with nicotinamide vs 0.996±4.190 μV with placebo, p=0.045) 1
• B-wave amplitude improvement (2.112±3.220 μV with nicotinamide vs 0.305±3.279 μV with placebo, p=0.032) 1
• 29% of patients showed clinically meaningful improvement (beyond twice the 95% coefficient of variation) with nicotinamide supplementation 1
• Dosing regimen: 1 g/day for 6 weeks, then 2 g/day for 6 weeks 1

Mechanistic Rationale

Nicotinamide works through NAD+ (nicotinamide adenine dinucleotide) repletion, which addresses the metabolic dysfunction underlying glaucomatous neurodegeneration 2:

• Age-related NAD+ decline renders retinal ganglion cells vulnerable to elevated intraocular pressure 2
• NAD+ is essential for mitochondrial function, protection against oxidative stress, and cellular metabolism 3
• Mitochondrial dysfunction is an early feature in glaucoma pathogenesis 2

Animal Model Evidence

In the DBA/2J mouse model of inherited glaucoma, nicotinamide demonstrated remarkable efficacy 2:

• 70% protection at the lowest dose tested (no detectable glaucomatous neurodegeneration) 2
• 93% protection at the highest dose (representing a ~10-fold decrease in glaucoma risk) 2
• Neuroprotective effect was independent of IOP reduction at lower doses 2

Guideline Position

No major ophthalmology guidelines currently recommend nicotinamide for glaucoma prevention or treatment. The American Academy of Ophthalmology's Primary Open-Angle Glaucoma guidelines from 2016 and 2021 do not mention nicotinamide as a treatment option 4.

For context, dermatology guidelines state there is insufficient evidence to make a recommendation on oral nicotinamide for chemoprevention of skin cancers, despite some positive trial data 4. This reflects the conservative approach taken when evidence is still emerging.

Clinical Considerations

When to Consider Nicotinamide

Nicotinamide supplementation may be considered as an adjunctive therapy (not replacement for IOP-lowering treatment) in:

• Normal-tension glaucoma patients with documented progression despite adequate IOP control 1
• Patients progressing despite optimal IOP management (approximately 25% of glaucoma patients continue to progress with adequate IOP control) 3
• Patients seeking additional neuroprotection beyond IOP reduction, after informed discussion about the investigational nature of this therapy 5

Dosing Protocol

Based on the 2025 clinical trial 1:

• Start with 1 g/day orally for 6 weeks
• Increase to 2 g/day for maintenance if tolerated
• Continue standard IOP-lowering therapy concurrently 1

Important Caveats

This remains an investigational therapy with several limitations:

• The 2025 trial showed functional improvement but no significant visual field changes at 12 weeks (mean deviation, pattern SD, or visual field index) 1
• Longer-term studies are needed to determine if functional improvements translate to preserved vision over years 1
• The optimal dose, duration, and patient selection criteria remain undefined 5
• Safety profile for long-term use in glaucoma patients requires further study 5

Standard Care Remains Essential

Prostaglandin analogues remain first-line therapy for IOP reduction and should not be replaced by nicotinamide 4:

• Prostaglandins (bimatoprost, latanoprost, travoprost, tafluprost) are most efficacious and well-tolerated 4
• They provide both IOP reduction and beneficial effects on optic nerve perfusion 6
• Nicotinamide should only be considered as an addition to, not replacement for, standard IOP-lowering therapy 1

Practical Implementation

If considering nicotinamide supplementation:

1. Ensure optimal IOP control first with standard medical or surgical therapy 4
2. Document baseline retinal function with optical coherence tomography and visual field testing 7
3. Discuss investigational nature with patient, including limited long-term data 5
4. Start with 1 g/day, advance to 2 g/day after 6 weeks if tolerated 1
5. Monitor for functional changes with electroretinography if available, or structural changes with OCT at regular intervals 1
6. Continue standard glaucoma monitoring every 2-4 months 4

The evidence suggests nicotinamide is a promising adjunctive neuroprotective strategy, but it remains investigational pending larger, longer-term trials demonstrating preservation of visual function and quality of life outcomes.