Vitamin B3 and Glaucoma: A New Hope for Neuroprotection

What Is Glaucoma — and Why Current Treatments Fall Short

Glaucoma is the world’s leading cause of irreversible blindness. It is estimated to affect approximately 80 PubMed million people, particularly women and people of Asian descent. The disease is characterised by the progressive loss of retinal ganglion cells (RGCs) — the neurons that carry visual signals from the eye to the brain — and their axons, which form the optic nerve.

The near-universal standard of care has been to lower intraocular pressure (IOP), yet glaucoma continues to be a primary contributor to permanent vision loss worldwide, frequently advancing even when intraocular pressure management is clinically adequate. MDPI This sobering reality has driven researchers to look beyond pressure and toward the metabolic health of the nerve cells themselves — and that search has led to an unexpected candidate: vitamin B3.

 

The Science: NAD⁺, Mitochondria, and the Metabolic Theory of Glaucoma

Several lines of evidence implicate oxidative stress and mitochondrial dysfunction in ageing and RGC loss in glaucoma. Nicotinamide adenine dinucleotide (NAD⁺) is an essential cofactor for ATP generation in mitochondria, and for NAD-consuming enzymes including sirtuins, with important roles in ageing, cell senescence, and stress resistance. medrxiv

Simply put: without adequate NAD⁺, the energy-generating machinery of nerve cells degrades, making them far more vulnerable to the stresses of glaucoma.

NAD⁺ is a potent mediator of axon neuroprotection and, recently, the therapeutic potential of modulating NAD⁺ metabolism has gained widespread attention in its role in ageing and neurodegenerative disease. medrxiv

This is where vitamin B3 enters the picture. Nicotinamide (NAM), the amide form of vitamin B3, is the body’s most direct dietary precursor to NAD⁺. It is cheap, widely available, has an excellent safety record — and it can be taken orally.

 

The French Connection: Discovering Nicotinamide Deficiency in Glaucoma Patients

A critical piece of evidence came from French researchers. A study published in Investigative Ophthalmology & Visual Science in 2019 by Kouassi Nzoughet and colleagues at Angers University Hospital investigated the plasma concentration of nicotinamide in primary open-angle glaucoma (POAG). The plasma of 34 POAG individuals was compared to that of 30 age- and sex-matched controls. ARVO Journals

The results showed that plasma nicotinamide concentration was significantly lower in the POAG group — roughly 30% lower (mean: 0.14 µM) compared to controls (mean: 0.19 µM). bioRxiv

The convergence between studies showing that oral administration of nicotinamide prevents glaucoma in mouse models, and this study on patients with POAG, opened promising therapeutic perspectives based on nicotinamide supplementation. biorxiv

This French study was a landmark: it was the first to confirm in human patients that those with glaucoma are systematically deficient in the very vitamin that could protect their retinal nerve cells. The Montpellier Institute for Neurosciences (INSERM, Université de Montpellier) has since been among the leading French academic centres contributing to reviews and advancing this research agenda within the European neuroscience community.

 

The First Human Trials: Small but Encouraging

The Australian Crossover Trial (2020)

A world-first clinical trial found significant improvement in the visual function of glaucoma patients who received a daily high dose of 3 grams of nicotinamide for 12 weeks in addition to their regular IOP-lowering treatment. Cera

This 12-week crossover randomised clinical trial in Australia of 57 participants found improved inner retinal function as assessed by electroretinography with nicotinamide supplementation of 3 g/day. Ophthalmologyglaucoma Electroretinography measures the electrical activity of retinal cells — a more sensitive, objective measure than a standard vision test.

Crucially, the benefit was measured on top of existing treatment: patients did not stop their eye drops; they added nicotinamide. This is exactly the kind of add-on neuroprotective therapy the field has sought for decades.

The US Phase 2 Trial (JAMA Ophthalmology, 2022)

A Phase 2 randomised controlled trial in the United States of 32 individuals with open-angle glaucoma found that oral supplementation with 3 grams/day of nicotinamide and 3 grams/day of calcium pyruvate for 9 weeks led to an improvement of a median of 8 visual field test locations as compared with placebo. American Academy of Ophthalmology

Visual field testing is the gold standard for measuring what a patient can actually see. Improvement in 8 locations on the visual field map is clinically meaningful and generated significant excitement within the ophthalmology community.

 

What Do “Phase 1,” “Phase 2,” and “Phase 3” Trials Mean?

For readers unfamiliar with clinical trial terminology, these phases are worth explaining clearly:

•         Phase 1 — The first time a treatment is tested in humans. The focus is on safety: what doses are tolerable, and are there serious side effects? These trials are small (often 10–30 people).

•         Phase 2 — The treatment is tested in a larger group (typically 30–200 people) to gather early evidence of whether it works (efficacy) while continuing to assess safety. Both the Australian and US trials described above were Phase 2.

•         Phase 3 — The definitive, large-scale test. Hundreds or thousands of patients across multiple centres are enrolled. Results from Phase 3 trials are what regulatory agencies (like the FDA or EMA) require before approving a drug. Nicotinamide for glaucoma is now entering this phase globally.

 

The Current Wave: Large-Scale Phase 3 Trials Worldwide

Several ongoing clinical trials are investigating the role of nicotinamide as a therapeutic neuroprotective treatment for glaucoma globally, including in the United States, the United Kingdom, Sweden, Australia, Hong Kong, China, Korea, Italy, and other countries, with a cumulative target enrollment of over 1,300 participants. American Academy of Ophthalmology

Key trials include:

The Glaucoma Nicotinamide Trial (Sweden & International, from 2022) This is a prospective, randomised, placebo-controlled, double-masked clinical trial that started in May 2022, with a projected end date of December 2026. It has two arms: the Swedish Glaucoma Nicotinamide Trial and the vitamin B3 in glaucoma study. Primary open-angle glaucoma patients will be randomised to receive NAM (1,500 mg for 6 weeks, then 3,000 mg) or a placebo. The primary outcome measure is the change in visual field progression over 2 years. PubMed Central

The UK Trial (UCL / Moorfields Eye Hospital) A major four-year clinical trial to test the effectiveness of nicotinamide as a treatment for glaucoma is to be led by UCL and Moorfields Eye Hospital researchers, supported by a £1.9 million grant from the National Institute for Health Research (NIHR). It will eventually recruit 496 glaucoma patients across seven UK sites. UCL

The study will measure the impact of nicotinamide on the capacity of mitochondria in peripheral blood lymphocytes (freely circulating white blood cells) to produce ATP, which provides energy to help cells function. UCL This is important: it provides a measurable biological explanation of why the drug works, not just that it works.

The Nicotinamide + Pyruvate Trial (Columbia University, USA) The objective of this study is to determine if a combination of oral nicotinamide and pyruvate can maintain eye health compared to placebo while standard-of-care IOP-lowering glaucoma medications are used. Up to 188 participants will be enrolled for 87 weeks (approximately 20 months). ClinicalTrials.gov

The Nicotinamide Riboside Trial (Hong Kong) This trial will randomise 125 patients with primary open-angle glaucoma with evidence of progressive thinning on OCT to receive oral nicotinamide riboside 300 mg/day or placebo for 24 months. nih Nicotinamide riboside is a slightly different form of vitamin B3 that also boosts NAD⁺.

 

What Does This All Mean for Patients and Clinicians?

Nicotinamide (NAM), Vitamin B3, has a well-established safety profile, with documented tolerance at high doses. It is a familiar molecule and is extremely affordable and accessible. Its oral route of administration, and the fact that it is a “familiar vitamin,” mean it is equally acceptable to clinicians and patients. PubMed Central

However, the scientific community urges caution before widespread adoption. The endpoints of these clinical studies include functional findings detectable in a research setting, but do not consistently translate to visual recovery that is impactful to the patient. Ophthalmologyglaucoma

The results of large-scale clinical trials are still awaited before NAD can be considered an accepted therapeutic modality for glaucoma. PubMed Central

Furthermore, glaucomatous damage to the optic nerve is almost always heterogeneous — the RGCs are in various states of physiological stress: some are normal, others dead, while some are combating neurodegeneration. The most important caveat to the use of NAD in glaucoma prophylaxis and treatment, therefore, is its differential impact on normal and diseased RGCs. Its impact on the physiology of non-diseased RGCs must also be documented before widespread clinical use. PubMed Central

 

Conclusion: A Vitamin at the Frontier of Neuroscience

Vitamin B3 has gone from a pellagra-prevention nutrient to one of the most exciting candidates in glaucoma neuroprotection research. The chain of evidence is compelling: glaucoma patients have lower blood levels of nicotinamide; animal models show that restoring it protects retinal nerves; and small human trials demonstrate measurable improvement in visual function.

The large Phase 3 trials now underway — spanning Europe, North America, Asia, and Australia — represent the true test. Results from the Swedish and UK trials expected around 2026–2027 could fundamentally change how glaucoma is managed, potentially adding a simple, affordable, safe vitamin supplement to the treatment toolkit alongside eye drops and surgery.

For the millions living with glaucoma, that would be genuinely sight-saving news.

 

This article is for informational purposes. Patients should not start high-dose nicotinamide supplementation without consulting their ophthalmologist or physician.