Nicotinamide for Glaucoma: Clinical Study Finds Nicotinamide Improved Retinal Function in Just 12 Weeks

The first human clinical trial of nicotinamide (vitamin B3) in glaucoma found significant improvements in retinal nerve cell function, building on years of research showing robust protection of retinal ganglion cells in preclinical studies.

Key Takeaways

• Australian researchers found that 12 weeks of nicotinamide supplementation improved retinal ganglion cell function in people with glaucoma.

• Retinal function improved by nearly 15% compared with baseline.

• More patients experienced measurable improvements in visual field performance compared with placebo.

• Benefits occurred without changes in eye pressure, suggesting a direct effect on retinal nerve cell health.

• This was the first randomized clinical trial to investigate nicotinamide supplementation in human glaucoma patients.

A New Frontier in Glaucoma Treatment

For decades, glaucoma treatment has focused on lowering intraocular pressure (IOP). While effective, this approach does not directly address the health of retinal ganglion cells—the nerve cells responsible for carrying visual information from the eye to the brain.

Many patients continue to lose vision despite having well-controlled eye pressure, leading researchers to search for therapies that directly protect these vulnerable nerve cells.

In recent years, attention has turned to nicotinamide, a form of vitamin B3 and a precursor to nicotinamide adenine dinucleotide (NAD+), a molecule essential for cellular energy production. NAD+ plays a central role in mitochondrial function, allowing cells to generate the energy needed for survival and repair.

This line of research emerged from an intriguing observation: retinal ganglion cells affected by glaucoma appear to experience a profound energy deficit. Rather than dying immediately, some cells may remain alive but function poorly because they lack sufficient energy to maintain normal activity.

Preclinical studies produced remarkable results. In animal models of glaucoma, nicotinamide supplementation provided robust protection of retinal ganglion cells, preserved visual function, prevented age-related cellular decline, and reduced optic nerve damage. Researchers also found that nicotinamide could reverse some of the molecular changes associated with aging and glaucoma.

These findings suggested that supporting cellular energy metabolism might offer a completely new approach to glaucoma treatment.

But an important question remained unanswered:

Could nicotinamide improve retinal function in people living with glaucoma?

This study was the first randomized clinical trial designed to answer that question.

Why This Study Matters

Glaucoma is the leading cause of irreversible blindness worldwide. Current therapies focus almost entirely on reducing eye pressure, but they do not directly address the metabolic health of retinal ganglion cells.

Researchers have increasingly come to view glaucoma not only as an eye-pressure disease but also as a neurodegenerative disease involving mitochondrial dysfunction and impaired cellular energy production.

Previous research found that patients with primary open-angle glaucoma have lower circulating levels of nicotinamide compared with healthy individuals. Combined with the dramatic findings from animal studies, this raised the possibility that restoring nicotinamide levels could improve retinal nerve cell function in humans.

What makes this study especially important is that it moves beyond laboratory experiments and demonstrates that retinal ganglion cells in glaucoma patients may retain a surprising capacity for recovery.

Rather than simply slowing future damage, nicotinamide appeared to improve the performance of existing retinal nerve cells.

Study Design: How Researchers Tested Nicotinamide in Glaucoma Patients

Researchers enrolled 57 adults with treated glaucoma in a randomized, double-masked, placebo-controlled crossover clinical trial conducted in Melbourne, Australia.

Participants received:

First 6 Weeks

• Nicotinamide 1.5 grams daily

Next 6 Weeks

• Nicotinamide 3.0 grams daily

A matching placebo group followed the same schedule.

After 12 weeks, participants switched treatments so that every participant eventually received both nicotinamide and placebo.

Importantly, patients continued their regular glaucoma medications throughout the study, allowing researchers to evaluate whether nicotinamide could provide additional benefits beyond standard care.

A total of 49 participants completed the trial.

Understanding the Measurement: What Is the Photopic Negative Response (PhNR)?

One challenge in glaucoma research is that visual field changes occur slowly and can take years to measure.

To detect changes more quickly, researchers used a highly sensitive test called electroretinography (ERG).

ERG measures tiny electrical signals generated by retinal cells in response to flashes of light.

The primary measurement was the Photopic Negative Response (PhNR), a signal generated primarily by retinal ganglion cells.

Think of the PhNR as a direct readout of retinal nerve cell performance.

• A weaker PhNR suggests impaired retinal ganglion cell function.
• A stronger PhNR suggests healthier and more responsive retinal ganglion cells.

Because the test measures nerve cell function directly, it can detect improvements long before structural changes become visible on eye scans.

Results: Nicotinamide Improved Retinal Ganglion Cell Function

After 12 weeks of high-dose nicotinamide supplementation, researchers observed significant improvements in retinal function.

Retinal Function Improved by Nearly 15%

Compared with baseline:

• Photopic Negative Response (PhNR) amplitude improved by 14.8%.
• PhNR-to-b-wave ratio improved by 12.6%.

Both improvements were statistically significant.

Nearly One in Four Patients Experienced Meaningful Improvement

Researchers also looked for improvements that exceeded normal testing variability.

They found:

• 23% of participants receiving nicotinamide improved beyond the threshold considered clinically meaningful.
• Only 9% of participants improved while taking placebo.

This suggests that the observed benefits were unlikely to be due to chance or measurement variability.

Did Nicotinamide Improve Vision?

Although the study was relatively short, the visual field findings were encouraging.

Among patients receiving nicotinamide:

• 27% improved by at least 1 decibel on visual field testing.
• Only 4% experienced worsening.

Among patients receiving placebo:

• 16% improved.
• 12% worsened.

Researchers also found that improvements in retinal electrical function correlated with improvements in visual field performance.

In other words, patients whose retinal ganglion cells functioned better on testing were also more likely to show improvement in their visual fields.

How Nicotinamide May Work in Glaucoma

One of the most important findings was what did not change.

Researchers found no significant differences in:

• Intraocular pressure (IOP)
• Blood pressure
• Retinal nerve fiber layer thickness
• Other measures of retinal function unrelated to retinal ganglion cells

This suggests nicotinamide was not working by lowering eye pressure.

Instead, the findings support the theory that nicotinamide improves the metabolic health of retinal ganglion cells by replenishing NAD+ and enhancing cellular energy production.

In simple terms, nicotinamide may help struggling retinal nerve cells generate more energy, allowing them to function more effectively despite the stress caused by glaucoma.

Safety and Side Effects of High-Dose of Nicotinamide

High-dose nicotinamide was generally well tolerated.

Patient adherence exceeded 94%, indicating that most participants were able to take the supplement consistently.

Reported side effects were mostly mild and included:

• Gastrointestinal discomfort
• Nausea
• Headache

No serious safety concerns emerged during the study.

What This Means for People With Glaucoma

This study does not prove that nicotinamide can cure glaucoma or prevent blindness.

The trial lasted only 12 weeks and was designed primarily as a proof-of-concept study.

However, it provides some of the strongest clinical evidence to date that retinal ganglion cell function can improve in people with glaucoma.

The findings suggest that some retinal nerve cells affected by glaucoma may remain alive but metabolically impaired. By supporting cellular energy production, nicotinamide may help these cells recover part of their lost function.

If future studies confirm these findings and demonstrate long-term benefits, nicotinamide could become an important adjunct therapy alongside traditional eye-pressure-lowering treatments.

For patients and researchers alike, the message is encouraging:

Some retinal ganglion cells affected by glaucoma may not be permanently lost. They may simply need more energy to function again.

Study Reference

Hui F, Tang J, Williams PA, et al. Improvement in Inner Retinal Function in Glaucoma with Nicotinamide (Vitamin B3) Supplementation: A Crossover Randomized Clinical Trial. Clinical & Experimental Ophthalmology. 2020.