When we think about glaucoma, we usually think about one thing:
Pressure inside the eye.
But emerging research suggests there may be another important part of the glaucoma story that receives far less attention:
Nitric oxide
Nitric oxide (NO) is a signalling molecule produced throughout the body. It helps blood vessels relax, supports circulation and regulates the delivery of oxygen and nutrients to tissues.
Importantly, nitric oxide is also produced inside the eye.
Research increasingly suggests that healthy NO signalling plays an important role in regulating intraocular pressure, drainage of fluid from the eye and ocular vascular function.
This relationship is now sufficiently established that pharmaceutical researchers have developed glaucoma medications specifically designed to exploit nitric oxide signalling.
So could supporting healthy nitric oxide production also be relevant to maintaining eye health as we age?
The research is fascinating.
Glaucoma Isn’t Just About Eye Pressure
Elevated intraocular pressure (IOP) remains the most important modifiable risk factor for glaucoma.
However, pressure doesn’t explain everything.
Some people develop normal-tension glaucoma, where progressive optic nerve damage occurs despite IOP measurements being within the normal range.
This has led researchers to investigate other contributing factors, including vascular dysfunction, oxidative stress and insufficient blood supply to the optic nerve.
Nitric oxide potentially connects several of these pathways.
1. Nitric Oxide Helps Regulate Pressure Inside the Eye
The eye continuously produces a clear fluid called aqueous humour.
This fluid needs to drain efficiently to maintain normal pressure.
One of the primary drainage pathways passes through the trabecular meshwork and Schlemm’s canal.
Nitric oxide appears to be an important regulator of this drainage system.
Research suggests that when pressure rises, cells within Schlemm’s canal increase NO production. NO then helps relax neighbouring trabecular meshwork cells and increases the permeability of Schlemm’s canal.
The result is reduced resistance to aqueous humour drainage.
In simple terms:
Improved NO signalling → improved aqueous outflow → better regulation of intraocular pressure.
A major review published in Progress in Retinal and Eye Research concluded that nitric oxide is a key regulator of intraocular-pressure homeostasis and that dysregulation of the endothelial nitric oxide system may contribute to ocular hypertension and primary open-angle glaucoma.
This isn’t simply theoretical.
NO-donating glaucoma drugs have already been developed because increasing NO signalling in the trabecular meshwork can increase aqueous humour outflow and lower IOP.
Research:
The vital role for nitric oxide in intraocular pressure homeostasis – PubMed Central
Nitric oxide: a drug target for glaucoma revisited – PubMed
2. Nitric Oxide and Circulation to the Eye
Nitric oxide’s importance may extend beyond pressure.
NO is one of the body’s primary regulators of vascular tone. Endothelial cells release NO to help blood vessels dilate and maintain appropriate blood flow.
This may be important in glaucoma because the optic nerve and retinal ganglion cells require a continuous supply of oxygen and nutrients.
Researchers are therefore increasingly interested in the relationship between vascular dysfunction, nitric oxide signalling and glaucoma, particularly in people whose optic nerve damage progresses despite relatively normal eye pressure.
This creates an interesting possibility:
For some people, glaucoma may involve not only the pressure inside the eye, but also the health of the circulation supplying the eye.
3. The Rotterdam study showed reduced incidence of glaucoma by 62%
This is where the nutritional NO story becomes particularly interesting.
Researchers from the large Rotterdam Study investigated whether dietary nitrate intake was associated with the development of open-angle glaucoma.
Dietary nitrate is important because the body can convert nitrate into nitrite and then into nitric oxide.
The researchers found that every additional 10 mg per day of dietary nitrate was associated with approximately 5% lower odds of developing open-angle glaucoma.
But the comparison between the highest and lowest nitrate consumers was particularly striking.
People in the highest nitrate-intake group consumed an average of approximately:
213 mg nitrate per day
Compared with approximately 49 mg per day in the lowest group.
The highest-intake group had an odds ratio of 0.38 for developing open-angle glaucoma.
That equates to approximately:
62% lower odds of developing open-angle glaucoma.
The association was also seen when the researchers specifically examined nitrate coming from vegetables. (PubMed Central (PMC))
This does not mean nitrate supplementation has been proven to reduce glaucoma by 62%.
This was an observational study, so it demonstrates an association rather than proving cause and effect.
But it is a remarkably interesting association when combined with what we already know about nitric oxide and the physiology of the eye.
Research:
Dietary Nitrate Intake Is Associated with Decreased Incidence of Open-Angle Glaucoma – Full Study
Why Dietary Nitrate Matters
Vegetables such as rocket/arugula, beetroot and leafy greens are naturally rich sources of nitrate.
The body can convert dietary nitrate through the nitrate-nitrite-NO pathway:
Nitrate → Nitrite → Nitric Oxide
This provides an alternative way of generating NO alongside the body’s endothelial nitric oxide synthase pathway:
L-arginine → eNOS → Nitric Oxide
L-citrulline can also support this pathway by increasing the body’s availability of L-arginine.
Rather than simply thinking about “taking nitric oxide”, therefore, a more useful strategy is to think about supporting the different pathways the body uses to maintain healthy nitric oxide signalling.
This becomes particularly interesting with ageing because endothelial NO production can decline as vascular function deteriorates.
And Then There’s Medicinal Mushrooms
Another emerging area of research caught my attention while looking into glaucoma.
Medicinal mushrooms.
The evidence isn’t nearly as established as the nitric oxide research, but some recent findings are fascinating.
The reason is that glaucoma ultimately damages a very specific type of neuron:
Retinal ganglion cells.
These cells transmit visual information from the retina through the optic nerve to the brain.
Once retinal ganglion cells and their axons are severely damaged, the body’s ability to regenerate them is extremely limited.
Researchers are therefore looking for compounds capable of protecting retinal ganglion cells or encouraging their neurites to regenerate.
Two mushrooms have produced particularly interesting early findings.
Cordyceps and Glaucoma
Research involving Cordyceps cicadae has investigated its potential effects on both intraocular pressure and retinal ganglion cells.
Preclinical research has reported that Cordyceps cicadae mycelium extracts can reduce experimentally elevated intraocular pressure and may provide protective effects against retinal ganglion-cell damage.
Again, these are experimental findings rather than evidence that taking Cordyceps treats glaucoma in humans.
But they have generated enough interest that researchers continue to investigate this mushroom specifically in relation to glaucoma and retinal health.
Lion’s Mane and Retinal Ganglion Cells
In February 2026, researchers published another fascinating study examining Cordyceps cicadae together with Lion’s Mane (Hericium erinaceus).
Instead of simply measuring antioxidant activity, researchers examined retinal tissue and isolated retinal ganglion cells.
Extracts of both mushrooms promoted neurite outgrowth in retinal tissue.
Researchers then isolated Erinacine S, a bioactive compound associated with Lion’s Mane.
Erinacine S also significantly enhanced neurite outgrowth in isolated retinal ganglion cells.
That’s particularly interesting because the inability of damaged retinal ganglion-cell axons to regenerate is one of the fundamental challenges in glaucoma.
However, this was laboratory/preclinical research.
We cannot conclude that consuming Lion’s Mane regenerates the optic nerve or treats glaucoma in humans.
What we can say is that the biological effect is interesting enough to justify considerably more research. (PLOS)
Research:
2026 PLOS ONE Study – Full Research
Free Full Text – PubMed Central
Looking at the Evidence?
For nitric oxide we have:
- Established physiological mechanisms explaining how NO regulates aqueous humour drainage and intraocular pressure.
- Evidence that impaired NO signalling may contribute to dysfunctional pressure regulation.
- Pharmaceutical glaucoma treatments specifically targeting the nitric oxide pathway.
- Large human observational studies associating higher dietary nitrate consumption with substantially lower glaucoma risk.
The mushroom research.
Cordyceps and Lion’s Mane have produced intriguing results involving intraocular pressure, retinal ganglion-cell protection and neurite growth, but these findings are predominantly preclinical.
They should therefore be viewed as complementary emerging research rather than established glaucoma treatments.
Supporting Nitric Oxide Naturally
The research gives us another reason to pay attention to maintaining healthy nitric oxide production as we age.
Some of the most important natural ways of supporting NO include:
Nitrate-rich vegetables such as rocket/arugula, beetroot and leafy greens.
L-citrulline, which supports the L-arginine/eNOS pathway.
Regular exercise, which stimulates endothelial NO production.
Maintaining healthy oral bacteria, because oral nitrate-reducing bacteria play an important role in converting dietary nitrate into nitrite.
And importantly, protecting endothelial function itself.
Rather than relying on one ingredient, the objective should be to support the body’s overall ability to produce and maintain healthy physiological nitric oxide signalling.
Where Ultimate 4 Fits
This is the philosophy behind Ultimate 4.
Rather than approaching NO through a single pathway, Ultimate 4 combines ingredients designed to support the body’s different mechanisms of nitric oxide production.
It combines beetroot and arugula extracts as dietary nitrate sources with L-citrulline and complementary nutrients supporting NO physiology.
That means supporting both sides of the equation:
Nitrate → Nitrite → NO
and
L-Citrulline → L-Arginine → eNOS → NO
The objective isn’t to claim that Ultimate 4 treats glaucoma.
It doesn’t.
The much more interesting proposition is supporting a biological pathway that research increasingly shows is important for vascular health, intraocular-pressure regulation and healthy ageing.
Where Medicinal Mushrooms Fit?
The mushroom research provides another interesting piece of the puzzle.
Our Boost 3 formula contains a blend of medicinal mushrooms alongside nutrient-dense greens.
The emerging research around medicinal mushrooms and retinal ganglion cells provides another fascinating reason to investigate these compounds further.
But again, this should be considered nutritional support rather than treatment for glaucoma.
The Bigger Picture
Glaucoma is increasingly looking like more than simply a pressure problem.
It involves an interaction between:
Intraocular pressure
Aqueous humour drainage
Vascular function
Oxidative stress
Neuroinflammation
Optic nerve health
Retinal ganglion-cell survival
Nitric oxide sits at the intersection of several of these pathways.
It regulates aqueous humour outflow.
It influences vascular function.
And perhaps most intriguingly, people consuming the highest levels of dietary nitrate in the Rotterdam Study had 62% lower odds of developing open-angle glaucoma than those consuming the lowest levels.
Medicinal mushrooms add another emerging dimension, particularly with the discovery that compounds from Lion’s Mane and Cordyceps can influence retinal ganglion-cell neurite growth in experimental models.
There is still much we don’t know.
But the research raises an important question:
Could maintaining healthy nitric oxide production be another piece of protecting the ageing eye? Yes
There is now enough evidence to make nitric oxide a very interesting area of glaucoma research.
Research References
1. Reina-Torres E, et al. The vital role for nitric oxide in intraocular pressure homeostasis.
Progress in Retinal and Eye Research.
Full Text – PubMed Central
PubMed
2. Dietary Nitrate Intake Is Associated with Decreased Incidence of Open-Angle Glaucoma: The Rotterdam Study.
-
Nutrients.*
Full Text – PubMed Central
Journal Article
3. Garhöfer G, Schmetterer L. Nitric oxide: a drug target for glaucoma revisited.
Drug Discovery Today.
PubMed
4. Chen FY, Chen CC, Chiao CC. Extracts from Cordyceps cicadae and Hericium erinaceus promote the neurite outgrowth of retinal ganglion cells.
PLOS ONE. 2026.
Full Study – PLOS ONE
PubMed
Full Text – PubMed Central
Important: Nutritional supplementation should not replace prescribed glaucoma drops, laser treatment, surgery or regular ophthalmological monitoring. Glaucoma can cause irreversible vision loss without obvious early symptoms. Anyone diagnosed with glaucoma should continue their prescribed treatment and discuss supplements with their ophthalmologist.