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NR vs NMN vs Nicotinamide for Glaucoma: Which NAD+ Booster Has the Strongest Evidence? · Glaucoma, Vision & Longevity: Supplements & Science

0:00
SPEAKER_00: NAD, and glaucoma, why vitamin B3 matters.
0:04
SPEAKER_00: Glaucoma is an aging-related eye disease in which retinal ganglion cells, RGCs, the nerve cells that carry visual signals from the eye to the brain, gradually die off.
0:14
SPEAKER_00: Pressure-lowering treatments, drops, lasers, surgery, are the standard of care, but many patients still experience slow vision loss.
0:21
SPEAKER_00: Researchers have therefore been exploring additional neuroprotection strategies.
0:26
SPEAKER_00: One promising idea is boosting NAD plus nicotinamide adenine dinucleotide, a vital cell energy molecule, because NAD supt sup levels naturally decline with age.
0:37
SPEAKER_00: Lower NAD sup plus may leave RGCs less able to meet their high energy needs, especially under glaucoma stress.
0:44
SPEAKER_00: In fact, one lab review notes that glaucoma is a neurodegenerative disease in which neuronal levels of NAD decline and shows that nicotinamide, vitamin B3, can protect RGCs in multiple animal glaucoma models.
0:58
SPEAKER_00: This finding has inspired human trials of NAD-boosting supplements in glaucoma.
1:03
SPEAKER_00: Current research has focused on three NAD precursors, nicotinamide, vitamin B3, nicotinamide riboside, NR, and nicotinamide mononucleotide, NMN.
1:13
SPEAKER_00: All three are natural forms of B3 that feed into the N8 SUP plus salvage pathway.
1:18
SPEAKER_00: Nicotinamide, often called niacinamide, is a form of vitamin B3 found in foods and multivitamins.
1:24
SPEAKER_00: NR and NMN are specialized NAD precursors found in small amounts in some foods and sold as supplements.
1:31
SPEAKER_00: But do they really help glaucoma?
1:33
SPEAKER_00: Below we compare what is known about each one in plain language.
1:37
SPEAKER_00: All claims below are backed by recent science and trials.
1:41
SPEAKER_00: Nicotinamide for glaucoma.
1:43
SPEAKER_00: Why is nicotinamide being studied?
1:45
SPEAKER_00: Researchers study nicotinamide because it directly boosts NAD plus via the cell's salvage pathway and has strong lab evidence in glaucoma models.
1:54
SPEAKER_00: In aging cells, NAD SUP PLUP declines with age at a systemic level.
1:59
SPEAKER_00: RGCs are very energy-hungry cells in a high stress environment.
2:03
SPEAKER_00: High pressure can damage mitochondria inside them.
2:05
SPEAKER_00: Boosting N8 plus SUP could supercharge RGC metabolism and help them survive.
2:11
SPEAKER_00: In rodent glaucoma experiments, high-dose nicotinamide dramatically protected RGC bodies and axons.
2:17
SPEAKER_00: For example, Triple et L.
2:18
SPEAKER_00: 2021 report that dietary nicotinamide blocked the early metabolic disruptions caused by high eye pressure and improved mitochondrial function in rat retinas.
2:28
SPEAKER_00: In simple terms, vitamin B3 helped the energy cells in the retina keep working properly under stress.
2:35
SPEAKER_00: This strong preclinical data has given researchers confidence to try nicotinamide in human glaucoma.
2:41
SPEAKER_00: Human trial evidence for nicotinamide PUN.
2:44
SPEAKER_00: Human studies are still small but encouraging.
2:47
SPEAKER_00: A 2022 trial in open-angle glaucoma with moderate field loss gave patients high dose nicotinamide plus another agent, pyruvate.
2:56
SPEAKER_00: Participants took 1 to 3 grams of nicotinamide daily.
3:00
SPEAKER_00: Over two months, the treatment group showed significantly more improvement in visual field test points than placebo did.
3:07
SPEAKER_00: Specifically, the median number of improved field locations was 15 in the nicotinamide group versus 7 in placebo, p equals.005.
3:16
SPEAKER_00: Secondary measures of field sensitivity also tended to improve more with treatment.
3:22
SPEAKER_00: Although this trial was short and combined with pyruvate, it provides a positive signal that NAD boosting can help glaucoma, and importantly, no serious side effects were reported.
3:33
SPEAKER_00: Another recent trial focused on normal tension glaucoma, a form of glaucoma without high eye pressure.
3:40
SPEAKER_00: Korean researchers gave 1.5 to 3.0 grams of nicotinamide daily to patients already on pressure-lowering drops.
3:47
SPEAKER_00: Over 12 weeks, they found measurable improvements in inner retinal function using specialized tests, the photopic negative response in an electroretinogram.
3:57
SPEAKER_00: In plain terms, injured retinal neurons worked better after taking nicotinamide.
4:02
SPEAKER_00: Most patients tolerated the doses well.
4:05
SPEAKER_00: This trial did not show changes in standard visual field tests, but the early functional recovery is promising.
4:12
SPEAKER_00: Safety data so far are reassuring with proper medical supervision.
4:16
SPEAKER_00: Nicotinamide, unlike niacin, does not cause facial flushing.
4:20
SPEAKER_00: Mild side effects at several grams may include nausea, headache, or dizziness, especially if taken without food.
4:28
SPEAKER_00: Very high doses, above 6 to 9 grams per day, have been linked to reversible liver enzyme elevations, which is why trials generally use 1 to 3 grams.
4:38
SPEAKER_00: Importantly, no serious adverse events were seen in the glaucoma studies above.
4:42
SPEAKER_00: In other fields, nicotinamide has a decade of human use.
4:46
SPEAKER_00: For example, it is being studied to prevent skin cancers and has a favorable safety profile in those trials.
4:53
SPEAKER_00: Overall, nicotinamide has the strongest evidence so far in glaucoma because of its proven lab effect on RGCs and some positive clinical signals.
5:02
SPEAKER_00: Ongoing studies, including larger phase 2-3 trials, will tell us more about visual benefits and optimal dosing.
5:09
SPEAKER_00: Comparing NAD plus SUP boosters, nicotinamide versus NMN, all three compounds raise NADZ plus SUP but enter the pathway differently.
5:17
SPEAKER_00: Nicotinamide, this is vitamin B3 in amide form.
5:21
SPEAKER_00: In cells, it is converted by the enzyme NMPT into NMN, then by NMN at enzymes.
5:27
SPEAKER_00: Thus nicotinamide needs two steps MT then NMAT to become NAD.
5:32
SPEAKER_00: It also very quickly turns into NAD if given in high doses, but it can compete with other NAD-related pathways.
5:38
SPEAKER_00: For example, high nicotinamide can inhibit SERTUN enzymes that use NAD.
5:42
SPEAKER_00: At normal nutritional doses, it's simply a vitamin.
5:45
SPEAKER_00: At high doses, it floods the NAD pathway.
5:48
SPEAKER_00: Nicotinamide ribicide.
5:50
SPEAKER_00: This is another form of B3 that cells can use.
5:53
SPEAKER_00: NR first converts into NMN by NR kinases, NRK enzymes, then into NAD by NMNAT.
5:59
SPEAKER_00: In other words, NR also takes two steps, NRK then NMAT, but the first step is different from nicotinamides.
6:06
SPEAKER_00: The advantage is that NR does not rely on NAMPT and does not raise nicotinamide levels, so it may avoid some feedback inhibition and methyl donor demand.
6:15
SPEAKER_00: In practice, NR is well absorbed orally and has been shown in human trials to dose dependently raise blood NAD SUP plus with few side effects.
6:24
SPEAKER_00: Nicotinamide mononucleotide, NMN.
6:27
SPEAKER_00: This compound sits just one step away from NAD.
6:30
SPEAKER_00: NMN is normally produced inside cells from nicotinamide, but it can also be taken up with help.
6:35
SPEAKER_00: NMN directly converts to NAD via NMN8, one step.
6:39
SPEAKER_00: This suggests NMN is one chemical step closer to NR or nicotinamide.
6:44
SPEAKER_00: However, whether orally taken NMN efficiently enters the eye retina is debated.
6:49
SPEAKER_00: A specialized transporter for NMN, SLC12A8, was identified in mouse intestine, but its relevance in humans isn't fully clear.
6:57
SPEAKER_00: In summary, NMN could theoretically boost NAD faster, but it is not as well validated in human nutrition.
7:04
SPEAKER_00: Cost and availability.
7:05
SPEAKER_00: Nicotinamide is extremely cheap, it's sold as generic vitamin B3.
7:10
SPEAKER_00: NR supplements, brand name niogen, etc., are much more expensive per dose.
7:14
SPEAKER_00: NMN is also costly and is not currently approved for supplements in some regions.
7:19
SPEAKER_00: For example, Europe classifies NMN as a novel food, so it cannot legally be marketed there as a supplement.
7:26
SPEAKER_00: In the US, NMN supplements recently became allowed, but NR and nicotinamide have long been standard nutraceuticals.
7:33
SPEAKER_00: In practical terms, nicotinamide tablets are widely available over the counter, whereas NR and NMN are sold as specialized, high-cost supplements.
7:42
SPEAKER_00: Why choose nicotinamide in trials?
7:45
SPEAKER_00: Clinical trials so far have focused on nicotinamide for several reasons.
7:49
SPEAKER_00: First, nicotinamide has decades of safety data as a vitamin supplement, making regulators comfortable with higher doses.
7:56
SPEAKER_00: Second, the preclinical glaucoma studies used nicotinamide, so there was a direct rationale to translate that into humans.
8:04
SPEAKER_00: Third, nicotinamide is cheap and easy to dose uniformly in trials.
8:09
SPEAKER_00: In contrast, NRNMN are newer molecules, they had to be produced under more stringent conditions and until recently had limited human data.
8:17
SPEAKER_00: Only now are trials, like NCT-069912, being planned to compare NR, NMN, and nicotinamide head-to-head in glaucoma patients.
8:28
SPEAKER_00: In short, researchers start with what works.
8:31
SPEAKER_00: Since nicotinamide already showed glaucoma benefits in animals, it makes sense to test it first in people.
8:37
SPEAKER_00: Evidence for NR and NMN in glaucoma.
8:40
SPEAKER_00: Nicotinamide ribicide, NR.
8:42
SPEAKER_00: As of 2025, there have been no published human glaucoma trials of NR.
8:46
SPEAKER_00: All evidence comes from lab studies.
8:48
SPEAKER_00: These animal studies are promising, but must be interpreted with caution.
8:52
SPEAKER_00: For instance, one rat model of chronic eye pressure, glaucoma, showed that feeding NR000 mm k day orally for three weeks increased retinal NAD plus levels and preserved RGC axons.
9:05
SPEAKER_00: Similarly, a mouse study used a combination of acute optic nerve injury and chronic microbead glaucoma models.
9:12
SPEAKER_00: It found that systemic NR treatment significantly preserved RGC survival and visual function.
9:18
SPEAKER_00: Collectively, these animal experiments demonstrate that NR can protect RGCs under stress.
9:24
SPEAKER_00: They argue that NR is bioavailable and well tolerated in rodents and may support the proposition of prospective human studies.
9:32
SPEAKER_00: There is also evidence that orally giving NR to healthy humans safely raises NAD plus SUP.
9:38
SPEAKER_00: In clinical trials of overweight adults, NR in doses up to 1,000 mg per day doubled blood NAD without causing flushing or serious side effects.
9:48
SPEAKER_00: NR supplementation did not increase homocysteine, a possible risk of NAD precursors, according to one study.
9:55
SPEAKER_00: Thus, NR appears very safe even at high doses.
9:58
SPEAKER_00: The bottom line, no direct glaucoma trials yet.
10:01
SPEAKER_00: But animal results suggest NR could help glaucoma in theory, and human safety data are strong.
10:07
SPEAKER_00: Nicotinamide mononucleotide NMN.
10:10
SPEAKER_00: Human glaucoma studies of NMN do not yet exist.
10:13
SPEAKER_00: NMN has some evidence in other eye contexts.
10:16
SPEAKER_00: For example, in a retinal detachment model, photoreceptor injury, NMN treatment increased retinal NAD and reduced cell death.
10:24
SPEAKER_00: However, that is a different part of the retina, photoreceptors, and a different injury.
10:29
SPEAKER_00: In the context of glaucoma, RGC injury, no published study has tested NMN in animals or humans yet.
10:36
SPEAKER_00: Therefore, any benefit of NMN in glaucoma is purely theoretical at this point.
10:40
SPEAKER_00: We do know some things about NMN from general research.
10:44
SPEAKER_00: In healthy adult trials for aging, NMN up to 900 mg daily was found to safely boost blood NAD without adverse events.
10:52
SPEAKER_00: In the 60-day dose ranging trial of 300 to 900 mg per day, no NMN-related adverse events and dropouts occurred.
11:00
SPEAKER_00: But whether NMN taken by mouth actually reaches retinal cells in glaucoma patients is an open question.
11:06
SPEAKER_00: Theoretical pros and cons.
11:09
SPEAKER_00: Could NR or NMN be better than nicotinamide?
11:12
SPEAKER_00: It's possible in theory.
11:13
SPEAKER_00: NR and NMN bypass the early NAMT step, which some believe is a bottleneck in aging.
11:19
SPEAKER_00: They may raise NAD more directly without creating excess nicotinamide, which uses up methyl groups.
11:24
SPEAKER_00: Animal studies suggest NR tasks cells in different ways, for example via AMPK pathways.
11:30
SPEAKER_00: If NR or NMN delivery to the eye is efficient, they might more strongly boost NAD inside RGCs.
11:37
SPEAKER_00: However, this is speculative.
11:39
SPEAKER_00: Importantly, raising blood NAD, as NR and NMN can do, does not guarantee retinal NAD increase due to tissue uptake differences.
11:47
SPEAKER_00: In early comparative studies, equimolar doses of NR, NMN, and nicotinamide are being tested in glaucoma patients exactly because nobody knows which will work best.
11:57
SPEAKER_00: Could nicotinamide be better?
11:59
SPEAKER_00: On the other hand, nicotinamide has practical advantages.
12:02
SPEAKER_00: It has decades of safety and a well-known pharmacology.
12:05
SPEAKER_00: It is cheapest and most stable to formulate.
12:08
SPEAKER_00: Nicotinamide is also readily converted into NAD in tissues.
12:12
SPEAKER_00: Some data suggests that in the eye it is quickly taken up to replenish NAD stores.
12:17
SPEAKER_00: In fact, nicotinamide was found to restore NAD in the injured retina in animal glaucoma models.
12:24
SPEAKER_00: So far, only nicotinamide has clear positive signals in human glaucoma.
12:28
SPEAKER_00: Researchers value this trial-first evidence.
12:31
SPEAKER_00: Thus, none of the NAD boosters has a definitive home run advantage yet.
12:35
SPEAKER_00: Nicotinamide's practical track record makes it a leading choice in current trials.
12:40
SPEAKER_00: Safety concerns of NAD boosters.
12:43
SPEAKER_00: While NAD boosters are generally safe when used appropriately, there are important precautions.
12:48
SPEAKER_00: Liver and metabolism.
12:50
SPEAKER_00: High dose nicotinamide, above 6 grams per day, has been associated with reversible liver enzyme elevations.
12:56
SPEAKER_00: In skin cancer trials, doses of 9 to 10 grams per day caused hepatitis in some patients.
13:02
SPEAKER_00: For glaucoma, trials use more moderate doses, 1 to 3 grams per day.
13:06
SPEAKER_00: Even so, patients should take nicotinamide with food and under doctor supervision if using multigram doses.
13:13
SPEAKER_00: NR and NMN so far at doses up to 1 Gay have shown no liver toxicity in trials.
13:20
SPEAKER_00: However, long-term safety years is still unknown.
13:23
SPEAKER_00: Methylation and homocysteine, nicotinamide is methylated in the body to N methyl nicinamide, which uses up the methyl donor SAM.
13:31
SPEAKER_00: Very high nicotinamide intakes could in theory deplete methyl donors and raise homocysteine, a vascular risk factor.
13:37
SPEAKER_00: Indeed, a single 300 mg dose of nicotinamide was shown to acutely raise plasma homocysteine.
13:44
SPEAKER_00: By contrast, NR in human trials did not raise homocysteine, likely because it bypasses the same methylation pathway.
13:51
SPEAKER_00: NMN's effect on homocysteine is less studied, but it eventually also feeds into the same NAD pool, so moderation is wise.
13:59
SPEAKER_00: Patients taking high doses may consider B vitamins, B6, B12, folate, to support methyl metabolism, as is sometimes recommended by integrated physicians.
14:09
SPEAKER_00: Other effects, NR and NMN, do not cause the flushing or itching that niacin, nicotinic acid, does.
14:15
SPEAKER_00: No effects on blood sugar or lipids have been seen at studied doses.
14:20
SPEAKER_00: Rare reports in industry suggest some people may experience mild nausea or headaches early on, but these resolved or were no different from placebo rates.
14:29
SPEAKER_00: Drug interactions.
14:31
SPEAKER_00: NAD boosters could theoretically interact with medications by altering metabolism enzymes, but no known clinically important interactions have been reported.
14:40
SPEAKER_00: As with any supplement, it is safest to discuss with your eye doctor or pharmacist, especially if you take multiple medications.
14:48
SPEAKER_00: Bottom line, NAD precursor supplements appear low risk at typical doses, but very high intakes should be approached cautiously.
14:56
SPEAKER_00: Always inform your physician before self-dosing vitamin B3 at gram levels.
15:01
SPEAKER_00: What glaucoma patients should take away?
15:04
SPEAKER_00: Clinical evidence.
15:05
SPEAKER_00: To date, nicotinamide vitamin B3 has the strongest glaucoma-specific evidence.
15:10
SPEAKER_00: Its benefits have been seen in animal studies and very small human trials of RGC function.
15:16
SPEAKER_00: In contrast, nicotamide ribicide and NMN remain mostly theoretical for glaucoma.
15:21
SPEAKER_00: There are promising animal studies for NR, but no published human trial results yet.
15:27
SPEAKER_00: NMN has no direct glaucoma data yet, just some lab studies and other eye models.
15:33
SPEAKER_00: No replacement for standard care.
15:35
SPEAKER_00: Importantly, none of these supplements should replace your prescribed glaucoma treatments.
15:40
SPEAKER_00: Controlling eye pressure, using your drops, having regular field tests and OCT scans are the evidence-based ways to slow vision loss.
15:48
SPEAKER_00: NAD boosters can be considered additional strategies, but only with doctor guidance.
15:53
SPEAKER_00: Until large clinical trials show clear benefits on vision or field loss, we should regard nicotinamide NRNN as experimental developmental.
16:02
SPEAKER_00: Dosage and safety.
16:04
SPEAKER_00: If considering nicotinamide, current research uses roughly 1 to 3 grams per day, divided doses.
16:10
SPEAKER_00: Lower doses, e.g., a typical multivitamin, are far below what's studied.
16:14
SPEAKER_00: Always talk to your doctor about any high-dose vitamin regimen because your health history, liver issues, diabetes, etc., matters.
16:22
SPEAKER_00: Nicotinamide is water soluble, so any excess is excreted, but large doses can still affect metabolism.
16:28
SPEAKER_00: Avoid self-prescribing megadoses without supervision.
16:31
SPEAKER_00: Similarly, NR or NMN supplements, if you have access to them, should be used cautiously and ideally under study conditions for now.
16:40
SPEAKER_00: Summary of evidence.
16:41
SPEAKER_00: In simple terms, nicotinum vitamin B3 is currently the front runner for glaucoma neuroprotection.
16:47
SPEAKER_00: It has a real biological rationale and some early human data.
16:51
SPEAKER_00: NR and NMN are scientifically interesting NAD boosters, but for glaucoma, their use is still unproven.
16:59
SPEAKER_00: Basically, we hope they might work based on basic science and bigger clinical trials are needed to see if that hope pans out.
17:06
SPEAKER_00: Continue standard monitoring.
17:08
SPEAKER_00: Don't skip your regular glaucoma checkups.
17:11
SPEAKER_00: NAD boosters, even if helpful, would only add a modest protective effect.
17:15
SPEAKER_00: Your main defenses remain lowering eye pressure when needed, taking prescribed drops faithfully, and monitoring your visual fields and retinal nerve health with your ophthalmologist.
17:25
SPEAKER_00: View any NAD booster as a possible extra credit strategy rather than a primary therapy.
17:30
SPEAKER_00: Comparison of NAD my precursors for glaucoma, NAD plus pathway, direct glaucoma, humocloma evida, theoretical data, theoretical benefit, safety, cost practicality, overall glaucoma evidence.
17:50
SPEAKER_00: Precursor, NMP, many lab models show RGC protection.
17:55
SPEAKER_00: Nicotinamide, vitamin B3, edumin PT, NMN, NAD mice.
18:02
SPEAKER_00: Strong, many lab models show RGC protection.
18:06
SPEAKER_00: Small trials show improved retinal function, ERG, some visual field gains, well-established NAD boost, directly used in studies, may buffer metabolic stress, well-known vitamin, generally safe 3 gram day, GIFX 6 grams, liver at 9 to 10 grams, very low cost, generic B3, easy to dose, moderate, best of the three, some clinical signals, nicotinamide riboside, NR, precursor, NRK NMN, NA.
18:34
SPEAKER_00: Fair, mouse rat models show RGC and axon protection.
18:38
SPEAKER_00: No published glaucoma trials yet.
18:39
SPEAKER_00: In general, safely raises NAD in humans, bypasses NAMPT, avoids excess NAM and methyl demand.
18:46
SPEAKER_00: Human safe.
18:47
SPEAKER_00: May activate AMPK pathways.
18:50
SPEAKER_00: Good.
18:50
SPEAKER_00: No flush.
18:51
SPEAKER_00: Up to 1000 mg day, well tolerated.
18:53
SPEAKER_00: Moderate, supplement form only, more costly than B3.
18:56
SPEAKER_00: Low to moderate per clinical support only.
18:59
SPEAKER_00: No human glaucoma data yet.
19:01
SPEAKER_00: Nicotinamide mononucleotide NMN, direct precursor to NAD, NMN, NA to my via NMN at.
19:07
SPEAKER_00: Poor.
19:08
SPEAKER_00: No direct studies in glaucoma.
19:09
SPEAKER_00: Some retina studies in other contexts.
19:11
SPEAKER_00: No published trials in glaucoma.
19:13
SPEAKER_00: Early studies in healthy adults, Co900 mg, show NAD rise in tolerability.
19:19
SPEAKER_00: One step to NAD theoretically bypasses multiple enzymes, may rapidly boost NAD CERT T1 activation.
19:26
SPEAKER_00: Appears safe in short trials, no AEs at 900 mg per day.
19:30
SPEAKER_00: Regulatory status varies.
19:32
SPEAKER_00: Novel food in EU.
19:33
SPEAKER_00: Moderate high, not as widely available, often higher price, NMN supplements restricted in some markets.
19:39
SPEAKER_00: Low, mostly hypothetical for glaucoma, awaiting clinical trial results.
19:44
SPEAKER_00: Conclusion.
19:46
SPEAKER_00: In summary, nicotinamide, vitamin B3, currently has the strongest case in glaucoma of the three NAD boosters.
19:52
SPEAKER_00: Its role in RGC metabolism is well-grounded, and small human studies hint at functional benefit.
19:58
SPEAKER_00: NR and NMN are promising in theory and show neuroprotective effects in animals, but they lack direct human glaucoma evidence.
20:06
SPEAKER_00: Future trials, including the ongoing ones, will clarify whether these newer boosters help patients.
20:12
SPEAKER_00: For now, glaucoma patients should not abandon proven treatments.
20:16
SPEAKER_00: If considering any NAD dye supplement, discuss it with your eye doctor.
20:20
SPEAKER_00: Remember that lowering intraocular pressure, following prescriptions, and regular monitoring fields OCT remain the top priorities for protecting vision.
20:30
SPEAKER_00: Sources Recent reviews and clinical studies on NAD biometabolism and glaucoma.
20:36
SPEAKER_00: All links to sources are available in the text version of this article.
20:40
SPEAKER_00: You can find the full article at visualfieldtest.com.
20:43
SPEAKER_00: Thanks for listening.
20:44
SPEAKER_00: To check your visual field, click the link at the bottom of this article or visit visualfieldtest.com.