Nicotinamide Adenine Dinucleotide (Vitamin B3) Protects Retinal Ganglion Cells in Glaucoma

by | Aug 26, 2020 | 2020, Eye Health, Vitamin B - General, Vitamins

Written by Joyce Smith, BS. In this study oral supplementation with Nicotinamide Adenine Dinucleotide (NAM) was associated with significant improvements in inner retinal function for glaucoma patients concurrently taking elevated intraocular pressure (IOP)-lowering medication.

eye healthToday the leading cause of worldwide irreversible blindness is glaucoma 1, a condition in which damage to the retinal ganglion cells (RGCs) of the optic nerve are damaged due to elevated IOP. Available treatment strategies slow the progressive vision loss by lowering IOP 2 rather than treating the neurodegenerative events that damage the optic nerve. Risk factors for glaucoma include age 3, genetics 4, and IOP 5. While lowering IOP has restored damaged RGCs and vision loss 6, vision recovery is hindered by advancing age 7. Many studies have implicated that levels of oxidative stress and mitochondrial dysfunction are associated with aging and the loss of RGCs in glaucoma 7,8; however,  in preclinical models, supplementation with nicotinamide has demonstrated a protective role in aging and neurodegenerative disease 9. Nicotinamide adenine dinucleotide (NAM), the amide of vitamin B3 and precursor for NAD+, is low in the serum of patients with primary open-angle glaucoma (POAG) 10 and its potential as a treatment for glaucoma has not yet been explored.

To examine the effect of NAM supplementation on visual function in glaucoma, a randomized, double-blind, crossover interventional study 11 was conducted to determine whether NAM could improve the inner retinal function in participants with glaucoma who were concurrently receiving glaucoma therapy. Fifty seven participants (mean age 65.5 years, 39% female), recruited from two tertiary care centers, supplemented for 6 weeks with 1.5g/day of either placebo or nicotinamide, followed by 6 weeks of 3.0 g /day and a crossover with no washout period. Participants were reviewed at the end of each six-week period at which time changes in inner retinal function were measured using electroretinography, a diagnostic test which measures electrical activity in the cells of the retina, and perimetry, a visual field test to determine any changes that have occurred.

After 12 weeks of supplementation, significant improvements in inner retinal function were evident in the 3 g dose of NAM. Combined results of low and high dose NAM revealed a 14.8% [95% CI: 2.8%, 26.9%], (P = .02) improvement in Vmax amplitude compared with a 5.2% [−4.2%, 14.6%], (P = .27) in placebo.  The combined high-low dose of NAM also improved Vmax ratio by 12.6% [5.0%, 20.2%], (P = .002) compared with a 3.6% [−3.4%, 10.5%], (P = .30) improvement in placebo. A trend for improved visual field mean deviation was observed. It should be noted that these effects were independent of IOP, therefore raising the possibility of oral NAM supplementation as a potential adjunct to existing IOP-lowering therapies.

As the amide form of Vitamin B3, NAM is often erroneously referred to as Vitamin B3. The B3 vitamin can include niacin/nicotinic acid and has demonstrated both ocular and systemic side effects at high doses 12. In contrast, NAM supplements are commercially available and relatively safe. Previous studies utilizing high doses of NAM (from 1.5 to 6 grams per day) have reported skin flushing and nausea in ≤1.5% of users. While the mechanisms by which NAD+ may improve RGC function in glaucoma are not known, studies utilizing animal models suggest that maintenance of mitochondrial integrity and function plays an important role. Longitudinal studies are warranted to determine the effects of long-term high-dose NAM supplementation.

Source: Hui, Flora, Jessica Tang, Pete A. Williams, Myra B. McGuinness, Xavier Hadoux, Robert J. Casson, Michael Coote et al. “Improvement in Inner Retinal Function in Glaucoma in Response to Nicotinamide (Vitamin B3 Supplementation: A Crossover Randomized Clinical Trial.” medRxiv (2020).

© 2020 Royal Australian and New Zealand College of Ophthalmologists

Posted August 26, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

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