Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial

This was a crossover randomized clinical trial conducted at two tertiary eye centers in Melbourne, Australia, enrolling adults with treated early-to-moderate glaucoma and visual field mean deviation of at least -10 dB. Participants were randomized 1:1 to NAM then placebo or placebo then NAM, with 49 participants in the primary analysis set and 43 in the per-protocol set.

Oral nicotinamide (NAM; vitamin B3 amide) was given in a crossover randomized regimen using matching placebo tablets. Each treatment period included 1.5 g/day for 6 weeks followed by 3.0 g/day for 6 weeks; the 3.0 g/day phase was taken as 1.5 g twice daily, morning and evening. Participants continued their usual intraocular pressure-lowering glaucoma therapy throughout.

Nicotinamide improved inner retinal function in glaucoma, with benefits seen on electroretinography but not on global visual field indices. The overall treatment effect favored NAM for PhNR Vmax by 1.35 μV [0.159, 2.551], P = .03 and for the PhNR Vmax/b-wave Vmax ratio by 0.01 [0.002, 0.025], P = .02; PhNR Vmax increased 14.8% [2.8, 26.9] on NAM versus 5.2% [-4.2, 14.6] on placebo, and the ratio increased 12.6% [5.0, 20.2] versus 3.6% [-3.4, 10.5]. No significant change was seen in visual field mean deviation (NAM-PL: 0.10 dB [-0.33, 0.53], P = .63), PSD (NAM-PL: -0.25 dB [-0.63, 0.14], P = .20), IOP, or RNFL thickness. NAM was well tolerated, and the authors concluded that further long-term studies are needed to determine durability and effects on glaucoma progression.

The trial was small and short, with only 49 participants in the primary analysis and 12 weeks per treatment period. It provides physiologic improvement rather than proven long-term disease modification, and visual field outcomes did not significantly improve. Generalizability is limited by enrollment from two tertiary centers and by the early-to-moderate glaucoma population studied.