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

Importance Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+, is low in serum of glaucoma patients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in human glaucoma is unknown. Background To examine the effects of nicotinamide on inner retinal function in glaucoma, in participants receiving concurrent glaucoma therapy. Design Crossover, double‐masked, randomized clinical trial. Participants recruited from two tertiary care centres. Participants Fifty‐seven participants, diagnosed and treated for glaucoma. Methods Participants received oral placebo or nicotinamide and reviewed six‐weekly. Participants commenced 6 weeks of 1.5 g/day then 6 weeks of 3.0 g/day followed by crossover without washout. Visual function measured using electroretinography and perimetry. Main outcome measures Change in inner retinal function, determined by photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b‐wave amplitude (Vmax ratio). Results PhNR Vmax improved beyond 95% coefficient of repeatability in 23% of participants following nicotinamide vs 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (P = .02) on nicotinamide and 5.2% [−4.2%, 14.6%], (P = .27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (P = .002) following nicotinamide, 3.6% [−3.4%, 10.5%], (P = .30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1 dB on nicotinamide and fewer deteriorating (4%) compared to placebo (P = .02). Conclusions Nicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long‐term nicotinamide supplementation.