Improvement in inner retinal function in glaucoma in response to nicotinamide (Vitamin B3) supplementation: a crossover randomized clinical trial

Abstract 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 determine whether nicotinamide supplementation alongside conventional IOP-lowering therapy improves retinal ganglion cell function in glaucoma. Design Crossover, double-masked, randomised clinical trial. Participants recruited from two tertiary care centres. Participants Fifty-seven participants, diagnosed and treated for primary glaucoma, enrolled. Methods Participants received oral placebo or nicotinamide and reviewed six-weekly. Participants commenced 6-weeks of 1.5 grams/day then 6 weeks of 3.0 grams/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 (COR) in 23% of participants following nicotinamide versus 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (p=0.02) on nicotinamide and 5.2% [−4.2%, 14.6%], (p=0.27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (p=0.002) following nicotinamide, 3.6% [−3.4%, 10.5%], (p=0.30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1dB on nicotinamide and fewer deteriorating (4%) compared to placebo (p=0.02). Conclusions Nicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long-term nicotinamide supplementation. Trial Registration ANZCTR trial ID: ACTRN12617000809336 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373001