Improvement in inner retinal function in glaucoma with 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 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).

Plasma GDF-15 concentration is not elevated in open-angle glaucoma

“…One explanation could be that mitochondrial dysfunction does not play a role in the pathology of glaucoma. This reasoning is very unlikely, given the accumulated evidence on the role of mitochondria in glaucoma [9,[11][12][13][14][15][16][43][44][45][46][47][48]. Alternatively, an explanation could be that GDF-15 is not a suitable biomarker.…”

“…Strikingly, bolstering mitochondrial function by administration of nicotinamide (the amide of vitamin B3), robustly protected the mice from glaucoma. Very recent results of a clinical trial suggest that OAG patients can also benefit from this therapeutic strategy, as supplementation of nicotinamide improves their inner retinal function [ 16 ].…”

Systemic Treatment with Nicotinamide Riboside Is Protective in Two Mouse Models of Retinal Ganglion Cell Damage

“…NAD + levels also decrease in models of glaucoma, suggesting that NAD + is critical to RGC health [ 18 , 19 ]. Treatment with nicotinamide (NAM), a precursor of NAD + , increases circulating NAD + and is protective in models of RGC degeneration [ 18 , 20 , 21 , 22 ] and is being tested in a glaucoma clinical trial [ 23 ]. The maximal efficacy in models was achieved only at doses that, by human equivalent dose (HED), may be above a good safety profile, and was not protective in a significant portion of the treated cohorts [ 24 , 25 , 26 ].…”

Suppression of Oxidative Stress as Potential Therapeutic Approach for Normal Tension Glaucoma

“…Studies from DBA/2J mice demonstrated that oral administration of niacin reduced RGC death [79] and the therapeutic role of niacin in glaucoma was supported by studies of NTG patients indicating that there was a reduced level of dietary niacin intake in NTG patients [80]. Recent clinical trials demonstrated that supplementation with niacin improved inner retinal function in glaucoma patients [81], and the long-term effects of niacin supplementation are under investigation at present.…”