Nicotinamide and Pyruvate for Neuroenhancement in Open-Angle Glaucoma

Abstract

IMPORTANCE Open-angle glaucoma may continue to progress despite significant lowering of intraocular pressure (IOP). Preclinical research has suggested that enhancing mitochondrial function and energy production may enhance retinal ganglion cell survival in animal models of glaucoma, but there is scant information on its effectiveness in a clinical setting.OBJECTIVE To test the hypothesis that a combination of nicotinamide and pyruvate can improve retinal ganglion cell function in human glaucoma as measured with standard automated perimetry.DESIGN, SETTING, AND PARTICIPANTS In this phase 2, randomized, double-blind, placebo-controlled clinical trial at a single academic institution, 197 patients were assessed for eligibility. Of these, 42 patients with treated open-angle glaucoma and moderate visual field loss in at least 1 eye were selected for inclusion and randomized. A total of 32 completed the study and were included in the final analysis. The mean (SD) age was 64.6 (9.8) years. Twenty-one participants (66%) were female. Participant race and ethnicity data were collected via self-report to ensure the distribution reflected that observed in clinical practice in the US but are not reported here to protect patient privacy. Recruitment took place in April 2019 and patients were monitored through December 2020. Data were analyzed from January to May 2021.INTERVENTIONS Ascending oral doses of nicotinamide (1000 to 3000 mg) and pyruvate (1500 to 3000 mg) vs placebo (2:1 randomization). MAIN OUTCOMES AND MEASURESNumber of visual field test locations improving beyond normal variability in the study eye. Secondary end points were the rates of change of visual field global indices (mean deviation [MD], pattern standard deviation [PSD], and visual field index [VFI]).RESULTS Twenty-two of 29 participants (76%) randomized to the intervention group and 12 of 13 participants (92%) randomized to placebo received their allocation, and 32 participants (32 eyes; ratio 21:11) completed the study (21 from the intervention group and 11 from the placebo group). Median (IQR) follow-up time was 2.2 (2.0-2.4) months. No serious adverse events were reported during the study. The number of improving test locations was significantly higher in the treatment group than in the placebo group (median [IQR], 15 [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] vs 7 [6-11]; P = .005). Rates of change of PSD suggested improvement with treatment compared with placebo (median, −0.06 vs 0.02 dB per week; 95% CI, 0.02 to 0.24; P = .02) but not MD (0.04 vs −0.002 dB per week; 95% CI, −0.27 to 0.09; P = .35) or VFI (0.09 vs −0.02% per week; 95% CI, −0.53 to 0.36; P = .71). CONCLUSIONS AND RELEVANCEA combination of nicotinamide and pyruvate yielded significant short-term improvement in visual function, supporting prior experimental research suggesting a role for these agents in neuroprotection for individuals with glaucoma and confirming the need for long-term studies to establish their usefulness in slowing progression.

Neuroprotection, Neuroenhancement, and Neuroregeneration of the Retina and Optic Nerve

“…20,[23][24][25] These findings have prompted small clinical trials of nicotinamide supplementation in patients with open-angle glaucoma, demonstrating modest but detectable improvements in the RGC-specific ERG photopic negative response and automated perimetry in as little as 6-10 weeks. 26,27 While still preliminary, these findings suggest potential avenues for improving visual function in patients with glaucoma using currently available nutritional supplements and they support the rationale for ongoing studies of longerterm neuroprotection by nicotinamide supplementation.…”

Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids

“…ORS therapy has been demonstrated in a top hospital to be effective in the patients of the whole hospital including those in the emergency room ( 110 ); however, Pyr-ORS has been shown to be more effective than WHO-ORS in various illnesses. Nevertheless, there has been no clinical study yet about the effects of IV or oral pyruvate on shock resuscitation, but novel oral pyruvate combined with nicotinamide has demonstrated its effectiveness in improving retinal ganglion cell function in human glaucoma ( 111 ).…”

Dietary Intervention in Glaucoma

“…17 Administration of nicotinamide up to 3 g/day prevented dysregulation of key metabolic pathways, loss of internal mitochondrial structure and size, and RGC loss. 18,19 However, the long-term effects of niacin administration are unknown. 6…”