Nicotinamide and pyruvate combo improves vision in patients with open-angle glaucoma: JAMA

USA: A combination of nicotinamide and pyruvate improved visual function significantly in the short term, reveals a recent study published in the journal JAMA Ophthalmology. This supports previous experimental research suggesting a role for these agents in glaucoma neuroprotection and confirming the need for long-term studies to establish their usefulness in slowing progression. 

Despite a large reduction in intraocular pressure (IOP), open-angle glaucoma may develop. Enhancing mitochondrial efficiency and energy generation may improve retinal ganglion cell survival in animal models of glaucoma, according to preclinical studies, but there is little evidence on its usefulness in a clinical environment.

This study was conducted by Carlos Gustavo De Moraes and his team with the objective to see if a combination of nicotinamide and pyruvate might enhance retinal ganglion cell activity in people with glaucoma, as evaluated by automated perimetry.

197 participants were evaluated for eligibility in this phase 2 randomized, double-blind, placebo-controlled clinical study at a single academic institution. 42 patients with treated open-angle glaucoma and moderate visual field loss in at least one eye were chosen and randomized from this group. The study was completed by 32 people, and 32 of them were included in the final analysis. The average age (SD) was 64.6 (9.8) years. Twenty-one (66%) of the participants were female.

To safeguard patient privacy, race and ethnicity data were acquired by self-report to ensure the distribution resembled that seen in clinical practice in the United States. Patients were recruited in April 2019 and were followed up on until December 2020. From January through May of 2021, data was examined. The dosages that were determined were as follows: Increasing nicotinamide (1000 to 3000 mg) and pyruvate (1500 to 3000 mg) oral dosages vs placebo (2:1 randomization). The main result was defined as the number of visual field test sites in the study eye improving beyond normal variability. The rates of change of visual field global indices served as secondary end goals.

The key findings of this study were as follow:

1. The study was completed by 32 individuals (32 eyes; ratio 21:11), with 22 of 29 participants (76%) assigned to the intervention group and 12 of 13 participants (92%) assigned to the placebo group.

2. The median (IQR) duration of follow-up was 2.2 (2.0-2.4) months.

3. During the trial, no significant adverse events were recorded.

4. The number of improved test sites in the therapy group was substantially greater than in the placebo group.

5. PSD rates of change indicated treatment benefit when compared to placebo, but not when compared to MD or VFI.

In conclusion, nutritional supplementation with nicotinamide and pyruvate, as proven earlier in murine glaucoma models, may improve retinal ganglion cell function in humans with glaucoma. These findings might aid in the development of novel neuroprotective treatments for glaucoma sufferers.

Reference:

De Moraes CG, John SWM, Williams PA, Blumberg DM, Cioffi GA, Liebmann JM. Nicotinamide and Pyruvate for Neuroenhancement in Open-Angle Glaucoma: A Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2022;140(1):11–18. doi:10.1001/jamaophthalmol.2021.4576