New Evidence for Neuroprotection
A clinical trial led by Melbourne researchers suggests vitamin B3 (nicotinamide) could play an important role in protecting against retinal ganglion cell damage that leads to blindness in glaucoma. The study demonstrated that there was a significant improvement in the visual function of glaucoma patients who received a daily dose of three grams of nicotinamide for 12 weeks in addition to their regular treatment to reduce intraocular pressure.
The need for a new approach that goes beyond lowering pressure was the catalyst for a clinical trial at the Centre for Eye Research Australia that examined the role of nicotinamide, a water-soluble form of vitamin B3, in improving visual function and potentially slowing glaucoma progression. Our research – published in Clinical and Experimental Ophthalmology last year – was the first clinical study to demonstrate the potential of vitamin B3 as a glaucoma therapy.
B3 studies of B3 are also happening in Sweden – We have confirmed nicotinamide’s neuroprotection in additional cell and animal models that recapitulate isolated features of glaucoma but are also common neurodegenerative features. We also have developed sensitive tools to investigate NAD metabolism, and the metabolism of other essential metabolites, in the visual system. We demonstrated that systemic nicotinamide administration has limited molecular side-effects, but provides a robust reversal of the disease metabolic profile of glaucoma prone animals, says James Tribble, a postdoctoral researcher in the Williams laboratory at St. Erik Eye Hospital and Karolinska Institutet, the first author of the study.
A long-term clinical Swedish Glaucoma Nicotinamide Trial, lead by Umeå University, Karolinska Institutet and St. Erik Eye Hospital has commenced in autumn 2021. Only patients with newly diagnosed and untreated glaucoma will be included in the clinical study.
What we have demonstrated in cell and animal models is now directly making its way to patients in the Swedish health care system, says Pete Williams. This exemplifies our commitment to generating translatable treatments for glaucoma, he concludes.
Why study B3 ?
Vitamin B3, or nicotinamide, is a precursor of NAD+ (nicotinamide adenine dinucleotide) and is critical co-enzyme found in every cell in the body. It is involved in hundreds of metabolic processes. There is some research that has indicated that glaucoma patients are low in NAD+ serum.
Retinal ganglion cells are the cells that form the optic nerve, the nerve of sight. Vision is the part of the body with one of the highest metabolic demands. Therefore, Retinal ganglion cells are normally under significant stress. In glaucoma, the retinal ganglion cells are under more stress than in a healthy eye. The theory is that B3 supplementation provides protection.
Recent work has indicated that patients with primary open-angle glaucoma (POAG) have reduced serum levels of nicotinamide (NAM, the amide of vitamin B3 and precursor for NAD+).
In order to avoid the side effects of vitamin B3, patients were given nicotinamide which is the amide of vitamin B3 and the precursor of NAD+.
The dosage used in this study was very high – 3 grams of nicotinamide over 3 months Patients were given the 1.5 grams/day for six weeks than then 3 grams daily for six weeks in addition to their regular glaucoma drops. The control group of patients received a placebo. The study design was a cross-over study. This means that after 12 weeks the patients in the treatment group were given placebo while the patients in the placebo group were given the B3.
To measure success, patients had visual field testing and electroretinography. Electroretinography is a test that measures the electrical conduction of the retina and optic nerve. It is analogous to how an ECG measures the conduction of the heart.
The results the researchers found was that 23% of participants who took B3 showed improvement in their electrical conduction. There was a trend towards improvement for visual fields as well.
Patients only experienced mild gastro-intestinal side-effects with nicotinamide.
If you are interested in using nicotinamide, please discuss it with your GP and ophthalmologist.
Dr Flora Hui
Centre for Eye Research Australia
Hui F, Tang J, Williams PA, McGuinness MB, Hadoux X, Casson RJ, Coote M, Trounce IA, Martin KR, van Wijngaarden P, Crowston JG Improvement in Inner Retinal Function in Glaucoma with Nicotinamide (Vitamin B3) Supplementation: A Crossover Randomised Clinical Trial at Clinical and Experimental Ophthalmology. DOI https://doi.org/10.1111/ceo.13818
The research was supported by the Jean Miller Foundation, Connie and Craig Kimberley Foundation, the Ophthalmic Research Institute of Australia, Jack Brockhoff Foundation, Marian and EH Flack Trust, Fund and Board of Research Faculty (Karolinska Institutet). The Centre for Eye Research Australia also receives funding under the Victorian Government’s Operational Infrastructure Program.
Dr Hui was the recipient of Glaucoma Australia’s Quinlivan 2020 Research Grant to support her work on the next phase of the research.