Mitochondria, nicotinamide and glaucoma.
A growing body of evidence is pointing at poor function of mitochondria playing a role in the nerve damage resulting from glaucoma. It could be that taking the vitamin nicotinamide is beneficial in prevention of ongoing nerve damage in those with glaucoma. At present the emerging evidence is for relatively high doses of 3 grams a day. This dose is at the high end but in line with doses used in other studies looking at its benefit in other diseases including cancer, kidney disease and Altzheimers.
RETINAL GANGLION CELL
The human eye is like an electronic camera with a front lens and back electronic receptor (retina) that turns the image produced by the lens into an electrical signal. This electrical signal is then sent down some wires (axons) to the brain for interpretation. The retinal ganglion cells, of which each eye has 0.7-1.5 million, are the cells that collect the electrical signals and transmit them to the brain. They are remarkable cells that start in the retina, leave the eye via the optic nerve and end in the brain (they go via the optic chiasm to the lateral geniculate nucleus). The cell body may be 30 micrometers wide and yet the axon can be over 450 milimeters long (450,000 micrometers). Scaled up this means if the cell body were the size of a 5mm pea then its axon could stretch for 75 meters! This clearly puts quite a lot of strain on the cell body to keep everything nourished and functioning. It is these cells that get damaged and die in glaucoma.
Mitochondria are the power houses of our cells producing the energy that makes them function, this fuel is ATP (adenosine triphosphate). It is believed they were once separate organisms (bacteria) that then became engulfed into our cells to help energy production. The number in a cell varies according to how active the cell is but can be up to over 1000. They are oval in shape measuring 0.75-3 micrometers in length. Interestingly all of your mitochondria come from you mother so their lineage is purely maternal! In addition to energy production they also play a role in cell death by a process called apoptosis, they store calcium (vital for many different cellular processes) and produce heat.
MITOCHONDRIA AND DISEASE
When they don’t work properly the major effect on a cell is loss of energy. Some level of mitochondrial dysfunction has been suggested in a wide range of diseases such as Parkinson’s, Altzheimer’s, schizophrenia, chronic fatigue syndrome, and diabetes.
Another area they may result in damage to a cell is through free radical production. The process of producing energy is very prone to producing free radicals in a cell. Free radicals, if not mopped up quickly, can be responsible for damage to the genetic code (DNA) of a cell.
MITOCHONDRIA AND GLAUCOMA
The story of mitochondria and glaucoma centres around the retinal ganglion cell. As noted above these cells have quite a task to gather the electrical information from the retina and transmit it out of the eye to the brain. This task involves a lot of energy, hence the cells heavily rely on mitochondria. Several strands of research have suggested that mitochondrial function may be impaired in those with glaucoma.
Kong, G; Van Bergen, N; Trounce, I; Crowston, J Mitochondrial Dysfunction and Glaucoma, Journal of Glaucoma: February 2009 - Volume 18 - Issue 2 - p 93-100 doi: 10.1097/IJG.0b013e318181284f
Lascaratos G, Garway-Heath D, Willoughby C, Chau K, Schapira A Mitochondrial dysfunction in glaucoma: Understanding genetic influences Mitochondrion, Volume 12, Issue 2, 2012, Pages 202-212, ISSN 1567-7249, https://doi.org/10.1016/j.mito.2011.11.004.
Van Bergen N, Crowston J, Craig,Kathryn J,Burdon P, Kearns L,Sharma S, Hewitt,David A, Mackey A, Trounce I Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy PLOS ONE Published: October 23, 2015https://doi.org/10.1371/journal.pone.0140919
Nicotinamide is a water-soluble form of vitamin B3 or niacin. It is found in foods such as fish, poultry, nuts, legumes, eggs, and cereal grains. Nicotinamide is a part of NAD (nicotinamide adenine dinucleotide) and NAD is a critical part of the making and using of ATP to power cells.
It is available as an oral supplement in four forms, nicotinic acid, extended release nicotinic acid, nicotinamide and inositol hexanicotinate. Nicotinamide is the one with most reliable adsorption and least side effects.
MacKay D, Hathcock J, Guarneri E Niacin: chemical forms, bioavailability, and health effects Nutrition Reviews, Volume 70, Issue 6, 1 June 2012, Pages 357–366, https://doi.org/10.1111/j.1753-4887.2012.00479.x
As an oral supplement at normal doses it has minimal side effects. At high doses liver problems may occur.
In addition to laboratory experiments there is evidence that it protects against metabolic damage in number of different scenarios.
Sambeat A, Ratajczak J, Joffraud M, Sanchez-Garcia J, Giner M, Valsesia A, Giroud-Gerbetant J, Valera-Alberni M, Cercillieux A, Boutant M, Kulkarni S, Moco S & Canto C Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage Nature Communications volume 10, Article number: 4291 (2019)
Connell N, Houtkooper R & Schrauwen P NAD+ metabolism as a target for metabolic health: have we found the silver bullet? Diabetologia volume 62, pages888–899(2019)
Yoshino J. Baur J, Imai S NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR Cell Metabolism 27, March 6, 2018
Low levels of nicotinamide have been reported in those with glaucoma.
Kouassi Nzoughet J, Chao de la Barca J, Guehlouz K, Leruez S, Coulbault L, Allouche S, Bocca C, Muller J, Amati-Bonneau P, Gohier P, Bonneau D, Simard G, Milea D, Lenaers G, Procaccio V, Reynier P Nicotinamide Deficiency in Primary Open-Angle Glaucoma Invest Ophthalmol Vis Sci 2019 Jun 3;60(7):2509-2514. doi: 10.1167/iovs.19-27099
Work, primarily from Jonathan Crowston’s group in Melbourne, has investigated nicotinamide in glaucoma. They have a study in which high doses of nicotinamide 3 grams a day were given compared to placebo and have found clear benefit with minimal side effects. In my view this is the first hopeful evidence to date of a dietary help for glaucoma. The advantage is that the tablet is freely available and seems to have minimal side effects. A look at online availability shows it comes in 500mg tablets/capsules when bought as a single vitamin supplement so the dose would be 6 tablets a day. These are best taken with food (otherwise it can cause some heartburn), the dose could be split to take some with breakfast, lunch and supper.
One of my patients has found a site with a journalist's view of some research on the topic. It is a bit jingoistic but the wording may help.
Another of my patients has requsted links to potential sources of this vitamin. I have googled nicotinamide 500mg and the following sites seem to offer pure nicotinamide at that dose with no added stuff.