Neuroprotection and nicotinamide

In ophthalmology, ‘neuroprotection’ usually refers to methods of preventing progressive glaucomatous visual field loss that are not intraocular pressure (IOP) reduction treatments. The term also includes the possibility of recovery of optic nerve function in glaucoma. Nicotinamide is a form of vitamin B3, which is transformed into nicotinamide adenine dinucleotide (NAD) within mitochondria. NAD is a major chemical in all the vital processes of cellular metabolism and is also critical for DNA repair through the Sirtuin pathway.

 

There are two pathways for making NAD: it can be built in the body using the amino acid tryptophan or it can be made from vitamin B3 sourced directly from meat. For most of human history being vegetarian was not a choice. For those of us with Scottish roots our ancestors ate oats, but their eyes were always on the lookout for a stray sheep!

 

A recent paper in Clinical and Experimental Ophthalmology provided evidence of the neuroprotective effect of nicotinamide (vitamin B3) in patients with glaucoma¹, using Blackmores Insolar (high-dose vitamin B3 in nicotinamide form) supplement, available throughout New Zealand.

 

So, should we be inspiring glaucoma patients to take Insolar, given that it is readily available?

 

Six months after informing one sceptical, fair-complexioned gentleman with advanced glaucoma about the possible benefits of vitamin B3, I asked him if he’d acted on the B3 information? “My dermatologist has got me taking two tablets of Insolar per day to prevent skin cancer,” he replied.

 

No doubt Insolar is so named because of the positive findings of a west Australian (where its invariably sunny) phase 3 trial of nicotinamide for skin cancer chemoprevention, published in the New England Journal of Medicine in 2015², leading to its recommendation by dermatologists for ageing skin.

 

Pellagra is the Italian word for ‘rough skin’ but in English it means a vitamin B3 deficiency. The hallmarks are: dermatitis, diarrhoea, dementia and death. Clearly, nicotinamide will be useful for treating pellagra, however there are many other surprising facets to nicotinamide.

 

The two pathways for making NAD, constitute the ‘nicotinamide switch’ with implications for the immune system. NAD made from tryptophan enhances the T-helper pathway, while NAD made from meat causes an imbalance of the immune system in favour of T-regulatory cells. Consequently, agrarian communities have high rates of fertility but suffer with chronic infectious diseases, such as tuberculosis (TB) and leprosy. In contrast, pastoralist communities (who source NAD from meat) have lower rates of fertility but are less frequently troubled by TB and leprosy. They are also, in general, taller, but suffer from higher rates of cancer and autoimmune diseases³.

 

TB is characterised by ball-shaped vascular scars called tuberculomas where the body has walled off active Mycobacteria. Regarded as a symbiosis between host and Mycobacterium, these tuberculomas elaborate vitamin B3. Thus, back in the day of TB sanatoriums, it was possible to cure some cases by providing a meat-enriched diet, while beef tea is an enduring folk remedy that remains in domestic use to this day.

 

Nicotinamide has been commercially available since 1936 and was demonstrated to be effective in treating TB but was passed over in favour of the antibiotic isoniazid and subsequently forgotten about. But it is now enjoying a renaissance as an antimicrobial for treating not only tuberculosis but also HIV and Covid-19⁴.

 

The amount of vitamin B3 given to subjects in the neuroprotection trial was equivalent to all the concentrated goodness of 40 Big Macs per day, leading one to ponder what the possible adverse effects might be! Patients were excluded from the study if they’d had cancer in the preceding five years. The skin cancer chemoprevention study also looked closely at the rate of all types of cancer, however, and concluded safety requirements were met.

 

This splendid study on nicotinamide and neuroprotection certainly gives cause for hope, but it was a preliminary study. I would not broadcast a recommendation for Insolar to all glaucoma patients, since the long-term benefit remains to be confirmed and characterised. However, the role of nutrition in glaucoma is certainly very important to consider for each patient, especially since many of the elderly are known to be vitamin deficient.

 

Given that I am now recommending eggs for macular degeneration, I shall not hesitate to recommend a hearty steak and eggs as a time-honoured method of building up those gaunt patients with thinning optic nerves!

 

References

  1. Flora Hui et al. Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial. Clin and Experiment Ophthalmol. (2020)
  2. Chen et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. NEJM (2015)
  3. Williams AC and Hill LJ. Nicotinamide and demographic and disease transitions: moderation is best. Int. J. Tryptophan Research (2019)
  4. Murray MF. Nicotinamide: an oral antimicrobial agent with activity against both Mycobacterium tuberculosis and human immunodeficiency Virus. Clin Inf Dis. (2013)

 

Dr Mark Donaldson is a consultant ophthalmologist at the Greenlane Clinical Centre and Eye Doctors in Auckland, NZ, specialising in cataract and glaucoma surgery and medical retina. He has no financial interest in Blackmore’s or Insolar.

 

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