For many years I have been taking a fairly high dose B vitamin supplement, which includes niacinamide, so I was quite disturbed when I found this article by medical researchers at the University of Birmingham, UK.
QJM. 2005 Mar;98(3):215-26.
Parkinson's disease: the first common neurological disease due to auto-intoxication?
Williams AC, Cartwright LS, Ramsden DB.
Division of Neurosciences, University of Birmingham, Edgbaston, Birmingham.
Parkinson's disease may be a disease of autointoxication. N-methylated pyridines (e.g. MPP+) are well-established dopaminergic toxins, and the xenobiotic enzyme nicotinamide N-methyltransferase (NNMT) can convert pyridines such as 4-phenylpyridine into MPP+, using S-adenosyl methionine (SAM) as the methyl donor. NNMT has recently been shown to be present in the human brain, a necessity for neurotoxicity, because charged compounds cannot cross the blood-brain barrier. Moreover, it is present in increased concentration in parkinsonian brain. This increase may be part genetic predisposition, and part induction, by excessive exposure to its substrates (particularly nicotinamide) or stress. Elevated enzymic activity would increase MPP+-like compounds such as N-methyl nicotinamide at the same time as decreasing intraneuronal nicotinamide, a neuroprotectant at several levels, creating multiple hits, because Complex 1 would be poisoned and be starved of its major substrate NADH. Developing xenobiotic enzyme inhibitors of NNMT for individuals, or dietary modification for the whole population, could be an important change in thinking on primary and secondary prevention.
PMID: 15728403
Basically they are saying that they have found a biochemical pathway that will convert excess nicotinamide into a toxic compound in the brain. It is mediated by an enzyme called N-methyltransferase (NNMT) which has only recently been found to exist in the brain naturally. There will be some individual variation in how much of this enzyme people have, but it can be increased by high levels of its substrate (nicotinamide), and it may produce a slow long term poisoning of dopaminergic brain cells.
The authors AC Williams and DB Ramsden seem to have done quite a bit of work on this. When I enter Williams Ramsden nicotinamine into Google, it lists 951 citatations.
The full text of the article is available here: http://qjmed.oxfordj...t/full/98/3/215
The disturbing part is that they are only referring to the levels of niacin you can get through enriched food. Supplemental niacin or niacinamide would be many times higher.
In the full text of the article they say, "Western societies who suffer more from PD may now have too much nicotinamide in their diet overall, and this may need to be addressed at the population level."
In a less technical article they talk about niacin enriched foods as a possible cause for increased rates of Parkinson's disease
Parkinsonism Relat Disord. 2005 Nov;11(7):413-20.
Nicotinamide: a double edged sword.
Williams A, Ramsden D.
Division of Neurosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. adrian.williams@uhb.nhs.uk
Enrichment of diet with Nicotinamide in the West was introduced in the 1940s to prevent the dietary deficiency disorder Pellagra. Pellagra was caused by a particular form of poor vegetarian diet leading to Nicotinamide and Tryptophan deficiency... Diets may sometimes now be too high in selected pyridines and inadvertently we have exchanged one neurodegenerative disease for another. Parkinson's disease triggered in contrast to Pellagra by a particular form of rich omnivorous diet. Moderation of Nicotinamide intake would be easy to begin with compared with other dietary manipulations as there is no behavior change necessary for individuals. A substantial amount of Nicotinamide can be removed when and where there is too much that has been introduced artificially and inserted where there is too little because meat is unaffordable.
PMID: 16183323
