Based upon the experience gained in spotting an acetaldehyde scavenger,
See "The Acetaldehyde Game" http://curezone.com/blogs/fm.asp?i=1998795
which molecular configuration, niacin or nicotinamide, would be more likely to react with acetaldehyde?
Remembering the amide structure of urea which formed ethylidene-diurea with acetaldehyde, in a like fashion, acetaldehyde may form a Schiff base with nicotinamide:
or cross-link two nicotinamide molecules to give a dinicotinamide:
In either case acetaldehyde has lost its dangerous aldehyde reactivity. Although this protects other body structures and processes, it has also denatured some of the body's precious vitamin B3 resources which in extreme situations may lead to a deficiency condition, pellagra. Pellagra, with a long list of symptoms including diarrhea, dermatitis, and dementia, was a scourge to the world until the 1930's when its association with niacin deficiency was established.
Since acetaldehyde is also reacting with just about anything it comes in contact with, an advanced recognizable B3 deficiency state because of the nicotinamide reaction is unlikely except when the diet is severely deficient as well. This may be why the treatment of arthritis [1], hyperactivity [2] and schizophrenia [3] with megadoses of nicotinamide and niacin (which is converted into nicotinamide in the body) by Abram Hoffer back in the 1950's was met with so much criticism. A deficiency condition requiring such high dosages would be rare.
However, from the perspective of this study, in the cases that Hoffer treated with this nutrient, the excess nicotinamide may have been functioning as an acetaldehyde scavenger rather than in its role as as essential vitamin. In retrospect, this implicates a connection between these apparently unrelated diseases with acetaldehyde and its yeast source as the common factor. This shouldn't come as a surprise given the reactivity of acetaldehyde that has been explored previously in this series.
Cellular respiration, involving the oxidation of sugar, amino acids, or fatty acids in the presence of molecular oxygen, takes place in every cell of the body to charge the cellular "batteries", molecules of adenosine triphosphate (ATP) which can release their stored energy later and in other places to accommodate a cell's daily routine of activities. The fundamental activity of cellular respiration is dependent upon the vitamin B3 derivative coenzyme nicotinamide adenine dinucleotide, NAD+, which facilitates the required exchange of electrons in redox reactions.
Since chemical reactions involve movement of electrons in both directions between different molecular configurations, this coenzyme is found in two forms in cells: NAD+ is an oxidizing agent, accepting electrons from other molecules to become reduced; and NADH, a reducing agent which can subsequently donate its electrons by becoming oxidized. The cellular ping-pong between these two agents is an ongoing and critical part of many chemical reactions in the body and a regulated NAD+ to NADH ratio, the redox state, is crucial for overall stability of an organism.
We have already explored what might happen to the exposed amide and amine groups on cobalamin (B12) and folic acid (B9) in relation to acetaldehyde exposure. NAD+ and related coeznyme NAD(P)+, which has an additional phosphate group on the adenine ribose ring, contain both an exposed amide and an exposed amine group that may be attractive to acetaldehyde.
The body's own superfamily of nineteen aldehyde dehydrogenase enzymes [4] for shifting harmful aldehydes to their corresponding carboxylic acids are NAD(P)+ dependent with an aldehyde-binding sulfur atom in a cysteine residue at the active site.
CH3CHO + NAD(+) + H2O --> CH3COOH + NADH + H(+)
Aldehydes which aren't handled adequately can react both locally and remotely through diffusion or transportation to other sites. When aldehyde dehydrogenase activity is impaired or genetically dysfunctional, then numerous diseases related to their cytotoxic, mutagenic, or carcinogenic attributes may manifest [5]. Studies on other organisms indicate that alcohol and aldehyde dehydrogenase activity are closely coordinated, something that minimizes the cellular exposure time to free aldehydes [6].
Spontaneous appearance of acetaldehyde emanating from yeast cells must be somewhat of a shock to the body with the result that its innate ability to scavenge it soon enough and rapidly enough is overloaded and in need of assistance. What it does manage to process will push the NAD+/NADH ratio towards the reduced form. Additionally, the appearance of rogue acetaldehyde molecules reacting with amide/amine groups on NAD+/NADH may further corrupt and skew the redox state of the body. This is something which could prevent the optimal functioning of all aldehyde dehydrogenase pathways in the body. In other words, even if the acetaldehyde emitted by yeast doesn't actually reach the cells in an area of the body where a disease like cancer is a potential threat, it may disrupt the body's redox state (NAD+/NADH ratio) sufficiently to indirectly increase the risk of disease everywhere.
Just because overt pellagra is not obvious from acetaldehyde interference with nicotinamide, this doesn't mean that symptoms related to vitamin B3 metabolism aren't surfacing. Are there indications that yeast-released acetaldehyde may, in fact, be upsetting the NAD+/NADH balance? Indeed, remarkably so... but this will be the topic of a future post.
See "Acetaldehyde + Bipolar Disorder" http://curezone.com/blogs/fm.asp?i=2016587
Although nicotinamide supplementation can help rectify the NAD+/NADH balance [7] and potentially scavenge acetaldehyde by binding directly to it, it may not be the best choice for an acetaldehyde scavenger. The megadose quantities required for effective scavenging may interfere with its alter ego as a nutrient, i.e. megadose quantities can inappropriately accelerate enzymatic pathways and lead to an imbalance of cofactor depletion in a manner similar to the use of megadose antioxidant supplementation for scavenging free radicals:
See "Acetaldehyde + Antioxidants" http://curezone.com/blogs/fm.asp?i=2001450
Given the staggering capability of yeast for production and emission of acetaldehyde:
See "Just A Teaspoon Of Sugar" http://curezone.com/forums/fm.asp?i=1954934
and the fact that each molecule of this toxin has the potential for inflicting damage, then the situation assumes a statistical probabilistic nature. Increasing the concentration of an ingested substance, any ingested substance, that harmlessly binds to acetaldehyde, reduces the probability of toxin-mediated damage to other critical areas and hence relieves the stressors that are leading to disease. This would explain why the results obtained by Hoffer were dependent upon megadose quantities of nicotinamide far above the normal nutritional requirements.
The level of scavenging required, of course, is related to the yeast load emitting the toxin -- the less yeast, the less emitted acetaldehyde, and the less scavenging that is necessary.
[1] Hoffer A, "Treatment of Arthritis by Nicotinic Acid and Nicotinamide", Can Med Assoc J. 1959 August 15; 81(4): 235238.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1831040
[2] Hoffer A, "Letter: Hyperactivity, allergy and megavitamins.", Can Med Assoc J. 1974 November 2; 111(9): 905907.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955901
[3] Hoffer A et al., "Treatment of schizophrenia with nicotinic acid and nicotinamide.", J Clin Exp Psychopathol. 1957 Apr-Jun;18(2):131-58.
http://www.ncbi.nlm.nih.gov/pubmed/13439009
[4] Marchitti SA et al., "Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily.", Expert Opin Drug Metab Toxicol. 2008 Jun;4(6):697-720.
http://www.ncbi.nlm.nih.gov/pubmed/18611112
[5] Lindahl R, "Aldehyde dehydrogenases and their role in carcinogenesis.", Crit Rev Biochem Mol Biol. 1992;27(4-5):283-335.
http://www.ncbi.nlm.nih.gov/pubmed/1521460
[6] Eisses KT et al., "Dual function of the alcohol dehydrogenase of Drosophila melanogaster: ethanol and acetaldehyde oxidation by two allozymes ADH-71k and ADH-F.", Mol Gen Genet. 1985;199(1):76-81.
http://www.ncbi.nlm.nih.gov/pubmed/3158799
[7] Volpi E et al., "Nicotinamide counteracts alcohol-induced impairment of hepatic protein metabolism in humans.", J Nutr. 1997 Nov;127(11):2199-204.
http://www.ncbi.nlm.nih.gov/pubmed/9349848