It has been suggested in this series that the apparent requirement for excessive amounts of supplementary antioxidants in so many cases is a consequence of the the disruption of the balance of paired-substance redox pools by the acetaldehyde released by C. albicans when it is fermenting carbohydrates.
• See "Acetaldehyde + Cysteine/Cystine" http://curezone.com/forums/fm.asp?i=1975696
• See "Acetaldehyde + Glutathione/GSSG" http://curezone.com/forums/fm.asp?i=1977665
• See "Acetaldehyde + NAD+/NADH " http://curezone.com/blogs/fm.asp?i=2004103
The NAD+/NADH balance is so critical that the body has a backdoor pathway for the production of vitamin B3, niacin, the precursor to NAD+. The liver can convert the dietary essential amino acid tryptophan to niacin in a multi-step pathway with support from cofactors riboflavin, pyridoxal and iron.
Right out of the starting gate in this sequence there is a potential problem when C. albicans levels are too high. The beta-carboline formed by the Pictet-Spengler condensation reaction of acetaldehyde with tryptophan can not only remove the raw material amino acid, but also inhibit the enzyme indoleamine 2,3-dioxygenase (IDO). Removing tryptophan is on a one to one basis (one acetaldehyde, one lost tryptophan) but the enzyme inhibition potentially has a much greater impact. Although one beta-carboline may inhibit one IDO, one IDO enzyme is responsible for converting a host of tryptophan substrates.
• See "Acetaldehyde + Enzymes " http://curezone.com/forums/fm.asp?i=1949530
The overall effect is that the backdoor niacin synthesis pathway may be blocked or severely impaired.
Tryptophan is such a key player in so many critical biochemical pathways, including the neurotransmitter serotonin and the neurohormone melatonin, that any interference with its reactions results in a cascade of consequences. The autoimmune disease ramifications of IDO inhibition in relation to the prevention of tryptophan starvation of T-cells, something absolutely necessary for immune system quiescence post-infection, have already been explored:
• See "Acetaldehyde + Tryptophan Starvation " http://curezone.com/blogs/fm.asp?i=2009683
With the potential blockage of the tryptophan to niacin pathway by acetaldehyde, there are now at least five different ways in which acetaldehyde from C. albicans can interfere with the NAD+/NADH balance:
• aldehyde dehydrogenase processing of acetaldehyde requires a NAD+ to NADH shift, potentially skewing the balance when acetaldehyde levels are high
• acetaldehyde can form a Schiff base with the amide group and denature nicotinamide, a precursor to NAD+
• acetaldehyde can form Schiff bases with the exposed amine and amide groups of NAD+/NADH directly removing either of the pair from the redox pool
• 3-MTBC (the tryptophan/acetaldehyde beta-carboline) diminishes the availability of the essential amino acid tryptophan used in the backdoor pathway from tryptophan to niacin, something required to replenish a depleting NAD+/NADH redox pool, especially when vitamin B3 intake is insufficient
• even when tryptophan is available, 3-MTBC can inhibit the IDO enzyme which converts it to N'-formyl-kynurenine, the first step In the backdoor pathway from tryptophan to niacin
Orthomolecular Psychokinesiology (OPK) techniques for using muscle strength as a biofeedback indicator of dynamic nutrient activity in the body [1] are not only applicable to the raw materials (vitamins and minerals) currently being sought after and utilized. Any biochemical process in the body can be queried through visualization to determine its status. The NAD+/NADH balance is no exception.
Adjust the hand grip so that it can just be compressed. Then visualize, in turn, NAD+ and NADH, and compress the squeezer for each to see if you get stronger or weaker. If both NAD+ and NADH are balanced, as they should be, then neither should return an easier-to-compress result. If one returns a stronger response and the other a weaker, then there may be a problem.
When NAD+ is too low mood symptoms include depression and anxiety; but when NAD+ is too high the symptoms shift to agitation and mania -- a form of bipolar disorder. Normally, the ratio of this redox pool is so closely regulated that both NAD+ and NADH are available on demand. However, if a situation arises which upsets the balance beyond a certain threshold, especially when acetaldehyde levels are interfering with the re-stabilizing processes, then the body appears to have a problem re-establishing the appropriate equilibrium. It overcompensates, shifting first into a state with too much NAD+ and then into too much NADH, either at one extreme or the other.
The amazing aspect of OPK is that it is often possible to rectify this balance using a visualization alone without any additional supplementation. Again adjust the hand grip so that it can just be compressed. Then continue to compress it, visualizing each of NAD+ and NADH in turn like a seesaw, until each returns a harder-to-compress result. The sensation is a bit like pumping up a deflated bicycle tire until you can feel a consistent feedback pressure for both. Mood symptoms should respond almost immediately.
The energetics of what is transpiring are not well understood. However, the fact that symptomatic improvement occurs very rapidly indicates that the body already has the necessary resources required to correct the imbalance. It is almost as if the imbalance is not being recognized as such until the visualizations superimpose a psychic homeopathic signal onto the body's energy field, thus alerting it to the fact that its biochemistry is out of kilter.
A similar phenomenon has been noticed in regards to absorption kinetics from the gastrointestinal tract. One prodromal biomarker for insufficient vitamin B3 availability in the body is under-arm wetness even in the absence of physical exertion. This may surface after the intake of a large proportion of foods with high vitamin A content, e.g. fish, without adequate B-vitamin support. Often this can be the result of an absorption imbalance that can be rectified just by OPK testing for the deficiency without additional supplementation [2].
Adjust the hand grip so that it can just be compressed. Then squeeze it, thinking of niacin, and continue to do so until the apparent tension in the hand grip increases. If this does not occur within a few compression tests, then additional supplementation of vitamin B3 may be required.
A cautionary note on the usage of the natural light therapy device Litebook® website [3] indicates that, in some cases, mania (periods of abnormally and persistently elevated, expansive or irritated mood) may be experienced after exposure to the intense LED light. OPK testing has shown that this corresponds to elevated levels of NAD+ in relation to the NAD+/NADH balance. This imbalance is less likely to occur if the light source is positioned so that the light impinges upon the eyes from above instead of from below. This suggests that the angle of incidence of the light is as an important factor in the biochemistry involved as the light itself. Since sunlight shines from above in the sky, mimicking the positioning of exposure is just as important as the wave length and brightness composition of the source.
If the yeast-disrupted NAD+/NADH balance model of bipolar disorder has merit, then there should be confirmation obtainable by examining the current molecular therapeutic techniques prescribed for this condition. Bipolar therapy uses mood stabilizing substances in an attempt to reverse the manic or depressive episodes. Lithium carbonate has been used to treat depression since 1886.
The polar nature of acetaldehyde allows the formation of coordination complexes with metal cations such as lithium [4] and when acetaldehyde has formed its enolate ion:
• See "Acetaldehyde + Enolate Ion" http://curezone.com/forums/fm.asp?i=1989003
it may combine with lithium to form the lithium enolate of acetaldehyde [5].
A multi-layer oxygen scavenging film with neutralizing compounds for by-products such as reactive aldehydes is described in an industrial patent [6]. Carbonates of Group IA and IIA elements are considered to be suitable for trapping acids, alcohols, and aldehydes. Lithium carbonate would fall into this category. Therapeutic administration of lithium carbonate could lead to the disappearance of acetaldehyde from its damaging form via any or all of these pathways.
Carbonate ions, CO3(--), are also efficient catalysts for the aldol condensation of carbonyl compounds [7]. Since an acetaldehyde to acetaldehyde aldol condensation can lead to crotonaldehyde, this is not necessarily beneficial since crotonaldehyde is still harmful to biological systems [8].
Lithium has also been shown to be able to trigger dissociation of C. albicans [9] and to suppress the morphogenesis and growth of this yeast [10]. This would reduce the levels of acetaldehyde released by its fermentation process.
• See "C. albicans Fermentation Process" http://curezone.com/forums/fm.asp?i=1986782
Lithium is a highly reactive hydrophilic substance with reported side effects including diabetes mellitus, depression, weight gain, type 2 diabetes mellitus, drug interaction, tremor, nausea, anxiety, vomiting [11]. Other side effects may include diarrhea, drowsiness, tinnitus, polyuria and thirst.
Valpromide (Depamide) is a carboxamide used in the treatment of epilepsy and some affective disorders.
Reported side effects include fall, drug interaction, thrombocytopenia, malaise, hypotension, tachycardia, respiratory distress, pyrexia[12].
The amide group is an attractive binding point for acetaldehyde as we have seen previously:
• See "Acetaldehyde + Industrial Contaminant " http://curezone.com/blogs/fm.asp?i=1995773
• See "Acetaldehyde + Cobalamin" http://curezone.com/blogs/fm.asp?i=1998795
• See "Acetaldehyde + Nicotinamide " http://curezone.com/blogs/fm.asp?i=2004103
We might expect valpromide to neutralize acetaldehyde via the formation of a Schiff base. This would be an off-label action of this drug reducing the impact of acetaldehyde on the NAD+/NADH balance.
Carbamazepine (Tegretol) is another anticonvulsant and mood-stabilizing drug used for epilepsy and bipolar disorder as well as trigeminalneuralgia. Its off-label usage includes attention-deficit hyperactivity disorder (ADHD), schizophrenia, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder, and post-traumatic stress disorder. The fact that it is used for such a wide suite of off-label conditions strongly hints of a hitherto unrecognized commonality between these conditions -- acetaldehyde toxicity perhaps?
Reported side effects include convulsion, pyrexia, dizziness, nausea, vomiting, rash, somnolence, drug interaction, headache, pain [13]. Both valproic acid and carbamazepine are linked to neurodevelopmental problems including spina bifida when used during pregnancy [14].
The reduction of acetaldehyde levels by both valproic acid and carbamazepine is not an unknown effect and has actually been studied in relation to alcoholic post-intoxication syndrome normalization of biogenic amines including adrenaline, noradrenaline, dopamine, serotonin (tryptophan derivative), 5-hydroxyindoleacetic acid and histamine in the brain and blood [15].
• See "Acetaldehyde + Tryptophan" http://curezone.com/forums/fm.asp?i=1963688
• See "Acetaldehyde + Serotonin" http://curezone.com/forums/fm.asp?i=1963129
• See "Acetaldehyde + Dopamine" http://curezone.com/forums/fm.asp?i=1956462
• See "Acetaldehyde + Histamine" http://curezone.com/forums/fm.asp?i=1963358
• See "Acetaldehyde + Monoamine Oxidase" http://curezone.com/forums/fm.asp?i=1972530
Lamotrigine is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder with off-label usage for depression.
Possible side effects include dizziness, drowsiness, headache, blurred/double vision, loss of coordination, shaking (tremor), nausea, vomiting, upset stomach, depression, suicidal thoughts/attempts, or other mental/mood problems, rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, and trouble breathing [16].
Lamotrigine has two amine side chains available for acetaldehyde binding.
Topiramate is a sulfonamide anticonvulsant used to treat epilepsy and bipolar disorder. It is most frequently prescribed for migraines.
Common side effects of topiramate are tiredness, dizziness, coordination problems, nervousness, nausea, weight loss, confusion, speech problems, changes in vision or double vision, eye pain, tingling or prickling sensation in hands and feet, difficulty with memory, and sensory distortion. [17].
This investigation strongly suggests that at least some, if not all, of the effectiveness of the known treatments for bipolar disorder are related to their ability to scavenge acetaldehyde or to impair its production from C. albicans [18]. If this is the case, then an alternate treatment regimen aimed directly at these causative agents could provide similar improvement and control without the side effects associated with many of the drug-based therapies.
Many drugs are designed to target particular enzymatic pathways with the intent of inhibiting those that are apparently out of control. This runs the risk of side effects that occur because of the introduction of a foreign substance that has other biochemical interactions besides those intended. Not all of these are necessarily deleterious. If the drug has a side chain that is attractive for acetaldehyde binding, then the effects of this toxin and its downstream consequences will be reduced. In clinical trials this off-label effect may provide false positive confirmation that a drug is actually acting as expected with symptoms responding favorably, but for other reasons.
Vitamins, minerals, and amino acids, on the other hand, tend to stimulate enzymatic pathways but, in large non-nutritional dosages, can also create peripheral symptoms because of cofactor depletion. Again if the nutrient (e.g. nicotinamide or cysteine) has a molecular configuration that renders acetaldehyde benign, then beneficial effects may ensue.
Other substances that do not fall into either of these clinical categories (e.g. MMS or hydrogen peroxide) can also produce results by neutralizing acetaldehyde but at the risk of their own toxic profiles. Wondrenic/wondreic acids (sulfurated linolenic/linoleic acids) [19] were neither drugs nor nutrients and functioned as acetaldehyde scavengers without enzymatic inhibition or over-stimulation.
The common factor in all of these scenarios is the interaction of the substance with acetaldehyde before this toxin has had a chance to react with something else essential to bodily function. As the list of conditions whose biochemical profiles can be traced back to acetaldehyde toxicity gets longer and longer, it should be obvious by now that this commensal yeast problem is more than just something experienced by a subset of immunocompromised humanity.
Truss was right [20] -- C. albicans is at the root of a global acetaldehyde pandemic aggravated by the exponential increase in the use of antibiotics without a concomitant fungistatic protocol! Given the multifaceted disruptive influences of acetaldehyde on all bodily functions, including the immune system, prior cumulative exposure to this toxin may be one of the reasons that antibiotics are indicated in so many situations, something which leads to a vicious cycle of acetaldehyde- and antibiotic-induced immuno-degradation.
The factors that obfuscate this are first, that this organism can be cultured from asymptomatic individuals and second, that those who do succumb to the cumulative effects of acetaldehyde poisoning do so in a host of different ways manifesting a specific diagnosable end-disease (or diseases) based upon their level and locale of yeast colonization, their innate acetaldehyde scavenging insufficiency, and in-born genetic vulnerabilities.
[1] "Orthomolecular Psychokinesiology" in "Astrophysiology… and Yeast", 2011.
http://www.scribd.com/doc/74090699
http://www.epubbud.com/book.php?g=7JQU45V8
[2] "Pseudo Deficiencies" in "Astrophysiology… and Yeast", op. cit.
[3] Litebook® A new generation of light therapy
http://www.litebook.com/Support/litebook-usage-information.html
[4] Blint RJ, "Competitive Coordination of Lithium Ion", J. Electrochem. Soc. 1997 volume 144, issue 3, 787-791.
http://jes.ecsdl.org/content/144/3/787.abstract
[5] Lynch TJ et al., "Molecular structure of the lithium enolate of acetaldehyde", J. Org. Chem., 1980, 45 (24), pp 5005–5006
http://pubs.acs.org/doi/abs/10.1021/jo01312a045
[6] Ching et al., "Oxygen-Scavenging System Including A By-Product Neutralizing Material", US Patent 6057013, 1996.
http://www.google.com/patents/US6057013?printsec=abstract#v=onepage&q&f=false
[7] Noziere B et al., "Inorganic ammonium salts and carbonate salts are efficient catalysts for aldol condensation in atmospheric aerosols.", Phys. Chem. Chem. Phys., 2010,12, 3864-3872.
http://pubs.rsc.org/en/content/articlelanding/2010/cp/b924443c
[8] Liu XY et al., "Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde.", Toxicol Lett. 2010 Aug 16;197(2):113-22.
http://www.ncbi.nlm.nih.gov/pubmed/20471460
[9] Mickle WA et al., "DISSOCIATION OF CANDIDA ALBICANS BY LITHIUM CHLORIDE AND IMMUNE SERUM", J Bacteriol. 1940 June; 39(6): 633–647.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC374604
[10] Martins LF et al., "Lithium-mediated suppression of morphogenesis and growth in Candida albicans.", FEMS Yeast Res. 2008 Jun;8(4):615-21.
http://www.ncbi.nlm.nih.gov/pubmed/18373681
[11] Adverse Event Reporting System Database, "LITHIUM Adverse Event Statistics", 2011.
http://www.adverse-effects.org/drugs/66626-lithium
[12] Adverse Event Reporting System Database, "DEPAMIDE Adverse Event Statistics", 2011.
http://www.adverse-effects.org/drugs/33250-depamide
[13] Adverse Event Reporting System Database, "TEGRETOL Adverse Event Statistics", 2011.
http://www.adverse-effects.org/drugs/33555-tegretol
[14] Jentink J et al., "Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study.", BMJ. 2010 Dec 2;341:c6581. doi: 10.1136/bmj.c6581.
http://www.ncbi.nlm.nih.gov/pubmed/21127116
[15] Mitina LV et al., "The evaluation of the efficacy of carbamazepine and valproic acid in the alcohol postintoxication syndrome based on ethanol and acetaldehyde kinetics and the content of biogenic monoamines.", Farmakol Toksikol. 1991 Sep-Oct;54(5):60-2.
http://www.ncbi.nlm.nih.gov/pubmed/1800156
[16] MedicineNet, "Lamotrigine Side Effects", 2012.
http://www.medicinenet.com/lamotrigine-oral/page2.htm#SideEffects
[17] MedicineNet, "Topiramate Side Effects", 2012.
http://www.medicinenet.com/topiramate/page2.htm
[18] Gainza-Cirauqui ML et al., "Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders.", J Oral Pathol Med. 2012 Aug 22.
http://www.ncbi.nlm.nih.gov/pubmed/22909057
[19] "Wondro -- Inside Out", 2012.
http://www.scribd.com/doc/101099776
http://www.epubbud.com/book.php?g=7D42SJH6
[20] Truss CO, "Metabolic abnormalities in patients with chronic candidiasis: the acetaldehyde hypothesis.", Orthomol Psychiatr 1984; 13:66–93.
http://orthomolecular.org/library/jom/1984/pdf/1984-v13n02-p066.pdf