Thank you for posting this question here. I am glad this man has sought out your support. I would agree with you given his history, both personal and family, that the issue with molds is likely an underlying culprit, and that there also is likely genetic susceptibility. There is an excellent mycotoxin testing panel that is now being offered by Great Plains Lab (https://tinyurl.com/y8xuaect) in the US, however, I did not see that it was available yet at Regenerus. You may want to call the company to find out more, and if the test will be available in the UK as well.
One of the issues with mycotoxins are that they can act as Nrf2 inhibitors. Ochratoxin A, one of the most common mycotoxins found in foods and water damaged houses, is known to be a Nrf2 inhibitor. This means that the body’s ability to regenerate glutathione and detoxify via other important detoxification enzymes and transporters is limited. Given subsequent insults of food sensitivities there also is likely intestinal permeability, contributing to a high systemic endotoxin load, which also blocks detoxification pathways.
Limonciel A, Jennings P. A review of the evidence that ochratoxin A is an Nrf2 inhibitor: implications for nephrotoxicity and renal carcinogenicity. Toxins (Basel). 2014 Jan 20;6(1):371-9. https://tinyurl.com/yb4m9cdw
Anton PM, Theodorou V, Bertrand V, et al. Chronic ingestion of a potential food contaminant induces gastrointestinal inflammation in rats: role of nitric oxide and mast cells. Dig Dis Sci. 2000 Sep;45(9):1842-9. https://tinyurl.com/ycbh2azy
Carbonell LF, Nadal JA, Llanos MC, et al. Depletion of liver glutathione potentiates the oxidative stress and decreases nitric oxide synthesis in a rat endotoxin shock model. Critical care medicine. 2000 Jun 1;28(6):2002-6. https://tinyurl.com/yczl8nz3
Kalitsky-Szirtes J, Shayeganpour A, Brocks DR, Piquette-Miller M. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos. 2004 Jan;32(1):20-7. https://tinyurl.com/y7mflnd2
Because of these things, it is important to support his glutathione levels and glutathione system, which is very important for detoxification. Glutathione is crucial for eliminating toxins from our cells, and many other enzymes, which are promoted by the transcription factor Nrf2 and promotor known as the antioxidant response element (ARE) are also necessary for detoxification. This includes the phase II enzymes glutathione S-transferase (GST), glutathione reductase (GSR), glutathione peroxidase (GPX), and nicotinamide adenine dinucleotide phosphate (NADPH), a reducing agent, as well as many of the Phase III transporters.
Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009 May 15;284(20):13291-5. https://tinyurl.com/ybpbw6xa
Harvey CJ, et al. Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med. 2009 Feb 15;46(4):443-53. https://tinyurl.com/ycgmqvpr
Depletion of glutathione can contribute to the development of allergies and a Th1/Th2 cytokine imbalance. Experimentally, Th1 dominance will shift to Th2 dominance (allergy/asthma) through depletion of intracellular glutathione, and introduction of glutathione will promote Th1 response. Glutathione can become depleted with continual exposure to toxins (ie a need for it) and our Nrf2 system which upregulates production of glutathione when needed becomes less capable with increasing age. Acetyl-Glutathione is a novel oral glutathione formulation that is stable in the stomach and gastrointestinal tract, well absorbed, and able to enter the cells directly and present to the cytosol for mitochondrial entry. Unlike other forms of glutathione, Acetyl-Glutathione tablets are odour-free and easy to take.
Berger A. Th1 and Th2 responses: what are they? BMJ. 2000 Aug 12;321(7258):424. http://tinyurl.com/h5k9b9s
Zhang H, et al. Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments. Free Radic Biol Med. 2012 May 1;52(9):2038-46. https://tinyurl.com/y8o47lxv
Fraternale A, et al. The increase in intra-macrophage thiols induced by new pro-GSH molecules directs the Th1 skewing in ovalbumin immunized mice. Vaccine. 2010 Nov 10;28(48):7676-82. http://tinyurl.com/z8ds6yp
Fraternale A, et al. Antiviral and immunomodulatory properties of new pro-glutathione (GSH) molecules. Curr Med Chem. 2006;13(15):1749-55. http://tinyurl.com/z4qr2ca
Although Nrf2 is maintained at a steady state level, it is constantly degraded in cells not experiencing stress. In cell cultures, Nrf2 has been shown to experience rapid degradation with a half-life of approximately 15 minutes, suggesting that in order to effectively increase its expression a sustained level of inducing substances, or stress, is necessary. Fortunately, we are aware of many natural substances and health-promoting practices which have evidence of inducing Nrf2 and thus our detoxification pathways and antioxidant defenses. This includes substances in items we consume like cruciferous vegetables (sulforaphane and 3,3′-diindolylmethane or DIM), tomatoes (lycopene) and green tea (epigallocatechin gallate, or EGCG). Although for healthy individuals without excessive toxin exposures these day-to-day activities or dietary habits may be adequate, this individual will likely need additional support.
Stewart D, Killeen E, Naquin R, et al. Degradation of transcription factor Nrf2 via the ubiquitin-proteasome pathway and stabilization by cadmium. J Biol Chem. 2003 Jan 24;278(4):2396-402. https://tinyurl.com/yap9b2lh
Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med. 2008 Oct;74(13):1526-39. https://tinyurl.com/ya6aaur2
Saw CL, Cintrón M, Wu TY, et al. Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos. 2011 Jul;32(5):289-300. https://tinyurl.com/yca3l2fx
Additional considerations are agents which support the reduction of histamine and improve the Th1/Th2 balance. This includes quercetin, vitamin C, and DIM. Quercetin is one substance which has been well studied for the reduction of a Th2 response as it inhibits histamine release and suppresses interleukin IL-4 production. It also has been shown to increase IFN-gamma and Th1 cytokine production. Because DIM also is an agent which supports the Nrf2 pathway you may want to try to introduce this first, possibly with vitamin C and glutathione directly.
Mlcek J, et al. Quercetin and Its Anti-Allergic Immune Response. Molecules. 2016 May 12;21(5). http://tinyurl.com/z67atbz
Park HJ, et al. Quercetin regulates Th1/Th2 balance in a murine model of asthma. Int Immunopharmacol. 2009 Mar;9(3):261-7. http://tinyurl.com/lrcw5ud
Chang HH, et al. High dose vitamin C supplementation increases the Th1/Th2 cytokine secretion ratio, but decreases eosinophilic infiltration in bronchoalveolar lavage fluid of ovalbumin-sensitized and challenged mice. J Agric Food Chem. 2009 Nov 11;57(21):10471-6. http://tinyurl.com/m7v9wsh
Huang Z, Jiang Y, Yang Y, et al. 3,3′-Diindolylmethane alleviates oxazolone-induced colitis through Th2/Th17 suppression and Treg induction. Mol Immunol. 2013 Apr;53(4):335-44. https://tinyurl.com/y72cocb3
The following supplements are suggested for you to consider in light of your relevant expertise and understanding of the needs of your client or patient. They may be used in isolation or as part of a multi supplement strategy, but at all times the consideration of their use should be tied into the specific needs of the individual you are responsible for.
Acetyl-Glutathione (ARG): 1 tablets twice daily. http://tinyurl.com/n68cpfy
Bio C Plus 1000 (BRC): 2 tablets twice daily. https://tinyurl.com/y76jx3lf
DIM Enhanced Delivery System (ARG): 1 capsule, twice daily. http://tinyurl.com/3xv4ycm
Quercetin 300 (ARG): 2 capsules twice daily. https://tinyurl.com/y7a6jf4a
Nrf2 Renew (ARG): 1-2 capsules twice daily. http://tinyurl.com/jkvywwg
For your information, here are the ingredients of the Nrf2 Renew per 2 caps:
Green Tea (standardised to 95% Polyphenols/75% Catechins/<0.5% Caffeine/40% EGCG) – 200 mg
Milk Thistle (standardised to 30% Silybines/80% Silymarin) – 200 mg
Pomegranate Extract (standardised to 40% Ellagic Acid) – 200 mg
Green Coffee PE (standardised to 45% Chlorogenic Acids/1-5% Caffeine) – 200 mg
Gingko (standardised to 24% Flavone Glycosides/6% Total Ginkgolides) – 120 mg
Olive Leaf (standardized to 20% Oleuropein) – 100 mg
Sulforaphane – 50 mg
Please consider these suggestions in light of the other clinical information pertaining to this individual. If you have any more information about the specific problems this individual is experiencing, further refinement of these suggestions may be considered. I hope this information is helpful, and if you have any further questions or information specific to the problems this individual is experiencing, please do provide feedback.
Registered Nutritional Therapist Helen Perks is collaborating with Clinical Education to bring you the first-ever Functional Medicine book club for Practitioners.
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