Monday, August 26, 2019

Mycotoxins Increase The Risk Of Cancer

Mycotoxins Increase The Risk Of Cancer

Mycotoxins have been shown to obstruct apoptosis or programmed cell death.

Mycotoxins are toxins are just as their name implies: myco = fungus and toxin = toxin. These toxins originate from a fungus that commonly grows in the food supply and in water damaged areas. Mycotoxins will increase the chance of cancer developing in the human body.

Mycotoxins have been shown to be [39] [40]:

  • Carcinogenic
  • Mutagenic
  • Teratogenic
  • Immunotoxic
  • Hepatoxic
  • Hemorrhagic
  • Nephrotic
  • Neurotoxic
  • Dermatoxic
  • Endocrine (hormone) disruptors

Mycotoxins can be defined as “natural products produced by fungi that evoke a toxic response when introduced in low concentration to higher vertebrates and other animals by a natural route“ [41]. Mycotoxins are some of the most well-known toxins to contaminate the food supply including but not limited to aflatoxin, ochratoxin, fumonisins, patulin, zearalenone (ZEA), and trichothecenes from the fungus Aspergillus, Fusarium, and Penicillium.

In addition, mycotoxins are found in water-damaged walls, wallpaper in homes, buildings… Not all mycotoxins are inherently toxic as the antibiotic penicillin is a mycotoxin. The question lies in where is the toxicity directed?

Mycotoxins Are Affecting People Globally

Mycotoxins are a world-wide problem affecting an approximate 25% [42] of the world’s food supply. Mycotoxins are most commonly found in the grain and cereal foods i.e. wheat, barley, nuts, corn, rice… Even the coffee in your morning cup of joe is a potential source—so sad.

These food items are commonly stored at room temperature in containers on the counter in the kitchen or in foods stored in the pantry or on the store shelf which is in part the origin of the risk. Don’t forget about animal products, such as beef, chicken, milk, eggs… that are raised on mycotoxin contaminated rich foods are also a potential exposure source.

Zearalenone is one of the most common mycotoxins that the U.S. food supply is at risk for. Animal and human studies have shown that zearalenone does accumulate in the body [43] [44]. This is huge because if these low exposures to 1,000s of potentially toxic chemicals are quickly cleared, then the risk and concern is limited; however, if these toxins bioaccumulate, then the low exposures to 1,000s of potentially toxic chemicals are, in fact, accumulating ticking time bombs.

Zearalenone is an endocrine disruptor; specifically, zearalenone mimics estrogen [45]. Zearalenone readily binds to the estrogen receptors (ER). Zearalenone stimulates an estrogenic signal through the specific binding to the ER-alpha receptors, not ER-beta [46].

This preferential ER-alpha affinity shifts the ER-alpha/ER-beta receptor balance to an ER-alpha dominance. This affinity of zearalenone for ER-alpha and ER-alpha dominance has been shown to increase the risk of breast cancer [47], esophageal [48], colorectal cancer [49] and prostate cancer [50].  Specifically, this mycotoxin has been shown to inhibit apoptosis (programmed cell death) stimulate proliferation, promote cancer cell invasion and metastatic spread of cancer cells 45 [51] [52].

Most interesting is that this powerful estrogenic signal, peak proliferation, and invasion occurred at the lowest levels of exposure. This has enormous implication as most people are not exposed to acute, high toxic loads of mycotoxins, or any toxin for that matter, but instead are exposed to small, regular, indolent exposures to hundreds of toxins every day.

Again, evidence shows that toxins like zearalenone can bioaccumulate in the environment and the human body. It is this regular exposure, bioaccumulation and synergistic toxic effects of these multiple toxins that change the environment in our body to increase the risk of cancer.

The Effects of Mycotoxins and EMF’s

 As in all things, disease such as cancer is never the result of 1 item. It is the collective, synergistic effects that come together to affect disease risk. This is no more evident than in the growing volume of research that points to the synergistic effect of EMFs and mycotoxins.  EMFs are all around us in our day-to-day activities and our home is the biggest offender.  Common sources of EMFs include:

  • Cellphones
  • Wi-Fi
  • Wi-Fi dependent devices
  • TVs
  • Radios
  • Power lines
  • Microwave ovens
  • Computers

Our home environment can no longer be simply defined by the walls and roof of our house/apartment/Condo… but these home sources of Wi-Fi exposure even travel with us in our personal cellphones, car Wi-Fi… In fact, with the 4G and the coming 5G wave, EMFs are essentially becoming another element in our atmosphere home: Oxygen—check, CO2–check, EMFs—check.

Yet, we really don’t know what the long-term impact will be. The same mistakes are repeated time and time again. The new definition of our home environment must now include the immediate environment of our body wherever it goes.

 EMFs have their own set of carcinogenic risk issues, such as leukemia [53].  The International Agency for Research on Cancer labeled EMFs as potentially carcinogenic in 2011. Research also shows, that in addition to isolated EMF exposure risk, EMFs can actually stimulate fungal growth [54] [55].

This post is not about EMFs specifically, but about their synergistic activity with fungi which can have significant implications in the increase in mycotoxin production and mycotoxin release. Whatever the mycotoxin source exposure is (food, water-damaged houses, vaping pens…), add EMF exposure, which is all around us, and the mycotoxin production, mycotoxin exposure and resultant risk i.e. estrogenic, carcinogenic risk, will increase.

It is the Consistent Exposure to Mycotoxins on a Daily Basis That Presents a Threat To Our Health

 When it comes to potential environmental toxins, in this case, mycotoxins, everybody is looking for the 1 hit phenomenon or the 1 giant bomb that definitively results in disease. That is a pie in the sky view and won’t be found except in very rare cases of exposure.

In fact, it is a basic misunderstanding of what and how toxicity can occur. In this day of 30-second commercials, sound bites, and attention, if the cause and effects are instantaneous, then they don’t exist.

This lack of patience has even permeated science. The reality is that environmental toxins can also work via what I like to call the rain of 1000 bullets. This mechanism is the regular, often unrecognized, smaller spray of hits of accumulative toxic effects will cause disease given adequate time.

It is like a shotgun versus a bomb. Odds are much better that you will survive the acute spray of a gunshot from the shotgun, compared to the direct hit by a bomb, but eventually, that spray of gunshots will do its damage and get the same job done given time.

These toxins were never approved based on long-term studies that detailed their long-term risk to the general public; except in the case of the long-term exposure tests ongoing of which we are the unwilling test subjects without our approval. Time will tell the final numbers that will be written in some future scientific publication and our unknowing participation will be a mere afterthought.

My purpose here is not to create fear, but enhance knowledge, because knowledge is power. Knowledge is the power to act. Knowledge is the power to make a difference.

39 Steyn PS. Mycotoxins, general view, chemistry, and structure. Toxicol Lett. Dec 1995;82–83: 843–851.

40 Wallace Hayes A. Mycotoxins: A review of biological effects and their role in human diseases. Clinical Toxicology.1983;17(1):45–83.

41 Bennett J.W. Mycotoxins, mycotoxicoses, mycotoxicology and mycopathologia. Mycopathologia. 1987;100:3–5. doi: 10.1007/BF00769561.

42 Alshannaq A, Yu JH. Occurrence, Toxicity, and Analysis of Major Mycotoxins in Food. Int J Environ Res Public Health. 2017;14(6):632. Published 2017 Jun 13. doi:10.3390/ijerph14060632.

43 Bennett JW, Klich M. Mycotoxins. Clin Microbiol Rev. 2003;16(3):497–516. doi:10.1128/CMR.16.3.497-516.2003.

44 Brera C., Debegnach F., De S.B., Di I.S., Gregori E., Neuhold S., Valitutti F. Exposure assessment to mycotoxins in gluten-free diet for celiac patients. Food Chem. Toxicol. 2014;69:13–17. doi: 10.1016/j.fct.2014.03.030.

45 Hueza IM, Raspantini PC, Raspantini LE, Latorre AO, Górniak SL. Zearalenone, an estrogenic mycotoxin, is an immunotoxic compound. Toxins (Basel). 2014;6(3):1080–1095. Published 2014 Mar 13. doi:10.3390/toxins6031080.

46 Kowalska K, Habrowska-Górczyńska DE, Urbanek KA, Domińska K, Piastowska-Ciesielska AW. Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells. Toxins (Basel). 2018;10(3):98. Published 2018 Feb 28. doi:10.3390/toxins10030098.

47 Pluciennik E. The role of WWOX tumor suppressor gene in the regulation of EMT process via regulation of CDH1-ZEB1-VIM expression in endometrial cancer. Int. J. Oncol. 2015;46:2639–2648. doi:10.3892/ijo.2015.2964.

48 Pitt J.I. Toxigenic fungi and mycotoxins. Br. Med. Bull. 2000;56:184–192. doi: 10.1258/0007142001902888.

49 Kwon O, Soung NK, Thimmegowda NR, et al. Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation. Cell Signal. 2011;24(4):943–950. doi:10.1016/j.cellsig.2011.12.017.

50 Kowalska K., Habrowska-Gorczynska D.E., Dominska K., Piastowska-Ciesielska A.W. The dose-dependent effect of zearalenone on mitochondrial metabolism, plasma membrane permeabilization and cell cycle in human prostate cancer cell lines. Chemosphere. 2017;180:455–466. doi: 10.1016/j.chemosphere.2017.04.027.

51 Liu Q., Wang Y., Gu J., Yuan Y., Liu X., Zheng W., Huang Q., Liu Z., Bian J. Zearalenone inhibits testosterone biosynthesis in mouse Leydig cells via the crosstalk of estrogen receptor signaling and orphan nuclear receptor Nur77 expression. Toxicol. In Vitro. 2014;28:647–656. doi: 10.1016/j.tiv.2014.01.013.

52 Ayed-Boussema I., Bouaziz C., Rjiba K., Valenti K., Laporte F., Bacha H., Hassen W. The mycotoxin Zearalenone induces apoptosis in human hepatocytes (HepG2) via p53-dependent mitochondrial signaling pathway. Toxicol. In Vitro. 2008;22:1671–1680. doi: 10.1016/j.tiv.2008.06.016.

53 Calvente I., Fernandez M. F., Villalba J., Olea N., Nuñez M. I. (2010). Exposure to electromagnetic fields (non-ionizing radiation) and its relationship with childhood leukemia: a systematic review. Sci. Total Environ. 408, 3062–3069.10.1016/j.scitotenv.2010.03.039

54 Voichuk SI, Podgorskii VS, Gromozova EN. Effect of radio-frequency electromagnetic radiation on physiological features of Saccharomyces cerevisiae strain UCM Y-517. Mikrobiol Z. 2004 May-Jun;66(3):51-7.

55 Hadjiloucas S, Chahal MS, Bowen JW. Preliminary results on the non-thermal effects of 200-350 GHz radiation on the growth rate of S. cerevisiae cells in microcolonies. Phys Med Biol. 2002 Nov 7;47(21):3831-9.

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Monday, August 19, 2019

Why Heavy Metals Are Toxic?

Why Heavy Metals Are Toxic

Why heavy metals and toxic and must be taken into consideration when being treated for cancer.

Heavy metals are some of the most well-known toxins. They include the big guns: Lead, Mercury, Aluminum and the #1 substance on the Agency for Toxic Substances and Disease Registry (ATSDR) toxin priority list—Arsenic. Heavy metals are:

  • Immunotoxic
  • Carcinogenic
  • Mutagenic (which is in and of itself carcinogenic)
  • Teratogenic

In addition to their toxicity, all have been shown to have estrogenic activity and thus have been labeled metalloestrogens. Think of that, a heavy metal that has estrogenic activity. Not only are they toxic, but they are hormonal.

How is this possible? Studies have shown these heavy metals exert their estrogenic activity through direct binding to estrogen receptors; ER-alpha to be exact. This affinity is so strong that these metals will even block estradiol (the most potent estrogen) from binding.

Through the estrogen receptors, metals will provide direct genomic signaling via what are called Estrogen Response Elements (ERE) and non-genomic signaling via activation of the well-known pro-growth signaling pathway proteins, activated in most cancers, of ERK (of the famous RAS-RAF-MEK-ERK pathway) and PI3K/Akt that interacts with mTOR.

Heavy Metals And Cancer Explained By Dr. Nathan Goodyear

Both pathways are uniformly unregulated in most types of cancers. In addition, the heavy metal cadmium has been shown to block the repair of damaged DNA [32].

One heavy metal that stands head and shoulders above the rest is cadmium.  Cadmium is the most well-known metalloestrogen.  The half-life of cadmium is an astonishing 20 years. Cigarette smoking and welding are the 2 most prominent sources of cadmium exposure.

In vitro and In vivo studies of cadmium have shown cadmium increases the cancer risk of the estrogen-sensitive uterus [33], breast [34] [35] and prostate [36] [37] organs. Even cadmium’s strong link to lung cancer is through estrogen receptor signaling [38]. The more we know, the more we realize we don’t know.

 In so many cases, the source of estrogen exposure or estrogen signaling is not through endogenous estrogen production or even through Hormone Replacement Therapy (HRT), but via these environmental estrogen-mimicking compounds.  The next example of some of these estrogen-mimicking compounds are the mycotoxins.

32 Byrne C, Divekar SD, Storchan GB, Parodi DA, Martin MB. Metals and breast cancer. J Mammary Gland Biol Neoplasia. 2013;18(1):63–73. doi:10.1007/s10911-013-9273-9

33 McElroy JA, Kruse RL, Guthrie J, Gangnon RE, Robertson JD. Cadmium exposure and endometrial cancer risk: A large midwestern U.S. population-based case-control study. PLoS One. 2017;12(7):e0179360. Published 2017 Jul 24. doi:10.1371/journal.pone.0179360

34 McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA. Cadmium exposure and breast cancer risk. J Natl Cancer Inst. 2006;98:869–873.

35 Gallagher CM, Chen JJ, Kovach JS. Environmental cadmium and breast cancer risk. Aging (Albany NY). 2010;2(11):804–814. doi:10.18632/aging.100226

36 Waalkes MK. Cadmium carcinogenesis. Mutat Res.2003;533:107–120.

37 Rapisarda V, Miozzi E, Loreto C, Matera S, Fenga C, Avola R, Ledda C. Cadmium exposure and prostate cancer: insights, mechanisms, and perspectives. Frontiers In Bioscience, Landmark. Mar 1 2018;23:1687-1700.

38 Mary O. Huff, Sarah L. Todd, Aaron L. Smith, Julie T. Elpers, Alexander P. Smith, Robert D. Murphy, Allison S. Bleser-Shartzer, Jacob E. Hoerter, Brandie N. Radde, Carolyn M. Klinge, Arsenite and Cadmium Activate MAPK/ERK via Membrane Estrogen Receptors and G-Protein Coupled Estrogen Receptor Signaling in Human Lung Adenocarcinoma Cells, Toxicological Sciences, Volume 152, Issue 1, July 2016, Pages 62–71, https://doi.org/10.1093/toxsci/kfw064

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Monday, August 12, 2019

Xenoestrogens And Cancer Connection

Xenoestrogens And Cancer

Xenoestrogens and cancer understanding the estrogenic effects in the body.

Xenoestrogens and other toxins that affect estrogen signaling. Estrogen signaling is not just confined to estradiol, estrone, and estriol. I want to take it deeper than the visible surface by stepping outside the estrogen that is produced within the body and look at estrogenic signaling that comes from environmental toxins.

You may know them as xenoestrogens. Xenoestrogens are compounds in our environment that have estrogenic effects in the body. The official definition is “man-made non-steroidal organic chemicals which have been released into the environment from agricultural spraying, industrial processes, urban waste or consumer products” [25].

Common, well-known xenoestrogens include polycyclic aromatic hydrocarbons (PAH), pesticides, polychlorinated biphenyl (PCB), dichloro diphenyl-trichloroethane (DDT), some drugs (e.g., antiepileptic drugs), fungicides, cotinine, phytoestrogens, mycotoxins, bisphenol A (a plastics additive), phthalates, alkylphenols [26].  Even heavy metals have been labeled as metalloestrogens due to their estrogenic activity [25]. All of these xenoestrogens mimic estrogen effect in estrogen signaling via the binding to estrogen receptors and through non-estrogen receptor pathways.

Dr. Nathan Goodyear Explains The Xenoestrogens and Cancer Link

What does the future hold for environmental toxins such as xenoestrogens? What does the future hold for our children and their children’s exposure? Look to the research.  A 2004 Environmental Working Group study in collaboration with outside labs found 287 chemicals in the umbilical cord blood of 10 randomly selected births of which 180 are known carcinogens.

Toxins such as Mercury, Lead, Organochlorine pesticides (OCP), Polychlorinated biphenyls (PCB) and many others were among the identified. This Environmental Work Group study was repeated in 2009 in collaboration with 5 independent labs in the U.S., Canada, and Europe and found 232 chemicals in the umbilical cord blood of babies born from 2007-2009. The toxins identified were similar and included Mercury, methylMercury, Lead, Polychlorinated biphenyls, Phalates, Bisphenol A, and Perchlorates.

BPA – bisphenol A is a Xenoestrogen

The perfect example of a xenoestrogen is bisphenol A (BPA). Bisphenol A is a xenoestrogen commonly found in plastics and is definitely one of the more ubiquitous and well-recognized xenoestrogens. BPA, as a xenoestrogen, is a very weak estrogen receptor stimulator [27].

Many discount the impact of BPA due to its weak estrogenic activity. That would be a mistake. As weak as BPA is in potency, it is strong in its ubiquitous presence in the environment. Prolonged exposure of a low potency toxin is just as dangerous as a short exposure of a high potency toxin. One could argue that it is perhaps more dangerous due to it’s indolent, gradual accumulation and effect.

What the body does with BPA is worse than the BPA itself. Scientists are discovering that the metabolites of BPA are equally prevalent and maybe even more toxic. One such metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl) pent-1-ene or MBP for short, is found to have 1,000 times the estrogenic activity of BPA alone [28] which makes up for the weak estrogenic activity of BPA.

Additionally, bisphenol A has been shown to cause a shift of the estrogen receptors from an ER-beta dominance to an ER alpha dominance by increasing the genetic encoding of ER-alpha [29] [30]. This shift to ER-alpha dominance favors inflammation and growth. All this in the low-level blood concentrations commonly found in humans. Most alarming, these low levels are found in our children and are changing our children’s response to hormones (estrogen receptors) even before they are even born [31].

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25  Darbre PD. Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. J. Appl. Toxicol. 2006; 26: 191–197.

26 Fucic A, Gamulin M, Ferencic Z, et al. Environmental exposure to xenoestrogens and oestrogen related cancers: reproductive system, breast, lung, kidney, pancreas, and brain. Environ Health. 2012;11 Suppl 1(Suppl 1):S8. Published 2012 Jun 28. doi:10.1186/1476-069X-11-S1-S8.

27 Timms BG et al. Estrogenic chemicals in plastic and oral contraceptives disrupt the development of the fetal mouse prostate and urethra. Proceedings of the National Academy of Sciences. 2005.

28 Okuda, T, Takiguchi M, Yoshihara S. In vivo estrogenic potential of 4-methyl-2,4-bis(4- hydroxyphenyl)pent-1-ene, an active metabolite of bisphenol A, in uterus of ovariectomized rats. Toxicol Lett. 2010;197:7-11.

29 Monje L, Varayoud J, Luque EH, Ramos JG. Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor alpha transcripts with alternative 5-untranslated regions in the femal rat preoptic area. J Endocrinol. July 1st, 2007;194:201-212.

30 Takao T et al. Exposure to the environmental estrogen bisphenol A differentially modulated estrogen receptor-alpha and beta immunoreactivity and mRNA in male mouse testis. Life Sci. Jan 24 2004;72(10):1159-69.

31 Schonfelder G, Flick B, Malsness C, Paul M, Chahoud I. In Utero Exposure to low doses of Bisphenol A lead to Long-term deleterious effects in the Vagina. Neoplasia. March 2002;4(2): 98-102.

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