Against the Grain: Mycotoxins in Our Food

The story of mycotoxins begins with the story of agriculture. In prehistoric times, humans initially began farming by forest gardening, planting along river banks, and planting in the wet foothills during monsoon season. Later, more organized farming began in the Fertile Crescent, India, Western Asia, and Egypt with these crops: wheat, barley, flax, vetch, lentils, peas, and chickpeas. As time passed, peoples in the Americas, Eastern Asia, and Africa began their own farming and agriculture techniques.

In anthropology class, we learn that modern civilization was born out of the practice of agriculture, which allows for surpluses of food to be created, stored, and moved across the world. With these processes, the consumption of most food occurs long after it has been harvested. It is this storage and transport of foodstuffs which allows fungus to grow on crops. Fungus loves a warm, dark environment; and where there is fungus, there are often mycotoxins.

Mycotoxin means “fungus poison,” and is a metabolite from fungal metabolism. The term is typically reserved for toxins produced by fungi that colonize crops. However, we also use the term to describe metabolites from molds that inhabit buildings and other indoor structures. This article will focus on the toxins to which we are exposed by our food supply.

Mycotoxins are not necessary for fungal growth or reproduction; it is speculated that they are produced in order to weaken the host. Some mycotoxins, such as the well-known penicillin, are toxic to other fungi or bacteria. They are not broken down by heat or time, but are stored in animal tissue, and thus concentrated as we move up the food chain.

From a clinical perspective, I’ve often asked myself, is it possible that grain-limiting diets, paleolithic diets, gluten-free diets, and carbohydrate-limiting diets are helpful because they also limit our exposure to mycotoxins? How exactly do mycotoxins harm us? And what can be done to limit our exposure?

Mycotoxins produce an array of damaging effects on human health, and even though research on these poisons is scarce, this article will attempt to detail what is currently known.

What Are the Major Groups of Mycotoxins?
There are six major types of mycotoxins: aflatoxins, fusarium toxins, patulin, ergot alkaloids, citrinin, and ochratoxin.

Aflatoxins
Aflatoxins are produced by Aspergillus, and refer to 4 different subtypes: B1, B2, G1, and G2. Aflatoxins are mutagenic, carcinogenic, hepatotoxic, and immunosuppressive. They negatively affect DNA synthesis, DNA repair, RNA synthesis, and protein synthesis. In one study, rats exposed to B1, the most common aflatoxin, grew hepatic tumors. Twenty percent also had colon tumors, and a small number had cancer of the kidney, oral cavity, and hematopoietic system.1 In a another study looking at the synergy between hepatitis B and liver cancer, the authors concluded that exposure to aflatoxin greatly magnifies the chance of liver cancer in individuals infected with both the hepatitis B and C viruses. They state that “reducing aflatoxin exposure to non-detectable levels could reduce [hepatitis] cases in high-risk areas by about 23%.”2

Aflatoxins and lung cancer. Another study demonstrated aflatoxin G1 induced lung cancers. Compared with control mice receiving no aflatoxin G1 (AFG1), bronchial epithelial hyperplasia, alveolar hyperplasia, and adenocarcinoma of lung were observed in mice receiving AFG1 treatment. The incidences of bronchial epithelial hyperplasia, alveolar hyperplasia, and adenocarcinoma of lung were 60.0%, 10.0%, and 30.0% respectively, for mice receiving 3 microgram/kg AFG1 and 28.6%, 35.7%, 42.9% for mice receiving 30 microgram/kg of the toxin, respectively.3

Aflatoxins and infertility. A review article on the effects of aflatoxins on reproduction looked at 121 potential studies, of which 25 were retained. One study found a higher concentration of aflatoxins in the semen of infertile men (40% of cases compared with 8% of controls). Six studies found significant associations or correlations between low birth weight and aflatoxins. One study found maternal serum aflatoxin to be a risk factor for jaundice in infants. In addition, maternal breast milk in developing countries had higher rates of aflatoxin contamination than in high-income countries.4

Aflatoxins and immunity. In addition to promoting cancer, aflatoxins exert an immunosuppressive response on their host. When macrophages were exposed to aflatoxin B1 and B2, followed by bacterial stimulation, they produced very high levels of IL-6 and low levels of IL-10 compared with controls. Other markers of immune reactivity varied as well.5 Another study demonstrated earlier apoptosis of human lymphocytes on exposure to aflatoxins.6

Can the effects of aflatoxin exposure be reduced? Aflatoxins are detoxified through the cytochrome p450 pathway, specifically the CYP3A4 pathway. This detoxification pathway creates high levels of oxidative stress in the body. In one research study, antioxidants such as vitamins A, C, and E were shown to reduce oxidation from aflatoxin processing in the liver.7

Lactic-acid producing bacteria have been reported to remove mycotoxins from aqueous solution through binding properties. In one study, researchers used Lactobacillus casei and Lactobacillus reuteri in mice exposed to aflatoxin. They measured many parameters and noted that aflatoxins decreased food intake and body weight, increased serum alkaline phosphatase, cholesterol, triglycerides, uric acid, creatinine, and lipid peroxidation in the liver, and decreased antioxidant status. Both strains of lactobacillus were effective in improving all biochemical parameters.8

Aflatoxins have been found in the majority of grain crops, including corn, cottonseed, millet, cassava, tobacco, peanuts, rice, sunflower seeds, wheat, and chilies. Aflatoxin has been found in eggs, milk, and meat when animals have been fed contaminated food.9

Fusarial Mycotoxins
Fusarial mycotoxins include fumonisins and trichothecenes. Pathogenic species of Fusarium will infect barley crops, especially if there is rain late in the season. They can also be found in wheat. Fusarial infections in humans can occur in the nailbeds or in the cornea. In immunocompromised patients (such as HIV patients), a fusarial infection can disseminate through the bloodstream and pose a serious health threat.10 The most important fusarial mycotoxin, zearalenone, will be discussed shortly.

Patulin
Patulin is a mycotoxin produced by both Aspergillus and Penicillum. It grows alongside apples and is milder in toxicity. Patulin is an antibiotic and is thought to be mildly carcinogenic. The World Health Organization recommends no more than 50 micrograms per liter in apple juice. In one study, researchers depleted intracellular levels of glutathione and noted an increase in chromosomal damage from patulin exposure.11

Ergot Alkaloids
Ergot alkaloids are produced by the Claviceps purpurae fungus, which infects rye and other cereal grains. Ergotism is the proposed mechanism for bewitchment in the Salem witch trials as well as the condition termed St. Anthony’s fire. Acute poisoning affects the nervous, gastrointestinal, and vascular systems. Symptoms include headaches, mania, diarrhea, nausea, vomiting, seizures, spasms, paresthesias, edema, and gangrene of the fingers and toes.12

Citrinin
Citrinin is found in wheat, rice, corn, barley, oats, rye, cheese, sake, miso, and soy sauce. It is produced by Penicillium species and Aspergillus species. Citrinin has been shown to reduce testosterone secretion from Leydig cells in rat models.13 Citrinin is known to be nephrotoxic and has been shown to damage chromosomes in human kidney cells. It has been proposed as the cause of an extremely high rate of endemic kidney disease in Eastern Europe.14

Ochratoxin
Ochratoxin is produced by Penicillium and Aspergillus species and is found in juices, beer, and wine. Ochratoxin has been found to increase CRP (C-reactive protein) levels in those with higher serum ochratoxin levels.15 In vitro, ochratoxin induced kidney cell apoptosis.16

Mycotoxins and Breast Cancer
One very interesting mycotoxin, zearalenone (ZEN), is considered a mycoestrogen. ZEN shares a molecular structure close to that of estrogen. It is known to activate estrogen receptors and create reproductive system changes in both animals and humans. Currently, the reduced form of this mycotoxin, alpha-ZEA ralenol, is used as an anabolic agent – a substance used to fatten up cattle. Alpha-ZEA ralenol and ZEN both have patents on them as human oral contraceptives. ZEN has been used since 1969 in the cattle industry to increase animal growth rate in the US, but has been banned by the European Union. ZEN has been associated with breast enlargement in humans, and has been included in some of the over-the-counter breast-enhancing dietary supplements. In vitro, ZEN has promoted breast cancer cell growth in estrogen receptor positive cancers.17 In another study, zearalenone was found in hyperplastic and neoplastic endometrial tissue, but not in normal endometrial tissue.18

How Much Mycotoxin Is in Our Food?
Mycotoxin levels in food for human and livestock consumption are being regulated by the US government. I could not, however, find the specifics on how this is done. Another route to answering this question is to look at kits marketed to farmers and food producers to test the grains that they feed their animals as well as the foods that they produce. Several online companies advertise testing for mycotoxin levels. These include Vicam, Trilogy, Pickering, and Neoventures.

How Can We Lower Our Exposure to Mycotoxins?
Limiting our consumption of these foods naturally limits mycotoxin exposure:

  • grains, including corn
  • dried fruits
  • dairy
  • meat that has been fed a grain-based diet
  • beer and wine
  • apple-based products
  • nuts, especially peanuts

There is very little research comparing organic and conventional food mycotoxin levels. However, studies that looked at 24 different foods noted a 50% decrease in mycotoxin levels in organic versus conventional foods. The authors speculated on several reasons for the difference seen. First, fungicides applied to crops actually increase mycotoxin amounts, as the chemical puts a stress on the organisms, triggering them to produce higher levels of mycotoxins. Second, synthetic nitrogen fertilizers used on conventional plants accelerate fungal growth on the plants.19 This is yet another reason to choose organic fruits, vegetables, and grains over conventional ones.

Can We Test for Exposure?
An extensive search on the Internet did not show any reliable clinical tests available for foodborne mycotoxins. There are, however, clinical tests available for exposure to environmental molds. In my practice, I would treat mycotoxin exposure like any other toxin exposure, with support through the detoxification cytochrome p450 and subsequent liver pathways with diet modification, nutraceuticals, herbs that support the liver, colon hydrotherapy, cardiovascular exercise, fiber, and probiotics.

More universally, I am seeing issues with grains from a fungal/mycotoxic perspective and not from gluten or allergic perspective. Even if a patient tests negative for gluten allergy or celiac disease, I am inclined to ask him or her to limit grain, corn, peanut, beer, and wine consumption – especially in the presence of any chronic disease. Patients simply feel better when they limit these foods.

Fungi are not our universal enemies; they are necessary for life on planet Earth. Fungi are the major decomposers and recyclers in ecosystems. They are responsible for degrading organic material into inorganic material, which then reenters anabolic pathways in plants and other organisms. But when we grow food to be consumed much later than it was harvested, the potential for fungal contamination is there. The issue of mycotoxins in our food is a result of how, as modern civilization, we have moved away from small-batch, local, and traditional farming practices. Always, fresh is best … and a diet of recently harvested organic fruits, vegetables, and non-grain-fed animal protein is the best way to limit our mycotoxin exposure.

Notes
1.  Ward JM, Sontag JM, Weisburger EK, Brown CA. Effect of lifetime exposure to aflatoxin b1 in rats. J Natl Cancer Inst. 1975 Jul;55(1):107–113.
2.  Liu Y, Chang CC, Marsh GM, Wu F. Population attributable risk of aflatoxin-related liver cancer: Systematic review and meta-analysis. Eur J Cancer. 2012 Mar 8.
3.  Huang XH, Zhang XH, Li YH, Wang JL, Yan X, Xing LX, Wang FR. [Experimental lung carcinogenic in vivo study of aflatoxin G1 in NIH mice]. Zhonghua Bing Li Xue Za Zhi. 2004 Jun;33(3):260–263.
4.  Shuaib FM, Ehiri J, Abdullahi A, Williams JH, Jolly PE. Reproductive health effects of aflatoxins: a review of the literature. Reprod Toxicol. 2010 Jun;29(3):262–270.
5.  Bruneau JC, Stack E, O’Kennedy R, Loscher CE. Aflatoxins B(1), B(2) and G(1) modulate cytokine secretion and cell surface marker expression in J774A.1 murine macrophages. Toxicol In Vitro. 2012 Mar 16.
6.  Wang H, Sun X, Zhang X, Zuo L. [Effect of deoxynivalenol and aflatoxin G1 on apoptosis of human blood lymphocytes in vitro]. Wei Sheng Yan Jiu. 1999 Mar 30;28(2):102–104.
7.  Alpsoy L, Yalvac ME. Key roles of vitamins A, C, and E in aflatoxin B1-induced oxidative stress. Vitam Horm. 2011;86:287–305.
8.  Hathout AS, Mohamed SR, El-Nekeety AA, Hassan NS, Aly SE, Abdel-Wahhab MA. Ability of Lactobacillus casei and Lactobacillus reuteri to protect against oxidative stress in rats fed aflatoxins-contaminated diet. Toxicon. 2011 Aug;58(2):179–186.
9.  Fratamico PM et al., eds. Foodborne Pathogens: Microbiology and Molecular Biology. Horizon Scientific Press; 2008.
10.Bourgeois GP, Cafardi JA, Sellheyer K, Andea AA. Disseminated Fusarium originating from toenail paronychia in a neutropenic patient. Cutis. 2010 April;85(4):191–194. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2926817.
11.Glaser N, Stopper H. Patulin: Mechanism of genotoxicity. Food Chem Toxicol. 2012 May;50(5):1796–801.
12.Schardl CL, Panaccione DG, Tudzynski P.Ergot alkaloids – biology and molecular biology. Alkaloids Chem Biol. 2006;63:45–86. Available at http://bitnest.ca/Silo42/10.1016/S1099-4831(06)63002-2.pdf.
13.Liu S, Wang D, Zhang J, et al. Citrinin reduces testosterone secretion by inducing apoptosis in rat Leydig cells. Toxicol In Vitro. 2012 May 4.
14.Frank HK. Citrinin. Z Ernahrungswiss. 1992 Sep;31(3):164–177.
15.di Giuseppe R, Bertuzzi T, Rossi F, et al. Plasma ochratoxin A levels, food consumption, and risk biomarkers of a representative sample of men and women from the Molise region in Italy. Eur J Nutr. 2011 Oct 29.
16.Li Z, Zhang X, Cui J, Kang W. Assessment on pollution of Ochratoxin A in grain in China and its apoptosis effect on vitro-cultured human tubular kidney cells. J Biochem Mol Toxicol. 2012 Mar–Apr;26(4):139–146.
17.Pazaiti A, Kontos M, Fentiman IS. ZEN and the art of breast health maintenance. Int J Clin Pract. 2012 Jan;66(1):28–36.
18.Tomaszewski J, Miturski R, Semczuk A, Kotarski J, Jakowicki J. [Tissue zearalenone concentration in normal, hyperplastic and neoplastic human endometrium]. Ginekol Pol. 1998 May;69(5):363–366.
19.Benbrook CM. Breaking the Mold: Impacts of Organic and Conventional Farming Systems on Mycotoxins in Food and Livestock Feed [online report]. Organic Center. Summary: http://www.organic-center.org/reportfiles/Mycotoxin2Pager.pdf.

Amy TerlisnerDr. Amy Terlisner attended the University of Georgia in Athens, Georgia, where she obtained a BS in holistic medicine, a degree that she customized for her later studies in naturopathic medicine. She graduated summa cum laude (with highest honor) and published an undergraduate thesis in health psychology. Dr. Terlisner then attended Bastyr University in Seattle, Washington. She has an extensive teaching background and has taught physiology, anatomy, clinical laboratory diagnosis, pharmacognosy, physical exam diagnosis, and manipulation at the doctorate level. Her specialties include women’s health, cardiovascular disease, gastroenterology, anti-aging medicine, and natural hormone replacement therapy. Dr. Terlisner is the current president of the Arizona Association of Naturopathic Physicians and owns ALETRIS Center of Integrative Medicine, located in Scottsdale, Arizona.

Tagged , , , , , , , . Bookmark the permalink.

Leave a Reply

Your email address will not be published. Required fields are marked *

* Copy This Password *

* Type Or Paste Password Here *