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Human

Effects of mycotoxins in humans

Mycotoxins can cause immunosuppression at levels that are undetectable by routine screening methods
Professor Vincent Cheng

 

Humans are exposed to mycotoxins due to various reasons. They can consume contaminated plant derived foods, like cereals, oilseeds, spices and tree nuts. Due to carry over of mycotoxins from animal feed, exposition can also accure by the consumption of animal products such as milk, meat and eggs. Furthermore they can be exposed to air or dust containing the toxins.1,2 Mycotoxins of greatest public health significance range from aflatoxins, ochratoxins, trichothecenes, fumonisins, zearalenone and ergot alkaloids.3 

In regions where food security standards are high, mycotoxin exposure does not represent a significant risk for humans. Risk can be high in regions where no regulations are enforced, climate promotes fungal growth or if food scarcity leads to consumption of unsuitable food. The symptoms of mycotoxicoses (diseases associated with mycotoxins) depend on the type of the mycotoxin, the amount and the duration of mycotoxin exposure, and the age, sex and health of the exposed individual. Furthermore there are many poorly understood synergistic effects that might play an important role in the development of mycotoxicoses.4

Aflatoxins

Aflatoxins can contaminate numerous food products, like cereals (maize, sorghum, rice, wheat), oilseeds (groundnut, soybean, sunflower), spices (chillies, black pepper, coriander), tree nuts (almonds, pistachios, walnuts, coconuts) and milk and milk products.5 Around 4.5 billion individuals of the world’s population are exposed to aflatoxins.6 Aflatoxins represent a group of naturally occurring carcinogens. The diseases resulting from aflatoxin intoxication are called aflatoxicoses and can be divided into acute and chronic diseases. Acute aflatoxicoses result from the consumption of moderate to high levels of aflatoxin and lead to hemorrhage, acute liver damage, malnutrition and possibly death (e.g. aflatoxin outbreak in 2003 in Kenya, where 120 people died), mainly in children. In children aflatoxins are associated with kwashiorkor and marasmus, diseases leading to death due to protein malnutrition. Chronic aflatoxicoses result from the ingestion of low to moderate levels of aflatoxins. Aflatoxins are highly liver carcinogenic with toxicity and carcinogenic potential decreasing from B1>M1>G1>B2>G2. Aflatoxin B1 is classified as group 1 carcinogen (human carcinogen) by the IARC and is strongly associated with primary hepatocellular carcinoma, especially in individuals already exposed to hepatitis B, representing a heavy cancer burden in developing countries.4,6,7 Aflatoxins have also been reported to have effects on the digestive system, like vomiting, diarrhea and intestinal hemorrhage. Furthermore Aflatoxins are associated with neoplasms in extrahepatic tissues, particularly in the lungs, reported for example in Dutch peanut processing workers.6 In recent years immunosuppressive effects as well as  nutritional and toxic encephalopathy have been reported. Encephalopathy can lead to loss of balance, recent memory decline, headaches, insomnia and loss of coordination.6,8 Strong evidence exists that aflatoxin exposure can increase susceptibility to infectious diseases. Only recently it has been published that co-occurrence of aflatoxin and human immunodeficiency virus (HIV) might lead to faster progression to acquired immune deficiency syndrome (AIDS) in infected individuals.9 Aflatoxin M1, the metabolite of aflatoxin B1 present in milk and milk products, is classified as group 2B carcinogen and affects mostly young individuals but also adults. It leads to vomiting, abdominal pain, pulmonary edema and also necrosis of the liver.6,10 This provides evidence that aflatoxin M1 is of great concern also for Serbian adult population.11,12

Aflatoxin B1

Ergot alkaloids

Ergot alkaloids can contaminate a variety of grass species, including small grains. Ergotism is one of the oldest known mycotoxicoses. Already in the Middle Ages a disease called “St. Anthony’s Fire” was described by affected individuals as sensation of fire shooting from the tips of their appendages.10 Two types of Ergotism exist: the gangrenous form (characterized by dermal lesions) and the convulsive form (provoking effects on central nervous and gastrointestinal tract).10

Ergotamine

Fumonisins

Fumonisins are mainly found in maize-containing food. Amongst the existing fumonisin compounds, the fumonisin B group is the most important regarding food contamination. Fumonisin B1, the most abundant one, was classified by the IRAC as group 2B carcinogen.4,7 Fumonisin B1 is suspected as tumor promotor. A probable link exists to esophageal cancer, as coincidence of esophageal cancer and high occurence of fumonisin B1 contamination was reported for example in the Transkei in South Africa.4,17 Fumonisins are also reported to lead to transient abdominal pain and diarrhea. Furthermore they are associated with neural tube defects like spina bifida or anencephaly, as they inhibit the uptake of folic acid.4,7

Fumonisin B1

Ochratoxins

The main toxin in this group, ochratoxin A (OTA), is found in wheat, corn, oats, cheese and meat products, but also may be found in soybeans, beans, nuts, dried fruit, coffee, grapes and grape products. In Chile studies have shown the presence of ochratoxin A in human breast milk. The OTA intake of breastfed infants exceeded the tolerable daily intake giving rise to the suggestion to give dietary recommendations for pregnant women and nursing mothers to reduce OTA exposure of newborn.13 Ochratoxin A was classified as a group 2B carcinogen (possibly carcinogenic in human) by the International Agency for Research of Cancer (IARC).7 Ochratoxin A is a potent nephrotoxin with the kidney as its primary target organ, but might also affect the liver.4 Furthermore ochratoxin A is suspected to cause a human disease called Balkan Endemic Nephropathy, affecting the kidneys and often resulting in tumors.10

Ochratoxin A

Trichothecenes

The most important representative of trichothecenes affecting human health is deoxynivalenol (DON). T-2 toxin and its metabolite HT-2 and Nivalenol can also occur in food. Trichothecenes occur mainly in grains and cereals, for example breakfast cereals, but they occur also in beer. DON is also called vomitoxin as it can be the reason for vomitus. Further symptoms related to DON are acute temporary nausea, diarrhea, abdominal pain, headaches, dizziness and fever.14 Historical evidence suggests that DON causes acute human illness, as outbreaks of human gastroenteritis after consumption of Fusarium-infested foods were reported in Korea and China.15 It also might act as an immunosuppressant and cause kidney problems.10 T-2 toxin and its metabolite HT-2 cause mainly diseases of the immune system and is associated with reduced food intake and vomiting.10 Historically, T-2 toxin in grain infected with different species of Fusarium led to a disease called “Alimentary Toxic Aleukia” during the second world war in Russia, an incredibly vicious disease including vomiting, diarrhea, profuse sweating, swelling, necrosis of the oral cavity and others.16 Furthermore direct skin contact with trichothecenes might lead to dermatosis.4

T2-Toxin

Zearalenone

Zearalenone (ZEN) is very often found in grains, but also a huge range of other commodities as soybeans can be contaminated. ZEN has limited, but due to its oestrogen-like activity it can disrupt steroid hormone functions when being consumed in sufficient levels. This might lead to hyper-oestrogenism in humans.7 Precocious pubertal changes in young children have been reported in Puerto Rico18 and gynecomastia with testicular atrophy in rural males in southern Africa.19 Cases of premature breast development in girls under 8 years of age related to ZEN-contaminated food intake were reported in Hungary and Italy.20

AFB1 – Aflatoxin B1 | AFM1 – Aflatoxin M1 | DON – Deoxynivalenol | FUM – Fumonisins | OTA – Ochratoxin A | T-2 – T-2 Toxin | HT-2 – HT-2 Toxin | ZEN - Zearalenone | Ergots – Ergot, Alkaloids
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