Zearalenone

Zearalenone is a mycotoxin produced by Fusarium fungi, commonly contaminating cereal crops like corn, wheat, barley, sorghum, and oats, especially under conditions of high humidity and low temperatures. 

Mycotoxins, produced by molds, can cause acute and chronic symptoms across multiple body systems.

Zearalenone exhibits potent estrogenic activity, resembling the hormone estrogen, and competes with 17β-estradiol for estrogen receptors. 

This property allows Zearalenoneto act as an endocrine disruptor, leading to various health issues in animals and humans, including reproductive disorders and potential carcinogenic effects. 

Zearalenone contamination in the food chain poses significant health risks, affecting a wide range of food products and leading to hyperestrogenism in animals, particularly swine and cattle. 

In humans, Zearalenoneexposure is associated with reproductive diseases and other health concerns, highlighting the importance of addressing and mitigating its presence in food and feed.

What is Zearalenone?

Zearalenone is a mycotoxin produced by Fusarium fungi species that frequently contaminates cereal crops [4., 7.].

It commonly contaminates corn, wheat, barley, sorghum, oats, and other crops, particularly under conditions of high humidity and low temperatures (10-15°C) [1.].

It exhibits potent estrogenic activity, which can be enhanced by certain metabolites [7.].  

Zearalenone's structure resembles estrogen, allowing it to compete with 17β-estradiol for estrogen receptors [4.].  This endocrine-disrupting property can lead to various health issues in animals and humans, including reproductive disorders and potential carcinogenic effects [4., 7.].

Zearalenone in the Food Chain

Zearalenone's presence in the food chain poses significant health risks. It can accumulate in living organisms and contaminate various trophic levels, from crops to human consumers [4.]. 

Zearalenoneis not removed during processing and affects various food products including cereals, meat, milk, wine, beer, dried fruits, and spices [9.].

In animals, Zearalenone is linked to hyperestrogenism, with swine being the most sensitive to its effects [1.]. 

Effects in swine include vulva swelling, vaginal prolapse, uterine enlargement, mammary gland enlargement, infertility, embryonic death, and reduced litter size [1., 16.]. 

In cattle, high zearalenone levels can cause infertility, mammary gland enlargement, reduced milk production, and vaginal issues, especially in immature dairy heifers [1.]. Poultry are less susceptible, but large concentrations can lead to vent enlargement and secondary sex characteristics [1.].

Some countries have established regulatory limits for Zearalenone in certain commodities [19.].

Zearalenone’s Effects on Human Health 

Zearalenone as a Xenobiotic and Endocrine-Disrupting Chemical

Zearalenone (ZEA), a mycotoxin produced by Fusarium fungi, is a xenoestrogen that can disrupt hormonal balance in humans [3.]. 

It structurally resembles estrogen, allowing it to bind to estrogen receptors and exert estrogen-like effects [17., 18.]. 

As a xenoestrogen Zearalenone mimics natural estrogens, binding to estrogen receptors and disrupting hormonal balance, potentially leading to reproductive diseases such as prostate, ovarian, cervical, and breast cancers [9.].

Studies have shown that Zearalenone exposure can result in conditions such as precocious puberty in young girls and hyperestrogenic syndromes in humans, highlighting its significant impact as an endocrine disruptor [17.].

Zearalenone’s Carcinogenic Potential

The structure of Zearalenone resembles natural estrogen, allowing it to bind to estrogen receptors and exhibit estrogenic activity [2.].

This can lead to endocrine disruption and promote the proliferation of estrogen receptor-positive cell lines [2.].

Zearalenone also causes oxidative damage, endoplasmic reticulum stress, apoptosis, and systemic toxic effects, including reproductive toxicity, hepatotoxicity, and immunotoxicity [2., 18.].

Zearalenone's carcinogenic potential is linked to its ability to stimulate cell proliferation at low doses and induce cell death at high doses through multiple mechanisms, including oxidative stress and DNA damage [2., 18.].

Mechanism of Action of Zearalenone

Zearalenone exhibits estrogenic activity, which is enhanced in certain reductive metabolites, potentially disrupting the endocrine system in humans and animals [3., 7.].

Zearalenone is efficiently metabolized in the human intestines, producing α-zearalenol and β-zearalenol as primary metabolites [14.].

The intestinal metabolism of Zearalenone produces α-zearalenol as the predominant metabolite, which has the strongest estrogenic activity and is preferentially transferred to the basal side of intestinal cells [14.]. 

In contrast, other metabolites remain primarily in the intestinal lumen [14.]

Once inside the body, Zearalenone and its metabolites, both of which have estrogenic activity, can affect the synthesis and secretion of sex hormones, including testosterone, estradiol, and progesterone, by influencing the production of FSH and LH in the pituitary gland [17.]. 

It can also reduce Leydig and granulosa cells through oxidative stress and cell apoptosis [17.].

Symptoms Associated with Endocrine-Disrupting Chemical Accumulation in Humans [6., 12.] 

Mycotoxins, produced by molds, can cause acute and chronic symptoms across multiple body systems [11.]. 

As a mycotoxin and an endocrine disrupting chemical (EDC), zearalenone buildup in the human body can manifest in a variety of ways.  Some of the more commonly seen symptoms include: 

Reproductive Disorders

• Decreased sperm count and quality

• Testicular and ovarian abnormalities

• Increased incidence of testicular, prostate, and breast cancers

Thyroid Disruptions

• Hypothyroidism or hyperthyroidism

• Altered thyroid hormone levels

Metabolic Issues

• Obesity

• Diabetes

• Cardiovascular problems

Neuropsychiatric Symptoms

• Alzheimer's disease

• Schizophrenia

• Nerve damage

Carcinogenic Effects

• Increased risk of hormone-dependent cancers such as cervical, ovarian, and prostate cancer

General Endocrine Disruptions

• Oxidative stress

• Altered steroid hormone metabolism

• Interference with estrogen, androgen, and thyroid hormone receptors

Homeostatic Imbalances

• Disturbed balance of hormonal functions

• Increased oxidative damage

• Endoplasmic reticulum stress

Developmental and Growth Issues

• Impaired sexual and reproductive development

• Developmental delays in offspring exposed during pregnancy

Laboratory Testing for Zearalenone

Challenge with Zearalenone Testing: Zeranol vs. Zearalenone [13.]

Zeranol (7α-zearalanol) is a semi-synthetic estrogenic veterinary drug with growth-promoting properties, banned in the European Union since 1981 and recognized as a prohibited substance in sports due to its anabolic effects. 

The challenge in differentiating between illegal use of zeranol and unintended contamination from the mycotoxin zearalenone, which naturally converts to zeranol, poses a significant issue.

Zeranol is banned in animal husbandry and sports. However, it can be metabolically derived from the mycotoxin zearalenone found in contaminated food.

Differentiating between deliberate doping and contamination is crucial. Routine doping controls monitor zeranol, its metabolites, and related mycotoxins using validated gas chromatography-mass spectrometry methods.

An administration study revealed only ultra-trace amounts of zearalenone metabolites after zeranol intake, suggesting contamination as the cause in doping cases rather than direct misuse.

Test Information, Sample Collection, and Preparation

Laboratory companies often utilize urine samples to test for the presence of mycotoxins such as zearalenone. 

Enzyme-linked immunosorbent assay (ELISA) is a widely used method for detecting zearalenone. These methods typically involve the production of monoclonal antibodies against zearalenone. 

ELISA methods have shown good specificity for Zearalenone, with some cross-reactivity observed for structurally similar compounds [5., 15.]. 

Samples can be collected from the comfort of home. It is essential to consult with the ordering provider prior to sample collection, as the provider may recommend the use of certain supplements or medications, or alternatively, the temporary avoidance of certain supplements or medications. 

Do not stop or alter any medications without speaking to a licensed healthcare provider. 

Interpreting Zearalenone Test Results

Optimal Levels of Zearalenone

Zearalenone is a mycotoxin, a xenobiotic and an endocrine-disrupting chemical, with no known benefit to human or animal health. Therefore, optimal levels are undetectable.

One laboratory reports the following optimal level of zearalenone as < 0.5 ppb, and equivocal levels as 0.5-0.7 ppb. Zearalenone is present at levels of 0.7 ppb or more [10.].

Clinical Significance of Elevated Zearalenone Levels

Elevated zearalenone testing indicates the presence of zearalenone in the body, which can cause hormone imbalance, reproductive and metabolic disturbances, and increase an individual’s risk of cancer. 

Treatments for Zearalenone Toxicity

The presence of elevated zearalenone in an individual should prompt further assessment for the presence of additional mycotoxins, as well as other environmental toxins such as glyphosate.

Mycotoxins, produced by molds, can cause acute and chronic symptoms across multiple body systems [11.]. Similarly, glyphosate, a widely used herbicide, has been detected in human urine, with higher levels found in chronically ill individuals, in children, and in people consuming a diet high in cereals [8.].

Once discovered, a comprehensive detoxification protocol should be considered under the guidance of a licensed healthcare professional. A protocol should take into consideration an individual’s test results, symptoms, nutrition status, lifestyle, and other essential factors. 

Always consult a licensed healthcare professional prior to beginning any new supplement, detoxification, or other protocols. 

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