Aflatoxin-A Common Food Mycotoxin
- Aflatoxins are a mycotoxin (mold toxin) made by the mold Aspergillus flavus, Aspergillus parasiticus and to a lesser amount, Aspergillus nominus. There are four main aflatoxins produced by A. flavus and A. parasiticus known as B1, B2, G1 and G2. "B" and "G" refer to the blue or green fluorescence observed upon exposure of the toxin to ultraviolet irradiation. (Aspergillus also makes Ochratoxin.)
In animals, and humans metabolism via hydroxylation of B1 and B2 will change them into the metabolites M1 and M2 which will appear in milk, eggs, urine and feces. Aflatoxin B1 or AFB1 is the most predominant in both human and animals foods. Since AFB1 is a strong carcinogen and is found on corn crops which is abundantly used as feed for animals and humans, contamination of corn is taken very seriously and there is much research on methods to lower contamination, and/or bind the aflatoxins so they are not absorbed by animals, or humans.
The World Health Organizations standards for aflatoxins in human food are as follows: The maximum levels for aflatoxins in various nuts, grains, dried figs and milk are in the range of 0.5 to 15 μg/kg(a μgram is one millionths [1×10-6] of a gram)
Where & When Aspergillus & Aflatoxins Are Found
Aspergillus is a soil-dwelling organism that is found all over the world but tends to be more common near the equator, and in areas that are hot, and humid, However, it grows on relatively low moisture content substrate foods. Many grains and nuts create an environment that Aspergillus thrives in.
Bombs an ballistic missles loaded with aflatoxin were stockpiled and possibly deplyed by Iraq during the first Golf War. It is thought it may have caused amyotrphic lateral sclerosis in veterans in Operation Desert Storm. There could be delayed neurotoxic effects caused by the aflatoxins.
The Discovery Of Aflatoxin
Aflatoxin was discovered in the food supply after 10,000 turkeys died from contaminated peanuts in England. Aflatoxin has been the cause of deaths in humans and animals as well as birds.
Specifics Of Where You Find Aflatoxin
Common Foods: Grains, Forage Crops, Assorted Foods
The food/forage crops that are known to be especially susceptible to Aspergillus flavus, and parasiticus are peanuts, corn and cottonseed. A. flavus is more common on corn, and cottonseed, while A. parasiticus is more common on peanuts. Corns containing higher oil contents are at greater risk for aflotaxins during the growing process.
Besides corn, cottonseed and peanuts, aflatoxins may contaminate many crops including sorghum, barley, rye, wheat, soybean, rice, brazil nuts, peanut, pistachios, almonds, walnuts, dried coconut, dried figs, spices (chilies, black pepper, coriander, turmeric and ginger), sunflower, cotton and milk. It is also found in tobacco leaves. Aflatoxin contamination is worse during drought years and during insect infestations.
Foods that are usually contaminated before harvest are corn, cottonseed, peanuts and tree nuts. Foods that are more likely to be contaminated after harvest are coffee, rice and spices. Other foods that may be suspect for aflatoxins are beans, rice, wheat, eggs, milk and meat.
Infection is more common after the grains have been damaged by insects, birds, mites, hail, frost, heat and drought stress, windstorms and other unfavourable weather conditions (Jacobsen et al., 1993).
Dairy May Contain Aflatoxins
Don't forget that dairy animals may be eating feed with aflatoxins in it and those aflatoxins are turned from AFB1 to AFM1 in the milk. Both humans and animals transform AFB1 to AFM1. AFB1 can be biotransformed in humans and animals by the cytochrome P450 system, specifically CYP1A2 changing AFB1 into the AFM1 metabolite which can be excreted through breast milk and has been found in milk from dairy animals as well as in human mothers who are nursing. In studies of animals the ingestion of AFB1 results in a dose dependent excretion of AFM1 in milk. This aflatoxin can end up in dairy products such as cheese or yogurt.
Since AFM1 is dose-dependently excreted in urine after ingetsion of AFB1, it can be measured in the urine as either AFB1 or AFM1. AFB1 is thought to be twice as toxic as AFM1. I would point out that moldy food that is pulled from human consumption is often fed to animals. No one seems to pay enough attention to the fact that aflatoxins are excreted in the milk of dairy animals and humans are drinking it. Additionally, mycotoxins have been shown to build up in tissues including muscles of animals and that meat may be eaten when someone consumes the meat from animals fed moldy food.
The Work Environment
Eating food is not the only way to get poisoned by aflatoxins. People who work with grains, or agricultural workers can be at serious risk for aflatoxin toxicity. Agricultural workers handling handling plants with Aspergillus species growing on them , Bakeries where large amounts of grain flour is airborne and farming communities are all at risk. Remember, spores become airborne and are found all over the world. Some areas just have more than others. Studies have claimed AFB1 is present at higher levels in grain dust compared to those found in contaminated human or animal food. Without protective clothing and masks, this dust would expose people both through their skin and respiratory system.
Workers who are processing corn, or other grains with aflatoxins floating around in the air, are exposing their lungs which can in turn cause inflammation, and eventually irreversible pulmonary interstitial fibrosis. (Scared lung tissue between the air sacs.)
Health Effects of Aflatoxins
Aflatoxins are highly liposuluble and can be quickly and easily absorbed from the gastrointestinal and respiratory tract into the blood stream where it can then be moved around the body.
The oxidative stress caused by AFB-1 may be one of the underlining mechanisms for AFB1-induced cell injury and DNA, protein and lipid damages, which lead to tumorigenesis. The toxicity of AFB1 is has been shown to be associated with cytotoxic effects from binding of the bioactivated AFBO to such cellular macromolecules as mitochondria, nulear nucleic acids, and nuceloproteins.
A study in chicken liver cells showed AFB1 to cause reactive oxygen species (ROS) generation, a significant impairment of mitochondrial functions, induced apoptosis, and was involved in Nrf2 signal pathway through mitochondria ROS‐dependent signal pathways.
Organs Most Affected By Aflatoxins And The Damage They Cause
People can be exposed to aflatoxins through their gastrointestinal tract, their respiratory system and skin. Damage can take place due to contact with these body organs or these organs can be points of absorbtion of the aflatoxins into the body.
Aflatoxins are known to be hepatotoxic (liver toxins), teratogenic (causes malformations of an embryo or fetus), mutagenic or genotoxic (causes mutations in genetic material), carcinogenic (cause cancer), nephrotoxicity (kidney damage) and immunotoxic (harm the immune system). They also have been shown to cause reproductive damage, inhibit pancreatic enzymes, decrease bile salts, clotting factor synthesis, decrease glucose metabolilsm as well as the creation of fatty acids and phopholipids. Afltoxins have also been shown in animals to decrease bile acids and bile production. Additionally, aflotoxins have been found to effect some nutrients. They lower A and D as well as zinc, selenium and iron.
Even at low levels aflatoxin may have devastating effects. A study with chicks from hatching stage until 3 weeks of age showed low levels of aflatoxin produced a malabsorption syndrome characterized by steatorrhea, hypocarotenoidemia, and decreased concentrations of bile salts, and pancreatic lipase, trypsin, amylase, and RNase.
In humans it appears the liver is the organ that appears to take the hardest hit by aflatoxins, ultimately causing liver cancer and death. This has been quite evident in exposure to humans in India where it has become a huge issue due to more extensive exposure to contaminated food.
Variables That May Increase The Reaction To Aflatoxin
It is known that some people have genetic susceptibilities that cause them to be more sensitive to mycotoxin exposure. Additionally, severe aflatoxin exposure is found more in underdeveloped countries where there may be more chance of malnutrition.
Most of the aflatoxin research is with animals, and it has been shown that different breeds of animals can be effected in dissimilar manners. Also age, sex, metabolic rates, duration of exposure, nutritional status and other disease processes can change how aflatoxins affect animals in studies. It is important to note that even in lower levels of exposure, researchers have noted suppresse immune systems of animals in both the cellular, and humoral part of the adaptive immune system. The animals have been shown to be more susceptible to fungal, parasitic, bacterial and viral infections due to low level exposure to aflatoxins.
Aflatoxin Metabolism & Methods To Decrease Toxicity
Most of the toxicity of aflatoxins appears to be related to the metabolism of AFB1. Aflatoxin induced carcinoma appears to be due to AFB1 being metabolized in the liver primarily (as well as other cells) via the detoxification cytochrome P450 enzyme system to a carcinogenic metabolite called AFB1-8,9-epoxide (AFBO) by the action of mixed function mono-oxygenase enzyme systems CYP450. AFB1-8,9-epoxide is highly unstable, and it reacts with cellular nucleophiles and can induce mutations by alkylating DNA. A study demonstrated a dominant contribution of CYP3A4 homologues in AFBO production. Use of CYP3A4 inhibitors like troleandomycin have been shown to inhibit AFBO production, while inducers of CYP3A4 activity such as 3-methylcholanthrene and rifampicin, increase AFB1 metabolism in cultured human hepatocytes . CYPs may also catalyze demethylation to aflatoxin P (AFP1) of the parent AFB1 molecule, resulting in products less toxic than AFB1.. Inhibition of AFBO formation (through disruption of the cytochrome P450 system) and/or adduct (adduct=DNA bound to a cancer causing chemical) formation are important strategies for prevention of these damaging mutations. Conjugation of AFBO with glutathione is a method to remove this toxic compound, so glutahione and glutathione S-transferase plays a critical role in the protection of tissues from AFBO. In animal models, metabolic detoxification of AFBO is facilitated by induction of glutathione S-transferase (GST). This enzyme catalyzes the reaction that binds glutathione to AFBO and renders AFBO noncarcinogenic.
In humans, the glutathione S-transferase (GST) with the highest activity toward AFBO is the polymorphic hGSTM1-1 which is absent in about 50% of individuals in most human populations. This means that in individuals lacking the assistance of hGSTM1-1, exposure to AFBO will be with elevated risk. Some reports have suggested that the GSTM1 genetic polymorphism may affect AFB1 detoxification in human liver and this may be why the liver is more affected than other organs. The cells with the lower levels of GSTs or lacking specific GST isoforms like the liver would have higher risk of toxicity.
The formation of glutathione conjugates, glucuronide and sulfate conjugates of AFB1 have also been described in some animals and the metabolites of aflatoxin B1 called AFM1, AFPa and AFQ1 can all undergo glucuronidation and sulfation. Some researchers have proposed that AFB1 itself may be able to undergo glucuronidation and sulfation too.
How Aflatoxins Are Removed From The Cells
The other thing to consider is how these aflatoxin-conjugated compounds are being removed from the cells. Both P-glycoprotein and the glutathione S-conjugate carrier are expressed in the liver and it is thought that both of them may be used to transport AFB1-glutathione conjugate out of the cell.
Aflatoxins And Cancer
The B1 and G1 mycotoxins are the most toxic with the highest carcinogenic effect on animal cells. Aflatoxin B1 is thought to be the most carcinogenic of all known cancer causing mycotoxins and it is capable of penetrating the cell membrane and attaching to the cell's DNA where it makes changes to the genome in order to become more stable.
The early observations that an epoxide of AFB1 created adducts with DNA led to the concept that mycotoxin-DNA adducts, such as AFB1-DNAs, initiate cancer—an observation which has been documented in vitro and in vivo. The current evidence is as follows: The very unstable aflatoxin-8, 9-epoxide created in the cytochrome P450 system binds to the DNA molecule with high affinity, it forms aflatoxin-N7-guanine that cause guanine (G) to thymine (T) transversion mutations which will directly affect the cell cycle by affecting the P53 gene which carries the codes for tumor suppressor proteins, meant to inhibit the development of tumors and cancers .
There is animal research showing many dietary factors can modulate the formation of AFB1-DNA adducts. Adducts(binding of mycotoxin to DNA) are the initial step of AFB1 carcinogenesis. Some of the substances that reduce this binding are vitamin A, vitamin C, and riboflavin. Restriction of carnitine, and choline lead to more adducts being formed. Low fat, high carb diet increase adducts being formed. Carnitine, choline, copper, selenium, food restriction indole-3-carbinol, curcumin (from turmeric), garlic, green tea and coffee decrease adduct formation. Phenolic compounds appear to have protective effects against AFB1-induced mutagenicity. (Many of our bright colored vegetables, fruits and herbs have phenolic compounds in them.)
Aflatoxin And Hepatitis B Together Increase Incidence Of Liver Cancer
Hepatocellular carcinoma (HCC), or liver cancer, is the third leading cause of cancer deaths worldwide according to the World Health Organization (WHO) - 2008, with roughly 841,000 new HCC cases globally in 2018. Aflatoxin exposure in food is a significant risk factor for HCC .
People who have Hepatitis B and consume food with aflatoxin are at increased risk of developing hepatocellular carcinoma much more than having one of these factors by themselves. Aflatoxin is implicated in hepatocellular carcinoma in humans and hepatic necrosis in horses. A cohort study of more than 18,000 individuals in China clearly showed a relative risk for hepatocellular carcinoma of 3.4 more in subjects who showed AFB1 exposure measured by urinary AFB1-N7-guanine, while the relative risk for subjects positive for hepatitis B antigen was 7.3 to get hepatocellular carcinoma. A combination of hepatitis B and AFB1 exposure increased the relative risk for hepatocellular carcinoma to 59.
Acute AFB1 consumption by animals and humans cause liver lesions. Common histopathological signs of AFB1-induced liver damage include focal necrotic hepatocytes or hemorrhages. The acute damage initiates inflammatory responses and leads to white blood cell infiltration and proliferation in the liver. Short-term exposure to higher doses can cause illness and death from extensive liver damage.
Adult humans have a high tolerance to aflatoxin while children seem more prone to be affected and even die. However, the dose and duration of time can make all the difference.
It has been found that human effects from aflatoxin can change with duration of exposure, quantity, age, and their health status. Ingestion of 2-6 mg of aflatoxin per day for a month is thought to lead to acute liver inflammation and death in humans.
The symptoms include low grade fever, jaundice, gastrointestinal bleeding, edema, depression, anorexia, diarrhea, abdominal pain, ascites, fatty liver, and may end in liver failure and even death.
The most common foods to cause liver inflammation from aflatoxins are peanuts and corn.
Kwashiorkor has been shown to be correlated to aflatoxin exposure in human populations. Animals given dietary aflatoxins have hypoalbuminemia, fatty liver and immunosuppression, which are also seen in Kwashiorkor.
Liver cancer - hepatocellular carcinoma is associated with chronic exposure. In people who are handling contaminated grains as part of their work, there is greater incidence of lung cancer. For people who have hepatitis B or C, the risk of developing liver cancer from aflatoxin exposure is about 10 times greater.
The entire body ends up affected by chronic aflatoxin toxicity. As mentioned previously it has a negative effect on multiple organ systems and many body processes are not able to function normally.
Preventing Aflatoxin Exposure
Regulation Of Aflatoxins
For aflatoxins B1, B2, G1, G2:
- The U.S. FDA allows 20 micrograms/kilogram for total aflatoxins B1, B2, G1, G2 in food.
- The European Union allows 2-12 micrograms/kilogram for B1 and 4-15 for total B1, B2, G1, G2 aflatoxins in food.
- The foods more commonly assumed may have these mycotoxins and therefore more likely to be tested are Corn, wheat, rice, peanut, sorghum, pistachio, almond, ground nuts, tree nuts, figs, cottonseed, and spices.
For aflatoxin M1: A metabolite of B1 found in milk.
- The U.S. FDA limits M1 to 0.5 microgram/kilogram in milk and milk products.
- The European Union limits limits M1 to 0.05 microgram/kilogram in milk and milk products and 0.025 microgram/kilogram in infant formula and infant milk.
The Role Of The Farmer
Aflatoxins are not visible to the eye, so they are often consumed by unaware humans. The farmer is key in preventing aflatoxin growth during farming, as well as following good harvesting methods. Farming practices such as supporting the soils healthy microbial/fungal/parasitic biome, rotating crops, and supplying nutrients to the soil, will all go a long way to supporting a healthy plant, that will do beter in droughts, and and not attract insects. This helps to decrease fungal growth and mycotoxin production. Keeping the plants healthy and happy will decrease plant stress, and decrease the plants susceptibility to all disease, including fungal disease. It has been noted that the stress of drought, and insects will increase mycotoxins, including aflatoxins on plants. Any physical damage to the growing plant that opens its protective surface can allow fungus to penetrate into the plant more easily. It has been shown that aflatoxin grows best when the moisture content is between 15-32%. In corn, the optimal temperture for growth of Apsergillus is 96.8 - 100.4 F. One method being used to control the Aspergillus species prior to harvest is to inoculate crops with the non-toxigenic Aspergillus flavus isolates which occupy the same niches as the toxigenic strains, and can compete and displace those toxigenic strains. Although this has worked, it is not consistently working. The application of lime and manure have been shown to be effective in reducing A. flavus contamination as well as aflatoxin levels by 50-90%. Lime contains calcium that helps thicken the cell walls of the plants to protect them, and the use of farm yard manure/compost facilitates growth of microorganisms that suppress soil infections.
The Role Of Processing And Storage
Good processing as well as storage and and transport practices also help to decrease mycotoxin formation on plants. All known contaminated food needs to be removed from the market. However, in countries where food may be less availble or if a farmer/processor is not honorable, mycotoxin contaminated food may end up on the market. Broken and damaged kernels usually contain most of mycotoxin contamination although they constitute only 3–6 % of the bulk food. Removing kernels with extensive mold growth, broken kernels, and fine materials such as dirt and debris can be achieved by sieve cleaning, which significantly lowers total mycotoxin contamination.
After harvest contamination can lead to throwing the food out or taking human food and giving it to animals. When contaminated food is given to animals, chemicals to decontaminate the product, or adsorbants, or even enterosobents are given with the feed being fed to animals. This lessens the mycotoxin load, but not completely.
There is processing that can lower mycotoxin contamination of food. However, some activities can actually release metabolites from "masked" mycotoxins also. There are enzymes that are known to decrease certain myctoxins. Methods that have been shown to reduce general mycotoxin contamination are cleaning; milling; brewing; fermentation; cooking; baking; frying; roasting; flaking; alkaline cooking; nixtamalization, hulling of grains and extrusion. Concentrations of some mycotoxins can be reduced substantially while others, such as DON (a trichothecene), are relatively resistant to degradation
Processing Methods To Decrease Aflatoxin
There has been research that has claimed Aflatoxins can not be destroyed by food pocessing techniques such as drying, roasting, canning, baking or cooking. However, aflatoxin can be reduced by food processing methods, but not completely and the temperatures used to destroy aflatoxin are often high. Roasting peanuts eradicates more aflatoxin than boiling them. Fermenting wheat flour reduces aflatoxin by 50%. Baking dough decreases it from 0-25% depending on the study you read. Alkaline processing or nixtamalization (the traditional process of cooking corn in lime water to produce nixtamal that is then ground to form masa) of corn also resulted in significant reductions of aflatoxin according to Torres et. al. 2001. However, there are reports of reformation or reactivation of aflatoxins post process. For example, initial loss of detectable aflatoxin was followed by detection once again upon acidification of the masa flour. The researchers speculated that this acidification could happen after consumption of nixtamalized aflatoxin-contaminated corn due to the acid content of the stomach. (It is thought that the aflatoxin lactone rings, which are opened during nixtamalization alkaline process, can be closed when tortillas are acidified in stomach.)
Nixtamalization consists of cooking the corn in abundant water and lime (2–3 L of water/kg of corn or maize processed, with 1–3% CaOH2) at boiling temperatures for 35–70 min, with a steeping period of 8–16 h. After the steeping, the lime cooking solution (nejayote) is decanted, and the corn is washed carefully to leave it ready for milling and making the maize dough for tortillas. This traditional method of nixtamalization has been shown to remove 85% of the aflatoxin present in maize.
Oxidant agents such as ozone and peroxides have been ablr to detoxify aflatoxins but it is thought that some of the smaller molecules obtained could also be toxic.
Avian (Bird) Pulmonary Aspergillosis
Aspergillus fumigatus is a common cause of avian pulmonary aspergillosis, although other species have also been implicated in aspergillosis. Environmental factors that cause this in birds are heavy contamination of feed with Aspergillus and contaminated air, as well as stress or immunosupression. In chickens this is called "brooders pneumonia".
Humans can also have some species of Aspergillus take up lodging in their body. Of the 180 known species of Aspergillus, only four are known to be associated with invasive infection. They can cause infections in healthy individuals but are more commonly associated with invasive infections in immunocompromised people. These species are A. flavus, A fumigatus, A. terreus and A. niger. These species are worldwide and produce large amounts of spores that are dispersed into air currents where anyone around them will be exposed by contact with skin, eyes, ears and by inhalation. When inhaled they can lodge in the lung. In most people their innate immune system protects them from infection unless they enter a wound and the person is under some type of trauma or severe stress. When the immune system is weakened, the inhaled spores can germinate and produce hyphae that invade the surrounding lung tissue. This can cause invasive pulmonary aspergillosis.
Aspergillus is known to also cause infections in people who are not thought to be immmunocompromised. There is an Aspergillus induced shpenoid sinusitis and intracranial invasive aspergillosis. (Originates in sphenoid sinus.) Agricultural workers who injure their eyes have been known to develop Aspergillus corneal infections. Aspergillus has been known to infect ears in healthy individuals in both the external and middle ear. Additionally, aspergillus has infected postoperative cavities and then migrated into the ear.
A. fumigatus is more often found in areas with temperate climates while A. flavus is more common in hot, tropical climates. A. fumigatus is responsible for about 90% of the cases of pulmonary fungal infections. A. flavus is less common in pulmonary aspergillosis but does cause invasive disease at other sites. A. terreus also causes infections in immunocompromised individuals. One study implicated potted plants in a hospital setting as a source of A. terreus that caused infections in nine patients.
Aspergillus Allergic Reactions
Aspergillus species cause four forms of respiratory hypersensitivity disorders; allergic bronchopulmonary aspergillosis, allergic Aspergillus sinusitis, IgE-mediated asthma and hypersensitivity pneumonitis. A. flavus has been known to cause allergic rhinosinusitis.
Testing for Aflatoxin Exposure
AFB1 metabolites can be measured in urine if suspected as a toxin in people or animals. However the World Health Organization claims the urinary metabolites are only present for 24 hours after exposure. There is however an aflatoxinB-albumin compound in the blood serum that can be found for weeks or even months after exposure. Enzyme Linked Immunosorbent Assay (ELISA)is used to determine qualitatively and quantitatively how much monoclonal antibody against AFB1 bound to albumin is in urine and blood samples.
Where To Find Labs
Great Plains Laboratory has a mycotoxin test called GPL-MycoTOX Profile that includes aflatoxin M1 which is the main metabolite of aflatoxin B1.
Real Time Labs has a mycotoxin urine test that evaluates aflatoxins by using ImmunoSorbant Columns containing antibodies to the group of aflatoxins (B1, B2, G1, and G2). Results are reported as PRESENT or NOT PRESENT.
Detoxification of Aflatoxins With Biotransformation & Binders
For food toxicity, preventing damage to crops and being careful during harvesting, processing, storage, transportation is key. I examined this previously in more detail.
However, once contamination has taken place there are processing methods that can decrease aflatoxin toxicity but not completely destroy them.
There are a number of things we know about the biotransformation of aflatoxins that gives us hints as to how we might support the bodies biotransformation process and help to remove aflatoxins. The body biotransforms aflatoxins through epoxidation, reduction, hydroxylation and conjugation. In the majority of animal species, the primary way to detoxify the AFB1 is through the conjugation of AFBO with reduced glutathione. This process is catalyzed by glutathione S transpherase and once AFBO is conjugated wtih glutathione, the conjugate can be excreted. Some researchers also believe AFB1 can go through glucuronidation and sulfation which are two other types of conjugation. (For more details on conjugation in realtion to the biotransformational/detox system check out this link.) It would be helpful to support production of glutathione, use glutathione supplements, and support Glutathione S traspherases. Although, glutathione has been shown to be ramped up in some studies when animals are given aflatoxins, their capacity to defend themselves can be overtaken by the amount of aflatoxins they are dealing wtih.
It appears glucuronidation and sulfation may also be alternate routes to remove aflatoxins.
We also know that CYP3A4 inhibitors have been able to inhibit production of the nasty AFBO from AFB1.
Binders have been used with varying degrees of success in binding alfatoxins and removing them from the intestinal tract via the feces.
Calcium-montmorillonite is considered the most effective adsorbent for aflatoxins currently known.
Additionally, we know that studies have shown antioxidants to be beneficial in protection from aflatoxin damage.
Biotransformation of Aflatoxins
Making enough glutathione for glutathione conjugation depends on the rate limiting amino acid, cysteine. Cysteine can be made from methionine with the aid of vitamin B6. Additionally, vitamins B2 and B3 are needed for the activity of glutathione reductase, which recycles oxidized glutathione. I have people take a low dose multiple B and then add extra specific Bs as they need. The basic building blocks of glutathione creation and recycling of glutathione are very important. Without glutathione, there simply will be no glutathione conjugation. Consider the need for methionine, selenium, zinc, cysteine, glutamine, glycine, Vitamin C, E, Bs, and magnesium. Check out this link for more details on glutathione and how to support it.
In birds, the addition of .1% methionine to their aflatoxin contaminated diet has had pronounced ameliorative effect on their performance in studies. See one study here.
Nuclear factor-erythroid 2-related factor 2 (Nrf2) To Enhance Gluathione
Nuclear factor-erythroid 2-related factor 2 (Nrf2) transcription controls the formation of glutathione as well as the formation of glutathione S-transferases (GSTs). Exposure to toxins, such as mycotoxins including aflatoxin and ochratoxin (both made by Aspergillus) have been shown to inhibit Nrf2 which in turn decreases glutathione synthesis.
Activators of NRF2
- Curcumin found in Curcuma longa
- Silymarin found in Silybum marianum
- Resveratrol found in Polygonum cuspidatum
- Grape skin
- Red wine
- Dark colored berries
- Catechins found in dark chocolate
- Raw cacao
- Catechins in Green tea
One of the strongest activators of NRF2 has been found to be the isothiocyanate called sulforaphane. Sulforaphane is the metabolite of glucoraphanin (GRN) which is contained in the cruciferous plants cell vacuole along with an enzyme called myrosinase (MYR) which are kept separate. When the plant cell wall ruptures and GRN and MYR come together, sulforaphane is enzymatically produced. All the Brassica/Crucifera plant family yields sulforaphane. The highest amounts are in broccoli and to be precise, broccoli sprouts. Cutting, chewing or otherwise opening the cell walls of these plants immediately causes synthesis of sulforaphane. However, it immediately begins to degrade. So, if you make yourself a broccoli drink you need to drink it sooner rather than later.
Broccoli Sprouts To Reduce Aflatoxin
There was a study that examined the use of broccoli sprouts at reducing the level of aflatoxin-N7-guanine in urine samples collected from the study participants. Aflatoxin-N7-guanine is a DNA adduct that is associated with liver cancer. There was a highly significant decrease of aflatoxin-N7-guanine found in urine samples collected on day 9 from participants in the broccoli sprout infusion group.
Remember that A genetic deficiency of GSTM1 is associated with increased susceptibility to aflatoxin B1 (AFB1)-mediated damage to human liver cells.(also susceptible to ozone-related asthma) These individuals with GSTM1 polymorphism may benefit from antioxidant supplementation.
The combination of GSTM1 null and GSTP1 Val was significantly associated with an increased risk of lung cancer and hepatocellular carcinoma. An inverse relationship between plasma selenium level, an indicator of the function of glutathione peroxidase and AFB1–albumin adducts were observed to be statistically significant among individuals with null (A null allele is a mutant copy of a gene at a locus that lacks the gene's normal function.) genotypes of GSTM1 and GSTT1, but not among the non-null genotypes. In carriers of hepatitis B virus, there was an increased risk of hepatocellular carcinoma in null genotypes of GSTM1 and T1 but not among individuals who had non-null genotypes. Additionally, GSTM1 null genotype is a risk factor for Alzheimer’s disease
Binders and Bile To Remove Aflatoxins
The aflatoxin metabolites as well as the parent compound AFB1 are excreted from the body primarily through the bile, but also through the urine and milk. So be sure you support bile productiong and flow. Unfortuantely some mycotoxins have been shown to slow production, or flow of bile down. Aflatoxin is one of those shown to do this in some animal research. See more details on bile and bile acids here or treatment for mold related illness.
Another way to remove aflatoxins is through use of binders. Both the primary aflatoxins arriving to the gastrointestinal tracts as well as those cycled through the enterohepatic system dumping into the digestive tract in the bile are susceptible to the appropriate binders. A variety of binders have been used, and many of them have some amount of binding ability to aflatoxins. It appears at the time of my writing this article that bentonite clays have the best binding capabilities for aflatoxins. This includes both sodaium and calcium bentonite clays. Novasil clay has both animal and human research showing it binds aflatoxins. Glucomannan from yeast cell walls also looks fairly good. Remember however, that often there is more than aflatoxin involved. For example Aspergillus is known to make two nasty mycotoxins; aflatoxin and ochratoxin. Clays are negatively charged as are many of the inorganic binders and ochratoxin does not bind to negatively charged binders very strongly.
Here is an example of how some of these binders are working. A 2004 study compared a variety of mycotoxin sequestering products for their ability to bind aflatoxin in cows consuming aflatoxin in feed. The milk of the cows was examined for aflatoxin M1. The results here are the amounts removed. Astra-Ben-20, a sodium bentonite was 61%, Flow Guard, a sodium bentonite was 65%, Mycrosorb, a sodium bentonite was 50%, MTB-100, an esterified glucomannan from yeast cell walls was 59% and Red Crown, a calcium bentonite was 31% and SA-20, an Activated carbon had no effect on the amount of aflatoxin M1 in the milk.
Activated carbon/charcoal will remove aflatoxins from water but not in animals with aflatoxicosis. Sodium bentonite and sodium monmorillonite (mostly what is in bentonite) have been shown to be effective as binders. These clays are used by farmers as well as human individuals.
Saccharomyces cerevisiae and mannan oligosaccharides (derived from cell wall of Saccharomyces cerevisiae) have been shown in some animal studies to be quite useful at binding aflatoxin B1. The amount that appears to be best of either the S. cerevisiae or mannan oligosaccharides is 0.2% of diet.
Aflatoxins have been shown to enhance reactive oxygen species and cause oxidative stress and damge in animal subjects. This oxidative stress is thought to be an underlying cause of AFB1-induced cellular injury and DNA damage that can lead to cancer growth. In a rat study there was oxidative stress oxidative stress shown by increased MDA level and the reduced GSH level, glutathione-S-transferase, catalase, glutathione peroxidase, superoxide dismutase, and glucose-6-phosphate dehydrogenase activities in tissues. The liver enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase activities were significantly increased. Kidney markers creatinine, and urea concentrations significantly increased, while plasma glucose, protein and sodium concentrations significantly decreased.
Some studies show AFB-1 is linked to such an increase in reactive oxygen species that the capacity of the antioxidant system is surpassed leaving cells vulnerable to oxidation. Therefore, using antioxidants seems like a no-brainer to support anyone who is under onslaught of aflatoxin poisoning.
Antioxidants can protect the structural and functional integrity of the cells and support the immune systems response to antigens (toxins).
Some of the nutritional antioxidants that would be most useful
- Vitamin A
- Vitamin C
- Vitamin E
Vitamin A status is associated with liver cancer induction from aflatoxins. Additionally, vitamin A was shown to upregulate glutathione-S-transferase activity in the liver cyotosol raction.
Vitamin E has been shown to considerably reduced plasma liver enzyme levels such as AST, ALT, ALP and LDH, as well as urea concentration and has decreased or negated the negative effects of aflatoxins on oxidative stress markers and pathological changes.
The fact is that a diet rich in vegetables and fruits will provide the antioxidants needed. I am talking about 7-10 cups (measured fresh) of organic fruits and vegetables (mostly vegetables and a lot of mustard family veggies and dark green leafies along with allium family members such as onions, leeks and garlic.) There are many herbs that are also antioxidants. Garlic by the way has been found to help prevent aflatoxin-induced toxicity and free radical generation in rats.
Chlorophyllin has been shown to protect against human AFB1 toxicity. Chlorophyllin is a mixture of semisynthetic, water-soluble derivatives of chlorophyll. Chlorophyllin consumption at each meal led to an overall 55% reduction in median urinary levels of this aflatoxin biomarker (aflatoxin-N7-guanine adducts in urine) compared with those taking placebo.
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