Aflatoxin and Fumonisin Exposure: International Survey and Enterosorption Mitigation Strategy in Humans

Aflatoxins (AFs) are toxic metabolites produced by Aspergillus flavus and A. parasiticus. Fumonisins (FBs) are also toxic products of fungi, specifically Fusarium verticilloides and F. proliferatum. Both toxins commonly contaminate staple grains and cereals such as maize and groundnuts. Aflatoxin B1 (AFB1) is the most toxic and prevalent of the AFs. Chronic dietary exposure to AFs is a known risk factor for hepatocellular carcinoma and may also affect protein metabolism and the immune system. Fumonisin B1 (FB1) is the most abundant and toxicologically significant of the congeners. In populations where AFs and FBs are inextricable contaminants, a multi-faceted approach must be implemented to reduce exposure to these toxins, especially in the young who are more susceptible. Alternative methods such as calcium montmorillonite clay (UPSN or ACCS100) as an enterosorbent therapy that focus on reducing biological exposure to AFs and FBs in foods already contaminated are desirable as a secondary defense to the harmful effects of these toxins. Therefore, I propose to test the efficacy of UPSN in food matrices, identify populations at high risk for AFs and FBs with urinary biomarkers, and finally, combine clay technology and biomarker analysis to intervene with UPSN or ACCS100 in frequently exposed human populations. In these studies UPSN was able to significantly reduce AFB1 under common cooking conditions in a corn meal matrix suggesting a potential delivery of the clay directly in the contaminated food. A high prevalence of exposure to variable AFB1 and FB1 levels in participants from Monterrey, Mexico was observed. After a two week crossover trial in a high risk area of Kenya with 3.0g ACCS100/day mixed in water, urinary aflatoxin M1 (an AFB1 metabolite) was significantly reduced compared to the placebo group. ACCS100 was found to be safe and well tolerated suggesting potential for reducing exposure to AF in this particular population during outbreak situations. In a 3-month intervention with 3.0g or 1.5g ACCS100/day (encapsulated) in San Antonio, Texas, AFB1-lysine (an AFB1 protein adduct) was significantly reduced in the Low Dose group (1.5g) compared to Placebo. ACCS100 was well tolerated in the majority of participants and no significant changes in serum biochemistry or hematology were detected in any treatment group. Thus, use of calcium montmorillonite clay at doses as low as 1.5g/day and delivered in capsules, food, drink, or water may provide a viable strategy to reduce dietary AFB1 bioavailability in populations exposed to this toxin for up to 3 months. Moreover, AF and FB exposure is a global and unavoidable public health concern and biomarkers are important tools for monitoring exposure