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Title: Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala

Author
item Riley, Ronald
item TORRES, OLGA - National Institute Of Public Health (INSP)
item MATUTE, JORGE - National Institute Of Public Health (INSP)
item GREGORY, SIMON G - Duke University Medical Center
item ASHLEY-KOCH, ALLISON E - Duke University Medical Center
item Showker, Adele
item Mitchell, Trevor
item Voss, Kenneth
item MADDOX, JOYCE R - Creighton University
item GELINEAU-VAN WAES, JANEE - Creighton University

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/4/2015
Publication Date: 9/3/2015
Citation: Riley, R.T., Torres, O., Matute, J., Gregory, S., Ashley-Koch, A., Showker, A.J., Mitchell, T.R., Voss, K.A., Maddox, J., Gelineau-Van Waes, J. 2015. Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala. Molecular Nutrition and Food Research. 59(11):2209-2224.

Interpretive Summary: Scope: Fumonisin (FB) is an inhibitor of ceramide synthase (CerS). We determined the urinary FB1 (UFB1) and the levels of sphingoid base 1-phosphates in blood from women consuming maize in high and low FB exposure communities in Guatemala. Methods and results: FB1 intake was estimated using the UFB1. Sphinganine 1-phosphate (Sa 1-P), sphingosine 1-phosphate (So 1-P), and the Sa 1-P/So 1-P ratio were determined in blood spots collected on absorbent paper at the same time as urine collection. In the first study, blood spots and urine were collected every three months (March 2011 to February 2012) from women living in low (Chimaltenango and Escuintla) and high (Jutiapa) FB exposure communities (1240 total recruits). The UFB1, Sa 1-P/So 1-P ratio, and Sa 1-P/ml in blood spots were significantly higher in the high FB1 intake community compared to the low FB1 intake communities. The results were confirmed in a follow-up study (February 2013) involving 299 women living in low (Sacatepéquez) and high (Santa Rosa and Chiquimula) FB exposure communities. Conclusions: High levels of FB1 intake are correlated with changes in Sa 1-P and the Sa 1-P/So 1-P ratio in human blood in a manner consistent with FB1 inhibition of CerS.

Technical Abstract: Fumonisin B1 (FB1) is a toxic chemical produced by molds. The molds that produce fumonisin are common in corn. Consumption of contaminated corn by farm animals has been shown to be the cause of disease. Fumonisin has been hypothesized to be an environmental risk factor for diseases in humans in countries where corn is a dietary staple and infection with the mold is likely. In order to determine if fumonisin contributes to disease in humans, we have developed methods to measure changes in the urine and blood levels of chemicals that are indicators of changes indicative of pre-disease states. Our studies have focused on populations in Guatemala where corn is a dietary staple. Intake of fumonisin in these populations can be very high. We have sampled corn, urine and blood from over 1500 women and the results show that fumonisin intake and changes in a unique class of fats (sphingoid base 1-phosphates) in the blood are correlated in a manner that mimics the effects of fumonisin in laboratory animals. The findings are consistent with the hypothesis that fumonisin inhibits the same enzyme in humans as it does in farm and laboratory animals consuming diets high in fumonisin.