Concomitant oral intake of purified clinoptilolite tuff (G-PUR) reduces enteral lead uptake in healthy humans

Karolina Samekova, Christa Firbas, Johanna Irrgeher, Christine Opper, Thomas Prohaska, Anika Retzmann, Cornelius Tschegg, Claudia Meisslitzer, Anastassiya Tchaikovsky, Ghazaleh Gouya, Michael Freissmuth, Michael Wolzt, Karolina Samekova, Christa Firbas, Johanna Irrgeher, Christine Opper, Thomas Prohaska, Anika Retzmann, Cornelius Tschegg, Claudia Meisslitzer, Anastassiya Tchaikovsky, Ghazaleh Gouya, Michael Freissmuth, Michael Wolzt

Abstract

Lead exposure can cause substantial organ damage. Enteral lead absorption may be reduced by concomitant intake of clinoptilolite tuff, a zeolite from natural sources. This study aimed to assess the effect of purified clinoptilolite tuff (G-PUR) on enteral lead uptake in adults using stable lead isotope 204Pb as a tracer. In this randomized, placebo-controlled, double-blind, parallel-group study, 42 healthy participants were randomized to receive oral G-PUR 2.0 g, 2 * 2.0 g, or placebo, together with 2.5 µg of 204Pb in water. The enrichment of 204Pb caused by the tracer in blood and urine was measured by mass spectrometry. G-PUR was well tolerated. The mean maximum 204Pb enrichment of 0.505% of total blood lead was significantly higher (p < 0.0001) in the placebo group compared to G-PUR 2.0 g (0.073%) or G-PUR 2 * 2.0 g (0.057%) group. Normalized 204Pb AUC0-192 was 86.5, 11.9, and 8.5% * h without and with G-PUR 2.0 g, and G-PUR 2 * 2.0 g, respectively (p < 0.0001 vs. placebo). This smaller 204Pb exposure was paralleled by a reduced urinary excretion in subjects receiving G-PUR. Concomitant oral intake of purified clinoptilolite tuff reduced enteral uptake of 204Pb in healthy humans by approximately 90%. The reduced bioavailability is demonstrable by a decrease of 204Pb tracer enrichment in blood and urine.Trial registration: clinicaltrials.gov identifier: NCT04138693, registered 24/10/2019.

Trial registration: ClinicalTrials.gov NCT04138693 NCT00413869.

Conflict of interest statement

The authors from Medical University of Vienna (K.S., C.F. and M.W.), Montanuniversität Leoben (J.I., C.O., T.P. and A.R.) and G.G. were reimbursed for all trial-related work hours, material and effort spent by the study sponsor. Investigators or study staff did not receive any payment. M.F. is the recipient of an unrestricted research endowment by G.H. Glock. C.T., C.M. and A.T. are employees at Glock Health, Science and Research G.m.b.H. and did not receive any extra payment.

© 2021. The Author(s).

Figures

Figure 1
Figure 1
Molar fraction of 204Pb of total blood lead (% of individual total Pb at each time point, normalized for haematocrit and body mass index) after single oral intake of 2.5 µg 204Pb with purified clinoptilolite (G-PUR) at 2.0 g, 2 * 2.0 g, or placebo. Means ± SD are indicated, n = 14 per group.

References

    1. Wani AL, Ara A, Usmani JA. Lead toxicity: A review. Interdiscip. Toxicol. 2015;8:55–64. doi: 10.1515/intox-2015-0009.
    1. ATSDR. Toxicological profile for Lead. Agency for Toxic Substances and Disease Registry, U.S. Department of Health and Human Services, Atlanta, GA (2019).
    1. Van de Wiele TR, et al. Comparison of five in vitro digestion models to in vivo experimental results: Lead bioaccessibility in the human gastrointestinal tract. J. Environ. Sci. Health A Toxicol. Hazard Subst. Environ. Eng. 2007;42:1203–1211. doi: 10.1080/10934520701434919.
    1. Chain, E. P. o. C. i. t. F. Scientific opinion on lead in food. EFSA J. 2010;8:1570. doi: 10.2903/j.efsa.2010.1570.
    1. Rosen JF. Adverse health effects of lead at low exposure levels: Trends in the management of childhood lead poisoning. Toxicology. 1995;97:11–17. doi: 10.1016/0300-483x(94)02963-u.
    1. Dart RC. Medical Toxicology. 3. Lippincott Williams & Wilkins; 2004. pp. 1423–1431.
    1. Smith HJ, et al. Five-years experience with intravascular lead extraction. U.S. Lead Extraction Database. Pacing Clin. Electrophysiol. 1994;17:2016–2020. doi: 10.1111/j.1540-8159.1994.tb03792.x.
    1. Leggett RW. An age-specific kinetic model of lead metabolism in humans. Environ. Health Perspect. 1993;101:598–616. doi: 10.1289/ehp.93101598.
    1. Barry PS. A comparison of concentrations of lead in human tissues. Occup. Environ. Med. 1975;32:119–139. doi: 10.1136/oem.32.2.119.
    1. Rabinowitz MB, Wetherill GW, Kopple JD. Kinetic analysis of lead metabolism in healthy humans. J. Clin. Investig. 1976;58:260–270. doi: 10.1172/JCI108467.
    1. Beltcheva M, et al. Modified natural clinoptilolite detoxifies small mammal’s organism loaded with lead I. Lead disposition and kinetic model for lead bioaccumulation. Biol. Trace Elem. Res. 2012;147:180–188. doi: 10.1007/s12011-011-9278-4.
    1. Perić J, Trgo M, Vukojević Medvidović N. Removal of zinc, copper and lead by natural zeolite—a comparison of adsorption isotherms. Water Res. 2004;38:1893–1899. doi: 10.1016/j.watres.2003.12.035.
    1. Thomson, K. T. Handbook of Zeolite Science and Technology Edited by Scott M. Auerbach (University of Massachusetts, Amherst), Kathleen A. Carrado (Argonne National Laboratory), Prabir K. Dutta (The Ohio State University). Marcel Dekker, Inc., New York, Basel. 2003. xii. J. Am. Chem. Soc.126, 8858–8859 (2004).
    1. Ghasemi-Fasaei, R., Gafari-Haghighi, M., Mousavi, S. M. & Dehghan, M. Sorption Characteristics of Heavy Metals onto Natural Zeolite of Clinoptilolite Type (2012).
    1. Jain SK. Protective role of zeolite on short- and long-term lead toxicity in the teleost fish Heteropneustes fossilis. Chemosphere. 1999;39:247–251. doi: 10.1016/s0045-6535(99)00106-x.
    1. Puschenreiter M, Horak O, Friesl-Hanl W, Hartl W. Low-cost agricultural measures to reduce heavy metal transfer into the food chain—A review. Plant Soil Environ. 2005;51:1–11. doi: 10.17221/3549-PSE.
    1. Zamzow MJ, Eichbaum BR, Sandgren KR, Shanks DE. Removal of heavy metals and other cations from wastewater using zeolites. Sep. Sci. Technol. 1990;25:1555–1569. doi: 10.1080/01496399008050409.
    1. Pond, W. G., Ellis, K. J., Krook, L. P. & Schoknecht, P. A. Modulation of dietary lead toxicity in pigs by clinoptilolite. In ZEOLITE'93, 4th International Conference on the Occurrence, Properties, and Utilization of Natural Zeolites, Boise-Idaho, June 20–28, pp. 170–172 (1993).
    1. Erdem E, Karapinar N, Donat R. The removal of heavy metal cations by natural zeolites. J. Colloid Interface Sci. 2004;280:309–314. doi: 10.1016/j.jcis.2004.08.028.
    1. Delkash M, Bakhshayesh B, Kazemian H. Using zeolitic adsorbents to clean up special wastewater streams: A review. Microporous Mesoporous Mater. 2015 doi: 10.1016/j.micromeso.2015.04.039.
    1. Hauptman M, Bruccoleri R, Woolf AD. An update on childhood lead poisoning. Clin. Pediatr. Emerg. Med. 2017;18:181–192. doi: 10.1016/j.cpem.2017.07.010.
    1. Colella C. A critical reconsideration of biomedical and veterinary applications of natural zeolites. Clay Miner. 2011;46:295–309. doi: 10.1180/claymin.2011.046.2.295.
    1. Bressler JP, Olivi L, Cheong JH, Kim Y, Bannona D. Divalent metal transporter 1 in lead and cadmium transport. Ann. N. Y. Acad. Sci. 2004;1012:142–152. doi: 10.1196/annals.1306.011.
    1. Canonne-Hergaux F, Gruenheid S, Ponka P, Gros P. Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood. 1999;93:4406–4417. doi: 10.1182/blood.V93.12.4406.
    1. Yanatori I, Kishi F. DMT1 and iron transport. Free Radic. Biol. Med. 2019;133:55–63. doi: 10.1016/j.freeradbiomed.2018.07.020.
    1. Bradman A, Eskenazi B, Sutton P, Athanasoulis M, Goldman LR. Iron deficiency associated with higher blood lead in children living in contaminated environments. Environ. Health Perspect. 2001;109:1079–1084. doi: 10.1289/ehp.011091079.
    1. Hammad TA, Sexton M, Langenberg P. Relationship between blood lead and dietary iron intake in preschool children. A cross-sectional study. Ann. Epidemiol. 1996;6:30–33. doi: 10.1016/1047-2797(95)00097-6.
    1. Serwint JR, et al. No difference in iron status between children with low and moderate lead exposure. J. Pediatr. 1999;135:108–110. doi: 10.1016/s0022-3476(99)70338-0.
    1. Tandy S, et al. Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells. J. Biol. Chem. 2000;275:1023–1029. doi: 10.1074/jbc.275.2.1023.
    1. Bannon DI, Abounader R, Lees PS, Bressler JP. Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells. Am. J. Physiol. Cell Physiol. 2003;284:C44–50. doi: 10.1152/ajpcell.00184.2002.
    1. Elsenhans B, Janser H, Windisch W, Schümann K. Does lead use the intestinal absorptive pathways of iron? Impact of iron status on murine 210Pb and 59Fe absorption in duodenum and ileum in vivo. Toxicology. 2011;284:7–11. doi: 10.1016/j.tox.2011.03.005.
    1. Rabinowitz M, Wetherill GW, Kopple JD. Studies of human lead metabolism by use of stable isotope tracers. Environ. Health Perspect. 1974;7:145–153. doi: 10.1289/ehp.747145.
    1. Rabinowitz MB, Wetherill GW, Kopple JD. Lead metabolism in the normal human: Stable isotope studies. Science. 1973;182:725. doi: 10.1126/science.182.4113.725.
    1. Tschegg C, et al. Petrogenesis of a large-scale miocene zeolite tuff in the eastern Slovak Republic: The Nižný Hrabovec open-pit clinoptilolite mine. Econ. Geol. 2019;114:1177–1194. doi: 10.5382/econgeo.4679.
    1. Tschegg C, et al. Fault zone structures and strain localization in clinoptilolite-tuff (Nižný Hrabovec, Slovak Republic) J. Struct. Geol. 2020;138:104090. doi: 10.1016/j.jsg.2020.104090.
    1. Glock, G. Method for the removal of heavy metals (Velden, Austria, Patent number WO2008/003101A1), World Intellectual Property Organization. (2006).
    1. Nizet S, et al. Clinoptilolite in dextran sulphate sodium-induced murine colitis: Efficacy and safety of a microparticulate preparation. Inflamm. Bowel Dis. 2017;24:54–66. doi: 10.1093/ibd/izx042.
    1. Bannon DI, Murashchik C, Zapf CR, Farfel MR, Chisolm JJ., Jr Graphite furnace atomic absorption spectroscopic measurement of blood lead in matrix-matched standards. Clin. Chem. 1994;40:1730–1734. doi: 10.1093/clinchem/40.9.1730.
    1. B. f. s. S. u. Generationen (Verordnung des Bundesministers für soziale Sicherheit und Generationen über die Qualität von Wasser für den menschlichen Gebrauch (Trinkwasserverordnung—TWV), BGBl. II Nr. 304/2001, [CELEX-Nr.: 398L0083]. . Accessed 11 Sept 2020.
    1. Hanousek O, Brunner M, Pröfrock D, Irrgeher J, Prohaska T. The performance of single and multi-collector ICP-MS instruments for fast and reliable 34S/32S isotope ratio measurements. Anal. Methods. 2016;8:7661–7672. doi: 10.1039/C6AY02177H.
    1. Hanousek O, Berger T, Prohaska T. MC ICP-MS δ (34)SVCDT measurement of dissolved sulfate in environmental aqueous samples after matrix separation by means of an anion exchange membrane. Anal. Bioanal. Chem. 2015 doi: 10.1007/s00216-015-9053-z.

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