Chelating with clinoptilolite

Dr. Weeks’s Comment: This mineral is a honeycomb shaped structure which is positively charged and binds and removes toxins safely. It is marketed mostly as a suspension (think dirt in water – eventually they dissociate) but if you can find it as a true solution (dissolved solid) then you have a powerful remedy.

 1

Review

Molecules. 2019 Apr 17;24(8):1517.

 doi: 10.3390/molecules24081517.

Zeolite Clinoptilolite: Therapeutic Virtues of an Ancient Mineral

Andrea Mastinu 1Amit Kumar 2Giuseppina Maccarinelli 3Sara Anna Bonini 4Marika Premoli 5Francesca Aria 6Alessandra Gianoncelli 7Maurizio Memo 8

Abstract

Zeolites are porous minerals with high absorbency and ion-exchange capacity. Their molecular structure is a dense network of AlO4 and SiO4 that generates cavities where water and other polar molecules or ions are inserted/exchanged. Even though there are several synthetic or natural occurring species of zeolites, the most widespread and studied is the naturally occurring zeolite clinoptilolite (ZC). ZC is an excellent detoxifying, antioxidant and anti-inflammatory agent. As a result, it is been used in many industrial applications ranging from environmental remediation to oral applications/supplementation in vivo in humans as food supplements or medical devices. Moreover, the modification as micronization of ZC (M-ZC) or tribomechanically activated zeolite clinoptilolite (TMAZ) or furthermore as double tribomechanically activated zeolite clinoptilolite (PMA-ZC) allows improving its benefits in preclinical and clinical models. Despite its extensive use, many underlying action mechanisms of ZC in its natural or modified forms are still unclear, especially in humans. The main aim of this review is to shed light on the geochemical aspects and therapeutic potentials of ZC with a vision of endorsing further preclinical and clinical research on zeolites, in specific on the ZC and its modified forms as a potential agent for promoting human brain health and overall well-being.

 2

Review

Front Pharmacol. 2018 Nov 27;9:1350

Critical Review on Zeolite Clinoptilolite Safety and Medical Applications in vivo

Sandra Kraljević Pavelić 1Jasmina Simović Medica 2Darko Gumbarević 1Ana Filošević 1Nataša Pržulj 3Krešimir Pavelić 1 4

Abstract

Unique and outstanding physical and chemical properties of zeolite materials make them extremely useful in a variety of applications including agronomy, ecology, manufacturing, and industrial processes. Recently, a more specific application of one naturally occurring zeolite material, clinoptilolite, has been widely studied in veterinary and human medicine. Due to a number of positive effects on health, including detoxification properties, the usage of clinoptilolite-based products in vivo has increased enormously. However, concerns have been raised in the public about the safety of clinoptilolite materials for in vivo applications. Here, we review the scientific literature on the health effects and safety in medical applications of different clinoptilolite-based materials and propose some comprehensive, scientifically-based hypotheses on possible biological mechanisms underlying the observed effects on the health and body homeostasis. We focus on the safety of the clinoptilolite material and the positive medical effects related to detoxification, immune response, and the general health status.

 3

Review

Nutr Hosp. 2015 Aug 1;32(2):573-81

ZEOLITE: “THE MAGIC STONE”; MAIN NUTRITIONAL, ENVIRONMENTAL, EXPERIMENTAL AND CLINICAL FIELDS OF APPLICATION

Carmen Laurino 1Beniamino Palmieri 1

Introduction: zeolites (clinoptilolites) are a family of alluminosilicates and cations clustered to form macro aggregates by small individual cavities. In the medical area they are involved in detoxification mechanisms capturing ions and molecules into their holes. Actually, we classify about 140 types of natural and 150 synthetic zeolites, for specific and selective use. Clinoptilolite is a natural zeolite and it is the most widespread compound in the medical market.

Objective: this review analyzes the main fields of zeolite utilization.

Methods: we searched Pubmed/Medline using the terms “zeolite” and “clinoptilolite”.

Results and discussion: in zoothechnology and veterinary medicine zeolite improves the pets’ fitness, removes radioactive elements, aflatoxines and poisons. Zeolite displays also antioxidant, whitening, hemostatic and anti-diarrhoic properties, projected in human care. However very scanty clinical studies have been run up to now in immunodeficiency, oncology after chemotherapy and radiotherapy as adjuvants.

Conclusions: further clinical investigations are urgently required after this review article publication which updates the state of the art.

4

Exp Biol Med (Maywood). 2021 Mar;246(5):529-537.

 doi: 10.1177/1535370220968752. Epub 2020 Nov 12.

Treatment of osteoporosis with a modified zeolite shows beneficial effects in an osteoporotic rat model and a human clinical trial

Sandra Kraljević Pavelić 1Vedran Micek 2Dragica Bobinac 3 4 5Edo Bazdulj 3 4Alessandra Gianoncelli 6Dalibor Krpan 7Marta Žuvić 8Sandra Eisenwagen 9Peter J Stambrook 10Krešimir Pavelić 5

Abstract

The severity of osteoporosis in humans manifests in its high incidence and by its complications that diminish quality of life. A societal consequence of osteoporosis is the substantial burden that it inflicts upon patients and their families. Several bone-modifying drugs have been prescribed to patients with osteoporosis. However, evidence for their anti-fracture efficacy remains inconclusive. To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. We now present an alternative and adjuvant approach for treatment of osteoporosis. The data derive from in vivo studies in an ovariectomized rat model and from a randomized double blind, placebo-controlled human clinical study. Both studies involved treatment with Panaceo Micro Activation (PMA)-zeolite-clinoptilolite, a defined cation exchange clinoptilolite, which clearly improved all bone histomorphometric parameters examined from ovariectomized animals, indicative for increased bone formation. Moreover, intervention with PMA-zeolite-clinoptilolite for one year proved safe in humans. Furthermore, patients treated with PMA-zeolite-clinoptilolite showed an increase in bone mineral density, an elevated level of markers indicative of bone formation, a significant reduction in pain, and significantly improved quality of life compared with patients in the control (placebo) group. These encouraging positive effects of PMA-zeolite-clinoptilolite on bone integrity and on osteoporosis warrant further evaluation of treatment with PMA-zeolite-clinoptilolite as a new alternative adjuvant therapy for osteoporosis.

 5Clinical Trial

J Mol Med (Berl). 2001;78(12):708-20.

 doi: 10.1007/s001090000176.

Natural zeolite clinoptilolite: new adjuvant in anticancer therapy

K Pavelić 1M HadzijaL BedricaJ PavelićI DikićM KatićM KraljM H BosnarS KapitanovićM Poljak-BlaziS KrizanacR StojkovićM JurinB SubotićM Colić

Abstract

Natural silicate materials, including zeolite clinoptilolite, have been shown to exhibit diverse biological activities and have been used successfully as a vaccine adjuvant and for the treatment of diarrhea. We report a novel use of finely ground clinoptilolite as a potential adjuvant in anticancer therapy. Clinoptilolite treatment of mice and dogs suffering from a variety of tumor types led to improvement in the overall health status, prolongation of life-span, and decrease in tumors size. Local application of clinoptilolite to skin cancers of dogs effectively reduced tumor formation and growth. In addition, toxicology studies on mice and rats demonstrated that the treatment does not have negative effects. In vitro tissue culture studies showed that finely ground clinoptilolite inhibits protein kinase B (c-Akt), induces expression of p21WAF1/CIP1 and p27KIP1 tumor suppressor proteins, and blocks cell growth in several cancer cell lines. These data indicate that clinoptilolite treatment might affect cancer growth by attenuating survival signals and inducing tumor suppressor genes in treated cells.

6Environ Geochem Health. 2018 Dec;40(6):2657-2665.

 doi: 10.1007/s10653-018-0129-5. Epub 2018 Jun 7.

Histamine-binding capacities of different natural zeolites: a comparative study

Thangaraj Selvam 1Wilhelm Schwieger 1Wilfried Dathe 2

Abstract

Two different natural zeolites from Cuba and Mexico, which are already being used as contemporaneous drugs or dietary supplements in Germany and Mexico, respectively, are applied in a comparative study of their histamine-binding capacities as a function of their particle sizes. The zeolites are characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM) and N2-sorption measurements (BET surface areas). The Cuban zeolite contains clinoptilolite and mordenite as major phases (78% zeolite), whereas the Mexican one contains only clinoptilolite (65% zeolite). Both zeolites are apparently free from fibrous materials according to SEM. Both zeolites adsorb significant amount of histamine under the experimental conditions. Nevertheless, the results showed that the histamine-binding capacity of the Cuban zeolite is higher than the Mexican one and the smaller the particle size of zeolite, the higher the histamine-binding capacity. This difference could be due to the variation in their mineralogical compositions resulting in varied BET surface areas. Thus, the high histamine-binding capacities of Cuban zeolites seem to be due at least partly to the presence of the large-pore zeolite mordenite, providing high total pore volumes, which will be discussed in detail. For the first time, we have shown that the mineralogical compositions of natural zeolites and their particle sizes play a key role in binding histamine, which is one of the most important regulators in human physiology.

7Water Sci Technol. 2004;50(6):149-56.

Removal of ammonium from human urine through ion exchange with clinoptilolite and its recovery for further reuse

B Beler-Baykal 1S BayramE AkkaymakS Cinar

Abstract

Ammonium, from separately collected human urine, had been removed through transfer onto the ammonium selective natural zeolite, clinoptilolite, through ion exchange. In the subsequent treatment steps of washing with tap water, ammonium removed from urine was eluted from the surface of the clinoptilolite to be recovered for further reuse. Different quantities of clinoptilolite were used for a survey of the capacity of the zeolite for the process and to identify removal efficiencies based on initial ammonium loads. The highest surface concentration attained under experimental conditions employed was 15.44 mg ammonium per gram of clinoptilolite for an initial concentration of 110 mg ammonia per litre, and the highest removal was 98%, obtained for a loading of 1 mg ammonium per gram clinoptilolite. In the subsequent elution process, better removals were observed as pH was increased and the highest removal was attained at pH 13. The recovery was calculated as 9.73 mg ammonium per gram of clinoptilolite, corresponding to an efficiency of 63% only through washing with tap water. The results have given positive indications for the possibility of using ion exchange with clinoptilolite for the removal of ammonium from human urine and an incentive for improving methods of elution for its recovery for further reuse.

8

Environ Sci Pollut Res Int. 2021 May;28(19):24355-24361.

 doi: 10.1007/s11356-020-08483-z. Epub 2020 Mar 24.

Zn 2+ and Cd 2+ removal from wastewater using clinoptilolite as adsorbent

Camilla Galletti 1Melodj Dosa 2Nunzio Russo 2Debora Fino 2

Abstract

Many industries discharge wastewater from processing into surface and underground waterways, and then, these waste waters must therefore be treated in order to remove heavy metals. The most common treatment used is the activated carbon adsorption, a particularly competitive and effective process; however, the use of activated carbon is not suitable due to the high costs. Then, in order to minimize processing cost, recent investigations have been focused on the use of low-cost adsorbents as zeolites. In particular, clinoptilolite is known to have high selectivity for certain heavy metals. In this paper, the capability of clinoptilolite as a low-cost adsorbent for the removal of zinc and cadmium ions from wastewater was analyzed in a batch system. Preliminary characterization was performed on adsorbent material in order to evaluate the chemical-physical structure. Tests in batch for analyzing adsorbing capacity of clinoptilolite were carried out varying zinc and cadmium concentrations between 10 and 200 mg/L with different amounts of sorbent in the solution (10-60 g/L). For both zinc and cadmium ions, complete adsorption was reached when the concentration was equal to 10 mg/L and adsorption capacity decreased increasing metals amount. In particular, clinoptilolite permitted high Cd2+ abatement, probably due to its greater affinity with adsorbent in the single system. Binary system was then analyzed, and, contrary to previous tests, the adsorbent in the simultaneous presence of the two metals demonstrated a greater affinity toward zinc, showing a higher percentage of absorption, due to a different absorption mechanism in the presence of two ions.

9

Clinical Trial

J Altern Complement Med. 2017 Sep;23(9):738-744.

 doi: 10.1089/acm.2016.0414. Epub 2017 Jun 12.

Clinoptilolite for Treatment of Dyslipidemia: Preliminary Efficacy Study

Milisav Cutovic 1 2Milica Lazovic 1 2Vesna Vukovic-Dejanovic 2Dejan Nikolic 1 3Ivana Petronic-Markovic 1 3Dragana Cirovic 1 3

Abstract

Objectives: A tribomechanically activated clinoptilolite (natural aluminosilicate mineral) has been used to increase growth in meat-producing animals, as an adjuvant in cancer therapy, and a heavy metal remover in humans. Because of its unique cation exchanging and chelating properties, we hypothesized that clinoptilolite may be beneficial for the treatment of dyslipidemia in the manner similar to bile acid sequestrants. Thus, specific aims of this pilot study were to orally administer clinoptilolite in different doses and granule size combinations to determine magnitude and time profile of changes in blood lipids.

Design: A phase I/IIa prospective, open-label, uncontrolled, dose/granule size-ranging study (treatment phase 8 weeks, follow-up 6 weeks). Blood lipids were examined every 2 weeks.

Settings: Outpatient clinic of a university-affiliated hospital.

Subjects: Forty-one subjects (all white, mean age 57.6 ± 6.8 years, 17 women) with blood lipids above the normative limits divided into three groups.

Intervention: A tribomechanically activated clinoptilolite was administered in three dose/grind combinations: 6 g/day of fine grind (6gF), 6 g/day of coarse grind (6gC), and 9 g/day of coarse grind (9gC).

Outcome measures: Blood concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and triglycerides (TG).

Results: For the 3 groups combined, all lipid fractions significantly improved after 8 weeks of treatment (20-25%, p < 0.001), which reversed to baseline after 6 weeks of clinoptilolite withdrawal. Early (week 2) and the most pronounced decrease in TC and LDLc was observed in the 6gF group (19% and 23% in week 8, respectively), with no difference in HDLc and TG between the three dose/grind groups. No side effects were reported.

Conclusions: These pilot results suggest that oral administration of clinoptilolite may improve lipid profile in individuals with dyslipidemia, which warrants further investigations.

10

J Biomater Appl. 2017 Mar;31(8):1148-1168.

 doi: 10.1177/0885328216680152. Epub 2016 Nov 23.

Clinoptilolite/PCL-PEG-PCL composite scaffolds for bone tissue engineering applications

Engin Pazarçeviren 1Özge Erdemli 2Dilek Keskin 1 3Ayşen Tezcaner 1 3

Abstract

The aim of this study was to prepare and characterize highly porous clinoptilolite/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) composite scaffolds. Scaffolds with different clinoptilolite contents (10% and 20%) were fabricated with reproducible solvent-free powder compression/particulate leaching technique. The scaffolds had interconnective porosity in the range of 55-76%. Clinoptilolite/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) scaffolds showed negligible degradation within eight weeks and displayed less water uptake and higher bioactivity than poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) scaffolds. The presence of clinoptilolite improved the mechanical properties. Highest compressive strength (5.6 MPa) and modulus (114.84 MPa) were reached with scaffold group containing 20% clinoptilolite. In vitro protein adsorption capacity of the scaffolds was also higher for clinoptilolite/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) scaffolds. These scaffolds had 0.95 mg protein/g scaffold adsorption capacity and also higher osteoinductivity in terms of enhanced ALP, OSP activities and intracellular calcium deposition. Stoichiometric apatite deposition (Ca/P=1.686) was observed during cellular proliferation analysis with human fetal osteoblasts cells. Thus, it can be suggested that clinoptilolite/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) composite scaffolds could be promising carriers for enhancement of bone regeneration in bone tissue engineering applications.

11

Environ Technol. 2020 Jun 19;1-15.

 doi: 10.1080/09593330.2020.1779821. Online ahead of print.

Arsenate removal from contaminated water using Fe 2 O 3-clinoptilolite powder and granule

Maryam Tahmasebpoor 1Shamin Hosseini Nami 1Masoumeh Khatamian 2Leila Sanaei 1

Abstract

Natural clinoptilolite (Clin) was modified with iron oxide using three different methods including precipitation, wet-impregnation and ion-exchange and then the modified adsorbent with highest As(V) removal efficiency was encapsulated into Alginate by a simple cross-linking method to obtain Fe-Clin granules. The surface morphology and chemical composition of the Fe-Clin sorbents were characterized by scanning electron microscope and X-ray diffraction analysis. The selected Fe-Clin powders and granules possessed enhanced affinity towards the highly toxic arsenic pollutant in a very short time. Batch adsorption experiments showed that the Fe-Clin adsorbent can be widely used within a wide range of pH (2-9). In addition, to reach a high removal percentage (over 90%) of As(V), the optimum dosage of powder and granule shaped adsorbents was obtained as 0.1 and 0.6 g L-1, respectively. Both adsorbents could successfully remove As(V) in a very short amount of time as 20 and 30 min in the case of powders and granules, respectively. The maximum adsorption capacity of Fe-Clin granules evaluated by using Langmuir adsorption isotherm was found to be 11.17 mg g-1. By testing the granules in a circulated fluidized column experiment, it was demonstrated that Fe-Clin granules could remove As(V) up to an acceptable level (93%) within 10 min. This study demonstrates that Fe-Clin granules, obtained by exploiting natural clinoptilolite, iron oxide and alginate, are efficient, sustainable and fairly cheap adsorbents for the removal of arsenate from the aquatic environment in a very short contact time.

 12

J Environ Manage. 2020 Nov 1;273:111113.

 doi: 10.1016/j.jenvman.2020.111113. Epub 2020 Jul 29.

Removal of polycyclic aromatic hydrocarbons from aqueous media using modified clinoptilolite

Monireh S Hedayati 1Loretta Y Li 2

Abstract

Carcinogenic polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment. In this study, the removal of PAHs from aqueous media was assessed using samples of clinoptilolite, a natural zeolite, pre-treated with 1 mol/L of NaCl, (Na pre-treated clinoptilolite, NC). Samples (10 g) of NC were separately modified with 5, 2, 2, and 20-mmol/L solutions of cetylpyridinium chloride (CPC), didodecyldimethyl ammonium bromide (DDAB), hexadecyltrimethylammonium bromide (HDTMA), and tetramethyl ammonium chloride (TMA) surfactants as potential cost-effective adsorbents. The kinetics, optimal sorbent dosage, and competitive effects were evaluated through batch adsorption tests using deionised water spiked with five PAHs (anthracene (50 μg/L), fluoranthene (100 μg/L), fluorene (100 μg/L), phenanthrene (100 μg/L), and pyrene (100 μg/L)). The surfactant non-modified (NC) and TMA-MC (modified clinoptilolite) exhibited PAH removal of <66% from the spiked concentration in aqueous solution, while CPC-MC, DDAB-MC, and HDTMA-MC achieved removal rates of >93% for the five PAHs after 24 h at a solid:liquid ratio of 1:100. The remaining concentrations of anthracene and fluoranthene were below 3 μg/L, and that of fluorene was <6 μg/L, lower than the water quality criteria of British Columbia, Canada, for protecting aquatic life. However, HDTMA-MC retained >83% of the fluorene. Over 80% of all PAHs were absorbed within 15 min for the CPC-MC and DDAB-MC, and the maximum adsorption was reached in <2 h. Three kinetic models were applied assuming pseudo-first-order, pseudo-second-order, and intra-particle equations, and the results were well-represented by the pseudo-second-order equation. The PAH sorption results indicated that the adsorption mechanism is based on PAH hydrophobicity, and π-π electron-donor-acceptor interaction with surfactant. CPC and DDAB with two long chain hydrocarbons had more PAH adsorption than HDTMA with one, and TMA with no long chain hydrocarbons (DDAB-MC > CPC-MC > HDTMA-MC ≫TMA-MC > NC). With a solid: liquid ratio of 1:200, over 90%, 80%, and 70% of the anthracene, fluoranthene, and pyrene were adsorbed by the CPC-MC, DDAB-MC, and HDTMA-MC, respectively.


 14Exp Biol Med (Maywood). 2021 Mar;246(5):529-537.

 doi: 10.1177/1535370220968752. Epub 2020 Nov 12.

Treatment of osteoporosis with a modified zeolite shows beneficial effects in an osteoporotic rat model and a human clinical trial

Sandra Kraljević Pavelić 1Vedran Micek 2Dragica Bobinac 3 4 5Edo Bazdulj 3 4Alessandra Gianoncelli 6Dalibor Krpan 7Marta Žuvić 8Sandra Eisenwagen 9Peter J Stambrook 10Krešimir Pavelić 5

Abstract

The severity of osteoporosis in humans manifests in its high incidence and by its complications that diminish quality of life. A societal consequence of osteoporosis is the substantial burden that it inflicts upon patients and their families. Several bone-modifying drugs have been prescribed to patients with osteoporosis. However, evidence for their anti-fracture efficacy remains inconclusive. To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. We now present an alternative and adjuvant approach for treatment of osteoporosis. The data derive from in vivo studies in an ovariectomized rat model and from a randomized double blind, placebo-controlled human clinical study. Both studies involved treatment with Panaceo Micro Activation (PMA)-zeolite-clinoptilolite, a defined cation exchange clinoptilolite, which clearly improved all bone histomorphometric parameters examined from ovariectomized animals, indicative for increased bone formation. Moreover, intervention with PMA-zeolite-clinoptilolite for one year proved safe in humans. Furthermore, patients treated with PMA-zeolite-clinoptilolite showed an increase in bone mineral density, an elevated level of markers indicative of bone formation, a significant reduction in pain, and significantly improved quality of life compared with patients in the control (placebo) group. These encouraging positive effects of PMA-zeolite-clinoptilolite on bone integrity and on osteoporosis warrant further evaluation of treatment with PMA-zeolite-clinoptilolite as a new alternative adjuvant therapy for osteoporosis.

17

Environ Geochem Health. 2018 Dec;40(6):2657-2665.

 doi: 10.1007/s10653-018-0129-5. Epub 2018 Jun 7.

Histamine-binding capacities of different natural zeolites: a comparative study

Thangaraj Selvam 1Wilhelm Schwieger 1Wilfried Dathe 2

Abstract

Two different natural zeolites from Cuba and Mexico, which are already being used as contemporaneous drugs or dietary supplements in Germany and Mexico, respectively, are applied in a comparative study of their histamine-binding capacities as a function of their particle sizes. The zeolites are characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM) and N2-sorption measurements (BET surface areas). The Cuban zeolite contains clinoptilolite and mordenite as major phases (78% zeolite), whereas the Mexican one contains only clinoptilolite (65% zeolite). Both zeolites are apparently free from fibrous materials according to SEM. Both zeolites adsorb significant amount of histamine under the experimental conditions. Nevertheless, the results showed that the histamine-binding capacity of the Cuban zeolite is higher than the Mexican one and the smaller the particle size of zeolite, the higher the histamine-binding capacity. This difference could be due to the variation in their mineralogical compositions resulting in varied BET surface areas. Thus, the high histamine-binding capacities of Cuban zeolites seem to be due at least partly to the presence of the large-pore zeolite mordenite, providing high total pore volumes, which will be discussed in detail. For the first time, we have shown that the mineralogical compositions of natural zeolites and their particle sizes play a key role in binding histamine, which is one of the most important regulators in human physiology.

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