clays and binders, gut health

Amine binding Zeolites

Zeolites are being explored as a means of removing excess 5-HT from the GI tracts of patients with neuro endocrine tumors. [1] These authors looked at three different zeolites..Histamine is a decarboxylation product of the amino acid histidine and the culprit in scombroid poisoning rfrom eating contaminated fish.

  • Detoxosan is a Cuban zeolite that consists of 43 wt% HEU, 35 wt% MOR and 22% non-identified materials.
  • Mordenite was synthesized as previously describe in a protocol referenced in this paper.
  • San Felipe, Guanajuato in Mexico was the source of the 3rd aeolite. .  The Mexican sample contains 65 wt% HEU (three letter code assigned by the international zeolite association (IZA) for clinoptilolite) 35 wt% amorphous unidentified material.  The Mexican zeolite was sieved to be under 40 µm to more closely resemble the Cuban zeolite.

Those in the United States are not going to be able to import Detoxosan from Cuba.  Making mordenite is not for everyone.  Importing from Mexico is an option. 

Table1 gives a nice atomic composition atomic composition and a definition of what mordenite is all about. The Na+ counter cation is claimed to be easily displaced from the channels.[1]

zeoliteSourceAl:Si:Na:K:Ca:Σ cc
Mordenite (MOR)Synthetic1.07.340.890.89
Clinoptilolite (HEU)Natural1.05.670.
DETOXSAN (HEU/MOR)Natural1.06.580.
Table 1 from reference [1]

The Cuban zeolite in Detoxosan contains more charge-compensating sodium ions than the natural Mexican one.  Synthetic zeolites are conventionally synthesized in presence of one or two different types of cations depending on their application.  The synthetic mordenite topology possesses only sodium as charge-compensating cation because of the composition of the synthesis gel. The Si/Al molar ratio of the microporous sample is 7.3. Table 2 from publication [1] is not being presented simply because the authors did not results profound differences in uptake and release of 5=HT..

Uptake and release studies. All uptake and release studies were performed in 100 ml three-neck flasks with stirring and temperature control.  Three pH were examined:
5, 7, and 9. The experiments at a pH 7 were performed in pure distilled water, whereas pH 5 and 9 were adjusted with 0.01 M aqueous hydrochloric acid (HCl) and
sodium hydroxide (NaOH), respectively.   A very slight objection to this is that they are using the 5-HT and the clay as the buffering agent.  Another very slight objection is that this is also a not so good simulation of the GI environment.  The temperature was adjusted to 36 °C. Then, 5-HT-hc was added to obtain a concentration of around 0.9 g l-1 in the liquid phase after its complete dissolution, and the zeolite adsorbent was added to obtain a concentration of 30
gzeolite l-1, independent of the chosen sample. After a certain time, the suspension was filtered using a Büchner funnel and checked for 5-HT-hc levels. For the release studies, the loaded zeolite was added again to 100 ml of the solution with the desired pH level. The 5-HT-hc concentration in the solution was monitored using UV–Vis spectroscopy until no further quantitative changes occurred.

Detoxosan binds about 35 wt% more histamine than HEU19, whereas HEU binds about 6 wt% more 5-HT-hc than Detoxosan… [2]

One of the goals of the Grass study was to find a therapy to reduce 5-HT level within the bowels, thereby reducing diarrhea, as shown in cancer patients with a responder rate of about 70%. It is essential to investigate whether enough binding sites for 5-HT still exist at zeolite surface or whether they have already been occupied by histamine during passage through the stomach. [2] The authors contemplated stomach protection.  Histamine is only the tip of the iceberg of materials that will bind to alumina in the stomach.  Nitrogen groups will be present in peptides of the digested meal if the clay is consumed with a meal.  In this study the Detoxosan out performed the Mexican clinoptiolite by about 2x in histamine absorption. [2]

From Selvam 2008 [2]

All they did was obtain some really nice electron microscope images and some X-Ray. X-ray diffraction XRD for mineral identification should not be confused with X-ray fluorescence XRF for elemental analysis. Problem areas like lead could be followed up by ICP-MS

Protocols for making your own…

A study by Alvarez-Aguiñaga and coworkers examined an obscure zeolite deposit in a very specific region of Mexico, [3] The authors found U.V. catalyzed degradation of caffeine that may not be of concern to us. The protocols they used to clean up the zeolite [3] are pretty interesting.

The natural zeolitic tuff employed in this study was obtained from the location Carranco Blanco, municipality Villa de Reyes, San Luis Potos´ı 21o50’33N 101o40’25”(1940 mamsl). The tuffis tertiary volcanic rock that has been formed from deposits of Tophaceous rocks from the upper Mesozoic and the Cenozoic with ignimbrite composition.

  1. The rock was ground and sieved to obtain a grain size within 2.38 and 3.36 mm.
  2. The particles exhibit a rough surface morphology with some clefts of different depth .
  3.  The selected particles were washed for 8 h with deionized water and dried in air at 150 oC to obtain NZ.
  4. When dry, 1 g of zeolite was suspended in 10 mL of an aqueous hydrochloric acid solution (1 mol/liter) stirred for 8 h at 60 oC to produce NH.
  5. NZ was ion-exchanged to produce NFe.
  6. 1 g of NZ and 10 mL of an ammonium hydroxide solution (1 mol L-1) were stirred for 8 h at room temperature.
  7. The resulting material was put in contact with 10 mL of a ferrous chloride solution (0.25 mmol L-1) and was stirred for 8 h at room temperature.
  8. The prepared NH and NFe were filtered, washed with deionized water and dried in air at 150oC overnight.

Alvarez-Aguiñaga used mixtures of synthetic clinoptilolite (C) and synthetic Na-mordenite (M) from commercial sources, mixed together, and washed in HCl. This they referred to as SH. [3]

Characterization of zeolites aka quality controls

  • SEM micrographies
  • X-ray diffraction (XRD) patterns of the zeolites.
  • The elemental composition was determined in duplicate by XRF.
  • The particles were ground and mixed with 20% Hoechst wax C micro-powder to form tablets for DRS-UV-Vis-NIR measurements.
  • The specific surface area (SL) obtained from the [3] …Not sure if I want to go in this direction.

Adsorption experiments were performed at pH 5.5 and 21oC. [3] The isoelectric point IEP of alumina is pH 8-9 and for silica it is pH 1.7-3.5. The alumina should carry a negative charge at this point and the silica a positive charge. This is where things get intriguing. Each zeolite variation will have a slightly different geometry and spacing of the alumina and silica groups.

Other Directions?

.Other amines not covered in the review of the literature are

  • Skatole, the tryptophan metabolite that give feces some of their characteristic odor.
  • Cadaverine, as the name suggests, is generally associated with the putrefaction of animal tissue. It is the byproduct of the decarboxylation of the amino acid lysine.
  • Putrescine, like cadaverine, is associated with decaying flesh. It is the decarboxylation product of the amino acid arginine.

Could some of these zeolites absorb these amines? What would be thebenefit? Following up on suggestions from Wikipedia authors, PubMed was searched for “Trace amine associated receptor” + “brain” Of all of the hits, [4] was perhaps the most interesting for those of us wishing to treat issues involving the gut-brain axis. The Katolikova 2022 study used public accessible data sets for mining for TAAR receptors. One in particular was a single cell dataset:

SCP1Single nucleus RNA-seq of cell diversity in the adult mouse hippocampu1367 single nucleiNuclei from hippocampal anatomical sub-regions DG, CA1, CA2, CA3 and lowly abundant GABAergic neurons were analyzed
A portion of Table 1 from Katolikova 2022 [4]

Distribution of TAARs expression in the murine hippocampal cell populations in the SCP1 dataset (picture was generated by the Single Cell Portal interactive interface). Expression levels are marked by color in accordance with the color scale.[4] The more limited human hippocampus mRNA data were not completely congruent with this particular mouse dataset. Katolikova et al. discussed previous experiments with TAAR2 and TAAR5 knock out mice and their neurological phenotypes.

One reference was quoated as finding a higher level of spermidine in DG. This was associated with decreased anxiety. Spermine in DG had a completely opposite pattern. Putrescine stimulates neural progenitor proliferation. Its depletion leads to the disorder of the neural progenitor cell cycle

The PubMed search yields association of TAAR receptors with many neurolo- psychiatric diseases. This post will stop here. The clay binders need to be watched. Can they prevent amines from our guts from arriving to our brains?


  1. Grass JP, Pals U, Inayat A, Schwieger W, Hartmann M, Dathe W. (2021) Uptake and release characteristics of serotonin hydrochloride by natural Cuban zeolite containing clinoptilolite and mordenite. Sci Rep. 2021 Jul 12;11(1):14277. PMC free article
  2. Selvam T, Schwieger W, Dathe W. (2018)Histamine-binding capacities of different natural zeolites: a comparative study. Environ Geochem Health. 2018 Dec;40(6):2657-2665. PMC free article
  3. Alvarez-Aguiñaga EA, Elizalde-González MP, Sabinas-Hernández SA. Unpredicted photocatalytic activity of clinoptilolite-mordenite natural zeolite. RSC Adv. 2020 Oct 26;10(64):39251-39260. Free article
  4. Katolikova NV, Vaganova AN, Efimova EV, Gainetdinov RR. Expression of Trace Amine-Associated Receptors in the Murine and Human Hippocampus Based on Public Transcriptomic Data. Cells. 2022 Jun 1;11(11):1813. PMC free article

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