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Must read links Excerpts from the Handbook of Clay Science CLAYS AND HUMAN HEALTH-- CLAYS AND MINERALS AS DRUGS
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CLAYS AND CLAY MINERALS AS DRUGS
M.T. DROY-LEFAIXa AND F. TATEOb
aBeaufour-IPSEN, F-75016 Paris, France
bIstituto di Ricerca sulle Argille, CNR, I-85050 Tito Scalo (PZ), Italy
(Please note that the terms bentonite and montmorillonite
Montmorillonite is the main constituent of the volcanic ash weathering
Montmorillonite is the main constituent of the volcanic ash weathering product, bentonite.)
Clay therapy is based on the ability of clays and clay minerals to adsorb and
retain harmful and toxic substances. The beneficial effects of these materials to
human health, notably in the treatment of gastrointestinal disorders, were recognized.
Indeed, the eating of clay (‘geophagy’) was practiced since antiquity in all
parts of the world. Among the variety of clays and clay minerals that were used by
primitive tribes are bentonite, kaolinite, montmorillonite, smectite (calcium and sodium bentonites), and ‘pascalite’
(a calcium bentonite from Wyoming, USA) (Eaton and Eaton, 1995).
Examination of the diets of certain tribes in the high Andes of South America and
central Africa, and those of Australian aborigines, showed that these people use clay
to avoid getting stomach-ache, dysentery, and food infections. Indeed, the Quetchus
Indians of South America used to dip their potatoes into an aqueous suspension of
clay, immediately before eating, in order to prevent the build-up of acidity in the
stomach. This dietetic procedure is still being followed by some tribes of American
Indians. A similar practice was traditionally carried out on board ships where sailors
used clays not only to adsorb odours and moisture but also to treat dysentery, burns,
boils, sore mouths, and other internal and external disorders.
Although recent research confirmed that clays and clay minerals possess general
curative properties, it is the treatment of disorders that remains the focus of attention.
By adsorbing ‘aggressors’ (infectious factors) of the gastrointestinal mucosa
barrier, these materials can serve as both prophylactic and therapeutic agents.
11.6.1. INTERACTIONS OF CLAY MINERALS WITH
At the surface of the gut, a mucus gel adheres to the epithelial cells of the mucosa.
This adherent mucus is dynamic, being continuously secreted by the caliciform cells
and regularly eroded by environmental ‘aggressors’ present in the gut lumen.
The mucus gel is largely composed of glycoprotein polymers, lipids, and proteins,
linked together by covalent bonds. As such, it acts as a physical barrier protecting
the mucosa against penetration by extraneous molecules and mechanical injury.
By maintaining a pH gradient and competing with the epithelial surface for microorganisms,
the mucus gel also acts as a chemical barrier.
Thus, a weakening of the mucus gel barrier may be at the origin of disorders such
as gastritis and colitis (Droy-Lefaix, 1987). Short-term treatment with clay minerals,
such as smectite (calcium and sodium bentonites)s (More´ et al., 1987) and attapulgite (More´ et al., 1992) increases the
thickness of the adherent mucus. This may be ascribed to interactions of mineral
particles with mucus components (Leonard et al., 1994) by which the gastrointestinal
glycoproteins are modified, and their polymerization is enhanced (Droy-Lefaix
et al., 1986). Similarly, aluminium (hydr)oxides (e.g., boehmite) can reduce mucus
degradation (Bouyssou et al., 1990). The beneficial effects of minerals are also associated
with improvements in the rheological properties of the mucus gel, such as
spinability. This reflects the increased extent of polymerization, and the improvement
in quality, of the adherent mucus (Droy-Lefaix et al., 1985). Changes in the
physico-chemical properties of the mucus, induced by the action of clay minerals,
were confirmed by electron paramagnetic resonance and fluorescence spectroscopy.
The results indicate that clay mineral ingestion decreases mucus solubility. At the
same time, the viscosity and hydrophobicity of the mucus increases, enhancing its
adhesion to epithelial cells.
11.6.2. CLAY MINERALS, MUCOSAL BARRIER, AND
By acting directly on the mucus gel, clays and clay minerals exert a stabilizing
effect on the mucosal barrier (Gwozdzinski et al., 1997), providing protection against
different ‘aggressors’ of the gastrointestinal mucosa.
Pepsin, a substance necessary for digestion, is a typical ‘aggressor’. Experiments
with rats showed that if pepsin secretion at the surface of the gastric mucosa is
strongly increased (due to pathological disregulation), the adherent mucus layer is
progressively disrupted. At the same time haemorrhagic mucosal lesions appear, and
significant bleeding occurs in the lumen as well as localized ulceration in an otherwise
intact epithelium. By binding to the mucus components, smectite (calcium and sodium bentonites) can completely
inhibit the damage induced by pepsin (Leonard et al., 1994).
Samson et al. (1995), for example, showed that patients with ulcerative colitis
show a six-fold greater mean total faecal proteinase activity (expressed in mmol
terminal NH2/min/g dry weight of faeces) than the control. smectite (calcium and sodium bentonites) totally inhibits
this enzyme activity. The effects of smectite (calcium and sodium bentonites) on mucus proteolysis are assessed using a
model of mucolytic activity, assayed by the release of degraded colonic mucin
from the adherent mucus gel of freshly prepared pig colonic bags in vitro. Similarly,
trypsin (2 mg/mL) releases three times more soluble mucin per bag than the
control. smectite (calcium and sodium bentonites) (100 mg/mL) inhibits trypsin activity, causing the level of degraded
mucin to fall below the normal value. This is ascribed to the interaction of smectite (calcium and sodium bentonites)
with the adherent mucus layer, and the binding of trypsin to the mineral (Samson
et al., 1995).
Clay minerals can also provide protection against attack by bile acids that cause
gastrointestinal ulceration. In rats, oral administration of sodium glycodeoxycholate
or sodium taurocholate induces severe erosion of the jejunal mucosa. After treatment
with smectite (calcium and sodium bentonites) (which interacts closely with the mucus glycoproteins) the severity of
surface erosion is greatly diminished (Fioramonti et al., 1990), while the rheological
properties of the adherent mucus gel are maintained within normal limits (Droy-
Lefaix et al., 1985).
Because of their strong bioadhesive properties, clay minerals also afford protection
of the colon against damage from reactive oxygen species. Oxygenated free
radicals, released by infiltration of white cells into the colonic mucosa barrier, are
very unstable. Their presence can induce severe erosion of the colonic mucosa,
leading to mucolysis. By maintaining the solution viscosity of the colonic mucin, and
inhibiting the hypersecretion of mucus, smectite (calcium and sodium bentonites) can prevent the onset of mucolysis
(Pearson et al., 1996; Knight et al., 1998).
In many digestive diseases, the intestinal barrier is weakened by the release of proinflammatory
cytokines, induced by abnormal activation of the epithelial cells and
the underlying immune system. These cytokines include a tumour necrosis factor–a
(TNF-a) and an interferon-g factor (INF-g). When intestinal cells (line HT 29-19 A)
are incubated with TNF-a and INF-g, intestinal function (assessed in Ussing chambers
by measuring ionic conductance, apicobasal fluxes of14C-mannitol, and intact
horseradish peroxidase) is altered, and the tight junction between cells is disrupted.
In the presence of smectite (calcium and sodium bentonites) (100 mg/mL) the values of these parameters are similar to
those of the control (Mahraoui et al., 1997).
The cytoprotective effects of clay minerals can also account for their ability to
prevent damage of the gastrointestinal mucosa caused by such ‘aggressors’ as
ethanol and anti-inflammatory drugs. Ethanol, directly administered into the stomach,
gives rise to severe gastric ulcerations and macroscopic necrosis of the
gastric mucosa. These deleterious effects are accompanied by a decrease in the gastric
transmural potential difference which serves as a criterion of the functional
integrity of the mucosa (Fioramonti et al., 1990). Erosion of the mucus layer leads to
a significant alteration of rheological properties (Droy-Lefaix et al., 1992; Slitine-
Bonet et al., 1994). smectite (calcium and sodium bentonites) treatment for two days can significantly counteract the
harmful effect of ethanol, reducing the irritative index (Fioramonti et al., 1990).
Clay minerals also provide protection against the action of anti-inflammatory
drugs. For example, the oral administration of aspirin (2 g) to pigs, and phenylbutazone
(200 mg/kg) to rats, decreases the gastric potential difference, and induces
severe ulceration due to mucus alteration (Fioramonti et al., 1990; Droy-Lefaix
et al., 1992). The extent of lesion and mucus degradation is significantly reduced
after treatment with smectite (calcium and sodium bentonites). In humans the symptoms of gastropathies, induced by
non-steroid anti-inflammatory drugs, can be successfully treated by ingestion of
smectite (calcium and sodium bentonites) (Peignot et al., 1997).
11.6.3. ADSORPTIVE PROPERTIES OF CLAYS AND CLAY MINERALS
The adsorptive properties of clay minerals provide the basis for the therapeutic
uses of clays.
Clays can adsorb a variety of toxic substances, such as strychnine (Droy-Lefaix,
1986), mycotoxins (e.g., T2 toxin) (Fioramonti et al., 1987b), aflatoxin (Schell et al.,
1993), enterotoxins (Brouillard and Rateau, 1989), and toxins produced by Vibrio
cholerae, Escherichia coli (Fioramonti et al., 1987b), and Yersinia pseudotuberculosis
(Carnoy et al., 2000).
By doing so, clays can provide active protection against disturbances during
gastrointestinal transit. In mice, for example, gastric emptying and small intestinal
transit are significantly accelerated after oral administration (1 mg/kg for 4 days) of
T2 toxin. However, if the toxin is incubated with smectite (calcium and sodium bentonites) for 24 h beforehand, no
increase in the rate of gastric emptying and small intestinal transit occurs (Fioramonti
et al., 1987a).
In conscious dogs, intraduodenal administration of cholera toxin (200 mg) affects
gastrointestinal transit, and disrupts the migrating motor complexes (MMCs) of the
stomach and jejunum. According to the duration of treatment (at a dose of 100 mg/
kg/day), smectite (calcium and sodium bentonites) can effectively counteract the effects of cholera toxin (Fioramonti
et al., 1987b).
smectite (calcium and sodium bentonites) can also adsorb the enterotoxin ofClostridium difficile (Martirosian
et al., 1998). In rats, this toxin causes intestinal permeability to increase through
hypersecretion of colonic water. Both these conditions can be alleviated by treatment
with51Cr-EDTA in the presence of smectite (calcium and sodium bentonites) (Fioramonti et al., 1994).
E. colitoxin is an infectious agent causing diarrhoea. Heat-stable toxin (ST) from
E. coli, directly administered to New Zealand rabbits, induces a significant increase
in intestinal permeability (as estimated by Evans Blue) and severe damage to ileal
loops (as revealed by scanning electron microscopy). The presence of smectite (calcium and sodium bentonites) in the
ileal loops has a protective effect (Pons et al., 1997).
Similar results are obtained with the enterotoxin ofBacteroides fragilis administered
to HT/29 C1 cells (human colon adenocarcinoma cell line). Prior incubation
of this toxin with smectite (calcium and sodium bentonites) suppresses its toxic effects (Martirosian et al., 1998).
Because of their high adsorptive capacity, clay minerals can also protect the digestive
mucosa against pesticide damage. Diquat, a widely used non-selective desiccant
herbicide, induces erosion of intestinal mucosa and fluid hypersecretion. In rats that
were given diquat, treatment with smectite (calcium and sodium bentonites) (500 mg/kg for 2 weeks) brings about a
normalization of mucus rheological properties and intestinal permeability, as
746Chapter 11.6: Clays and Clay Minerals as Drugs
indicated by urine analysis using51Cr-EDTA (Theodorou et al., 1995). Similarly,
montmorillonite and bentonite are good adsorbents, and may be recommended for
the treatment of pesticide poisoning (Meredith and Vale, 1987).
Clay minerals are efficient drugs for treating disorders of the gastrointestinal mucosa,
induced by microorganisms. Kaolinite and montmorillonite are capable of
adsorbing viruses (Lipson and Stotzky, 1984). As such, these minerals can induce
rapid recovery when administered to children suffering from gastroenteritis.
Similarly, the strong adsorptive power of smectite (calcium and sodium bentonites) lies behind its ability to aggregate
bacteria, such as strains ofE. coli with the plasmid P, carrying a virulence factor
in the form of an external protein CS 31A (Girardeau, 1987).
In the stomach,Helicobacter pylori is associated with gastritis and gastroduodenal
ulcers. This bacterium is also one of the most important ethiopathogenic factors
causing peptic ulcer. smectite (calcium and sodium bentonites), on HeLa cells infected byH. pylori isolated from
human biopsies, significantly reduces adhesion of the bacteria to the surface of
epithelial cells (Bonneville et al., 1990). This is why smectite (calcium and sodium bentonites) is effective in treating
the symptoms of people with non-ulcer dyspepsia who are infected byH. pylori
(DeKorwin et al., 1993).
In the intestine, smectite (calcium and sodium bentonites) is effective against diarrhoea as shown by clinical data for
new-born calves with neonatal gastroenteritis. Faeces analysis reveals the presence of
rotavirus in 41.3% of the animals as well as that ofE. coli K99, coronavirus, and
Salmonella. Recovery is observed in 72% of calves after 2.8 and 2.2 days of receiving
250 and 500mg/kg smectite (calcium and sodium bentonites), respectively, and after 4.2 days in calves which do not
receive smectite (calcium and sodium bentonites). After 4 days of treatment, the consistency of the faeces is significantly
better in calves receiving smectite (calcium and sodium bentonites) than in the control animals (Espinasse et al., 1987).
Clay minerals can serve as gas adsorbents in patients with symptoms of flatulence
and abdominal distension. Thus, smectite (calcium and sodium bentonites) can reduce the amount of hydrogen
emitted during colonic fermentation (Frexinos et al., 1986; Arbeille et al., 1991).
E. Alimentary Allergy
Food allergy is also responsible for disturbances in colonic transit, water absorption,
and intestinal permeability. Guinea pigs that were sensitized byb-lactoglobulin from
cow milk show colonic transit acceleration, a colonic hypersecretory response, a
strong increase in intestinal permeability, and a decrease in faecal dry matter. These
effects are not observed in animals that were treated with smectite (calcium and sodium bentonites). Clays can inhibit
anaphylaxia probably by controlling the release of mediators at the origin of the
degranulation of the mast cells (Theodorou et al., 1994).
11.6.4. CLAY MINERALS AND CLINICAL APPLICATIONS
Being good adsorbents and mucostabilizers, clay minerals are efficacious against
several aggressive agents causing severe intestinal disorders. Acute gastroenteritis is a
major cause of morbidity and mortality among children worldwide (Madkour et al.,
1993). By adsorbing viruses, bacteria, and other digestive irritants, clay minerals can
shorten the course of acute diarrhoea, and reduce the occurrence of prolonged diarrhoea.
Furthermore, these minerals do not interfere with the electrolyte balance,
and are well tolerated by patients (Buttron, 1987; DuPont et al., 1990; Bauer and
Hirschbrunn, 1992; Charritat et al., 1992; Dupont et al., 1992; Vivatvakin et al.,
1992; Lexomboon et al., 1994; Karas, 1996; Milocco et al., 1999; Guarino et al.,
2001; Narkeviciute et al., 2002).
Clay minerals also provide protection against diarrhoeas induced by antibiotics
treatments (Benhamou et al., 1995), alleviate chronic diarrhoeas induced by chemotherapy
and radiation (Hornbrink et al., 1995; Ippolite, 1998; Santantonio et al.,
2000), enteral nutrition (Perrotin et al., 1990), and HIV infection (Phanuphak et al.,
1992; Mastroianni et al., 1998).
Clay minerals are promising drugs in the treatment of irritable bowel syndrome
(IBS), a rather frequent disease in adults with a complex pathogenic mechanism.
By enhancing the thickness of the mucus barrier, both colon movement function and
faeces consistency are restored, and the symptoms of IBS are alleviated (Opriu et al.,
1996; Secondulfo et al., 2002). In parallel, clay minerals have a positive effect on
flatulence and abdominal distension (Lukas and Lukas, 2000).
Clay minerals protect and are efficient against several ‘aggressors’ that cause major
disorders of the gut. These beneficial effects of clay minerals (on the gastrointestinal
mucosa) are associated with two mechanisms of action: (1) adsorption of the ‘aggressors’
or their toxic secretions and (2) modification of the thickness and rheological properties
of the adherent mucus, reinforcing the natural defenses of the gastrointestinal mucosa.
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