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Functional foods with digestion-enhancing properties

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On analyzing the traditional societies' plant lore by treatment and plant categories, one cannot but notice the greater weight given to treatment of digestive disturbances and ailments compared to modern Western pharmacopoeias, and the blurred boundaries between medicines and foods, in contrast to the clear-cut distinction made in contemporary industrialized societies. Hence, there is an interest in exploring the issue of multifunctional food and traditional ingredients with digestive properties. In this paper, I examine the coevolutionary foundations for digestive activities, the problems and ambiguities that emerge in the analysis of traditional data, and the possible biological mechanisms underlying the actions of bitter, aromatic and pungent compounds. After these premises, this paper presents a short review of those plants with a significant body of research supporting the claims that they have a digestive action, with particular emphasis on clinical data. The plants that have a substantial body of data in support of their digestion-enhancing activities mainly belong to one of three groups: bitter, aromatic and pungent plants. Amongst the most important we can find ginger, peppermint, aniseed and fennel, citrus fruits, dandelion and artichoke, melissa and chamomile, but many more have a significant body of experimental data available.
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Functional foods with digestion-enhancing properties
MARCO VALUSSI
European Herbal and Traditional Medicine Practitioners Association (EHTPA), 25 Lincoln Close, Tewkesbury, GL20 5TY, UK
Abstract
On analyzing the traditional societies’ plant lore by treatment and plant categories, one cannot but notice the greater weight
given to treatment of digestive disturbances and ailments compared to modern Western pharmacopoeias, and the blurred
boundaries between medicines and foods, in contrast to the clear-cut distinction made in contemporary industrialized societies.
Hence, there is an interest in exploring the issue of multifunctional food and traditional ingredients with digestive properties.
In this paper, I examine the coevolutionary foundations for digestive activities, the problems and ambiguities that emerge in
the analysis of traditional data, and the possible biological mechanisms underlying the actions of bitter, aromatic and pungent
compounds. After these premises, this paper presents a short review of those plants with a significant body of research
supporting the claims that they have a digestive action, with particular emphasis on clinical data. The plants that have a
substantial body of data in support of their digestion-enhancing activities mainly belong to one of three groups: bitter, aromatic
and pungent plants. Amongst the most important we can find ginger, peppermint, aniseed and fennel, citrus fruits, dandelion
and artichoke, melissa and chamomile, but many more have a significant body of experimental data available.
Keywords: medicinal foods, spices, TAS2R, TRP, ethnobotany
Introduction: plants used for gastrointestinal
complaints in the folk traditions
Modern ethnobotanical literature shows that indigen-
ous plant remedies and functional foods (FFs) are
focused, more than Western pharmacopoeias, on
gastrointestinal (GI) disorders, which represent
10% 50% of the indications (see e.g. Etkin and Ross
1994; Balick and Cox 1996; Pieroni and Price 2006).
One possible explanation for this trend is that the
genus Homo had to evolve in a world rich in alimentary
toxins, and had to develop a system of detection,
management and defence against those same toxins.
The GI tract, the first diaphragm between the external
world (xenobiotics) and the internal physiology, is the
site for this system and hence a preferred site of
interaction with medicinal plants and FF (Johns 1990).
FF used for GI complaints in the folk traditions
Two main data that emerge from a review of FF
used worldwide for digestive complaints, supported
by other published data:
.A significant percentage, between 20% and 56%
(on average 40%), of edible wild plants is used in
traditional societies as a medicine (Pieroni and
Price 2006).
.There is a high prevalence of species belonging to
three taxa Asteraceae, Lamiaceae and Apiaceae
and of species containing molecules belonging to
three phytochemical groups: essential oils, bitter
compounds and pungent compounds (Leonti et al.
2006; Ali-Shtayeh et al. 2008).
Coevolution and gut sensorium
A recent model of neurohumoral control of GI
function seems to be able to connect these apparently
disconnected data. According to this model, the GI
tract can be seen as a sense organ (via tastant-sensing
cells) that has coevolved with some phytochemicals
(such as bitter or pungent compounds), and which
allows their detection and appropriate response by
means of paracrine and endocrine release (Kitamura
et al. 2010). Bitter and pungent taste receptors are the
main mediators of these actions (see Figure 1).
ISSN 0963-7486 print/ISSN 1465-3478 online q2011 Informa UK, Ltd.
DOI: 10.3109/09637486.2011.627841
Correspondence: M. Valussi, European Herbal and Traditional Medicine Practitioners Association (EHTPA), 25 Lincoln Close, Tewkesbury,
GL20 5TY, UK. Current address: Via della Pace 9, 37124 Verona, Italy. Tel: 00390459251461. E-mail: marco@infoerbe.it; www.ehpa.eu;
ehpa@globalnet.co.uk
International Jour nal of Food Sciences and Nutrition,
2011; Early Online: 1–8
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Bitter receptors
In Homo and in mammals, the capacity to detect
the presence of toxic substances is strongly associated
with the development of bitter receptors (taste
receptor type 2 TAS2R) in the oral cavity,
an evolutionary-conserved mechanism to prevent
ingestion of bitter-tasting dietary toxins (Meyerhof
et al. 2005; Scott 2005) (see Table I).
In the last 10 years, there have been various
reports on the presence of the receptors in extraoral
sites, with non-gustatory functions (Wu et al. 2002),
whose activation promotes the release of GI peptides,
in particular cholecystokinin (CCK) (Dockray 2003;
Flemstrom and Sjoblom 2005). This in turn triggers
the release of pancreatic enzymes and of bile salts,
regulates GI motility, gastric acid secretion, inhibits
gastric emptying (Wicks et al. 2005) and satiation
(Sternini 2007). Bitter receptor activation, mediated
by CKK, seems to be aimed at reducing the absorption
of the bitter compounds and at maximizing the
absorption of complex carbohydrates, essential fatty
acids and fat-soluble vitamins (Jeon et al. 2008) (see
Figure 2).
Pungent receptors
A set of ion channels [transient receptor potential
(TRP) channels] expressed in the gut responds to
a varied class of pungent compounds (see Figure 3
and Table II)
A repertoire of digestive plants
The plants analyzed in the following section represent
but a very small percentage of the FFs with a tradition
of digestive use. The plants were chosen on the basis of
existent clinical and experimental data on digestion-
enhancing effects, irrespective of representativeness in
the diet.
The Bitter Artichoke (Cynara cardunculus
subsp. cardunculus Hayek – Asteraceae) (cfr. Valussi
2011 and references therein) was traditionally used as
a digestive and liver aid, to help stimulate the appetite,
provide relief from nausea, stomach ache, flatulence
and a sense of fullness, and both the German
Commission E and the ESCOP monograph approve
of its use for digestive problems. It contains bitter
sesquiterpene lactones (e.g. cynaropicrin) that might
bind to receptor TAS2R46 (Brockhoff et al. 2007).
A mode of action randomized, double-blind clinical
study on 20 subjects with acute or chronic metabolic
disorders showed that intraduodenal administration
caused a 100% 150% peak increase in bile 1 h later,
which lasted for 3 h.
A post-marketing surveillance study on 417 patients
with hepatic and biliary tract disease showed
elimination of abdominal pain, bloating, flatulence,
constipation, lack of appetite and nausea in about
80% of patients after 4 weeks.
A second post-marketing study including 553
subjects with dyspepsia showed a clinically relevant
reduction of dyspeptic symptoms in 71% of the
subjects within 6 weeks of treatment. A patient subset
with key symptoms of irritable bowel syndrome (IBS)
experienced significant reductions in symptoms
(emesis, nausea, abdominal pain).
In a similar open study on 203 subjects with
dyspepsia, there was an average reduction of 66% of
the symptoms. The global efficacy was evaluated by
the physicians as being good or excellent in 85.7% of
the cases. In a more recent double-blind, randomized
controlled trial vs. placebo on 244 patients with
functional dyspepsia the verum treatment reduced
symptoms and improved the quality of life after
6 weeks.
In an open study on 454 patients with dyspepsia, the
dry extract reduced 40% of the global dyspepsia score.
A subset analysis of the study on subjects suffering
Figure 1. Tastant receptors in the gastrointestinal tract as
mediators of local and systemic responses via paracrine and
endocrine release of peptides.
Table I. Members of the TAS2R family and bitter phytochemicals
shown to bind to them.
TASR2 receptors Active molecules
TAS2R10 Strychnine, humulones
TAS2R14 Picrotoxin, a-thujone
TAS2R16 Salicin
TAS2R43/44 Aristolochic acid
TAS2R50 Andrographolide, amarogentin
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from IBS showed a significant fall in disease incidence
of 26.4%.
When consumed by 30 subjects as ingredient of
an iced dessert, the extract intensified the positive
effects of the dessert on the symptoms of functional
dyspepsia.
A prospective cohort study on 311 patients with
functional dyspepsia analyzed the efficacy of a mixture
of dry extracts of artichoke leaf, dandelion radix and
turmeric rhizome, plus rosemary micro-encapsulated
essential oil. After 60 days of treatment, a statistically
significant gradual reduction in symptom severity was
noted, and a global clinical response was recorded in
38% of patients.
Dandelion (Taraxacum officinale G.H. Weber ex
F. H. Wigg Asteraceae) roots and leaves (cfr. Valussi
2011 and references therein) have been used
extensively since ancient times in Europe as a bitter
tonic and for the treatment of various disorders such
as dyspepsia, heartburn, spleen and liver complaints,
hepatitis and anorexia. Both Commission E and
ESCOP support using T. officinale to treat disturbed
bile flow, loss of appetite and dyspepsia. It contains
bitter sesquiterpene lactones (e.g. eudesmanolides,
guaianolides) which might bind to receptor TAS2R46
(Brockhoff et al. 2007).
An herbal combination containing Calendula
officinalis,T. officinale,Hypericum perforatum,Melissa
officinale and Foeniculum vulgare reduced intestinal
pain in 96% of 24 patients by the 15th day in an
uncontrolled trial involving patients with chronic
colitis. Defecation was normalized in patients with
diarrhoea syndrome.
A prospective cohort study on 311 patients with
functional dyspepsia analyzed the efficacy of a mixture
of dry extracts of artichoke leaf, dandelion radix,
turmeric rhizome and rosemary essential oil. After
60 days of treatment, a statistically significant gradual
reduction in symptom severity was noted, and a global
clinical response defined as a 50% reduction in
the total scores of all symptoms was recorded in
38% of patients in 30 days.
The Lemon fruit (Citrus limon (L.) Burmann fil.
Rutaceae) (cfr. Valussi 2011 and references therein)
has been used both in the West and in the East as a
tonic digestive, strongly aromatic and slightly bitter,
used in decoction and alcoholic extracts. The juice
has traditionally been used as a digestive, astringent,
stomachic, antispasmodic and carminative, used
Figure 2. The relationships between bitter receptors activation, gut peptide release, CNS activation and gastrointestinal effects.
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for the treatment of inappetence, gastralgy, nausea
and gastric acid reflux. The rind contains a bitter
compound, the nortriterpene limonin, which activates
the receptor TAS2R38 (Meyerhof et al. 2010).
It is well known that both lemon aroma and flavour
influence the cephalic phase of digestion (salivation).
In an interesting study comparing the effects of
different visual stimuli, Christensen and Navazech
show that there is a stronger response (a higher salivary
volume) to visual stimuli of acidic (lemon juice) and
pungent foods (pizza with hot peppers). Both lemon
odour and the introduction of lemon juice in the oral
cavity cause an increase in the volume of saliva,
statistically higher than that caused by a non-stimulus
(pure air or pure water).
The study by Bauslaugh showed a relation-
ship between salivation and GI motility during
olfactory stimulation (Bauslaugh 1994), and it is well
Figure 3. The relationships between pungent receptors activation, gut peptide release, and gastrointestinal effects.
Table II. Effects of phytochemicals shown to bind to different TRP channels.
TRP channels Active molecules Effects
Vanilliod channel TRPV1 Capsaicin, piperine, allicin, gingerols,
shogaols, zingerone, camphor,
en-docannabinoids
Piperine increases pancreatic activity, reduces intestinal transit time
(Purhonen et al. 2008).
Capsaicin targets duodenal receptors, stimulates gastrin secretion
(Kidd et al. 2009), evokes dyspeptic symptoms acutely,
reduces them if used chronically, affects gastric sensorimotor
function (van Boxel et al. 2010), stimulates (at low doses)
CGRP secretions, which in turn stimulates microcirculation
and protects gastric mucosa from irritant compounds
(Abdel-Salam et al. 1997).
Shogaol induced nociceptive responses via TRPV1 in rats.
Zingerone desensitized rat neurons by repeated applications
(Iwasaki et al. 2006)
Melastatin channel
TRPM8
Menthol 1,8-cineole Menthol causes cold hyperalgesia (Namer et al. 2005)
TRPA1 channel Allyl isothiocyanate, methyl salicylate,
eugenol, cinnamaldheyde
Stimulation causes serotonin release, 5-HT3 receptor-mediated
contraction of isolated strips of intestine, stimulation of vagal
afferents and enteric nerves, and of various GI reactions
(vomiting, peristaltic reflux) (Nozawa et al. 2009). At duodenal
level seems to mediate the release of CCK. (Purhonen et al. 2008)
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known that pepsinogen, gastrin and HCl secretions are
influenced by cephalic stimulations, hence possibly by
the organoleptic stimulation by lemon juice.
Apart from sensory activities, lemon juice can
directly affect GI secretions. Hundred microliters of
orange and lemon juice have shown very potent
stimulant action on pancreatic secretion compared to
other stimuli, and the peak response was observed
earlier.
In general, the juice stimulated a response quanti-
tatively and qualitatively comparable to that of
secretin.
The fruits of Fennel (F. vulgare Mill. – Apiaceae)
(cfr. Valussi 2011 and references therein) are
commonly employed as a culinary herb and as a
remedy to improve digestion in traditional systems of
medicine; they have been used since ancient Roman
and Egyptian times as a valuable warming carminative
and aromatic digestive, used for dyspepsia, bloating,
flatulence and poor appetite.
A randomized,placebo-controlled trial tested a
fennel seed oil emulsion on 125 infants with colics.
It eliminated colic in 65% of infants, compared to
23.7% in the control group.
A mixture containing chamomile (Matricaria recu-
tita), fennel (F. vulgare) and lemon balm (M. officinalis)
was found to have significant benefits in the treat-
ment of infantile colics in a double-blind, placebo-
controlled study on 93 breast-fed infants treated
twice a day for 1 week, although according to two
subsequent experimental studies in rats the major
contribution to the antispasmodic activity was due to
M. recutita and M. officinalis.
In an uncontrolled clinical study on 24 patients
with chronic non-specific colitis, a herbal combination
of T. officinale,Hipericum perforatum,M. officinaliss,
C. officinalis and F. vulgare eliminated spontaneous
and palpable pains along the large intestine in 95.83%
of the patients.
The essential oil seems able to reduce smooth
muscle spasms in various in vitro models, but this
activity seems concentration dependent, with
spasmogenic effect at lower doses, and spasmolytic at
higher ones.
The ethanol extract and the aqueous infusion show
spasmolytic effects.
In animal models, the administration of fennel
increased spontaneous gastric motility and gastric acid
secretions.
The admixture of 0.5% fennel fruits to the diet of
rats for 6 weeks reduced the food transit time by 12%,
while the admixture of fennel fruits (0.5%) and mint
(1%) for 8 weeks stimulated a higher rate of secretion
of bile acids in rats and a significant enhancement
of secreted intestinal enzymes, particularly lipase
and amylase.
Lemon balm (M. officinalis L. Lamiaceae) (cfr.
Valussi 2011 and references therein) is a very popular
traditional herb used in infusion for restlessness and
dyspepsia, especially among children.
A randomized, double-blind, placebo-controlled
trial testing lemon balm in combination with
chamomile and fennel showed significant improve-
ment of infantile colics.
A fixed commercial combination of extracts of
M. officinalis,Mentha spicata, and Coriandr um sativum
was tested on 32 IBS patients and compared with
placebo for 8 weeks in a clinical study. The study
shows that the combination reduces the severity and
frequency of abdominal pain and of bloating better
than placebo.
The ethanol extracts and the essential oil have
shown inhibition of artificially induced contraction of
smooth muscles, but there are also contrasting data.
Peppermint (Mentha xpiperita L. Lamiaceae) (cfr.
Valussi 2011 and references therein) has always been
used in traditional learned and folk medicine as a
carminative, antispasmodic, antiemetic and digestive,
both in the West and in the East. The plant contains
an essential oil characterized by the presence of the
alcohol menthol, which binds to the melastatin
channel TRPM8, causing cold hyperalgesia (Namer
et al. 2005).
The essential oil reduces intracolonic pressure. In an
open study of 20 patients, peppermint essential oil
used alongside a colonoscope relieved colonic spasms,
and it had the same effect when administered with
barium enemas.
The essential oil is also able to reduce tension
in hypertonic intestinal smooth muscle in case of IBS.
In healthy volunteers, intragastric administration of
a dose equivalent to 180 mg peppermint oil, reduced
intraoesophageal pressure within 1 –7 min of infusion.
Oral administration of the essential oil delayed
the gastric emptying time in healthy volunteers
and in patients with dyspepsia, and it slowed small
intestinal transit time in 12 healthy volunteers.
A combination of essential oils (peppermint
and caraway) produced smooth muscle relaxation
of stomach and duodenum; in a double-blind,
placebo-controlled multicentric trial with 45 patients,
it improved symptoms of dyspepsia, reducing pain
in 89.5% of patients and improving clinical global
impression scores in 94.5% of patients.
The same combination tested on 223 dyspeptic
patients in a prospective, randomized and double-
blind controlled multicentric trial, significantly
reduced pain, and when tested on 96 outpatients
with dyspepsia significantly reduced pain by 40% and
reduced sensations of pressure, heaviness and fullness.
The formula was shown to be as effective as
cisapride in reducing both the magnitude and
frequency of pain, and it had a relaxing effect on the
gallbladder.
In a systematic review of herbal medicines for
functional dyspepsia, the authors found 17 random-
ized clinical trials, nine of which involved peppermint
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and caraway combination preparations. Symptoms
were reduced by all treatments; 60% 95% of patients
reported improvements in symptoms.
Choleretic activity has been demonstrated in animal
models for the herb, various flavonoid fractions,
flavomentin, the essential oil, and menthol. The effect
probably derives from the spasmolytic activity of
menthol and other terpenes on the Oddi’s sphincter.
The antiemetic and prokinetic effects of peppermint
oil and of (-)-menthol are due at least partly to the
binding to the 5-HT(3) receptor ion-channel complex,
in a manner similar to that of ginger.
Chamomile (Matricaria chamomilla L. – Astera-
ceae) (cfr. Valussi 2011 and references therein) has
been a highly popular family herb since antiquity,
generally used for nervous excitability and digestive
disorders, stomach cramping, dyspepsia and
flatulence.
In an open, multicentric study, 104 patients with GI
complaints (gastritis, flatulence and mild intestinal
spasms) were treated for 6 weeks with an oral
chamomile extract (standardized for 0.05% alpha-
bisabolol and 0.15% apigenin-7-glucoside), with
44.2% of subjects self-reporting to be symptom free.
In a double-blind study, a herbal decoction
(150 ml/day containing M. chamomilla,Verbena offici-
nalis,Glycyrrhiza glabra,F. vulgare and M. officinalis)
was tested for 7 days on 68 healthy infants with colic.
Fifty-seven percentage of the infants experienced relief
compared to 26% in the placebo group.
Whole extracts and isolated components demon-
strate a dose-dependent antispasmodic effect in vitro.
The major activity was related to (-)-a-bisabolol, the
cis-spiroethers and the flavonoids (in particular,
apigenin).
Ginger rhizome (Zingiber officinale Roscoe –
Zingiberaceae) (cfr. Valussi 2011 and references
therein) is probably one of the oldest domesticated
spices in human history. It has a prominent role in
Asian systems of medicine where it is used for the
treatment of dyspepsia, flatulence, colic, vomiting,
diarrhoea, spasms and for stimulating the appetite.
It contains an essential oil (1 4%) and a pungent
resin, and it stimulates the flow of saliva, bile and
gastric secretions (Platel and Srinivasan 2000). Some
of the components of the oleo-resin (shogaols,
gingerols, zingerone) bind to the vanilloid channel
TRPV1, with capsaicin-like nociceptive responses and
desensitization effects. The essential oil activates
receptor TRPA1 (Bandell et al. 2004).
An extract containing the oleoresin and adminis-
tered intraduodenally to rats produced an increase in
the bile secretion, and it was shown that [6]-gingerol
and [10]-gingerol were mainly responsible for the
cholagogic effect. An oral dose of ginger enhanced rat
pancreatic lipase, sucrase, and maltase activity and
stimulated trypsin and chymotrypsin.
The essential oil, a 95% ethanol extract, a hot water
extract and of a formula containing ginger, Pinellia
ternata,Citr us aurantium,Pachyma hoelen and G. glabra
were all shown to possess antispasmodic activity on
intestinal smooth muscles.
In a clinical study, ginger consumed before meals,
increased the number and frequency of contractions
in the corpus and in the antr um, and frequency of
contractions in the duodenum; when consumed after
meals it was less active.
Both ginger and a Japanese formula (Dai-Kenchu-
To ) containing ginger, Zanthoxylum fruit and ginseng
root induced phasic contractions in the gastric antr um.
Previous clinical data had shown that ginger did
not affect the gastric emptying rate but the studies
used low dosages of ginger rhizome.
The prokinetic activity was confirmed in other
in vitro and in vivo tests. Ginger extracts had a
spasmogenic effect and enhanced the intestinal transit
of charcoal meal. At the same time, they showed
spasmolytic activity at the intestinal level, probably
through a Ca
2þ
antagonist effect.
Various constituents found in ginger, 6-, 8- and
10-gingerol, 6-shogaol, and galanolactone, act as
serotonin receptor antagonists, which could explain
the antispasmodic effects on visceral smooth muscle.
They could exert their effect by binding to receptors
in the signal cascade behind the 5-HT(3) receptor
ion-channel complex, perhaps substance P receptors
or muscarinic receptors.
At the same time, two compounds (10-shogaol and
1-dehydro-6-gingerdione), and particularly the whole
lipophilic extract have shown to partially activate the
5-HT(1A) receptor (20 60% of maximal activation).
The serotonin receptor antagonist activity may
partly explain the antiemetic effect of ginger, since
these receptors do mediate peristalsis and emesis, and
the constituents active on these receptors were also
active as anticholinergic antiemetics, in the following
descending order of potency: 6-shogaol .or ¼8-
gingerol .10-gingerol .or ¼6-gingerol.
Many clinical studies have shown the positive
antiemetic effects (prevention and treatment of
nausea) of ginger and many of its constituents under
different circumstances. A systematic review of six
controlled studies found that ginger was more effective
than placebo in some studies of post-operative nausea
and vomiting.
A recent Cochrane review on 20 trials concluded
that ginger might be of benefit in case of nausea and
emesis, but that the evidence to date was weak.
Hot pepper (Capsicum annuum L. – Solanaceae)
(cfr. Valussi 2011 and references therein) is a native
American plant that has been exported all over the
world. Capsicum’s main active chemical group is that
of the capsaicinoids, a group of pungent alkaloids
whose prototype is capsaicin (8-methyl-N-vanillyl-6-
nonenamide), which binds to the duodenal vanilloid
channel TRPV1, affecting gastric sensorimotor func-
tion, stimulating gastrin secretion and (at low doses)
calcitonin gene-related peptide (CGRP) secretions,
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which in turn stimulates microcirculation and protects
gastric mucosa from irritant compounds.
The scientific evidence about capsicum and
capsaicinoids and their effects on the GI tract is rather
contrasting. Capsaicin interacts with the vanilloid
receptor and this interaction causes a selective
impairment of the activity of nociceptive C-type fibres,
causing, on chronic dosage, analgesic and anti-
inflammatory effects. These have been evaluated in
patients suffering from heartburn and functional
dyspepsia, with encouraging results.
The data on gastric secretions and motility are less
clear: some studies found a stimulation of gastric
emptying and of secretions, others found no difference
and others even found a reduction in activity.
The intake of red pepper has caused a reduced
energy intake, suppression of hunger and increased
satiety, an activity in line with a possible effect on the
secretion of CCK.
Four other plants, namely lemongrass (Cymbopogon
citratus (DC.) Stapf. Poaceae), Lemon Verbena
(Aloysia citrodora Palau Verbenaceae), Star Anise
(Illicium verum, Hook. f. Illiciaceae) and Aniseed
(Pimpinella anisum L. Apiaceae) are traditionally
used as GI remedies and are interesting essential
oil-containing plants with positive experimental data,
but do not have a significant corpus of clinical data
(cfr. Valussi 2011 and references therein).
Conclusions
The filter used to select plants examined in depth
in this article (clinical and experimental data) has
left out a very great number of plants, and has
probably favoured those plants which are already well
known and categorized as “digestive,” and that for this
reason have received a large share of scientific interest.
A more comprehensive review is needed, one that
would comprise a larger number of plants, comparing
and contrasting their phytochemical composition and
hypothetical mechanisms of action, and that would
take into account the role of accompanying foods in
modulating the effects of the plants. Particularly
interesting, in the author’s opinion, would be studying
the evidence for GI activity of fruits like Aegle
marmelous,Emblica officinalis,Terminalia spp., Ananas
comosus,Carica papaya,Tamarindus indica, etc., which
are closer than bitters and pungent to the paradigmatic
FFs, and which are almost always used in a food
context.
Within the limits already highlighted, experimental
evidence seems to support traditional knowledge
about bitter and digestive plants, and in particular
gives an evolutionary support to the almost universal
use of bitters as GI remedies. The review highlights the
fruitfulness of combining ethnobotanical and clinical
data with suggestions and conceptual tools from the
field of evolutionary theory.
The data also support the hypothesis that the
presence of these three groups of plants in the diet
could promote better health in a number of ways:
Bitter could be used to reduce the gastric emptying
rate (allowing for a longer action of gastric
secretions on foodstuff) and enhance the post-
gastric digestion of fats and complex carbohydrates.
Clinical data also point towards an antidyspeptic
activity of the examined bitter-tasting plants.
Indirect evidence on functional variants in TASR2
suggests that people with lower sensitivity for bitters
exhibit poorer health measure and are more likely
linked to alcohol dependency (Wang et al. 2007),
adiposity (Tepper et al. 2008), eating disorders
(Dotson et al. 2010), altered glucose homeostasis
(Straub et al. 2003; Dotson et al. 2008) and body-
mass index (Feeney et al. 2011).
The increase in sensation of satiety and the
reduction of food intake derived from bitter
consumption could explain the link with eating
disorders and could help control food intake.
Altogether it seems that bitter plants might
influence overeating and compulsive behaviour.
Bile salt metabolites variably stimulate growth in
bacterial populations (Parsonett 1995); hence, bitter
plants might have an indirect effect on intestinal
bacterial population.
Pungent and aromatic plants have shown in some
instances to have opposite effects to the bitter ones, for
instance in increasing the gastric emptying rate
occasionally with antiemetic effects.
Pungent plants seem to be able to generically
increase the health and functionality of the GI tract by
stimulating gastric secretions, increasing blood flow to
the gastric mucosa and reducing GI spasms.
Finally, the study of tastants on GIT receptors could
pave the way for therapeutic or preventative interven-
tions with systemic effects that do not need systemic
absorption.
Declaration of interest: The author reports no
conflicts of interest. The author alone is responsible
for the content and writing of the paper.
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M. Valussi8
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... At week six of the program, the participant was counseled to continue with increased consumption of omega-3 fatty fish, animal protein, and organ meats. She was counseled to take AIP-compliant digestive bitters to support improved lipid and nutrient absorption [27]. She was counseled on the removal of high FODMAP-containing foods given her gastrointestinal symptoms, including belching, bloating, and constipation [25]. ...
... She was educated on foods highest in copper and magnesium and encouraged to decrease high FODMAP-containing foods given her gastrointestinal symptoms of bloating, abdominal pain, diarrhea, and constipation [25]. She was instructed on folate and vitamin B6-rich foods, including organ meats, beef, leafy greens, spinach, mushrooms, and beets, as well as the use of AIP-compliant bitters to improve digestion [27]. ...
... She was encouraged to try removing high FODMAP-containing foods, given her gastrointestinal symptoms of bloating and abdominal pain [25]. She was educated on riboflavin, vitamin B6, and vitamin B12-rich foods, and the use of AIP-compliant digestive bitters to aid digestion [27]. ...
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Background Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is an autoimmune disorder affecting the thyroid gland and is the most common cause of hypothyroidism in the US. Despite medical management with thyroid hormone replacement, many individuals with HT continue to experience symptoms and impaired quality of life. Given the limited number of efficacious treatments outside of hormone replacement and the overall burden of continued symptomatic disease, this pilot study was designed to determine the efficacy of a multi-disciplinary diet and lifestyle intervention for improving the quality of life, clinical symptom burden, and thyroid function in a population of middle-aged women with HT. Materials and methods The study recruited 17 normal or overweight (body mass index (BMI) <29.9) female subjects between the ages of 20 and 45 with a prior diagnosis of HT. The 17 women participated in a 10-week online health coaching program focused on the implementation of a phased elimination diet known as the Autoimmune Protocol (AIP). The 36-Item Short Form Health Survey (SF-36) and Cleveland Clinic Center for Functional Medicine's Medical Symptoms Questionnaire (MSQ) were used to measure the participant's health-related quality of life (HRQL) and clinical symptom burden, respectively, before and after the 10-week program. The participants completed serologic testing that included a complete blood cell count (CBC) with differential, complete metabolic profile (CMP), thyroid function tests, including thyroid stimulating hormone (TSH), total and free T4, and total and free T3, thyroid antibodies, including thyroid peroxidase antibodies (TPO) and anti-thyroglobulin antibodies (TGA), and high-sensitivity C-reactive protein (hs-CRP). Results Sixteen women (n = 16) completed the SF-36 and MSQ before and after the 10-week program. There was a statistically significant improvement in HRQL as measured by all eight subscales of the SF-36 with the most marked improvements noted in the physical role functioning, emotional role functioning, vitality, and general health subscales. The clinical symptom burden, as measured by the MSQ, decreased significantly from an average of 92 (SD 25) prior to the program to 29 (SD 20) after the program. There were no statistically significant changes noted in any measure of thyroid function, including TSH, free and total T4, free and total T3 (n = 12), as well as thyroid antibodies (n = 14). Inflammation, as measured by hs-CRP (n = 14), was noted to significantly decrease by 29% (p = 0.0219) from an average of 1.63 mg/L (SD 1.72) pre-intervention to 1.15 mg/L (SD 1.31) post-intervention. Conclusions Our study suggests that an online diet and lifestyle program facilitated by a multi-disciplinary team can significantly improve HRQL and symptom burden in middle-aged female subjects with HT. While there were no statistically significant changes noted in thyroid function or thyroid antibodies, the study's findings suggest that AIP may decrease systemic inflammation and modulate the immune system as evidenced by a decrease in mean hs-CRP and changes in white blood cell (WBC) counts. Given the improvements seen in the HRQL and participants' symptom burden as well as markers of immune activity and inflammation, further studies in larger populations implementing AIP as part of a multi-disciplinary diet and lifestyle program are warranted.
... Beside all well-known pharmacological properties (27), curcumin stimulates appetite (28), promotes normal food digestion by either regulating digestive hormones, bile and gastric acids or Downloaded from https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddz247/5599714 by Biblioteca IRCCS Istituto Neurologico Mediterraneo Neuromed -Pozzilli (IS) user on 23 October 2019 by modulating smooth muscles functions (29)(30)(31) and, significantly increases bowel motility in humans (32). ...
... In line with previous evidence (28,29,31), curcumin-supplemented diet stimulated appetite and regularized the overall function of GI tract in treated R6/2 mice. All these finding clearly indicated a role of dietary curcumin in inhibiting GI complication and preserving the homeostasis of intestine in HD mice. ...
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... Foeniculum vulgare (fennel) is an aromatic herb native to Mediterranean areas, Asia and Europe belonging to family Umbelliferae and is also included in functional foods (Valussi, 2012). The biochemicals of fennel are utilized for various purposes like in food, alcoholic beverages, cosmetics and pharmacy industry and as flavoring agent in readymade products like candy, ice cream, toothpaste and non-alcoholic beverages (Hammouda et al., 2013). ...
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Spices - cumin, coriander, ajowan, fennel, mint, and garlic, were examined for their influence on bile secretion rate and bile acid content of bile in experimental rats both as a result of continued dietary intake and single oral dose of the test spice. Groups of animals were maintained for 8 weeks on the following spice diets : Cumin (1.25 %), Coriander (2.0 %), Ajowan (0.2 %), Fennel (0.5 %), Mint (1.0 %), and Garlic (0.5%). In a separate set of rats, these test spices were also administered as a single intragastric dose (mg/kg body wt : Cumin, 600; Coriander, 400; Ajowan, 80; Fennel, 200; Mint, 400; and Garlic oil, 0.02. Bile flow rate was significantly enhanced by dietary cumin, ajowan, and garlic. Ajowan had this beneficial effect even with a single oral dose. The biliary solids were higher in the case of dietary cumin, coriander, ajowan, fennel and mint. A pronouncedly higher rate of secretion of bile acids was caused by all the test spices except garlic, compared to control, both in dietary treatment as well as in single oral dosage of the spice. Higher rate of bile acids secretion would probably contribute to the digestive stimulant action of the test spices.
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The choleretic action of artichoke extract [main ingredient: cynarin (1.5-di-caffeoyl-D-quinc acid)] was investigated in a randomised placebo-controlled double-blind cross-over study (pilot study) [n = 20]. The effect of the standardized, artichoke extract: Hepar SL forte (administered as a single dose: 1.92 g, by the intraduodenal route in a solution of 50 ml of water) was studied by measuring intra-duodenal bile secretion using multi-channel probes. Thirty minutes after the test-substance was administered, a 127.3% increase in bile secretion was recorded, after 60 minutes, 151.5%, and after another 60 minutes, 94.3%, each in relation to the initial value. The relevant differences for the placebo were significant to the extent of p < 0.01 and were clinically relevant. The highest increase in the case of the placebo (139.5%) was seen after 30 minutes. At 120 and 150 minutes the volume of bile secreted under the active treatment was also significantly higher than under the placebo (p < 0.05). In the placebo group, bile secretion fell below the initial level after 3 hours. An effective period of about 120-150 minutes was regarded as satisfactory to influence enzymatic digestion and the motor function of the intestine when the test substance was given postprandially. No side effects nor changes in the laboratory parameters in connection with the experiment were observed. Results indicate that artichoke extract can be recommended for the treatment of dyspepsia, especially when the cause may be attributed to dyskinesia of the bile ducts or disorder in the assimilation of fat.
Article
Background: A novel family of G protein-coupled receptors, TAS2Rs, has recently been characterized and linked to sensitivity to bitter taste compounds. We have previously reported that a missense mutation in the TAS2R16 gene reduces the sensitivity of the receptor to bitter-taste stimuli and that it is associated with risk for alcohol dependence. Other family-based studies on the genetic transmittance of taste perception have previously demonstrated a correlation between genetic variation in TAS2R38 and sensitivity to bitter-taste compounds such as phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP). Haplotypes resulting from 3 common nonsynonymous coding single-nucleotide polymorphisms in the TAS2R38 gene have been shown to alter receptor functions and taste sensitivity to PTC and PROP. The perceived bitterness of PROP has also been associated with oral sensation and drinking behaviors. Methods: We used family-based association methods to test for association between TAS2R38 haplotypes and alcohol dependence as well as a measure of alcohol consumption (Maxdrinks) and age of onset of drinking behaviors in a sample of families densely affected with alcoholism. We have also extended our analysis of TAS2R16 to include the Maxdrinks phenotype. Results: A positive correlation was observed between TAS2R38 haplotypes and Maxdrinks in Collaborative Study on the Genetics of Alcoholism (COGA) high-risk women of African-American origin. The common taster haplotype is significantly associated with a lower mean Maxdrinks compared with the other haplotypes. Similarly, the allele of TAS2R16 that is associated with a lower risk for alcohol dependence is also associated with lower mean Maxdrinks scores in African-American families. In contrast to the previously reported significant association between TAS2R16 and alcohol dependence, we found no evidence that TAS2R38 haplotypes influence alcohol dependence in the COGA dataset. Conclusion: Functional variants in both TAS2R16 and TAS2R38 correlate with alcohol consumption in African-American families.