FUNCTIONAL FOODS WITH DIGESTION-

ENHANCING PROPERTIES
Marco Valussi

Digestive Functional Foods

In this presentation I aim to show: an ethnobotany-derived definition of Folk

FFs

the results of a preliminary analysis of

ethnobotanical literature on digestive FFFs

the experimental and clinical data on a

selection of FFFs

Introduction to the terms

Administrative, legislative, industry,

regulatory terms

Nutraceutical Functional food Pharmafood Phytoceutical Phytonutrient

Functional Foods: consumed as foods but acting

beyond their basic nutritional function as food by providing protection or reducing the risk of chronic disease.

Introduction to the terms

FOSHU: foods with documented evidence of aiding

specific physiological functions beyond whatever conventional nutrient exist in the food.

Nutraceutical:

any substance that may be considered a food or a part of a food and demonstrates to have a physiological ... medical or health benefits, including the prevention and treatment of ... chronic disease ... sold in pills, powders, (potions) and other medical forms not

Introduction to the terms

We

need terms derived from actual folk use, descriptive more than normative.

The

intersections between foods and medicines has been mapped and explored by recent ethnobotanical literature

I will therefore use a distinction based on

the work by Pieroni and Quave (2006)

Introduction to the terms

Medicinal AND Food plants Folk Functional Foods Food Medicines/Medicinal

Foods

Medicinal AND Food plants

Plants used multifunctionally,

both for food and medicines, but without any kind of relationship between these two fields of uses

Adapted from Pieroni & Quave (2006)

Folk Functional Foods

Weedy species or foods eaten

because they are healthy but with a general rather than unique and specific health action.

Besides their main nutritional or

enjoyment purposes they have other effects on body functions.

Adapted from Pieroni & Quave (2006)

Food Medicines/Medicinal Foods

Ingested in a food context but

assigned specific medicinal properties; or consumed in order to obtain a specific medicinal action.

Adapted from Pieroni & Quave (2006)

Three main data emerge from a still

Medicines, foods and the GIT

preliminary analysis of the ethnobotanical literature:

1.High percentage of food plants used also as medicinal plants 2.Prevalence of medicinal plants (and, to a lesser extent, FF) used for GIT complaints 3.Significant segregation of GIT medicinal and FF plants into few botanical taxa

Food plants/medicinal plants This overlap reveals:

the
partial artificiality food/medicines divide
in shaping this divide

of

the

the role of coevolution and agricolture and questions the epistemic direction:
food then medicine or medicine then

Prevalence of GIT indications Saliency Danger perception

Ease
of identification and prevalence of diseases

Conservatorism
pharmacopoeias

of

traditional

Taxonomical segregation

High prevalence of species belonging to

three taxa: Asteraceae, Lamiaceae and Apiaceae (to a lesser extent Brassicaceae, Solanaceae, Fabaceae)

These families are characterized by the

presence of chemicals belonging to three groups: essential oils, bitter compounds, and pungent compounds.

Spices and bitters

Spices:

great economic and cultural importance. Contain volatile aromatic and pungent compounds (terpenes, shikimic acid derivatives, thioethers, isothiocyanates) and non volatile pungent compounds (acid amine group, like capsaicin and piperine).

Bitters: recognized role all over the world

in promoting the state of health: aperitif, digestives fasting tools. Toxic and non toxic compounds: terpenes, saponines, alkaloids, flavonoids, etc.

Coevolution and gut sensorium

GIT has a luminal sensory role via tastantsensing cells that coevolved with toxins/phytochemicals. Neurohumoral control of gastrointestinal and other organs functions Alarm responses: vomiting, aversion, regulation of appetite and satiety, alteration of stomach and intestinal motility and secretions. Enteroendocrine cells: secretion of cholecystokinin (CCK) and other peptides (GLP-1, PYY, histamine, serotonin)

Bitter receptors
Bitter taste universally recognized as aversive and related to the capacity to detect the presence of toxic substances (via oral and extraoral taste receptor type 2 - TAS2R). Examples

aristolochic acid papavarine picrotin

Bitter of peptides (CCK, PYY, GLPreceptors Activation: release

1)
CCK = release of pancreatic digestive enzymes and bile salts. Regulates gastrointestinal motility, gastric acid secretion, inhibition of gastric emptying, satiety. High doses nausea and emesis. Lower doses disgusting, fix the offensive food in memory Hypotesis = reduced toxins absorption (satiety, delayed gastric emptying) + increased absorption carbohydrates, EFA, fat-soluble vitamins (gallbladder contractions, bile acid excretion) + modulation glucose homeostasis

Pungent taste universally recognized as aversive, mediated by Transient Receptor Potential (TRP) channels:

Pungent receptors

Vanilloid channel TRPV1 (capsaicine, piperine,

allicin, camphor): affects gastric sensorimotor function, increases pancreatic activity, gastrin secretion and reduces the intestinal transit time.

TRPA1 channel (mustard oil, methyl salicylate,

eugenol, cinnamaldheyde): release of CCK and of 5HT, increase of intestinal motility, vomiting and peristaltic reflux.

Melastatin channel TRPM8 (menthol, 1,8-cineole) TRP activation: in general stimulation of gastric

Indirect effects

Essential oils

Perception of organoleptically salient compounds (EOs, pungent, astringents, etc.) alters the salivary volume and proteic composition of saliva There is a relationship between salivation and gastrointestinal motility during olfactory stimulation

Pepsinogen, gastrin and HCl secretions are influenced by cephalic olfactory stimulations

Direct effects
Pepsinogen, gastrin and HCl secretions are influenced by cephalic olfactory stimulations

Reduction of GIT spasms via Ca2+ channels blockade

Preliminary conclusions Irrespective of the specific species,

This activity seems sensorium-mediated, A long term, low dose intake (food-like)
seems more appropiate and rational than a short term, high dose intake (drug-like)
limiting the possibility of toxic effects bitter, pungent and aromatic plants hold the potential to modify the physiology of the GIT

Iberogast
Caraway (Carum carvi); A
Peppermint (Mentha xpiperita); A German chamomile recutita); A (Matricaria

Lomatol
Caraway (Carum carvi); A
Peppermint (Mentha xpiperita); A Fennel (Foeniculum vulgare); A

Gasex
Crowfoot (Aconitum palmatum); O
Mint (Mentha arvensis); A Black pepper (Piper nigrum); P, A

Clown's mustard (Iberis amara); B Angelica (Angelica archangelica); A Milk thistle (Silybum marianum); B Lemon balm (Melissa officinalis); A Celandine (Chelidonium majus); B

Wormwood (Artemisia absinthium); False black pepper (Embelia ribes); B, A P, A

Legenda A = essential oils B = bitter compounds P = pungent compounds

Ginger (Zingiber officinale); P , A Amalaki (Emblica officinalis); O Vibhitaka (Terminalia bellerica); O Haritaki (Terminalia chebula); O

Licorice (Glycyrrhiza glabra); O

O = other compounds

Lemon (Citrus limon); B, A

A repertoire of (mainly Western) digestive FF

Bitter Artichoke Dandelion Milk Thistle Lemon Fennel Lemon balm Peppermint Chamomile

Hayek - Asteraceae

Experimental: choleretic and digestive

activities, increase of gastrointestinal peristalsis.

Bitter Artichoke

2 post-marketing studies: dyspeptic

symptoms

1 RCT: dyspepsia and QoL. 1 mode of action study: inferred therapeutic

benefit for dyspepsia

2 open studies: dyspeptic symptoms, IBS

incidence

Taraxacum officinale G.H. Weber ex F. H.

Wigg -- Asteraceae

Dandelion

Experimental: increased bile secretion Uncontrolled trial of Marigold, Dandelion,

Prospective cohort study on Artichoke,
Dandelion, Turmeric and Rosemary EO:
St. Johns Wort, Lemon Balm and Fennel reduced intestinal pain in chronic colitis, and normalized defecation

Citrus limon (L.)Lemonfil. - Rutaceae Burmann

Experimental: rubefacient , Human study:
choleretic/cholagogue, antispasmodic, carminative. Aroma and flavor are sialagogues (quantity and proteic quality of saliva). 100 mL of orange + lemon juice stimulates pancreatic secretion (output, bicarbonate content, enzymatic content) gastrointestional adverse symptoms have already been tested in a commercial product containing

The palatability and the absence of

Foeniculum vulgare Fennel Mill. -- Apiaceae Experimental: antispasmodic, prokinetic, biliary,

intestinal and gastric secretagogue

1 RCT:
1 RCT:

Fennel OE emulsion eliminated colic in 65% (vs. 23.7%) of infants mixture of Fennel, Chamomile and Lemon Balm effective for infantile colic in 85.4% of subjects (but Chamomile and Lemon Balm seem more important)

1 uncontrolled clinical study: mixture of Fennel,

Dandelion, St. Johns Wort, Lemon Balm, Marigold effective in reducing palpable pain in chronic colitis

Traditional and experimental: bloating, flatulence,

 Mentha xpiperita L.Peppermint -- Lamiaceae

Experimental: smooth muscle relaxant, choleretic and

prokinetic (Ca-channel blocking), antiemetic (binding to the 5HT(3) receptor ion-channel complex,)

1 open study: EO with a colonoscope or with barium enemas.

relieved colonic spasms

Human study: 180 mg EO reduced intraesophageal pressure Human study: EO delayed gastric emptying time and slowed
small intestinal transit time

RCTs:

Peppermint + Caraway EO combinatio produced smooth muscle relaxation of stomach and duodenum; improved symptoms of dyspepsia, reduced pain, sensations of pressure, heaviness and fullness, relaxing effect on the gall bladder.

Matricaria chamomilla L. -- Asteraceae Chamomile

Experimental: cholagogue, dose-dependent
antispasmodic related to (-)--bisabolol, the cis-spiroethers, and the flavonoids, via inhibition of cAMP- and cGMPphosphodiesterases.

Open multicentre study: 44.2% of subjects

self-reporting symptom free (flatulence and mild intestinal spasm)

RCT: mix of

Chamomile, Vervain, Liquorice, Fennel and Lemon Balm effective in relieving

Ginger
Zingiber officinale Roscoe -- Zingiberaceae Experimental Secretagogue (saliva, bile, pancreatic juices, gastric juices),
antiemetic, intestinal spasmolytic, gastric prokinetic.

Gastric spasmogenic: cholinergic agonist on post-synaptic

muscarinic M3 receptors + inhibitory effect on pre-synaptic muscarinic autoreceptors.

Intestinal spasmolytic: Ca2 +

antagonism. Binding to receptors in the signal cascade behind the 5-HT(3) receptor ion-channel complex, perhaps substance P receptors or muscarinic receptors. Partial activation of the 5-HT(1A) receptor.
antiemetic effect of ginger, since these receptors do mediate peristalsis and emesis

The serotonin receptor antagonist activity may partly explain the

 Clinical studies:Ginger duodenal gastric and RCT:

prokinetic, less after a meal. Previous clinical negative data on gastric emptying rate (low dose?) Ginger, Pinellia ternata, Citrus aurantium, Pachyma hoelen, Liquorice show intestinal antispasmodic activity

RCT: Ginger and a mix of Ginger, Zanthoxylum

and Ginseng induced phasic contractions in the gastric antrum.

Systematic review of 6 RCT: Ginger more

effective than placebo in some studies of postoperative nausea and vomiting.

Capsicum annuum L. -- Solanaceae Hot pepper Main active chemical group: pungent alkaloids,
capsaicinoids

Experimental: capsaicin interacts with the vanilloid

receptor VR1 with impairment of nociceptive C-type fiber and, on chronic dosage, analgesic and anti-inflammatory effects.

Clinical studies: encouraging results in patients with

heartburn and functional dyspepsia (long term)

Less clear results on gastric secretions and motility:

some studies show increased gastric emptying and secretions, others no difference, others a reduction in activity.

Dietary intake causes a reduced energy intake, and

Milk Thistle

Silybum marianum (L.) Gaertn. -- Asteraceae Experimental: increase volume of bile. 2 RCTs on Iberogast (Iberis amara, Lemon balm,
Chamomile, Caraway, Peppermint, Liquorice, Angelica, Milk Thistle and Chelidonium majus): dyspepsia, reduced gastric acid, increased mucin, gastric mucosa protection.

Lemongrass

Cymbopogon citratus (DC.) Stapf. -- Poaceae Contains EO, triterpenoids and flavonoids.
Traditionally used as carminative, light sedative, analgesic, antiemetic, antispasmodic. data on antispasmodic and carminative. activity of EO.

No clinical data available, only experimental

Lemon--Verbena Aloysia citrodora Palau Verbenaceae Used as an aromatic ingredient foods and

Various reports of digestive, spasmolytic,

stomachic, and carminative activity

beverages

No clinical data, only some experimental data: EO aperitive, antinociceptive, antispasmodic.

1,8-cineole and borneol choleretics and secretagogues.

Chlorogenic acids digestives, vitexin

antispasmodic.

Aniseed (Pimpinella anisum L. -- Apiaceae) and Star

Anise (Illicium verum, Hook. f. -- Illiciaceae)

Aniseeed and the likes

Deemed carminative and stomachic, used for abdominal

pain and digestive disturbances, indigestion, childrens digestive upsets

Star Anise is characterized by its content in anethole,

estragole, eugenol

Aniseed is characterized by its content in trans-anethole. No clinical evidence, limited experimental data: EO antispasmodics via Ca-channel blockage and the NOcGMP pathway.