Digestive Functional Foods 3

Nella terza installazione digestiva ho deciso di scardinare l’ordine cronologico della discussione saltando ad una serie di minimonografie di piante con un certo bagaglio di letteratura sperimentale e clinica, e che, più o meno tirate per i tricomi, possono dirsi piante anche alimentari. Ci sarà tempo per ritornare a discorsi di ordine più teorico.


Cynara cardunculus subsp. cardunculus Hayek — Asteraceae

Native to the Mediterranean area; the basal leaves were used as medicine as far back as ancient Roman times. It was used, as was characteristic of bitter remedies, primarily as a digestive and liver aid, to help stimulate the appetite, provide relief from nausea, stomach ache, flatulence, and a sense of fullness. More recently it has been described as liver protective, a choleretic, and a cholagogue. As with many members of the Asteraceae, it contains bitter-tasting sesquiterpene lactones, although the most characteristic and active compounds are caffeoylquinic acids (e.g. chlorogenic acid; 1,5-dicaffeoylquinic acid, neochlorogenic acid, criptochlorogenic acid, plus cinarine – 1,3-dicaffeoylquinic acid – only in hot acqueous extracts) and flavonoids.

Various experimental studies have shown promising choleretic and digestive activities of the dry extract of artichoke leaves. Total extract, fenolic acids and caffeoylquinic acids all show choleretic effects both in vitro1 and in vivo2 and they increases gastrointestinal peristalsis.3

These experimental studies are partly supported by clinical investigations that have shown that artichoke preparations may relieve digestive complaints (sensation of fullness, loss of appetite, nausea and abdominal pain) through an increase in the formation and flow of bile, probably mainly due to the presence of flavonoids and caffeoylquinic acids, but also via the bitter-tasting sesquiterpene lactones.4 In fact, the German Commission E approves the use of fresh or dried artichoke leaf for dyspeptic problems due to its choleretic action,5 and the ESCOP monograph reports as indications digestive disorders such as stomachache, nausea, emesis, sensation of fullness, flatulence.6

A post-marketing surveillance study reported by Held7 included 417 patients with hepatic and biliary tract disease treated for four weeks with artichoke leaf extract (1% caffeoylquinic acids, 1500 mg/day). In 65-77 % of patients, abdominal pain, bloating, meteorism, constipation, lack of appetite, and nausea were eliminated after one week, and in 52-82% of patients, after four weeks.

A mode of action study (a crossover, randomized, double blind clinical study, vs. placebo, with one-day treatment periods separated by an eight-day washout period) using an aqueous dry extract (4.5-5:1) on 20 subjects with acute or chronic metabolic disorders, showed that administration of six capsules (total weight 1.92 g) intraduodenally caused a peak increase (100 to 150 % compared to baseline) in bile one hour later, which lasted for three hours. The study inferred, but did not demonstrate, therapeutic benefit for dyspepsia. It suffered from many shortcomings: the study was too short, the sample size was small, it wasn’t conducted on subjects with dyspepsia, and the product was not delivered orally.8

A second post-marketing surveillance study included 553 subjects with dyspepsia, who were administered an average of 1.5 g of dry extract (3.8-5.5:1) for an average of 43.5 days. There was a clinically relevant reduction in dyspeptic symptoms for 71% of the subjects in 6 weeks of treatment (66% flatulence, 76% abdominal pain, 82% nausea and 88% emesis).9

Walker, Middleton, and Petrowicz reported an analysis of a patient subset from the initial survey by Fintelmann and Menssen with key symptoms of irritable bowel syndrome (n=279). These patients experienced significant reductions in symptoms (emesis 95%, nausea 85%, abdominal pain 75%).10

In a similar open study that lasted six months on 203 subjects suffering from dyspepsia, there was an average reduction (after 21 days) of 66% of the same range of symptoms. The global efficacy was evaluated by the physicians as being good or excellent in 85.7% of the cases.11

In a more recent double-blind, randomized controlled trial vs. placebo on 244 patients with

functional dyspepsia, the verum treatment (1920 mg dry extract/die) improved/reduced? symptoms and improved quality-of-life measures after six weeks.12

In an open, dose-ranging postal study, 454 healthy patients with self-reported dyspepsia were treated with a dry extract, at 320 or 640 mg daily. Both dosages reduced all dyspeptic symptoms, with an average reduction of 40% in global dyspepsia score.13 A subset analysis of the study, identifying post hoc 208 subjects suffering with IBS, showed a significant fall in disease incidence of 26.4% after 2 months.14

Thirty subjects with functional dyspepsia consumed an iced dessert with or without artichoke extract. The results show that ingestion of the dessert induces a reduction of symptom severity and range even without the extract, but that the presence of the extract intensifies the effects.15

A prospective cohort study on 311 patients with functional dyspepsia analyzed the efficacy of a commercial mixture of dry extracts of artichoke leaf (15% of chlorogenic acid – 150 mg per capsule), dandelion radix (Taraxacum officinalis – 2% of inulin), turmeric rhizome (Curcuma longa – 95% of curcumin) and rosemary (Rosmarinus officinalis) microencapsulated 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 at 30 days.16

Taraxacum officinale G.H. Weber ex F. H. Wigg — Asteraceae

A perennial weed widely distributed in the warmer temperate zones of the Northern Hemisphere. Its roots and rhizomes 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.17

The intensely bitter-tasting compounds are sesquiterpene lactones of the eudesmanolide, guaianolide and germacranolide types18 (previously known as taraxacin) and are unique to Taraxacum. The drug contains also triterpene alcohols (taraxastane-type), phytosterols , lupane-type triterpene and hydroxycinnamic acids.19

In Germany, Commission E supports using Taraxacum officinale folia to treat loss of appetite, dyspepsia, bloating and flatulence, while radix with folia is recommended to treat disturbed bile flow, loss of appetite and dyspepsia.20

ESCOP recommends T. officinale radix for restoring hepatic and biliary function, dyspepsia and loss of appetite.21

Intragastric administration of an aqueous or 95% ethanol extract of the whole plant (dose non specified) to rats increased bile secretion by 40% in over 2 hours.22

Dandelion decoction administered by injection to dogs doubled the volume of bile secreted.23 A similar effect was observed following intraduodenal administration to rats.24

An herbal combination containing Calendula officinalis, Taraxacum 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 diarrhea syndrome.25

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 at 30 days.26

Silybum marianum (L.) Gaertn. — Asteraceae

Plant indigenous to North Africa, Asia Minor and southern Europe, have been used since ancient times for the treatment of gastrointestinal and hepatic complaints like anorexia,27 colic and abdominal cramps,28 and nausea.29

It is nowadays mainly known for its important hepatoprotective and hepartoregenerative activity but, being a bitter remedy, it shows classic digestive activity, although the clinical evidence is lacking (Commission E recognizes this by suggesting its use as a treatment of dyspeptic complaints). The seeds contain a complex mixture of flavolignans termed silymarin, which seems to be the main active principle ingredient?.30 Other important compounds are the flavonoids quercetin, dehydroksampferol and (+)-taxifolin, saponins, poliacetylenes and essential oils.

An experimental study has shown that intragastric administration of an acetone extract of fruit containing silybin increased the volume and dry mass of excreted bile in rats.31

Although there are no direct clinical data, Silybum marianum has been tested in a fixed preparation combining Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica, Silybum marianum and Chelidonium majus. This preparation has shown a general activity on dyspepsia,32 in particular: a reduced acid output, increased mucin secretion, prostaglandin E(2) release and a decrease in leukotriene levels.33 A second study showed protection against the development of gastric acidity rebound/reflux? and inhibited the serum gastrin level in rats.34

Citrus limon (L.) Burmann fil. — Rutaceae

The rind 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. In Traditional Chinese Medicine it is used to resolve gastrointestinal disorders such as abdominal and epigastric bloating, belching, nausea and emesis, inappetence and diarrhea, and in the West for colicky indigestions, abdominal bloating, slow digestion, and nervous dyspepsia. The juice has traditionally been used as a digestive, astringent, stomachic, antispasmodic and carminative, used for the treatment of inappetence, gastralgy, nausea, and gastric acid reflux.35

The epicarp is very rich in an essential oil dominated by monoterpenes (60-95%) in particular R(+)-limonene (up to 70%), and linear aldheides (citrals), but also characterized by photoactive furocoumarins (more than 5%).36 Also present are phenolic compounds, flavonoids, pectin and various organic acids from the juice.37

Lemon juice and extracts exert both indirect and direct actions on gastrointestinal activity. Particularly interesting are the indirect (cognitive and sensory mediated) ones.

It is well known that both lemon aroma and flavor are sialagogues, that is, that they 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).38 Lemon odor and the introduction of lemon juice into the oral cavity both cause an increase in the volume of saliva, statistically higher than that caused by a non-stimulus (pure air or pure water).39 Moreover, according to Davenport, the lemon juice seems to be able to influence not only the quantity but also the quality (in terms of compositions) of the saliva, which becomes richer in proteins.40 This suggests that prior knowledge of the food items can modify the cephalic phase of digestion, and reinforces the thesis of a relationship between secondary metabolites and gastrointestinal physiology: the presence or the supposed presence of possibly hazardous substances (irritant, bitter, astringents, etc.) not only alters the salivary volume but increases the percentage of compounds like praline, which offer a certain degree of protection from irritant compounds such as tannins.

The study by Bauslaugh showed a relationship between salivation and gastrointestinal motility during olfactory stimulation,41 and it is well known that pepsinogen, gastrin and HCl secretions are influenced by cephalic stimulations,42 hence possibly by the organoleptic stimulation by lemon juice.

The palatability and the absence of gastrointestional adverse symptoms have already been tested in a commercial product containing lemon juice and various herb extracts.43

Apart from sensory, indirect activities, lemon juice can directly affect gastrointestinal secretions. 100 ml. of orange and lemon juice have shown very potent stimulant action on pancreatic secretion (higher output, higher bicarbonate content, higher enzymatic content), compared to other stimuli, and the peak response was observed earlier (60 minutes for the juice, 90 minutes for the other stimuli). In general the juice had a response quantitatively and qualitatively comparable to secretin.44

The fruit juice and some of its components (caffeic acid, ferulic acid, hesperidine, p-coumaric acid) show choleretic/cholagogue and antispasmodic action.45

The essential oil and many of its components are rubefacient46 and stimulant carminative;47 limonene is myorelaxant and antispasmodic at high doses, as are many of the other essential oil components: a-pinene, a-terpinene, bergapten, b-pinene, cariophillen, geraniol, mircene, nerale, terpinen-4-olo.48 Hence, they may? could play a role in the antispasmodic and carminative activity of lemon rind extract and lemon juice.

Pectin shows stomachic action and gastrointestinal protective activity.49

Foeniculum vulgare Mill. — Apiaceae

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. Fennel has? also had a persistent/consistent reputation as an ingredient in “gripe water” and other remedies for infant colic.

Given in the form of a homemade tea or infusion, fennel is a useful standby for dyspepsia, bloating and flatulence, and poor appetite.50

It contains an essential oil mainly composed of trans-anethole (30-90%), (+)-fenchone (6-30%) and estragole (methylchavicol – ca. 5% ); and also contains flavonoids and coumarines.

Only a handful of modern clinical trials are reported in the literature, demonstrating – together with its widespread traditional use – a reduction in colic in babies, and a reduction in the symptoms of chronic colitis.

A randomized placebo-controlled trial tested a fennel seed oil emulsion, compared with placebo, on 125 infants, 2 to 12 weeks of age, diagnosed with colic. The emulsion eliminated colic in 65% of infants in the treatment group, compared to 23.7% of infants in the control group with an Absolute Risk Reduction (ARR) = 41%.51

A mixture containing chamomile (Matricaria recutita), fennel (Foeniculum vulgare) and lemon balm (Melissa officinalis) was found to have significant benefits in the treatment of infantile colic in a double-blind, placebo-controlled study on 93 breastfed infants, treated twice a day for 1 week. Crying time reduction was observed in 85.4% of subjects.52

However, two subsequent experimental studies in mice, while confirming the reduction of intestinal motility at dosages similar to those used in human trials, showed that the major contribution to the antispasmodic activity is due to Matricaria recutita and Melissa officinalis.53

In an uncontrolled clinical study twenty-four patients with chronic non-specific colitis were treated with a herb combination of Taraxacum officinale, Hipericum perforatum, Melissa officinaliss, Calendula officinalis and Foeniculum vulgare. As a result of the treatment, the spontaneous and palpable pains along the large intestine disappeared in 95.83 per cent of the patients by the 15th day of their admission to the clinic.54

Backed by weaker clinical evidence, but supported by very widespread and validated traditional use, are the indications for digestive complaints: dyspepsia with bloating and flatulence, poor appetite and indigestion.55

In animal studies, fennel has been shown to be antispasmodic, prokinetic and secretagogue.

Isolated trans-anethole reduced contractions of a rat diaphragm preparation;56 the essential oil seems able to reduce smooth muscle spasms in various in vitro models,57 but this activity seems concentration -dependent, with spasmogenic effect at lower doses, and spasmolytic at higher ones.58

The ethanol extract59 and the aqueous infusion show60 spasmolytic effects.

Intragastric administration of 24.0 mg/kg bw of the fruits increased spontaneous gastric motility in unanaesthetized rabbits.61

An aqueous extract of the fruits (10% p/v), administered to anaesthetized rats via gastric perfusion at 0.15 ml/minutes, significantly increased gastric acid secretions.62

The admixture of 0.5% fennel fruits to the diet of rats for 6 weeks reduced the food transit time by 12%,63 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.64

Melissa officinalis L. — Lamiaceae

A very popular traditional herb used in infusion for restlessness and dyspepsia, especially among children. It contains very low amounts of essential oil (0.02-0.37%), organoleptically characterized by the aldheydes geranial and neral, and 6% of rosmarinic acid.

There is a dearth of clinical research on the digestive activity of Lemon balm, and the only two existing clinical studies are based on formulas and not on the single herb extract.

A randomized, double-blind, placebo-controlled trial showed significant improvement of colic in babies given a chamomile, fennel and lemon balm preparation compared with babies given a placebo.65

A fixed commercial combination of extracts of Melissa officinalis, Mentha spicata and Coriandrum sativum was tested on 32 irritable bowel syndrome patients and compared to 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.66

There is little doubt that the ethanol fraction of the plant, and in particular the volatile oil component, is responsible for the antispasmodic activity of the herb. The ethanol extracts and the essential oil have shown inhibition of artificially-induced contraction of smooth muscles,67 but there are also contrasting data.68 The essential oil was more effective than its isolated components, but it has been observed that neral and geranial were more active than citronellal and β-cariophillen.69

Mentha xpiperita L. — Lamiaceae

Without doubt one of the most world-renowned aromatic plants, and the most important one in terms of annual production, both of the dried herb and essential oil. It 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.

It contains a large amount of essential oil characterized by the presence of a monoterpene alcohol, menthol, which is responsible for many of the activities of the herb and for its characteristic aroma. It also contains flavonoid compounds and hydroxycinnamic compounds.70

Peppermint has also been the focus of a fair amount of good quality research, both experimental and clinical, that supports many of the traditional claims. In particular it has shown antispasmodic, carminative and choleretic activities.

The essential oil reduces intracolonic pressure.71 In an open study of 20 patients, peppermint essential oil used alongside a colonoscope relieved colonic spasms,72 and it had the same effect when administered with barium enemas.73

The essential oil is also able to reduce tension in hypertonic intestinal smooth muscles? in cases? of IBS.74

In healthy volunteers, intragastric administration of a dose equivalent to 180 mg peppermint oil, reduced intraesophageal pressure within 1-7 minutes of infusion.75

Oral administration of the essential oil delayed the gastric emptying time in healthy volunteers and in patients with dyspepsia,76 and it slowed small intestinal transit time in 12 healthy volunteers.77

A combination of essential oils (90 mg of peppermint and 50 mg of caraway in an enteric-coated capsule) was tested in various studies.

The combination produced smooth muscle relaxation of stomach and duodenum;78 in a double-blind, placebo-controlled multicentre 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.79

The same combination tested on 223 dyspeptic patients in a prospective, randomized, reference and double-blind controlled multicentre trial, significantly reduced pain,80 and tested on 96 outpatients with dyspepsia, significantly reduced pain by 40% and reduced sensations of pressure, heaviness and fullness.81

The formula was shown to be as effective as Cisapride in reducing both the magnitude and frequency of pain,82 and it had a relaxing effect on the gall bladder.83

In a systematic review of herbal medicines for functional dyspepsia, the authors found 17 randomized clinical trials, nine of which involved peppermint and caraway combination preparations. Symptoms were reduced by all treatments; 60- 95% of patients reported improvements in symptoms.84

The essential oil and fractions of it have been shown to have gastrointestinal smooth muscle relaxant activity and to inhibit spontaneous smooth muscle contractions both in vitro and in vivo.85 Some data are also available on the antispasmodic effects of the ethanol extract, as well as flavonoids isolated from the leaf.86

The carminative activity of peppermint is, in fact, probably due to a relaxing action on the gastrointestinal sphincters,87 and to a reduction of the volume of intestinal gas by the antimicrobial, anti-fermentative and antifoaming effects of the essential oil.88

Choleretic activity (increased bile secretion and increased synthesis of bile acids) has been demonstrated in animal models for the herb, various flavonoid fractions, flavomentin, the essential oil and menthol.89 The effect probably derives from the spasmolytic activity of menthol and other terpenes on the Oddi’s sphincter.90

The essential oil seems to be acting by interacting with smooth muscle Ca channels probably by inhibiting the influx of extracellular Ca ions without effects on their intracellular mobilization, and menthol has been isolated as the most important compound.91

The antiemetic and prokinetic effects of peppermint oil and of (-)-menthol are due at least partly to their binding to the 5-HT(3) receptor ion-channel complex, in a manner similar to that of ginger.92

Matricaria chamomilla L. — Asteraceae

It has been a highly popular family herb since antiquity, generally used for nervous excitability and digestive disorders, stomach cramping, dyspepsia and flatulence. This tradition of use notwithstanding, much of the research data concentrate on antinflammatory and vulnerary activity.

However, its antispasmodic and relaxant effects provide a theoretical basis for its use in gastrointestinal conditions, and the German Commission E approves chamomile for gastrointestinal spasms and inflammatory diseases of the gastrointestinal tract.

It contains an essential oil, flavonoids (in particular apigenin and its related flavonoid glycosides), and proazulenes (sesquiterpene lactones) including matricin, matricarin and desacetlymatricarin.93

Although a well-known and widely used herb, almost no substantial clinical research exists into the remedy’s use for digestive disorders, and only a few well designed clinical studies are available There are however some experimental studies pointing to antispasmodic activity of the plant and its constituents on smooth muscle.

In an open, multicentre study, 104 patients with gastrointestinal 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 symptom free.94

In a double-blind study, a herbal decoction (150 mL/day containing Matricaria chamomilla, Verbena officinalis, Glycyrrhiza glabra, Foeniculum vulgare and Melissa officinalis) was tested for seven days on 68 healthy infants with colic. 57% of the infants experienced relief compared to 26% in the placebo group.95

In another trial – prospective, double-blind and randomized – a preparation containing chamomile extract and pectin was tested on children aged 6 months to 5.5 years with uncomplicated diarrhea. The preparation reduced duration and severity of diarrhea significantly faster than the placebo.96

Whole extracts and isolated components demonstrate a dose-dependent antispasmodic effect in vitro.97 The major activity was related to (-)-α-bisabolol, the cis-spiroethers,98 and the flavonoids (in particular apigenin).99 Bisabolol oxides A and B, the essential oil, other flavonoids and the small amount of coumarins were less active in vitro.100

The mechanisms for chamomile antispasmodic activity are still unclear. However, at least one mechanism has been proposed: the inhibition of cAMP- and cGMP-phosphodiesterases by flavonoids.101

Chamomile also increases production of bile by the liver.102

Cymbopogon citratus (DC.) Stapf. — Poaceae

An aromatic tropical grass, whose essential oil is characterized by the presence of citrals (up to 90%) and monoterpenes. It also contains triterpenoids and flavonoids. It has been traditionally deemed a carminative, a light sedative, an analgesic, an antiemetic and an antispasmodic.103

It is most frequently used as a remedy for gastrointestinal disorders, in particular stomachache, acids indigestion, abdominal cramps, diarrhea, and dyspepsia.104

There are, however, no clinical data available, and only a few experimental data showing that di essential oil is strongly antispasmodic and carminative.105

Aloysia citrodora Palau — Verbenaceae

Used in Latin America, USA and Europe as an aromatic ingredient in fruit salads, jams, cold drinks or as an infusion.106 The plant is rich in an essential oil dominated by citrals. It also contains flavonoids, phenolic acids and tannins.107

Various authors report its digestive,108 spasmolytic,109 stomachic,110 and carminative activity,111 and it has been used for gastrointestinal and spasmodic disorders, e.g. flatulence, dyspepsia, colic, nausea, etc.112

There are, however, no clinical data in support of these claims, but there are some experimental data.

The essential oil and many of its components are aperitive, analgesic/antinociceptive, and antispasmodic.113 . Cineole and borneol are choleretics and secretagogues.114

Chlorogenic acids could act synergistically with the essential oil as digestives, and vitexin shows an antispasmodic activity.115

Caceres reports of a clinical study (impossible to track down) which allegedly shows a positive effect of the plant on inappetence, slow digestion, gastralgy and emesis.116

Illicium verum, Hook. f. — Illiciaceae and Pimpinella anisum L. — Apiaceae

Both popular aromatic remedies: the first in China, where it is a component of the very famous five spice powder, together with cinnamon/cassia, cloves, fennel and Sichuan pepper; and the second in Europe and North America. Both are used quite often in food recipes (Star Anise in garam masala spice blends and the rice dish biriyani, and Aniseed in many flavored drinks)

These two fruits are deemed carminative and stomachic and they are taken internally in the treatment of abdominal pain and digestive disturbances. They are often included in remedies for indigestion, and they are believed to be effective for children’s digestive upsets, including colic pain.117 Some people chew the fruits after meals for better digestion. The essential oils are used as a stimulant, stomachic, carminative.

Star Anise is characterized by its essential oil content, particularly rich in prenylated C6-C3 compounds (phenylpropanoids: anethole and its analogues, estragole, eugenol), but contains also neolignans and sesquiterpenes in addition to several common flavonoids, diterpenoids and triterpenoids.118

Aniseed contains an essential oil whose major component is trans-anethole.

Their traditional use notwithstanding, there is no clinical evidence supporting it, but there are limited experimental data. The essential oil of Aniseed and trans-anethole both seem to act as antispasmodics in vitro and in vivo on animal models. They antagonize artificially-induced spasms and decrease the rate and extent of contractions of smooth muscle preparations,119 possibly via Ca-channel blockage and the NO-cGMP pathway.120 Many authors point to antispasmodic,121 carminative122 and digestive activities,123 suggesting use for abdominal colic, inappetence, dyspepsia, flatulence.

Zingiber officinale Roscoe — Zingiberaceae

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, diarrhea, spasms and to stimulate the appetite, but over the centuries has become part of western cuisine and pharmacopoea as well.124

The ginger rhizome contains an essential oil (1-4%) and a resin, known collectively as oleoresin. The chief constituents of the essential oil are the sesquiterpenes a-, and b-zingiberene, which are responsible for the characteristic aroma. The resin contains pungent phenolic compounds called gingerols, gingerdioles and gingerdiones, and their corresponding dehydration products known as shogaols.125

According to the studies, ginger exerts several effects in the gastrointestinal tract: secretagogue (saliva, bile, pancreatic juices, gastric juices), antiemetic, intestinal antispasmodic and gastric prokinetic.

It stimulates the flow of saliva, bile and gastric secretions.126 An extract containing the oleoresin and administered intraduodenally to rats produced an increase in the bile secretion, while the aqueous extract was not active. These results point towards the oleoresin as the active principle, and in fact it was shown that [6]- gingerol and [10]-gingerol were mainly responsible for the cholagogic effect.127 An oral dose of ginger enhanced rat pancreatic lipase, sucrase and maltase activity, and stimulated trypsin and chymotrypsin.128

The essential oil,129 a 95% ethanol extract,130 a hot water extract131 and of a formula containing ginger, Pinellia ternata, Citrus aurantium, Pachyma hoelen, and Glycyrrhiza glabra,132 were all shown to possess antispasmodic activity on intestinal smooth muscles.

The rhizome extract, shogaols and gingerols all increased gastric motility in animal models and in humans.

In a clinical study ginger, assumed before meals, increased number and frequency of contractions in the corpus and in the antrum, and frequency of contractions in the duodenum. Assumed after meals, it contributed to motility to a lesser degree.133

Ginger and a Japanese formula (Dai-Kenchu-To) containing ginger, Zanthoxylum fruit and ginseng root, both induced phasic contractions in the gastric antrum..134

Previous clinical data had shown that ginger did not affect the gastric emptying rate.135 There were suggestions, however, that this lack of activity was due to low dosage of ginger rhizome.

The prokinetic activity was confirmed in other in vitro and in vivo tests, that showed that ginger extract enhances the intestinal transit of charcoal meal and that it acts through a spasmogenic, dose-dependant cholinergic agonistic effect on the post-synaptic muscarinic M3 receptors in the stomach fundus. It also has a possible inhibitory effect on pre-synaptic muscarinic autoreceptors. At the same time it shows spasmolytic activity at the intestinal level (also possessed by 6-shogaol, 6-gingerol, 8-gingerol and 10-gingerol), probably through a Ca2 + antagonist effect.136

Various constituents found in Ginger, 6-, 8- and 10-gingerol, 6-shogaol, and galanolactone, act as serotonin receptor antagonists, which could explains the antispasmodic effects on visceral smooth muscle.137 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.138

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).139

The serotonin receptor antagonist activity may partly explain the antiemetic effect of ginger, since these receptors do mediate peristalsis and emesis,140 and the constituents active on these receptors were also active as anticholinergic antiemetics, in the following descending order of potency: 6-shogaol> or= 8-gingerol>10-gingerol> or = 6-gingerol.141

Many clinical studies have shown the positive antiemetic effects (prevention and treatment of nausea) of Ginger and many of its constituents (shogaols, gingerols, zingerones) under different circumstances.142

A systematic review of six controlled studies found that Ginger was more effective than placebo in some studies of postoperative nausea and vomiting. Of the three studies conducted in postoperative nausea and vomiting, two suggested that Ginger was superior to placebo and equally as effective as metoclopramide, whereas one found no benefit.143

A recent Cochrane review on 20 trials concluded that Ginger might be of benefit in cases of nausea and emesis, but that the evidence to date was weak.144

Capsicum annuum L. — Solanaceae

A native American plant that has been exported all over the world and has conquered both the cuisine and the medicine of Europe, Africa and Asia, in a very interesting reverse spice journey.

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 has been tested for its analgesic effect.145

The scientific evidence about capsicum and capsaicinoids and their effects on the gastrointestinal tract is rather contrasting. It is well known that capsaicin can interact with the vanilloid receptor VR1 and that this interaction can lead to direct and indirect effects. The interaction causes a selective impairment of the activity of nociceptive C-type fibers carrying pain sensations to the central nervous system, causing, on chronic dosage, analgesic and anti-inflammatory effects.146 These have been evaluated in patients suffering from heartburn147 and functional dyspepsia, with encouraging results.148

The data on gastric secretions and motility are less clear: some studies found a stimulation of gastric emptying149 and of secretions,150 others found no difference,151 and others even found a reduction in activity.152

The intake of red pepper has caused a reduced energy intake, suppression of hunger and increased satiety,153 an activity in line with a possible effect on the secretion of CCK.

Carica papaya L. — Caricaceae

A tropical plant original to the dry flatlands of Mesoamerica (South Mexico and Guatemala). The fruit is one of the most important fruits in the tropics and worldwide, and its fermented products are well known in the field of FF for its antioxidant properties.154 Its juice and jams made out of the fruit pulp are used also for digestive complaints (constipation, diarrhea, dyspepsia, enteritis), and it is supposed to possess carminative, cholagogue and digestive activities.155 It contains various proteolytic enzymes like papaine and chymopapaine; carotenoids, monoterpenoids; and organic acids.156

Papaine is a proteasis (similar to bromelin) with wide-range specificity, it hydrolyses polypeptides, amides and esters, particularly when used in an alkaline environment, and is used in digestive disorders; chymopapaine is very similar but less active. Although the mature fruit is less rich in papaine than the unripe one, the quantity is still sufficient to give a biological bases to the traditional digestive claims for the fruit and its derivatives.



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104 Duke and Vasquez Martinez 1994 Op. Cit.; Arvigo and Balick 1993 Op. Cit.; Peirce, A. The APhA Practical Guide to Natural Medicines, Stonesong Press Book, Wm. Morrow & Co., Inc., New York, 1999; Gupta 1995 Op. Cit.; ICMR – Indian Council of Medical Research Medicinal Plants of India, Vol. 2, Indian Council of Medical Research, Cambridge Printing Works, New Delhi, 1987; Germosén-Robineau 1997 Op. Cit.; Duke, J.A. and Ayensu, E.S. Medicinal Plants of China, 2 vols., Reference Publications, Algonac, 1985.

105 Caceres 1996 Op. Cit.

106 De Vincenzi, M. et al. “Monographs on botanical flavouring substances used in foods. Part IV”. Fitoterapia. 1994; 66(3):206-207.

107 Williamson, Evans 1988 Op. Cit.; Caceres 1996 Op. Cit.; Torrent Martí, M.T. “Algunos aspectos farmacognósticos y farmacodinámicos de Lippia citriodora H.B.K.” Revista de la Real Academia de Farmacia de Barcelona. 1985a; (14): 39-55; Carnat A., Carnat A.-P., Chavignon O., Heitz A., Wylde R., Lamaison J.-L., Planta Med. 1995;, 61, 490; Lamaison, J.L. et al. “Le verbascoside, compose phenolique majeur del feuilles de frene (Fraxinus excelsior) et de verveine (Aloysia triphylla)”. Pl. Medic. et Phytother. 1993; 26(3):225-233; Skaltsa. H. e G. Shammas. “Flavonoids from Lippia citriodora“. Planta Medica. 1988; (5):465; Valentão P., Andrade P. B., Areias F., Ferreres F., Seabra R. M. J. Agric. Food Chem. 1999; 47, 4579–4582; Andrade P. B., Seabra R. M., Valentão P., Areias F. J. Liq. Chrom. & Rel. Technol. 1998; 21, 2813-2820.

108 Newall, Anderson, Phillipson 1996 Op. Cit.

109 Baudi, O. Plantas Medicinales existentes en Venezuela y Latinoamérica. Editorial América. Caracas, 1987; Torrent Martí, M.T. “Acción farmacológica de algunas esencias de origen biológico”. Revista de la Real Academia de Farmacia de Barcelona. 1985; (1): 43-56; Torrent Martí 1985a Op. Cit.; Newall, Anderson., Phillipson 1996 Op. Cit.; Duke 1985 Op. Cit.; Fleming 1998 Op. Cit.

110 Duke 1985 Op. Cit.; List, P.H. and Hohammer, L., Hager’s Handbuch der Pharmazeutischen Praxis, Vols. 2-6, Springer-Verlag, Berlin, 1969-1979

111 García, B. H. Flora Medicinal de Colombia. Editorial Tercer Mundo. Editores Bogotá. Colombia. 1982; Newall, Anderson., Phillipson 1996 Op. Cit.; Jain, S.K. and deFillips, R., Medicinal Plants of India, 2 vols., Reference Publications, Algonac, 1991; Council of Scientific and Industrial Research (CSIR) The Wealth of India: A Dictionary of Indian Raw Materials and Industrial Products, Revised, Vols. 1-3, CSIR, New Delhi, 1992

112 Caceres 1996 Op. Cit.; Newall, Anderson., Phillipson 1996 Op. Cit.

113 Dabroy L. “Confirmacion de la actividad antibacteriana de algunas especies del genere Lippia contra bacterias que causan infeccion respiratoria” (Tesis) Giatemala Fac CCQQ y Farm, 1994; Arteche A Fitoterapia. Vademecum de prescripcion. Bilbao, CITA, 1994

114 Williamson and Evans 1988 Op. Cit.

115 Ragone MI, Sella M, Conforti P, Volonté MG, Consolini AE. “The spasmolytic effect of Aloysia citriodora, Palau (South American cedrón) is partially due to its vitexin but not isovitexin on rat duodenums”. J Ethnopharmacol. 2007; 113(2):258-66.

116 Caceres 1996 Op. Cit.

117 Yeung Him-Che Handbook of Chinese Herbs and Formulas, Institute of Chinese Medicine, Los Angeles, 1985

118 Jodral MM Illicium, Pimpinella, and Foeniculum CRC Press, Boca Raton, 2004

119 Reiter, M., and W. Brandt. “Relaxant effects on tracheal and ileal smooth muscles of the guinea pig”. Arzneim- Forsch 1985; 35(1): 408-414.; Albuquerque AA, Sorenson AL, Leal-Cardoso JH. “Effects of essential oil of Croton zehntneri, and of anethole and estragole on skeletal muscles”. Journal of Ethnopharmacology. 1995; 49:41-49

120 Melzig, M e Teuschen, E. “Investigations of the influence of essential oil and their main components on the adenosine uptake by cultivated endothelial cells”. Planta Medica. 1991; 57(1):41-42; Tirapelli CR, de Andrade CR, Cassano AO, D Souza FA, Ambrosio SR, da Costa FB, de Oliveira AM. “Antispasmodic and relaxant effects of the hidroalcoholic extract of Pimpinella anisum (Apiaceae) on rat anococcygeus smooth muscle”. J Ethnopharmacol. 2007; 1;110(1):23-9

121 Peirce, A., The APhA Practical Guide to Natural Medicines, Stonesong Press Book, Wm. Morrow & Co., Inc., New York, 1999; Duke 1985 Op. Cit.; Leung, A.Y. and Foster, S., Encyclopedia of Common Natural Ingredients, 2nd ed., John Wiley & Sons, New York, 1995; Gruenwald, J. et al., PDR for Herbal Medicines, 2nd ed., Medical Economics Co., Montvale, NJ, 2000; Blumenthal et al. 1998 Op. Cit.

122 Peirce 1999 Op. Cit.; Duke 1985 Op. Cit.; Williamson and Evans 1988 Op. Cit.; Gruenwald et al. 2000 Op. Cit.

123 Peirce 1999 Op. Cit.; Duke 1985 Op. Cit.; Gruenwald et al. 2000 Op. Cit.; Blumenthal et al. 1998 Op. Cit.

124 ASEAN Standard of ASEAN herbal medicine, Vol. I. Jakarta, ASEAN Countries, 1993; Farnsworth Op. Cit.; Blumenthal et al. 1998 Op. Cit.; Bisset NG. Max Wichtl’s herbal drugs & phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994; Ghazanfar SA. Handbook of Arabian medicinal plants. Boca Raton, FL, CRC Press, 1994; Chang HM, But PPH, eds. Pharmacology and applications of Chinese materia medica, Vol. 1. Singapore, World Scientific Publishing, 1986.

125 ASEAN 1993 Op. Cit.; Awang, D. V. C. “Ginger”, Canadian Pharmaceutical Journal. 1992; 125(7):309-311; Yoshikawa, M., Chatani, N., Hatakeyama, S., Nishino, Y., Yamahara, J., & Murakami, N. “Crude drug processing by far-infrared treatment. II. Chemical fluctuation of the constituents during the drying of Zingiberis Rhizoma”, Yakugaku Zasshi. 1993; 113(10):712-717.

126 Platel, K. & Srinivasan, K. “Influence of dietary spices or their active principles on digestive enzymes of small intestinal mucosa in rats” International Journal of Food Sciences & Nutrition. 1996; 47(1):55-59; Platel, K., and K. Srinivasan. “Influence of dietary spices and their active principles on pancreatic digestive enzymes in albino rats”. Nahrung 2000; 44(1): 42-46; Yamahara, J., Miki, K., & Chisaka, T. “Cholagogic effect of ginger and its active constituents” Journal of Ethnopharmacology. 1985; 13(2):217-225..

127 Yamahara et al. 1985 Op. Cit..

128 Platel and Srinivasan 1996 Op. Cit.; Platel and Srinivasan 2000 Op. Cit.

129 Reiter and Brandt 1985 Op. Cit..

130 Itokawa et al. 1983 Op. Cit.

131 Kato, M., J. Nagao, M. Hayashi, and E. Hayashi. “Pharmacological studies on saiko-prescriptions. I. Effects of saiko- prescriptions on the isolated smooth muscles”. Yakugaku Zasshi 1982; 102: 371-380.

132 Hung, N. D., I. K. Chang, H. C. Jung, and N. J. Kim. “Studies on the efficacy of combined preparation of crude drugs (XII)”. Korean J Pharmacog 1983; 14(1): 9-16.

133 Gupta, Y. K. & Sharma, M. “Reversal of pyrogallol-induced delay in gastric emptying in rats by ginger (Zingiber officinale)” Methods & Findings in Experimental & Clinical Pharmacology. 2001; 23(9):501-503; Micklefield, G. H., Redeker, Y., Meister, V., Jung, O., Greving, I., & May, B. “Effects of ginger on gastroduodenal motility”, Int J Clin Pharmacol Ther. 1999; 37(7):341-6; Yamahara, J., Huang, Q., Li, Y., Xu, L., & Fujimura, H. “Gastrointestinal motility enhancing effect of ginger and its active constituents”, Chemical & Pharmaceutical Bulletin. 1990; 38(2):430-431.

134 Shibata, C., I. Sasaki, H. Naito, T. Ueno, and S. Matsuno. “The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs”. Surgery 1999; 126(5): 918-924.

135 Stewart, J. J., Wood, M. J., Wood, C. D., & Mims, M. E. “Effects of ginger on motion sickness susceptibility and gastric function” Pharmacology. 1991; 42(2):111-120; Phillips, S., Hutchinson, S., & Ruggier, R. “Zingiber officinale does not affect gastric emptying rate: A randomised, placebo-controlled, crossover trial”, Anaesthesia. 1993; 48(5):393-395.

136 Ghayur MN, Gilani “Pharmacological basis for the medicinal use of ginger in gastrointestinal disorders”. AH Dig Dis Sci. 2005; 50(10):1889-97; Ghayur MN, Gilani AH. “Species differences in the prokinetic effects of ginger”. Int J Food Sci Nutr. 2006; 57(1-2):65-73; Ghayur MN, Khan AH, Gilani AH. “Ginger facilitates cholinergic activity possibly due to blockade of muscarinic autoreceptors in rat stomach fundus”. Pak J Pharm Sci. 2007; 20(3):231-5.

137 Huang, Q. R., Iwamoto, M., Aoki, S., Tanaka, N., Tajima, K., Yamahara, J., Takaishi, Y., Yoshida, M., Tomimatsu, T., & Tamai, Y. “Anti-5-hydroxytryptamine3 effect of galanolactone, diterpenoid isolated from ginger”, Chem Pharm Bull . 1991; 39(2):397-9; Yamahara J et al. “Inhibition of cytotoxic drug-induced vomiting in suncus by a ginger constituent”. Journal of ethnopharmacology. 1989; 27:353-355. Mustafa T, Srivastava KC, Jensen KB. “Drug development report 9. Pharmacology of ginger, Zingiber officinale“. Journal of drug development, 1993, 6:25-39; Yamahara, et al. 1990 Op. Cit.

138 Abdel-Aziz H, Windeck T, Ploch M, Verspohl EJ. “Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum”. Eur J Pharmacol. 2005;530(1-2):136-43

139 Nievergelt A, Huonker P, Schoop R, Altmann KH, Gertsch J. “Identification of serotonin 5-HT1A receptor partial agonists in ginger”. Bioorg Med Chem. 2010; 18(9):3345-51

140 Huang et al. 1991 Op. Cit.; Mustafa, Srivastava, Jensen 1993 Op. Cit.; Yamahara, J., Huang, Q., Li, Y., Xu, L., & Fujimura, H. “Gastrointestinal motility enhancing effect of ginger and its active constituents”. Chemical & Pharmaceutical Bulletin. 1990; 38(2):430-431.

141 Abdel-Aziz et al. 2006 Op. Cit.

142 Meyer, K., Schwartz, J., Crater, D., & Keyes, B. “Zingiber officinale (ginger) used to prevent 8-Mop associated nausea” Dermatol Nurs. 1995; 7(4):242-4. Arfeen Z, Owen H, Plummer JL, Ilsley AH, Sorby-Adams RAC, Doecke CJ. “A double-blind randomized controlled trial of ginger for the prevention of postoperative nausea and vomiting.” Anaesth Intens Care 1995; 23:449-452; Phillips S, Ruggier R, Hutchinson SE. “Zingiber officinale (ginger)–an antiemetic for day case surgery”. Anaesthesia 1993; 48:715-717; Fisher-Rasmussen W, Kjaer SK, Dahl C, Asping U. “Ginger treatment of hyperemesis gravidarum“. Eur J Obstet Gynecol Reprod Biol 1990; 38:19-24; Wood CD, Manno JE, Wood MJ, Manno BR, Mims ME. “Comparison of efficacy of ginger with various antimotion sickness drugs”. Clin Res Pr Drug Regul Aff. 1988; 6(2):129-136; Bone ME, Wilkinson DJ, Young JR, McNeil J, Charlton S. “Ginger root–a newantiemetic”. Anesthesia 1990; 45:669-671; Ernst, E. & Pittler, M. H. “Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials” Br J Anaesth. 2000; 84(3):367- 71; Visalyaputra S, Petchpaisit N, Somcharoen K, Choavaratana R. “The efficacy ofginger root in the prevention of postoperative nausea and vomiting after outpatient gynaecological laproscopy”. Anaesthesia 1998; 53:486-510; Vutyavanich T, Kraisarin T, Ruangsri RA. “Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial”. Obstet Gynecol 2001; 97(4):577-582; Grontved A, Brask T, Kambskard J, Hentzer E. “Ginger root against seasickness”. Acta Otolaryngol 1988;105:45-49; Stewart et al. Op. Cit.; 1991.

143 Ernst, Pittler 2000 Op. Cit.

144 Jewell, D. & Young, G. “Interventions for nausea and vomiting in early pregnancy”, Cochrane Database Syst Rev. 2002; 1, CD000145.

145 Watson CP, Tyler KL, Bickers DR, Millikan LE, Smith S, Coleman E. “A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia”. Clin Ther 1993; 15: 510-25; Epstein JB, Marcoe JH. “Topical application of capsaicin for treatment of oral neuropathic pain and trigeminal neuralgia”. Oral Surg Oral Med Oral Pathol 1994; 77:135-40; Sicuteri F, Fusco BBM, Marabini S, et al. “Beneficial effect of capsaicin application to the nasal mucosa in cluster headache”. Clin J Pain 1989; 5: 49-53. The Capsaicin Study Group. “Treatment of painful diabetic neuropathy with topical capsaicin. A multicenter, doubleblind, vehicle-controlled study”. Arch Intern Med 1991; 151:2225-9; Barbanti G, Maggi CA, Beneforti P, Baroldi P, Turini D. “Relief of pain following intravesical capsaicin in patients with hypersensitive disorders of the lower urinary tract”. Br J Urol 1993; 71: 686-91

146 Lynn B. “Capsaicin: actions on nociceptive C-fibres and therapeutic potential”. Pain 1990; 41: 61-9; Holzer P. “Capsaicin: cellular targets, mechanism of action, and selectivity for thin sensory neurons”. Pharmacol Rev 1991; 43: 143-201; Mayer EA, Gebhart GF. “Basic and clinical aspects of visceral hyperalgesia”. Gastroenterology 1994; 107: 271-93

147 Rodriguez-Stanley S, Collings KL, Robinson M, Owen W, Miner JR. “The effects of capsaicin on reflux, gastric emptying and dyspepsia”. Aliment Pharmacol Ther 2000; 14: 129-34;

148 Bortolotti M, Coccia G, Grossi G, Miglioli M “The treatment of functional dyspepsia with red pepper” Aliment Pharmacol Ther 2002; 16: 1075-1082

149 Debreceni A, Abdel-Salam OM, Juricskay I, Szolesanyi J,Mozsik G. “Capsaicin increases gastric rate in healthy human subjects measured by 13C-labeled octanoic acid breath test”. J Physiol (Paris) 1999; 93: 455-60

150 Lippe ITH, Pabst MA, Holzer P. “Intragastric capsaicin enhances rat gastric acid elimination and mucosal blood flow by afferent nerve stimulation”. Br J Pharmacol 1989; 96: 91-100

151 Alfoldi P, Obal F, Toth E, Hideg J. “Capsaicin pretreatment reduces the gastric acid secretion elicited by histamine but does not affect the responses to carbachol and pentagastrin”. Eur J Pharmacol 1986; 123: 321-7; Rodriguez-Stanley et al. 2000 Op. Cit.; 14: 129-34; Park HJ, Na SK, Lee SI, Kang JK, Park IS. “The effect of red pepper and capsaicin on gastric emptying in human volunteers”. Gastroenterology 1998; 114: G3361

152 Alfoldi et al. 1986 Op. Cit.; Mozsik G, Debreceni A, Abdel-Salam OM, et al. “Small doses of capsaicin given intragastrically inhibit gastric basal acid secretion in healthy human subjects”. J Physiol (Paris) 1999; 93: 433-6.; Gonzalez R, Dunkel R, Koletzko B, Schusdziarra V, Allesher HD. “Effect of capsaicin-containing red pepper sauce suspension on upper gastrointestinal motility in healthy volunteers”. Dig Dis Sci 1998; 43: 11 165-71; Vazquez-Olivencia W, Shah P, Pitchumoni CS. “The effect of red and black pepper on orocecal transit time”. J Am Coll Nutr 1992; 11: 228-31; Horowitz M, Wishart J, Maddox A, Russo A. “The effect of chilli on gastrointestinal transit”. J Gastroenterol Hepatol 1992; 7: 52-6

153 Reinbach HC, Smeets A, Martinussen T, Møller P, Westerterp-Plantenga MS. “Effects of capsaicin, green tea and CH-19 sweet pepper on appetite and energy intake in humans in negative and positive energy balance”. Clin Nutr. 2009; 28(3):260-5

154 Aruoma OI, Hayashi Y, Marotta F, Mantello P, Rachmilewitz E, Montagnier L. “Applications and bioefficacy of the functional food supplement fermented papaya preparation”. Toxicology. 2010; 278(1):6-16. Epub 2010 Sep 24.

155 Duke et al. 2002 Op. Cit.; Caceres 1996 Op. Cit.

156 Williamson 2002 Op. Cit.

Digestive Functional Foods 2

Nella seconda installazione mi concentro su due dati interessanti: l’importanza dei disturbi gastrointestinali nelle farmacopee tradizionali, e la predominanza di alcuni taxa nelle piante medicinali ad attività gastrointestinale: Asteraceae, Lamiaceae ed Apiaceae.

Plants used for gastrointestinal complaints in the folk traditions
In analyzing the literature on traditional remedies, it is quite evident that there is a prevalence of plant remedies used for gastrointestinal complaints. In a comparison between indigenous and biomedical pharmacopoeias cited by Balick and Cox, and summarized data referring to 15 different geographical areas, it was shown that “indigenous plant remedies are focused more on gastrointestinal disorders then western Pharmacopoeas”. In fact, the main indication for plant-based remedies was gastrointestinal disturbances (accounting for 15% of the total), equal only to dermatological complaints.[1]

These data are confirmed by more recent research.
In the now famous paper by Etkin and Ross on Hausa folk medicinal knowledge, of the 781 recipes registered, 184 (23.5%) were used for gastrointestinal complaints. Limiting the analysis to the naturalistic maladies, the percentage rises to 32%.[2]
Amongst the most cited uses of the remedies of the Masai in Kenya, gastrointestinal indications play a major role: stomachache is cited 100% of the time, loss of appetite 92% and indigestion 45%.[3] In more recent study on Kenyan ethnobotany, plant remedies for stomach problems were cited 20% of the times.[4]
Very similar percentages are found in other African areas. The proportion of remedies used for treatment of gastrointestinal related disease are for instance high in most studies conducted in Ethiopia, going from 23%[5] to 35%.[6]

In a comparison of Mediterranean folk pharmacopoeias, the percentage of plants used for gastrointestinal complaints went from 31.2 in Uzbekistan, to 21.68 in Turkey, to 16.93 in Greece, to 10.6 in Italy.[7]
In an ethnobotanical survey of the western Pyrenees the plants were used primarily for gastrointestinal or RT disorders,[8] and a survey done in a Peruvian clinic showed that gastrointestinal problems were the second most important reason for patients to use plants.[9]
In the ethnobotany of the South West of the US, around 23.6% of the remedies are used for gastrointestinal disorders.[10]

According to two papers on Brazilian ethnomedicine, 22 to 30% of the medicinal plants were used for digestive disorders, the second most frequent use of all.⁠[11]
A very similar percentage is apparent in a study on Mexican ethnobotany, where roughly 30% of all plants were used to treat colics and stomachaches.[12]
According to Volpato and coworkers, almost 50% of the remedies used by Haitian immigrant to Cuba are intended to treat general gastrointestinal disorders, and about 20% are used as digestive and carminative.[13]
In Perù, 20.3% of the 402 medicinal plant species were used to treat gastrointestinal disturbances, the second most important indication of all,[14] and 6,68% of all plant mixtures (the highest percentage of all uses) was used to treat colic and intestinal problems.[15]
The use of medicinal plants for the treatment of gastrointestinal disorders has a high prevalence in other Andean societies as well.[16]

Many papers have recorded the very high percentage of plants used for gastrointestinal disorders in India, usually the most frequent use af all. The data vary between 25,3% for indigestion,[17] to 30% for stomach related disorders,[18] to 51,2% for generic gastrointestinal disorders.[19] Even when the indications are not the most important, the percentages are still very relevant, as in two recent studies reporting percentages of 9 and 18% for gastrointestional uses.[20]
In a review of remedies used in Pakistan, 16% of the plants were used for gastric problems.[21]
In a recent paper on Nepali remedies, 14,3% of plant species were taken for indigestion, and 10,7% were used as appetite stimulants.[22]
In East Timor the digestive uses were 4th by frequency, adding uo to 6,7%.[23]
⁠In an ethnobotanical study based in China, 40,52% of plants were used to treat gastrointestinal disorders.[24]

These data refer to medicinal plants but, even when selecting only those remedies that can be ascribed to the food-medicine continuum, this trend remains evident.[25] In a study in Mediterranean Spain, the functional or medicinal foods were used in great prevalence for gastrointestinal disorders (up to 20.4%),[26] and the same was true in a study in northwest Patagonia, where a great number of edible medicinal plants were used for gastrointestinal disorders.[27]

In Cuba viandas (starchy roots and tuber crops) and fruits, typical foods used also as medicinal resources, are particularly important for gastrointestinal distress. Viandas are usually boiled in water or milk and eaten as mashed vegetables (Xanthosoma spp., given as a stomachic, for gastritis and stomach ulcers), or grated and sun dried and eaten with milk (Maranta arundinacea, given to kids as a digestive).[28] Fruits are used as simple remedies to improve digestion (Carica papaya, Mangifera indica, Citrus sinensis for example), to prevent colic and “stomach congestion” in kids.[29]

Various reasons have been proposed to explain the prevalence of use for gastrointestinal disorders. Balick and Cox put forward reasons of saliency and of danger perception: the gastrointestinal ailments were, according to the authors, easily identifiable, contrariwise to, for example, tumors; and in traditional societies or in ancient periods of our history the main risks for people were infective diarrheas, gastrointestinal parasitic diseases, alimentary intoxications, etc., much more than cardiovascular diseases, CNS disturbances or neoplastic diseases.[30] Traditional pharmacopoeias are also probably quite conservative and tend to favor gastrointestinal remedies even when the prevalence of diseases has changed.[31]

This prevalence would also be partly explained by the ancient, pre-cultural link between plants and humans. Herbal remedies were (and still are) mainly used per os, thus human beings have “explored” the secondary metabolites sphere mainly through the gastrointestinal tract, which then has a pivotal role as a first diaphragm between the external world and its dangers (xenobiotics) and the internal physiology, and had to “measure itself” against plant constituents: those constituents that represented at the same time a health risk and a pharmacological opportunity.

If the thesis that man had to live in a world rich in alimentary toxins, and at times had to adapt and “learn” to use the same toxins to his own advantage; it is possible that he developed systems of detection, management and defense and that these systems are mainly present in the same gastrointestinal tract.[32]

In fact, according to Johns, the effects of wild foods on the gastrointestinal tract has probably been one of the primary factors in the evolution of medicine and of the use of medicinal foods. Because taste has always been the messenger of many chemical messages, it has been interpreted in many contextualized manners, so that even bitter and pungent tastes could be accepted or even desired.[33]

[1] Balick, M., Cox, L. (1996) Plants, people, and culture: the science of ethnobotany. New York: Scientific American Library
[2] Etkin NL, e Ross PJ (1994) “Pharmacological implications of “wild” plants in Hausa diet”. In NL Etkin (ed.) Eating on the wild side: The pharmacological, ecological, and social implications of using noncultigens. Arizona University Press
[3] Kiringe, John Warui (2006) “A Survey of Traditional Health Remedies Used by the Maasai of Southern Kaijiado District, Kenya”. Ethnobotany Research & Applications; 4:061-073
[4] Bussmann, R. W. (2006) “Ethnobotany of the Samburu of Mt. Nyiru, South Turkana, Kenya”. Journal of ethnobiology and ethnomedicine, 2, 35. doi: 10.1186/1746-4269-2-35.
[5] Teklehaymanot, T., & Giday, M. (2007) “Ethnobotanical study of medicinal plants used by people in Zegie Peninsula, Northwestern Ethiopia.” Journal of ethnobiology and ethnomedicine, 3, 12. doi: 10.1186/1746-4269-3-12.
[6] Tessema T, Giday M, Aklilu N (2001) “Stacking and information on the medicinal plants of Ethiopia”. In National Biodiversity strategy and action plan project Medicinal plant Team, Addis Ababa: IBDA; 2001.
[7] Everest, A and Ozturk, E (2005) “Focusing on the ethnobotanical uses of plants in Mersin and Adana provinces (Turkey)”. Journal of Ethnobiology and Ethnomedicine, 1:6
[8] Akerreta, S, Cavero, RY, Calvo, MI (2007) “First comprehensive contribution to medical ethnobotany of Western Pyrenees” Journal of Ethnobiology and Ethnomedicine; 3:26
[9] Bussmann, RW, Sharon D, Lopez A (2007) “Blending traditional and western medicine: medicinal plant use among patients at the Clinica Anticona in El Porvenir, Peru”. Ethnobotany Research and Applications; 5:185-199
[10] Curtin, L.S.M. (1997) Healing herbs of the upper rio grande: Traditional Medicine of the South West. Revised and edited by Michael Moore. Western Edge Press
[11] Almeida, C. D. F. C. B. R., Amorim, E. L. C. de, Albuquerque, U. P. de, & Maia, M. B. S. (2006). “Medicinal plants popularly used in the Xingó region – a semi-arid location in Northeastern Brazil”. Journal of ethnobiology and ethnomedicine, 2, 15. doi: 10.1186/1746-4269-2-15; Albuquerque, U. P. de. (2006) “Re-examining hypotheses concerning the use and knowledge of medicinal plants: a study in the Caatinga vegetation of NE Brazil”. Journal of ethnobiology and ethnomedicine, 2, 30. doi: 10.1186/1746-4269-2-30.
[12] Estrada, E., Villarreal, J. a, Cantú, C., Cabral, I., Scott, L., & Yen, C. (2007) “Ethnobotany in the Cumbres de Monterrey National Park, Nuevo León, México”. Journal of ethnobiology and ethnomedicine, 3, 8. doi: 10.1186/1746-4269-3-8
[13] Volpato, G., Godínez, D., Beyra, A., & Barreto, A. (2009) “Uses of medicinal plants by Haitian immigrants and their descendants in the Province of Camagüey, Cuba”. Journal of ethnobiology and ethnomedicine, 5, 16. doi: 10.1186/1746-4269-5-16.
[14] Luziatelli, G., Sørensen, M., Theilade, I., & Mølgaard, P. (2010) “Asháninka medicinal plants: a case study from the native community of Bajo Quimiriki, Junín, Peru”. Journal of ethnobiology and ethnomedicine, 6(1), 21. doi: 10.1186/1746-4269-6-21.
[15] Bussmann, R. W., Glenn, A., Meyer, K., Kuhlman, A., & Townesmith, A. (2010) “Herbal mixtures in traditional medicine in Northern Peru”. Journal of ethnobiology and ethnomedicine, 6, 10. doi: 10.1186/1746-4269-6-10.
[16] Bussmann, R. W., & Sharon, D. (2006) “Traditional medicinal plant use in Loja province, Southern Ecuador”. Journal of ethnobiology and ethnomedicine, 2, 44. doi: 10.1186/1746-4269-2-44; Alexiades MN, Lacaze D. (1996) “FENAMADs program in traditional medicine: an integrated approach to health care in the Peru- vian Amazon”. In Balick MJ, Elisabetsky E, Laird SA (eds.) Medicinal Resources of the Tropical Forest Columbia University Press, New York:341-365; Arrázola S, Atahuachi M, Saravia E, Lopez A. (2002) “Diversidad floristica medicinal y potencial etnofarmacólogico de las plantas de los valles secos de Cochabamba Bolivia”. Revista Boliviana de Ecología y Conservación Ambiental; 12:53-85; Bastien J (1987) Healers of the Andes: Kallawaya Herbalists and Their Medicinal Plants University of Utah Press, Salt Lake City; Bastien J (1992) Drum and Stethoscope: Integrating Ethnomedicine and Biomedicine in Bolivia University of Utah Press, Salt Lake City
[17] Kala, C. P. (2005) “Ethnomedicinal botany of the Apatani in the Eastern Himalayan region of India”. Journal of ethnobiology and ethnomedicine, 1, 11. doi: 10.1186/1746-4269-1-11.
[18] Pradhan, B. K., & Badola, H. K. (2008) “Ethnomedicinal plant use by Lepcha tribe of Dzongu valley, bordering Khangchendzonga Biosphere Reserve, in North Sikkim, India”. Journal of ethnobiology and ethnomedicine, 4, 22. doi: 10.1186/1746-4269-4-22.
[19] Sajem, A. L., & Gosai, K. (2006) “Traditional use of medicinal plants by the Jaintia tribes in North Cachar Hills district of Assam, northeast India”. Journal of ethnobiology and ethnomedicine, 2, 33. doi: 10.1186/1746-4269-2-33.
[20] Ragupathy, S., & Newmaster, S. G. (2009) “Valorizing the “Irulas” traditional knowledge of medicinal plants in the Kodiakkarai Reserve Forest, India”. Journal of ethnobiology and ethnomedicine, 5, 10. doi: 10.1186/1746-4269-5-10; Ragupathy, S., Steven, N. G., Maruthakkutti, M., Velusamy, B., & Ul-Huda, M. M. (2008) “Consensus of the “Malasars” traditional aboriginal knowledge of medicinal plants in the Velliangiri holy hills, India”. Journal of ethnobiology and ethnomedicine, 4, 8. doi: 10.1186/1746-4269-4-8.
[21] Hayat, M. Q., Khan, M. A., Ahmad, M., Shaheen, N., Yasmin, G., & Akhter, S. (2008) “Ethnotaxonomical approach in the identification of useful medicinal flora of tehsil Pindigheb (District Attock) Pakistan”. Ethnobotany Research & Applications, 6, 035-062
[22] Kunwar, R. M., Nepal, B. K., Kshhetri, H. B., Rai, S. K., & Bussmann, R. W. (2006) “Ethnomedicine in Himalaya: a case study from Dolpa, Humla, Jumla and Mustang districts of Nepal”. Journal of ethnobiology and ethnomedicine, 2, 27. doi: 10.1186/1746-4269-2-27.
[23] Collins, S. W. M., Martins, X., Mitchell, A., Teshome, A., & Arnason, J. T. (2007) “Fataluku medicinal ethnobotany and the East Timorese military resistance”. Journal of ethnobiology and ethnomedicine, 3, 5. doi: 10.1186/1746-4269-3-5.
[24] Long, C., Li, S., Long, B., Shi, Y., & Liu, B. (2009) “Medicinal plants used by the Yi ethnic group: a case study in central Yunnan”. Journal of ethnobiology and ethnomedicine, 5, 13. doi: 10.1186/1746-4269-5-13.
[25] Ruffo, C.K., Birnie, A., Tengnas, B. (2002) Edible wild plants of Tanzania. RELMA, Kenya; Williamson, G.; Yongping Bao; Chen, K.; Bucheli, P. (2004) “Effects of Phytochemicals in Chinese Functional Ingredients on Gut Health” In Choon Nam Ong and B. Halliwell (eds.) Herbal and Traditional Medicine Molecular Aspects of Health. Lester Packer
[26] Rivera-Nunez D., Obion-de-Castro C (1993) “Plant food as medicine in Medittìerranean Spain” In Actes du 2e Colloque Européen d’Ethnophannacologie et de la 1 le Conference internationale d’Ethnomédecine, Heidelberg, 24-27 mars 1993;
[27] Ladio AH (2006) “Gathering of wild plant foods with medicinal use in a Mapuche community of Northwest Patagonia” in Pieroni A, & Price LL Eating and Healing: Traditional Food As Medicine, The Haworth Press.
[28] Volpato G, Godìnez D “Medicinal foods in Cuba: Promoting health in the household”, in Pieroni and Price 2006 Op. Cit.
[29] Volpato, Godinez 2006 Op. Cit.
[30] Balick and Cox 1996 Op. Cit.
[31] Rivera-Nunez, Obon-de-castro, 1993 Op. Cit.
[32] Johns 1990, Op. Cit.
[33] Johns, T (1994) “Ambivalence to the palatability factor in wild food plants”. In NL Etkin (ed.) Eating on the wild side: The pharmacological, ecological, and social implications of using noncultigens. Arizona University Press

Digestive Functional Foods 1

Necessitato a fare un po’ di lavoro di background per un articolo prossimo venturo su cibi funzionali con attività digestiva, pubblico qui parte del materiale raccolto, in alcuni pezzi. La versione in italiano? Speriamo in tempi brevi :-).

Inizio con un volo d’uccello sui termini del discorso: i cibi funzionali.


Functional foods and nutraceuticals
During the 1980s the Japanese Health Authorities identified special foods with extra-nutritional values as an important object of discussion, and in 1984 the Japanese Ministry of Education Science and Culture used the term “physiologically functional foods” or “functional foods” for the first time. In 1991, a formal category for alimentary items that had extra-nutritional activities was introduced: that of the “Foods for Specified Health Uses” (FOSHU), defined as: “foods with documented evidence of aiding specific physiological functions beyond whatever conventional nutrient exist in the food”.[1]

Around the time when the FOSHU system was under discussion in Japan, the term “nutraceutical” was introduced in the U.S., which included “any substance that may be considered a food or a part of a food and demonstrates to have a physiological benefit, or to provide medical or health benefits, including the prevention and treatment of protection against chronic  disease”,[2]  and which, although “produced from foods”, is  “sold in pills, powders, (potions) and other medical forms not generally associated with food[3] “.

Functional foods have been defined in many ways, but recent definitions describe them as: “products that have physiologic benefits beyond nutritive qualities, and are offered in the form of foodstuffs, including those that have been fortified or have ingredients reduced or removed”;[4] or as items that are: “similar in appearance to conventional foods, (…) consumed as part of a usual diet, and have demonstrated physiological benefits and / or reduce the risk of chronic disease beyond basic nutritional functions.”

Since then, many other terms have been used to describe the complex and multifaceted gray area of food-and-medicine: pharmafood, phytoceutical, phytonutrient, medicinal food, designer food, etc. However, functional food and nutraceutical remain the two most commonly encountered terms, and are often used interchangeably in the generalist news media. In fact one is the subset of the other, since by definition nutraceuticals are those functional foods that are transformed and offered in a pill or otherwise concentrated form, different from normal, common foodstuff.

Traditional functional foods
Although these two term have perhaps been around for 20 years, foods which are “good for your health” (Traditional or Folk Functional Foods) have been around for much longer. Medical historians have stressed the fact that the distinction between medicines and food was blurred and at times non-existent in ancient and preliterate societies, and that it was the advent of modern medicine which artificially constructed a defined hiatus between diet and therapy, food and medicine.[5]  Quoting Albala: ”most complex societies codify their foods investing in them a significance beyond satisfying hunger. In the West, at least since the ancient Greeks, this significance has been medical.”[6] Galen, following the Hippocratic spirit of preventive medicine of the Regimen, codified the age old belief that a good doctor should also be a good cook.[7] Boorde and Cogan could, in the middle of the 16th century, still hotly debate in favor of this belief, the first saying that: ”A good coke is halfe a physycyon. For the chefe physycke (the counseyll of a physycyon excepte) doth come from the kytchyn”,[8] the second referring to: ”cunning Cookes, or to the learned Physitian, who is or ought to be a perfect Cooke in many points”.[9]

The same can be said of ancient Chinese Medicine,[10] where the term Wei meant “taste” but carried all the potency of astronomical, political, ritual and medical theory association with the five agents (wood, fire, earth, metal, water), and the five flavors were to extend a framework of knowledge that had existed since/been constructed in early imperial times.[11]

Examples of FF are also available in contemporary times, both in pre-industrial societies and, although vanishing, in industrialized societies.[12] In the introduction to the collection of essays dedicated to medicinal foods, Pieroni and Price present some memories that could well be our own: the chestnut-meal polenta cooked in red wine as a cough remedy recalled by Pieroni[13] and the chicken soup used for colds cited by Price;[14] and  since the 1970s ethnobotanical literature has made it clear that the blurring of  boundaries between food and medicine is present in contemporary traditional societies, and that, as many studies have shown, non-cultivated wild gathered plants play an important role in the health benefits attributed to the Mediterranean diets.[15]

Ethnobotanists have pointed out that it would be more appropriate to talk about a continuum linking the opposite poles of medicines and foods in folk knowledge,[16] and Pieroni and Quave have come up with an often-cited mapping of this continuum, describing three other categories beyond those of food and medicine:[17]

  • Functional Foods: consumed as foods but acting beyond their basic nutritional function as food by providing protection or reducing the risk of chronic disease.
  • 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 denjoyment purposes they have other effects on body functions.[18]
  • Food medicines/Medicinal foods are ingested in a food context but are assigned specific medicinal properties; or they are consumed in order to obtain a specific medicinal action.

Some other plants are used multifunctionally, simultaneously used as food and medicines without any relationship between the two uses.[19]

It is, therefore, clear that, when talking about traditional functional foods, we need to go beyond the marketing hype, which often puts together (without blending them) the themes of the “natural” hence “safe” traditional food, with the scientific authority of biomedicine bestowed on the term functional.
Any research on this subject needs to be done across fields of research, combining historical, ethnobotanical and biomedical knowledge and insights, to avoid the fallacy of seeing FF as a mere container/vessel for phytochemicals, discounting the cultural construction of the objects of research.  Not only would this be methodologically incorrect, it would also  lead to an important mistake: namely, ascribing functional potential to a material simply due to the presence of an identified compound with known experimental activity; or, conversely, of choosing one compound as the sole element responsible for  the “medicinal” dimension of a food.

[1] Etkin, N.L. Edible medicines: An ethnopharmacology of food. The University of Arizona Press. 2006. p. 207; Dai Y, Luo X., “Functional food in China”. Nutr Rev. 1996 Nov; 54 (11 Pt 2):S21-3.
[2] DeFelice, S.L. “Preface”. In S.L. DeFelice (ed.) Nutraceuticals: Developing, Claiming, and Marketing Medical Foods. Pp. V-viii. Marcel Dekker, New York
[3] Recommendations for Defining and Dealing with Functional Foods, Report of the Bureau of Nutritional Sciences Committee on Fuctional Foods, Health Canada, 1996
[4] Etkin, N.L. 2006 Op. Cit. Pp. 207-208
[5] Etkin, N.L. Chapter 2: “Food in the history of biomedicine”. In N.L. Etkin 2006 Op. Cit. p. 207
[6] Albala, Kenneth “Dietary regime in the Renaissance”, in Malloch Room Newsletter, Jan. 1994,7: 1–2.
[7] Grant, M Galen on food and diet, London, Routledge, 2000, p. 62.; Powell, O Galen: On the properties of foodstuffs, Cambridge University Press, 2003
[8] Boorde, A The first boke of the introduction of knowledge and a compendyous regyment, ed. F J Furnivall, Early English Text Society, Extra Series, 10 London, Early English Text Society, 1870, p. 277; from the edition of 1547. As quoted in Andrew Wear, Knowledge and practice in English medicine, 1500–1680, Cambridge University Press, 2000, p. 170
[9] Cogan, T The haven of health: chiefely gathered for the comfort of students, and consequently of all those that have a care of their health, amplified upon five words of Hippocrates, written Epid. 6, Labor, cibus, potio, somnus, Venus .. . Hereunto is added a preservation from the pestilence, with a short censure of the late sicknes at Oxford of Thomas Cogan, London, printed by Henrie Midleton, for William Norton, 1584, p. 98, as cited in Wear, op. cit., note 2 above, p. 170.
[10] Unschuld, Paul U. Medicine in China: A History of Ideas. University of California Press, 1985; Unschuld, Paul U. Medicine in China: a history of pharmaceutics. Berkeley: University of California Press; Lo, Vivienne, and Penelope Barrett. “Cooking up fine remedies: on the culinary aesthetic in a sixteenth-century Chinese Materia Medica.” Medical History 49, no. 4 (2005): 395-422..
[11] Graham, A Disputers of the Tao, La Salle, ILL, Open Court, 1989, pp. 314–70
[12] Rivera-Nunez D., Obion-de-Castro C “Plant food as medicine in Meditterranean Spain” Actes du 2e Colloque  Européen  d’Ethnophannacologie  et  de  la 1 le Conf6rence  internationale  d’Ethnomédecine, Heidelberg, 24-27 mars 1993; Sandhu DS, Heinrich M. “The use of health foods, spices and other botanicals in the Sikh community in London”. Phytother Res. Jul 2005;19(7):633-42
[13] Pieroni A, & Price LL “Introduction” in Eating and Healing: Traditional Food As Medicine, The Haworth Press, 2006
[14] Pieroni and Price 2006 Op. Cit.
[15] Pieroni A, Nebel S, Quave C, Munz H, Heinrich M. “Ethnopharmacology of liakra: traditional weedy vegetables of the Arbereshe of the Vulture area in southern Italy”. Journal of Ethnopharmacology 2002, 81:165-185.; Bonet, M.A. and J. Vallés. “Use of non-crop food vascular plants in Montseny biosphere reserve (Catalonia, Iberian Peninsula)”. International Journal of Food Science and Nutrition; 2002. 53:225– 248; Rivera, D., C. Obon, C. Inocencio, M. Heinrich, A. Verde, J. Fajardo, and R. llorach. “The ethnobotanical study of local mediterranean food Plants as Medicinal Resources in Southern Spain”. Journal of Physiology and Pharmacology. 2005. 56 (S):97–114; Tardío, J., H. Pascual, and R. Morales. “Wild food plants traditionally used in the province of Madrid, Central Spain”. Economic Botany. 2005;  59:122– 136; Tardío, J., M. Pardo de Santayana, and R. Morales. “Ethnobotanical review of edible plants in Spain” Botanical Journal of the Linnean Society, 2006, 152, 27–71; The Local Food-Nutraceuticals Consortium “Understanding local Mediterranean diets: A multidisciplinary pharmacological and ethnobotanical approach”. Pharmacological Research. 2005; 52 (2005) 353–366
[16] Etkin, N.L. and P.J. Ross “Food as medicine and medicine as food: An adaptive framework for the interpretation of plant utilisation among the Hausa of northern Nigeria”. Social Science and Medicine. 1982; 16: 1559-1573; Johns, T. With bitter herbs they shall eat it. Tucson: University of Arizona Press. 1990; Grivetti, L.E. and B.M. Ogle “Value of traditional foods in meeting macroand micronutrients needs: The wild plant connection”. Nutrition Research Review. 2000; 13: 31-46; Ogle, B.M. and L.E. Grivetti “Legacy of the chameleon: Edible wild plants in the kingdom of Swaziland, southern Africa. A cultural, ecological, nutritional study. Part I–Introduction, objectives, methods, Swazi culture, landscape and diet”. Ecology of Food and Nutrition. 1985a; 16: 193-208; Ogle, B.M. and L.E. Grivetti “Legacy of the chameleon: Edible wild plants in the kingdom of Swaziland, southern Africa. A cultural, ecological, nutritional study. Part II–Demographics, species, availability and dietary use, analysis by ecological zone”. Ecology of Food and Nutrition. 1985b; 17: 1-30; Ogle, B.M. and L.E. Grivetti “Legacy of the chameleon: Edible wild plants in the kingdom of Swaziland, southern Africa. A cultural, ecological, nutritional study. Part III–Cultural and ecological analysis”. Ecology of Food and Nutrition. 1985c; 17: 31-40; Ogle, B.M. and L.E. Grivetti “Legacy of the chameleon: Edible wild plants in the kingdom of Swaziland, southern Africa. A cultural, ecological, nutritional study. Part IV–Nutritional values and conclusions”. Ecology of Food and Nutrition. 1985d; 17: 41-64
[17] Pieroni, A. e Quave, C. “Functional foods or food medicines? On the consumption of wild plants among Albanians and Southern Italians in Lucania” in A., Pieroni e L., Leimar Price (eds.) Eating and Healing, Haworth Press,  2006, p. 110
[18] Preuss, A. “Characterisation of functional food”. Deutsche Lebensmittel-Rundschau, 1999. 95:468-472
[19] Ceuterick, Melissa, Ina Vandebroek, Bren Torry, Andrea Pieroni “The Use of Home Remedies for Health Care and Well-Being by Spanish-Speaking Latino Immigrants in London: A Reflection on Acculturation” in Andrea Pieroni & Ina Vandebroek (eds.) Traveling cultures and plants: The ethnobiology and ethnopharmacy of human migrations. Bergham Books, New York, 2007