Michael Thomsen

Herbal Medicine and the Gastrointestinal System HERBAL MEDICINE AND THE GASTROINTESTINAL SYSTEM..................1

THE SOURCE OF ALL ILLNESS............................................................................5

Digestion & Asthma ..............................................................................................6 Digestion & Skin....................................................................................................6

HCL, HERBS & SPICES............................................................................................6

DIGESTIVE BITTER FORMULATION..............................................................................7

HERBS FOR THE GIT...............................................................................................8

MAIN CATEGORIES .....................................................................................................8 Bitter herbs.............................................................................................................8 Carminative herbs ..................................................................................................8 Anti-inflammatory herbs........................................................................................8 Sedative herbs ........................................................................................................8 Liver herbs .............................................................................................................8

SELECECTED MONOGRAPHS ............................................................................10

DIETARY FIBRE.........................................................................................................10 Soluble Fibre........................................................................................................10 Insoluble Fibre .....................................................................................................10 Resistant Starch....................................................................................................10 What are the benefits?..........................................................................................10 Fibre for young and old........................................................................................10 Getting the most out of your fibre........................................................................10 Ways to increase the fibre in your daily diet .......................................................11

SLIPPERY ELM (ULMUS RUBRA/ ULMUS FULVA) .......................................................11 CHAMOMILE .............................................................................................................12

Other actions ........................................................................................................15 Clinical use...........................................................................................................16 Other Uses............................................................................................................17 Dosage range........................................................................................................18 External application .............................................................................................18 Adverse reactions.................................................................................................18 Significant interactions ........................................................................................18 Practice points/patient counselling ......................................................................19 Answers to patients frequently asked Questions .................................................19

PEPPERMINT..............................................................................................................24 Description...........................................................................................................24 Latin binomial/class .............................................................................................24 Plant part used......................................................................................................24 Chemical components..........................................................................................24 Main actions.........................................................................................................24 Clinical use...........................................................................................................26

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Other uses.............................................................................................................29 Dosage range........................................................................................................29 Adverse reactions.................................................................................................30 Significant interactions ........................................................................................30 Contraindications and precautions.......................................................................31 Pregnancy use ......................................................................................................31 Practice points/patient counseling........................................................................31 Answers to patients’ frequently asked Questions ................................................31 References............................................................................................................32

GINGER.....................................................................................................................35 Historical note......................................................................................................35 Scientific name.....................................................................................................35 Other names .........................................................................................................35 Plant part used......................................................................................................35 Chemical components..........................................................................................36 Main actions.........................................................................................................36 Clinical use...........................................................................................................39 Musculoskeletal disorders....................................................................................41 Other uses.............................................................................................................42 Dosage range........................................................................................................42 Adverse reactions.................................................................................................42 Significant interactions ........................................................................................42 Contraindications and precautions.......................................................................42 Pregnancy use ......................................................................................................43 Practice points/patient counseling........................................................................43 Answers to patients’ frequently asked Questions ................................................43 References............................................................................................................43

PROBIOTICS – TO IMPROVE INTESTINAL FLORA .........................................................50 Historical note......................................................................................................50 Background and relevant pharmacokinetics ........................................................50 Clinical note – Prebiotics .....................................................................................51 Clinical note – The hygiene hypothesis ...............................................................51 Chemical components..........................................................................................52 Food sources ........................................................................................................52 Deficiency signs and symptoms...........................................................................52 Main actions.........................................................................................................52 Clinical use...........................................................................................................53 Urogenital infections............................................................................................55 Irritable bowel syndrome (IBS) ...........................................................................56 Inflammatory bowel diseases...............................................................................56 Helicobactor pylori infection...............................................................................57 Other uses.............................................................................................................57 Dosage range........................................................................................................59 Clinical note – dosage forms tailored to increase probiotic survival...................59

Michael Thomsen

Adverse reactions.................................................................................................59 Contraindications and precautions.......................................................................59 Pregnancy use ......................................................................................................60 Practice points/patient counseling........................................................................60 Answers to patients’ frequently asked Questions ................................................60

HERBAL THERAPY OF GIT DISORDERS.........................................................65 MOUTH ULCERS........................................................................................................65

Mouth Ulcers: Sample formulation ....................................................................65 NAUSEA ....................................................................................................................65 GASTRO-OESOPHAGEAL REFLUX (GER) ..................................................................66

Herbs for GER .....................................................................................................66 PEPTIC ULCER...........................................................................................................66

Herbal Treatment for Ulcers ................................................................................67 Gastric Ulcer : Sample Formulation ....................................................................67 Duodenal Ulcer : Sample Formulation................................................................67

IRRITABLE BOWEL SYNDROME .................................................................................68 Treatment of IBS..................................................................................................68 IBS: Sample Formulation ....................................................................................68 Faeces Report.......................................................................................................69

INTESTINAL INFECTIONS: SAMPLE FORMULATION....................................................69 ACUTE DIVERTICULITIS: SAMPLE FORMULATION....................................................69 HERBAL TREATMENT OF CONSTIPATION...................................................................70

Constipation: Sample Formulation .....................................................................70 HAEMORRHOIDS .......................................................................................................70 INFLAMMATORY BOWEL DISEASE ............................................................................71

Ulcerative Colitis: Sample Formulation .............................................................71 Case: ulcerative colitis .........................................................................................71 History..................................................................................................................71 Treatment and rationale .......................................................................................72 Crohn’s Disease: Sample Formulation ...............................................................73

COELIAC DISEASE AND GLUTEN SENSITIVITY ..........................................................73 Symptoms of CD..................................................................................................73

LIVER DISORDERS.................................................................................................76 LIVER DETOXIFICATION............................................................................................76

Liver Toxins & Disease .......................................................................................76 Processing of Toxins by the Body .......................................................................76 Beneficial Action of Herbs to the Liver...............................................................76 Biotransformation of Toxins by the Liver ...........................................................76 Phase I Reactions .................................................................................................76 Phase II Reactions................................................................................................77 Bioactivation ........................................................................................................77 Phase l & ll Balance.............................................................................................77

IMPORTANT LIVER HERBS.........................................................................................77 Schisandra chinensis ............................................................................................77

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Curcuma longa (Turmeric) ..................................................................................77 Silybum marianum...............................................................................................78

DIETARY FACTORS....................................................................................................78 The Brassicas .......................................................................................................78

POOR LIVER FUNCTION & GALL STONES..................................................................78 ACUTE VIRAL HEPATITIS..........................................................................................79 CHRONIC VIRAL HEPATITIS ......................................................................................79 CIRRHOSIS OF THE LIVER ..........................................................................................79

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The source of all illness There is a common saying amongst natural therapists that “all disease begins in the gut”. This is because many seemingly unrelated diseases such as autoimmune disorders, skin diseases, and even chronic fatigue syndrome have their origin in gastrointestinal disorders. Gut health may be key to allergy prevention 17/01/2005 - Changes in gut microflora caused by widespread use of antibiotics and today’s high-fat, low-fibre diet could be responsible for a major increase in allergies in recent years, say researchers. A US team is the first to link gut health to an allergic response in the lung.

Their results, published in the current issue of Infection & Immunity (73, pp30-38), show that changes in the gut microflora of mice following antibiotic use caused an overzealous allergic response.

The findings have implications for foods and supplements that can help balance gut health, already worth some £111 million in the UK alone during 2002, and forecast by Datamonitor to reach £159.3 million by 2007.

“Our research indicates that microflora lining the walls of the gastrointestinal tract are a major underlying factor responsible for the immune system's ability to ignore inhaled allergens,” said Gary Huffnagle, an associate professor of internal medicine and of microbiology and immunology at the University of Michigan.

“Change the microflora in the gut and you upset the immune system's balance between tolerance and sensitization.”

To test their hypothesis, Huffnagle and colleagues gave normal Balb/C laboratory mice a five-day course of antibiotics, which killed their gut bacteria, followed by a single oral introduction of the yeast Candida albicans. Increased growth of C. albicans in the gut is a common side-effect of antibiotics.

After stopping the antibiotics, they inserted ovalbumin – a commonly used experimental allergen derived from egg whites – via the nasal cavities of all the mice in the study.

The antibiotic-treated mice showed increased airway hypersensitivity to ovalbumin compared to mice that had not received antibiotics.

The results confirmed previous experiments, in which the researchers used a genetically different strain of laboratory mice [C57BL/6] and a different type of allergen – mold spores - instead of ovalbumin.

This research, published in the August issue of the same journal, was the first study linking changes in GI tract microflora to an allergic response in the lung.

“In our new study, we found that differences in host genetics and the type of allergen used didn't matter. The immune responses were literally identical,” Huffnagle said.

“It confirms our earlier findings that gut microflora are the key to maintaining a balanced immune response, that changing the composition of microflora in the gut predisposes animals to allergic airway disease, and that allergic sensitization can occur outside the lungs.”

Over the last few decades, asthma and allergies have increased significantly throughout Europe, with an average 10 per cent of children now suffering from asthmatic symptoms. But in western Europe, the symptom rate is up to ten times that in eastern countries.

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For 1995-1996, the International Study of Asthma and Allergies in Childhood (ISAAC) found prevalence of self-reported asthma symptoms in children aged 13–14 years at 2.6–4.4 per cent in Albania, Romania, Georgia, Greece and the Russian Federation. But these rates reached 32 per cent in Ireland and the United Kingdom. This suggests that a western lifestyle is associated with allergic diseases in childhood.

“If lungs are repeatedly exposed to an allergen, regulatory T cells learn to recognize the allergen as not dangerous and something that can be safely ignored,” Huffnagle said.

“Most researchers think that tolerance develops in the lungs, but we believe it actually occurs in the gut. When immune cells in the GI tract come in contact with swallowed allergens, that interaction triggers the development of regulatory T cells, which then migrate to the lungs.”

The researchers believe that dietary changes like taking antibiotics, switching from breast milk to formula, or eating a high-sugar, low-fat diet can impact tolerance.

“One short course of antibiotics is not going to give everyone allergies,” Huffnagle explained. “But if you are taking antibiotics while your diet consists of white bread and fried food, you are not going to maintain the healthy microflora balance you need to maintain tolerance. If you inhale mold spores or pollen during this period, our studies indicate you are much more likely to become sensitized to them.”

The researchers are planning to investigate whether changing only the diet of the experimental mice will alter gut microflora and change the immune response to allergens in the same way as antibiotics.

They will also look at how probiotic supplements can affect this microbial balance.

Source: NutraIngredients [newsletter@NutraIngredients.com] Digestion & Asthma In some circumstances asthma is related to disorders of upper gastrointestinal function, as vagal stimulation is connected to broncho-constriction. 36 to 80% of asthmatics have been shown to have low HCl, whereas only 20% of non-asthmatics have low HCl. Therefore giving bitter tonics to improve digestion and absorption of nutrients is a useful protocol to employ as an adjunct in the treatment of asthma. Other respiratory disorders may also be linked to poor digestion. In addition to the bitter tonics, Slippery Elm bark which is high in mucilage and has a soothing effect on the GIT, has been shown to have a reflex action on the lungs. Digestion & Skin Most herbalists will begin the treatment of skin disorders by treating both the GIT and the liver. For example, acne rosacea has also been shown to be associated with low HCl as well as poor oral hygiene, oral infection, tonsillitis, and decreased pancreatic lipase with fat intolerance. Chronic low HCl and low pancreatic enzymes have also been linked to dermatitis and eczema.

HCl, Herbs & Spices Herbalists focus on the upper digestion, ie. the mouth and stomach, or the lower intestinal GIT, or in some cases both. Such protocol would include improving vagal stimulation which: • increases HCl • increases pepsin • increases gall-bladder motility • primes pancreatice enzymes.

Michael Thomsen

The use of bitter tonics on to the tongue stimulates the vagus nerve. The hormone gastrin stimulates HCl and pepsin. Additionally the level of HCl has been shown to decline with age. Most menopausal women demonstrate decreased HCl. Herbal bitters and digestive tonics are especially useful in treating elderly patients. Bitter tonics increase gastrin, tighten the cardiac sphincter, increase cholegogue activity (ie increase bile flow from the gall bladder), improve vagal stimulation by their bitter taste, and thereby increase HCl. Aromatic spices such as Ginger, Cardamom, Cinnamon and Cayenne increase gastrin and lipase. The herb Coleus has been shown to increase pancreatic digestion, pancreatic enzymes and HCl. Capsicum may stimulate gastric activity by vagal stimulation or may activate H2 receptors. Angelica and Vervain are also bitter herbs but milder tasting and therefore may be useful when treating children. Alcohol increases gastric acid and gastrin, therefore herbalists often use aromatic and bitter herbs in alcohol. The mixture is best sipped slowly before meals. In gastric hyperacidity a herbalist would also employ mucous membrane tonics and anti-inflammatory herbs with the bitter tonics. This would therefore normalise gastric secretion. Generally speaking, a herbalist will try to maximise production and release of gastric enzymes rather than giving these in tablet form.

Digestive Bitter Formulation Gentiana lutea (Gentian) 1:5 10 mL Coleus forskohlii (Coleus) 1:1 65 mL Zingiber officinale (Ginger) 1:2 25 mL

Total 100 mL Dose: 2 mL with water 20 minutes before meals. Best results are obtained if the bitter taste is experienced on the tongue - this is where vagal stimulation occurs.

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Herbs for the GIT Main Categories Bitter herbs Bitter herbs, eg. Gentian, at low doses can increase lower oesophageal sphyncter (LOS) tone and improve gastric emptying. Carminative herbs Carminative herbs and essential oils in high doses will aggravate GER by reducing LOS tone, but they may be indicated in the treatment of functional dyspepsia. Given in lower doses they can improve gastrointestinal motility. • Anethum graveolens (dill) • Angelica archangelica (archangelica) • Chamomilla recutita (chamomile) • Cinnamomum zeylanicum (cinnamon quills) • Foeniculum vulgare (fennel) • Melissa officinalis (lemon balm) • Mentha x piperita (peppermint) • Nepeta cataria (catmint) • Pimpinella anisum (aniseed) Anti-inflammatory herbs Anti-inflammatory herbs such as Filipendula ulmaria (Meadowsweet), Stellaria media (Chickweed), Calendula (Marigold) and Matricaria chamomila (Chamomile) are of benefit. Chickweed is high in mucilage, and it can also be given as a fresh juice in the treatment of gastric ulceration. Sedative herbs Sedative herbs or nervine tonics would be indicated as stress is usually a contributing factor. These may include Valeriana spp (Valerian), Piper methysticum (Kava) and Scutellaria lateriflora (Skullcap). Liver herbs Hepatoprotective • Andrographis paniculata (andrographis) • Angelica sinensis (dong quai) • Bupleurum falcatum (bupleurum) • Curcuma longa (turmeric) • Cynara scolymus (globe artichoke) • Panax ginseng (korean ginseng) • Phyllanthus amarus (phyllanthus) • Picrorrhiza kurroa (picrorrhiza) • Salvia miltiorrhiza (dan shen) • Schisandra chinensis (schizandra) • Silybum marianum (St. Mary’s thistle)

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Hepatorestorative • Cynara scolymus (globe artichoke) • Silybum marianum (St. Mary’s thistle) Hepatotonic • Andrographis paniculata (andrographis) • Berberis aquifolium (oregon grape ) • Berberis vulgaris (barberry) • Bupleurum falcatum (bupleurum) • Cynara scolymus (globe artichoke) • Panax ginseng (korean ginseng) • Peumus boldus (boldo) • Phyllanthus amarus (phyllanthus) • Picrorrhiza kurroa (picrorrhiza) • Salvia miltiorrhiza (dan shen) • Schisandra chinensis (schizandra) • Silybum marianum (St. Mary’s thistle) • Taraxacum officinale radix (dandelion root)

Michael Thomsen

Selecected Monographs Dietary Fibre By Melanie Koeman, Naturopath and former technical writer for Nutrimedicine. Dietary fibre is essential for health. It is found only in plant foods – animal foods such as meat, cheese and eggs have no fibre. There are two major types - soluble and insoluble. Soluble Fibre Soluble fibre is often described as mucilaginous or slippery, since it has the capacity to absorb and carry lots of water. This fibre can help lower LDL ('bad') cholesterol, while maintaining the HDL ('good') cholesterol and help constipation and irritable bowel. Soluble fibre is found in fruit and vegetables, some cereals (e.g. oats, barley), psyllium, linseed, slippery elm and in legumes (dried peas, beans and lentils). Insoluble Fibre Insoluble fibre is often described as ‘roughage’. This fibre is more resistant to digestion, and is fermented by bacteria to produce special fatty acids for the health of the gut wall. Insoluble fibre is found mainly in wholegrain foods (especially wheat bran and rice bran), the skins of fruits and vegetables, nuts and dried beans. It helps prevent constipation by producing bulky stools. Both types of fibre are beneficial and most plant foods contain a mix of both types. Resistant Starch Resistant starch is found in whole grains, cold cooked potatoes, lentils, firm bananas and as ‘Hi Maize’, which is added to bread and breakfast cereals. Resistant starch is fermented in the gut in a similar way as other fibres, resulting in beneficial effects on the bowel and blood cholesterol levels. What are the benefits? Foods high in fibre tend to be low in fat and low in glycaemic index and so fit well into weight reduction, low fat and diabetic diets. A high fibre diet helps prevent constipation, haemorrhoids and diverticular disease and may be protective against bowel polyps and cancer. A high fibre diet is also associated with a lower risk of heart disease and gallbladder disease, obesity and diabetes. Fibre for young and old Most Australians don't consume enough fibre at around 20g daily. The Australian Heart Foundation recommends adults consume approximately 30 - 35g daily. Children should eat 10g of fibre a day plus an additional gram for every year of age. Eg. a 10 year old child should eat 15-20g of fibre per day. A high fibre diet is important for the elderly due to a slowing of the digestive system with age. Getting the most out of your fibre If your current diet is low in fibre increase it slowly to help avoid abdominal discomfort or wind. A high fibre diet may not prevent or cure constipation unless you drink enough water every day – Aim for at least 8 glasses a day. If you suffer from constipation regular exercise is important.

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Large amounts (more than 2 Tbsp/day) of unprocessed brans are undesirable. They can bind essential minerals like iron, and also produce excessive abdominal flatulence, pain and loose bowel actions. To reduce the gas when using dried beans, soak the beans for 18 hours to remove a large percentage of the oligosaccharides (these ferment in the colon to release gas). Throw away the soaking water and cook in fresh water. Always try to increase your fibre from food sources rather than from supplements since food contains other important nutrients. You may need a supplement if you have particular needs. Ways to increase the fibre in your daily diet • Add dried peas, beans and lentils to soups, casseroles, salads and as a side dish • Switch to wholemeal or multigrain breads, brown rice and wholemeal flours over their white

counterparts • Eat baked beans on wholegrain toast for breakfast • If you eat cereal, aim for those containing oats, linseed, barley, psyllium or nuts • Eat nuts, seeds & fresh or dried fruit as a snack • Snack on hummous and carrot sticks before dinner instead of Jatz and cheese • Eat the fruit instead of the fruit juice (which has lost all its fibre) • Aim for 2/3rds of your plate covered by plant food, and meat or animal foods to 1/3 • Add an extra vegetable to every evening meal. • Check out the fibre content of foods with a nutritional panel to inform yourself of high fibre

food options • Avoid excessive intake of meat, fatty foods, fast foods and sugar as these are very low in fibre

Slippery elm (Ulmus rubra/ Ulmus fulva) Slippery elm bark contains both soluble and insoluble fibre. Soluble fibres decrease blood lipids and cholesterol. It is broken down by intestinal bacteria and has little bulking effect on the stool. Insoluble fibre has a bulking effect on the stool but no known effect on blood lipids. The soluble fibre consists primarily of mucilage (the main polysaccharides being a linear polymer of D-galacturonic acid and L-rhamnose residues with side branches, on the rhamnose residues, of galactose or 3-0-methyl-galactose). Mucilages are very efficient at absorbing and retaining water due to their branched structures and the presence of glucuronic acid, which has a high affinity for water. It also contains starch, small amount of minerals and tannin. Mucilage does not dissolve in alcohol and absorbs water at many times its own weight. Slippery Elm is therefore most effectively used as a powder. Actions Demulcent, emollient, nutrient, bulk laxative (in large doses) Pharmacology • Slippery Elm Bark mucilage has excellent demulcent and emollient properties,

and taken orally, it protects and soothes any irritation or inflammation of the mucous membranes in the digestive tract.

• Slippery Elm has considerable nutritive value and has a long reputation of benefit to convalescents.

• Slippery Elm lubricates bowel contents due to its ability to retain water and the ‘slimy’ nature of mucilage, and therefore has a laxative action.

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• It has a reflex soothing effect on other mucous membranes, for example in the respiratory and urinogenital systems.

• Slippery Elm slows the intestinal absorption of sugar, inhibits the activity of pancreatic enzymes (slows down the metabolism of di- and polysaccharides (starches)) and delays gastric emptying, giving a more gradual release of sugars into the blood stream, so having a beneficial effect on blood sugar disorders such as diabetes mellitus.

• A recent study found that slippery elm has antioxidant properties and may scavenge peroxyl and superoxide free radicals. Slippery elm was found to reduce oxygen free radical release in mucosal biopsies from patients with active ulcerative colitis. It was concluded that slippery elm may be beneficial for inflammatory bowel diseases. Langmead L, Dawson C, Hawkins C, Banna N, Loo S, Rampton DS: Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease: an in vitro study. Aliment Pharmacol Ther 2002;16:197-205.

Indications • Inflammation and ulceration of gastrointestinal tract, such as gastritis, colitis,

oesophagitis, gastric or duodenal ulcers • Intestinal Dysbiosis • Diarrhoea • Irritable bowel syndrome Contraindications None known Dosage One heaped teaspoon (4 g) twice daily.

Chamomile Reference: Braun L, Herbs & Natural Supplements - An Evidence-based Guide Common name German chamomile Scientific name Chamomilla recutita (L.), family Asteraceae (Compositae). There has been considerable confusion over botanical classification since the plant, formerly known as Matricaria recutita L., was added to the genus Chamomilla in 1974. Matricaria chamomilla L. is also used. Other names Wild chamomile, single chamomile, Hungarian chamomile, pin heads matricaria, blue chamomile Flos chamomillae vulgaris (Lat). Plant part used Flowerheads, gathered in summer when they are dry, and carefully dried at low temperatures. Essential oil: extracted by steam distillation of the flower heads. Clinical note The difference between German and Roman chamomile Chamomilla recutita is widely distributed in waste lands and in the neglected fields of Europe, particularly in Croatia and Hungary. Selected varieties are cultivated.(Bruneton J. 1995) Many plants are referred to as chamomile or have the

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word ‘chamomile’ as part of their common name. Of the large number of species of chamomile growing in Europe, North Africa and the temperate region of Asia, five grow wild in the United Kingdom and Europe. Wild varieties are German chamomile (Chamomilla recutita), Roman chamomile (Chamaemelum nobile (L.)), foetid or stinking mayweed (Anthemis cotula), corn chamomile (Anthemis arvensis), and yellow chamomile.(Grieve M. 1976) Roman chamomile, or Chamaemelum nobile (L.); Anthemis nobile L. is the ‘chamomile’ often referred to in English herbals. It has similar uses as the German chamomile such as an aromatic bitter for digestive conditions, antispasmodic agent, mild sedative, and topically for its anti-inflammatory and mild analgesic properties. The Eclectics, a group of American Herbalists who combined physiomedicalism with orthodox medicine in the late 19th Century, were disinclined to use it. History and Traditional Use Chamomiles have been used as medicines since antiquity and have been traditionally grouped in botanical texts under the same general heading. They were probably used interchangeably during this time. Roman chamomile was reportedly used to embalm the Egyptian Pharaoh, Rhamses II, and is thought to have been introduced into Britain by the Romans during their conquests. The Anglo-Saxons used chamomile, presumably the Roman chamomile, as one of their nine sacred herbs. Culpeper lists numerous ailments for which chamomile was used such as jaundice, fevers, kidney stones, colic, retention of urine and inflammation of the bowel.(Culpeper N. 1995) It was also widely used to treat common conditions in children including colic in infants, teething pains and fever.(Grieve M. 1976) It is used in the treatment of gout and to reduce the severity of sciatic pain, either taken internally or applied as a poultice externally.(Culpeper N. 1995) Today, chamomile tea is one of the most popular herbal teas in Australia and New Zealand and extracts are also used in cosmetics as bath preparations, in hair dye for blonde hair, shampoos, mouthwashes and preparations to prevent sunburn.(Foster S. & Leung A. 1996) Chemical components • Essential oil (see below) 0.24–1.9% • Flavonoids (including flavonols and methoxylated flavones) apigenin (other

flavonols are partially hydrolysed to apigenin leading to concentrations of up to 8%), apigetrin (apigenin-7-D-glucoside), apigenin-7-acetylglucoside, apiin (apigenin-7-apiosylglucoside), rutin (quercetin-3-rutinoside), luteolin, quercimeritrin (quercetin-7-D-glucoside), quercetin and isorhamnetin.

• Coumarins – umbelliferone (7-hydroxycoumarin) and herniarin (methyl ether of umbelliferone).

• Proazulenes (sesquiterpene lactones) including matricin, matricarin and desacetlymatricarin.

• Plant acids (acidic mucilage), fatty acids, polysaccharide, choline, amino acids. Essential Oil Chamomile extract produced by a cold extraction process is yellow; steam distillation produces the blue essential oil. This is derived from matricine, also known as proazulene or prochamazulene, a precursor of chamazulene. Chamazulene (1–15%), farnesene, alpha-bisabolol and bisabolol oxides A and B (up to 50% of the essential oil; proportions vary depending on the chemotype), bisabolone oxide, chamazulene (from matricin on distilation), matricin, chamaviolin, spathulenol and cis and trans -enyne dicylo ethers (spiroether, polyacetylenes).

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German chamomile has four chemotypes (variations of the plant product according to chemical composition). These relate to slight variations in the bisabolol oxide content of the essential oil.(Gasic et al. 1986) Chemotypes which contain highest levels of α-bisabolol (known as C & D chemotypes) should be sourced when an essential oil is required for antiphlogistic or spasmolytic properties. Main actions Anti-inflammatory activity Chamomile extract and various isolated constituents within chamomile have demonstrated anti-inflammatory activity in a variety of tests. Chamomile extract showed anti-inflammatory effects when applied topically in animal models of inflammation.(Al-Hindawi et al. 1989;Plevova 1999;Shipochliev, Dimitrov, & Aleksandrova 1981) In a comparative trial, hydro-alcoholic extracts of chamomile produced anti-inflammatory actions when applied topically in the croton ear test in the mouse. The hydro-alcoholic extract reduced oedema in a dose-dependent manner and was equivalent in effectiveness to benzydamine at twice the usual clinical dose, but hydrocortisone was found to be the most effective treatment.(Tubaro et al. 1984) Another comparative study investigated the anti-inflammatory effects of i) an extract prepared from dried flowers, ii) an extract based on fresh flowers, and iii) the volatile oil, in croton oil-induced dermatitis of mouse ear. The activity of fresh chamomile equalled the activity of the reference drug (benzydamine). The anti-inflammatory activity of the herb appears to be due to several different constituents, chiefly apigenin, matricine, chamazulene and alpha-bisabolol, although others may also exist. The previous study determined that apigenin exerts the strongest anti-inflammatory action which is ten times greater than matricine, which is ten times greater than chamazulene.(Della Loggia et al. 1990) Alpha-bisabolol has demonstrated anti-inflammatory and analgesic effects in a number of experimental inflammatory models: rat paw oedema, adjuvant arthritis of the rat, ultraviolet erythema of the guinea pig, and yeast fever of the rat.(Jakovlev et al. 1979) Most studies have investigated the effects of topically applied chamomile or isolated constituents; however, one study using the carrageenin inflammation test on rat paw showed that orally administered matricine produces anti-inflammatory activity which was greater than chamazulene and almost as effective as (-)-α-bisabolol.(Jakovlev, Isaac, Thiemer, & Kunde 1979;Shipochliev 1981a) Chamazulene has been found to inhibit leukotriene B4 formation and blocks chemical peroxidation of arachidonic acid.(Safayhi et al. 1994) Antispasmodic effect Chamomile extract and several constituents demonstrate a dose-dependent antispasmodic effect in vitro. The major activity is related to bisabolol, spiroethers, and apigenin. (-)-α-bisabolol has an effect equal to papaverine; apigenin was the most potent flavonoid, being significantly more potent than papaverine. The extract of chamomile also has a good spasmolytic activity.(Achterrath-Tuckermann et al. 1980) Sedative effects Extracts of chamomile showed sedative activity on the mouse CNS(Della Loggia, Tubaro, & Redaelli 1981) and extracts of chamomile as well as isolated apigenin have been shown to bind to the central benzodiazepine receptor in vitro. Apigenin showed

Michael Thomsen

anti-anxiety and sedative activity with intraperitoneal injection in mice.(Viola et al. 1995) Ovariectomised rats given inhalations of chamomile oil showed decreased levels of stress-induced ACTH levels compared with controls; the experiment suggested an activity similar to benzodiazepine agonists.(Yamada et al. 1996) Antimicrobial activity According to in vitro studies the essential oil has bactericidal and fungicidal activities against Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus) and Candida albicans in concentrations above 0.05 % v/v but has no effect against Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa).(Aggag & Yousef 1972) In contrast, extracts of chamomile have demonstrated antimicrobial activity against E. coli.(Ceska et al. 1992) The growth of Staphylococcus aureus, Streptococcus mutans, group B Streptococcus was inhibited by chamomile extract at concentrations of 10 mg/mL.(Cinco et al. 1983) In vitro tests using apigenin have identified inhibitory activity against HIV activation, possibly by affecting viral transcription.(Critchfield et al. 1997;Trovato et al. 2000) Additionally, a semi-purified extract of chamomile has been shown to inhibit herpes virus in vitro.(Suganda et al. 1983) Antiulcer effect Chamomile extract protected rats from developing experimentally induced ulcers. Bisabolol (and extracts of chamomile) have been shown to prevent the formation of ulcers in experimental animals exposed to indomethacin (NSAID) stress, and alcohol; and to reduce the healing time of ulcers induced by chemical stress (acetic acid) or by heat coagulation. Alpha-bisabolol promotes granulation and tissue regeneration in burns, ulcers, and protects against their formation.(Szelenyi, Isaac, & Thiemer 1979) Other actions Immune enhancement Chamomile extract increased T-lymphocyte rosette formation in vitro in blood samples taken from ENT patients with immunodeficiency.(Kliachko et al. 1994) The polysaccharides (heteroglycans) showed significant immunostimulating activities according to the granulocytes and carbon clearance tests.(Wagner H., Proksch A., & Riess-Maurer I. 1985) Antioxidant Chamazulene is also antioxidant. It has been found to inhibit lipid peroxidation(Goeters et al. 2001) and has been shown to inhibit lipid peroxidation in vitro in a concentration and time dependent manner.(Rekka, Kourounakis, & Kourounakis 1996) Choleretic action Chamomile increases production of bile by the liver.(Pasechnik 1966) Drug dependence Chamomile extract was shown to inhibit the development of morphine dependence and expression of abstinence syndrome in rats. Chamomile reduced frequencies of behaviours associated with withdrawal (paw tremor, rearing, teeth chattering, body shakes, ptosis, diarrhoea and urination) and weight loss.(Bonnafoux-Clavere, Clavere, & Bonnetblanc 2003) Anticarcinogenic

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Apigenin has been shown inhibit carcinogenesis in a number of in vitro and animal studies.(Aguilera, Souza, & Miglioranza 2000;Ali-Shtayeh, Yaniv, & Mahajna 2000;Birt et al. 1986;Birt et al. 1997;Lepley et al. 1996;Lepley & Pelling 1997;Panes et al. 1996;Umezu 1999;Wei et al. 1990) Uterine effects Water extracts of chamomile increased uterine tonus in isolated rabbit and guinea pig uterine horn.(Shipochliev 1981b) Pigmentation Chamomile extract has been found to decrease UV-induced pigmentation as well as the hyperpigmentation found in lentigo senilis (aged or liver spots). Endothelin-1 is a cytokine responsible for stimulating melanocyte function leading to hyperpigmentation. Chamomile has been shown to interrupt the endothelin-1 induced signalling, thereby reducing the ability of melanocytes to proliferate and to synthesise melanin.(Ichihashi et al. 1999) Clinical use Chamomile is most widely taken as a tea, often after meals or as an alternative to caffeine-containing beverages. In clinical practice, the oral dose form most often used is a concentrated extract, in order to produce stronger therapeutic effects. Skin conditions Chamomile is used topically for a variety of dermatological conditions. The most tested topical product is known commercially as Kamillosan®. Wound healing According to a double-blind trial, external application of a chamomile extract improves wound healing. In the study, chamomile extract significantly decreased weeping and improved wound healing after dermabrasion of tattoos.(Glowania, Raulin, & Swoboda 1987) Eczema In one comparative study, 161 patients with eczema on the arms and lower legs were treated with 0.25 % hydrocortisone, 5 % bufexamac (NSAID), 0.75 % fluocortin (glucocorticoid) or a chamomile cream known commercially as Kamillosan®. The chamomile cream was as effective as hydrocortisone and was superior to the other two treatments(Aertgeerts et al. 1985) (Kamillosan® is reportedly made from a high bisabolol-containing chemotype of chamomile). Dermatitis Another study involving experimentally-induced toxic dermatitis found that chamomile ointment (Kamillosan®) produced a more soothing effect on human skin than a chamomile ointment base or hydrocortisone ointment 0.1 %. (Note: the hydrocortisone cream used in this study was quite weak compared to the usual strength of 0.5–2.5%.)(Nissen, Biltz, & Kreysel 1988) Chamomile cream helped protect against skin radiation damage in breast cancer patients receiving radiation.(Maiche, Grohn, & Maki-Hokkonen 1991) Chamomile cream (Kamillosan®) has been shown to be slightly less effective than 0.25% hydrocortisone, but superior to fluocortin butyl ester and 5% bufexamac in relieving inflammation associated with dermatoses.(Aertgeerts 1984;Aertgeerts, Albring, Klaschka, Nasemann, Patzelt-Wenczler, Rauhut, & Weigl 1985)

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Commission E approves the external use of chamomile for inflammation of the skin and mucous membranes, as well as for bacterial skin diseases, including those of the oral cavity and gums. Sedation Both oral dose forms and the essential oil of chamomile are used for this indication. A placebo-controlled study involving 22 volunteers found that inhalation of chamomile oil produced sedative effects and improved mood.(Roberts & Williams 1992) Chamomile tea (two teabags in 150 ml of hot water given to 12 patients during cardiac catheterisation induced a deep sleep in 10 patients, even though the procedure usually causes pain and anxiety.(Gould, Reddy, & Gomprecht 1973) Gastrointestinal conditions Chamomile is widely used to relieve stomach cramping, dyspepsia and flatulence. The herb’s anti-spasmodic and relaxant effects provide a theoretical basis for its use in these conditions. In an open, multicentre study, 104 patients with gastrointestinal complaints including gastritis, flatulence and minor spasms of the intestines were treated for 6 weeks with -mg alphaٱmL/day of an oral chamomile preparation (standardised to contain 50ٱ5bisabolol and 150–300ٱmg apigenin-7-glucoside per 100ٱg). By self-evaluation, all patients improved with 44.2% becoming symptom free.(Stiegelmeyer 1978) Diarrhoea in children In Europe, chamomile is widely used to treat a variety of paediatric complaints. A prospective, double-blind, randomised trial was used to document the efficacy of a preparation containing chamomile extract and pectin in children aged 6 months to 5.5 years with uncomplicated diarrhoea. The chamomile preparation reduced the duration and severity significantly faster than placebo.(de la Motte et al. 1997) The German Commission E approves chamomile for gastrointestinal spasms and inflammatory diseases of the gastrointestinal tract. Antibacterial preparations – Negative studies A Phase III, double-blind, placebo-controlled clinical trial of 164 patients assessed the efficacy of chamomile mouthwash in preventing 5-flurouracil induced stomatitis and found no difference between chamomile and placebo.(Fidler et al. 1996) Chamomile extract spray administered before intubation was not able to prevent postoperative sore throat and hoarseness compared to saline spray in a randomised, double-blind study.(Chan, Rappaport, & Kemper 2003) Other Uses Haemorrhagic cystitis Chamomile extract decreased the symptoms of haemorrhagic cystitis. Thirty-two patients were randomly assigned to receive either the antibiotic cotrimoxazole (trimethoprim/sulfamethoxazole) alone or with a chamomile extract administered on day one as a bladder instillation, followed by daily hipbath use. Symptoms were evaluated after 10 days and indicated that the chamomile group experienced more rapid alleviation of symptoms than the group treated with only cotrimoxazole. The product used was Kamillenextrakt, an ethanolic extract of chamomile flowers.(Barsom, Mossmayr, & Sakka 1993) The British Herbal Pharmacopoeia recommends chamomile for flatulent nervous dyspepsia, travel sickness, nasal catarrh, nervous diarrhoea and restlessness. Externally, chamomile is recommended for haemorrhoids, mastitis and leg ulcers. The

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specific indication is for gastrointestinal disturbance with nervous irritability in children and for teething and colic in infants. Commission E approves the use of inhalations for inflammation and irritation of the respiratory tract and baths and irrigations for anogenital inflammation. Dosage range German chamomile is used either as a tea made from the dried flower heads, or as an extract. • Dried flower heads: 2–8ٱg 3 times daily by infusion. • Fluid extract (1:2): 3–4ٱmL/daily. The quality of chamomile varies greatly. For maximum efficacy, use high-grade chamomile (high in α-bisabolol). Standardised extracts are usually standardised to either bisabolol or apigenin. External application • The dried flowers can also be made into a poultice with the addition of hot water

and applied directly to the skin; or the tea can be used to bathe inflamed skin and eyes.

• Essential oil (external use): 5 drops per 100ٱmL of oil, or per 100ٱg of cream or ointment.

• In baths and water for compresses, the dose should not exceed 10 drops. • Inhalation: 5 drops of essential oil in 1ٱL hot water. Adverse reactions Allergic reactions Occasional rare cases of allergic skin reactions have been reported. However, a bibliographic review of 50 reports of ‘chamomile’ sensitivity revealed that in only 5 papers was the botanical identification of the plant material correlated with Chamomilla recutita. In the majority of other instances, the effects were caused by species of the genus Anthemis, frequently also called chamomile. Experimental studies on pigs using a rigorous testing technique proved that Chamomilla recutita possesses low sensitising capacity. The suspected allergen is the sesquiterpene lactone, anthecotulide, found in Anthemis cotula L. (stinking mayweed), which only occurs in trace amounts in the bisabolol oxide B-chemotype of genuine chamomile.(Hausen, Busker, & Carle 1984) Allergic conjunctivitis has been reported with the use of chamomile tea eyewashes, and the pollens contained in the teas have been identified as the allergens responsible. The reaction occurred after first exposure and was thought to be due to cross-reactivity to Artemesia pollen.(Subiza et al. 1989) Pollens are not likely to be present or active in aqueous alcohol extracts of chamomile. German chamomile is thought to be less allergenic than Roman chamomile, but any variety of chamomile can potentially cause allergic reactions. An enema made from German chamomile (Kamillosan®) given during labour to a 35-year-old woman with no history of atopy resulted in life-threatening anaphylaxis and fatal asphyxia of the newborn.(Jensen-Jarolim et al. 1998) Chamomile enemas are not a usual form of administration. Significant interactions Controlled studies are not available, therefore interactions are based on evidence of activity and are largely theoretical and speculative.

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Benzodiazepines Theoretically, an additive effect can occur with concurrent use, so observe patients taking this combination. Drugs metabolised by CYP 3A4 Chamomile has been shown to inhibit cytochrome P450 enzymes in vitro,(Budzinski et al. 2000) although no human drug interaction data is available to determine the clinical significance of this finding. Observe patients taking such drugs and chamomile. Contraindications and precautions Chamomile is contraindicated in hypersensitivity or known allergy to chamomile or other members of the Compositae family (e.g. yarrow, tansy, feverfew, artemesia). Pregnancy use Safety has not been established scientifically. Practice points/patient counselling • German chamomile has demonstrated anti-inflammatory, antispasmodic, sedative

and antimicrobial activity. • It is taken orally either as a tea or tincture, used externally as a poultice, cream or

ointment or inhaled as an essential oil. • Internally, it is used to relieve flatulence, gastrointestinal spasm, dyspepsia and

induce a sense of relaxation. It is also used for infants with teething pain and colic. • Externally, chamomile preparations are used to treat dermatitis, enhance wound

healing, and soothe irritated skin. Comparative studies show it has an anti-inflammatory effect equivalent to low-dose hydrocortisone preparations.

• There is some evidence from clinical trials to support the use of chamomile in the treatment of wounds, eczema, dermatitis, nervousness and tension, diarrhoea in children and for the symptoms of haemorrhagic cystitis (in association with antibiotic therapy).

Answers to patients frequently asked Questions What can this herb do for me? Chamomile is taken to relieve stomach spasms and flatulence, to induce relaxation and promote sleep. It is also popular for children with teething pain and digestive complaints such as colic or diarrhoea. Applied externally as a cream, ointment or poultice, it is used to reduce skin irritation and inflammation. When will it start to work? Chamomile relieves gastrointestinal symptoms quickly, within several minutes. For more chronic problems, it may need to be used long term. Are there any safety issues? Chamomile is considered a very safe herb. While there have been reports of allergic reactions, the majority have been due to adulteration with other herbs. Chamomile tea is more likely to cause allergic reactions than either extracts or essential oil. Chamomile should not be used by persons with hypersensitivity or known allergy to chamomile or other members of the Compositae family (e.g. yarrow, tansy, feverfew, artemesia).

References Achterrath-Tuckermann, U., Kunde, R., Flaskamp, E., Isaac, O., & Thiemer, K. 1980, "[Pharmacological investigations with compounds of chamomile. V. Investigations on

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the spasmolytic effect of compounds of chamomile and Kamillosan on the isolated guinea pig ileum]", Planta Med, vol. 39, no. 1, pp. 38-50.

Aertgeerts, J. 1984, "Experiences with Kamillosan(TM). A standardised camomille extract in dermatological practice. [Dutch]", Ars Medici Revue Internationale de Therapie Pratique, vol. 39, no. 5, pp. 65-68.

Aertgeerts, P., Albring, M., Klaschka, F., Nasemann, T., Patzelt-Wenczler, R., Rauhut, K., & Weigl, B. 1985, "[Comparative testing of Kamillosan cream and steroidal (0.25% hydrocortisone, 0.75% fluocortin butyl ester) and non-steroidal (5% bufexamac) dermatologic agents in maintenance therapy of eczematous diseases]", Z Hautkr, vol. 60, no. 3, pp. 270-7.

Aggag, M. E. & Yousef, R. T. 1972, "Study of antimicrobial activity of chamomile oil", Planta Med, vol. 22, no. 2, pp. 140-4.

Aguilera, D. B., Souza, & Miglioranza, E. 2000, "The effect of controlled release fertilizer and earthworm compost on Chamomile (Matricarla chamomilla L.) yield. [Portuguese]", Revista Brasileira de Plantas Medicinais, vol. 3, no. 1, pp. 61-65.

Al-Hindawi, M. K., Al-Deen, I. H., Nabi, M. H., & Ismail, M. A. 1989, "Anti-inflammatory activity of some Iraqi plants using intact rats", J Ethnopharmacol, vol. 26, no. 2, pp. 163-8.

Ali-Shtayeh, M. S., Yaniv, Z., & Mahajna, J. 2000, "Ethnobotanical survey in the Palestinian area: A classification of the healing potential of medicinal plants", Journal of Ethnopharmacology, vol. 73, no. 1-2, pp. 221-232.

Barsom, V. S., Mossmayr, A., & Sakka, M. 1993, "Behandlung der hamorrhagischen cystitis (harnblasenschleimhautblutungen) mit kamillenextrakt.", Erfahrungsheilkunde no. 3, pp. 138-139.

Birt, D. F., Mitchell, D., Gold, B., Pour, P., & Pinch, H. C. 1997, "Inhibition of ultraviolet light induced skin carcinogenesis in SKH-1 mice by apigenin, a plant flavonoid", Anticancer Res, vol. 17, no. 1A, pp. 85-91.

Birt, D. F., Walker, B., Tibbels, M. G., & Bresnick, E. 1986, "Anti-mutagenesis and anti-promotion by apigenin, robinetin and indole-3-carbinol", Carcinogenesis, vol. 7, no. 6, pp. 959-63.

Bonnafoux-Clavere, A., Clavere, P., & Bonnetblanc, J. M. 2003, "Acute and chronic radiodermatitis. [French]", Annales de Dermatologie et de Venereologie, vol. 130, no. 5, pp. 565-568.

Bruneton J. 1995, "Pharmacognosy, Phytochemistry, Medicinal Plants," Lavosir, Paris, pp. 455-457.

Budzinski, J. W., Foster, B. C., Vandenhoek, S., & Arnason, J. T. 2000, "An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures", Phytomedicine, vol. 7, no. 4, pp. 273-82.

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Ceska, O., Chaudhary, S. K., Warrington, P. J., & Ashwood-Smith, M. J. 1992, "Coumarins of chamomile, Chamomilla recutita", Fitoterapia, vol. 63, no. 5, pp. 387-394.

Chan, E., Rappaport, L. A., & Kemper, K. J. 2003, "Complementary and alternative therapies in childhood attention and hyperactivity problems", Journal of Developmental and Behavioral Pediatrics, vol. 24, no. 1, pp. 4-8.

Cinco, M., Banfi, E., Tubaro, A., & Dellaloggia 1983, "A microbiological survey on the activity of a hydroalcoholic extract of camomile", International Journal of Crude Drug Research, vol. 21, no. 4, pp. 145-151.

Critchfield, J. W., Coligan, J. E., Folks, T. M., & Butera, S. T. 1997, "Casein kinase II is a selective target of HIV-1 transcriptional inhibitors", Proc Natl Acad Sci U S A, vol. 94, no. 12, pp. 6110-5.

Culpeper N. 1995, "Culpepers's Complete herbal," Wordsworth Reference, Hertfordshire, UK, pp. 54-55.

de la Motte, S., Bose-O'Reilly, S., Heinisch, M., & Harrison, F. 1997, "[Double-blind comparison of an apple pectin-chamomile extract preparation with placebo in children with diarrhea]", Arzneimittelforschung, vol. 47, no. 11, pp. 1247-9.

Della Loggia, R., Carle, r., Sosa, S., & Tubaro, A. 1990, "Evaluation of the anti-inflammatory activity of Chamomile preparations", Planta Medica, vol. 56, no. 6, pp. 657-658.

Della Loggia, R., Tubaro, A., & Redaelli, C. 1981, "[Evaluation of the activity on the mouse CNS of several plant extracts and a combination of them]", Riv Neurol, vol. 51, no. 5, pp. 297-310.

Fidler, P., Loprinzi, C. L., O'Fallon, J. R., Leitch, J. M., Lee, J. K., Hayes, D. L., Novotny, P., Clemens-Schutjer, D., Bartel, J., & Michalak, J. C. 1996, "Prospective evaluation of a chamomile mouthwash for prevention of 5-FU-induced oral mucositis", Cancer, vol. 77, no. 3, pp. 522-5.

Foster S. & Leung A. 1996, "Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics," John Wiley and Sons Inc., New York, pp. 146-147.

Gasic, O., Lukic, V., Adamovic, D., & Canak, N. 1986, "Variation in the content and the composition of the essential oils in flower heads of Matricaria chamomilla L. during its ontogenetical development", Acta Pharm Hung, vol. 56, no. 6, pp. 283-8.

Glowania, H. J., Raulin, C., & Swoboda, M. 1987, "[Effect of chamomile on wound healing--a clinical double-blind study]", Z Hautkr, vol. 62, no. 17, pp. 1262, 1267-71.

Goeters, S., Imming, P., Pawlitzki, G., & Hempel, B. 2001, "On the absolute configuration of matricin", Planta Med, vol. 67, no. 3, pp. 292-4.

Gould, L., Reddy, C. V., & Gomprecht, R. F. 1973, "Cardiac effects of chamomile tea", J Clin Pharmacol, vol. 13, no. 11, pp. 475-9.

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Grieve M. 1976, "A Modern Herbal," Penguin, Middlesex, England, p. 185.

Hausen, B. M., Busker, E., & Carle, r. 1984, "[The sensitizing capacity of composite plants. VII. Experimental studies with extracts and compounds of Chamomilla recutita (L.) Rauschert and Anthemis cotula L.]", Planta Med, vol. 50, no. 3, pp. 229-34.

Ichihashi, M., Kobayashi, A., Okuda, M., & Imokawa, G. 1999, "Effect of Chamomilla extracts application on UV-induced pigmentation. [Japanese]", Skin Research, vol. 41, no. 4, pp. 475-480.

Jakovlev, V., Isaac, O., Thiemer, K., & Kunde, R. 1979, "[Pharmacological investigations with compounds of chamomile ii. new investigations on the antiphlogistic effects of (-)-alpha-bisabolol and bisabolol oxides (author's transl)]", Planta Med, vol. 35, no. 2, pp. 125-40.

Jensen-Jarolim, E., Reider, N., Fritsch, R., & Breiteneder, H. 1998, "Fatal outcome of anaphylaxis to camomile-containing enema during labor: A case study", Journal of Allergy & Clinical Immunology, vol. 102, no. 6 I, pp. 1041-1042.

Kliachko, L. L., Ankhimova, E. S., Svitina, N. N., & Iaremenko, K. V. 1994, "[The effect of medicinal herbs on lymphocyte rosette-forming function]", Vestn Otorinolaringol no. 2, pp. 31-3.

Lepley, D. M., Li, B., Birt, D. F., & Pelling, J. C. 1996, "The chemopreventive flavonoid apigenin induces G2/M arrest in keratinocytes", Carcinogenesis, vol. 17, no. 11, pp. 2367-75.

Lepley, D. M. & Pelling, J. C. 1997, "Induction of p21/WAF1 and G1 cell-cycle arrest by the chemopreventive agent apigenin", Mol Carcinog, vol. 19, no. 2, pp. 74-82.

Maiche, A. G., Grohn, P., & Maki-Hokkonen, H. 1991, "Effect of chamomile cream and almond ointment on acute radiation skin reaction", Acta Oncol, vol. 30, no. 3, pp. 395-6.

Nissen, H. P., Biltz, H., & Kreysel, H. W. 1988, "[Profilometry, a method for the assessment of the therapeutic effectiveness of Kamillosan ointment]", Z Hautkr, vol. 63, no. 3, pp. 184-90.

Panes, J., Gerritsen, M. E., Anderson, D. C., Miyasaka, M., & Granger, D. N. 1996, "Apigenin inhibits tumor necrosis factor-induced intercellular adhesion molecule-1 upregulation in vivo", Microcirculation, vol. 3, no. 3, pp. 279-86.

Pasechnik, I. K. 1966, "[Choleretic action of Matricaria officinalis]", Farmakol Toksikol, vol. 29, no. 4, pp. 468-9.

Plevova, P. 1999, "Prevention and treatment of chemotherapy- and radiotherapy-induced oral mucositis: A review", Oral Oncology, vol. 35, no. 5, pp. 453-470.

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Rekka, E. A., Kourounakis, A. P., & Kourounakis, P. N. 1996, "Investigation of the effect of chamazulene on lipid peroxidation and free radical processes", Res Commun Mol Pathol Pharmacol, vol. 92, no. 3, pp. 361-4.

Roberts, A. & Williams, J. M. 1992, "The effect of olfactory stimulation on fluency, vividness of imagery and associated mood: a preliminary study", Br J Med Psychol, vol. 65 ( Pt 2), pp. 197-9.

Safayhi, H., Sabieraj, J., Sailer, E. R., & Ammon, H. P. 1994, "Chamazulene: an antioxidant-type inhibitor of leukotriene B4 formation", Planta Med, vol. 60, no. 5, pp. 410-3.

Shipochliev, T. 1981a, "Antiinflammatory activity of aqueous and liofilized plant extracts at carrageenin induced inflammation. [Bulgarian]", Farmatsija, vol. 31, no. 2, pp. 47-53.

Shipochliev, T. 1981b, "[Uterotonic action of extracts from a group of medicinal plants]", Vet Med Nauki, vol. 18, no. 4, pp. 94-8.

Shipochliev, T., Dimitrov, A., & Aleksandrova, E. 1981, "[Anti-inflammatory action of a group of plant extracts]", Vet Med Nauki, vol. 18, no. 6, pp. 87-94.

Stiegelmeyer, H. 1978, "Therapie unspezifischer Magenbeschwerden mit Kamillosan.", Kassenarzt no. 18, pp. 3605-3606.

Subiza, J., Subiza, J. L., Hinojosa, M., Garcia, R., Jerez, M., Valdivieso, R., & Subiza, E. 1989, "Anaphylactic reaction after the ingestion of chamomile tea: a study of cross-reactivity with other composite pollens", J Allergy Clin Immunol, vol. 84, no. 3, pp. 353-8.

Suganda, A. G., Amoros, M., Girre, L., & Fauconnier, B. 1983, "[Inhibitory effects of some crude and semi-purified extracts of indigenous French plants on the multiplication of human herpesvirus 1 and poliovirus 2 in cell culture]", J Nat Prod, vol. 46, no. 5, pp. 626-32.

Szelenyi, I., Isaac, O., & Thiemer, K. 1979, "[Pharmacological experiments with compounds of chamomile. III. Experimental studies of the ulcerprotective effect of chamomile (author's transl)]", Planta Med, vol. 35, no. 3, pp. 218-27.

Trovato, A., Monforte, M. T., Forestieri, A. M., & Pizzimenti, F. 2000, "In vitro anti-mycotic activity of some medicinal plants containing flavonoids", Bollettino Chimico Farmaceutico, vol. 139, no. 5, pp. 225-227.

Tubaro, A., Zilli, C., Redaelli, C., & Della Loggia, R. 1984, "Evaluation of antiinflammatory activity of a chamomile extract topical application", Planta Med, vol. 50, no. 4, p. 359.

Umezu, T. 1999, "Anticonflict effects of plant-derived essential oils", Pharmacology, Biochemistry & Behavior, vol. 64, no. 1, pp. 35-40.

Viola, H., Wasowski, C., Levi de Stein, M., Wolfman, C., Silveira, R., Dajas, F., Medina, J. H., & Paladini, A. C. 1995, "Apigenin, a component of Matricaria recutita

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flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects", Planta Med, vol. 61, no. 3, pp. 213-6.

Wagner H., Proksch A., & Riess-Maurer I. 1985, "Immunostimulating action of polysaccharides (heteroglycans) from higher plants", Arzneimittelforschung, vol. 35, no. 7, pp. 1069-1075.

Wei, H., Tye, L., Bresnick, E., & Birt, D. F. 1990, "Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice", Cancer Res, vol. 50, no. 3, pp. 499-502.

Yamada, K., Miura, T., Mimaki, Y., & Sashida, Y. 1996, "Effect of inhalation of chamomile oil vapour on plasma ACTH level in ovariectomized-rat under restriction stress", Biol Pharm Bull, vol. 19, no. 9, pp. 1244-6.

Peppermint Reference: Braun L, Herbs & Natural Supplements - An Evidence-based Guide Description Peppermint has been used for generations as a digestive aid and carminative. More recently, enteric-coated peppermint oil capsules have been widely prescribed for the relief of irritable bowel syndrome (IBS). Latin binomial/class Mentha x piperita Plant part used Leaf or steam – essential oil is distilled from the above-ground parts. Chemical components Peppermint leaves contain about 2.5% essential oil, 19% total polyphenolic compounds, 12% total flavonoid compounds (eriocitrin, luteolin-7- rutinoside, hesperidoside) and 7% total hydroxycinnamic compounds (including rosmarinic acid) (Duband et al 1992). Essential oil Over 100 constituents have been identified in Peppermint oil. The principal constituents are menthol (35–55%), menthones (10–35%), isomenthone, menthyl acetate, menthofuran and cineole. To comply with the European Pharmacopoeia, the oil must not contain more than 4% pulegone and not more than 1% carvone. Main actions The actions of the leaf as an infusion or liquid extract are largely dependent on the essential oil content. Other compounds such as the flavonoids also contribute to the overall activity, especially the antioxidant and antiallergic activities. Antispasmodic activity Both the ethanol extract and the essential oil have demonstrated antispasmodic (spasmolytic) effects. Studies have examined the effects of Peppermint on isolated gut preparations. Ethanol extract, as well as flavonoids isolated from the leaf, has been shown to have antispasmodic effects on the isolated guinea pig ileum (ESCOP 1997) and peppermint oil has been shown to relax gastrointestinal smooth muscle in vitro by interacting with smooth muscle calcium channels (Hills and Aaronson 1991).

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In the peripheral nerves, this effect may be responsible for the characteristic cooling sensation experienced on the oral ingestion of mint. In healthy volunteers, intragastric administration of a dose equivalent to 180 mg peppermint oil, reduced intraoesophageal pressure within 1–7 minutes of infusion (Kingham 1995). Enteroplant, an enteric-coated capsule containing 90 mg peppermint and 50 mg caraway oil as well as its constituents was shown to act locally in the stomach and duodenum to produce smooth muscle relaxation (Micklefield et al 2003). Carminative activity Peppermint also has a carminative activity, which refers to its ability to relax the tonus of the gastrointestinal sphincters. Carminatives are thought to alleviate symptoms of bloating and gas by facilitating eructation and passage of flatus. The classic carminatives are essential oils, such as spearmint and Peppermint. Studies from the 1950s on the effect of carminatives on the gut suggest that they work by inducing relaxation of the lower oesophageal sphincter (Massey 2001). A later study has shown that peppermint oil canalised into the gallbladder and duodenal areas was able to counteract morphine hydrochloride-induced constriction of the sphincter of Oddi (Giachetti et al 1988) Choleretic activity Choleretic activity has been demonstrated for peppermint tea, flavonoids and the essential oil in dogs and rats (ESCOP 1997). Peppermint oil and caraway oils have shown a relaxing effect on the gall bladder and peppermint oil has been shown to slow small intestinal transit time in 12 healthy volunteers. The gastric emptying time did not differ significantly between placebo, peppermint oil and caraway oil (Goerg & Spilker 2003). Antimicrobial activity Peppermint oil has shown evidence in several studies of having antimicrobial activity. Peppermint oil has been shown to inhibit Helicobactor pylori, Staphyllococcus aureus (Imai et al 2001), E. coli (Pattnaik et al 1995), Salmonella enteritidis, Listeria monocytogenes, Shigella sonei and Micrococcus flavus (Mimica-Dukic et al 2003) and a variety of fungi (Anon 1998, Pattnaik et al 1996). Peppermint oil, and its constituents menthone and isomenthone, have also been shown to be antioxidant (Mimica-Dukic et al 2003). Anti-allergic effects The flavonoid luteolin-7-O-rutinoside isolated from the aerial part of Peppermint has been shown to inhibit histamine release from rat peritoneal mast cells in a dose-dependent manner (100–300 mg/kg) and to reduce antigen-induced allergic nasal symptoms (Inoue et al 2002). It would be difficult to achieve such doses of luteolin with a commercially available Peppermint extract or oil. However, an extract of the whole herb may be beneficial in alleviating nasal symptoms associated with allergic rhinitis in association with other medicines. A 50% hydro-ethanolic extract of Peppermint leaves has been shown to inhibit chemically induced histamine release from rat peritoneal mast cells in vitro. The Peppermint extract was also shown to reduce nasal symptoms (sneezing and nasal rubbing) in rats with experimentally induced allergic rhinitis. Significant inhibition of sneezing and nasal rubbing was observed at oral doses of 300 and 1000 mg/kg, respectively (Inoue et al 2001). Other actions Stimulant effect

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Intraperitoneal and intravenous injections of peppermint oil and its constituents, 1,8-cineol, menthone, isomenthone, menthol, pulegone, menthyl acetate and caryophyllene, dramatically increased ambulatory activity in mice. It is thought that the effect is mediated via a dopaminergic effect of menthol. This may explain the traditional use of Peppermint for mental fatigue (Umezu and Morita 2003, Umezu et al 2001). A combination of peppermint oil, eucalyptus oil and ethanol was shown in a cross-over, double-blind study to increase cognitive performance, relax muscles and mentally relax 32 healthy subjects (Gobel et al 1994). Coolant effect Peppermint oil has been shown to interact with smooth muscle calcium channels (Hills and Aaronson 1991). In the peripheral nerves this effect may be responsible for the characteristic cooling sensation experienced on oral ingestion of mint. Diuretic effect A spray dried peppermint infusion has been found to be mildly diuretic (Della et al 1990). Sedative effects A spray dried peppermint infusion produced weak sedative action in several tests when administered orally to mice (Della et al 1990). Analgesic effect A significant analgesic effect with a reduction in sensitivity to headache was produced by a combination of peppermint oil and ethanol applied externally in 32 healthy males undergoing artificial pain stimulation in a double-blind, placebo-controlled, randomised, 7-day crossover study (Gobel et al 1994). Clinical use In practice, Peppermint and its derivatives are used in many forms and administered by various routes. This review will focus only on those methods which are commonly used by the public and preparations which are available over the counter, such as oral dose forms, topical applications and inhalations. Irritable Bowel Syndrome There have been several studies examining the effects of peppermint oil in the treatment of IBS (Rees et al 1979, Dew et al 1984). Newer studies have tended to use an enteric-coated peppermint oil capsules. Enteric coating prevents dissolution of the capsules until it has reached the target site in the intestines. This allows administration of a higher dose than would otherwise be possible to tolerate and, importantly, avoids the risk of excessively relaxing the lower oesophageal sphincter, thus causing reflux. A prospective, randomised, double-blind, placebo-controlled clinical study of 110 outpatients with IBS found that one enteric-coated peppermint oil capsule (Colpermin) taken 3–4 times daily, 15–30 minutes before meals significantly, reduced symptoms compared to placebo (P<0.05; Mann-Whitney U-test). Of the 41 patients taking the peppermint capsule, 79% experienced an alleviation of the severity of abdominal pain (29 were pain free); 83% had less abdominal distension, 83% had reduced stool frequency, 73% had fewer borborygmi, and 79% had less flatulence. One patient experienced heartburn (because of chewing the peppermint capsules) and one developed a mild transient skin rash. There were no significant changes in liver function test results (Liu et al 1997).

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Pittler and Ernst published a critical review and meta-analysis of peppermint oil for IBS in 1998. They found eight randomised, controlled trials of which five were also double blind. Although they noted some methodological flaws in the studies and that more studies are needed, the authors concluded that the meta-analysis of the five placebo-controlled, double blind trials seems to support peppermint oil as efficacious for symptom relief in IBS (Pittler and Ernst 1998). Since this time there have been further positive studies. A randomised, double-blind controlled trial of 42 children with IBS found that treatment with enteric-coated peppermint oil capsules reduced the severity of the pain associated with IBS in 75% of the children (Kline et al 2001). Bacterial overgrowth of the small intestine is associated with a number of functional somatic disorders, including IBS, fibromyalgia and chronic fatigue syndrome. There have been two reports of successful treatment of IBS due to intestinal overgrowth with enteric-coated peppermint oil capsules. The effect may in part be associated with the antimicrobial activities of peppermint oil (Gaby 2003, Logan and Beaulne 2002). Clinical note – The pathophysiology of IBS The pathophysiology of IBS is poorly understood, but it is believed to occur when the intestinal muscles are contracting faster or slower than normal. Colonic contractions cause abdominal pain, cramping, wind and diarrhoea or constipation. It has been proposed that IBS may result from dysregulation of gastrointestinal motor and enhanced sensory functions, as modulated by the central nervous system. However, clinical and laboratory investigations have failed to uncover any histological, microbiological, or biochemical abnormalities in IBS patients. Patients with IBS demonstrate increased motility and abnormal contractions of the intestinal muscles when faced with an emotionally or physically stressful situation (Greenberg et al 2002). It is likely that IBS is also associated with dietary habits, poor upper digestion and intestinal dysbiosis (bacterial overgrowth of the bowels). Common symptoms of IBS (Greenberg et al 2002) • Cramping pain in the lower abdomen • Bloating and excess gas (wind) • Changes in bowel habits • Diarrhoea or constipation, either one dominant or both alternating • Immediate need for a bowel movement on awakening or during or after meals • Relief of pain after bowel movements • Feeling of incomplete emptying after bowel movements • Mucus in the stool Dyspepsia An enteric-coated capsule (Enteroplant) containing 90 mg peppermint oil and 50 mg caraway oil has been shown in a double-blind, placebo-controlled multicentre trial with 45 patients to improve symptoms of non-ulcer dyspepsia. The primary outcome variables were changes in the intensity of pain and the global clinical impression. Nearly 90% of patients experienced a reduction in pain, and after 4 weeks nearly 95% had improved Clinical Global Impression scores compared to placebo (P=0.015 and 0.008, respectively). Before the start of treatment all patients in the test preparation group reported moderate to severe pain, while by the end of the study 63.2% of these patients were free of pain. The peppermint/caraway oil combination was well

Michael Thomsen

tolerated. There were a total of 7 adverse events reported (4 in the active group) and only one being causally associated with the active treatment (May et al 1996) Since then there have been two further trails of this particular peppermint oil combination. In a prospective, randomised, reference and double-blind controlled multicentre trial with 223 patients with non-ulcer dyspepsia and irritable bowel syndrome, the peppermint oil combination was found to significantly reduce pain (P<0.001) (Freise and Kohler 1999). In a study of 96 outpatients, the same Peppermint formulation was found to significantly improve symptoms of functional dyspepsia compared to placebo. After 4 weeks, the average intensity of pain was reduced by 40% vs. baseline in the active group and by 22% in the placebo group. The Peppermint combination also reduced pressure, heaviness and fullness. Six patients (5 in the active group and 1 in the placebo group) reported adverse events. These were found to be either unrelated to the trial, or attributable to an aggravation of the disease under investigation.(May et al 2000). Comparative studies The same peppermint oil combination has been compared to cisapride. Cisapride (Prepulsid) increases the lower oesophageal sphincter pressure, thereby reducing the risk of reflux. Cisapride is also used to treat irritable bowel syndrome dominated by constipation. Cisapride has, however, been linked to serious cardiac arrhythmias and should be used with caution. In the 4- week study, the Peppermint and caraway oil combination (Enteroplant, 2 capsules daily) was shown to be as effective as cisapride in reducing both the magnitude and frequency of pain. Physicians rated the two treatments comparable in regard to other dyspeptic symptoms in addition to intestinal and extra-intestinal autonomic symptoms as measured by the Dyspeptic Discomfort Score and Clinical Global Impressions scale. Corresponding results were also found in Helicobacter pylori-positive patients and patients who initially presented with intense epigastric pain in the two treatment groups. Both medications were tolerated well (adverse events were reported in 12 patients of the PCC group and in 14 patients of the CIS group) (Madisch et al 1999). In a systematic review of herbal medicines for functional dyspepsia, Thompson Coon and Ernst found 17 randomised 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 (Coon and Ernst 2002). Diffuse Oesophageal Spasm Diffuse oesophageal spasm (DES) is a relatively rare motor disorder. Associated manometric abnormalities may include hypertensive and repetitive contractions. The lower oesophageal sphincter (LES) may also be hypertensive. Although LES relaxation with deglutition is generally normal, disturbances in LES function are often seen. These abnormalities are, however, not required for the diagnosis (Massey 2001). In a study of eight DES patients with chest pain or dysphagia, peppermint oil had no effect on lower oesophageal sphincter pressures or contractile pressures and durations in the oesophagus. However, the peppermint oil completely eliminated simultaneous oesophageal contractions in all patients (P<0.01). The number of multiphasic, spontaneous and missed contractions also improved. Two of the eight patients had chest pain that resolved after the peppermint oil (Pimentel et al 2001). Headache

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A solution of 10% peppermint oil in ethanol has been shown in a randomised, placebo-controlled, double-blind, crossover study to efficiently alleviate tension-type headache. The study analysed 164 headache attacks in 41 patients of both sexes ranging between 18 and 65 years of age, suffering from tension-type headache. The peppermint oil was spread largely across forehead and temples and repeated after 15 and 30 minutes. Using a headache diary, the headache parameters were assessed after 15, 30, 45 and 60 minutes. Compared to the application of a placebo, the peppermint oil significantly reduced the intensity of the headache after 15 minutes (P<0.01). The analgesic effect of the peppermint oil was comparable to 1000 mg paracetamol (acetaminophen). Simultaneous ingestion of 1000 mg of paracetamol and application of 10% peppermint oil in ethanol solution leads to an slight additive effect (Gobel et al 1996). Other uses Post-herpetic neuralgia A case report describes the treatment of post-herpetic neuralgia with the application of undiluted peppermint oil containing 10% menthol directly to the affected area. The pain relief persisted for 4–6 hours after application of the oil. At a 2-months follow-up the patient had only minor side effects and continued to use the medication (Davies et al 2002) Postoperative nausea Inhalation of peppermint oil vapors has been shown in a study to reduce postoperative nausea in gynaecological patients. The study used a three-condition experimental design using statistical analysis to compare groups. The control, placebo and experimental groups of gynaecological patients were compared, using variables known to affect postoperative nausea. They were found to be homogeneous for the purposes of the study. There was a significant reduction in nausea in the Peppermint group compared to placebo (P=0.02). The patients were free to inhale the peppermint oil as frequently as desired. In view of the increased number of intra-abdominal procedures, the increased amount of opioids, the reduced amount of anti-emetics and the qualitative data obtained from patients, the authors concluded that there is evidence to suggest that peppermint oil may improve postoperative nausea in gynaecological patients (Tate 1997). A hot peppermint oil compress is used in China to prevent abdominal distension in postoperative gynaecological patients (Feng 1997). Respiratory tract infections Peppermint and menthol have an established tradition in the treatment of respiratory infections. Chest rubs containing menthol are frequently used to treat coughs and bronchitis. Inhalation of various antiseptic and anti-inflammatory essential oils are often used in the treatment of respiratory infections including bronchitis (Shubina et al 1990). Peppermint oil has been found to have a pronounced antimycobacterial effect in vitro and long-term use of peppermint oil in a humidifier has been used in the Ukraine as an adjunctive treatment to multidrug therapy for pulmonary tuberculosis (Shkurupii et al 2002). Dosage range Leaf • Infusion: 3–6 g 3 times daily (Blumenthal et al 2000) • Liquid extract (1:2): 10–30 mL weekly

Michael Thomsen

• These dosages are for adults; adjust according to size for children. Essential oil • Digestive disorders: 0.2–0.4 mL 3 times daily in dilute preparations or in

suspension.(ESCOP 1997) • IBS: 0.2–0.4 mL 3 times daily in enteric-coated capsules or tables. (Dew et al

1984, Rees et al 1979) • Inhalation: 3–4 drops added to hot water • Lozenge: 2–10 mg • External use (for analgesic, anaesthtic or antipruritic activity): 0.1–1.0% m/m

(ESCOP 1997) • External use (counter irritant): 1.25–16% m/m (ESCOP 1997) Adverse reactions A single dose of 4000 mg/kg of a spray-dried infusion did not produce any macroscopic signs of toxicity in mice (Della et al 1990). Peppermint oil has been shown to be minimally toxic in acute oral studies. Short-term and subchronic oral studies reported brain lesions in rats that were given very large doses of peppermint oil containing pulegone, pulegone alone or large amounts (>200 mg/kg/day) of menthone. Pulegone is also a recognised hepatotoxin. Repeated intradermal dosing with peppermint oil produced moderate and severe reactions in rabbits, although peppermint oil did not appear to be phototoxic. Peppermint oil was negative in an Ames test and a mouse lymphoma mutagenesis assay, but gave equivocal results in a Chinese hamster fibroblast cell chromosome aberration assay. Although sensitisation to peppermint oil and/or its constituents have been reported, a solution containing 8% peppermint oil was shown not to be a sensitiser (Nair 2001). Contact dermatitis to Peppermint and menthol has been reported (Morton et al 1995); however, as long as the pulegone content is kept to a minimum, peppermint oil and peppermint extract is considered to have a very good safety profile. Significant interactions Controlled studies are not available, therefore interactions are based on evidence of activity and are largely theoretical and speculative. Felodipine Peppermint oil has been shown to increase the oral bioavailability of felodipine in animal studies (Anon 2002). Use this combination with caution. Simvastatin Peppermint oil has been shown to increase the oral bioavailability of simvastatin in animal studies (Anon 2002). Observe - monitor drug requirements – interaction may be beneficial. Cyclosporin Peppermint oil has been shown to increase the oral bioavailability of cyclosporin in animal studies (Anon 2002). Avoid concurrent use unless under medical supervision. drugs metabolised by CYP 3A4 liver enzyme Peppermint may increase the oral bioavailability of certain drugs by inhibition of CYP3A4-mediated drug metabolism, which has been demonstrated in vitro but not in test animals (Dresser et al 2002, Maliakal and Wanwimolruk 2001). Although these studies seem to suggest that Peppermint may modulate drug metabolising enzymes,

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the clinical significance of this is unknown and requires further investigation. Therefore caution is advised. Contraindications and precautions Hypersensitivity to peppermint oil (Morton et al 1995). Non-enteric coated peppermint may be best avoided in patients with reflux oesophageal symptoms. Avoid chewing enteric coated capsules as it may cause heartburn (Liu et al 1997). Avoid the use of peppermint oil on the face of infants and small children. Capsules containing Peppermint oil is contraindicated in biliary duct occlusion, gallbladder inflammation and sever liver damage (Blumenthal et al 2000). Pregnancy use Safe dosages in pregnant women have not been determined. Practice points/patient counseling • The clinical trials have used enteric-coated peppermint oil capsules in the

treatment of irritable bowel syndrome. The capsules contain 90 mg peppermint and may be combined with other oils including 50 mg caraway oil.

• Although enteric-coated capsules were also used in the dyspepsia trials, traditional extracts of Peppermint, including hydro-ethanolic and infusions, may also be effective.

• The German Commission E approved Peppermint for spasmodic complaints in the gastrointestinal region and of the gall bladder and bile ducts. (Blumenthal et al 2000). The British Herbal Pharmacopoeia recommends Peppermint leaf extract for dyspepsia, flatulence, intestinal colic and biliary disorders. Note, however that Peppermint oil is contraindicated in inflammation of the gallbladder and severe liver disease.

• Peppermint leaf extract combines well with chamomile, caraway, liquorice, lemon balm, angelica, St Mary’s thistle and the bitter candytuft (Iberis amara) in the treatment of functional dyspepsia (Madisch et al 2001).

• Peppermint oil can be used as an inhalation or chest rub for coughs, sinusitis and bronchitis. The Commission E approved peppermint oil for internal use in the treatment of respiratory tract inflammation (Blumenthal et al 2000).

• Hot peppermint leaf infusion is used as a diaphoretic tea in the treatment of colds and influenza.

• Pure peppermint oil can be inhaled to reduce nausea. Peppermint extract may also be used internally.

• Peppermint or pure menthol is used in heat rub ointments for arthritis, fibromyositis, tendonitis and other musculoskeletal conditions. The Commission E approved peppermint oil externally for neuralgia and myalgia (Blumenthal et al 2000).

• 10% peppermint oil in ethanol solution can be applied externally for tension headaches. Spread across the forehead and temples, and repeat after 15 and 30 minutes.

• Pure peppermint oil can be applied over affected areas for post-herpetic neuralgia. Dilute in ethanol if necessary.

Answers to patients’ frequently asked Questions • What can this herb do for me?

Michael Thomsen

Peppermint is a safe herb for gastrointestinal disorders including dyspepsia and irritable bowel syndrome. It is also safe for children, particularly as a herbal tea. • When will it start to work? Peppermint will generally have an immediate effect with the condition continuing to improve with long-term use. • Are there any safety issues? Concentrated peppermint oil preparations may theoretically interact with a number of different medications. It is unlikely any interaction will occur with peppermint tea or simple liquid extracts. Avoid the use of peppermint oil on the face of infants and small children. References Anon. 1998, "Essential oils of peppermint, orange or lemongrass kill most strains of fungal and bacterial infections", Posit Health News no. No 17, pp. 26-7.

Anon. 2002, "Peppermint oil increases the oral bioavailability of felodipine and simvastatin", Clinical Pharmacology & Therapeutics February, vol. 71, no. 2, p. P67.

Blumenthal, M., Goldberg A, & Brinckmann J. Herbal Medicine - Expanded Commission E Monographs. 297-303. 2000. Newton, MA, USA, Integrative Medicine Communications. COON, J. T. & Ernst, E. 2002, "Systematic Review: Herbal medicinal products for non-ulcer dyspepsia. [Article]", Alimentary Pharmacology & Therapeutics October, vol. 16, no. 10, pp. 1689-1699.

Davies, S. J., Harding, L. M., & Baranowski, A. P. 2002, "A novel treatment of postherpetic neuralgia using peppermint oil", Clin J Pain, vol. 18, no. 3, pp. 200-2.

Della, L. R., Tubaro, A., & Lunder, T. L. 1990, "Evaluation of some pharmacologica activities of a peppermint extract", Fitoterapia, vol. 61, no. 3, pp. 215-221.

Dew, M. J., Evans, B. K., & Rhodes, J. 1984, "Peppermint oil for the irritable bowel syndrome: a multicentre trial", Br J Clin Pract, vol. 38, no. 11-12, pp. 394, 398.

Dresser, G. K., Wacher, V., Wong, S., Wong, H. T., & Bailey, D. G. 2002, "Evaluation of peppermint oil and ascorbyl palmitate as inhibitors of cytochrome P4503A4 activity in vitro and in vivo", Clin Pharmacol Ther, vol. 72, no. 3, pp. 247-55.

Duband, F., Carnat, A. P., Carnat, A., Petitjean-Freytet, C., Clair, G., & Lamaison, J. L. 1992, "[Aromatic and polyphenolic composition of infused peppermint, Mentha x piperita L.]", Ann Pharm Fr, vol. 50, no. 3, pp. 146-55.

ESCOP. Menthae Piperitae Folium- Peppermint Leaf. 1997. Ref Type: Generic

Feng, X. Z. 1997, "[Effect of peppermint oil hot compresses in preventing abdominal distension in postoperative gynecological patients]", Zhonghua Hu Li Za Zhi, vol. 32, no. 10, pp. 577-8.

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Freise, J. & Kohler, S. 1999, "[Peppermint oil-caraway oil fixed combination in non-ulcer dyspepsia-- comparison of the effects of enteric preparations]", Pharmazie, vol. 54, no. 3, pp. 210-5.

Gaby, A. R. 2003, "Treatment with enteric-coated peppermint oil reduced small-intestinal bacterial overgrowth in a patient with irritable bowel syndrome", Altern Med Rev, vol. 8, no. 1, p. 3; author reply 4-5.

Giachetti, D., Taddei, E., & Taddei, I. 1988, "Pharmacological activity of essential oils on Oddi's sphincter", Planta Med., vol. 54, no. 5, pp. 389-392.

Gobel, H., Fresenius, J., Heinze, A., Dworschak, M., & Soyka, D. 1996, "[Effectiveness of Oleum menthae piperitae and paracetamol in therapy of headache of the tension type]", Nervenarzt, vol. 67, no. 8, pp. 672-81.

Gobel, H., Schmidt, G., & Soyka, D. 1994, "Effect of peppermint and eucalyptus oil preparations on neurophysiological and experimental algesimetric headache parameters", Cephalalgia, vol. 14, no. 3, pp. 228-34.

Goerg, K. J. & Spilker, T. 2003, "Effect of peppermint oil and caraway oil on gastrointestinal motility in healthy volunteers: a pharmacodynamic study using simultaneous determination of gastric and gall-bladder emptying and orocaecal transit time", Aliment Pharmacol Ther, vol. 17, no. 3, pp. 445-51.

Greenberg, M. R. M. M., Amitrone, H. P.-C. A., & Galiczynski, J. E. M. B. 2002, "A Contemporary Review of Irritable Bowel Syndrome", Physician Assistant August, vol. 26, no. 8, pp. 26-33.

Hills, J. M. & Aaronson, P. I. 1991, "The mechanism of action of peppermint oil on gastrointestinal smooth muscle. An analysis using patch clamp electrophysiology and isolated tissue pharmacology in rabbit and guinea pig", Gastroenterology, vol. 101, no. 1, pp. 55-65.

Imai, H., Osawa, K., Yasuda, H., Hamashima, H., Arai, T., & Sasatsu, M. 2001, "Inhibition by the essential oils of peppermint and spearmint of the growth of pathogenic bacteria", Microbios, vol. 106 Suppl 1, pp. 31-9.

Inoue, T., Sugimoto, Y., Masuda, H., & Kamei, C. 2001, "Effects of peppermint (Mentha piperita L.) extracts on experimental allergic rhinitis in rats", Biol Pharm Bull, vol. 24, no. 1, pp. 92-5.

Inoue, T., Sugimoto, Y., Masuda, H., & Kamei, C. 2002, "Antiallergic effect of flavonoid glycosides obtained from Mentha piperita L", Biol Pharm Bull, vol. 25, no. 2, pp. 256-9.

Kingham, J. G. C. 1995, "Peppermint oil and colon spasm", Lancet, vol. 346, no. 8981, p. 986.

Kline, R. M., Kline, J. J., Di Palma, J., & Barbero, G. J. 2001, "Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children", J Pediatr, vol. 138, no. 1, pp. 125-8.

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Liu, J. H., Chen, G. H., Yeh, H. Z., Huang, C. K., & Poon, S. K. 1997, "Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial", J Gastroenterol, vol. 32, no. 6, pp. 765-8.

Logan, A. C. & Beaulne, T. M. 2002, "The treatment of small intestinal bacterial overgrowth with enteric-coated peppermint oil: a case report", Altern Med Rev, vol. 7, no. 5, pp. 410-7.

Madisch, A., Heydenreich, C. J., Wieland, V., Hufnagel, R., & Hotz, J. 1999, "Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride. A multicenter, reference-controlled double-blind equivalence study", Arzneimittelforschung, vol. 49, no. 11, pp. 925-32.

Madisch, A., Melderis, H., Mayr, G., Sassin, I., & Hotz, J. 2001, "[A plant extract and its modified preparation in functional dyspepsia. Results of a double-blind placebo controlled comparative study]", Z Gastroenterol, vol. 39, no. 7, pp. 511-7.

Maliakal, P. P. & Wanwimolruk, S. 2001, "Effect of herbal teas on hepatic drug metabolizing enzymes in rats", J Pharm Pharmacol, vol. 53, no. 10, pp. 1323-9.

Massey, B. T. 2001, "Diffuse esophageal spasm: a case for carminatives?", J Clin Gastroenterol, vol. 33, no. 1, pp. 8-10.

May, B., Kuntz, H. D., Kieser, M., & Kohler, S. 1996, "Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia", Arzneimittelforschung, vol. 46, no. 12, pp. 1149-53.

May, B. 1., Kohler, S. 2., & Schneider, B. 2. 2000, "Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia", Alimentary Pharmacology & Therapeutics December, vol. 14, no. 12, pp. 1671-1677.

Micklefield, G., Jung, O., Greving, I., & May, B. 2003, "Effects of intraduodenal application of peppermint oil (WS(R) 1340) and caraway oil (WS(R) 1520) on gastroduodenal motility in healthy volunteers", Phytother Res, vol. 17, no. 2, pp. 135-40.

Mimica-Dukic, N., Bozin, B., Sokovic, M., Mihajlovic, B., & Matavulj, M. 2003, "Antimicrobial and antioxidant activities of three Mentha species essential oils", Planta Med, vol. 69, no. 5, pp. 413-9.

Morton, C. A., Garioch, J., Todd, P., Lamey, P. J., & Forsyth, A. 1995, "Contact sensitivity to menthol and peppermint in patients with intra- oral symptoms", Contact Dermatitis, vol. 32, no. 5, pp. 281-4.

Nair, B. 2001, "Final report on the safety assessment of Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, and Mentha Piperita (Peppermint) Leaf Water", Int J Toxicol, vol. 20 Suppl 3, pp. 61-73.

Pattnaik, S., Subramanyam, V. R., & Kole, C. 1996, "Antibacterial and antifungal activity of ten essential oils in vitro", Microbios, vol. 86, no. 349, pp. 237-46.

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Pattnaik, S., Subramanyam, V. R., & Rath, C. C. 1995, "Effect of essential oils on the viability and morphology of Escherichia coli (SP-11)", Microbios, vol. 84, no. 340, pp. 195-9.

Pimentel, M., Bonorris, G. G., Chow, E. J., & Lin, H. C. 2001, "Peppermint oil improves the manometric findings in diffuse esophageal spasm", J Clin Gastroenterol, vol. 33, no. 1, pp. 27-31.

Pittler, M. H. & Ernst, E. 1998, "Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis", Am J Gastroenterol, vol. 93, no. 7, pp. 1131-5.

Rees, W. D., Evans, B. K., & Rhodes, J. 1979, "Treating irritable bowel syndrome with peppermint oil", Br Med J, vol. 2, no. 6194, pp. 835-6.

Shkurupii, V. A., Kazarinova, N. V., Ogirenko, A. P., Nikonov, S. D., Tkachev, A. V., & Tkachenko, K. G. 2002, "[Efficiency of the use of peppermint (Mentha piperita L) essential oil inhalations in the combined multi-drug therapy for pulmonary tuberculosis]", Probl Tuberk no. 4, pp. 36-9.

Shubina, L. P., Siurin, S. A., & Savchenko, V. M. 1990, "[Inhalations of essential oils in the combined treatment of patients with chronic bronchitis]", Vrach Delo no. 5, pp. 66-7.

Tate, S. 1997, "Peppermint oil: a treatment for postoperative nausea", J Adv Nurs, vol. 26, no. 3, pp. 543-9.

Umezu, T. & Morita, M. 2003, "Evidence for the involvement of dopamine in ambulation promoted by menthol in mice", J Pharmacol Sci, vol. 91, no. 2, pp. 125-35.

Umezu, T., Sakata, A., & Ito, H. 2001, "Ambulation-promoting effect of peppermint oil and identification of its active constituents", Pharmacol Biochem Behav, vol. 69, no. 3-4, pp. 383-90.

Ginger Reference: Braun L, Herbs & Natural Supplements - An Evidence-based Guide Historical note Ginger has been used as both a food and medicine since ancient times. Records suggest that it was widely used in ancient Rome, Greece, Arabia and China. It is still extremely popular in the practice of phytotherapy, particularly in traditional Chinese medicine which distinguishes between the dried and fresh root. It is widely used to stimulate circulation, treat various gastrointestinal disorders and as a stimulant heating agent. Scientific name Zingiber officinale Roscoe, family: Zingiberaceae Other names Jamaica ginger, African ginger, Indian ginger, common ginger, Rhizoma Zingiberis, Shokyo (Japanese) Plant part used

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Rhizome Chemical components The ginger rhizome contains an essential oil and resin known collectively as oleoresin. The composition of the essential oil varies according to the geographical origin, but the chief constituents, sesquiterpene hydrocarbons, which are responsible for the characteristic aroma, are fairly constant. The oleoresin contains: • Sesquiterpenes: zingiberene, ar-curcumene, beta-sesquiphellandrene and beta-

bisabolene. • Pungent phenolic compounds: gingerols and their corresponding degradation

products, known as shogaols. • Other constituents include diarylheptanoids galanolactone (diterpenoid), 6-

Gingesulfonic acid), monoacyldigalactosylglycerols (Awang 1992;Bhattarai, Tran, & Duke 2001;Charles, Garg, & Kumar 2000;Kikuzaki, Usuguchi, & Nakatani 1991;World Health Organisation 2003;Yamahara et al. 1992;Yoshikawa et al. 1992;Yoshikawa et al. 1993)

Main actions Antiemetic activity Ginger has demonstrated anti-emetic activity in both experimental models and human studies, the exact mechanism of action of which is still unknown. It appears that several key constituents and several different mechanisms are responsible. Shogaols and gingerols have both been shown to have anti-emetic activity(Kawai et al. 1994). According to both animal and human studies, Ginger reduces emesis due to a peripherally acting mechanism, acting on the gastrointestinal tract alone (Holtmann et al. 1989). One constituent found in Ginger, galanolactone, is a serotonin receptor antagonist which may partly explain the antiemetic effect (Huang et al. 1991a;Mustafa, Srivastava, & Jensen 1993;Yamahara et al. 1990). It also explains the inhibitory effect of Ginger on serotonin-induced diarrhoea and antispasmodic effects on visceral and vascular smooth muscle. Ginger has been shown to blunt gastric dysrhythmias and nausea evoked by acute hyperglycaemia in humans. The antiarrhythmic and antiemetic effects are thought to be due to a blockade of prostaglandins rather than inhibition of their release (Gonlachanvit 2001). Gastrointestinal activity Ginger exerts several effects in the gastrointestinal tract. It stimulates the flow of saliva, bile and gastric secretions (Platel & Srinivasan 1996;Platel & Srinivasan 2001;Yamahara, Miki, & Chisaka 1985). Ginger has been shown to increase gastrointestinal motility without affecting gastric emptying in several animal models and human studies (Gupta & Sharma 2001;Micklefield et al. 1999;Phillips, Hutchinson, & Ruggier 1993). These findings appear to support to the traditional use of Ginger in the treatment of gastrointestinal discomfort and bloating. Antiulcer activity A number of in vivo studies have identified anti-ulcer activity for ginger extract and several of its isolated constituents. The orally administered acetone extract of ginger at a dose of 1000 mg/kg and zingiberene, the main terpenoid in this extract, at 100 mg/kg significantly inhibited

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gastric lesions by 97.5% and 53.6%, respectively. Additionally, the pungent principle, 6-gingerol at 100 mg/kg significantly inhibited gastric lesions by 54.5%. These results suggest that both zingiberene and 6-gingerol are important constituents responsible for the anti-ulcer activity of Ginger (Yamahara et al. 1988). Other constituents demonstrating antiulcer properties in gastric ulcer models in rats include beta-sesquiphellandrene, beta-bisabolene, ar-curcumene and shogaol isolated from ginger rhizome. (Sertie et al. 1992;Yoshikawa et al. 1994). Hypolipidemic activity High doses of a water extract of ginger (500 mg/kg) significantly reduced serum cholesterol according to an animal study which used oral doses of a raw aqueous extract of ginger administered daily for a period of 4 weeks (Thomson et al. 2002). Effects on triglyceridev levels are more difficult to determine as one study demonstrated that 250 µg of ginger extract/day reduced serum triglyceride levels by 27% in mice (Fuhrman et al. 2000) whereas another study using a high dose of 500 mg/kg found no significant effects (Thomson, Al-Qattan, Al-Sawan, Alnaqeeb, Khan, & Ali 2002). An ex-vivo study found that a 250 µg/daily of a standardised ginger extract significantly reduced plasma LDL cholesterol levels, the LDL basal oxidative state, as well as LDL and serum cholesterols susceptibility to oxidation and aggregation compared with placebo. Ginger also reduced aortic atherosclerotic lesions by 44% in atherosclerotic mouse aorta (Fuhrman, Rosenblat, Hayek, Coleman, & Aviram 2000). Anti-inflammatory and analgesic activity The anti-inflammatory effects of Ginger may be due to its effects on the arachidonic acid cascade as cyclo-oxygenase and lipoxygenase inhibition has been shown in vitro, resulting in decreased prostaglandin and leukotriene formation (Kobayashi, Shoji, & Ohizumi 1987). Additionally, ginger extract has been shown to inhibit thromboxane synthase (Langner, Greifenberg, & Gruenwald 1998). This has been shown in vivo with high oral doses of aqueous extract of ginger (500 mg/kg) which significantly lower serum prostaglandin E2 and thromboxane B2 levels in rats (Thomson, Al-Qattan, Al-Sawan, Alnaqeeb, Khan, & Ali 2002). No one single constituent seems to be responsible for the anti-inflammatory effect of Ginger. An acetone extract containing gingerols, shogaols and minor compounds like gingerenone A, [6]-gingerdiol, hexahydrocurcumin and zingerone have been shown synergistically to produce a dose-dependent anti-inflammatory effect (Schuhbaum & Franz 2000). Other studies have identified the gingerols and diarylheptanoids and gingerdione as the key compounds responsible (Flynn, Rafferty, & Boctor 1986;Kiuchi et al. 1992). Topical application of ginger cream or compresses produces an analgesic effect which is likely to be due to a capsaicin-like effect on the release of the immunoreactive substance P from primary afferent neurons (Onogi et al. 1992). In an animal study of chemically induced inflammation, ginger extract reduced oedema which was partly caused by serotonin receptor antagonism (Penna et al. 2003). Additionally, ginger oil showed anti-inflammatory activity, significantly suppressing both paw and joint swelling in severe adjuvant arthritis in rats (Sharma, Srivastava, & Gan 1994). Antiplatelet activity Ginger exerts an antiplatelet activity when taken in very high doses of at least 10 g according to one human study (Bordia, Verma, & Srivastava 1997). According to one randomised, double-blind study, lower doses up to 2 g have no effect on bleeding

Michael Thomsen

time, platelet aggregation or platelet count (Lumb 1994). This lack of effect has been demonstrated in healthy volunteers and those with non-insulin-dependent diabetes mellitus or coronary artery disease (Bordia, Verma, & Srivastava 1997) or healthy subjects (Janssen et al. 1996). Antimicrobial activity Ginger extract and several of its main constituents exhibit antimicrobial activity in vitro and in vivo. Ginger extract has been shown to have an antibacterial effect against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae and Haemophilus collected from throat swaps of infected individuals. The Minimum Inhibitory Concentration (MIC) of Ginger ranged from 0.0003–0.7 µg/mL, while Minimum Bactericidal Concentration (MBC) ranged from 0.1.35–2.04 µg/mL (Akoachere et al. 2002). Ginger has also shown anti-schistosomal activity. Gingerol and shogaol exhibited potent molluscicidal activity in vivo. Gingerol (5.0 ppm) completely abolished the infectivity of Schistosoma spp. (blood flukes) in animal studies (Adewunmi, Oguntimein, & Furu 1990). Gingerols demonstrated antibacterial activity against Bacillus subtilis and Escherichia coli in vitro (Yamada, Kikuzaki, & Nakatani 1992) and the essential oils of ginger have been shown to have antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi in vitro (Martins et al. 2001). Shogaol and gingerol have demonstrated antinematode activities; 6.25 µg/mL 6-shogaol destroyed Anisakis larvae within 16 hours in vitro, whereas the anti-nematodal medication pyrantel pamoate had no lethal effect at 1 mg/mL (Goto et al. 1990). Ginger constituents have also been shown to be antifungal and antiviral. Shogaol and zingerone strongly inhibited Salmonella typhi, Vibrio cholerae and Tricophyton violaceum. Aqueous extracts have also been shown to be effective against Trichomonas vaginalis (Henry & Piggott 1987). Several sesquiterpenes, but especially beta-sesquiphellandrene, isolated from Ginger have also been shown to have anti-rhinoviral activity in vitro (Denyer et al. 1994). Antioxidant According to in vivo research, Ginger exerts significant direct and indirect antioxidant effects. Orally administered Ginger significantly lowered levels of free radicals and raised the activities of endogenous antioxidants superoxide dismutase and catalase and had a sparing effect on vitamins C and E (Jeyakumar, Nalini, & Menon 1999). Hepatoprotective activity Ginger has significant hepatoprotective effects which are comparable to silymarin according to research with experimental models of alcohol-induced liver damage (Bhandari et al. 2003). Antihistamine activity Shogaols and certain gingerols exhibit dose-dependent inhibition of drug-induced histamine release from rat peritoneal mast cells in vitro (Yamahara et al. 1995). Anxiolytic A combination of Ginger and Ginkgo biloba has been shown to reduce anxiety in an animal model (elevated plus-maze test). The effect was similar to diazepam (Hasenohrl et al. 1996). A highly non-polar fraction of a ginger extract has been shown to possess anticonvulsant, anxiolytic and antiemetic activities in animals (Vishwakarma et al. 2002). Antifibrotic activity

Michael Thomsen

Supplementation with 5 g Ginger not only prevented a decrease, but also significantly increased fibrinolytic activity in 30 healthy adult volunteers who consumed 50 g of fat in a meal in an open clinical study (Verma & Bordia 2001). Apoptosis A pungent phenolic substance found in Ginger ([6]-paradol) effectively inhibits tumour promotion in mouse skin carcinogenesis. [6]-paradol and structurally related derivatives have also been shown to induce apoptosis through a caspase-3-dependent mechanism (caspase is a ‘suicidal’ cell protein, which, when activated, induces the cell to kill itself) (Keum et al. 2002). Positive inotropic activity Gingerols and shogaols isolated from Ginger have positive inotropic activity, as demonstrated on isolated heart muscle (Shoji, Iwasa, & Takemoto 1982;Yamahara, Matsuda, Yamaguchi, Shimoda, Murakami, & Yoshikawa 1995). The effect of gingerol seems to be rather specific to SR Ca2+-ATPase activity (Kobayashi, Shoji, & Ohizumi 1987). Immunomodulation In vitro and in vivo research suggests ginger extract exerts some degree of immunomodulatory activity and has been shown to prolong the survival of cardiac allografts in mice significantly (Wilasrusmee, Bruch, & Kittur 2003). Thermogenic activity Ginger helps to maintain body temperature and inhibit serotonin-induced hypothermia in vivo (Huang et al. 1991b;Kano, Zong, & Komatsu 1991). However, the addition of a ginger-based sauce to a meal did not to produce any significant effect on metabolic rate in humans (Henry & Piggott 1987). Clinical use Although Ginger is used in many forms, including fresh Ginger used in cooking or chai (Indian spicy tea), pickled or glazed ginger, ethanol extracts and concentrated powdered extracts, preparations made with the root are used medicinally. Prevention of nausea and vomiting Several clinical studies have investigated the effects of Ginger in the prevention and treatment of nausea and vomiting under different circumstances (Arfeen et al. 1995;Bone et al. 1990;Meyer et al. 1995;Phillips, Ruggier, & Hutchinson 1993;Visalyaputra et al. 1998). In 2000, a systematic review of six controlled studies investigating the effects of Ginger in nausea and vomiting was published which found that although Ginger was more effective than placebo in some studies of postoperative nausea and vomiting, a non-significant difference was detected between the dose of 1 g Ginger (taken before surgery) and placebo groups. More specifically, 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. Additionally, Ginger was found to be of benefit in seasickness, morning sickness and chemotherapy-induced nausea compared to placebo (Ernst & Pittler 2000). More recently, a Cochrane review involving 20 trials of antiemetic medications concluded that Ginger might be of benefit, but that the evidence to date was weak (Jewell & Young 2002). Commission E approves the use of Ginger root for the prevention of motion sickness. Clinical note – Morning Sickness

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Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70% and 85% of women. About half of pregnant women experience vomiting (Jewell 2002). Hyperemesis gravidarum is more severe and affects between 0.3% and 2% of all pregnant women. It is a multifactorial disease in which pregnancy-induced hormonal changes associated with concurrent gastrointestinal dysmotility and possible Helicobacter pylori infection function as contributing factors (Eliakim, Abulafia, & Sherer 2000). Nausea of pregnancy A recent double-blind, placebo-controlled, randomised clinical trial found that the ingestion of 1 g Ginger in syrup in divided doses may be useful in some patients experiencing nausea and vomiting in the first trimester of pregnancy. After 9 days, 10 of the 13 (77%) subjects receiving Ginger had at least a 4-point improvement on the nausea scale. In regards to vomiting, 8 of the 12 (67%) women in the ginger group who were vomiting daily at the beginning of the treatment stopped by day 6 (Keating & Chez 2002). An Australian randomised, placebo-controlled trial study with 120 women less than 20 weeks pregnant, using the Rhodes Index of Nausea, Vomiting and Retching, found that Ginger significantly reduced nausea after the first day of treatment and onwards compared to placebo. Retching was also reduced by the ginger extract although to a lesser extent. However, no significant effect was observed on vomiting. Follow-up of the pregnancies revealed normal ranges of birth weight, gestational age, Apgar scores and frequencies of congenital abnormalities compared to the general population of infants born at the same hospital (Willetts, Ekangaki, & Eden 2003). Motion sickness Several clinical studies have assessed the effects of Ginger in the prophylaxis or treatment of motion sickness. An early double-blind randomised placebo – controlled study involving 80 naval cadets found that Ginger was significantly superior to placebo in reducing symptoms of vomiting and cold sweats due to seasickness. Remarkably fewer symptoms of nausea and vertigo were also reported; however, the difference between Ginger treatment and placebo was not statistically significant in this instance (Grontved & Hentzer 1986). In another randomised, double-blind study of seasickness involving over 1700 tourists on a whale-watching safari 300 km north of the Arctic cycle, 500 mg Ginger was found to be as effective for the treatment of motion sickness as several common antiemetic medications (cinnarizine, cyclizine, dimenhydrinate, domperidone, meclizine and scopolamine). On ethical grounds, a placebo group was not included. Ginger treatment prevented seasickness in 80% of the subjects during the six-hour boat trip, although the incidence of severe vomiting did not differ significantly between treatment groups (Schmid et al. 1994). Two clinical studies have been conducted in experimental models whereby subjects are seated in a rotating chair to initiate motion sickness and the effects of test drugs are documented. The first study published involved 28 volunteers and found no significant protective effects for powdered Ginger (whole root, 500 mg or 1000 mg) or fresh ginger root (1000 mg) (Stewart et al. 1991). More recently, a double-blind, randomised placebo-controlled crossover study showed positive benefits with Ginger pretreatment on prolonging time before nausea, shortening recovery time and effectively reducing nausea (Lien et al. 2003). This study used higher pretreatment doses of 1000 mg and 2000 mg, which were also shown to reduce tachygastria and plasma vasopressin. Postoperative nausea

Michael Thomsen

Ginger may be useful for the prevention of postoperative nausea, although not all studies have produced positive results. One randomised, double-blind study failed to show any benefit in patients undergoing gynecological laparoscopy (Eberhart et al. 2003),whereas two other randomised, placebo-controlled, double-blind studies found Ginger reduced the incidence of nausea and vomiting in women undergoing gynaecological surgery (Bone, Wilkinson, Young, McNeil, & Carlton 1990;Phillips, Ruggier, & Hutchinson 1993). These last two studies have been criticised as the use of the propofol (Diprivan), which has antiemetic properties, was also used during anaesthesia and may have influenced the results. No beneficial effect for Ginger (500 mg or 1000 mg) was observed in a similar study of nausea after gynaecological surgery (Arfeen, Owen, Plummer, Ilsley, Sorby-Adams, & Doecke 1995). Alternately, a 2003 study found that Ginger (1000 mg) taken 1 hour before surgery was significantly superior to placebo in reducing the incidence of nausea after outpatient gynecological laparoscopy during the first 2–4 hours after surgery. The incidence and frequency of vomiting were lower compared to placebo, but not statistically different (Pongrojpaw & Chiamchanya 2003). Chemotherapy-induced nausea Powdered ginger root effectively reduced cyclophosphamide-induced nausea and vomiting in a randomised, prospective, crossover, double-blind study. The antiemetic effect of Ginger was found to be equal to metoclopramide, although ondansetron was superior to both of these treatments (Sontakke, Thawani, & Naik 2003). In an open study, 1.5 grams of Ginger was found to decrease psoralen-induced nausea in 11 patients treated with photopheresis for cutaneous T-cell lymphoma (Meyer, Schwartz, Crater, & Keyes 1995). Musculoskeletal disorders Ginger is described in Ayurvedic (Traditional Indian) and Tibb (Traditional Arabian) systems of medicine to be useful in inflammation and rheumatism. Ginger is considered a dual inhibitor of the inflammatory eicosanoids by being an inhibitor of both prostaglandin and leukotriene biosynthesis. A randomised, double-blind, placebo controlled, multicenter, parallel-group, 6-week study of 261 patients found that a highly purified and standardised ginger extract moderately reduced the symptoms of osteoarthritis of the knee (Altman & Marcussen 2001). An open retrospective study involving 56 patients (28 with rheumatoid arthritis, 18 with osteoarthritis and 10 with muscular discomfort) revealed that more than three-quarters experienced varying degrees of relief of pain and swelling from the long-term use of powdered ginger. Although encouraging, the lack of placebo makes it difficult to determine the clinical significance of these effects (Srivastava & Mustafa 1992). Comparative study Ginger extract was compared with placebo or ibuprofen in patients with osteoarthritis of the hip or knee under double-blind, crossover study conditions and was found to produce a statistically significant effect as demonstrated by explorative statistical methods in the first period of treatment before crossover. Interestingly, a significant difference was not observed in the study as a whole. The authors noted that Ginger might need to be administered for longer than 3 weeks, and possibly in a higher dosage to be clinically effective (Bliddal et al. 2000). Dyspepsia

Michael Thomsen

Ginger stimulates the flow of saliva, bile and gastric secretions and therefore, is traditionally used in the symptomatic treatment of dyspepsia. Additionally, it has been used to stimulate appetite, reduce flatulence and colic, gastrointestinal spasms and generally act as a digestive aid. Commission E approves the use of Ginger root for the treatment of dyspepsia. Other uses Ginger is also used to prevent and treat migraine headache. Its ability to inhibit thromboxane A2 and exert antihistamine, anti-inflammatory and gastric actions make it a theoretically attractive choice (Mustafa & Srivastava 1990b). It is also used to treat dysmenorrhea. Externally, ginger cream or compress is used for mastitis. Dosage range The recommended dose ranges from 500 mg to 9 g daily of dried root or equivalent, depending on the indication for use. Doses according to clinical studies • Chemotherapy-induced nausea: 1.5 g dried root (Meyer, Schwartz, Crater, &

Keyes 1995). • Poor appetite, indigestion: 2–4 g dried root (World Health Organisation 2003) • Hyperemesis gravidarum: 1–2 g dried root daily (Fischer-Rasmussen et al. 1991). • Migraine: 1.5–2 g dried root (Mustafa & Srivastava 1990a). • Motion sickness: 1 g dried root 30 minutes before travel, then 0.5–1.0 g every 4

hours (Muller JL & Clauson KA 1997). • Nausea/vomiting: 0.5–2.0 g dried root daily (Grontved & Hentzer 1986;Schmid,

Schick, Steffen, Tschopp, & Wilk 1994). • Postoperative nausea: 0.5–1.0 g dried root daily (Pongrojpaw & Chiamchanya

2003). Higher doses may be more beneficial (The World Health Organisation monograph recommends 0.5 g, 2-4 times daily) (World Health Organisation 2003).

• Arthritis: 1.0–2.0 g dried root daily or higher (Srivastava & Mustafa 1992). Adverse reactions Gastric irritation, heartburn and bloating have been reported in clinical trials (Arfeen, Owen, Plummer, Ilsley, Sorby-Adams, & Doecke 1995). Contact dermatitis of the fingertips has also been reported (Seetharam & Pasricha 1987). Significant interactions Controlled studies are not available for many interactions; therefore they are based on evidence of activity and are largely theoretical and speculative. Warfarin Due to the herb’s antiplatelet effects at high doses, a theoretical interaction exists so caution is advised. However, there is no evidence of an interaction with warfarin (Stenton, Bungard, & Ackman 2001;Vaes & Chyka 2000) and Ginger has been shown not to alter prothrombin times in pooled human plasma collected from male volunteers between the ages of 18 and 57 years (Jones, Miederhoff, & Karnes 2001). A standardised ginger extract, EV.EXT 33 has been shown to have no significant effect on coagulation parameters or on Warfarin-induced changes in blood coagulation in rats (Weidner & Sigwart 2000). Contraindications and precautions

Michael Thomsen

Ginger is not recommended for children under 6 years of age due to the pungent nature of Ginger. Commission E suggests people with gallstones consult with their physician before using Ginger. Pregnancy use Although Commission E suggests ginger is contraindicated in pregnancy, more recent research in pregnant women suggests that ginger is not contraindicated in pregnancy. Doses up to 2 g daily of dried ginger root have been used safely. No adverse effects on pregnancy were observed in study of 70 women treated for nausea and vomiting with 1 g Ginger for four days (Vutyavanich, Kraisarin, & Ruangsri 2001) A study of 27 pregnant women suffering hyperemesis gravidarum found that 1 g Ginger for four days caused no adverse reactions during pregnancy and all infants were normal (Fischer-Rasmussen, Kjaer, Dahl, & Asping 1991). Practice points/patient counseling • Ginger exerts myriad different pharmacological effects in the body. However, its

anti-emetic, anti-inflammatory and gastrointestinal effects are most often employed clinically.

• There is good clinical support for the use of Ginger in the treatment of nausea and vomiting associated with motion sickness, vomiting in pregnancy and seasickness. Evidence of effectiveness in postoperative nausea is less convincing.

• Ginger is traditionally used for gastrointestinal disorders including dyspepsia, poor appetite, flatulence, colic, vomiting, diarrhoea and spasms, as well as a diaphoretic in the treatment of the common cold and influenza.

• It is also used as an anti-inflammatory agent for arthritis, although large controlled studies have yet to produce strong support for this use.

• Although antiplatelet effects have been reported, this requires very large doses and is not likely to be significant in normal therapeutic doses or dietary intake levels.

Answers to patients’ frequently asked Questions • What can this herb do for me? Ginger may be useful in the treatment of nausea and vomiting associated with motion sickness, postoperative nausea, vomiting in pregnancy and seasickness. It is also useful for treating symptoms of dyspepsia and may have anti-inflammatory effects in arthritis, although this is less certain. • When will it start to work? In the case of dyspepsia and motion sickness prevention, Ginger will have an almost immediate effect, with improvement reported within 30 minutes. For motion sickness, 0.5–1.0 g Ginger should be taken 30 minutes before travel and repeated four hourly. For nausea of pregnancy it should be taken for at least four days. • Are there any safety issues? Ginger is well tolerated, although it should be used with caution by people with gall stones. References

Adewunmi, C. O., Oguntimein, B. O., & Furu, P. 1990, "Molluscicidal and antischistosomal activities of Zingiber officinale", Planta Medica, vol. 56, no. 4, pp. 374-376.

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Akoachere, J. F., Ndip, R. N., Chenwi, E. B., Ndip, L. M., Njock, T. E., & Anong, D. N. 2002, "Antibacterial effect of Zingiber officinale and Garcinia kola on respiratory tract pathogens", East Afr Med J, vol. 79, no. 11, pp. 588-92.

Altman, R. D. & Marcussen, K. C. 2001, "Effects of a ginger extract on knee pain in patients with osteoarthritis", Arthritis & Rheumatism, vol. 44, no. 11, pp. 2531-2538.

Arfeen, Z., Owen, H., Plummer, J. L., Ilsley, A. H., Sorby-Adams, R. A. C., & Doecke, C. J. 1995, "A double-blind randomized controlled trial of ginger for the prevention of postoperative nausea and vomiting", Anaesthesia & Intensive Care, vol. 23, no. 4, pp. 449-452.

Awang, D. V. C. 1992, "Ginger", Canadian Pharmaceutical Journal, vol. 125, no. 7, pp. 309-311.

Bhandari, U., Shamsher, A. A., Pillai, K. K., & Khan, M. S. Y. 2003, "Antihepatotoxic activity of ginger ethanol extract in rats", Pharmaceutical Biology, vol. 41, no. 1, pp. 68-71.

Bhattarai, S., Tran, V. H., & Duke, C. C. 2001, "The stability of gingerol and shogaol in aqueous solutions", Journal of Pharmaceutical Sciences, vol. 90, no. 10, pp. 1658-1664.

Bliddal, H., Rosetzsky, A., Schlichting, P., Weidner, M. S., Andersen, L. A., Ibfelt, H. H., Christensen, K., Jensen, O. N., & Barslev, J. 2000, "A randomized, placebo-controlled, cross-over study of ginger extracts and Ibuprofen in osteoarthritis", Osteoarthritis & Cartilage, vol. 8, no. 1, pp. 9-12.

Bone, M. E., Wilkinson, D. J., Young, J. R., McNeil, J., & Carlton, S. 1990, "Ginger root - a new antiemetic. The effect of ginger root on postoperative nausea and vomiting after major gynaecological surgery", Anaesthesia, vol. 45, no. 8, pp. 669-671.

Bordia, A., Verma, S. K., & Srivastava, K. C. 1997, "Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease", Prostaglandins Leukotrienes & Essential Fatty Acids, vol. 56, no. 5, pp. 379-384.

Charles, R., Garg, S. N., & Kumar, S. 2000, "New gingerdione from the rhizomes of Zingiber officinale", Fitoterapia, vol. 71, no. 6, pp. 716-8.

Denyer, C. V., Jackson, P., Loakes, D. M., Ellis, M. R., & Young, D. A. B. 1994, "Isolation of antirhinoviral sesquiterpenes from ginger (Zingiber officinale)", Journal of Natural Products, vol. 57, no. 5, pp. 658-662.

Eberhart, L. H. J., Mayer, R., Betz, O., Tsolakidis, S., Hilpert, W., Morin, A. M., Geldner, G., Wulf, H., & Seeling, W. 2003, "Ginger does not prevent postoperative nausea and vomiting after laparoscopic surgery", Anesthesia and Analgesia, vol. 96, no. 4, pp. 995-998.

Eliakim, R., Abulafia, O., & Sherer, D. M. 2000, "Hyperemesis gravidarum: A current review", American Journal of Perinatology, vol. 17, no. 4, pp. 207-218.

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Ernst, E. & Pittler, M. H. 2000, "Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials", Br J Anaesth, vol. 84, no. 3, pp. 367-71.

Fischer-Rasmussen, W., Kjaer, S. K., Dahl, C., & Asping, U. 1991, "Ginger treatment of hyperemesis gravidarum", Eur J Obstet Gynecol Reprod Biol, vol. 38, no. 1, pp. 19-24.

Flynn, D. L., Rafferty, M. F., & Boctor, A. M. 1986, "Inhibition of human neutrophil 5-lipoxygenase activity by gingerdione, shogaol, capsaicin and related pungent compounds", Prostaglandins Leukotrienes and Medicine, vol. 24, no. 2-3, pp. 195-198.

Fuhrman, B., Rosenblat, M., Hayek, T., Coleman, R., & Aviram, M. 2000, "Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice", Journal of Nutrition, vol. 130, no. 5, pp. 1124-1131.

Gonlachanvit 2001, Neurogastroenterol Motil, vol. 13, no. 3, p. 266.

Goto, C., Kasuya, S., Koga, K., Ohtoma, H., & Kagei, N. 1990, "Lethal efficacy of extract from Zingiber officinale (traditional Chinese medicine) or [6]-shogaol and [6]-gingerol in Anisakis larvae in vitro", Parasitology Research, vol. 76, no. 8, pp. 653-656.

Grontved, A. & Hentzer, E. 1986, "Vertigo-reducing effect of ginger root. A controlled clinical study", ORL, vol. 48, no. 5, pp. 282-286.

Gupta, Y. K. & Sharma, M. 2001, "Reversal of pyrogallol-induced delay in gastric emptying in rats by ginger (Zingiber officinale)", Methods & Findings in Experimental & Clinical Pharmacology, vol. 23, no. 9, pp. 501-503.

Hasenohrl, R. U., Nichau, C., Frisch, C., De Souza Silva, M. A., Huston, J. P., Mattern, C. M., & Hacker, R. 1996, "Anxiolytic-like effect of combined extracts of Zingiber officinale and ginkgo biloba in the elevated plus-maze", Pharmacology, Biochemistry & Behavior, vol. 53, no. 2, pp. 271-275.

Henry, C. J. & Piggott, S. M. 1987, "Effect of ginger on metabolic rate", Hum Nutr Clin Nutr, vol. 41, no. 1, pp. 89-92.

Holtmann, S., Clarke, A. H., Scherer, H., & Hohn, M. 1989, "The anti-motion sickness mechanism of ginger. A comparative study with placebo and dimenhydrinate", Acta Oto-Laryngologica, vol. 108, no. 3-4, pp. 168-174.

Huang, Q., Iwamoto, M., Aoki, S., Tanaka, N., Tajima, K., Yamahara, J., Takaishi, Y., Yoshida, M., Tomimatsu, T., & Tamai, Y. 1991a, "Anti-5-hydroxytryptamine3 effect of galanolactone, diterpenoid isolated from ginger", Chemical & Pharmaceutical Bulletin, vol. 39, no. 2, pp. 397-399.

Huang, Q. R., Iwamoto, M., Aoki, S., Tanaka, N., Tajima, K., Yamahara, J., Takaishi, Y., Yoshida, M., Tomimatsu, T., & Tamai, Y. 1991b, "Anti-5-hydroxytryptamine3

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effect of galanolactone, diterpenoid isolated from ginger", Chem Pharm Bull (Tokyo), vol. 39, no. 2, pp. 397-9.

Janssen, P. L., Meyboom, S., Van Staveren, W. A., De Vegt, F., & Katan, M. B. 1996, "Consumption of ginger (Zingiber officinale roscoe) does not affect ex vivo platelet thromboxane production in humans", Eur J Clin Nutr, vol. 50, no. 11, pp. 772-4.

Jewell, D. 2002, "Nausea and vomiting in early pregnancy", Clin Evid no. 7, pp. 1277-83.

Jewell, D. & Young, G. 2002, "Interventions for nausea and vomiting in early pregnancy", Cochrane Database Syst Rev no. 1, p. CD000145.

Jeyakumar, S. M., Nalini, N., & Menon, V. P. 1999, "Antioxidant activity of ginger (Zingiber Officinale Rosc) in rats fed a high fat diet", Medical Science Research, vol. 27, no. 5, pp. 341-344.

Jones, S. C., Miederhoff, P., & Karnes, H. T. 2001, "The development of a human tissue model to determine the effect of plant-derived dietary supplements on prothrombin time", Journal of Herbal Pharmacotherapy, vol. 1, no. 1, pp. 21-34.

Kano, Y., Zong, Q. N., & Komatsu, K. 1991, "Pharmacological properties of galenical preparation. XIV. Body temperature retaining effect of the Chinese traditional medicine, "goshuyu-to" and component crude drugs", Chem Pharm Bull (Tokyo), vol. 39, no. 3, pp. 690-2.

Kawai, T., Kinoshita, K., Koyama, K., & Takahashi, K. 1994, "Anti-emetic principles of Magnolia obovata bark and Zingiber officinale rhizome", Planta Medica, vol. 60, no. 1, pp. 17-20.

Keating, A. & Chez, R. A. 2002, "Ginger syrup as an antiemetic in early pregnancy", Alternative Therapies in Health & Medicine, vol. 8, no. 5, pp. 89-91.

Keum, Y. S., Kim, J., Keun, H. L., Kwang, K. P., Surh, Y. J., Jong, M. L., Lee, S. S., Jung, H. Y., So, Y. J., In, H. C., & Jong, I. Y. 2002, "Induction of apoptosis and caspase-3 activation by chemopreventive [6]-paradol and structurally related compounds in KB cells", Cancer Letters, vol. 177, no. 1, pp. 41-47.

Kikuzaki, H., Usuguchi, J., & Nakatani, N. 1991, "Constituents of Zingiberaceae. I. Diarylheptanoids from the rhizomes of ginger (Zingiber officinale roscoe)", Chemical & Pharmaceutical Bulletin, vol. 39, no. 1, pp. 120-122.

Kiuchi, F., Iwakami, S., Shibuya, M., Hanaoka, F., & Sankawa, U. 1992, "Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids", Chemical & Pharmaceutical Bulletin, vol. 40, no. 2, pp. 387-391.

Kobayashi, M., Shoji, N., & Ohizumi, Y. 1987, "Gingerol, a novel cardiotonic agent, activates the Ca2+-pumping ATPase in skeletal and cardiac sarcoplasmic reticulum", Biochimica et Biophysica Acta - Biomembranes, vol. 903, no. 1, pp. 96-102.

Langner, E., Greifenberg, S., & Gruenwald, J. 1998, "Ginger: History and use", Advances in Therapy, vol. 15, no. 1, pp. 25-44.

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Lien, H. C., Sun, W. M., Chen, Y. H., Kim, H., Hasler, W., & Owyang, C. 2003, "Effects of ginger on motion sickness and gastric slow-wave dysrhythmias induced by circular vection", American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 284, no. 3 47-3, p. G481-G489.

Lumb, A. B. 1994, "Effect of dried ginger on human platelet function", Thrombosis & Haemostasis, vol. 71, no. 1, pp. 110-111.

Martins, A. P., Salgueiro, L., Goncalves, M. J., Proenca da Cunha, A., Vila, R., Canigueral, S., Mazzoni, V., Tomi, F., & Casanova, J. 2001, "Essential oil composition and antimicrobial activity of three Zingiberaceae from S.Tome e Principe", Planta Medica, vol. 67, no. 6, pp. 580-584.

Meyer, K., Schwartz, J., Crater, D., & Keyes, B. 1995, "Zingiber officinale (ginger) used to prevent 8-Mop associated nausea", Dermatol Nurs, vol. 7, no. 4, pp. 242-4.

Micklefield, G. H., Redeker, Y., Meister, V., Jung, O., Greving, I., & May, B. 1999, "Effects of ginger on gastroduodenal motility", Int J Clin Pharmacol Ther, vol. 37, no. 7, pp. 341-6.

Muller JL & Clauson KA 1997, "Pharmaceutical considerations of common herbal medicine", Am J Managed Care, vol. 3, no. 11, pp. 1753-1770.

Mustafa, T. & Srivastava, K. C. 1990a, "Ginger (Zingiber officinale) in migraine headache", J Ethnopharmacol, vol. 29, no. 3, pp. 267-73.

Mustafa, T. & Srivastava, K. C. 1990b, "Possible leads for arachidonic acid metabolism altering drugs from natural products", Journal of Drug Development, vol. 3, no. 1, pp. 47-60.

Mustafa, T., Srivastava, K. C., & Jensen, K. B. 1993, "Pharmacology of ginger, Zingiber officinale", Journal of Drug Development, vol. 6, no. 1, pp. 25-39.

Onogi, T., Minami, M., Kuraishi, Y., & Satoh, M. 1992, "Capsaicin-like effect of (6)-shogaol on substance P-containing primary afferents of rats: A possible mechanism of its analgesic action", Neuropharmacology, vol. 31, no. 11, pp. 1165-1169.

Penna, S. C., Medeiros, M. V., Aimbire, F. S. C., Faria-Neto, H. C. C., Sertie, J. A. A., & Lopes-Martins, R. A. B. 2003, "Anti-inflammatory effect of the hydralcoholic extract of Zingiber officinale rhizomes on rat paw and skin edema", Phytomedicine, vol. 10, no. 5, pp. 381-385.

Phillips, S., Hutchinson, S., & Ruggier, R. 1993, "Zingiber officinale does not affect gastric emptying rate: A randomised, placebo-controlled, crossover trial", Anaesthesia, vol. 48, no. 5, pp. 393-395.

Phillips, S., Ruggier, R., & Hutchinson, S. E. 1993, "Zingiber officinale (ginger)--an antiemetic for day case surgery", Anaesthesia, vol. 48, no. 8, pp. 715-7.

Platel, K. & Srinivasan, K. 1996, "Influence of dietary spices or their active principles on digestive enzymes of small intestinal mucosa in rats", International Journal of Food Sciences & Nutrition, vol. 47, no. 1, pp. 55-59.

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Platel, K. & Srinivasan, K. 2001, "Studies on the influence of dietary spices on food transit time in experimental rats", Nutrition Research, vol. 21, no. 9, pp. 1309-1314.

Pongrojpaw, D. & Chiamchanya, C. 2003, "The efficacy of ginger in prevention of post-operative nausea and vomiting after outpatient gynecological laparoscopy", Journal of the Medical Association of Thailand, vol. 86, no. 3, pp. 244-250.

Schmid, R., Schick, T., Steffen, R., Tschopp, A., & Wilk, T. 1994, "Comparison of Seven Commonly Used Agents for Prophylaxis of Seasickness", J Travel Med, vol. 1, no. 4, pp. 203-206.

Schuhbaum, H. & Franz, G. 2000, "Ginger: Spice and versatile medicinal plant. [German]", Zeitschrift fur Phytotherapie, vol. 21, no. 4, pp. 203-209.

Seetharam, K. A. & Pasricha, J. S. 1987, "Condiments and contact dermatitis of the finger-tips", Indian Journal of Dermatology, Venereology & Leprology, vol. 53, no. 6, pp. 325-328.

Sertie, J. A. A., Basile, A. C., Oshiro, T. T., Silva, F. D., & Mazella, A. A. G. 1992, "Preventive anti-ulcer activity of the rhizome extract of Zingiber officinale", Fitoterapia, vol. 63, no. 1, pp. 55-59.

Sharma, J. N., Srivastava, K. C., & Gan, E. K. 1994, "Suppressive effects of eugenol and ginger oil on arthritic rats", Pharmacology, vol. 49, no. 5, pp. 314-318.

Shoji, N., Iwasa, A., & Takemoto, T. 1982, "Cardiotonic principles of ginger (Zingiber officinale Roscoe)", Journal of Pharmaceutical Sciences, vol. 71, no. 10, pp. 1174-1175.

Sontakke, S., Thawani, V., & Naik, M. S. 2003, "Ginger as an antiemetic in nausea and vomiting induced by chemotherapy: A randomized, cross-over, double blind study", Indian Journal of Pharmacology, vol. 35, no. 1, pp. 32-36.

Srivastava, K. C. & Mustafa, T. 1992, "Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders", Medical Hypotheses, vol. 39, no. 4, pp. 342-348.

Stenton, S. B., Bungard, T. J., & Ackman, M. L. 2001, "Interactions between warfarin and herbal products, minerals, and vitamins: A pharmacist's guide", Canadian Journal of Hospital Pharmacy, vol. 54, no. 3, pp. 184-190.

Stewart, J. J., Wood, M. J., Wood, C. D., & Mims, M. E. 1991, "Effects of ginger on motion sickness susceptibility and gastric function", Pharmacology, vol. 42, no. 2, pp. 111-120.

Thomson, M., Al-Qattan, K. K., Al-Sawan, S. M., Alnaqeeb, M. A., Khan, I., & Ali, M. 2002, "The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent", Prostaglandins Leukotrienes & Essential Fatty Acids, vol. 67, no. 6, pp. 475-478.

Vaes, L. P. J. & Chyka, P. A. 2000, "Interactions of warfarin with garlic, ginger, ginkgo, or ginseng: Nature of the evidence", Annals of Pharmacotherapy, vol. 34, no. 12, pp. 1478-1482.

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Verma, S. K. & Bordia, A. 2001, "Ginger, fat and fibrinolysis", Indian J Med Sci, vol. 55, no. 2, pp. 83-6.

Visalyaputra, S., Petchpaisit, N., Somcharoen, K., & Choavaratana, R. 1998, "The efficacy of ginger root in the prevention of postoperative nausea and vomiting after outpatient gynaecological laparoscopy", Anaesthesia, vol. 53, no. 5, pp. 506-510.

Vishwakarma, S. L., Pal, S. C., Kasture, V. S., & Kasture, S. B. 2002, "Anxiolytic and antiemetic activity of Zingiber officinale", Phytotherapy Research, vol. 16, no. 7, pp. 621-626.

Vutyavanich, T., Kraisarin, T., & Ruangsri, R. A. 2001, "Ginger for nausea and vomiting in pregnancy: Randomized, double-masked, placebo-controlled trial", Obstetrics & Gynecology, vol. 97, no. 4, pp. 577-582.

Weidner, M. S. & Sigwart, K. 2000, "The safety of a ginger extract in the rat", Journal of Ethnopharmacology, vol. 73, no. 3, pp. 513-520.

Wilasrusmee, C., Bruch, D., & Kittur, DS. 2003, "Zingiber officinale (ginger) extract prolongs cardiac allograft surviaval", Pediatric Transplantation Supplement, vol. 7, no. 4, p. 131.

Willetts, K. E., Ekangaki, A., & Eden, J. A. 2003, "Effect of a ginger extract on pregnancy-induced nausea: A randomised controlled trial", Australian & New Zealand Journal of Obstetrics & Gynaecology, vol. 43, no. 2, pp. 139-144.

World Health Organisation. Rhizoma Zingiberis. World Health Organisation . 15-12-2003. http://www.who.int/medicines/library/trm/medicinalplants/pdf/277to287.pdf Ref Type: Electronic Citation

Yamada, Y., Kikuzaki, H., & Nakatani, N. 1992, "Identification of antimicrobial gingerols from ginger (Zingiber officinale Roscoe)", Journal of Antibacterial & Antifungal Agents, Japan, vol. 20, no. 6, pp. 309-311.

Yamahara, J., Hatakeyama, S., Taniguchi, K., Kawamura, M., & Yoshikawa, M. 1992, "Stomachic principles in ginger. II. Pungent and anti-ulcer effects of low polar constituents isolated from ginger, the dried rhizoma of Zingiber officinale Roscoe cultivated in Taiwan. The absolute stereostructure of a new diarylheptanoid. [Japanese]", Yakugaku Zasshi, vol. 112, no. 9, pp. 645-655.

Yamahara, J., Huang, Q., Li, Y., Xu, L., & Fujimura, H. 1990, "Gastrointestinal motility enhancing effect of ginger and its active constituents", Chemical & Pharmaceutical Bulletin, vol. 38, no. 2, pp. 430-431.

Yamahara, J., Matsuda, H., Yamaguchi, S., Shimoda, H., Murakami, N., & Yoshikawa, M. 1995, "Pharmacological study on ginger processing. I. Antiallergic activity and cardiotonic action of gingerols and shogaols. [Japanese]", Natural Medicines, vol. 49, no. 1, pp. 76-83.

Yamahara, J., Miki, K., & Chisaka, T. 1985, "Cholagocic effect of ginger and its active constituents", Journal of Ethnopharmacology, vol. 13, no. 2, pp. 217-225.

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Yamahara, J., Mochizuki, M., Rong, H. Q., Matsuda, H., & Fujimura, H. 1988, "The anti-ulcer effect in rats of ginger constituents", Journal of Ethnopharmacology, vol. 23, no. 2-3, pp. 299-304.

Yoshikawa, M., Chatani, N., Hatakeyama, S., Nishino, Y., Yamahara, J., & Murakami, N. 1993, "Crude drug processing by far-infrared treatment. II. Chemical fluctuation of the constituents during the drying of Zingiberis Rhizoma", Yakugaku Zasshi, vol. 113, no. 10, pp. 712-717.

Yoshikawa, M., Hatakeyama, S., Taniguchi, K., Matuda, H., & Yamahara, J. 1992, "6-Gingesulfonic acid, a new anti-ulcer principle, and gingerglycolipids A, B and C, three new monoacyldigalactosylglycerols from Zingiberis rhizoma originating in Taiwan", Chemical & Pharmaceutical Bulletin, vol. 40, no. 8, pp. 2239-2241.

Yoshikawa, M., Yamaguchi, S., Kunimi, K., Matsuda, H., Okuno, Y., Yamahara, J., & Murakami, N. 1994, "Stomachic principles in ginger. III. An anti-ulcer principle, 6- gingesulfonic acid, and three monoacyldigalactosylglycerols, gingerglycolipids A, B, and C, from Zingiberis Rhizoma originating in Taiwan", Chemical & Pharmaceutical Bulletin, vol. 42, no. 6, pp. 1226-1230.

Probiotics – to improve intestinal flora

Reference: Braun L, Herbs & Natural Supplements - An Evidence-based Guide Historical note The term probiotics was first coined in 1965 in reference to substances produced by protozoa, which stimulated the growth of other organisms. It has since been applied to those microorganisms found naturally in foods which are able to improve health by stimulating the growth of beneficial organisms. The use of foods containing microorganisms for improving health has a long traditional use. Metchnikoff, a Nobel laureate, stated in 1908 that ‘ingested lactobacilli can displace toxin-producing bacteria, promoting health and prolonging life’ (Elmer 2001). Although it has taken the most part of a century for scientists to investigate their health benefits, there are now over 1200 studies on probiotics on Medline, the majority published since 2000. Background and relevant pharmacokinetics The generally accepted definition of probiotics is ‘a live microbial food supplement which beneficially affects the host animal by improving its intestinal microbial balance’. This definition is, however, rather limited as some probiotics are transient and do not take up residence in the intestinal tract. A better definition may be that probiotics are a ‘microbial dietary supplement that beneficially affect the host physiology by modulating mucosal and systemic immunity, as well as improving nutritional and microbial balance of the intestinal tract’.(Salminen et al. 1998) The gastrointestinal tract is sterile at birth. Normal gut flora develops gradually over time and is influenced by factors such as composition of the maternal gut microflora, diet, degree of hygiene, use of antibiotics or other medication, the environment and possibly genetic aspects. Once established, a person’s individual gut flora remains surprisingly constant throughout life. This is likely to be due to the fact that the gut immune system learns to recognise and tolerate those bacterial species acquired during early infancy. It is therefore very difficult to alter the composition of the gut

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flora after this time. Successful colonisation with probiotics is therefore most often transient as the gastrointestinal tract has many defenses that inhibit this process.(Vanderhoof & Young 2002) The intestines are host to 1014 microbes representing 400 to 500 different species.(Ouwehand, Isolauri, & Salminen 2002) Clinical note – Prebiotics There is another concept associated with the microflora and intestinal health: pre-biotics. Prebiotic refers to the use of compounds that modify the environment of the gastrointestinal tract to favour proliferation of the beneficial components of the intestinal microflora.(Gibson & Roberfroid 1995) Herbal and nutritional prebiotics include the fibre-supplement known as slippery elm (Ulmus fulva), oligofructose and inulin. The prebiotic approach, while promising, has not been thoroughly tested by controlled clinical trials. Clinical note – The hygiene hypothesis The intestinal tract is the largest immune organ of the body. It produces more antibodies than any other part of the body and contains 80% of all antibody-producing cells. The intestinal mucosa functions as a barrier against infections, but it also provides communication between the different mucosal surfaces of the body.(Ouwehand, Isolauri, & Salminen 2002) At birth, the gastrointestinal tract is sterile. Normal gut flora develops gradually over time and is influenced by factors such as composition of the maternal gut microflora, diet, degree of hygiene, use of antibiotics or other medication, the environment and possibly genetic aspects. Studies in germ-free mice have shown that without these bacteria, the systemic immune system will not function normally.(Vanderhoof & Young 2002) In the absence of microbes, a mammal develops fewer Peyer’s patches (part of the gut-associated lymphoid tissue (GALT)) and less than 10% of the number of IgA producing B cells compared to a conventional animal. However, on exposure to a normal microflora, previously germ-free animals develop their immune system very much like conventional animals. This indicates that the intestinal microflora is instrumental in the proper development of the immune system(Ouwehand, Isolauri, & Salminen 2002) and has led to the emergence of the ‘hygiene theory of immune disorders’. More specifically, the hygiene hypothesis suggests that improved hygienic conditions and vaccinations, which reduce early-life exposure to microbes, are associated with a heightened risk of allergic disease and other immune disorders. This is because reduced exposure may result in reduced stimulation of the immune system. As a result, lymphocytes that would normally differentiate to become Th1 type, differentiate to Th2 types cells and produce inflammatory cytokines in the allergic response in much greater quantities. As such, very early stimulation of the immune system is important in dampening the Th2 dominance and reducing the development of IgE-mediated food reactions as well as other allergic reactions. In a closely observed cohort of 329 Finnish children it was shown that the earlier an acute respiratory infection occurred, the greater the protective effect was against atopic eczema.(Vanderhoof & Young 2003) The obvious solution for increasing microbial exposure without increasing the health risk is the use of prebiotics and probiotics. Supplementation with probiotics has been shown to both reduce the risk and treat the symptoms of childhood eczema (see below).

Michael Thomsen

Modulating the intestinal microflora with probiotics and prebiotics (fibre) may be an effective and safe therapy for the natural development of a balanced immune defence in infants and children. In adults and the elderly, prebiotica and probiotics may be used to improve the general functioning of the immune system. Chemical components Probiotics include Streptococcus thermophilus, Bifidobacterium bifidum, Lactobacillus reuteri, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus plantarum, bifidobacteria, Lactobacillus casei, Lactobacillus strain LB, Saccharomyces boulardii (a yeast), Streptococcus salivarius, Lactobacillus gassen and Lactobacillus GG (named after Drs Gorbach and Goldin who first isolated the strain in 1980). Food sources Yoghurt may contain probiotics, especially Lactobacillus acidophilus and bifidobacterium strains. Deficiency signs and symptoms Clear deficiency signs are difficult to establish as the symptoms may vary enormously. Local signs and symptoms of an imbalance of the intestinal flora (intestinal dysbiosis) include bloating, flatulence, abdominal pain, diarrhoea and/or constipation and fungal overgrowth (such as candia). Imbalance of the intestinal flora may result from the use of antibiotics, chronic diarrhoeal states or constipation. Additionally, babies exclusively fed on infant formulas will have slower colonisation of the gut than those who are breastfed as breast milk allows for the transfer of oligosaccharides to the baby. This appears to be of particular concern in premature babies requiring intensive care as they acquire intestinal organisms slowly, which allows for the colonisation of bacterial species which tend to be virulent. It has been suggested that the aberrant colonisation of the premature infant’s gut may contribute to the development of necrotising enterocolitis and therefore probiotics supplementation may be a useful approach for prevention.(Dai & Walker 1999) Main actions The positive effects of probiotics are a result of several different mechanisms at work. Enhanced immune response Immune system modulation and the prevention of gastrointestinal tract (GIT) colonisation by a variety of pathogens are perhaps the most important actions of probiotics. Probiotics bind to intestinal epithelial cells and inhibit the binding of pathogenic bacteria to the gut wall by production of inhibitory substances such as bacteriocins, lactic acid and toxic oxygen metabolites. Of the toxic oxygen metabolites, hydrogen peroxide is of major importance as it exerts a bactericidal effect on many pathogens.(Kaur, Chopra, & Saini 2002) Binding to the gut wall also initiates signalling events that result in the synthesis of cytokines.(Vanderhoof & Young 2003) Studies in germ-free mice have proven that intestinal bacteria are essential for a healthy systemic immune system.(Falk et al. 1998) The LGG strain (Lactobacillus GG, a variant of Lactobacillus casei subsp. Rhamnosus) has been well studied in this regard and shown to modulate intestinal immunity by increasing the number of IgA and other immunoglobulin-secreting cells in the intestinal mucosal and stimulates the local release of interferons.

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Helicobacter pylori infection Several in vitro studies have shown that certain probiotics inhibit or kill H. pylori, prevent its adhesion to mammalian epithelial cells and prevent interleukin-8 release. In vivo models demonstrate that pretreatment with a probiotic can prevent H. pylori infections and/or that administration of probiotics markedly reduced an existing infection. Digestive processes The gut bacteria carry out a number of biochemical functions including deconjugation and dehydroylation of bile acids, the conversion of bilirubin to urobilinogen, the metabolism of cholesterol to coprostanol, production of vitamins K, B1, B2, B6, B12 and generation of short-chain fatty acids. Probiotics are involved in balancing colonic microbiota and aid in the treatment of diarrhoea associated with travel and antibiotic therapy, and control of rotavirus and Clostridium difficile-induced colitis. Chemopreventative effects A variety of mechanisms is responsible for the chemopreventative effect demonstrated for some probiotics strains. Anti-mutagenic activity against chemical mutagens and promutagens has been demonstrated for different strains of Lactobacillus acidophilus, Bifidobacteria and of organic acids usually produced by these probiotic bacteria, with live cells producing the most positive results.(Lankaputhra & Shah 1998) Some probiotics also reduce faecal enzymes implicated in cancer initiation, by producing butyric acid which affects the turnover of enterocytes and neutralises the activity of dietary carcinogens, such as nitrosamines. Additionally, enhancing host immunity and qualitative and quantitative changes to the intestinal microflora and physicochemical conditions are important contributing factors.(Hirayama & Rafter 1999) Cholesterol lowering activity This has been established in several clinical trials. Allergy High level antigen exposure during the first few months of life is suspected of predisposing individuals to allergic sensitisation and therefore various atopic conditions. The intestinal microflora plays a major protective role against the development of allergy because it reduces antigen transport through the intestinal mucosa. Clinical use It is generally agreed that a probiotic must be capable of colonising the intestinal tract to influence human health. Currently, one of the most extensively studied probiotics is Lactobacillus GG (LGG), a variant of Lactobacillus casei subsp. Rhamnosus. Infantile diarrhoea In a double-blind, placebo-controlled trial, infants aged five to 24 months who were admitted to a chronic medical care hospital were randomly assogned to receive a standard infant formula or the same formula supplemented with Bifidobacterium bifidum and S. thermophilus; 55 subjects were evaluated for 17 months. The infant formula supplemented with the probiotics reduced the incidence of acute diarrhoea and sharply reduced rotavirus shedding in infants admitted to hospital.(Elmer 2001;Saavedra 2000)

Michael Thomsen

Another study of 175 children aged six to 36 months found that children receiving bifidobacteria-supplemented milk-based formula may be protected against symptomatic rotavirus infection.(Phuapradit et al. 1999) Travelers’ diarrhoea Travelers’ diarrhea is the most common health problem in those visiting developing countries, affecting 20% to more than 50% of tourists. Although it is usually benign, travelers’ diarrhoea represents a considerable socioeconomic burden for both the traveler and the host country. The most common enteropathogens are Escherichia coli. Some clinical studies have found various probiotics somewhat effective against travelers’ diarrhoea, however no probiotic has been able to demonstrate clinically relevant protection worldwide.(Rendi-Wagner & Kollaritsch 2002) A large randomised, placebo-controlled, double-blind study was conducted on the efficacy of Lactobacillus GG in preventing travelers’ diarrhoea which involved 820 people on holiday to Turkey to two destinations. The group was randomly assigned either Lactobacillus GG or placebo in identical sachets. On the return flight each participant completed a questionnaire indicating the incidence of diarrhoea and related symptoms during the trip. Of the original group 756 (92%) subjects completed the study. The overall incidence of diarrhoea was 43.8% (331 cases) and the total incidence of diarrhoea in the Lactobacillus GG group was 41.0% compared to 46.5% in the placebo group, indicating an overall protection of 11.8%. Protection rates varied between two different destinations with the maximum protection rate reported as 39.5% and no side effects reported.(Oksanen et al. 1990) In another placebo-controlled, double-blind study, various doses (250ٱmg and mg) of Saccharomyces boulardii were administered prophylactically to 3000ٱ1000Austrian travellers to distant regions. A significant reduction in the incidence of diarrhoea was observed, with success depending directly on the rigorous use of the preparation. A tendency was noted for Saccharomyces boulardii to have a varying regional effect, which was particularly marked in North Africa and in Turkey. In addition, the effect also proved to be dose-dependent and considered very safe.(Kollaritsch et al. 1993) Acute diarrhoea Different probiotic preparations are of benefit as an addition to oral rehydration for acute diarrhoea. L. reuteri, S. boulardii, E. faecium, SF68 and L. rhamnosus GG have all been shown to reduce the number of days of diarrhoea in studies conducted in various countries. The most consistent benefit was observed in patients with rotaviral diarrhoea.(Dorren 2002) Treatment with S. boulardii was found to speed up recovery from acute diarrhoea both in adults and infants. Two studies have found probiotics beneficial in the treatment of AIDS-related diarrhoea. AIDS-associated diarrhoea resolved in 10 of 18 patients given S. boulardi (3ٱg daily of the yeast) for 1 week, compared with 1 of 11 patients given placebo. In another study, a similar protocol improved the condition of 7 of 11 patients in weeks 2 to 4.(Elmer 2001) Antibiotic induced diarrhoea According to a 2002 meta-analysis, Lactobacilli and Saccharomyces boulardii is superior to placebo in preventing antibiotic-associated diarrhoea. Nine randomised, double-blind, placebo-controlled trials of probiotics were identified, two of which involved children, four using the yeast S. boulardii, four using Lactobacilli, one using a strain of enterococcus-producing lactic acid, and three using a combination of probiotic strains of bacteria.

Michael Thomsen

In all nine trials, probiotics were given in combination with antibiotics whereas the control groups received placebo with their antibiotic treatment. The odds ratio in favour of active treatment over placebo in preventing diarrhoea associated with antibiotics was 0.39 (P<0.001) for S. boulardii and 0.34 (P<0.01) for lactobacilli.(D'Souza et al. 2002) Urogenital infections Probiotics are widely used to decrease the frequency of recurrent bacterial vaginosis and candidal vulvovaginitis and have undergone clinical testing which supports this use. They are administered both orally and intravaginally for this purpose. Additionally, intravaginal administration of probiotics such as Lactobacillus GR-1 and B-54 or RC-14 strains has been shown to reduce the risk of urinary tract infections, and improve the maintenance of normal flora.(Reid & Burton 2002) The mechanisms by which lactobacillus reduces bacterial vaginosis and urinary tract infections appear to involve anti-adhesion factors, byproducts such as hydrogen peroxide and bacteriocins lethal to pathogens, and perhaps immune modulation or signaling effects. Bifidobacteria in particular are considered well suited to this activity and have therefore been investigated for their effects in the treatment of female genitourinary infections.(Korshunov et al. 1999) Oral supplementation In a study of ten women whose vaginal bacterial flora were abnormal and had suffered repeated bacterial vaginosis, yeast infections and/or urinary tract infections, a regimen was prescribed of ingesting 109 viable GR-1 and RC-14 bacteria each day. In a majority of patients with symptoms of suprapubic and micturition pains, frequency, dysuria and urgency, or vaginal irritation, the symptoms disappeared within 1–2 weeks and all the patients remained healthy for several months following treatment.(Reid 2001a) In another study, forty-two healthy women were randomly assigned to receive either Lactobacillus rhamnosus GR-1 with L. fermentum RC-14; or L. rhamnosus GG by itself. On assessment, the vaginal flora was only normal in 40% of cases and 14 patients had asymptomatic bacterial vaginosis. Oral treatment with 108 viable L. rhamnosus GR-1/L. fermentum RC-14 once and twice daily re-established a healthy vaginal flora in up to 90% of patients, and 7/11 patients with bacterial vaginosis converted to normal or intermediate scores within 1 month. Treatment with L. rhamnosus GG failed to have an effect.(Reid et al. 2001) A randomised, placebo-controlled study of 64 healthy women has confirmed that oral administration of probiotics including Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 can restore asymptomatic bacterial vaginosis microflora to a normal lactobacilli colonised microflora and reduce pathogenic bacteria. Significant results were obtained after 60 days’ treatment with no adverse effects reported.(Reid et al. 2003) It is sometimes asked how oral ingestion of probiotics can have an effect on the urogenital tract. Recent research has discovered that orally ingested Lactobacillus strains GR1 and RC-14 pass through the gut and ascend from the rectum to colonise the vagina and/or enhance the indigenous vaginal lactobacilli numbers. Probiotic enriched dairy products A small, randomised study of 46 participants showed that ingestion of 150ٱmL of L. acidophilus-enriched yoghurt was associated with an increased prevalence of colonisation of the rectum and vagina by the bacteria and may have contributed to

Michael Thomsen

reduced episodes of bacterial vaginosis.(Dorren 2002) Another crossover study of 33 women with recurrent vaginitis found that daily ingestion of 240ٱmg of yogurt containing Lactobacillus acidophilus for one year decreased both candidal colonisation and infection.(Hilton et al. 1992) Vaginal insertion A randomised, double-blind, study investigated the effectiveness of treatment with a weekly suppository containing either 0.5ٱg L. rhamnosus GR-1 and L. fermentum B-54 or a Lactobacillus growth factor for one year in 55 premenopausal women. Treatment resulted in the urinary tract infection rate decreasing by 73% and 79% respectively with no adverse effects reported.(Reid 2001b) Irritable bowel syndrome (IBS) People suffering from IBS sometimes experience symptoms of abdominal cramping and either diarrhoea, constipation or a combination of both. Although the aetiology of IBS is still unknown, there is growing suspicion that it is associated with an imbalance of intestinal flora. As such, clinical trials have been conducted to clarify the role of probiotics in this condition, so far producing promising results. In a 4-week, double-blind, placebo-controlled trial, 60 people with IBS were treated with L. plantarem or placebo. The patients recorded their own gastrointestinal function starting 2 weeks before the study and continuing throughout the study period. Twelve months after the end of the study, all patients were asked to complete a questionnaire. The study showed significant reductions in intestinal flatulence in the treatment group compared to placebo. At the 12-month follow-up, patients in the test group maintained a better overall gastrointestinal function than control patients.(Nobaek et al. 2000) In another study, 40 patients were randomly assigned either Lactobacillus plantarum 299V in liquid suspension or placebo over a period of 4 weeks. All patients treated with the probiotic reported resolution of their abdominal pain as compared to 11 patients from a placebo group. There was also a trend towards normalisation of stool frequency in constipated patients for 6 out of 10 patients treated with the probiotic compared with 2 out of 11 treated with placebo. With regard to all IBS symptoms, an improvement was noted in 95% of patients in the active group compared to 15% of patients in the placebo group (P<0.0001).(Niedzielin, Kordecki, & Birkenfeld 2001) Inflammatory bowel diseases Clostridium difficile is the most common cause of diarrhoea from treatment with antimicrobial/antibiotic medication and has the potential for progression to colitis, pseudomembranous colitis, toxic megacolon and death. In spite of antimicrobial therapy, recurrence is common. The S. boulardii strain of bacteria is being used to restore microbial balance and inhibit C. difficile proliferation.(Elmer 2001) A placebo-controlled study of 124 patients with documented, symptomatic C. difficile-associated disease, compared the effects of a standard course of metronidazole or vancomycin together with 4 weeks of 0.5ٱg S. boulardii treatment twice daily. Statistical analysis showed that the probiotic group had a significantly lower relative risk of recurrence (0.43) than the placebo group.(McFarland et al. 1994) A larger double-blind, multicentre trial of 168 patients demonstrated that S. boulardii plus a 10-day regimen of vancomycin 2ٱg/day reduced the rate of recurrence of C. difficile-associated disease to 16.7% versus 50% for the placebo group.(Surawicz et al. 2000)

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Probiotics are also being used as adjunctive therapy for Crohn’s disease and inflammatory bowel disease.(Goh & O'Morain 2003;Guslandi 2003a;Guslandi 2003b;Jonkers & StockbrUgger 2003;Kanauchi et al. 2003;Karthik 2003;Marteau, Seksik, & Shanahan 2003;Rutgeerts 2003) Pouchitis Pouchitis is the most common long-term complication of ileal pouch-anal anastomosis in patients with underlying ulcerative colitis. Clinical symptoms of pouchitis are not specific, and they can be caused by other conditions such as rectal cuff inflammation and irritable pouch syndrome. Therefore, to make an accurate diagnosis, endoscopic evaluation together with symptom assessment is necessary. Although antibacterial therapy can induce and maintain remission, probiotics can also be used to maintain clinical remission and prevent relapse in patients with relapsing or chronic pouchitis.(Kailasapathy & Chin 2000) Helicobactor pylori infection A review(Hamilton-Miller 1997) of thirteen clinical trials published on probiotics and helicobactor infection summarises the results as follows: • In six trials involving a total of 180 patients, sole treatment with probiotics

produced positive results in five studies. In three trials, there were significantly reduced breath test readings and in two others some patients were cleared of infection.

• In seven further trials of 682 patients in total, probiotics were added to a therapeutic regimen of antibiotics, resulting in an increased cure rate in two studies, and reduced side effects in four. Trials in which fermented milk products or whole cultures of lactobacilli were used tended to show better results than when the probiotic was taken in the form of bacteria alone.

It must be noted that not all the studies were randomised, double-blind and placebo controlled, and some involved only small numbers of patients. However, the positive results obtained suggest that probiotics may have a place as adjunctive treatment in H. pylori infections and possibly in prophylaxis. Other uses Food allergies High level antigen exposure during the first few months of life is suspected of predisposing individuals to allergic sensitisation and therefore various atopic conditions such as skin reactions and even systemic or respiratory manifestations. Intestinal inflammation seems to be a predisposing factor in increased sensitisation of a subject (Holt 1994) which in turn, promotes further inflammation when antigen exposure occurs. Considering that gut microflora is an important factor in regulating both the intestinal and systemic immune system, probiotics are used to promote endogenous barrier mechanisms, reduce gut permeability and alleviate intestinal inflammation in patients with atopic dermatitis and food allergy.7,(Majamaa & Isolauri 1997) A one-month study of 10 breast-fed infants who had atopic eczema and cow’s milk allergy found that Lactobacillus GG reduced certain faecal inflammatory markers. Eczema A randomised, double-blind placebo-controlled study showed that perinatal administration of probiotics (Lactobacillus rhamnosus GG) reduced the development of atopic eczema in children by half during the first 2 years of life. Some 159 mothers

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were randomly allocated to receive two capsules of placebo or 1010 viable Lactobacillus GG daily for 4 weeks before expected delivery. After delivery, capsules were taken postnatally for 6 months. During lactation either the mother or the infant consumed the preparations. In a 4-year follow-up study, it was revealed that the preventive effect of the probiotic on atopic eczema extended beyond infancy.(Kalliomaki et al. 2003) A recent randomised, double-blind study has found that supplementation of infant formulas with viable but not heat-inactivated Lactobacillus GG may have benefits for the management of atopic eczema and cow’s milk allergy.(Kirjavainen, Salminen, & Isolauri 2003) Immune stimulation In a 12-week, double-blind, placebo-controlled three-stage before-and-after intervention trial of 25 healthy elderly individuals, one-half were given milk containing a specific strain of Bifodobacterium lactic HN019, while the other half were given milk alone. Dietary consumption of the probiotic enhanced immune function of two different types of leucocytes; the degree of enhancement was increased by consuming B. lactis in an oligosaccharide-rich substrate.(Chiang et al. 2000) In another 7-month, double-blind, placebo-controlled study of 571 children in daycare centres in Finland, milk fortified with Lactobacillus GG reduced the number and severity of respiratory infections. The effects of the probiotic were modest but consistent.(Hatakka et al. 2001) A 9-week, three-stage, pre and post-intervention trial with 52 healthy middle-aged and elderly volunteers found that dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolysed low-fat milk, enhanced systemic cellular immune responses. The phagocytic activity of peripheral blood polymorphonuclear (PMN) leukocyte activity and in vitro tumoricidal activity of natural killer (NK) leukocytes increased by 19% and 15%, respectively. The relative level of NK cell tumour killing activity increased by 71% and 147%.(Sheih et al. 2001) High Cholesterol A meta-analysis of six studies of a probiotic dairy product containing Enterococcus faecium found that the fermented yoghurt product produced a 4% decrease in total cholesterol and a 5% decrease in LDL-cholesterol.(Agerholm-Larsen et al. 2000) In another study, 32 subjects with serum total cholesterol ranging from 5.7 to mg/dL were randomly assigned to two treatments: 1) intake of a low-fat drinkingٱ7.25yogurt prepared with ordinary yogurt starters composed of S. thermophilus and L. delbrueckii subsp. bulgaricus (placebo group) and 2) intake of a low-fat drinking yogurt prepared with the two ordinary yogurt starters plus B. longum strain BL1 (probiotic group). After intake for 4 weeks at 3 x 100ٱmL/day, reduction of serum total cholesterol was observed in approximately half of the probiotic group subjects; a particularly significant decrease in serum total cholesterol was found among subjects with moderate hypercholesterolaemia (serum total cholesterol >6.2ٱmg/dL). The serum lipid concentrations in the placebo group subjects were almost stable during the experimental periods.(Xiao et al. 2003) A cross-over study of 29 healthy women, aged 19–56 years, found that the long-term daily consumption of 300ٱg of two different types of yoghurt over a period of 21 weeks increased the serum concentration of HDL cholesterol and led to the desired improvement of the LDL/HDL cholesterol ratio. The normal yoghurt contained 3.5% fat and starter cultures of Streptococcus thermophilus and L. lactis while the probiotic

Michael Thomsen

yoghurt was enriched with L. acidophilus 145, B. longum 913 and 1% oligofructose. The mean serum concentration of total cholesterol and the LDL cholesterol was not influenced by the normal yoghurt (P>0.05). However, both the normal and the probiotic yoghurt increased the HDL concentration significantly, by 0.3ٱmmol/L (P=0.002) and decreased the LDL/HDL ratio decreased from 3.24 to 2.48 (P=0.001).(Kiessling, Schneider, & Jahreis 2002) A recent controlled, randomised, double-blind study of 36 heavy smokers found that mL/d of a rose-hip drink containing L. plantarum 299v (5 x 10(7) colony-formingٱ400units/mL) led to a reduction in cardiovascular disease risk factors. Significant decreases in systolic blood pressure and fibrinogen were recorded in the experimental group. No such changes were observed in the control group. Decreases in F(2)-isoprostanes (markers of oxidative stress) (37%) and interleukin-6 (42%) were also noted in the experimental group in comparison with baseline. Monocytes isolated from subjects treated with L. plantarum showed significantly reduced adhesion (P<0.001) to endothelial cells.(Naruszewicz et al. 2002) Dosage range As more information is gathered from probiotic research, it is becoming evident that certain strains or combination of strains are suitable for different conditions. Different strains of probiotics are chosen and combined to produce specific products for diarrhoea in children, antibiotic-induced diarrhoea, travellers’ diarrhoea, inflammatory bowel diseases etc. Probiotic doses are usually standardised in terms of the amount of living bacteria per unit of volume. A quality product may contain 1x109 cfu/g (colonies/g). The viable bacteria are mixed in a suitable matrix that may contain maltodextrin, amylase and prebiotics such as fruto-oligosaccharides (FOS) and inulin. Clinical note – dosage forms tailored to increase probiotic survival Several attempts have been made to ensure the survival of the probiotics through the acid environment of the stomach and exposure to bile acid. Microencapsulating the probiotics is one method which has been used.(Kailasapathy 2002) Enteric-coated tablets containing probiotics which are gastric acid resistant have also been produced.(Stadler & Viernstein 2003) More studies, however, are needed to examine the efficacy of these administration forms to deliver and release the probiotic at the appropriate target sites in the gastrointestinal tract. Studies are also needed to establish if such measures are actually necessary. With a suitable matrix, a probiotic powder may survive the passage through the digestive tract without either microencapsulation or enteric coating of tablets. Adverse reactions There have only been two documented adverse reactions. In a 74-year-old diabetic with hypertension and in a 67-year-old patient with endocarditis undergoing tooth extraction, L. rhamonosus preparations caused adverse reaction. The causality was not established.(Sanders 2003) Significant interactions No drug interactions have been reported. Clinical trials have indicated that probiotics can safely be administered with antibiotics. Contraindications and precautions Specific strains of probiotics are appropriated for different disorders. Certain strains are suitable for children.

Michael Thomsen

Probiotics are contraindicated in those people who are hypersensitive to any component of the probiotics-containing product. Pregnancy use Likely to be safe in pregnancy; however, use of concentrated forms should be supervised by a healthcare professional. Practice points/patient counseling • There is good clinical evidence that probiotics may be beneficial in the treatment

of infant diarrhoea, travellers’ diarrhoea, acute diarrhoea, antibiotic-induced diarrhoea, urogenital infections, irritable bowel syndrome, inflammatory bowel diseases, Helicobactor pylori infections, food intolerances and allergies, leaky gut and eczema.

• There is also some evidence that probiotics are essential for both the development and maintenance of a healthy immune system.

• There is some evidence that probiotics have a modest effect improving the LDL/HDL cholesterol ratio.

• Probiotics can be administered orally as a supplement of viable bacteria or inserted intravaginally. They can also be taken as yoghurt or other cultured dairy products. It should be noted that only products containing actual probiotic strains would be beneficial. The so-called starter cultures do not necessarily have the same beneficial effects.

• Although probiotics may improve the long-term bowel flora, probiotic supplementation has other benefits not associated with direct colonisation of the gastrointestinal tract.

Answers to patients’ frequently asked Questions • What can probiotics do for me? Probiotics are beneficial in the treatment of digestive disorders such as diarrhoea and inflammatory bowel diseases and other conditions not directly connected with the digestive tract. Clinical studies have found probiotics to be beneficial in the treatment of antibiotic-induced and travelers’ diarrhoea, for vaginal thrush and recurrent cystitis, irritable bowel syndrome, colitis, food allergies and eczema. • When will it start to work? Probiotics can start to exert beneficial effects in digestive disorders within a few days. Long-term benefits are seen after weeks to months of continuous use. Greater results may be obtained if the so-called prebiotics are also added to the diet. Prebiotics refer to the use of compounds that modify the environment of the gastrointestinal tract to favour proliferation of the intestinal microflora. Herbal and nutritional prebiotics include the fibre known as slippery elm (Ulmus fulva), oligofructose and inulin. • Are there any safety issues? Many species of probiotics are integral to the production of fermented foods and have been consumed safely as part of the daily diet for millennia. Other probiotics used as supplements are actually normal, non-pathogenic inhabitants of the human intestinal tract. There have been no reports of probiotics interacting with prescription medication. References

Michael Thomsen

Agerholm-Larsen, L., Bell, M. L., Grunwald, G. K., & Astrup, A. 2000, "The effect of a probiotic milk product on plasma cholesterol: a meta-analysis of short-term intervention studies", Eur J Clin Nutr, vol. 54, no. 11, pp. 856-860. Chiang, B. L., Sheih, Y. H., Wang, L. H., Liao, C. K., & Gill, H. S. 2000, "Enhancing immunity by dietary consumption of a probiotic lactic acid bacterium (Bifidobacterium lactis HN019): optimization and definition of cellular immune responses", Eur J Clin Nutr, vol. 54, no. 11, pp. 849-855. D'Souza, A. L., Rajkumar, C., Cooke, J., & Bulpitt, C. J. 2002, "Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis", BMJ, vol. 324, no. 7350, p. 1361. Dai, D. & Walker, W. A. 1999, "Protective nutrients and bacterial colonization in the immature human gut", Adv Pediatr., vol. 46, pp. 353-382. Dorren, R. 2002, "Probiotics: a review", Pharmacy Post, vol. 10, no. 5, p. C1. Elmer, G. W. 2001, "Probiotics: "living drugs"", Am J Health Syst.Pharm, vol. 58, no. 12, pp. 1101-1109. Falk, P. G., Hooper, L. V., Midtvedt, T., & Gordon, J. I. 1998, "Creating and maintaining the gastrointestinal ecosystem: what we know and need to know from gnotobiology", Microbiol Mol Biol Rev, vol. 62, no. 4, pp. 1157-1170. Gibson, G. R. & Roberfroid, M. B. 1995, "Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics", J Nutr, vol. 125, no. 6, pp. 1401-1412. Goh, J. & O'Morain, C. A. 2003, "Review article: nutrition and adult inflammatory bowel disease", Aliment.Pharmacol Ther, vol. 17, no. 3, pp. 307-320. Guslandi, M. 2003a, "Of germs in inflammatory bowel disease and of how to fight them", J Gastroenterol Hepatol, vol. 18, no. 1, pp. 115-116. Guslandi, M. 2003b, "Probiotics for chronic intestinal disorders", Am J Gastroenterol, vol. 98, no. 3, pp. 520-521. Hamilton-Miller, J. M. 1997, "Living in the 'post-antibiotic era': could the use of probiotics be an effective strategy?", Clin Microbiol Infect, vol. 3, no. 1, pp. 2-3. Hatakka, K., Savilahti, E., Ponka, A., Meurman, J. H., Poussa, T., Nase, L., Saxelin, M., & Korpela, R. 2001, "Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial", BMJ, vol. 322, no. 7298, p. 1327. Hilton, E., Isenberg, H. D., Alperstein, P., France, K., & Borenstein, M. T. 1992, "Ingestion of yogurt containing Lactobacillus acidophilus as prophylaxis for candidal vaginitis", Ann.Intern.Med, vol. 116, no. 5, pp. 353-357. Hirayama, K. & Rafter, J. 1999, "The role of lactic acid bacteria in colon cancer prevention: mechanistic considerations", Antonie Van Leeuwenhoek, vol. 76, no. 1-4, pp. 391-394. Holt, P. 1994, "A potential vaccine strategy for asthma and allied atopic diseases during early childhood", The Lancet, vol. 344, no. 8920, pp. 456-458. Jonkers, D. & StockbrUgger, R. 2003, "Probiotics and inflammatory bowel disease", J R Soc.Med, vol. 96, no. 4, pp. 167-171. Kailasapathy, K. 2002, "Microencapsulation of probiotic bacteria: technology and potential applications", Curr Issues Intest.Microbiol, vol. 3, no. 2, pp. 39-48.

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Kailasapathy, K. & Chin, J. 2000, "Survival and therapeutic potential of probiotic organisms with reference to Lactobacillus acidophilus and Bifidobacterium spp", Immunol Cell Biol, vol. 78, no. 1, pp. 80-88. Kalliomaki, M., Salminen, S., Poussa, T., Arvilommi, H., & Isolauri, E. 2003, "Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial", Lancet, vol. 361, no. 9372, pp. 1869-1871. Kanauchi, O., Mitsuyama, K., Araki, Y., & Andoh, A. 2003, "Modification of intestinal flora in the treatment of inflammatory bowel disease", Curr Pharm Des, vol. 9, no. 4, pp. 333-346. Karthik, S. V. 2003, "Probiotics in inflammatory bowel disease", J R Soc.Med, vol. 96, no. 7, p. 370. Kaur, I. P., Chopra, K., & Saini, A. 2002, "Probiotics: potential pharmaceutical applications", Eur J Pharm Sci, vol. 15, no. 1, pp. 1-9. Kiessling, G., Schneider, J., & Jahreis, G. 2002, "Long-term consumption of fermented dairy products over 6 months increases HDL cholesterol", Eur J Clin Nutr, vol. 56, no. 9, pp. 843-849. Kirjavainen, P. V., Salminen, S. J., & Isolauri, E. 2003, "Probiotic bacteria in the management of atopic disease: underscoring the importance of viability", J Pediatr.Gastroenterol Nutr, vol. 36, no. 2, pp. 223-227. Kollaritsch, H., Holst, H., Grobara, P., & Wiedermann, G. 1993, "[Prevention of traveler's diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study]", Fortschr.Med, vol. 111, no. 9, pp. 152-156. Korshunov, V. M., Gudieva, Z. A., Efimov, B. A., Pikina, A. P., Smeianov, V. V., Reid, G., Korshunova, O. V., Tiutiunnik, V. L., & Stepin, I. I. 1999, "[The vaginal Bifidobacterium flora in women of reproductive age]", Zh.Mikrobiol.Epidemiol.Immunobiol. no. 4, pp. 74-78. Lankaputhra, W. E. & Shah, N. P. 1998, "Antimutagenic properties of probiotic bacteria and of organic acids", Mutat.Res, vol. 397, no. 2, pp. 169-182. Majamaa, H. & Isolauri, E. 1997, "Probiotics: a novel approach in the management of food allergy", J Allergy Clin Immunol, vol. 99, no. 2, pp. 179-185. Marteau, P., Seksik, P., & Shanahan, F. 2003, "Manipulation of the bacterial flora in inflammatory bowel disease", Best Pract.Res Clin Gastroenterol, vol. 17, no. 1, pp. 47-61. McFarland, L. V., Surawicz, C. M., Greenberg, R. N., Fekety, R., Elmer, G. W., Moyer, K. A., Melcher, S. A., Bowen, K. E., Cox, J. L., Noorani, Z., & . 1994, "A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease", JAMA, vol. 271, no. 24, pp. 1913-1918. Naruszewicz, M., Johansson, M. L., Zapolska-Downar, D., & Bukowska, H. 2002, "Effect of Lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers", Am J Clin Nutr, vol. 76, no. 6, pp. 1249-1255. Niedzielin, K., Kordecki, H., & Birkenfeld, B. 2001, "A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome", Eur J Gastroenterol Hepatol, vol. 13, no. 10, pp. 1143-1147. Nobaek, S., Johansson, M. L., Molin, G., Ahrne, S., & Jeppsson, B. 2000, "Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in

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patients with irritable bowel syndrome", Am J Gastroenterol, vol. 95, no. 5, pp. 1231-1238. Oksanen, P. J., Salminen, S., Saxelin, M., Hamalainen, P., Ihantola-Vormisto, A., Muurasniemi-Isoviita, L., Nikkari, S., Oksanen, T., Porsti, I., Salminen, E., & . 1990, "Prevention of travellers' diarrhoea by Lactobacillus GG", Ann.Med, vol. 22, no. 1, pp. 53-56. Ouwehand, A., Isolauri, E., & Salminen, S. 2002, "The role of the intestinal microflora for the development of the immune system in early childhood", Eur J Nutr, vol. 41 Suppl 1, p. I32-I37. Phuapradit, P., Varavithya, W., Vathanophas, K., Sangchai, R., Podhipak, A., Suthutvoravut, U., Nopchinda, S., Chantraruksa, V., & Haschke, F. 1999, "Reduction of rotavirus infection in children receiving bifidobacteria-supplemented formula", J Med Assoc.Thai., vol. 82 Suppl 1, p. S43-S48. Reid, G. Could Probiotics Be an Option for Treating and Preventing Urogenital Infections? Medscape General Medicine 3[4]. 2001a. Ref Type: Electronic Citation Reid, G. 2001b, "Probiotic agents to protect the urogenital tract against infection", Am J Clin Nutr, vol. 73, no. 2 Suppl, pp. 437S-443S. Reid, G., Beuerman, D., Heinemann, C., & Bruce, A. W. 2001, "Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora", FEMS Immunol Med Microbiol, vol. 32, no. 1, pp. 37-41. Reid, G. & Burton, J. 2002, "Use of Lactobacillus to prevent infection by pathogenic bacteria", Microbes.Infect, vol. 4, no. 3, pp. 319-324. Reid, G., Charbonneau, D., Erb, J., Kochanowski, B., Beuerman, D., Poehner, R., & Bruce, A. W. 2003, "Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women", FEMS Immunol Med Microbiol, vol. 35, no. 2, pp. 131-134. Rendi-Wagner, P. & Kollaritsch, H. 2002, "Drug prophylaxis for travelers' diarrhea", Clin Infect Dis., vol. 34, no. 5, pp. 628-633. Rutgeerts, P. 2003, "Modern therapy for inflammatory bowel disease", Scand.J Gastroenterol Suppl no. 237, pp. 30-33. Saavedra, J. 2000, "Probiotics and infectious diarrhea", Am J Gastroenterol, vol. 95, no. 1 Suppl, p. S16-S18. Salminen, S., von Wright, A., Morelli, L., Marteau, P., Brassart, D., De Vos, W. M., Fonden, R., Saxelin, M., Collins, K., Mogensen, G., Birkeland, S. E., & Mattila-Sandholm, T. 1998, "Demonstration of safety of probiotics -- a review", Int J Food Microbiol, vol. 44, no. 1-2, pp. 93-106. Sanders, M. E. 2003, "Probiotics: considerations for human health", Nutr Rev, vol. 61, no. 3, pp. 91-99. Sheih, Y. H., Chiang, B. L., Wang, L. H., Liao, C. K., & Gill, H. S. 2001, "Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001", J Am Coll.Nutr, vol. 20, no. 2 Suppl, pp. 149-156. Stadler, M. & Viernstein, H. 2003, "Optimization of a formulation containing viable lactic acid bacteria", Int J Pharm, vol. 256, no. 1-2, pp. 117-122. Surawicz, C. M., McFarland, L. V., Greenberg, R. N., Rubin, M., Fekety, R., Mulligan, M. E., Garcia, R. J., Brandmarker, S., Bowen, K., Borjal, D., & Elmer, G. W. 2000, "The search for a better treatment for recurrent Clostridium difficile disease:

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use of high-dose vancomycin combined with Saccharomyces boulardii", Clin Infect Dis., vol. 31, no. 4, pp. 1012-1017. Vanderhoof, J. A. & Young, R. J. 2002, "Probiotics in pediatrics", Pediatrics, vol. 109, no. 5, pp. 956-958. Vanderhoof, J. A. & Young, R. J. 2003, "Role of probiotics in the management of patients with food allergy", Ann.Allergy Asthma Immunol, vol. 90, no. 6 Suppl 3, pp. 99-103. Xiao, J. Z., Kondo, S., Takahashi, N., Miyaji, K., Oshida, K., Hiramatsu, A., Iwatsuki, K., Kokubo, S., & Hosono, A. 2003, "Effects of milk products fermented by Bifidobacterium longum on blood lipids in rats and healthy adult male volunteers", J Dairy Sci, vol. 86, no. 7, pp. 2452-2461.

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Herbal Therapy of GIT Disorders When treating any disorders, a herbalist will generally decide on the required actions and prescribe the herbs accordingly. For GIT disorders such actions will include • soothing and healing to inflamed mucous membrane: for example Slippery Elm

lines the mucous membranes but is not broken down in the GIT (for babies’ colic carminative herbs could be included)

• supporting the nervous system with nervine tonics as stress is often a major factor in digestive disorders

• restoring digestive and absorptive mechanisms by maintaining correct secretions • rebuilding debilitated and degenerated tissues • correcting liver and gallbladder functions. Herbalists often treat liver function

even when there is no obvious pathology • supporting eliminative function via liver and kidney and therefore through the

bowels and urine • stimulatory remedies could include revitalising herbs, for example Ginger, which

is also warming to the system

Mouth Ulcers Required actions for mouth ulcers may include • anti-inflammatory, soothing and adaptogenic (helps to deal with stress), eg

Licorice root would fulfill all these criteria • immune-enhancing and anti-inflammatory, for example Echinacea. Echinacea

also stimulates saliva because of its content of alkylamides. • vulnerary and antiseptic, eg Propolis resin. Propolis, as it is a resin, is not water

soluble. It disolves in 70 to 90% alcohol and will actually coat the mouth ulcers and be preventative against further damage.

• local anaesthetic. Kava is a strong local anaesthetic which numbs the mucous membrane and therefore is useful for temporary relief. Kava is also an axiolytic herb and therefore useful if stress is a factor.

• If PMS is a contributing factor, Vitex would be indicated. It is used in almost all conditions that are worse premenstrually.

• Antiseptic and vulnerary (healing), Calendula is both antiseptic and healing, especially to mucous membranes. It also improves lymphatic function. Rhubarb is also antiseptic, astringent and vulnerary.

Mouth Ulcers: Sample formulation Glycyrrhiza glabra (Licorice) 1:1 25 mL Propolis 1:5 25 mL Echinacea purpurea 1:2 30 mL Calendula officinalis (Marigold) 1:2 20 mL

Total 100 mL Dose 5 mL with water three times a day If stress is a factor, nervine tonics or anxiolytics could be of benefit, for example Valerian spp., Eleutherococcus senticosus, Piper methysticum (Kava).

Nausea

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A herbal formula for the treatment of simple nausea may include • Bitters (eg. Gentian) • Ginger • Peppermint • Cinnamon • Black Horehound • Chamomile • Meadowsweet For example, for nausea in pregnancy, a combination of Ginger, Peppermint and Cinnamon extracts is extremely effective. However if vomiting is frequent, the Ginger in particular can be extremely unpleasant, and one of the milder tasting herbs, such as Chamomile, may be more appropriate.

Gastro-Oesophageal Reflux (GER) In the treatment of GER, lifestyle measures may include • Raising the head of the bed by 10 to 15 cm. • Avoiding stress whenever possible while eating. Refrain from overeating • Avoidance of foods which reduce lower oesophageal sphincter tone. These

include chocolate, fatty foods, coffee, tomato concentrates and onions, spicy foods, alcohol and cigarettes. Carminative herbs relax the sphincter muscle (therefore they are useful for flatulence as the sphincter will relax and release gas), however they may exacerbate GER.

• Treating food intolerances. • Avoiding drugs which reduce lower oesophageal sphincter (LOS) tone such as

theophylline, calcium channel blockers and progesterone. • Avoidance of food or drink at bedtime. • Losing weight if overweight, as excess weight will increase pressure on the

sphincter. Herbs for GER Glycyrrhiza glabra (Licorice) and mucilaginous herbs such as Ulmus rubra (Slippery Elm) and Althaea officinalis (Marshmallow Root) will assist mucoprotection. Slippery Elm absorbs excess fluid from the bowel and is therefore useful in the treatment of diarrhoea. As Slippery Elm also soothes and coats the mucous membrane, it is effective in the treatment of ulcerative colitis. Slippery Elm is best given as a powder as the mucilage is not well extracted in alcohol because the mucopolysaccharides are water soluble.

Peptic Ulcer General lifestyle measures may include: • Regular meal times and not eating on the run. • Giving up smoking and/or excessive alcohol intake. • High protein foods should be kept to a minimum as protein stimulates gastric acid. • Duodenal ulcer patients should have regular meals but should avoid bedtime

snacks which will stimulate acid secretion during the night. • NSAID’s which damage the mucosal barrier should be avoided.

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Herbal Treatment for Ulcers • Soothing, anti-inflammatory and healing herbs for the mucous membranes: Chickweed,

Chamomile, Licorice, Slippery Elm • Restore function of mucous membranes with Hydrastis canadensis (Golden Seal).

For some time Golden Seal was threatened as a wildcrafted species. The herb is now cultivated and therefore herbalists can use it with a free conscience. It is also strongly antiseptic and therefore protective against further damage.

• Antiseptic treatments such as Propolis and raw crushed Garlic. Some patients may find the Garlic difficult to take, however Propolis is generally well tolerated.

• Treat poor immunity with Echinacea or Andrographis. Andrographis is a Chinese/Indian bitter and immune system tonic.

• Improve ulcer healing with astringents. In herbal medicine astringent herbs are known as those which tighten and draw in the surrounding tissue. Examples of astringent herbs include Bistort, Agrimony and Meadowsweet. These herbs would be useful in diarrhoea treatment as they tighten the tissue and decrease fluid loss in the bowel.

• Treat pain and spasm with spasmolytic and carminative herbs such as Crampbark or Fennel

• Treat stress and anxiety with nervine tonics such as Skullcap, Valerian, Eleutherococcus senticosus (Siberian Ginseng).

The benefit of using herbs in a formula is that we create a synergistic effect. This means that the individual benefits are enhanced by the other herbs in the formula. Gastric Ulcer : Sample Formulation Gentiana lutea (Gentian) 1:2 02 mL (very low dose) Filipendula ulmaria (Meadowsweet) 1:2 20 mL (anti-inflammatory,

reduces gastric acid secretions) Glycyrrhiza glabra (Licorice) 1:1 15 mL Matricaria chamomilla (Chamomile) 1:2 20 mL Calendula officinalis (Marigold) 1:2 15 mL Echinacea purpurea 1:2 20 mL Hydrastis canadensis (Golden Seal) 1:3 10 mL (mucous membrane tonic) Total 102 mL Dose 5 mL with water three times a day before meals. Slippery Elm powder: 1 teaspoon before meals Duodenal Ulcer : Sample Formulation

Filipendula ulmaria (Meadowsweet) 1:2 20 mL Matricaria chamomilla (Chamomile) 1:2 25 mL Glycyrrhiza glabra (Licorice) 1:1 15 mL Echinacea purpurea 1:2 20 mL Propolis 1:5 10 mL Hydrastis canadensis (Golden Seal) 1:3 10 mL Total 100 mL

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Dose 5 mL with water three times a day half an hour before meals Slippery Elm powder: 1 teaspoon after meals In this formula there is a greater emphasis on preventing infection. The Propolis resin in the formula is anti-inflammatory, soothing, healing and antiseptic. It aids restoration of function to mucous membranes, especially when given with tonics such as Golden Seal.

Irritable Bowel Syndrome 20 to 25% of the population are said to suffer from IBS which is also known as mucous colitis. The female to male ratio is 2.5:1, although it is often true that more women report symptoms. IBS is a chronic disorder which causes abdominal pain, distension and disturbed bowel habits, and frequently alternation of constipation and diarrhoea. 15% of sufferers have disturbed bile acid absorption and therefore malabsorption of fats. Intestinal motility is abnormal and can be either increased or decreased. Food intolerance is a common factor in IBS, and sufferers may need to avoid specific allergens, at least while undergoing treatment. 25% of cases are associated with a specific episode of gastroenteritis. Treatment of IBS • Treat food allergies with exclusion diet • Spasmolytics (antispasmodics). These relax intestinal smooth muscle. • Sedatives, nervine tonics and adaptogens for stress • Hepatorestoratives (improve liver function) and choleretics • Treat constipation/diarrhoea • GIT antiseptics: golden seal, propolis • GIT anti-inflammatories: eg, Meadowsweet, Chamomile, Calendula, Chickweed,

Slippery Elm IBS: Sample Formulation Filipendula ulmaria (Meadowsweet) 20 mL (anti-inflammatory) Matricaria chamomilla (Chamomile) 25 mL (anti-inflammatory, healing, nervine tonic) Silybum marianum (St Mary’s Thistle) 20 mL (liver tonic, hepatorestorative) Viburnum opulus (Cramp Bark) 20 mL (spasmolytic) Hydrastus canadensis (Golden Seal) 15 mL (anti-inflammatory, antiseptic,

restores mucous membrane function)

Total 100 mL Slippery Elm: one tablespoon, BD Probiotics Should be taken between meals to recolonise gut with friendly bacteria. Bitter tonics, eg Gentian, Ginger, Angelica, Vervain: to improve digestion in upper GIT. Assc. Prof. Tim Roberts, University of Newcastle is conducting research into chronic fatigue syndrome. Roberts maintains that the majority of CFS sufferers have a history of IBS. The University have instigated a series of tests which validate this:

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Bioscreen Pathology Tests www.bioscreen.com.au Tel: 02 4961 6513 • Urine test: anomalies in the excretion of amino and organic acids • Blood lipid test: anomalies in fatty acid homeostasis • Faeces test: anomalies in bowel flora and fat malabsorption • Coagulase Negative Staphyloccocal test (membrane-damaging toxins associated

with chronic pain) • Organochlorine Pesticide test Faeces Report These test for: • Short and medium chain fatty acids. A high degree of these are associated with

colonic dysfunction • High levels of C18 fatty acids indicate fat malabsorption • Total bacterial count • Aerobes: common feature is low E. Coli (One finding is that autistics have been

demonstrated to have almost no E. Coli present.) • Anaerobes: predominence of bacteroides (lack of probiotics) • Aerobes/anaerobes Balance: should be 95% aerobes • Level of fungal infection

Intestinal Infections: Sample Formulation Echinacea purpurea 1:2 25 mL Andrographis panculata 1:2 20 mL Hydrastis canadensis (Golden Seal) 1:2 15 mL Propolis 1:5 10 mL Calendula officinalis (Marigold) 1.2 15 Ml Matricaria chamomilla (Chamomile) 1:2 15 mL Total 100 mL Dose 5 mL with water three times a day Echinacea and Andrographis stimulate immune function but are not antiseptic. The Propolis and Calendula are, however, antiseptic, while the Calendula and Golden Seal are anti-inflammatory. The emphasis in treament is on immune stimulants and antiseptics. Fresh Garlic Lactobacillus culture between meals Slippery Elm If the Garlic is taken with the Slippery Elm, it should reduce burning and irritation. While Garlic is highly antiseptic and antimicrobial, it is also a mucous membrane irritant. Hein Zeylstra, an experienced British herbalist, successfully treats both ulcerative colitis and Crohn’s disease with just Slippery Elm and Garlic in high doses.

Acute Diverticulitis: Sample Formulation Echinacea purpurea 1:2 25 mL Hydrastis canadensis (Golden Seal) 1:3 20 mL

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Viburnum opulus (Crampbark) 1:2 20 mL Matricaria chamomilla 1:2 20 mL Propolis 1:5 15 mL Total 100 mL Dose 5 mL with water three times a day. Slippery Elm powder, 1 tablespoon with water before meals The Echinacea and Golden Seal in this formula will help prevent any infection in the diverticulae. The Chamomile is anti-inflammatory while the Propolis is antiseptic.

Herbal Treatment of Constipation • Cholagogues would be part of the treatment here, to improve production and flow

of bile. For example, Taraxacum officinale (Dandelion), Silybum marianum (St Mary’s Thistle, Milk Thistle), Cynara scolymus (Globe Artichoke)

• Gastrointestinal spasmolytics (antispasmodics), eg. Chamomile, Mentha spp. (Peppermint), Viburnum opulus (Crampbark)

• Improve GI lubrication with linseeds or psyllium seeds or husks • Anthraquinone glycoside containing herbs, eg. Rumex crsipus (Yellow Dock),

Juglans cinera (Butternut), Cassia spp. (Senna), Cascara. Both Cassia and Cascara are strong laxatives and may need to be used with antispasmodics.

• Bulk laxatives, eg. Slippery Elm and psyllium husks • Drink lots of water and increase excercise Constipation: Sample Formulation Taraxacum officinale (Dandelion root) 1:2 20 mL Silybum marianum (St Mary’s Thistle) 1:1 20 mL Viburnum opulus (Crampbark) 1:2 15 mL Mentha piperita (Peppermint) 1:2 10 mL Cassia spp. (Senna) 1:2 20 mL Glycyrrhiza glabra (Licorice) 1:1 15 mL Total 100 mL Slippery Elm powder, increase water intake, increase exercise. Stronger laxatives should only be used in the short-term. In the long-term, liver herbs, diet and digestive tonics would be the preferred treatment.

Haemorrhoids The treatment of haemorrhoids would include measures to improve bowel function, but importantly the tone of venous and connective tissue needs to be improved. • Slippery Elm and psyllium, contain mucilage which is healing and soothing,

making the stool soft and bulky • Increase dietary fibre • Choleretic and hepatoprotective herbs improve constipation by reducing liver

congestion. • Venous and connective tissue tone can be improved with herbs such as Aesculus

hippocastanum (Horsechestnut), Ruscus aculeatus (Butcher’s Broom), Polygonum multiflorum, Gingko biloba, Bilberry and Vitis vinifera (Grape Seed)

• Topically, healing and astringent herbs such as Witch Hazel, Comfrey and Calendula can be employed. Horse Chestnut also works well topically, but should

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not be applied if the piles are bleeding, because it contains saponins which are haemolytic.

Inflammatory Bowel Disease Indications to consider in the treatment of inflammatory bowel disease would include: • Anti-inflammatory, eg. Matricaria chamomilla, Calendula officinalis • Astringents, eg. Agrimony officinalis, Hamamelis virginiana • Mucous membrane tonics, eg. Hydrastis canadensis, Plantago lanceolata • Demulcents, eg. Ulmus rubra, Althae officinalis • Adaptogenics, eg. Rehmannia glutinosa • Antiallergics, eg. Albizia lebeck, Scutellaria baicalensis • Liver tonics, eg. Silybum marianum • Immunenhancing, eg. Echinacaea spp • Haemostatics, eg, Achillea millifolium, Panax notoginseng Ulcerative Colitis: Sample Formulation Achillea millefolium (Yarrow) 1:2 20 mL Dioscorea villosa (Wild Yam) 1:2 20 mL Calendula officinalis (Marigold) 1:2 20 mL Matricaria chamomilla 1:2 20 mL Echinacea spp. 1:2 20 mL Total 100 mL 5 mL TDS If there is blood in the stool the Yarrow will act as an astringent. The Wild Yam is anti-inflammatory and antispasmodic. The Calendula and Chamomile are healing and anti-inflammatory. The Echinacea is of course immune stimulating. Bitter tonic before meals Slippery Elm: one tablespoon before meals Fresh Garlic (improves immune function and is antiseptic against various organisms). Dietary restriction: bland, simple food, check allergies Restore bowel flora Case: ulcerative colitis By Naturopath Jenny Adams Reference: Phytomedicine Focus, No 2, 2001 Joan, aged 52, was referred by her GP for treatment of ulcerative colitis. She was somewhat desperate for help, being unable to use the standard medical treatment sulfasalazine because of interaction with warfarin. Symptoms had begun four months before with cramping abdominal pain, flatulence and explosive diarrhoea every few days with loose bloody stools, alternating with periods of constipation. She was feeling very fatigued and “thoroughly sick” of having to race to the toilet 4-5 times daily during the episodes of diarrhoea. History The combination of a congenital heart defect and rheumatic fever in childhood had lead to the necessity for an aortic valve replacement two years ago combined with long term treatment with warfarin. A painful bilateral sciatica started at the same time

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as the colitis. There was a strong family history of ulcerative colitis and chronic colitis. Joan had modified her diet considerably since the onset of her symptoms, as she could no longer tolerate meat or oily foods. She had increased fibre in her diet under the instruction of her gastroenterologist, by including Sultana Bran for breakfast, regular fruit, and salad vegetables. On examination Joan demonstrated extreme tenderness in the left iliac fossa. Colonoscopy had shown that the ulcerative colitis was limited to the distal colon. Treatment and rationale • Phytomedicine’s Boswellia Compound: one tablet three times daily. • Probiotic powder containing Lactobacillus acidophilus and Bifidobacterium

bifidum: ½ teaspoon twice daily - to re-establish good gut flora and modulate immune response.

• Slippery elm powder: 2 heaped teaspoons twice daily - a soothing mucilaginous demulcent to the gastrointestinal tract.

Boswellia Compound contains Boswellia serrata stem bark resin 1400 mg Harpagophytum procumbens dry tuber 500 mg Zingiber officinalis rhizome powder 400 mg Guaiacum officinale resin 100 mg Although Boswellia Compound may be more specific for arthritis, it is also suitable for ulcerative colitis, primarily due to the fact that Boswellia serrata and Harpagophytum procumbens are also anti-inflammatory in the GIT. Harpagophytum procumbens normalises diarrhoea/constipation and reduces flatulence. A basic elimination diet excluding caffeine, alcohol, wheat, dairy, meat, eggs, raw fruit and salads (cooked fruit and vegetables were allowed) was recommended for the first week, followed by trial reintroduction of individual foods over subsequent weeks. A symptom diary was suggested to monitor bowel frequency and pain, and to record exacerbations related to stress. I notified her doctor outlining the prescribed treatment. I had some concern that the ginger in the Boswellia Compound might potentiate the warfarin because of ginger’s antiplatelet activity so I requested that I was kept informed of Joan’s internationalised normalised ratio (INR) level. (INR is used to monitor the risk of bleeding for patients on warfarin. An increased INR indicates an increased risk of bleeding). Second appointment (2 weeks later) Bowel movements had settled to three times weekly and stools were soft and formed. No further diarrhoea and only one episode of mild cramping and wind, which occurred during a particularly stressful day at work. Sciatic pain relieved. INR being monitored fortnightly; last reading low at 1.4 (target range 2.5-3.5) possibly due to change in diet. This was the opposite of what I had anticipated but was reassuring to know that the ginger at this dosage did not reduce her blood clotting time. The GP increased warfarin dose to 7 mg. On examination, no specific abdominal tenderness was noticed. Joan was getting bored with the diet so I suggested trial reintroduction of some of the foods she was missing. Continue Boswellia compound 1 three times daily, and slippery elm powder 2 tsp twice daily. Third appointment (3 weeks later)

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One episode of diarrhoea with rectal bleeding occurred after a meal that included salami. By this stage Joan had successfully reintroduced the odd glass of wine, pasta and raw fruits. INR stabilised at 2.8. Feeling much better. Continue Boswellia compound one table twice daily. Telephone contact 3 months later No further episodes of diarrhoea. Recently stopped all herbal medication. Continuing to avoid processed meats and fatty foods but otherwise enjoying wide range of foods. Very grateful. Crohn’s Disease: Sample Formulation Bupleurum falcatum 1:2 25 mL (anti-inflammatory/liver tonic) Glycyrrhiza glabra (Licorice) (HG) 1:1 15 mL Dioscorea villosa (Wild Yam) 1:2 15 mL Echinacea spp. 1:2 25 mL Hydrastis canadensis (Golden Seal) 1:3 20 mL (contains berberine which is

strongly antimicrobial) Total 100 mL 5 mL TDS In this formula there is a great emphasis on an anti-inflammatory action via the adrenals because of the high relationship of stress in this disorder. Bitter tonics before meals, Slippery Elm: one tablespoon before meals, Fresh Garlic Dietary restriction: bland, simple food, check allergies Restore bowel flora (probiotics)

Coeliac Disease and Gluten Sensitivity By Melanie Koeman, former technical writer for Nutrimedicine. Gluten is a protein found in all forms of wheat (including durum, semolina, and spelt), rye, barley and related grain hybrids such as triticale and kamut. It is present in smaller amounts in oats and is also undisclosed in an endless variety of processed foods. Coeliac Disease (CD) is also known as gluten-induced enteropathy or sprue. It is an autoimmune disease that leads to a permanent intestinal intolerance to gluten. The gluten causes inflammation of the intestinal wall and a flattening of the villi, finger-like projections that line the inside of the bowel. When these villi atrophy (flatten) the surface area for absorption is greatly reduced resulting in deficiencies of a number of nutrients. The overall prevalence of CD is estimated as 1 in approximately 130, however if you have a family history of CD your risk is increased to approximately 1 in 10. Gluten Sensitivity (GS) is a condition that involves a degree of gluten intolerance without the presence of immune markers associated with CD. The treatment approach is similar however, since removal of gluten often results in clinical improvement and symptom relief. After a period of avoidance, small amounts of gluten-containing foods may be well tolerated. Guidance will be given to you from your healthcare practitioner.

Symptoms of CD

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Although there may be no symptoms of CD, the most common ones involve the digestive system and include abdominal bloating or pain, diarrhoea, constipation, flatulence, heartburn, or nausea with or without vomiting. Other possible symptoms include sinusitis, asthma, skin disorders including eczema and dermatitis hepetiformis, fatigue, bone, joint and muscle pains, mouth ulcers, loss of tooth enamel, mood and behavioural problems, poor growth or development in children, weight loss, hair loss and menstrual problems. CD is associated with a higher risk of osteoporosis, iron deficiency anaemia, menstrual problems including amenorrhoea, miscarriage and infertility, and thyroid or other autoimmune diseases. Helpful hints • Read all food labels carefully. • The Australian food standards code requires that foods labeled as ‘gluten free’ must not

contain any detectable gluten. Food labeled as ‘low gluten’ must contain less than 0.02% gluten.

• Lactose intolerance is a common accompanying problem to CD. Your practitioner may recommend the removal of dairy products as part of their treatment.

• Avoid cross contamination in the kitchen by developing gluten-free kitchen habits, storage plans and procedures for mixing, cooking and baking.

• Gluten-free breads taste better toasted and should be stored in the fridge or freezer. • When eating out select food without crumbing, ‘creaming’, coatings, gravies and sauces.

Ideally, call ahead to notify the chef of your dietary requirements. • Obtain your fibre from brown rice, buckwheat, unpeeled potatoes, fresh and dried beans

& legumes, fresh fruit & vegetables (see Nutrimedicine Fibre Information Sheet) • Nutritional deficiencies are common, particularly of iron, zinc, vitamins B2, folate and

B12. (See Nutrimedicine Nutrient Food List for the best sources of these nutrients) • Avoid skipping meals, eat slowly and chew all food thoroughly. Enjoy your food! • Plan your meals and carry snacks with you so you are prepared for all eventualities. What to Include What to Avoid

Grains /Flours /Roots /Tubers and Legumes Grains: Buckwheat, brown rice, basmati rice, wild rice, maize (corn), quinoa, amaranth, millet, sorghum. (Some CD patients may have a secondary sensitivity to the grains quinoa, amaranth, buckwheat & millet) Roots and Tubers: potato, tapioca, arrowroot, sweet potato. Legumes: Beans, soy, lentils, peanut, pea, chickpea. Flours: Any flours made from the above sources, chickpea flour.

Grains: Wheat (including, durum, semolina, triticale), rye, barley, burglur, couscous and possibly oats. (Spelt and kamut are ancient grains but may be suitable for people with wheat intolerance.) Roots and Tubers: French fries (check labels) Legumes: Baked Beans unless gluten-free. Flours: Wheat flour, wholemeal flour, bakers flour, semolina, barley, rye (avoid battered or crumbed food).

Breads and Cereals Breads: Gluten free breads based on buckwheat, corn, rice, chickpea flour and/or soya flour. Cereals: Gluten free muesli, homemade muesli made from a combination of: Brown rice flakes, millet flakes, organic cornflakes, puffed corn, puffed rice, soy bran, soy grits, raw nuts & seeds, shredded coconut.

Breads: Wheat breads - wholegrain or white, rye bread, oat bread, barley bread, burritos, pumpernickel bread. (Spelt may be suitable for some people with wheat intolerance) Cereals: Commercial cereals (rice bubbles, weetbix, wheat containing muesli, coco pops etc) wheat germ, wheat bran, porridge oats, oat bran, oat germ. Any cereal containing malt.

Michael Thomsen

Pastas Buckwheat noodles, rice noodles, vegetable, corn, spinach or quinoa pasta.

Durum wheat pasta (spaghetti, macaroni etc), egg noodles, hokkein noodles, barley pasta, spelt pasta. (Spelt may be suitable for some people with wheat intolerance)

Crackers Rice cakes, corn cakes, gluten free products. Wheat crackers, bran biscuits, ryvita, kavli, oatcakes. Snacks and Desserts Popcorn, dried fruit (limit), fresh fruit, carob, sesame snacks, fruit and nut bars, gluten free biscuits or other snack.

Commercial biscuits, cookies, cakes, scones, pastries, liquorice, some lollies and ice creams, some commercial fruit pies, flavoured or frozen yoghurts, processed cheeses & creams.

Stock, seasonings and thickeners Bouillon stock powder, sesame salt, tamari (check label), mustard seeds, fresh dried herbs and spices, potato flour, apple cider vinegar, authentic balsamic vinegar, wine vinegar, maize corn flour, soy flour, arrowroot, kuzu and agar-agar.

Malt, malt vinegar, Vegemite, wheat starch, modified starch, mustard pickles, soy sauce, gravy mixes and seasoning ‘rubs’; Hydrolyzed vegetable protein (HVP), texturized vegetable protein (TVP); Some binders, fillers, excipients, extenders etc (It is best to contact the manufacturer or your state Coeliac Society).

Beverages White wine, light rum, gin, tequila without dyes or additives, potato vodka; Teas, coffee, soft drinks, mineral water, fresh fruit and vegetable juices.

Beers, ale and lager, cereal and malted beverages, malted or flavoured milk drinks, instant tea, coffee substitutes.

Other sources of gluten Some medications use gluten as a binder. Contact your doctor or pharmacist for more information. If ingredients are not itemised, check with the manufacturer of the product or with your state Coeliac Society.

Adult Coeliacs, parents of Coeliac children and those with Dermatitis Herpetiformis have formed Coeliac Societies in all Australian States. These Societies provide information on the disease, gluten free diet, ingredients, where to buy, cooking and recipes, overseas travel, education material, etc. If you would like to become a member or would like more information, please contact your State Society. www.coeliac.org.au

Michael Thomsen

Liver Disorders Liver Detoxification Sources of toxins to liver include: • Chemicals from the environment (xenobiotics) • Drugs (and some herbs) • Infectious organisms • Normal metabolites eg. bile acids, steroid hormones • Endogenous toxins eg. abnormal metabolites Liver Toxins & Disease Liver toxins can potentially have a causative effect in the aetiology of many diseases including: • Chronic fatigue syndrome • Immune deficiency • Neurological disorders • Chronic inflammatory disorders • Allergies • Autoimmune diseases • Chemical sensitivities • Cancer • Liver damage, kidney damage etc • Leaky gut syndrome • Probably almost any chronic disease process • Hormonal imbalance Processing of Toxins by the Body • Storage in adipose tissue • Direct elimination via the kidneys, lungs etc without further processing • Elimination via the urine, bile etc after processing (biotransformation) by the liver Beneficial Action of Herbs to the Liver • Protect the liver from toxic damage – hepatoprotective • Restore the liver after toxic damage – hepatic trophorestorative (restores function) • Stimulate the flow of bile – choleretic • Stimulate Kupffer cell function • Stimulate hepatic detoxification processes (biotransformation) – depurative

(alterative) (traditionally known as “blood cleansers”). Biotransformation of Toxins by the Liver The aim of biotransformation is to render the toxin more easily excreted. Reactions involved in the biotransformation of toxins by the liver can be divided into two distinct categories: Phase I Reactions • typically involves oxidation or reduction reactions.

Michael Thomsen

• largely dependent on enzymes associated with smooth endoplasmic reticulum (ie microsomes) known mainly as the mixed function oxidase system (cytochrome P450)

• generally involves exposing or adding a functional group, usually oxygen, by a free radical mechanism.

• involves the generation of free radicals Phase I Reactions activate Phase II Phase II Reactions Phase II reactions involve the coupling of a highly polar (water-soluble) endogenous chemical to the toxin Product is more water-soluble and less toxic. Large molecules are excreted in the bile, smaller in the urine. Bioactivation Bioactivation by Phase I reactions may result in the production of a more toxic compound, especially for xenobiotics. • May cause tissue damage (eg hepatotoxicity, teratogenicity). • May react with Phase II enzymes and be rendered harmless and excreted. • May react with a cell protein forming an antigen (haptenization). This may lead to

immunological reactions such as drug-induced lupus. • May bind with DNA causing mutation which can lead to cancer. (Many

carcinogens are first activated by hepatic microsomes). Phase l & ll Balance Sometimes overload of Phase II reactions can lead to a toxin being primarily metabolised by a Phase I mechanism, with toxic consequences. The balance between Phase I and Phase II enzymes is an important determinant of whether exposure to xenobiotics will result in toxicity and cancer. Stimulating Phase I reactions without a matching stimulation of Phase II reactions can be detrimental. Increased Phase II activity probably prevents cancer.

Important Liver Herbs Schisandra chinensis Schisandra extract enhances hepatic glutathione status and induces Phase I enzyme activity. Schisandrin B increases glutathione S-transferase (GST) (Phase II) and microsomal cytochrome P450 enzymes (Phase I). Gomisin A (in Schisandra) has been shown to: • stimulate liver regeneration • prevent acetaminophen toxicity (as does Schisandra) • improve bile acid metabolism (Phase II) • increase GST (Phase II) Curcuma longa (Turmeric) • Turmeric and curcumin (a constituent of Turmeric) reduce cancers by altering the

activation and/or detoxification processes in carcinogen metabolism. • Curcumin inhibits both Phase I and II enzymes in vitro. However, turmeric in

vivo causes significant increases in Phase II enzymes (as does curcumin) and decreases some Phase I enzyme activity

Michael Thomsen

• Turmeric and curcumin inhibit aflatoxin-induced liver toxicity. • Turmeric (1.5 g/day) reduces the excretion of urinary mutagens in smokers. Silybum marianum Silybum marianum (St Mary’s Thistle) is more protective and regenerative to the liver than detoxifying. • Silybin inhibits GST in vitro. • In contrast silymarin (which is a combination of three different compounds) is an

inducer of Phase I enzymes in vivo. • However, when 210 mg of silymarin was fed to human subjects over 28 days,

there was no influence on the metabolism of aminopyrine and phenylbutazone. • Silymarin causes hepatic regeneration and increases hepatic glutathione in vivo. Quality tablets are usually standardised to “silymarin calc. silybum” content. These are the best for the treatment of actual liver damage.

Dietary Factors • Rosemary and Sage contain carnosol which is antioxidant and inhibits

bioactivation of benzo-alpha-pyrene and induces GST and NAD(P)H:quinone reductase (important Phase II enzymes).

• Garlic and its components have a chemopreventative activity against carcinogenesis and increase Phase II enzyme activity and may inhibit Phase I enzymes. Garlic oil induces Phase I enzymes in vivo.

• Myristicin in Parsley leaf oil is an active inducer of GST activity. • Citrus fruit oils increase GST activity. • Green Tea polyphenolics have a pronounced chemopreventative activity against

carcinogenesis and increase Phase I and Phase II enzyme activity in vivo. The chemopreventative effects of green tea and coffee were examined in 52 male cigarette smokers. Only for green tea drinkers (2 to 3 cups per day) were the frequency of sister chromatid exchange (SCE, which is indicative of chromosomal damage − possibly cancer-causing) in smokers comparable to that in nonsmokers. The conclusion was that green tea can block the cigarette-induced increase in SCE frequency. Source: Shim, J S and co-workers, Cancer Epidemiol Biomarkers Prev 4, 387

(1995). The Brassicas Cruciferous vegetables (eg Brussels sprouts and broccoli) and herbs (eg Horseradish, Mustard, Nasturtium, Watercress) contain sulfur glucosides known as glucosinolates. Upon cooking, grating (damage to the plant cells), digestion or steam distillation, glucosinolates are converted to isothiocyanates which also contain sulfur. Broccoli and Brussels sprouts are rich in a glucosinolate called glucoraphanin which yields the isothiocyanate sulforaphane. Sulforaphane is one of the most potent inducers of Phase II enzymes discovered so far. Glucosinolates (via their isothiocyanate products) have also shown anticancer and cancer-preventing activities.

Poor Liver Function & Gall Stones

Treatment is aimed at increasing and improving bile flow and therefore softening or reducing the size of stones.

Michael Thomsen

• Hepatoprotectives, eg. St Mary’s Thistle, Globe Artichoke • Cholagogues (increase flow), eg. Peppermint, Calendula • Choleretics (increase bile production), eg. Dandelion root, Golden Seal, Barberry,

Greater Celandine • Detoxifiers, eg. Schisandra, Turmeric • Alteratives, eg. Yellow Dock, Burdock, Fumitory

Acute Viral Hepatitis Causes: hepatitis A, B and C viruses, Epstein-Barr virus and cytomegalovirus. These viruses are surrounded by a protein shell so Hypericum may be of benefit. • Diaphoretics, eg. Lime Flowers, Elder, Yarrow, Ginger • Antivirals, eg. St John’s Wort, Phyllanthus, Thuja • Immune-stimulants, eg. Echinacea, Picrorrhiza, Andrographis, Astragalus • Hepatoprotectives, eg. St Mary’s Thistle, Dandelion root, Globe Artichoke,

Picrorrhiza, Schisandra, Bupleurum

Chronic Viral Hepatitis Causes: hepatitis B or C. May have auto-immune elements. • Antivirals, eg. St John’s Wort, Phyllanthus, Thuja • Immune-enhancers, eg. Echinacea, Picrorrhiza • Hepatoprotectives, eg. St Mary’s Thistle, Dandelion root, Globe Artichoke,

Picrorrhiza, Schisandra, Dan Shen • Adaptogens, eg. Ginseng, Bupleurum, Rehmannia, Withania

Cirrhosis of the Liver • Hepatoprotectives, eg. St Mary’s Thistle, Globe Artichoke, Picrorrhiza • Adaptogens, eg. Ginseng, Bupleurum, Rehmannia • Liver tonics, eg. Dandelion root Use non-alcohol products such as Silybum marianum glycerol extract or Silymarin tablets.