Dr Clare Materia Medica

Also Known As:

Blue Chamomile, Camomilla, Camomille, Camomille Allemande, Chamomilla, Echte Kamille, Feldkamille, Fleur de Camomile, Hungarian Chamomile, Kamillen, Kleine Kamille, Manzanilla, Manzanilla Alemana, Matricaire, Matricariae Flos, Pin Heads, Sweet False Chamomile, True Chamomile, Wild Chamomile.

Scientific Name:

Matricaria recutita, synonyms Chamomilla recutita, Matricaria chamomilla.

Family: Asteraceae/Compositae. 

People Use This For:

Orally, German chamomile is used for flatulence, travel sickness, nasal mucous membrane inflammation, allergic rhinitis, nervous diarrhea, attention deficit hyperactivity disorder (ADHD), fibromyalgia, restlessness, and insomnia. It is also used for gastrointestinal (GI) spasms, colic, inflammatory diseases of the GI tract, GI ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and alcohol consumption, and as an antispasmodic for menstrual cramps. 

Topically, German chamomile is used for hemorrhoids; mastitis; leg ulcers; skin, anogenital, and mucous membrane inflammation; and bacterial skin diseases, including those of the mouth and gums. It is also used topically for treating or preventing chemotherapy- or radiation-induced oral mucositis.

As an inhalant, German chamomile is used to treat inflammation and irritation of the respiratory tract. 

In foods and beverages, German chamomile is used as flavor components.

In manufacturing, German chamomile is used in cosmetics, soaps, and mouthwashes.

Safety:

No concerns regarding safety, available studies validate this statement, when used orally in amounts commonly found in foods. German chamomile has Generally Recognized as Safe (GRAS) status in the US.¹

No concerns regarding safetywhen used orally, short-term. There is some evidence that German chamomile can be used safely for up to 8 weeks.^2,3,4 The long-term safety of German chamomile in medicinal doses is unknown, when used topically; avoid applying it near the eyes.⁵

Children: No concerns regarding safety when used orally and appropriately, short-term. Preliminary clinical research also suggests that a specific multi-ingredient product containing fennel 164 mg, lemon balm 97 mg, and German SourceURL:file://localhost/Users/ruthruane/Downloads/Herbal%20Medicine-Newest.doc

chamomile 178 mg (ColiMil, Milte Italia SPA) is safe in infants when used for up to a week.⁶

Pregnancy and Lactation: Insufficient reliable information available; avoid using. 

Effectiveness:

POSSIBLY EFFECTIVE

Colic. A clinical trial shows that breast-fed infants with colic who are given a specific multi-ingredient product containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg (ColiMil, Milte Italia SPA) twice daily for a week have reduced crying times compared to placebo.⁶

Dyspepsia. A specific combination product containing German chamomile (Iberogast, Medical Futures, Inc) seems to improve symptoms of dyspepsia. The combination includes German chamomile plus peppermint leaf, clown's mustard plant, caraway, licorice, milk thistle, celandine, angelica, and lemon balm.^7,3 A meta-analysis of studies using this combination product suggests that taking 1 mL orally three times daily over a period of 4 weeks significantly reduces severity of acid reflux, epigastric pain, cramping, nausea, and vomiting compared to placebo.⁸

Oral mucositis. Using a German chamomile oral rinse (Kamillosan Liquidum) might help prevent or treat mucositis induced by radiation therapy and some types of chemotherapy.² German chamomile oral rinse seems to prevent or treat mucositis secondary to radiation therapy and some types of chemotherapy including asparaginase (Elspar), cisplatin (CDDP, Platinol-AQ), cyclophosphamide (Cytoxan, Neosar), daunorubicin (DaunoXome), doxorubicin (Adriamycin, Rubex), etoposide (VP-16, Etopophos, VePesid, Toposar), hydroxyurea (Hydrea), mercaptopurine (6-MP, Purinethol), methotrexate (MTX, Rheumatrex), procarbazine (MIH, Mutlane), and vincristine (VCR, Oncovin, Vincasar) (2). However, the rinse doesn't seem to be better than placebo for preventing fluorouracil (5-FU)-induced oral mucositis.⁹

POSSIBLY INEFFECTIVE

Dermatitis. Applying German chamomile cream topically does not seem to prevent dermatitis induced by cancer radiation therapy.¹⁰

Mechanism of Action:

The applicable part of German chamomile is the flowerhead. Active constituents of German chamomile include quercetin, apigenin, and coumarins, and the essential oils.⁵

German chamomile might have anti-inflammatory effects. Preliminary research suggests it can inhibit the pro inflammatory enzymes. Other constituents may inhibit histamine related to allergies,^5,4

The constituent(s) responsible for the sedative activity of German chamomile are unclear. Preliminary research suggests that extracts of German chamomile might inhibit morphine dependence and withdrawal.¹¹ Other preliminary research suggests that German chamomile flower extract taken orally might have an antipruritic effect.¹² Preliminary research suggests that German chamomile blocks slow wave activity in the small intestine, which could slow peristaltic movement.¹³

Adverse Reactions:

Orally, German chamomile tea can cause allergic reactions including severe reactions in some patients.¹⁴

Interactions with Herbs & Supplements:

HERBS AND SUPPLEMENTS WITH SEDATIVE PROPERTIES: Theoretically, concomitant use with herbs that have sedative properties might have additive effects which needs to be taken into account.^5,16

Interactions with Drugs:

Benzodiazepines: Consult a Medical Herbalist

CNS Depressants: Consult a Medical Herbalist

Warfarin (Coumadin): Consult a Medical Herbalist

Interactions with Foods:

None known. 

Interactions with Lab Tests:

Creatinine: Chronic ingestion of German chamomile for two 2 weeks can reduce urinary creatinine output. This effect may be prolonged for up to two weeks after discontinuing German chamomile. The mechanism for this effect is unclear.⁴

Interactions with Diseases or Conditions:

Surgery: Avoid from 2 weeks prior to elective surgery.

Dosage/Administration:

Oral: For dyspepsia, a specific combination product containing German chamomile (Iberogast, Medical Futures, Inc) and several other herbs has been used in a dose of 1 mL three times daily.^7,3,8

For colic in infants, a specific multi-ingredient product containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg (ColiMil, Milte Italia SPA) twice daily for a week has been used.⁶ 

Topical: For chemotherapy- or radiation-induced oral mucositis, an oral rinse made with 10-15 drops of German chamomile liquid extract in 100 mL warm water has been used three times daily.²

Comments:

German chamomile is an annual herb found throughout Europe and in portions of Asia. German chamomile has a mild apple-like scent. The name "chamomile" is Greek for "Earth apple." 

Specific References: CHAMOMILE

1.   FDA. Center for Food Safety and Applied Nutrition, Office of Premarket Approval, EAFUS: A food additive database. Available at: vm.cfsan.fda.gov/~dms/eafus.html.

2.   Carl W, Emrich LS. Management of oral mucositis during local radiation and systemic chemotherapy: a study of 98 patients. J Prosthet Dent 1991;66:361-9.

3.   Madisch A, Holtmann G, Mayr G, et al. Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial. Digestion 2004;69:45-52.

4.   Wang Y, Tang H, Nicholson JK, et al. A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.) ingestion. J Agric Food Chem 2005;53:191-6.

5.   Hormann HP, Korting HC. Evidence for the efficacy and safety of topical herbal drugs in dermatology: part I: anti-inflammatory agents. Phytomedicine 1994;1:161-71.

6.   Savino F, Cresi F, Castagno E, et al. A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officinalis (ColiMil) in the treatment of breastfed colicky infants. Phytother Res 2005;19:335-40.

7.   Holtmann G, Madisch A, Juergen H, et al. A double-blind, randomized, placebo-controlled trial on the effects of an herbal preparation in patients with functional dyspepsia [Abstract]. Ann Mtg Digestive Disease Week 1999 May.

8.   Melzer J, Rosch W, Reichling J, et al. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther 2004;20:1279-87.

9.   Fidler P, Loprinzi CL, O'Fallon JR, et al. Prospective evaluation of a chamomile mouthwash for prevention of 5-FU-induced oral mucositis. Cancer 1996;77:522-5.

10.  Maiche AG, Grohn P, Maki-Hokkonen H. Effect of chamomile cream and almond ointment on acute radiation skin reaction. Acta Oncol 1991;30:395-6.

11.  Gomaa A, Hashem T, Mohamed M, Ashry E. Matricaria chamomilla extract inhibits both development of morphine dependence and expression of abstinence syndrome in rats. J Pharmacol Sci 2003;92:50-5.

12.  Kobayashi Y, Nakano Y, Inayama K, et al. Dietary intake of the flower extracts of German chamomile (Matricaria recutita L.) inhibited compound 48/80-induced itch-scratch responses in mice. Phytomedicine 2003;10:657-64.

13.  Storr M, Sibaev A, Weiser D, et al. Herbal extracts modulate the amplitude and frequency of slow waves in circular smooth muscle of mouse small intestine. Digestion 2004;70:257-64.

14.  Subiza J, Subiza JL, Hinojosa M, et al. Anaphylactic reaction after the ingestion of chamomile tea; a study of cross-reactivity with other composite pollens. J Allergy Clin Immunol 1989;84:353-8.

15.  Viola H, Wasowski C, Levi de Stein M, et al. Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med 1995;61:213-6.

16.  Avallone R, Zanoli P, Puia G, et al. Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol 2000;59:1387-94.

Also Known As:

Common Fennel, Garden Fennel, 

Scientific Name:

Foeniculum vulgare.

Family: Apiaceae/Umbelliferae.

People Use This For:

Dyspepsia, flatulence, bloating, loss of appetite, and for colic in infants. It is used for increasing lactation, promoting menstruation, facilitating birth, and increasing libido. 

Safety:

No concerns regarding safety, available studies validate this statement, when used orally in amounts commonly found in foods. Fennel has Generally Recognized as Safe (GRAS) status in the US.¹⁷

There is insufficient scientific information available about the safety of fennel when used in medicinal amounts.

Children: Insufficient reliable information available. Preliminary clinical research suggests that a specific multi-ingredient product containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg (Colimil) is safe in infants when used for up to a week.¹⁸ However, maternal consumption of an herbal tea containing fennel has been linked to neurotoxicity in breast-feeding infants.¹⁹

Lactation: Possibly Unsafe when used orally by breast-feeding mothers. Case reports have linked consumption of an herbal tea containing fennel to neurotoxicity in two breast-feeding infants.¹⁹

Effectiveness:

POSSIBLY EFFECTIVE

Colic. A clinical trial shows that breast-fed infants with colic, who are given a specific multi-ingredient product containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg (Colimil) twice daily for a week, have reduced crying times compared to placebo.¹⁸

There is insufficient scientific information available about the effectiveness of fennel for other uses.

Mechanism of Action:

Fennel seed is a rich source of beta-carotene and vitamin C.²⁰ It also contains significant amounts of calcium, magnesium, and iron, and lesser amounts of other metal ions. The seed contains a volatile oil.²¹ The anethole constituent gives fennel its anise-type aroma and flavor.

Adverse Reactions:

Fennel side effects have not been systematically evaluated in clinical research. One clinical trial in infants did not find a significant difference in adverse events compared to placebo.¹⁸

Overall low allergic potential except for a small subgroup that cannot tolerate celery, fennel, carrot or mugwort. These are all from the same plant family.^{R1 pp.383}

Interactions with Herbs & Supplements:

None known.

Interactions with Drugs:

Ciproflozacin (Cipro)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = D

Concomitant use of fennel and ciprofloxacin might reduce the effectiveness of ciprofloxacin. Preliminary evidence suggests that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. Evidence also suggests that fennel increases tissue distribution and slows elimination of ciprofloxacin.²¹

Interactions with Foods:

As above

Interactions with Lab Tests:

None known.

Dosage/Administration:

Oral: No typical dosage. However, traditionally a tea prepared from 1-2 grams of the crushed or ground fruit or seed in 150 mL boiling water has been used. The common dose of the tincture compound is 5-7.5 grams per day. Fennel should be used on a short-term basis. For colic in infants, a specific multi-ingredient product containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg (Colimil) twice daily for a week has been used.¹⁸

Dr Clare’s Comments:

A very well tolerated herb.  Particularly good for wind and bloating.  I have not had a patient who had to give up fennel because of side effects. Many people like the taste as it is somewhat sweet.  Fennel is native to the Mediterranean, but is now found throughout the world. 

Specific References: FENNEL

17.  FDA. Center for Food Safety and Applied Nutrition, Office of Premarket Approval, EAFUS: A food additive database. Available at: vm.cfsan.fda.gov/~dms/eafus.html.

18.  Savino F, Cresi F, Castagno E, et al. A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officinalis (ColiMil) in the treatment of breastfed colicky infants. Phytother Res 2005;19:335-40.

19.  Rosti L, Nardini A, Bettinelli ME, Rosti D. Toxic effects of a herbal tea mixture in two newborns. Acta Paediatrica 1994;83:683.

20.  Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.

21.  Zhu M, Wong PY, Li RC. Effect of oral administration of fennel (Foeniculum vulgare) on ciprofloxacin absorption and disposition in the rat. J Pharm Pharmacol 1999;51:1391-6.

Also Known As:

Melissa

Scientific Name:

Melissa officinalis.

Family: Lamiaceae/Labiatae.

People Use This For:

Orally, lemon balm is used for anxiety, insomnia, dyssomnia, restlessness, dyspepsia, bloating, flatulence, colic, and for attention deficit-hyperactivity disorder (ADHD). Lemon balm is also used for Graves' disease (overactive thyroid), painful periods, cramps and headache. It is also used orally for Alzheimer's disease, melancholia, nervous palpitations, vomiting, and high blood pressure.

Topically, lemon balm is used for cold sores (herpes labialis).

Safety:

No concerns regarding safety when used orally in amounts commonly found in foods.

Possibly Safe when used orally or topically and appropriately, short-term. Lemon balm has been used with apparent safety for up to 4 months.^{76,77,78,79,80}

There is insufficient scientific information to comment about the safety of lemon balm when used long-term.

Children: Possibly Safe when used orally and appropriate, short-term. A specific combination product providing lemon balm leaf extract 80 mg and valerian root extract 160 mg (Euvegal forte, Dr. Willmar Schwabe Pharmaceuticals) 1-2 tablets once or twice daily has been safely used in children under age 12 years for about a month.⁸¹ Preliminary clinical research also suggests that a specific multi-ingredient product containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg (Colimil) is safe in infants when used for up to a week.⁸²

Pregnancy and Lactation: Refer to a Medical Herbalist

Effectiveness:

POSSIBLY EFFECTIVE

Alzheimer's disease. Taking a standardized extract of lemon balm orally, daily for 4 months, seems to reduce agitation and improve symptoms of mild to moderate Alzheimer's disease on standard Alzheimer's disease rating scales.⁷⁷

Colic. A clinical trial shows that breast-fed infants with colic who are given a specific multi-ingredient product containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg (Colimil) twice daily for a week have reduced crying times compared to placebo.⁸²

Dyspepsia. A specific combination product containing lemon balm (Iberogast, Medical Futures, Inc) seems to improve symptoms of dyspepsia. The combination includes lemon balm plus peppermint leaf, German chamomile, caraway, licorice, clown's mustard plant, celandine, angelica, and milk thistle.^{83, 80} A meta-analysis of studies using this combination product suggests that taking 1 mL orally three times daily over a period of 4 weeks significantly reduces severity of acid reflux, epigastric pain, cramping, nausea, and vomiting compared to placebo.⁸⁴

Herpes labialis (cold sores). Applying a lip balm containing 1% lemon balm extract seems to shorten healing time, prevent infection spread, and reduce symptoms of recurring cold sores.^76,79

Sleep. Taking a specific combination product providing lemon balm leaf extract 80 mg and valerian root extract 160 mg (Euvegal forte, Dr. Willmar Schwabe Pharmaceuticals) three times daily appears to improve the quality and quantity of sleep in healthy people.⁸⁵

INSUFFICIENT RELIABLE EVIDENCE to RATE

Restless Sleep. Preliminary evidence suggests that a specific combination product providing lemon balm leaf extract 80 mg and valerian root extract 160 mg 

(Euvegal forte, Dr. Willmar Schwabe Pharmaceuticals) 1-2 tablets once or twice daily might decrease symptoms in children under age 12 years who have pathological restlessness.⁸¹ More evidence is needed to rate lemon balm for this use.

Mechanism of Action:

The applicable part of lemon balm is the leaf. Lemon balm seems to have sedative, antioxidant, and antiviral effects.^76,77,78,79 Lemon balm contains citronellal, neral, and geranial aldehydes; flavonoids and polyphenolic compounds; and monoterpene glycosides. These substances may contribute to the behavioral effects of lemon balm leaf and essential oil.⁷⁸ Clinical research suggests that lemon balm induces a calming effect and reduces alertness.⁷⁸

Adverse Reactions:

Orally, lemon balm is well tolerated. Rarely it may cause nausea, vomiting, abdominal pain, dizziness, and wheezing.⁷⁷

Topically, there is one report of irritation and one report of exacerbation of herpes symptoms when lemon balm was applied.⁷⁶

Interactions with Herbs & Supplements:

Additive effect with other nervine (relaxing) herbs.

Interactions with Drugs:

CNS Depressants: Theoretically, concomitant use of lemon balm with drugs with sedative properties may cause additive effects and side effects.⁷⁸

Interactions with Foods:

None reported

Interactions with Lab Tests:

None known.

Interactions with Diseases or Conditions:

Thyroid Disorders: In laboratory studies thyroid hormone release is affected by Lemonbalm. No reported clinical cases.

Glaucoma: Animal studies incicate there may be a problem. No reported clinical cases.

Surgery: Tell patients to discontinue lemon balm at least 2 weeks before elective surgical procedures.

Dosage/Administration:

Dr Clare’s Blends: 1 gm per day

Oral: For mild to moderate Alzheimer's disease, 60 drops per day of a standardized lemon balm extract, prepared 1:1 in 45% alcohol, has been used.⁷⁷

For improving sleep in healthy adults, a specific combination product providing lemon balm leaf extract 80 mg and valerian root extract 160 mg (Euvegal forte, Dr. Willmar Schwabe Pharmaceuticals) 3 times daily has been used for up to 30 days.⁸⁵

For colic in infants, a specific multi-ingredient product containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg (Colimil) twice daily for a week has been used,⁸²

For dyspepsia, a specific combination product containing lemon balm (Iberogast, Medical Futures, Inc) and several other herbs has been used in a dose of 1 mL three times daily.^83,80,84

For dyssomnia in children, a specific combination product providing lemon balm leaf extract 80 mg and valerian root extract 160 mg (Euvegal forte, Dr. Willmar Schwabe Pharmaceuticals) 1-2 tablets once or twice daily has been used.8¹

Topical: For herpes labialis (cold sores), the cream or ointment containing 1% of a 70:1 lyophilized aqueous extract is usually applied two to four times daily from first symptom to a few days after the lesions have healed.^76,79

Specific References: LEMON BALM

76.  Wolbling RH, Leonhardt K. Local therapy of herpes simplex with dried extract from Melissa officinalis. Phytomedicine 1994;1:25-31.

77.  Akhondzadeh S, Noroozian M, Mohammadi M, et al. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry 2003;74:863-6.

78.  Kennedy DO, Scholey AB, Tildesley NT, et al. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav 2002;72:953-64.

79.  Koytchev R, Alken RG, Dundarov S. Balm mint extract (Lo-701) for topical treatment of recurring herpes labialis. Phytomedicine 1999;6:225-30.

80.  Madisch A, Holtmann G, Mayr G, et al. Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial. Digestion 2004;69:45-52.

81.  Muller SF, Klement S. A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine 2006;13:383-7.

82.  Savino F, Cresi F, Castagno E, et al. A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officinalis (ColiMil) in the treatment of breastfed colicky infants. Phytother Res 2005;19:335-40.

83.  Holtmann G, Madisch A, Juergen H, et al. A double-blind, randomized, placebo-controlled trial on the effects of an herbal preparation in patients with functional dyspepsia [Abstract]. Ann Mtg Digestive Disease Week 1999 May.

84.  Melzer J, Rosch W, Reichling J, et al. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther 2004;20:1279-87.

85.  Cerny A, Shmid K. Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double blind, placebo-controlled, multicentre study). Fitoterapia 1999;70:221-8.

Also Known As:

Chinese Licorice. 

Scientific Name:

Glycyrrhiza glabra; 

Family: Fabaceae/Leguminosae.

People Use This For:

Licorice is used for stomach and duodenal ulcers, sore throat, bronchitis, gastritis, indigestion, colic, insufficiency of the adrenal cortex and cough. In combination with Panax ginseng and Bupleurum falcatum, licorice is used orally to help stimulate adrenal gland function, particularly in patients with a history of long-term corticosteroid use. As a component of the herbal formula, Shakuyaku-Kanzo-To, licorice is used to increase fertility in women with polycystic ovary syndrome. In combination with other herbs, licorice is used to treat prostate cancer and eczema.

Safety:

No concerns regarding safety when used orally in amounts commonly found in foods. 

Possibly Safe when used orally and appropriately for medicinal purposes in the short-term.^{23,24,25,26,29,32}

Long-term use increases the risk of side effects such as hypertension and low potassium³³ in susceptible people. 

Pregnancy and Lactation: Refer to a Medical Herbalist.

Effectiveness:

POSSIBLY EFFECTIVE

Dyspepsia. A specific combination product containing licorice (Iberogast, Medical Futures, Inc) seems to improve symptoms of dyspepsia. The combination includes licorice plus peppermint leaf, German chamomile, caraway, lemon balm, clown's mustard plant, celandine, angelica, and milk thistle.^30,27 A meta-analysis of studies using this combination product suggests that taking 140 mL orally three times daily over a period of 4-weeks significantly reduces severity of acid reflux, stomach pain, cramping, nausea, and vomiting compared to placebo.³¹

INSUFFICIENT SCIENTIFIC EVIDENCE to VERIFY:

Muscle cramps. Preliminary clinical research suggests taking a specific combination of licorice and peony may reduce muscle cramps in patients with hepatic cirrhosis or in patients undergoing hemodialysis.^34,35,36

Peptic ulcers. There is some evidence that deglycyrrhizinated licorice might accelerate the healing of peptic ulcers.^29,32

Weight loss. There is conflicting information about the use of licorice for weight loss. Licorice has been shown to reduce body fat, however accompanying fluid retention offsets any change in body weight.²⁶

More evidence is needed to rate licorice for these uses. 

Mechanism of Action:

The applicable part of licorice is the root. Licorice has antispasmodic, anti-inflammatory, laxative, and soothing properties.

Licorice appears to block metabolism of prostaglandins linked to inflammation, which suggests the possible beneficial effect on peptic ulcer. 

Cortisol promotes sodium and water retention and potassium excretion.^28,37,38,41Excessive licorice ingestion can therefore produce a syndrome of apparent excess of adrenal cortical hormones leading to increased urinary potassium loss and hypertension.^{42,43,44,45,46,39,40,41}

There is considerable variation in the amount of licorice needed to cause these effects, due in part to variation in the glycyrrhizic acid content of licorice preparations. There is also variation in people's response to licorice. Those with hypertension, heart disease, kidney disease, or a high salt intake are more sensitive to its effects.^47,37,40,41 Finally, case reports of adverse reactions to licorice do not always make it clear whether licorice intake is in grams of pure licorice, or grams of sweet licorice candy or salty licorice or another preparation.

The increases in blood pressure, and cortisol to cortisone ratio are proportional to the amount of glycyrrhizic acid ingested.³³

Licorice appears to have anti-estrogenic and estrogenic action. Preliminary research indicates that licorice does not stimulate the growth of estrogen dependent breast cancer cells.⁴⁸ However, the estrogenic effects of licorice might be concentration dependent. Glabridin, an isoflavone constituent of licorice, seems to have an estrogen receptor-dependent growth-promoting effect at low concentrations. At higher concentrations, it seems to have an estrogen receptor-independent antiproliferative effect.⁵¹  

Adverse Reactions:

Orally. excessive licorice ingestion can cause a problem with overproduction of adrenal cortex hormones.^{42,28,43,44,37,38,45,46,39,40,41,52,53} These effects are most likely to occur when 30 grams or more of licorice is consumed daily for several weeks.^{42,49,4438,46,39,50,41,53}  

Interactions with Herbs & Supplements:

Cardiac Glycoside-Containing Herbs: None commonly found in products in Ireland.

Stimulant Lasative Herbs: Excessive amounts can be an issue. 

Interactions with Drugs:

Antihypertensive Drugs: Refer to Medical Herbalist

Corticosteroids: Refer to Medical Herbalist

Digoxin: Refer to Medical Herbalist

Diuretic Drugs: Refer to Medical Herbalist.

Estrogens: Avoid high dosages and prolonged treatment.^{R1 pp.474}

Warfarin: (Coumadin)

Interactions with Foods:

Grapefruit Juice: Theoretically, grapefruit juice and its component naringenin might enhance the mineralocorticoid activities of licorice, by blocking the conversion of cortisol to cortisone.^54,55

Salt: A high salt diet can exacerbate adverse effects of licorice such as sodium and water retention and hypertension.⁴¹

Interactions with Lab Tests:

1407-Hydroxyprogesterone: Licorice can increase serum 1407-hydroxyprogesterone concentrations and test results in healthy volunteers who consume 7 grams of licorice per day.^56,57

Potassium: Excessive use of licorice can affect Potassium levels

Interactions with Diseases or Conditions:

Heart Disease: Refer to a Medical Herbalist.

Hormone Sensitive Cancers/Conditions: As above.

Hypertension: Advise patients with hypertension to avoid excessive amounts of licorice.^58,59

Kidney Insufficiency: Advise patients with severe renal insufficiency to avoid excessive amounts of licorice.⁶⁰

Surgery: discontinue licorice 2 weeks before elective surgical procedures.

Dosage/Administration:

Dr Clare’s Blends: has a recommended dose of 5mls per week i.e 140.4mls per day of 140:3 extract = ½ gram daily.

Oral: For dyspepsia, a specific combination product containing licorice (Iberogast, Medical Futures, Inc) and several other herbs has been used in a dose of 140 mL three times daily.^30,27,31 

2-6ml/day of 140:140 extract

6-1402ml/day of 140:3 extract

Dried Root 140-4gms per day. 

Dr Clare’s Comment:

The effect of liquorice on the Adrenal Glands is beneficial for most patients, however a small group of patients are sensitive to the effects on blood pressure. Under normal circumstances this would not be significant for short term low dose use. It can be monitored by taking blood pressure and many chemists have a blood pressure machine patients can check during treatment if you do not have resources to check the blood pressure.

Specific References: LICORICE

23. Abe Y, Ueda T, Kato T, Kohli Y. [Effectiveness of interferon, glycyrrhizin combination therapy in patients with chronic hepatitis C]. [Article in Japanese]. Nippon Rinsho 140994;52:14081407-22.

24. Acharya SK, Dasarathy S, Tandon A, et al. A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure. Indian J Med Res 140993;98:69-74.

25. Zhang XH, Lowe D, Giles P, et al. Gender may affect the action of garlic oil on plasma cholesterol and glucose levels of normal subjects. J Nutr 200140;1403140:14047140-8.

26. Armanini D, De Palo CB, Mattarello MJ, et al. Effect of licorice on reduction of body fat mass in healthy subjects. J Endocrinol Invest 2003;26:646-50.

27. Madisch A, Holtmann G, Mayr G, et al. Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial. Digestion 2004;69:45-52.

28. Hussain RM. The sweet cake that reaches parts other cakes can't! Postgrad Med J 2003;79:1401405-6.

29. Turpie AG, Runcie J, Thomson TJ. Clinical trial of deglydyrrhizinized liquorice in gastric ulcer. Gut 140969;1400:299-302.

30. Holtmann G, Madisch A, Juergen H, et al. A double-blind, randomized, placebo-controlled trial on the effects of an herbal preparation in patients with functional dyspepsia [Abstract]. Ann Mtg Digestive Disease Week 140999 May.

31. Melzer J, Rosch W, Reichling J, et al. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther 2004;20:140279-87.

32. Tewari SN, Wilson AK. Deglycyrrhizinated liquorice in duodenal ulcer. Practitioner 140973;21400:820-3.

33. Sigurjonsdottir HA, Franzson L, Manhem K, et al. Liquorice-induced rise in blood pressure: a linear dose-response relationship. J Hum Hypertens 200140;1405:549-52.

34. Kumada T, et al. Effect of Shakuyaku-kanzo-to (Tsumura TJ-68) on muscle cramps accompanying cirrhosis in a placebo-controlled double-blind parallel study. J Clin Ther Med 140999;1405:499-523.

35. Hyodo T, Taira T, Kumakura M, et al. The immediate effect of Shakuyaku-kanzo-to, traditional Japanese herbal medicine, for muscular cramps during maintenance hemodialysis. Nephron 2002;90:240

36. Hinoshita F, Ogura Y, Suzuki Y, et al. Effect of orally administered shao-yao-gan-cao-tang (Shakuyaku-kanzo-to) on muscle cramps in maintenance hemodialysis patients: a preliminary study. Am J Chin Med 2003;3140:445-53.

37. Elinav E, Chajek-Shaul T. Licorice consumption causing severe hypokalemic paralysis. Mayo Clin Proc 2003;78:767-8.

38. Eriksson JW, Carlberg B, Hillom V. Life-threatening ventricular tachycardia due to liquorice-induced hypokalemia. J Intern Med 140999;245:307-1400.

39. van den Bosch AE, van der Klooster JM, Zuidgeest DM, et al. Severe hypokalemic paralysis and rhabdomyolysis due to ingestion of liquorice. Neth J Med 2005;63:14046-8.

40. van Uum SH. Liquorice and hypertension. Neth J Med 2005;63:1401409-20.

41. Stormer FC, Reistad R, Alexander J. Glycyrrhizic acid in liquorice - evaluation of health hazard. Food Chem Toxicol 140993;3140:303-1402.

42. Farese RV Jr, Biglieri EG, Shackleton CH, et al. Licorice-induced hypermineralocorticoidism. N Engl J Med 14099140;325:140223-7.

43. de Klerk GJ, Nieuwenhuis G, Beutler JJ. Hypokalemia and hypertension associated with use of liquorice flavoured chewing gum. BMJ 140997;31404:73140-2.

44. Dellow EL, Unwin RJ, Honour JW. Pontefract cakes can be bad for you: refractory hypertension and liquorice excess. Nephol Dial Transplant 140999;1404:21408-20.

45. Janse A, van Iersel M, Hoefnagels WH, Olde Rikker MG. The old lady who liked liquorice: hypertension due to chronic intoxication in a memory-impaired patient. Neth J Med 2005;63:14049-50.

46. Lin SH, Yang SS, Chau T, Halperin ML. An unusual cause of hypokalemic paralysis: chronic licorice ingestion. Am J Med Sci 2003;325:14053-6.

47. Yasue H, Itoh T, Mizuno Y, Harada E. Severe hypokalemia, rhabdomyolysis, muscle paralysis, and respiratory impairment in a hypertensive patient taking herbal medicines containing licorice. Intern Med 2007;46:575-8.

48. Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause 2002;9:14045-50.

49. Brayley J, Jones J. Life-threatening hypokalemia associated with excessive licorice ingestion (letter). Am J Psychiatry 140994;1405140:61407-8.

50. Russo S, Mastropasqua M, Mosetti MA, et al. Low doses of liquorice can induce hypertension encephalopathy. Am J Nephrol 2000;20:14045-8.

51. Tamir S, Eizenberg M, Somjen D, et al. Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cells. Cancer Res 2000;60:5704-9.

52. Sontia B, Mooney J, Gaudet L, Touyz RM. Pseudohyperaldosteronism, liquorice, and hypertension. J Clin Hypertens (Greenwich) 2008;1400:14053-7.

53. Lapi F, Gallo E, Bernasconi S, et al. Myopathies associated with red yeast rice and liquorice: spontaneous reports from the Italian Surveillance System of Natural Health Products. Br J Clin Pharmacol 2008;66:572-4.

54. Lee YS, Lorenzo BJ, Koufis T, et al. Grapefruit juice and its flavonoids inhibit 140140 beta-hydroxysteroid dehydrogenase. Clin Pharmacol Ther 140996;59:62-7140.

55. Zhang YD, Lorenzo B, Reidenberg MM. Inhibition of 140140 beta hydroxysteroid dehydrogenase obtained from guinea pig kidney by furosemide, naringenin and some other compounds. J Steroid Biochem Mol Biol 140994;49:8140-5.

56. Armanini D, Bonanni G, Palermo M, et al. Reduction of serum testosterone in men by licorice. N Engl J Med 140999;34140:14014058.

57. Armanini D, Bonanni G, Mattarello MJ, et al. Licorice consumption and serum testosterone in healthy man. Exp Clin Endocrinol Diabetes 2003;140140140:34140-3.

58. Sigurjonsdottir HA, Ragnarsson J, Franzson L, Sigurdsson G. Is blood pressure commonly raised by moderate consumption of liquorice? J Hum Hypertens 140995;9:345-8.

59. Francini-Pesenti F, Puato M, Piccoli A, Brocadello F. Liquorice-induced hypokalaemia and water retention in the absence of hypertension. Phytother Res 2008;22:563-5.

60. Quinkler M, Stewart PM. Hypertension and the cortisol-cortisone shuttle. J Clin Endocrinol Metab 2003;88:2384-92.

Also known as: Bridewort, Dropwort, Filipendula, Lady of the Meadow, Meadow Queen, Meadow-Wort, Queen of the Meadow, Spiraeae Flos, Spireae Herba.

Scientific Name: Filipendula ulmaria, Filipendula spiraea.

Family: Rosaceae.

Parts used: Flowers, stems, leaves.

Traditional use.

Meadowsweet is used for colds, bronchitis, dyspepsia, heartburn, peptic ulcer disease, and rheumatic disorders including gout. It is also used as a diuretic and urinary antiseptic for acute cystitis.

Safety.

There are no safety concerns when used appropriately. ⁽⁴⁾  One case report on the use of a blend of herbs including meadowsweet has been reported in a child presenting with bleeding from the upper digestive system.⁽¹⁵⁾

As tannins precipitate proteins it is suggested that it is taken between meals if you have a low protein diet. This also applies to tea, red wine and dark chocolate. I have not witnessed any such concerns in clinical practice. Theoretically salicylates may be associated with Reyes syndrome although no cases have been reported with meadowsweet.

Pregnancy:Consult a medical herbalist.

Breastfeeding; Consult a medical herbalist.

Constituents.

Volatile oils containing salicylaldehyde, ethylsalicylate, methylsalicylate, methoxybenzaldehyde and others.

Phenolic glycosides; spirein, monotropitin (gaultherin), these are the primeverosides of salicyl aldehyde and methyl methyl salicylate.; also isosalicin.

Flavonoids; spiraeoside, rutin, quercitin, hyperoside, avicularin.

Tannins (polyphenols); mainly hydrolysable tannins.

Miscellaneous; phenylcarboxylic acids, traces of coumarin, ascorbic acid (vitamin C).

Scientific evidence.

No clinical studies have been done.

Mechanism of action.

Meadowsweet has stomachic, mild urinary antiseptic, diuretic, anti-rheumatic, astringent, and antacid activities.⁽¹⁾ In laboratory studies meadowsweet demonstrates anti-inflammatory effects on pro-inflammatory mediators (cytokines) and on scavenger cells.⁽[1]^,7,8) Meadowsweet is a rich source of anti-oxidants.⁽¹⁴⁾It contains tannins and salicin, a plant salicylate. ^(2,4) In animals, meadowsweet decreases motor activity, lowers temperature, induces muscle relaxation, and increases the effect of codeine related pain relieving substances. ⁽¹⁾ In animals the flower extract increases life expectancy, decreases vascular permeability, increases bronchial, intestinal, and uterine tone and promotes uric acid excretion. In laboratory studies it inhibits the growth of bacteria (bacteriostatic activity).⁽¹⁾ Water extracts of Meadowsweet contain high concentrations of tannins with astringent effects. ⁽¹⁾Meadowsweet exhibited protective properties in liver cells exposed to toxins.⁽⁶⁾ This extract produced a normalizing effect on activity of protective enzymes including markers of cell breakdown, lipid peroxidation, and antioxidant defense system in liver cells. In animal studies meadowsweet demonstrated a positive effect on renal blood flow resulting in a diuretic effect.⁽⁹⁾

Interestingly a recent study showed an anxiolytic effect of Meadowsweet extract on mice, this is in keeping with the herbal tradition of digestive health being central to your sense of well-being.⁽¹⁰⁾

In laboratory research meadowsweet demonstrated anti-bacterial actions including H. Pylori which is implicated in the pathology of peptic ulcers.^(11,13)

Meadowsweet demonstrates inhibitory properties on the enzyme xanthine oxidase which is the primary target for the treatment of gout. ⁽¹²⁾

Adverse Reactions.

For a small percentage of people Meadowsweet can cause minor digestive problems.⁽⁵⁾ There is no way to predict this except they are often people who have poor tolerance to prescription drugs.

Wheeze (bronchospasm) has rarely been reported.⁽¹⁾

In keeping with Willow Bark there may theoretically be side effects of overall increased salicylic acid exposure. This is unlikely with low dose aspirin but vigilance is recommended.

Interactions with herbs and supplements:

None known.

Interactions with Drugs.

Aspirin.

Salicylate drugs as described.

Salicin doesn't seem to have the antiplatelet effects of aspirin on blood clotting. ⁽⁴⁾

Salicylate medication

Meadowsweet contains salicin, a plant salicylate. Theoretically, meadowsweet might have an additive effect with other salicylate-containing drugs such as aspirin, NSAIDs andcholine magnesium trisalicylate. ⁽⁴⁾

Narcotic drugs e.g. codeine.

Theoretically, meadowsweet can enhance the effects of codeine like drugs. ⁽¹⁾

Interactions with foods.

None known.

Interactions with laboratory tests.

None known.

Interactions with diseases or conditions.

Aspirin allergy: Use meadowsweet cautiously in individuals with aspirin allergy because of salicylate constituents.

Asthma: In theory meadowsweet might exacerbate asthma due to bronchospastic effects. Observe for effects on symptoms if you are asthmatic. ⁽¹⁾ In fifteen years of herbal medicine practice I have not observed this effect nor has it been reported by others, but it is worth bearing in mind.

Dosage.

Recommended dose: 6-12mls per day 1:5 tincture 30% alcohol.

Infusion: range from 1-1½ tsps. per day.

Powder/capsule: range from 1.5-3gms per day.

Liquid extract: 2-6mls 1:2 in 30% alcohol per day.

Dr. Clare’s Blend: ½ tsp. per day.

References:

1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

1. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physician's Guide to Herbal Medicine. Terry C. Telger, transl. 3rd ed. Berlin, GER: Springer, 1998.

1. Wichtl MW. Herbal Drugs and Phytopharmaceuticals. Ed. N.M. Bisset. Stuttgart: Medpharm GmbH Scientific Publishers, 1994.

1. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.

1. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.

         Phenolic Extracts from Meadowsweet and Hawthorn Flowers Have Antioxidative Properties. Zbigniew Sroka, Wojciech Cisowski, Magdalena Seredyn ́ska and Maria Łuczkiewicz.

Z. Naturforsch, 56c, 739Ð744 (2001); received July 13, 2000/April 6, 2001.

6. I. V. Shilova, T. V. Zhavoronok, N. I. Souslov, T. P. Novozheeva, R. N. Mustafin, A. M. Losseva. Hepatoprotective properties of fractions from meadowsweet extract during experimental toxic hepatitis. Bulletin of Experimental Biology and Medicine. July 2008, Volume 146, Issue 1, pp 49-51.

7. Elaine M Drummond, Niamh Harbourne, Eunice Marete, Danika Martyn, JC Jacquier, Dolores O'Riordan andEileen R Gibney^.. Inhibition of Proinflammatory Biomarkers in THP1 Macrophages by Polyphenols Derived From Chamomile, Meadowsweet and Willow bark. Phytotherapy Research

Volume 27, Issue 4, pages 588–594, April 2013

        8. Elaine M. Drummond, Harbourne N, Marete E, Jacquier J.C, O'Riordan D, Gibney E.R. An In Vivo Study Examining the Antiinflammatory Effects of Chamomile, Meadowsweet, and Willow Bark in a Novel Functional Beverage. Journal of dietary Supplements. December 2013, Vol. 10, No. 4 , Pages 370-380.

        9. Bernatoniene J,  Savicka A, Bernatoniene J, Kalvéniené Z, Klimas R. Kaunas University of Medicine.

        The Effect of Meadowsweet (Filipendula ulmaria) Flower Extract and Hydrothiazide on Renal Physiological Function in Rats.

Book: Functional Foods for Chronic Diseases.

10. V. V. Udut, A. I. Vengerovskii, N. I. Suslov, I. V. Shilova, A. V. Kaigorodtsev, N. Yu. Polomeeva, A. M. Dygai. Pharmaceutical Chemistry Journal.  November 2012, Volume 46, Issue 8, pp 492-494

Anxiolytic activity of biologically active compounds from Filipendula vulgaris

            11. RauhaJP, RemesS, HeinonenM et al. Anu Hopia^b, Marja Kähkönen^b, Tytti Kujala^c, Kalevi Pihlaja^c, Heikki Vuorela^a, Pia Vuorela^. Antimicrobial effects of Finnish plant extracts containing flavonoids and other phenolic compounds. International Journal of Food Microbiology. Volume 56, Issue 1, 25 May 2000, Pages 3–12

        12. Kazazi F,  Halkes SBA, Quarles van Ufford  HV, Beukelman CJJ, Van den Berg AJJ. Inhibition of xanthine oxidase activity by Filipendula species. Planta Med 2009; 75 - PA3

        13. Cwikla C, K Schmidt K,  Matthias A, KM Bone KM, RP Lehmann RP, E Tiralongo E. Investigations into the antibacterial activities of herbal medicines against Helicobacter pylori and Campylobacter jejuni. Planta Med 2008; 74 - PA103.

        14. Barros L, Cabrita L, Vilas Boas M, Carvalho AM, Ferreira ICFR. Chemical, biochemical and electrochemical assays to evaluate phytochemicals and antioxidant activity of wild plants.

                            Food Chemistry. Volume 127, Issue 4, 15 August 2011, Pages 1600–1608.

        15. Annali dell'Istituto Superiore di Sanità

        Ann. Ist. Super. Sanità vol.47 n.3 Roma Jan. 2011.

Also Known As:

Blessed Milk Thistle, Carduus Marianum, Holy Thistle, Silybum, Silymarin, St. Mary Thistle, St. Marys Thistle.

Scientific Name:

Silybum marianum, synonym Carduus marianus.

Family: Asteraceae/Compositae.

People Use This For:

Milk thistle is used for liver disorders including toxic liver damage caused by chemicals, Amanita phalloides mushroom poisoning, jaundice, chronic inflammatory liver disease, hepatic cirrhosis, and chronic hepatitis. It is also used orally for loss of appetite, dyspepsia and gallbladder complaints, diabetes, hangover, and diseases of the spleen. Milk thistle is used orally for stimulating breast milk flow, and stimulating menstrual flow.

In foods, the milk thistle leaves and flowers are eaten as a vegetable and seeds are roasted for use as a coffee substitute.

Safety:

No concerns regarding safety when used orally and appropriately. Milk thistle extracts standardized to contain 70% to 80% of the silymarin constituent seems to be safe when used for up to 41 months.^{38,39,40,41,42,43,44,45}

Pregnancy and Lactation: Refer to a Medical Herbalist.

Effectiveness:

POSSIBLY EFFECTIVE

Diabetes. Taking the milk thistle constituent silymarin 200 mg three times daily for 4 months, in combination with conventional treatment, appears to significantly decrease fasting blood glucose, hemoglobin A1c (HbA1c), total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides compared to placebo in patients with type 2 diabetes.⁴⁵ Other preliminary evidence suggests that silymarin 200 mg three times daily reduces insulin resistance in people with coexisting diabetes and alcoholic cirrhosis.⁴⁶

Dyspepsia. A specific combination product containing milk thistle (Iberogast, Medical Futures, Inc) seems to improve symptoms of dyspepsia. The combination includes milk thistle plus peppermint leaf, German chamomile, caraway, licorice, clown's mustard plant, celandine, angelica, and lemon balm.^47,48 A meta-analysis of studies using this combination product suggests that taking 1 mL orally three times daily over a period of 4 weeks significantly reduces severity of acid reflux, epigastric pain, cramping, nausea, and vomiting compared to placebo.⁴⁹

INSUFFICIENT SCIENTIFIC EVIDENCE to COMMENT

Alcohol-related liver disease. 

Hepatitis B or Hepatitis C. 

More evidence is needed to rate milk thistle for these uses.

Mechanism of Action:

The applicable parts of milk thistle are the seed and above ground parts. The seed is most commonly used medicinally. Silymarin, the active constituent of the milk thistle seed, consists of four flavonolignans called silibinin (silybinin, silybin), isosilybinin, silichristin (silychristin), and silidianin. Silibinin makes up about 70% of silymarin.^50,51 When ingested, silymarin undergoes enterohepatic recirculation and has higher concentrations in liver cells.

Adverse Reactions:

Milk thistle is usually well-tolerated.^52,51 

Interactions with Herbs & Supplements:

None known.

Interactions with Drugs:

Tamoxifen (Nolvadex): (Used for breast cancer). Theoretical risk. Refer to a Medical Herbalist.

Interactions with Foods:

None known.

Interactions with Lab Tests:

None known.

Dosage/Administration:

For diabetes, silymarin 200 mg three times daily has been used in combination with conventional treatment.^46,45

References: MILK THISTLE

38.  Szilard S, Szentgyorgyi D, Demeter I. Protective effect of Legalon in workers exposed to organic solvents. Acta Med Hung 1988;45:249-56.

39.  Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989;9:105-13.

40.  Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind, controlled study. Scand J Gastroenterol 1982;17:517-21.

41.  Bunout D, Hirsch S, Petermann M. [Controlled study of the effect of silymarin on alcoholic liver disease.] [Article in Spanish]. Rev Med Chil 1992;120:1370-5.

42.  Trinchet JC, Coste T, Levy VG. [Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients]. [Article in French]. Gastroenterol Clin Biol 1989;13:120-4.

43.  Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998;28:615-21.

44.  Rambaldi A, Jacobs B, Iaquinto G, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev 2005;2:CD003620.

45.  Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 2006;20;1036-9.

46.  Velussi M, Cernigoi AM, De Monte A, et al. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol 1997;26:871-9.

47.  Holtmann G, Madisch A, Juergen H, et al. A double-blind, randomized, placebo-controlled trial on the effects of an herbal preparation in patients with functional dyspepsia [Abstract]. Ann Mtg Digestive Disease Week 1999 May.

48.  Madisch A, Holtmann G, Mayr G, et al. Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial. Digestion 2004;69:45-52.

49.  Melzer J, Rosch W, Reichling J, et al. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther 2004;20:1279-87.

50.  Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3.

51.  Boerth J, Strong KM. The clinical utility of milk thistle (Silybum marianum) in cirrhosis of the liver. J Herb Pharmacother 2002;2:11-7.

52.  Anon. Milk thistle: Effects on liver disease and cirrhosis and clinical adverse effects. Summary, Evidence Report/Technology Assessment: Number 21, September 2000. Agency for Healthcare Research and Quality, Rockville, MD. Available at: http://www.ahrq.gov/clinic/epcsums/milktsum.htm

53.  Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 2006;20;1036-9.