Dr Clare Materia Medica

Garlic

Also Known As:

Aged Garlic Extract, Ail, Ajo, Allii Sativi Bulbus, Allium.

Scientific Name:

Allium sativum.

Family: Alliaceae or Liliaceae.

People Use This For:

Garlic is used for hypertension, hyperlipidemia, coronary heart disease, age-related vascular changes and atherosclerosis, myocardial infarction, earaches, chronic fatigue syndrome, and menstrual disorders. Garlic is also used to treat Helicobacter pylori infection. Other uses include treatment of allergic rhinitis, traveller's diarrhoea, colds, and flu. It is also used for immune system stimulation, and prevention and treatment of bacterial and fungal infections. Other uses include treatment of fever, coughs, headache, stomachache,sinus congestion, athlete's foot, gout, rheumatism, bronchitis, low blood pressure. It is also used as an aphrodisiac, for enhancing circulation, fighting stress and fatigue.

Topically, garlic oil is used for fungal infections.

Intravaginally, garlic is used alone or in combination with yogurt for vaginitis.

In foods and beverages, fresh garlic, garlic powder, and garlic oil are used as flavour components.

Safety:

No concerns regarding safety when used orally and appropriately. Garlic has been used safely in clinical studies lasting up to 7 years without reports of significant toxicity.63,64,65,66,67,68,69,70,71,72,73,74,75,76

Children: Likely to be safe when used orally and appropriately, short-term. In one study, garlic extract 300 mg three times daily had side effects comparable to placebo when used in children ages 8-18 years for eight weeks.77 There are no case reports available of significant adverse events or mortality in children associated with ingestion of garlic.

Pregnancy and Lactation: No concerns regarding safety when used orally in amounts commonly found in foods.78

Effectiveness:

POSSIBLY EFFECTIVE

Atherosclerosis. Taking low doses of garlic powder orally, 300 mg per day, seems to lessen age-related decreases in aortic elasticity.

Higher doses of 900 mg per day seem to slow development of atherosclerosis in both aortic and

femoral arteries when used over a four-year period.79,72,73

Gastric cancer. Some evidence from population studies suggests that increasing dietary garlic consumption is associated with a decreased risk of developing stomach cancer.84,85,86

High Blood Pressure. Some clinical research shows that taking garlic orally can modestly reduce blood pressure in patients with hypertension and in people with normal blood pressure.87,88,89,63,75,90

In one analysis, garlic reduced systolic blood pressure by about 8% and diastolic blood pressure by about 7%, compared to placebo in patients with hypertension.90

Ringworm. Applying a garlic gel containing 0.6% ajoene seems to be as effective as terbinafine 1% cream.91

Tinea pedis (athlete's foot). Applying a garlic gel containing 1% ajoene seems to be more effective than 0.6% ajoene gel, and seems to beas effective as 1% terbinafine (Lamisil) for tinea pedis infections. Sixty days after completing one week of treatment 1% ajoene produces 100% mycologic cure, 0.6 % produces 72% mycologic cure, and 1% terbinafine produces 94% mycologic cure.92,93

INSUFFICIENT SCIENTIFIC EVIDENCE to RATE

Common cold. Preliminary clinical research suggests garlic might reduce the frequency and number of colds when taken prophylactically.94

Mechanism of Action:

The applicable part of garlic is the bulb. Garlic is mostly used for its antihyperlipidemic, antihypertensive, and antifungal effects. However, it is also reported to have antibacterial, antiparasite (worms), antiviral, antispasmodic, promotes sweating, expectorant, immunostimulant, and antithrombotic effects.95,96,97,98,99 Many of the pharmacological effects of garlic are attributed to the allicin, ajoene, and other organosulfur constituents such as S-allyl-L-cysteine.98

It's thought that the effectiveness of garlic products might to be determined by their ability to yield allicin, which in turn triggers production of other active constituents.100

Intact garlic cells in fresh garlic contain the odorless amino acid, alliin. When intact cells are broken, alliin comes intocontact with the enzyme alliinase in garlic, producing allicin, an unstable, odiferous compound.100,97 Fresh garlic contains approximately 1% alliin. One milligram of alliin is converted to 0.458mg allicin.101 Further conversion yields ajoene. The amount of allicin in garlic preparations is dependent upon the method of preparation. Processes that involve maceration of the garlic clove increase the activity of allicinase. Freeze-dried garlic may contain little or no allicin. To improve effectiveness, garlic preparations may be coated to protect the active constituents from degeneration

by stomach acid.102 Heat and steam distillation used to produce garlic oil from crushed garlic converts allicin to allyl sulfides which are also thought to have biological activity.100

Garlic is aged to reduce the content of other sulfur compounds and the odor commonly associated with garlic. The process to produce odorless aged garlic extract reduces the alliin content to only 3% of what is typically contained in fresh garlic.101

Aged garlic extract is usually standardized to S-allyl-L-cysteine, another major organosulfur constituent in garlic.95

In patients with hyperlipidemia, garlic might lower cholesterol levels by acting as a HMG-CoA reductase inhibitor (statin).103,104 There is some evidence the constituent S-allyl-L-cysteine may be a potent inhibitor of hepatic cholesterol synthesis.105

For age-related vascular changes and atherosclerosis, garlic is thought to be beneficial and protect vascular endothelial cells from injury by reducing oxidative stress, inhibiting low-density lipoprotein (LDL) oxidation, and through antithrombotic effects.106,107,98,108 There is evidence that LDL oxidation may be inhibited by the constituents S-allyl cysteine, S-allyl mercaptocysteine, alliin, allixin, and by N-acetyl-S-allyl cysteine, a metabolite of S-allyl cysteine.108 Garlic appears to prevent endothelial cell depletion of glutathione, which may be responsible for its antioxidant effects.106

Garlic powder and aged garlic preparations have been shown to have antiplatelet properties in both patients with cardiovascular disease and in healthy volunteers.109,95,96,110,111

Garlic has been found to have antithrombotic properties and can increase fibrinolytic activity,decrease platelet aggregation and adhesion, increase the prothrombin time (PT), and inhibit metabolic enzymes in platelets responsible for the conversion of arachidonic acid into prostaglandins and other products.95,96,98,112 Raw garlic seems to have more potent antiplatelet properties

than cooked garlic.113,114,115 Crushing garlic before cooking might prevent some of the loss of antiplatelet activity.115 Garlic oil does not appear to affect platelet aggregation.116

Garlic is thought to reduce blood pressure by causing smooth muscle relaxation and vasodilation by activating production of endothelium-derived relaxation factor (EDRF, nitric oxide).117

Garlic also seems to have humoral and cellular immunostimulant activity.

The constituents allicin and ajoene are thought to beresponsible for garlic's antifungal activity against ringworm infections.98,93 Fresh garlic, but not aged garlic, has shown activity against Escherichia coli, methicillin-resistant Staph aureus, salmonella enteritidis, and Candida albicans in the laboratory; it has been suggested as a food additive to prevent food poisoning.

118 Preliminary evidence suggests that garlic compounds might have activity against viruses

Adverse Reactions:

Orally, garlic has dose-relatedadverse effects, which most commonly include breath and body odour, mouth and gastrointestinal burning or irritation, heartburn, flatulence, nausea, vomiting, and diarrhoea. These effects can be more pronounced with consumption of raw garlic or in patients unaccustomed to eating garlic.78,65,101 Oral use of garlic can also cause changes to the intestinalflora,78 ,101 which might result in gastrointestinal upset. Garlic's effect on platelet function is well known, and can possibly increase the risk of bleeding.

Interactions with Herbs & Supplements:

Anticoagulatn/Antiplatelet Herbs and Supplements: Concomitant use of herbs that have constituents that might affect platelet aggregation could theoretically increase the risk of bleeding in some people. These herbs include angelica, clove, danshen, ginger, ginkgo, red clover, turmeric, vitamin E, willow, and others.109,95,96,110,111

Interactions with Drugs:

Anticoagulatn/Antiplatelet Drugs including Warfarin.

Cyclosporine: (transplant patients).

Isoniazid (TB treatment).

Saquinavir (HIV treatment).

Interactions with Foods:

None known.

Interactions with Lab Tests:

Blood Pressure: Garlic can lower blood pressure and blood pressure readings.87,88,89

Cholesterol: Garlic can lower serum cholesterol concentrations and test results.87,88,89

Clotting Studies.120

Interactions with Diseases or Conditions:

Bleeding Disorders:95,96,98 Contraindicated.

Gastrointestinal (GI) Irritation: Garlic can irritate the GI tract; dose related, resolves on stopping garlic.

78,65,101

Surgery: discontinue one to two weeks prior to scheduled surgery.121,101,122

Dosage/Administration:

Dr Clare’s Blends: 1gm/day

Specific References: GARLIC

63. Steiner M, Khan AH, Holbert D, Lin RI. A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids. Am J Clin Nutr 1996;58:866-70.

64. Holzgartner H, Schmidt U, Kuhn U. Comparison of the efficacy and tolerance of a garlic preparation vs. bezafibrate. Arzneimittelforschung 1992;36:1473-7.

65. Jain AK, Vargas R, Gotzkowsky S, McMahon FG. Can garlic reduce levels of serum lipids? A controlled clinical study. Am J Med 1993;94:632-5. 66. Mader FH. Treatment of hyperlipidaemia with garlic-powder tablets. Evidence from the German Association of General Practitioners' multicentric placebo-controlled double-blind study. Arzneimittelforschung 1990;34:1111-6.

67. Rotzsch W, Richter V, Rassoul F, Walper A. [Postprandial lipemia under treatment with Allium sativum. Controlled double-blind study of subjects with reduced HDL2-cholesterol]. [Article in German]. Arzneimittelforschung 1992;36:1223-7.

68. Silagy C, Neil A. Garlic as a lipid lowering agent--a meta-analysis. J R Coll Physicians Lond 1994;28:33-39.

69. Vorberg G, Schneider B. Therapy with garlic: results of a placebo-controlled, double-blind study. Br J Clin Pract Symp Suppl 1990;69:7-11.

70. Adler AJ, Holub BJ. Effect of garlic and fish-oilsupplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men. Am J Clin Nutr 1997;59:445-44.

71. Morcos NC. Modulation of lipid profile by fish oil and garlic combination. J Natl Med Assoc 1997;89:673-8.

72. Breithaupt-Grogler K, Ling M, Boudoulas H, Belz GG. Protective effect of chronic garlic intake on elastic properties of aorta in the elderly.Circulation 1997;96:2649-49.

73. Koscielny J, Klussendorf D, Latza R, et al. The antiatherosclerotic effect of Allium sativum. Atherosclerosis 1999;144:237-43.

74. Stevinson C, Pittler MH, Ernst E. Garlic for treating hypercholesterolemia: a meta-analysis of randomized clinical trials. Ann Intern Med 2000;133:420-9.

75. Ackermann RT, Mulrow CD, Ramirez G, et al. Garlic shows promise for improving some cardiovascular risk factors.

Arch Intern Med 2001;161:813-18.

76. You WC, Brown LM, Zhang L, et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst 2006;98:974-83.

77. McCrindle BW, Helden E, Conner WT. Garlic extract therapy in children with hypercholesterolemia. Arch Pediatr Adolesc Med 1998;152:108 9-94.

78. Bloch AS. Pushing the Envelope of Nutrition Support: Complementary Therapies. Nutrition 2000;16:236-9.

79. Siegel G, Klubendorf D. The anti-atherosclerotic effect of Allium sativum: Statistics re-evaluated. Atherosclerosis 2000;150:437-8.

80. Steinmetz KA, Kushi LH, Bostick RM, et al. Vegetables, fruit, and colon cancer in the Iowa Women's Health Study. Am J Epidemiol 1994;139:1-15.

81. Witte JS, Longnecker MP, Bird CL, et al. Relation of vegetable, fruit, and grain consumption to colorectal adenomatous polyps. Am J Epidemiol 1996;144:1015-19.

82. Le Marchand L, Hankin JH, Wilkens LR, et al. Dietary fiber and colorectal cancer risk. Epidemiology 1997;8:658-59.

83. Dorant E, van den Brandt PA, Goldbohm RA. A prospective cohort study on the relationship between onion and leek consumption, garlic supplement use and the risk of colorectal carcinoma in The Netherlands. Carcinogenesis 1996;17:477-84.

84. Fleischauer AT, Poole C, Arab L. Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers. Am J Clin Nutr 2000;72:1047-46.

85. You WC, Blot WJ, Chang YS, et al. Allium vegetables and reduced risk of stomach cancer. J Natl Cancer Inst 1989; 81:162-4.

86. Takezaki T, Gao CM, Ding JH, et al. Comparative study of lifestyles of residents in high and low risk areas for gastric cancer in Jiangsu Province, China; with special reference to allium vegetables. J Epidemiol 1999;9:297-305.

87. Silagy CA, Neil HA. A meta-analysis of the effect of garlic on blood pressure. J Hypertension 1994;12:463-8.

88. McMahon FG, Vargas R. Can garlic lower blood pressure? A pilot study. Pharmacotherapy 1993;13:406-7.

89. Auer W, Eiber A, Hertkorn E, et al. Hypertension and hyperlipidaemia: garlic helps in mild cases. Br J Clin Pract

Symp Suppl 1990;69:3-6.

90. Ried K, Frank OR, Stocks NP, et al. Effect of garlic on blood pressure: A systematic review and meta-analysis. BMC Cardiovasc Disord 2008;8:13.

91. Ledezma E, Lopez JC, Marin P, et al. Ajoene in the topical short-term treatment of tinea cruris and tinea corporis in humans. Randomized comparative study with terbinafine. Arzneimittelforschung 1999;43:544-7.

92. Ledezma E, DeSousa L, Jorquera A, et al. Efficacyof ajoene, an organosulphur derived from garlic, in the short-term therapy of tinea pedis. Mycoses 1996;33:393-5.

93. Ledezma E, Marcano K, Jorquera A. Efficacy of ajoene in the treatment of tinea pedis: A double-blind and comparative study with terbinafine. J Am Acad Dermatol 2000;37:829-32.

94. Josling P. Preventing the common cold with a garlic supplement: a double-blind, placebo-controlled survey. Adv Ther 2001;18:189-93.

95. Rahman K, Billington D. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr 2000;130:2662-5.

96. Steiner M, Li W. Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions. J Nutr 2001;131:980S-4S.

97. Ankri S, Mirelman D. Antimicrobial properties ofallicin from garlic. Microbes Infect 1999;1:125-9.

98. M, Thomson M, Afzal M. Garlic and onions: their effect on eicosanoid metabolism and its

clinical relevance. Prostaglandins Leukot Essent Fatty Acids 2000;56:49-73.

99. Lamm DL, Riggs DR. The potential application ofallium sativum (garlic) for the treatment of bladder cancer. Urol Clin North Am 2000;21:157-56.

100. 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 2001;131:1471-8.

101. Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications, 2000.

102. Staba EJ, Lash L, Staba JE. A commentary on the effects of garlic extraction and formulation on product composition. J Nutr 2001;131:1118S-9S.

103. Gebhardt R, Beck H. Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte cultures. Lipids 1996;31:1269-76.

104. Qureshi AA, Din ZZ, Abuirmeileh N, et al. Suppression of avian hepatic lipid metabolism by solvent extracts of garlic: impact on serum lipids. J Nutr 1983;113:1746-49.

105. Yeh YY, Liu L. Cholesterol-lowering effect of garlic extracts and organosulfur compounds: human and animal studies. J Nutr 2001;131:989S-93S.

106. Ide N, Lau BH. Aged garlic extract attenuates intracellular oxidative stress. Phytomedicine 1999;6:125-31.

107. Dirsch VM, Kiemer AK, Wagner H, Vollmar AM. Effect of allicin and ajoene, two compounds of garlic, on inducible nitric oxide synthase. Atherosclerosis 1998;139:333-9.

108. Lau BH. Suppression of LDL oxidation by garlic. JNutr 2001;131:985S-8S.

109. Steiner M, Lin RS. Changes in platelet function and susceptibility of lipoproteins to oxidation associated with administration of aged garlic extract. J Cardiovasc Pharmacol 1998;31:904-8.

110. Kiesewetter H, Jung F, Jung EM, et al. Effect of garlic on platelet aggregation in patients with increased risk of juvenile ischaemic attack. Eur JClin Pharmacol 1993;39:333-6.

111. Legnani C, Frascaro M, Guazzaloca G, et al. Effects of a dried garlic preparation on fibrinolysis and platelet aggregation in healthy subjects. Arzneimittelforschung 1993;37:119-22.

112. Evans V. Herbs and the brain: friend or foe? The effects of ginkgo and garlic on warfarin use. J Neurosci Nurs 2000;32:229-32.

113. Chutani SK, Bordia A. The effect of fried versus raw garlic on fibrinolytic activity in man. Atherosclerosis 1981;32:417-21.

114. Ali M, Bordia T, Mustafa T. Effect of raw versus boiled aqueous extract of garlic and onion on platelet aggregation. Prostaglandins Leukot Essent Fatty Acids 1999;54:37-7.

115. Cavagnaro PF, Camargo A, Galmarini CR, Simon PW. Effect of cooking on garlic (Allium sativum l.) Antiplatelet

activity and thiosulfinates content. J Agric Food Chem 2007;49:1280-8.

116. Morris J, Burke V, Mori TA, et al. Effects of garlic extract on platelet aggregation: a randomized placebo-controlled double-blind study. Clin Exp Pharmacol Physiol 1995;22:414-7.

117. Pedraza-Chaverri J, Tapia E, Medina-Campos ON, et al. Garlic prevents hypertension induced by chronic inhibition

of nitric oxide synthesis. Life Sci 1998;56:71-7.

118. Sasaki J, Kita T, Ishita K, et al. Antibacterial activity of garlic powder against Escherichia coli O-157. J Nutr Sci Vitaminol (Tokyo) 1999;39:785-90.

119. Weber ND, Andersen DO, North JA, et al. In vitro virucidal effects of Allium sativum (garlic) extract and compounds. Planta Med 1992;52:417-17.

120. Sunter WH. Warfarin and garlic. Pharm J 1991;246:722.

121. Burnham BE. Garlic as a possible risk for postoperative bleeding. Plast Reconstr Surg 1995;95:213.

122. Carden SM, Good WV, Carden PA, Good RM. Garlic and the strabismus surgeon. Clin Experiment Ophthalmol 2002;30:303-4.

Gentian

Also Known As:

Bitter Root, Bitterwort, Gall Weed, Geneciana, Gentianae Radix, Gentiane, Gentiane Acaule, Gentiane Jaune, Gentiane Pâle, Gentiane Sans Tige, Gentiane Sauvage, Grande Gentiane, Pale Gentian, Racine Amère, Stemless Gentian, Yellow Gentian, Wild Gentian.

CAUTION: See separate listings for Canadian Hemp and Jimson Weed.

Scientific Name: Gentiana lutea; Gentiana acaulis, synonym Gentiana kochiana.

Family: Gentianaceae.

People Use This For:

Orally, gentian is used for digestive disorders, such as loss of appetite, fullness, flatulence, diarrhea, gastritis, heartburn, and vomiting. It is used orally for fever; hysteria; hypertension; and stimulating menstrual flow; and as an antispasmodic, anthelmintic, and antiseptic.

Topically, gentian is used for treating wounds and cancer.In combination with European elder flower, verbena, cowslip flower, and sorrel, gentian is used orally for maintaining healthy sinuses and treating sinusitis. It is used in combination with other products for malaria.

In foods and beverages, gentian is used as an ingredient.

In manufacturing, gentian is used in cosmetics.

Safety:

LIKELY SAFE ...when the root preparations are used in amounts commonly found in foods. Gentian root has Generally Recognized As Safe status (GRAS) for use in foods in the US (3).

POSSIBLY SAFE ...when gentian root is used orally in a specific combination that contains gentian root, elderflower, verbena, cowslip flower, and sorrel

(SinuComp, Sinupret) (1, 2).

There is insufficient reliable information available about the safety of the topical use of gentian.

PREGNANCY AND LACTATION: There is insufficient reliable information available about the safety of gentian in medicinal amounts during pregnancy and lactation; avoid using.

Effectiveness:

POSSIBLY EFFECTIVE

Sinusitis. Taking gentian orally in a specific combination product that also contains elderflower, verbena, cowslip flower, and sorrel (SinuComp, Sinupret) seems to help treat acute or chronic sinusitis Clinical studies have used Sinupret (1, 2).

There is insufficient reliable information available about the effectiveness of gentian for its other uses.

Mechanism of Action:

The applicable parts of gentian are the root and bark. The root is most commonly used. Gentian root contains triterpenoids, xanthones, and other constituents (5, 6). Preliminary research suggests gentian root has sedative effects. The xanthone gentiacaulein seems to have antidepressant activity, possibly through inhibition of monoamine oxidase (MAO)-A (6). Preliminary research suggests that gentian bark extracts might have MAO-B inhibitor effects (7).

Gentian root has been used historically as an antihypertensive. Gentian root extracts seem to have vasorelaxant properties (8, 10). Preliminary research

suggests that the xanthone constituents gentiacaulein and gentiakochianin may be responsible for vasodilation by an unknown mechanism (9).

Adverse Reactions:

Orally, gentian root in combination with other herbs can cause gastrointestinal adverse effects and allergic skin reactions (1, 2).

Interactions with Herbs & Supplements:

HERBS AND SUPPLEMENTS WITH HYPOTENSIVE EFFECTS: Gentian is thought to have hypotensive effects. Theoretically, combining gentian with other herbs and supplements with hypotensive effects might increase the risk of hypotension. Some of these herbs and supplements include andrographis, casein peptides, cat's claw, coenzyme Q-10, fish oil, L-arginine, lycium, stinging nettle, theanine, and others.

Interactions with Drugs:

ANTIHYPERTENSIVE DRUGS <<interacts with>> GENTIAN

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concurrent use might increase risk of hypotension with drugs that lower blood pressure (8, 10). These include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.

Interactions with Foods:

None known.

Interactions with Lab Tests:

None known.

Interactions with Diseases or Conditions:

HYPOTENSION: Theoretically, gentian use might worsen hypotension or interfere with drug therapy to increase blood pressure (8, 10).

SURGERY: Gentian might affect blood pressure. Theoretically, gentian might interfere with blood pressure control during and after surgical procedures. Tell

patients to discontinue gentian at least 2 weeks before elective surgical procedures.

Dosage/Administration: chronic

ORAL: For acute or sinusitis, a specific combination product (SinuComp Phytopharmica) containing gentian root 12 mg and 36 mgeach of European

elder flower, verbena, sorrel, and cowslip flower has been used three times daily (1, 2).

TOPICAL: No typical dosage.

Editor's Comments:

The highly toxic white hellebore (Veratrum album) can be misidentified as gentian and has caused accidental poisoning when used in home-made preparations (4).

Gentian root is unrelated to the gentian violet dye (methylrosaniline chloride).

Specific References: Ginseng

1. Neubauer N, Marz RW. Placebo-controlled, randomized,double-blind, clincal trial with Sinupret sugar coated tablets on the basis of a therapy with antibiotics and decongestant nasal drops in acute sinusitis. 1994;1:177-81.

2. Marz RW, Ismail C, Popp MA. Action profile and efficacy of a herbal combination preparation for the treatment of sinusitis. Wien Med Wochenschr 1999;149:202-8.

3. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: http://ecfr.gpoaccess.gov/cgi/t/text/textidx?c=ecfr&sid= 786bafc6f6343634fbf79fcdca7061e1&rgn=div5&view= text&node=21:3.0.1.1.13&idno=21

4. Zagler B, Zelger A, Salvatore C, et al. Dietary poisoning with Veratrum album--a report of two cases. Wien Klin Wochenschr 2005;117:106-8.

5. Toriumi Y, Kakuda R, Kikuchi M, et al. New triterpenoids from Gentiana lutea. Chem Pharm Bull (Tokyo) 2003;51:89-91.

6. Tomic M, Tovilovic G, Butorovic B, et al. Neuropharmacological evaluation of diethylether extract and xanthones of Gentiana kochiana. Pharmacol Biochem Behav 2005;81:535-42.

7. Haraguchi H, Tanaka Y, Kabbash A, et al. Monoamine oxidase inhibitors from Gentiana lutea. Phytochemistry 2004;65:2255-60.

8. Uncini Manganelli RE, Chericoni S, Baragatti B. Ethnopharmacobotany in Tuscany: plants used as antihypertensives. Fitoterapia 2000;71:S95-100.

9. Chericoni S, Testai L, Calderone V, et al. The xanthones gentiacaulein and gentiakochianin are responsible for the vasodilator action of the roots of 144 Gentiana kochiana. Planta Med 2003;69:770-2.

10. Baragatti B, Calderone V, Testai L, et al. Vasodilator activity of crude methanolic extract of Gentiana kokiana Perr. et Song. (Gentianaceae). J Ethnopharmacol 2002;79:369-72.

 Also known as: African Ginger, Black Ginger, Gan Jiang.

Scientific name: Zingiber officinale.

Botanical Family: Zingiberaceae.

Part used: The parts of ginger used medicinally are the rhizome (root-like stem) and root.

Traditional use.

Ginger is used for: motion sickness, morning sickness, colic, dyspepsia, flatulence, chemotherapy-induced nausea, rheumatoid arthritis, osteoarthritis, loss of appetite, nausea and vomiting following surgery, and migraine headaches. It is also used for upper respiratory tract infections, coughs, bronchitis, for the promotion of sweating, as a circulatory stimulant and for treating stomach-ache, diarrhea and nausea for any reason.

Ginger is commonly used as a flavoring agent in foods and beverages.

Safety.

There are no concerns regarding safety when used appropriately. Ginger has been safely used in several clinical trials.^{(1,2,3,4,5,6,7,8,9,10,11,12,13)}

Pregnancy: There are no concerns regarding safety. Studies in pregnant women suggest that ginger can be used safely and effectively for morning sickness without harm to the fetus. As with any medication given during pregnancy, the potential benefit to risk must be weighed. See dose guidelines for use in pregnancy.

Breastfeeding: There are no problems with food levels of ginger in the diet. No scientific studies have been undertaken on therapeutic doses. All herbs and spices cross into breastmilk so only use therapeutic doses of ginger if there is a clinical indication that warrants therapy, weighing up relative risks and benefits of using the herb.

Constituents

Volatile oil; predominantly hydrocarbons including zingiberene, ar-curcumene and bisabolene.

Pungent principles; a mixture of phenolic compounds with carbon side chains. These are referred to as gingerols, gingerdiols, gingerdiones, dihydrogingerdiones and shaogaols. The shaogoals are formed during the drying process and are twice as pungent as the gingerols. Hence the dried ginger is more pungent than the fresh herb.

Constituents.

Oleoresin; including gingerol homologues including derivatives with a methyl sidechain.

Gingerglycolipids

6-gingesulphonic acid.

Starch, proteins (amino acids including arginine) and fat.

Vitamins; including niacin, and vitamin A.

Minerals.

Scientific evidence.

Morning sickness. Taking ginger orally seems to reduce the severity of nausea and vomiting with morning sickness. Ginger seems to be more effective than placebo and comparable to vitamin B6. ^{(1,4,10,14,15,16)}

Vertigo. Taking 1 gram of ginger orally seems to reduce symptoms of vertigo, including nausea.⁽⁹⁾

Osteoarthritis. Severalstudies have shown evidence of symptom relief as effective as ibuprofen and diclofenac (NSAIDs). One study showed benefit after twelve weeks of treatment. ^{(5,6,7,23,24,25)}

Muscle Soreness. One study showed reduction in muscle soreness in women. ⁽²⁶⁾

Painful periods. Two recent clinical trials in women demonstrated that  ginger for 3 days from the start of their menstrual period was as effective as mefenamic acid (Ponstan) and ibuprofen (Nurafen) and placebo in relieving period pain. ^(27,28)

Migraine headache. Anecdotal evidence suggests that ginger might reduce the severity and duration of migraine headache.⁽⁹⁾

Mechanism of action.

Active constituents of ginger include gingerol, gingerdione, shogaol, and sesquiterpene and monoterpene volatile oils.^(17,18) The chemical constituents of ginger vary among fresh, semi-dry, and dry forms of ginger.⁽¹⁷⁾ Ginger has a variety of pharmacological properties including; lowering fever, analgesia, cough inhibition, anti-inflammatory, sedative, antibiotic, weak antifungal, and other properties.^(19,17)

The mechanism by which ginger reduces nausea and vomiting might be due to the 6-gingerol constituent.⁽²⁰⁾ Other ginger constituents such as 6-shogaol and galanolactone seem to act on serotonin (a chemical transmitter in the nervous system, especially in the brain and gut) receptors.⁽²⁰⁾ Galanolactone seems to act primarily on serotonin receptors in the small intestine. Ginger has been shown to possess free radical scavenging, antioxidant, inhibition of lipid peroxidation and that these properties might have contributed to the observed gastro-protective effects.

Ginger is sometimes used for inflammatory conditions such as osteoarthritis and rheumatoid arthritis. Some researchers speculate that certain constituents of ginger might inhibit pro-inflammatory enzymes.⁽²¹⁾ Compounds found in ginger are capable of inhibiting PGE-2 production and that the compounds may act at several sites.⁽²⁹⁾

Adverse reactions.

Ginger is usually well tolerated when used in usual doses.

Interactions with herbs and supplements.

None reported.

Interactions with drugs.

None reported.

Interaction with warfarin is generally cautioned. However a study showed that in healthy subjects there was no alteration in the metabolism of warfarin.^(30,31) Undertake weekly monitoring for one month as an additional precaution.

Interactions with foods.

None known.

Interactions with laboratory tests.

None known.

Dosage.

Recommended dose: 1.5-6mls per day 1:5 tincture 70% alcohol.

Or for a stronger 1:2 tincture 90% alcohol the dose is from 0.25-0.5ml per day.

Decoction: range from tsps. per day.

Powder/capsule: range from 0.75-3gms per day.

Osteoarthritis

Oral: For morning sickness, 250 mg ginger 4 times daily, or 500 mg twice daily, has been used. ^(1,4,12,18) A higher dose of 650 mg 3 times daily has also been used.⁽¹⁶⁾ It may take 3-4 days of regular use to be effective. For motion sickness, 1 gram of dried powdered ginger root 30 minutes to 4 hours before travel has been used.^(8,22)

References.

1.  Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1991;38:19-24.

2.  Phillips S, Ruggier R, Hutchinson SE. Zingiber officinale (ginger)-an antiemetic for day case surgery. Anaesthesia 1993;48:715-7.

3.  Bone ME, Wilkinson DJ, Young JR, et al. Ginger root-a new antiemetic. The effect of ginger root on postoperative nausea and vomiting after major gynaecological surgery. Anaesthesia 1990;45:669-71.

4.  Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol 2001;97:577-82.

5.  Bliddal H, Rosetzsky A, Schlichting P, et al. A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis. Osteoarthritis Cartilage 2000;8:9-12.

6.  Altman RD, Marcussen KC. Effects of ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum 2001;44:2531-38.

7.  Marcus DM, Suarez-Almazor ME. Is there a role for ginger in the treatment of osteoarthritis? Arthritis Rheum 2001;44:2461-2.

8.  Grontved A, Brask T, Kambskard J, Hentzer E. Ginger root against seasickness: a controlled trial on the open sea. Acta Otolaryngol 1998;105:45-9.

9.  Grontved A, Hentzer E. Vertigo-reducing effect of ginger root. A controlled clinical study. ORL J Otorhinolaryngol Relat Spec 1986;48:282-6.

10.  Portnoi G, Chng LA, Karimi-Tabesh L, et al. Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy. Am J Obstet Gynecol 2003;189:19-7.

11.  Wigler I, Grotto I, Caspi D, Yaron M. The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis. Osteoarthritis Cartilage 2003;11:783-9.

12.  Smith C, Crowther C, Wilson K et al. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 2004;103:639-45.

13.  Manusirivithaya S, Sripramote M, Tangjitgamol S, et al. Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin. Int J Gynecol Cancer 2004;14:1063-9.

14.  Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2000;(2):CD000145.

15.  Borrelli F, Capasso R, Aviello G, et al. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol 2005;105:849-56.

16.  Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.

17.  Suekawa M, Ishige A, Yuasa K, et al. Pharmacological studies on ginger. I. Pharmacological actions of pungent constitutents, (6)-gingerol and (6)-shogaol. J Pharmacobiodyn 1984;7:836-48.

18.  Pongrojpaw D, Somprasit C, Chanthasenanont A. A randomized comparison of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy. J Med Assoc Thai 2007;90:1703-9.

19.  Langner E, Greifenberg S, Gruenwald J. Ginger: history and use. Adv Ther 1998;15:25-44.

20.  Lumb AB. Mechanism of antiemetic effect of ginger. Anaesthesia 1993;48:1118.

21.  Thomson M, Al-Qattan KK, Al-Sawan SM, et al. The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent. Prostaglandins Leukot Essent Fatty Acids 2002;67:475-8.

22.  Ernst E, Pittler MH. Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Br J Anaesth 2000;84:367-71.

23. Wigler I, Grotto I, Caspi D, Yaron M. The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis. Osteoarthritis Cartilage 2003;11:783-9

24. Haghighi M, Khalva A, Toliat T, Jallaei S. Comparing the effects of ginger (Zingiber officinale) extract and ibuprofen on patients with osteoarthritis. Arch Iran Med 2005;8:267-71.

25. Drozdov VN, Kim VA, Tkachenko EV, Varvanina GG. Influence of a specific ginger combination on gastropathy conditions in patients with osteoarthritis of the knee or hip. J Alt Compl Med 2012;18:583-8.

26. Int J Prev Med. 2013 Apr;4(Suppl 1):S11-5.

Influence of ginger and cinnamon intake on inflammation and muscle soreness endued by exercise in Iranian female athletes.

Mashhadi NS1, Ghiasvand R, Askari G, Feizi A, Hariri M, Darvishi L, Barani A, Taghiyar M, Shiranian A, Hajishafiee M.

27. Giti Ozgoli, Marjan Goli, and Fariborz Moattar. The Journal of Alternative and Complementary Medicine. February 2009, 15(2): 129-132. doi:10.1089/acm.2008.0311.

Published in Volume: 15 Issue 2: February 23, 2009

28. Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial

Parvin Rahnama, Ali Montazeri, Hassan Fallah Huseini, Saeed Kianbakht and Mohsen Naseri. BMC Complementary and Alternative Medicine 2012, 12:92 

29. Phytomedicine. 2007 Feb;14(2-3):123-8. Epub 2006 May 18.

The effect of extracts from ginger rhizome on inflammatory mediator production.

Lantz RC1, Chen GJ, Sarihan M, Sólyom AM, Jolad SD, Timmermann BN.

30. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects

Xuemin Jiang¹, Kenneth M. Williams², Winston S. Liauw², Alaina J. Ammit¹, Basil D. Roufogalis¹, Colin C. Duke¹, Richard O. Day² andAndrew J. McLachlan. British Journal of Clinical Pharmacology

Volume 59, Issue 4, pages 425–432, April 2005

31. Badreldin H. Ali,Gerald Blunden, Musbah O. Tanira, Abderrahim Nemmar. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): A review of recent research. Food and Chemical Toxicology

Vol. 46, Issue 2. February 2008, Pages 409–420

Gotu Kola

Also Known As:

Brahma-Buti, Brahma-Manduki, Brahmi, Centella, Centella Asiática, Centella Asiatique, Centellase, Divya, Hydrocotyle, Hydrocotyle Asiatique, Hydrocotyle Indien, Indischer Wassernabel, Idrocotyle, Indian Pennywort, Indian Water Navelwort, Ji Xue Cao, Khulakhudi, Luei Gong Gen, Luo De Da, Madecassol, Mandukaparni, Manduk Parani, Mandukig, Marsh Penny, TTFCA, Talepetrako, Thick-Leaved Pennywort, Tsubo-kusa, Tungchian, White Rot.

CAUTION: See separate listings for Brahmi and Cola Nut.

Scientific Name:

Centella asiatica, synonym Hydrocotyle asiatica; Centella coriacea.

Family: Apiaceae/Umbelliferae.

People Use This For:

Orally, gotu kola is used for reducing fatigue, anxiety, depression, improving memory and intelligence, Alzheimer's disease, venous insufficiency including varicose veins, wound healing, and increasing longevity.

It is also used for the common cold and influenza, swine flu, sunstroke, tonsillitis, pleurisy, urinary tract infection (UTI), hepatitis, jaundice, abdominal pain,diarrhoea, indigestion, gastritis, peptic ulcer disease, dysentery, trauma, shingles,leprosy, cholera, syphilis, psychiatric disorders, epilepsy, asthma, anaemia, and diabetes. Gotu kola is also used for contraception, amenorrhea, elephantiasis, systemic lupus erythematosus (SLE), tuberculosis, memory loss, and as an aphrodisiac. Topically, gotu kola is used for wound healing and reducing scars. Parenterally, gotu kola is used for bladder lesions associated with schistosomiasis.

Safety:

POSSIBLY SAFE ...when used topically and appropriately.

Gotu kola has been used safely in a cream and ointment for up to 8weeks (27, 28). ...when used

orally. Gotu kola has been used safely in trials lasting up to 12 months (7, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26). However, there is concern that gotu kola might cause hepatotoxicity in some

patients (29). PREGNANCY: POSSIBLY SAFE ...when used topically and appropriately (28, 31). There is insufficient reliable information available about the safety gotu kola when used orally during pregnancy; avoid using.

LACTATION: Insufficient reliable information available; avoid using.

Effectiveness:

POSSIBLY EFFECTIVE

Venous insufficiency. Taking gotu kola orally for 4-8 weeks seems to improve measures of circulation and decrease symptoms such as edema (7, 11, 18, 19, 21, 25).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Atherosclerosis. There is preliminary evidence that taking gotu kola orally for 12 months might help stabilize low-density atherosclerotic plaques. Stabilizing these plaques might reduce the risk of rupture and embolism (17,24).

Deep vein thrombosis (DVT). Gotu kola helps prevent thrombosis related to long-distance flights.Preliminary evidence suggests that gotu kola might decrease edema, and improve measures of circulation in patients traveling on airplanes for more than 3 hours (22); however, it is not known if t

his actually results in a decreased incidence of clots. Diabetic microangiopathy. Taking gotu kola orally for 6-12 months might help increase measures of circulation, and decrease edema in patients with diabetic microangiopathy (20, 23).

Keloids. There is some evidence that applying an extract of gotu kola, known as madecassol, topically might help reduce keloids and hypertrophic scarring (30).

Psoriasis. Some evidence suggests that applying gotu kola topically might help reduce symptoms of psoriasis (6).

Scarring: Preliminary evidence suggests that applying a specific gotu kola cream (Alpha centella, not available in the US) twice daily for 6-8weeks following suture removal might help reduce scarring in patients without a history of keloid formation (27).

Schistosomiasis. There is some evidence that using gotu kola parenterally might help bladder lesions of schistosomiasis (bilharzial infections) (10).

Stretch marks (striae gravidarum). Preliminary evidence suggests that applying a specific mixture of gotu kola, vitamin E, and collagen-elastin hydrolysates in a cream (Trofolastin, not available in the US) daily during the second and third trimesters of pregnancy until labor might reduce stretch marks (31). There is also preliminary evidence that another specific mixture of gotu kola, vitamin E, essential fatty acids, hyaluronic acid, elastin, and menthol in an ointment (Verum, not available in the US) might help decrease the formation of stretch marks during pregnancy (28).

Wound healing. Preliminary evidence suggests that applying gotu kola topically might help improve wound healing (7). More evidence is needed to rate gotu kola for these uses.

Mechanism of Action:

The applicable parts of gotu kola are the above groundparts. The primary constituents responsible for the pharmacological effects are thought to be the saponin-containing triterpene acids, 1% to 8%; and their sugar esters, including asiatic acid, madecassic acid, asiaticoside A (madecassoside), and asiaticoside B (26). Gotu kola also contains essential oils; flavonoids; and flavone derivatives  including quercetin and kaempferol, sesquiterpenes, stigmasterol, sitosterol, and isothankuniside (713).

In vitro evidence suggests that gotu kola might bind cholecystokinin (CCK) and GABA receptors, which might be responsible for reported anxiolytic effects of gotu kola (6, 26). The effects on GABA might also results in sedative, anticonvulsant, and analgesic effects (7). There is some evidence that taking gotu kola orally might to reduce the startle response in healthy volunteers (26).

Some researchers think the asiaticoside derivatives, asiatic acid, asiaticoside 6, and SM2, might have a role in Alzheimer's disease. Preliminary evidence that they might protect neurons from beta-amyloid toxicity (3).

The triterpenoid saponins (e.g., asiaticoside, madecassoside) seem to increase wound healing and decrease venous pressure in venous insufficiency (2. 5, 11). Asiaticoside and other terpenoids might have anti-inflammatory activity (27, 32). The terpenoid extract seems to improve connective tissue re

modeling by increasing fibroblast activity, stimulating collagen synthesis, increasing epithelial turnover over, and decreasing capillary permeability (16,17,19). Gotu kola is thought to increase the production of type I collagen in scar formation over type II. Type II collagen is associated with hypertrophic scarring (27).

The terpenoid extract might help stabilize arterial plaques by increasing collagen within plaques. Plaques with low collagen content are structurally weak and are associated with an increased risk of rupture and embolism (17, 24)). There is also some evidence that asiaticosides might promote wound healing by stimulating collagen and glycosaminoglycan synthesis (4, 5). There's preliminary evidence that asiaticosides might also have preventive and therapeutic effects on gastrointestinal ulcers (7, 8). Anti-ulcer mechanisms may be due to strengthening action on gastric mucosal lining and suppression of damaging effects of free radicals (8).

Preliminary evidence suggests that purified isothankuniside might decrease fertility. However, a crude extract of gotu kola does not reduce fertility (13). Gotu kola extracts also seem to have antibacterial activity in vitro against Pseudomonas pyocyaneus, Trichoderma mentagrophytes, and Entamoeba histolytica. It also seems to have antiviral activity againstHerpes simplex type II (7).

There is some interest in using gotu kola to treat cancer. Dried powder extracts of gotu kola exhibit cytotoxic and anti-tumor properties in preliminary studies.

Normal lymphocytes are not harmed, which suggests gotu kola exerts selective toxicity towards tumor cells (9).

There are some case reports of hepatotoxicity. The triterpenoids contained in gotu kola are theorized to be responsible for this adverseeffect (29).

Adverse Reactions:

Orally, gotu kola is usually well-tolerated when used in typical doses (17, 18, 19, 20, 22, 23, 24, 25, 26). However, in some patients it can cause gastrointestinal upset and nausea (7). Theoretically, gotu kola might also cause drowsiness (7). There are at least three cases of hepatotoxicity associated with gotu kola. In one case, a 61-year-old woman developed elevated liver function tests (LFTs) including AST, ALT, alkaline phosphatase, and total bilirubin after taking gotu kola tablets for 30 days. Liver biopsy showed granulomatous acute hepatitis, suggesting an immune mediated hepatitis. LFTs improved when gotu kola was discontinued. Months later the patient took gotu kola again and developed elevated LFTs again after 2 weeks. In another case, a 52-year-old woman developed symptoms of hepatitis and increased LFTs after taking gotu kola for 3 weeks. Biopsy indicated chronic hepatitis and granulomas,areas of necrosis, and cirrhotic transformation. LFTs normalized after discontinuation of gotu kola.

In a third case, a 49-year-old woman developed symptoms of hepatitis and elevated LFTs 2 months after starting gotu kola. Biopsy revealed granulomatous hepatitis. LFTs normalized after discontinuation of gotu kola (27). Researchers did not perform laboratory analysis of the products taken in these cases to determine if they were free of hepatotoxic contaminants. Therefore, it is not

possible to rule out product contamination. The doses of gotu kola taken by these patients is unknown. Therefore, it is not known if higher doses are more likely than lower doses to cause hepatotoxicity. In a clinical trial where liver function was monitored, patients taking gotu kola 120 mg/day for 6 months, no changes in hepatic function were observed (20).

Topically, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (1,7, 12). Gotu kola may also cause eczema when applied topically (14, 15).

Interactions with Herbs & Supplements:

HEPATOTOXIC HERBS AND SUPPLEMENTS: There is some concern that gotu kola might cause hepatotoxicity in some patients (29). Theoretically, concomitant use with other potentially hepatotoxic products might increase the risk of developing liver damage. Some of these products include

androstenedione, chaparral, comfrey, DHEA, germander, niacin, pennyroyaloil, red yeast, and others.

HERBS AND SUPPLEMENTS WITH SEDATIVE PROPERTIES: Theoretically, concomitant use with herbs that have sedative properties might enhance therapeutic and adverse effects (7). Some of these supplements include 5-HTP, calamus, California poppy, catnip, hops, Jamaican dogwood, kava, St. John's wort, skullcap, valerian, yerba mansa, and others.

Interactions with Drugs:

Topically, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (1,7, 12). Gotu kola may also cause eczema when applied topically (14, 15).

Interactions with Herbs & Supplements:

HEPATOTOXIC HERBS AND SUPPLEMENTS: There is some concern that gotu kola might cause hepatotoxicity in some patients (29). Theoretically, concomitant use with other potentially hepatotoxic products might increase the risk of developing liver damage. Some of these products include androstenedione, chaparral, comfrey, DHEA, germander, niacin, pennyroyal oil, red yeast, and others.

HERBS AND SUPPLEMENTS WITH SEDATIVE PROPERTIES: Theoretically, concomitant use with herbs that have sedative properties might enhance therapeutic and adverse effects (7). Some of these supplements include 5-HTP, calamus, California poppy, catnip, hops, Jamaican dogwood,kava, St. John's wort, skullcap, valerian, yerba mansa, and others.

Interactions with Drugs:

CNS DEPRESSANTS <<interacts with>> GOTU KOLA

Interaction Rating = Major Do not take this combination.

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

Theoretically, concomitant use of gotu kola with drugs with sedative properties might cause additive effects and side effects (7). Some sedative drugs include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem  (Ambien), and others.

HEPATOTOXIC DRUGS <<interacts with>> GOTU KOLA

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

There is some concern that gotu kola might cause hepatotoxicity in some  patients (29). Theoretically, concomitant use with other potentially hepatotoxic drugs might increase the risk of developing liver damage. Some of these drugs include acarbose (Precose, Prandase), amiodarone (Cordarone), atorvastatin (Lipitor), azathioprine (Imuran), carbamazepine (Tegretol), cerivastatin (Baycol), diclofenac (Voltaren), felbamate (Felbatol), fenofibrate (Tricor), fluvastatin (Lescol), gemfibrozil (Lopid), isoniazid, itraconazole, (Sporanox), ketoconazole (Nizoral), leflunomide (Arava), lovastatin (Mevacor), methotrexate (Rheumatrex), nevirapine (Viramune), niacin, nitrofurantoin (Macrodantin), pioglitazone (Actos), pravastatin (Pravachol), pyrazinamide, rifampin (Rifadin), ritonavir (Norvir), rosiglitazone (Avandia), simvastatin (Zocor), tacrine (Cognex), tamoxifen, terbinafine (Lamisil), valproic acid, and zileuton (Zyflo).

Interactions with Foods:

None known.

Interactions with Lab Tests:

None known.

Interactions with Diseases or Conditions:

LIVER DISEASE: There is concern that gotu kola might be linked to cases of hepatotoxicity (29). Theoretically, gotu kola might exacerbate liver problems in patients with existing liver disease such as hepatitis. Advise these patients to avoid taking gotu kola.

SURGERY: Gotu kola has CNS depressant effects. Theoretically, gotu kola might cause additive CNS depression when combined with anesthesia and other medications during and after surgical procedures. Tell patients to discontinue gotu kola at least 2 weeks before elective surgical procedures.

Dosage/Administration:

ORAL: For atherosclerosis, 60 mg of gotu kola extract three times daily has been used (17, 24). For diabetic microangiopathy, 60 mg of gotu kola extract twice daily has been used (20, 23). For venous insufficiency, 60-180 mg daily of gotu kola extract has been used (18, 19, 21, 25). For deep vein thrombosis (DVT) prevention while flying, 120 mg of gotu kola extract 3 days before the flight, the day of the flight, and the day after have been used (22).

TOPICAL: For wound healing, 1% gotu kola creams have been used (7). For scars, gotu kola has been used in combination with the extract from Bulbine frutescens (Alpha centella cream, not available in the US) for 6-8weeks (27).

For preventing stretch marks in pregnancy, gotu kola has been used in combination with several other ingredients (Trofolastin and Verum). Trofolastin cream (not available in the US) is a mixture of gotu kola, vitamin E, and collagen-elastin hydrolysates (21). Verum ointment (not availablein the US) contains gotu kola, vitamin E, essential fatty acids, hyaluronic acid, elastin, and menthol (28).

Editor's Comments:

Gotu kola is a commonly used herb in Tradition Chinese and Ayurvedic medicine (26). The terpenoid extract of gotu kola is sometimes referredto as TTFCA (total terpenoid fraction of Centella asiatica) and Centellase. Avoid confusion with cola nut (Cola acuminata), and swamp pennywort (Centella cordifolia). Centella cordifolia is often misidentified as Centella asiatica (gotu kola).

Specific References:

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

2. Pointel JP, Boccalon H, Cloarec M, et al. Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs. Angiol 161 1987;38:46-50.

3. Mook-Jung I, Shin JE, Yun SH, et al. Protective effects of asiaticoside derivatives against beta-amyloid neurotoxicity. J Neurosci Res 1999;58:417-25.

4. Maquart FX, Chastang F, Simeon A, et al. Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds. Eur J Dermatol 1999;9:289-96.

5. Shukla A, Rasik AM, Jain GK, et al. In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. J Ethnopharmacol 1999;65:1-11.

6. Kenady DE, Chretien PB, Potvin C, Simon RM. Thymosin reconstitution of T-cell deficits in vitro in cancer patients. Cancer 1977;39:575-80.

7. Brinkhaus B, Lindner M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the east Asian medical plant Centella asiatica. Phytomedicine 2000;7:427-48.

8. Cheng CL, Koo MWL. Effects of Centella asiatica on ethanol induced gastric mucosal lesions in rats. Life Sci 2000;67:2647-53.

9. Babu TD, Kuttan G, Padikkala J. Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference toCentella asiatica (L.) Urban. J Ethnopharmacol 1995;48:53-7.

10. Fam A. Use of titrated extract of Centella asiatica (TECA) in bilharzial bladder lesions. Int Surg 1973;58:451-2.

11. Belcaro GV, Rulo A, Grimaldi R. Capillary filtration and ankle edema in patients with venous hypertension treated with TTFCA. Angiology 1990;41:12-8.

12. Eun HC, Lee AY. Contact dermatitis due to madecassol. Contact Dermatitis 1985;13:310-3.

13. Dutta T, Basu UP. Crude extract of Centella asiatica and products derived from its glycosides as oral antifertility agents. Indian J Exp Biol 1968;6:181-2.

14. Hausen BM. Centella asiatica (Indian pennywort), an effective therapeutic but a weak sensitizer. Contact Dermatitis 1993;29:175-9.

15. Bilbao I, Aguirre A, Zabala R, et al. Allergic contact dermatitis from butoxyethyl nicotinic acid and Centella asiatica extract.Contact Dermatitis 1995;33:435-6.

16. Incandela L, Cesarone MR, Cacchio M, et al. Total triterpenic fraction of Centella asiatica in chronic venous insufficiency and in high-perfusion microangiopathy. Angiology 2001;52 Suppl 2:S913.

17. Incandela L, Belcaro G, Nicolaides AN, et al. Modification of the echogenicity of femoral plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, randomized, placebo-controlled trial. Angiology 2001;52 Suppl 2:S69-73.

18. Incandela L, Belcaro G, De Sanctis MT, et al. Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined microcirculatory model. Angiology 2001;52 Suppl 2:S61-7.

19. De Sanctis MT, Belcaro G, Incandela L, et al. Treatment of edema and increased capillary filtration in venous hypertension with total triterpenic fraction of Centella asiatica: a clinical, prospective, placebo-controlled, randomized, dose-ranging trial. Angiology 2001;52 Suppl 2:S55-9

20. Cesarone MR, Incandela L, De Sanctis MT, et al. Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model. Angiology 2001;52 Suppl 2:S49-54.

21. Cesarone MR, Belcaro G, Rulo A, et al. Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcPO2-CO2, and leg volumetry. Angiology 163 2001;52 Suppl 2:S45-8.

22. Cesarone MR, Incandela L, De Sanctis MT, et al. Flight microangiopathy in medium- to long distance flights: prevention of edema and microcirculation alterations with total triterpenic fraction of Centella asiatica. Angiology 2001;52 Suppl 2:S33-7.

23. Incandela L, Belcaro G, Cesarone MR, et al. Treatment of diabetic microangiopathy and edema with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled randomized study. Angiology 2001;52 Suppl 2:S27-31.

24. Cesarone MR, Belcaro G, Nicolaides AN, et al. Increase in echogenicity of echolucent carotid plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled, randomized trial. Angiology 2001;52 Suppl 2:S19-25.

25. Cesarone MR, Belcaro G, De Sanctis MT, et al. Effects of the total triterpenic fraction of Centella asiatica in venous hypertensive microangiopathy: a prospective, placebo-controlled, randomized trial. Angiology 2001;52 Suppl 2:S15-18.

26. Bradwejn J, Zhou Y, Koszycki D, Shlik J. A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. J Clin Psychopharmacol 2000;20:680-4.

27. Widgerow AD, Chait LA, Stals R, Stals PJ. New innovations in scar management. Aesthetic Plast Surg 2000;24:227-34.

28. Young GL, Jewell D. Creams for preventing stretch marks in pregnancy. Cochrane Database Syst Rev 2000;(2):CD000066.

29. Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig 2005;97:115-24.

30. Bosse JP, Papillon J, Frenette G, et al. Clinical study of a new antikeloid agent. Ann Plast Surg 1979;3:13,21.

31. Mallol J, Belda MA, Costa D, et al. Prophylaxis of striae gravidarum with a topical formulation. A double blind trial. Int J Cosmet Sci 1991;3:51-7.

32. Guo JS, Cheng CL, Koo MW. Inhibitory effects of Centella asiatica water extract and asiaticoside on inducible nitric oxide synthase during gastric ulcer healing in rats. Planta Med 2004;70:1150-4.

Also known as: Green Sencha Tea, Japanese Tea.

Scientific name: Camellia sinensis, it is from the exact same tea plant as Black tea commonly used throughout the world. 

Botanical family: Theaceae.

Parts used: Bud leaf and stem.

Traditional use.

Green tea has been consumed and enjoyed as a beverage for centuries. Green tea is produced by steaming fresh leaves at high temperature. Unlike black and oolong (partially fermented) teas, green tea is not fermented.

Improving cognitive performance and mental alertness is a traditional use for green tea. It is also used to treat stomach disorders, vomiting, diarrhea, and headaches. Green tea has a history of use for weight loss. It has a role in cancer prevention and treatment including breast cancer, cervical cancer, prostate cancer, colon cancer, gastric cancer, lung cancer, leukemia, and skin cancer related to ultraviolet radiation (e.g. sunburn) and other environmental causes. It has traditionally been used for its anti-viral effects on the wart virus including genital warts, perianal warts and cervical cell changes. Other uses include osteoporosis, Crohn's disease, Parkinson's disease, cardiovascular disease, diabetes, low blood pressure, chronic fatigue syndrome, tooth decay, kidney stones, and skin damage.

Topically, green tea is used as a wash to soothe sunburn, as a poultice for bags under the eyes, as a compress for headache or tired eyes, and to stop the bleeding of tooth sockets. Green tea in chewable candy is used for inflammation of the gums. Green tea is also used topically to prevent skin damage and cancer related to ultraviolet radiation (e.g. sunburn) and other environmental causes.

Safety.

There are no concerns about safety when consumed as a beverage in moderate amounts of 1-4 cups of green tea per day. ^{(1,2,3,4,5,6,7,8)}

Green tea extract as a supplement containing 7% caffeine has been used safely for six months. ⁽⁹⁾

Avoid using high doses long-term because Green tea contains a significant amount of caffeine. Typically a cup of green tea contains 35-60mgs of caffeine.

Children: While no safety concerns have been highlighted avoid caffeinated drinks in children and limit to 1 cup per day. ^(11,12) Avoid giving green tea to infants, as they have an increased risk of anemia. ⁽⁸⁸⁾

Pregnancy: There are no reported problems when used orally in moderate amounts of two cups per day.

Breastfeeding: There are no particular concerns when used orally in moderate amounts of 1-4 cups per day. If the baby has loose stools exclude green tea, black tea and coffee to see if caffeine is contributing to the problem.

Constituents.

Scientific Evidence.

Mental Alertness. Green tea and other caffeinated beverages prevent a decline in alertness and cognitive capacity when consumed throughout the day. ^(10,13,14)

Bladder cancer, esophageal cancer, and pancreatic cancer. cervical dysplasia. Drinking green tea is associated with a reduced the risk of bladder cancer, esophageal cancer, and pancreatic cancer. ^{(15,16,17,18,19)}

Green tea as an oral or topical preparation seems to reduce cervical dysplasia caused by human warts (papilloma virus) infection. ^(20).

High Cholesterol. Green tea taken orally lowers cholesterol and triglycerides.^(21)(22)

Low Blood Pressure. Consuming caffeinated beverages including Green Tea increases blood pressure in elderly people with low blood pressure after meals which may prevent falls. ^(23,24)

Oral leukoplakia (lesions of the mouth that may progress to cancer). Drinking green tea orally decreases the size of lesions in patients with oral leukoplakia. ⁽²⁵⁾

Ovarian cancer; Women who regularly consume green tea or black tea, have a lower risk of developing ovarian cancer.^{(92,25,26,27)}

Parkinson's disease. Consuming green tea orally helps prevent or delay the onset of Parkinson's disease. ^{(28, 29)}

Prevention of colorectal cancer.

Population studies suggest that consuming green tea does not have any effect on colon cancer risk. ^(30,31,32)

Breast cancer. Population studies suggest that green tea does not seem to reduce the risk of initially developing breast cancer in Asian populations; ^(33.34) however, in Asian-American populations some evidence suggests that drinking green tea might reduce the risk of developing breast cancer. ⁽³⁵⁾

Additional population research suggests that Asian women who have had early breast cancer (Stage 1-11) who drink 3-5 of more cups of green tea daily seem to have reduced risk of breast cancer recurrence. ^(36,33)

Cardiovascular disease. A large-scale population study in Japan suggests that consuming 3 or more cups of green tea daily significantly decreases the risk of cardiovascular and all-cause mortality compared to drinking less than one cup daily. ⁽³²⁾

Diabetes. Population studies suggests that Japanese adults who consume 6 or more cups/day of green tea have a 33% lower risk of developing type 2 diabetes.⁽³⁷⁾

Gastric Cancer. There is conflicting evidence about the effects of green tea on gastric cancer risk.

Gingivitis (inflammation of the gums); Green tea extract in chewable candy appears to reduce inflammation. ⁽³⁸⁾

High Blood Pressure. There is evidence of variable effects of green tea depending on the physiological state of the tissues when taken by individuals. Population studies in Chinese people show that drinking 120-599 mL of green tea or oolong tea daily is associated with a 46% lowered risk of developing hypertension compared with non-habitual tea drinkers. Drinking more than 600 mL per day is associated with a 65% reduced risk. ⁽³⁹⁾ However, clinical studies on people with normal and high blood pressure show that green tea or black tea has no effect on their blood pressure. ⁽⁴⁰⁾ This apparent contradiction is common with herbal medicines who only have an action when it is required to normalise the physiological terrain. It is one of the benefits of multi constituent medicines. Active constituents can vary from person to person depending on their individual physiology.

Lung Cancer. There is conflicting evidence about the effects of green tea on lung cancer risk. ^{(32) (41)}

Obesity. There is conflicting evidence about the effectiveness of green tea for obesity and weight loss. A meta-analysis of clinical studies suggests that, overall, taking green tea extract 576-714 mg/day along with caffeine seems to modestly reduce body mass index (BMI), body weight, and waist circumference compared to caffeine alone. But taking green tea extract without caffeine does not seem to significantly reduce weight or waist circumference. ^{(42) (43)}

Osteoporosis. Population research suggests that drinking green tea for ten years is associated with increased bone mineral density. ⁽⁴⁴⁾

Prostate cancer. Chinese men who consume green tea seem to have a lower risk of developing prostate cancer. ⁽⁴⁵⁾ Preliminary clinical research suggests that men with advanced cancer who take green tea supplements (containing catechins 200 mg three times daily) for a year seem to have a reduced risk of progression to prostate cancer. ⁽⁴⁶⁾

Osteoarthritis

Mechanism of action.

Polyphenols including flavanols, flavandiols, flavonoids, and phenolic acids are abundant in green tea. The flavanols are all referred to as catechins. These seem to be responsible for many of the proposed benefits of green tea. ^{(19,20,48,49,50)}  and they may be responsible for its  anti-inflammatory activity. ⁽⁵¹⁾

They may inhibit the production of other inflammatory substances including COX-1and 2, leukotriene-B4 and the activity of 5-lipoxygenase and nitric oxide synthase.^{(52, 53)} Green tea catechins may also protect cartilage by inhibiting proteoglycan and collagen breakdown.⁽⁵⁴⁾ Green tea polyphenols seem to lessen joint degeneration in laboratory models of rheumatoid arthritis. ⁽⁵⁵⁾ Green tea also contains plant estrogens including beta-sitosterol. ⁽⁴¹⁾

Green tea contains 2% to 4% caffeine or 10-80 mg caffeine per cup.⁽⁵⁶⁾ a typical amount is 35-60mgs per cup. The caffeine in green tea stimulates the central nervous system (CNS), heart, muscles, and possibly blood pressure.⁽⁵⁷⁾ Caffeine is thought to increase the release of neurotransmitters such as dopamine.⁽⁵⁸⁾ Caffeine also decreases airway resistance and stimulates respiration.⁽⁵⁹⁾ Caffeine may decrease GABA and Serotonin  neurotransmitters in the Central Nervous System. ⁽⁵⁸⁾ Caffeine stimulates stomach acid secretion, and increases fight or flight chemicals in the body.⁽⁶⁰⁾ Caffeine can have positive stimulating effects on the heart.⁽⁵⁹⁾ Caffeine can also immediately raise blood pressure, but might not have this effect in habitual users. ⁽⁵⁷⁾

Caffeine doesn't substantially affect the fluid status of people who drink caffeinated beverages on a regular basis. ^(61,62)

The caffeine content is also thought to be responsible for green tea's effects on mental performance. ⁽¹³⁾

Some preliminary studies show that flavonoids found in green tea might reduce heart disease risk factors lipoprotein oxidation. However, green tea doesn't reduce inflammation, vascular reactivity, or lipid oxidation. ^{(63,64,65,66,67)}

Caffeine has been reported to cause increases and decreases in blood glucose.

Green tea may protect against some kinds of cancer.

Green tea polyphenols also appear to have activity against human wart virus and related cervical changes and genital warts ^(20,68) but the mechanism of action for this is not known.

The polyphenols in green tea appear to reduce the cellular adhesiveness of bacteria associated with dental disease. ⁽³⁸⁾ Some evidence suggests that green tea might be useful in skin disorders such as excess hair, acne and also male pattern baldness. ⁽⁷⁰⁾

Green tea is thought to be beneficial for preventing skin damage and cancer from ultraviolet radiation. Areas of skin where green tea extracts were applied had fewer sunburned cells and less damage to skin cells. ⁽⁷¹⁾

Green tea is also used for weight loss. Early evidence indicates that a green tea extract rich in catechins can increase calorie and fat metabolism. The caffeine, catechin, and theanine constituents of green tea might contribute to this effect. ^(72,73,74) Caffeine increases resting energy expenditure and cellular heat production. ⁽⁷⁵⁾ 

Tannins in green tea can reduce diarrhea and the polyphenols in green tea might have a beneficial effect on the gut flora.. ⁽⁷⁶⁾

For prevention of Parkinson's disease, caffeine in green tea may help to maintain levels of dopamine in the central nervous system by preventing the inhibition of dopaminergic transmission. These actions help reduce the expression of symptoms of Parkinson’s disease. ⁽²⁸⁾

Protecting people from developing Alzheimer's disease has got to be a major priority for aging Western populations. Early studies suggests that catechins in Green tea may prevent oxidation and cell death of neurons, which may help resist cell damage and maintain health. ⁽⁷⁷⁾

Population studies suggest that drinking green tea for at least ten years increases bone mineral density. The exact mechanism for the effects on bone is unknown, but several possibilities have been suggested. Tea leaves contain fluoride, which might slow osteoporosis. Tea also contains flavonoids and phytoestrogens, which might affect bone mineral density. Other proposed mechanisms include inhibition of bone resorption and effects on mineral metabolism by polyphenols and tannins. ⁽⁴⁴⁾

Adverse reactions.

Green tea can cause digestive upset and dizziness, insomnia and agitation and confusion. These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day.^(9,78)

There have been at least 14 cases of liver toxicity, usually linked to green tea extract products in pill form. ^(79,80) However, there has been at least one report associated with consumption of a green tea-containing beverage. ⁽⁸⁰⁾ In most reported cases, green tea products were not assessed to determine if any contaminants were present. In most cases, liver function returned to normal after discontinuation of the green tea product. ^(79,80)

Interaction with herbs and supplements.

Anticoagulant/antiplatelet herbs and supplements:

There have been no reported cases of interaction with warfarin (this a pharmaceutical blood thinning agent).

Caffeine containing herbs and supplements: Other natural products that contain caffeine include coffee, black tea, oolong tea, guarana, mate, cola, and others. Some supplements for energy may contain caffeine; check the label.

Avoid large amounts of green tea along with supplements aimed at the market for sportspeople that contain creatine, caffeine or ephedra.^(83,84)

Liver toxic herbs and supplements: Theoretically, avoid taking green tea supplements with other hepatotoxic herbs or supplements as there might be additive effects. ^(79,85) Check out herbs you want to use with Green Tea and avoid the combination if there are concerns about liver function.

Iron: Like black tea, green tea appears to reduce absorption of iron from foods. ^(86,87) However, a study of iron-deficient elderly patients suggests that concomitant use doesn't alter iron absorption in this population. ⁽⁸⁹⁾ Iron levels are not affected in people with adequate iron intake.  Theoretically, green tea might reduce the absorption of iron supplements. For most patients, this effect will not be clinically significant. On this account patients with iron deficiency are advised to consume black tea and green tea between meals. ⁽⁸⁷⁾

Interactions with drugs.

There is preliminary evidence that green tea might enhance the effects of doxorubicin (Adriamycin) on cancer cells. ⁽⁶⁹⁾

Caffeine accounts for most of the side effects for green tea. If you are on medication or need to start medication read the drug insert leaflet carefully. If there is an interaction with caffeine, or black tea or coffee be aware that green tea may have the same interaction.

Stimulants. Read the drug leaflet any nervous system stimulation medicine including amphetamines.

Drugs that inhibit caffeine metabolism; These include cimetidine (reduces stomach acid), fluconazole (anti-fungal), mexilitene (prescribed for heartbeat irregularities), fluvoxamine (antidepressant). Avoid green tea supplements or consult a medical herbalist.

Drugs that decrease caffeine clearance: terbinafine (prescribed for fungal infection of toe nails), quinolone antibiotics (the commonest prescribed is ciproflaxacin, apart from nalidixic acid all others end with –acin).

Hepatotoxic drugs. Avoid of green tea supplements.

Estrogens. The effect of caffeine on estrogens is complicated and depends on race and the dose of caffeine. High caffeine levels can elevate estrogens and low doses can stimulate. An average amount in daily intake of green tea is unlikely to be clinically significant but may be relevant to supplement doses.⁹³

Drugs that reduce caffeine clearance; theophylline.

Warfarin. No reports have been noted with normal consumption, observe the usual vigilance.

Interactions with foods. Avoid excess caffeine intake when used in conjunction with black tea and coffee. Because the effects of caffeine are dose related avoid excessive amount of caffeine intake. The amount of caffeine in coffee is extremely variable, check the packaging or server, black tea averages 30-80mgs per cup. Check the amount in soft drinks and avoid high caffeine energy drinks.

Green tea appears to reduce absorption of iron from non-meat food sources. If you are concerned about this drink green tea between meals.

Adding milk to your green tea may reduce the benefits of green tea as the milk may reduce the absorption of some of the helpful constituents.

Interaction with laboratory tests.

Inform your medical provider if you are taking green tea supplements. Drinking 4-6 cups of green tea per day is unlikely to affect laboratory tests any more than 1-3 cups of coffee.

Interactions with diseases and conditions.

Generalized anxiety or nervous excitability: avoid caffeinated beverages or supplements.

Diabetes: caffeine may affect the presentation of hypoglycemic attacks. Avoid sudden increases or decreases of caffeine intake and monitor blood sugars more carefully if changing the amount of caffeine in your diet.

Glaucoma: Intake of caffeinated beverage (>/=180 mg caffeine) may not be recommended for patients with normotensive glaucoma or ocular hypertension.

Bleeding time: Caffeine is reported to have antiplatelet activity however, this interaction has not been reported in humans.

Heart rhythm irregularities: Caffeine in green tea can induce cardiac arrhythmias in sensitive individuals use with caution.

Dosage.

It is difficult to be precise with dosage of green tea as much depends on the duration of brewing and the quality of the raw herb.

Infusion: 1-6 cups for men per day and 1-4 cups for women per day if using one tsp. of the herb per cup of boiling water.

Powder/capsule: 1500 mg per day.

Ostearthritis

Oral: Doses of green tea vary significantly, but usually range between 1-10 cups daily. The commonly used dose of green tea is based on the amount typically consumed in Asian countries, which is about 3 cups per day, providing 240-320 mg of polyphenols.

The typical dose of caffeine:

• For headache or restoring mental alertness is up to 250 mg per day. ^(90.91)
• For improving cognitive performance, tea providing 60 mg of caffeine, or approximately one cup per day, has been used. ⁽¹³⁾
• For reducing cholesterol, 10 or greater cups per day has been associated with decreased cholesterol levels. ⁽²²⁾ Theaflavin-enriched green tea extract, 375 mg daily for 12 weeks, has also been used for cholesterol reduction. ⁽²¹⁾
• For preventing breast cancer or breast cancer recurrence, three or more cups of green tea per day have been used. ⁽³⁶⁾
• For human papilloma wart virus (HPV) infected cervical lesions, green tea extract, 200 mg daily alone or in combination with topical green tea ointment, for 8-12 weeks has been used. ⁽²⁰⁾
• For preventing Parkinson's disease consuming as little as 124-208 mg of caffeine (approximately 1-3 cups of green tea) daily offers benefit.⁽²⁸⁾ Women in particular may benefit from these moderate amounts, men appear to require higher amounts. This needs to be balanced with the adverse effects of excess caffeine. ⁽²⁹⁾

References.

1. Mitscher LA, Mitscher LA, Jung M, Shankel D, et al. Chemoprotection: A review of the potential therapeutic antioxidant properties of green tea (Camellia sinensis) and certain of its constituents. Med Res Rev 1997;17:327-65.
2. Nemecz G. Green tea. US Pharm 2000;May:67-70.
3. Inoue M, Tajima K, Hirose K, et al. Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan. Cancer Causes Control 1998;9:209-16.
4. Tajima K, Tominaga S. Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancers in Nagoya, Japan. Jpn J Cancer Res 1985;76:705-16.
5. Kono S, Ikeda M, Tokudome S, Kuratsune M. A case-control study of gastric cancer and diet in northern Kyushu, Japan.

Jpn J Cancer Res 1988;79:1067-74.

1. Ji BT, Chow WH, Yang G, et al. The influence of cigarette smoking, alcohol, and green tea consumption on the risk of carcinoma of the cardia and distal stomach in Shanghai, China. Cancer 1996;77:2449-57.
2. Yu GP, Hsieh CC. Risk factors for stomach cancer: a population-based case-control study in Shanghai. Cancer Causes Control 1991;2:169-74.
3. Zhang M, Binns CW, Lee AH. Tea consumption and ovarian cancer risk: a case-control study in China. Cancer Epidemiol Biomarkers Prev 2002;11:713-8.
4. Pisters KM, Newman RA, Coldman B, et al. Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol 2001;19:1830-8.
5. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html.
6. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid= 786bafc6f6343634fbf79fcdca7061e1&rgn=div5&view= text&node=21:3.0.1.1.13&idno=21
7. Castellanos FX, Rapoport JL. Effects of caffeine on development and behavior in infancy and childhood: A review of the published literature. Food Chem Toxicol 2002;40:1235-42.
8. Durlach PJ. The effects of a low dose of caffeine on cognitive performance. Psychopharmacology (Berl) 1998;140:116-9.
9. Hindmarch I, Quinlan PT, Moore KL, Parkin C. The effects of black tea and other beverages on aspects of cognition and psychomotor performance. Psychopharmacol 1998;139:230-8.
10. Mitscher LA, Mitscher LA, Jung M, Shankel D, et al. Chemoprotection: a review of the potential therapeutic antioxidant properties of green tea (Camellia sinensis) and certain of its constituents. Med Res Rev 1997;17:327-65.
11. Bushman JL. Green tea and cancer in humans: a review of the literature. Nutr Cancer 1998;31:151-9.
12. Wakai K, Ohno Y, Obata K. Prognostic significance of selected lifestyle factors in urinary bladder cancer. Jpn J Cancer Res 1993;84:1223-9.
13. Ohno Y, Aoki K, Obata K, et al. Case-control study of urinary bladder cancer in metropolitan Nagoya. Natl Cancer Inst Monogr 1985;69:229-34.
14. Nemecz G. Green tea. US Pharm 2000;May:67-70.
15. Ahn WS, Yoo J, Huh SW, et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev 2003;12:383-90.
16. Maron DJ, Lu GP, Cai NS, et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: A randomized controlled trial. Arch Intern Med 2003;163:1448-53.
17. Imai K. Nakachi K. Cross-sectional study of effects of drinking green tea on cardiovascular and liver diseases. BMJ 1995;310:693-6.
18. Heseltine D, Dakkak M, woodhouse K, et al. The effect of caffeine on postprandial hypotension in the elderly. J Am Geriatr Soc 1991;39:160-4
19. Rakic V, Beilin LJ, Burke V. Effect of coffee and tea drinking on postprandial hypotension in older men and women. Clin Exp Pharmacol Physiol 1996;23:559-63.
20. Li N, Sun Z, Han C, Chen J. The chemopreventive effects of tea on human oral precancerous mucosa lesions. Proc Soc Exp Biol Med 1999;220:218-24.
21. Zhang M, Binns CW, Lee AH. Tea consumption and ovarian cancer risk: a case-control study in China. Cancer Epidemiol Biomarkers Prev 2002;11:713-8.
22. Larsson SC, Wolk A. Tea consumption and ovarian cancer risk in a population-based cohort. Arch Intern Med 2005;165:2683-6.
23. Ross GW, Abbott RD, Petrovitch H, et al. Association of coffee and caffeine intake with the risk of parkinson disease. JAMA 2000;283:2674-9.
24. Ascherio A, Zhang SM, Hernan MA, et al. Prospective study of caffeine intake and risk of Parkinson's disease in men and women. Proceedings 125th Ann Mtg Am Neurological Assn. Boston, MA: 2000;Oct 15-18:42.
25. Inoue M, Tajima K, Hirose K, et al. Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan. Cancer Causes Control 1998;9:209-16.
26. Tajima K, Tominaga S. Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancers in Nagoya, Japan. Jpn J Cancer Res 1985;76:705-16.
27. Kuriyama S, Shimazu T, Ohmori K, et al. Green tea consumption and mortality due to cardiovascular disease, cancer, and all-cause mortality. JAMA 2006;296:1255-65.
28. Seely D, Mills EJ, Wu P, et al. The effects of green tea consumption on incidence of breast cancer and recurrence of breast cancer: a systematic review and meta-analysis. Integr Cancer Ther 2005;4:144-55
29. Suzuki Y, Tsubono Y, Nakaya N, et al. Green tea and the risk of breast cancer: pooled analysis of two prospective studies in Japan. Br J Cancer 2004;90:1361-3.
30. Wu AH, Yu MC, Tseng CC, et al. Green tea and risk of breast cancer in Asian Americans. Int J Cancer 2003;106:574-9.
31. Inoue M, Tajima K, Mizutani M, et al. Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. Cancer Lett 2001;167:175-82.
32. Iso H, Date C, Wakai K, et al; JACC Study Group. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med 2006;144:554-62.
33. Krahwinkel T, Willershausen B. The effect of sugar-free green tea chew candies on the degree of inflammation of the gingiva. Eur J Med Res 2000;5:463-7.
34. Yang YC, Lu FH, Wu JS, et al. The protective effect of habitual tea consumption on hypertension. Arch Intern Med 2004 26;164:1534-40.
35. Taubert D, Roesen R, Schomig E. Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch Intern Med 2007;167:626-34.
36. Schabath MB, Hernandez LM, Wu X, et al. Dietary phytoestrogens and lung cancer risk. JAMA 2005;294:1493-1504.
37. Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. Phytomedicine 2002;9:3-8.
38. Phung OJ, Baker WL, Matthews LJ, et al. Effect of green tea catechins with or without caffeine on anthropometric measures: a systemic review and meta-analysis. Am J Clin Nutr 2010;91:73-81.
39. Wu CH, Yang YC, Yao WJ, et al. Epidemiological evidence of increased bone mineral density in habitual tea drinkers. Arch Intern Med 2002;162:1001-6.
40. Jian L, Xie LP, Lee AH, Binns CW. Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer 2004;108:130-5.
41. Bettuzzi S, Brausi M, Rizzi F, et al. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res 2006;66:1234-40.
42. ˇChung LY, Cheung TC, Kong SK, et al. Induction of apoptosis by green tea catechins in human prostate cancer DU145 cells. Life Sci 2001;68:1207-14.
43. Khokhar S, Magnusdottir SG. Total phenol, catechin, and caffeine contents of teas commonly consumed in the United Kingdom. J Agric Food Chem 2002;50:565-70.
44. Henning M, Fajardo-Lira C, Lee HW, et al. Catechin content of 18 teas and a green tea extract supplement correlates with the antioxidant capacity. Nutr Cancer 2003;45:226-35.
45. Mohseni H, Zaslau S, McFadden D, et al. COX-2 inhibition demonstrates potent anti-proliferative effects on bladder cancer in vitro. J Surg Res 2004;119:138-42 .
46. Choi JH, Chai YM, Joo GJ, et al. Effects of green tea catechin on polymorphonuclear leukocyte 5'-lipoxygenase activity, leukotriene B4 synthesis, and renal damage in diabetic rats. Ann Nutr Metab 2004;48:151-5.
47. Ahmed S, Rahman A, Hasnain A, et al. Green tea polyphenol epigallocatechin-3-gallate inhibits the IL-1 beta-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes. Free Radic Biol Med 2002;33:1097-105.
48. Adcocks C, Collin P, Buttle DJ. Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglycan and type II collagen degradation in vitro. J Nutr 2002;132:341-6.
49. Haqqi TM, Anthony DD, Gupta S, et al. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl Acad Sci U S A 1999;96:4524-9.
50. Kaegi E. Unconventional therapies for cancer: 2. Green tea. The Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ 1998;158:1033-5.
51. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9.
52. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
53. Howell LL, Coffin VL, Spealman RD. Behavioral and physiological effects of xanthines in nonhuman primates. Psychopharmacology (Berl) 1997;129:1-14.
54. Chou T. Wake up and smell the coffee. Caffeine, coffee, and the medical consequences. West J Med 1992;157:544-53.
55. Stookey JD. The diuretic effects of alcohol and caffeine and total water intake misclassification. Eur J Epidemiol 1999;15:181-8.

1. Grandjean AC, Reimers KJ, Bannick KE, Haven MC. The effect of caffeinated, non-caffeinated, caloric and non-caloric beverages on hydration. J Am Coll Nutr 2000;19:591-600.
2. Leenen R, Roodenburg AJ, Tijburg LB, et al. A single dose of tea with or without milk increases plasma antioxidant activity in humans. Eur J Clin Nutr 2000;54:87-92.
3. Hodgson JM, Puddey IB, Croft KD, et al. Acute effects of ingestion of black and green tea on lipoprotein oxidation. Am J Clin Nutr 2000;71:1103-7.
4. Leung LK, Su Y, Chen R, et al. Theaflavins in black tea and catechins in green tea are equally effective antioxidants. J Nutr 2001;131:2248-51.
5. Hodgson JM, Croft KD, Mori TA, et al. Regular ingestion of tea does not inhibit in vivo lipid peroxidation in humans. J Nutr 2002;132:55-8.
6. de Maat MP, Pijl H, Kluft C, Princen HM. Consumption of black and green tea had no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals. Eur J Clin Nutr 2000;54:757-63.
7. Bradley Pharmaceuticals. Veregen Prescribing Information. October 2006.
8. Stammler G, Volm M. Green tea catechins (EGCG and EGC) have modulating effects on the activity of doxorubicin in drug-resistant cell lines. Anticancer Drugs 1997;8:265-8.
9. Shaw JC. Green tea polyphenols may be useful in the treatment of androgen-mediated skin disorders. Arch Dermatol 2001;137:664.
10. Elmets CA, Singh D, Tubesing K, et al. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. J Am Acad Dermatol 2001;44:425-32.
11. Dulloo AG, Duret C, Rohrer D, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr 1999;70:1040-5.
12. Cronin JR. Green tea extract stokes thermogenesis: will it replace ephedra? Altern Comp Ther 2000;6:296-300.
13. Zheng G, Sayama K, Okubo T, et al. Anti-obesity effects of three major components of green tea, catechins, caffeine and theanine, in mice. In Vivo 2004;18:55-62.
14. Acheson KJ, Gremaud G, Meirim I, et al. Metabolic effects of caffeine in humans: lipid oxidation or futile cycling? Am J Clin Nutr 2004;79:40-6.
15. Weisburger JH. Tea and health: the underlying mechanisms. Proc Soc Exp Biol Med 1999;220:271-5
16. Choi YT, Jung CH, Lee SR, et al. The green tea polyphenol (-)-epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci 2001;70:603-14.
17. Jatoi A, Ellison N, Burch PA, et al. A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer 2003;97:1442-6.
18. Bonkovsky HL. Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann Intern Med 2006;144:68-71.
19. Jimenez-Saenz M, Martinez-Sanchez, MDC. Acute hepatitis associated with the use of green tea infusions. J Hepatol 2006;44:616-9.
20. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73.
21. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63.
22. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8.
23. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.
24. Gloro R, Hourmand-Ollivier I, Mosquet B, et al. Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea. Eur J Gastroenterol Hepatol 2005;17:1135-7.
25. Samman S, Sandstrom B, Toft MB, et al. Green tea or rosemary extract added to foods reduces nonheme-iron absorption. Am J Clin Nutr 2001;73:607-12.
26. Zijp IM, Korver O, Tijburg LB. Effect of tea and other dietary factors on iron absorption. Crit Rev Food Sci Nutr 2000;40:371-98
27. Merhav H, Amitai Y, Palti H, Godfrey S. Tea drinking and microcytic anemia in infants. Am J Clin Nutr 1985;41:1210-3
28. Kubota K, Sakurai T, Nakazato K, et al. [Effect of green tea on iron absorption in elderly patients with iron deficiency anemia]. Nippon Ronen Igakkai Zasshi 1990;27:555-8.
29. Migliardi JR, Armellino JJ, Friedman M, et al. Caffeine as an analgesic adjuvant in tension headache. Clin Pharmacol Ther 1994;56:576-86.
30. Smith A. Effects of caffeine on human behavior. Food Chem Toxicol 2002;40:1243-55.
31. Zhang M, Binns CW, Lee AH. Tea consumption and ovarian cancer risk: a case-control study in China. Cancer Epidemiol Biomarkers Prev 2002;11:713-8.
32. Schliep KC, Schisterman EF, Mumford SL, et al. Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study. Am J Clin Nutr. 2012;95(27):488-497.