The Handbookof Clinically TestedHerbal Remedies

Volume 1

Part I: Fundamentals of Herbal MedicinePart II: Methods

Part III: Botanical Profiles-Product and Clinical Trial Information

(A rtichoke-Ginseng)

Marilyn Barrett, PhDEditor

The Haworth Herbal Press®Pharmaceutical Products Press®

The Haworth Medical Press®Imprints of The Haworth Press, Inc.

New York • London • Oxford

CONTENTS

VOLUME 1

About the Editor xxi

Contributors xxiii

Preface xxxi

Acknowledgments xxxv

Editor's Note xxxvii

PART I: FUNDAMENTALS OF HERBAL MEDICINE

Chapter 1. History and Regulation of Botanicalsin the United States 3

Loren D. IsraelsenMarilyn Barrett

Introduction 3History 3DSHEA Explained 5Drugs: OTC and Rx 10Prospectus 11

Chapter 2. Product Definition Deficiencies in ClinicalStudies of Herbal Medicines 13

Varro E. Tyler

Chapter 3. Identifying and Characterizing BotanicalProducts 23

Marilyn BarrettIdentifying Plants by Name 24Means of Assuring Plant Identity 26Preparations and Formulations 30Dose 30Bioavailability 30Guidelines 31Appendix: Preparations and Formulations 32

Chapter 4. Standardization of Botanical Preparations:What It Does and Does Not Tell Us 37

Uwe KoetterMarilyn Barrett

Introduction 37Standardization of Therapeutic Activity 38Standardization to Meet a Chemical Norm 39Standardization As a Reflection of Quality

Assurance Programs 41Guidance 43Situation in the Marketplace 44Perspective 45

Chapter 5. The Importance and Difficulty in Determiningthe Bioavailability of Herbal Preparations 49

Anton BiberFriedrich Lang

Chapter 6. "Borrowed Science" and "Phytoequivalence":Can Two Herbal Products Be Judged Equivalent? 59

Marilyn BarrettChemical or Pharmaceutical Equivalency 61Bioequivalency or Therapeutic Equivalency 62Application of the Concepts, Ginkgo As an Example 63Meta-Analyses 65Perspective 66

Chapter 7. Determining Efficacy of Herbal Preparations 69Tieraona Low Dog

Observational Medicine 70"Evidence-Based" Medicine 71Summary 74

Chapter 8. Evaluating Safety of Herbal Preparations 77Ezra Be jarJoseph M. BetzMarilyn Barrett

Evaluation of Safety 78Adverse Reactions 80Adverse-Event Reporting Systems 81Categorization According to the Degree of Safety 82

Product Quality As an Aspect of Safety 84Contraindications 85Drug-Herb Interactions 85Improving Our Knowledge of Safety 87

Chapter 9. Conducting Clinical Trials on Herbal DietarySupplements in North America: Commercialization,Confidence, and Conflicts 91

Anthony L. Alniada

The Spirit to Sponsor: Is There an Adequate EconomicIncentive to Fund Research? 92

Extracting Value from Science 95Competitor Kevlar: Preventing Piracy of Product-Specific

Data 96How Much Data Is Enough? 100We Have Data—Now What? 103Who Has Science and How Did They Acquire It? 105Conclusion 105

Chapter 10. Motives for Conducting Clinical Trialson Botanicals in Europe: A Focus on Germany 107

Joerg GruenweildStefan Spiess

Chapter 11. Pharmacopoeias and Botanical Monographs 115Marilyn BarrettRoy UptonV. Srini Srinivasan

United States Pharmacopeia and National Formulary(USP-NF) ' 116

American Herbal Pharmacopoeia (AHP) and TherapeuticCompendium 1 18

European Pharmacopoeia (EP) 119British Herbal Pharmacopoeia (BHP) and British Herbal

Compendium (BHC) 119German Commission E 120European Scientific Cooperative on Phytotherapy (ESCOP) 121Chinese Pharmacopoeia 121African Pharmeicopoeia 122The Pharmacopoeia of Japan 122The Pharmacopoeias of India 123

World Health Organization (WHO) 123Other Pharmacopoeias 124Summary and Perspective 124Sources of Pharmacopoeias 125

PART II: METHODS

Chapter 12. Methods of Product and Trial Inclusionand Evaluation 129

Marilyn BarrettGathering Information on Products and Trials 129Data on Products and Trials 134Evaluation of Clinical Trial Quality 137

Chapter 13. Clinical Trial Reviewer's Guidanceand Checklist 141

Tieraona Low DogLevels of Evidence 141Guidelines for Reviewer Checklist: Part I 142Guidelines for Reviewer Checklist: Part II 144Scoring 146

PART HI: BOTANICAL PROFILES-PRODUCT AND CLINICAL TRIAL INFORMATION

(Artichoke-Ginseng)

Single Herbs 151

Artichoke 151

Preparations Used in Reviewed Clinical Studies 151Artichoke Summary Table 152Summary of Reviewed Clinical Studies 153Postmarketing Surveillance Studies 154Adverse Reactions or Side Effects 154Information from Pharmacopoeial Monographs 155Details on Artichoke Products and Clinical Studies 157

Bilberry 163

Preparations Used in Reviewed Clinical Studies 163Bilberry Summary Table 164

Summary of Reviewed Clinical Studies 165Adverse Reactions or Side Effects 167Information from Pharmacopoeia] Monographs 168Details on Bilberry Products and Clinical Studies 171

Black Cohosh 185

Preparations Used in Reviewed Clinical Studies 185Black Cohosh Summary Table 186Summary of Reviewed Clinical Studies 187Postmarketing Surveillance Studies 189Adverse Reactions or Side Effects 189Information from Pharmacopoeia! Monographs 190Details on Black Cohosh Products and Clinical Studies 194

Boxwood 207

Preparations Used in Reviewed Clinical Studies 207Summary of Reviewed Clinical Studies 207Boxwood Summary Table 208Adverse Reactions or Side Effects 209Details on Boxwood Products and Clinical Studies 210

Butterbur, Purple 213

Preparations Used in Reviewed Clinical Studies 213Butterbur Summary Table 214Summary of Reviewed Clinical Studies 215Adverse Reactions or Side Effects 216Information from Pharmacopoeial Monographs 216Details on Butterbur Products and Clinical Studies 218

Cat's Claw 225

Preparations Used in Reviewed Clinical Studies 225Cat's Claw Summary Table 226Summary of Reviewed Clinical Studies 227Adverse Reactions or Side Effects 227Details on Cat's Claw Products and Clinical Studies 228

Chaste Tree 231

Preparations Used in Reviewed Clinical Studies 231Chaste Tree Summary Table 232Summary of Reviewed Clinical Studies 233Postmarketing Surveillance Studies 235Adverse Reactions or Side Effects 236Information from Pharmacopoeial Monographs 236Details on Chaste Tree Products and Clinical Studies 240

Cordyceps 255

Preparations Used in Reviewed Clinical Studies 255Summary of Reviewed Clinical Studies 255Cordyceps Summary Table 256Adverse Reactions or Side Effects 258Information from Pharmacopoeial Monographs 258Details on Cordyceps Products and Clinical Studies 260

Cranberry 265

Preparations Used in Reviewed Clinical Studies 265Summary of Reviewed Clinical Studies 265Cranberry Summary Table 266Adverse Reactions or Side Effects 267Information from Pharmacopoeial Monographs 268Details on Cranberry Products and Clinical Studies 270

Devil's Claw 277

Preparations Used in Reviewed Clinical Studies 277Summary of Reviewed Clinical Studies 277Devil's Claw Summary Table 278Adverse Reactions or Side Effects 280Information from Pharmacopoeial Monographs 280Details on Devil's Claw Products and Clinical Studies 283

Dragon's Blood Croton 291

Preparations Used in Reviewed Clinical Studies 291Dragon's Blood Croton Summary Table 292Summary of Reviewed Clinical Studies 293

Adverse Reactions or Side Effects 293Details on Dragon's Blood Products and Clinical Studies 295

Echinacea 303

Preparations Used in Reviewed Clinical Studies 303Echinacea Summary Table 304Summary of Reviewed Clinical Studies 307Reviews and Meta-Analyses of Clinical Studies 311Adverse Reactions or Side Effects 312Information from Pharmacopoeial Monographs 313Details on Echinacea Products and Clinical Studies 321

Elderberry 351

Preparations Used in Reviewed Clinical Studies 351Elderberry Summary Table 352Summary of Reviewed Clinical Studies 353Adverse Reactions or Side Effects 353Information from Pharmacopoeial Monographs 353Details on Elderberry Products and Clinical Studies 356

Evening Primrose 359

Preparations Used in Reviewed Clinical Studies 359Evening Primrose Summary Table 360Summary of Reviewed Clinical Studies 362Systematic Reviews and Meta-Analyses 367Adverse Reactions or Side Effects 368Details on Evening Primrose Products and Clinical Studies 370

Garlic 403

Preparations Used in Reviewed Clinical Studies 403Garlic Summary Table 404Summary of Reviewed Clinical Studies 408Meta-Analyses and Systematic Clinical Reviews 419Epidemiological Studies 421Adverse Reactions or Side Effects 421Information from Pharmacopoeial Monographs 422Details on Garlic Products and Clinical Studies 429

Ginger 493

Preparations Used in Reviewed Clinical Studies 493Ginger Summary Table 494Summary of Reviewed Clinical Studies 495Systematic Reviews and Meta-Analyses 501Adverse Reactions or Side Effects 501Information from Pharmacopoeial Monographs 502Details on Ginger Products and Clinical Studies 508

Ginkgo 547

Preparations Used in Reviewed Clinical Studies 547Ginkgo Summary Table 548Summary of Reviewed Clinical Studies 551Meta-Analyses and Systematic Reviews 562Adverse Reactions or Side Effects 565Information from Pharmacopoeial Monographs 566Details on Ginkgo Products and Clinical Studies 575

Ginseng 673

Preparations Used in Reviewed Clinical Studies 673Ginseng Summary Table 674Summary of Reviewed Clinical Studies 676Systematic Reviews 683Epidemiological Studies 683Adverse Reactions or Side Effects 684Information from Pharmacopoeial Monographs 685Details on Ginseng Products and Clinical Studies 691

VOLUME 2

PART III: BOTANICAL PROFILES-PRODUCT AND CLINICAL TRIAL INFORMATION

(Grape Seed-Valerian and Herbal Formulas)

Grape Seed 745

Preparations Used in Reviewed Clinical Studies 745Grape Seed Summary Table 746Summary of Reviewed Clinical Studies 747Adverse Reactions or Side Effects 750Details on Grape Seed Products and Clinical Studies 752

Grass Pollen 773

Preparation Used in Reviewed Clinical Studies 773Summary of Reviewed Clinical Studies 773Grass Pollen Summary Table 774Systematic Reviews 776Adverse Reactions or Side Effects 777Information from Pharmacopoeial Monographs 777Details on Grass Pollen Products and Clinical Studies 780

Green Tea 787

Preparations Used in Reviewed Clinical Studies 787Green Tea Summary Table 788Summary of Reviewed Clinical Studies 789Epidemiological Studies 792Adverse Reactions or Side Effects 793Details on Green Tea Products and Clinical Studies 796

Hawthorn 809

Preparations Used in Reviewed Clinical Studies 809Hawthorn Summary Table 810Summary of Reviewed Clinical Studies 811Postmarketing Surveillance Studies 813Adverse Reactions or Side Effects 814Information from Pharmacopoeial Monographs 814Details on Hawthorn Products and Clinical Studies 820

Horse Chestnut 843

Preparations Used in Reviewed Clinical Studies 843Horse Chestnut Summary Table 844Summary of Reviewed Clinical Studies 845Systematic Reviews 849Adverse Reactions or Side Effects 850Information from Pharmacopoeial Monographs 851Details on Horse Chestnut Products and Clinical Studies 855

Kava 887

Preparations Used in Reviewed Clinical Studies 887Summary of Reviewed Clinical Studies 887Kava Summary Table 888Systematic Reviews 892Adverse Reactions or Side Effects 893Information from Pharmacopoeial Monographs 895Details on Kava Products and Clinical Studies 899

Lemon Balm 923

Preparations Used in Reviewed Clinical Studies 923Summary of Reviewed Clinical Studies 923Lemon Balm Summary Table 924Adverse Reactions or Side Effects 925Information from Pharmacopoeial Monographs 926Details on Lemon Balm Products and Clinical Studies 928

Milk Thistle 933

Preparations Used in Reviewed Clinical Studies 933Milk Thistle Summary Table 934Summary of Reviewed Clinical Studies 935Meta-Analyses and Systematic Reviews 941Adverse Reactions or Side Effects 942Information from Pharmacopoeial Monographs 943Details on Milk Thistle Products and Clinical Studies 947

Pygeum 981

Preparations Used in Reviewed Clinical Studies 981Pygeum Summary Table 982Summary of Reviewed Clinical Studies 983Systematic Reviews 987Adverse Reactions or Side Effects 987Details on Pygeum Products and Clinical Studies 990

Red Clover 1011

Preparations Used in Reviewed Clinical Studies 1011Summary of Reviewed Clinical Studies 1011Red Clover Summary Table 1012Adverse Reactions or Side Effects 1015Information from Pharmacopoeial Monographs 1015Details on Red Clover Products and Clinical Studies 1017

Red Yeast Rice 1027

Preparations Used in Reviewed Clinical Studies 1027Red Yeast Summary Table 1028Summary of Reviewed Clinical Studies 1029Adverse Reactions or Side Effects 1031Details on Red Yeast Products and Clinical Studies 1033

Saw Palmetto 1043

Preparations Used in Reviewed Clinical Studies 1043Saw Palmetto Summary Table 1044Summary of Reviewed Clinical Studies 1046Meta-Analyses and Systematic Reviews 1052Adverse Reactions or Side Effects 1053Information from Pharmacopoeial Monographs 1053Details on Saw Palmetto Products and Clinical Studies 1059

St. John's Wort 1101

Preparations Used in Reviewed Clinical Studies 1101St. John's Wort Summary Table 1102Summary of Reviewed Clinical Studies 1105Systematic Reviews and Meta-Analyses 1114Postmarketing Surveillance Studies 1115Adverse Reactions or Side Effects 1116Drug Interactions 1117Information from Pharmacopoeial Monographs 1121Details on St. John's Wort Products and Clinical Studies 1131

Valerian 1197

Preparations Used in Reviewed Clinical StudiesValerian Summary TableSummary of Reviewed Clinical StudiesAdverse Reactions or Side EffectsInformation from Pharmacopoeial MonographsDetails on Valerian Products and Clinical Studies

119711981200120712081214

Herbal Formulas 1249

2nd Wind™ 1249

Preparations Used in Reviewed Clinical StudiesSummary of Reviewed Clinical Studies2nd Wind™ Summary TableAdverse Reactions or Side EffectsDetails on 2nd Wind Product and Clinical Studies

12491249125012511252

Cystone®

Preparations Used in Reviewed Clinical StudiesCystone® Summary TableSummary of Reviewed Clinical StudiesAdverse Reactions or Side EffectsDetails on Cystone Product and Clinical Studies

1257

12571258125912601261

Gastrim® 1265

Preparations Used in Reviewed Clinical Studies 1265Gastrim® Summary Table 1266Summary of Reviewed Clinical Studies 1267Adverse Reactions or Side Effects 1268Details on Gastrim Product and Clinical Studies 1269

Geriforte® 1275

Preparations Used in Reviewed Clinical Studies 1275Geriforte® Summary Table 1276Summary of Reviewed Clinical Studies 1277Adverse Reactions or Side Effects 1277Details on Geriforte Product and Clinical Studies 1279

Iberogast™ 1283

Preparations Used in Reviewed Clinical Studies 1283Summary of Reviewed Clinical Studies 1283Iberogast™ Summary Table 1284Adverse Reactions or Side Effects 1286Details on Iberogast Product and Clinical Studies 1288

Padma® 1295

Padma® Summary Table 1296Preparations Used in Reviewed Clinical Studies 1297Summary of Reviewed Clinical Studies 1298Adverse Reactions or Side Effects 1301Details on Padma Product and Clinical Studies 1303

Phytodolor™ 1321

Preparations Used in Reviewed Clinical Studies 1321Phytodolor™ Summary Table 1322Summary of Reviewed Clinical Studies 1323Systematic Reviews 1324Adverse Reactions or Side Effects in Clinical Studies 1325Details on Phytodolor Product and Clinical Studies 1326

Prostane® 1333

Preparations Used in Reviewed Clinical Studies 1333Summary of Reviewed Clinical Studies 1333Prostane® Summary Table 1334Adverse Reactions or Side Effects 1335Details on Prostane Product and Clinical Studies 1336

Resistex™ 1339

Preparations Used in Reviewed Clinical Studies 1339Summary of Reviewed Clinical Studies 1339Resistex™ Summary Table 1340Adverse Reactions or Side Effects 1341Details on Resistex Product and Clinical Studies 1343

Sinupret® 1347

Preparations Used in Reviewed Clinical Studies 1347Summary of Reviewed Clinical Studies 1347Sinupret® Summary Table 1348Postmarketing Surveillance Study 1350Adverse Reactions or Side Effects 1350Details on Sinupret Product and Clinical Studies 1353

Appendix A. Products Listed by Manufacturer/Distributor 1359

Appendix B. Manufacturer/Distributor ContactInformation 1367

Index 1377