Thromb Haemost 2005; 93(01): 03-07
DOI: 10.1160/TH04-05-0285
Review Article
Schattauer GmbH

Herbal remedies and anticoagulant therapy

Noah Samuels
1   Unit of Complementary Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
› Institutsangaben
Weitere Informationen

Correspondence to:

Dr. Noah Samuels
130 Rachmilevich Street
Jerusalem 97791, Israel
Telefon: 972–2–5850371   
Fax: 972–2–5849825   

Publikationsverlauf

Received 07. Mai 2004

Accepted after resubmission 21. Oktober 2004

Publikationsdatum:
14. Dezember 2017 (online)

 

Summary

Herbal remedies, considered to be both safe and effective by most consumers, may interact with conventional drugs.Warfarin, a vitamin K antagonist originally derived from the sweet clover plant, has a narrow therapeutic window which can be monitored using prothrombin international normalized ratios (PT-INR). Many herbs can increase the risk for bleeding when combined with warfarin, either by augmenting the anticoagulant effects of the drug (with increased PT-INR levels) or through intrinsic anti-platelet properties (without altering PT-INR levels). The increased risk for bleeding among such patients may be difficult to predict, especially when formulas which contain many herbs are used. Further research into herb-drug interactions is warranted, as are guidelines for the use of herbal remedies by patients on chronic anticoagulation therapy.


#

 


#
  • References

  • 1 Eisenberg DM, Davis RB, Ettner SL. et al Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 1998; 280: 1569-75.
  • 2 Kaufman DW, Kelly JP, Rosenberg L. et al Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 2002; 287: 337-44.
  • 3 Gulla J, Singer AJ. Use of alternative therapies among emergency department patients. Ann Emerg Med 2000; 35: 226-7.
  • 4 De Smet PAGM. Herbal remedies. N Engl J Med 2002; 347: 2046-56.
  • 5 Schulman S. Care of patients receiving long-term anticoagulant therapy. N Engl J Med 2003; 349: 675-83.
  • 6 Schulman S. Oral anticoagulation. In Butler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U. eds Williams Hematology. 6th ed.. New Yok: McGraw-Hill; 2001: 1777-92.
  • 7 Burnham BE. Garlic as a possible risk for postoperative bleeding. Plastic Recon Surg 1995; 95: 213.
  • 8 Rose KD, Croissant PD, Parliament CF. et al Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurgery 1990; 26: 880-2.
  • 9 German K, Kumar U, Blackford HN. Garlic and the risk of TURP bleeding. Br J Urol 1995; 76: 518.
  • 10 Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of ginkgo biloba extract. N Engl J Med 1997; 336: 1108.
  • 11 Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology 1996; 46: 1775-6.
  • 12 Gilbert GJ. Ginkgo biloba. Neurology 1997; 48: 1137.
  • 13 Matthews MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998; 50: 1933-4.
  • 14 Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet 1998; 352: 36.
  • 15 Wong ALN, Chan TYK. Interaction between warfarin and the herbal product Quilinggao. Ann Pharmacother 2003; 37: 836-8.
  • 16 Hogan RP. Hemorrhagic diathesis caused by drinking an herbal tea. JAMA 1983; 249: 2679-80.
  • 17 Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997; 54: 692-3.
  • 18 Hopkins MP, Androff L, Benninghoff AS. Ginseng face cream and unexplained vaginal bleeding. Am J Obstet Gynecol 1988; 159: 1121-2.
  • 19 Greenspan EM. Ginseng and vaginal bleeding. JAMA 1983; 249: 2018.
  • 20 Yu CM, Chan JCN, Sanderson JE. Chinese herbs and warfarin potentiation by ‘Danshen’. J Int Med 1997; 241: 337-9.
  • 21 Tam LS, Chan TYK, Leung WK. et al Warfarin interactions with Chinese traditional medicines: danshen and methyl salicylate medicated oil. Aust N Z J Med 1995; 25: 258.
  • 22 Izzat MB, Yim AP, El-Zufari MH. A taste of Chinese medicine. Ann Thorac Surg 1998; 66: 941-942.
  • 23 Shaw D, Leon C, Kolev S. et al Traditional remedies and food supplements: a 5-year toxicological study (1991–1995). Drug Saf 1997; 17: 342-56.
  • 24 Norred CL, Brinker F. Potential coagulation effects of preoperative complementary and alternative medicines. Alt Ther Health Med 2001; 7: 58-67.
  • 25 Heck AM. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000; 57: 1221-30.
  • 26 Hoult JRS, Paya M. Pharmacological and biochemical actions of simple coumarins: Natural products with therapeutic potential. Gen Pharmac 1996; 27: 713-22.
  • 27 Lindberg RL, Negishi M. Alteration of mouse cytochrome P450cho substrate specificity by muation of a single amino-acid residue. Nature 1989; 339: 632-4.
  • 28 Gong X, Sucher NJ. Stroke therapy in traditional Chinese medicine (TCM): prospects for drug discovery and development. Trends Pharmacol Sci 1999; 20: 191-6.
  • 29 Mashour NH, Lin I G, Frishman WH. Herbal medicine for the treatment of cardiovascular disease: clinical considerations. Arch Intern Med 1998; 158: 2225-34.
  • 30 Chan K, Lo ACT, Yeung JHK. et al The effects of Danshen ( Salvia miltiorrhiza) on warfarin pharmacodynamics and pharmacokinetics of warfarin enantiomers in rats. J Pharm Pharmacol 1995; 47: 402-6.
  • 31 Chan TY. Interaction between warfarin and danshen ( Salvia miltiorrhiza). Ann Pharmacother 2001; 35: 501-4.
  • 32 Li BQ, Fu T, Yan YD. et al Inhibition of HIV infection by baicalin – a flavonoid compound purified from Chinese herbal medicine. Cell Mol Biol Res 1993; 39: 119-24.
  • 33 Kubo M, Matsuda H, Tani T. et al Studies on Scutellariae radix XII. Anti-thrombic actions of various flavonoids from Scutellariae radix. Chem Pharm Bull 1985; 33: 2411-5.
  • 34 Dong H, Chen SX, Kini RM. et al Effects of tannins from Geum japonicum on the catalytic activity of thrombin and factor Xa of blood coagulation cascade. J Nat Prod 1998; 61: 1356-60.
  • 35 Teng CM, Ko FN, Wang JP. et al Antihaemostatic and antithrombotic effect of some antiplatelet agents isolated from Chinese herbs. J Pharm Pharmacol 1991; 43: 667-9.
  • 36 Ackerman RT, Mulrow CD, Ramirez G. et al Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med 2001; 161: 813-24.
  • 37 Stevinson C, Pittle MH, Ernst E. Garlic for treating hypercholesterolemia. A meta-analysis of randomized clinical trials. Ann Intern Med 2000; 133: 420-9.
  • 38 Bordia A. Effect of garlic on human platelet aggregation in vitro. Atherosclerosis 1978; 30: 355-60.
  • 39 Bordia A, Bansal HC, Arora SK. et al Effect of the essential oils of garlic and onion on alimentary hyperlipemia. Atherosclerosis 1975; 21: 15-19.
  • 40 Bordia A, Verma SK. Srivastava KC. Effect of garlic ( Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1998; 58: 257-63.
  • 41 Mohammad SF, Woodward SC. Characterization of a potent inhibitor of platelet aggregation and release reaction isolated from allium sativum (garlic). Thromb Res 1986; 44: 793-806.
  • 42 Makheja AN, Vanderhoek JY, Bailey JM. Inhibition of platelet aggregation and thromboxane synthesis by onion and garlic. Lancet 1979; 1: 781.
  • 43 Lawson LD, Ransom DK, Hughes BG. Inhibition of whole blood platelet-aggregation by compounds in garlic clove extracts and commercial garlic products. Thromb Res 1992; 65: 141-56.
  • 44 Apitz-Castro R, Cabrera S, Cruz MR. et al Effects of garlic extract and of three pure components isolated from it on human platelet aggregation, arachidonate metabolism, release reaction and platelet ultrastructure. Thromb Res 1983; 32: 155-69.
  • 45 Rahman K, Billington D. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr 2000; 130: 2662-65.
  • 46 Makheja AN, Bailey JM. Antiplatelet constituents of garlic and onion. Agents Actions 1990; 29: 360-3.
  • 47 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.
  • 48 Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2003; 4: CD 000145.
  • 49 Srivastava KC. Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids 1989; 35: 183-5.
  • 50 Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1997; 56: 379-84.
  • 51 Srivastava KC. Isolation and effects of some ginger components of platelet aggregation and eicosanoid biosynthesis. Prostaglandins Leukotr Med 1986; 25: 187-98.
  • 52 Vogler BK, Pittler MH, Ernst E. Feverfew as a preventive treatment for migraine: a systematic review. Cephalgia 1998; 18: 704-8.
  • 53 Pittler MH, Vogler BK, Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev 2000; 3: CD002286.
  • 54 Ernst E, Pittler MH. The efficacy and safety of feverfew (Tanacetum parthenium L.): an update of a systematic review. Public Health Nutr 2000; 3: 509-14.
  • 55 Makheja AN, Bailey JM. The active principle in feverfew. Lancet 1981; 2: 1054.
  • 56 Heptinstall S, Groenewegen WA, Spangenberg P. et al Extracts of feverfew may inhibit platelet behaviour via neutralization of suphydryol groups. J Pharm Pharmacol 1987; 39: 459-65.
  • 57 Biggs MJ, Johnson ES, Persaud NP. et al Platelet aggregation in patients using feverfew for migraine. Lancet 1982; 2: 776.
  • 58 Groenewegen WA, Heptinstall S. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity invitro. J Pharm Pharmacol 1990; 42: 553-7.
  • 59 Collier HO, Butt NM, McDonald-Gibson WJ. et al Extract of feverfew inhibits prostaglandin biosynthesis. Lancet 1980; 2: 922-3.
  • 60 Dragland S, Senoo H, Wake K. et al Several culinary and medicinal herbs are important sources of dietary antioxidants. J Nutr 2003; 133: 1286-90.
  • 61 Srivastava KC. Antiplatelet principles from a food spice clove (Syzygium aromaticum L). Prostaglandins Leukot Essent Fatty Acids 1993; 48: 363-72.
  • 62 Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci 2001; 58: 1234-45.
  • 63 Morita AH, Uchida DA, Taussig SJ. et al Chromatogographic fractionation and characterization of the active platelet aggregation inhibitory factor from bromelain. Arch Int Pharmacodyn Ther 1979; 239: 340-50.
  • 64 Tawata M, Yoda Y, Aida K. et al Anti-platelet action of GU-7, a 3-arylcoumarin derivative, purified fro Glycyrrhizae radix. Planta Med 1990; 56: 259-63.
  • 65 Tawata M, Aida K, Noguchi T. et al Anti-platelet action of isoliquiritigenin, an aldose reductase inhibitor in licorice. Eur J Pharmacol 1992; 25: 87-92.
  • 66 Wang Z, Roberts JM, Grant PG. et al The effects of a medicinal Chinese herb on platelet function. Thromb Haemost 1982; 48: 301-6.
  • 67 Murray MT. Panax ginseng. In The Healing Power of herbs. Prima Publishing; 1995. USA: pp 265-279.
  • 68 Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomized clinical trials. Eur J Clin Pharmacol 1999; 55: 567-75.
  • 69 Yun YP, Do JH, Ko SR. et al Effects of Korean red ginseng and its mixed prescription on the high molecular weight dextran-indced blood stasis in rats and human platelet aggregation. J Ethnopharm 2001; 77: 259-64.
  • 70 Pittler MH, Ernst E. Gingko biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med 2000; 108: 276-81.
  • 71 Canter PH, Ernst E. Ginkgo biloba: a smart drug? A systematic review of controlled trials of the cognitive effects of ginkgo biloba extracts in healthy people. Psychopharmacol Bull 2002; 36: 108-23.
  • 72 Le Bars PL, Katz MM, Berman N. et al A placebocontrolled, double-blind randomized trial of an extract of Ginkgo biloba for dementia. JAMA 1997; 278: 1327-32.
  • 73 Chung KF McCusker, Page CP. et al Effect of a ginkgolide mixture (BN 52063) in antagonizing skin and platelet responses to platelet activating factor in man. Lancet 1987; 1: 248-51.
  • 74 Halat KM, Dennehy CE. Botanicals and dietary supplements in diabetic peripheral neuropathy. J Am Board Fam Pract 2003; 16: 47-57.
  • 75 Wang JP, Hsu MF, Teng CM. Antiplatelet effect of capsacain. Thromb Res 1984; 36: 497-507.
  • 76 Wasantapruek S, Poolsuppasit S, Pibolnukarintr O. Enhanced fibriolytic activity after capsicum ingestion. N Engl J Med 1974; 290: 1259-60.
  • 77 Bensky D, Barole R. Chinese Herbal Medicine: Formulas and Strategies. Eastland Press; 1990. Seattle WA: pp 3-27.
  • 78 Makino T, Wakushima H, Okamoto T. et al Pharmacokinetic interactions between warfarin and kangen-karyu, a Chinese traditional hebal medicine, and their synergistic action. J Ethnopharmacol 2002; 82: 35-40.
  • 79 Makino T, Wakushima H, Okamoto T. et al Effects of Kangen-karyu on coagulation system and platelet aggregation in mice. Biol Pharm Bull 2002; 25: 523-5.
  • 80 Makino T, Wakushima H, Okamoto T. et al Pharmacokinetic and pharmacological interactions between ticlopidine hydrochloride and Kangen-Karyu – Chinese traditional herbal medicine. Phytother Res 2003; 17: 1021-4.
  • 81 Gou YL, Ho ALS, Rowlands DK. et al Effects of Bak Foong pill on blood coagulation and platelet aggregation. Biol Pharm Bull 2003; 26: 241-6.
  • 82 Gaudineau C, Beckerman R, Welbourn S. et al Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem Biophys Res Commun 2004; 318: 1072-8.
  • 83 Sugiyama T, Kubota Y, Shinozuka K. et al Gingko biolbab extract modifies hypoglycemic action of tolbutamied via hepatic cytochrome P450 mediated mechanism in aged rats. Life Sci 2004; 75: 1113-22.
  • 84 Engelsen J, Nielsen JD, Winther K. Effect of Coenzyme Q 10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomized, double blind, placebo-crossover trial. Thromb Haemost 2002; 87: 1075-6.
  • 85 Cui J, Garle M, Eneroth P. et al What do commercial ginseng preparations contain?. Lancet 1994; 344: 134.
  • 86 National Center for Complementary and Alternative Medicine (NCCAM): Get the facts: Herbal supplements: consider safety, too nccam.nih.gov/ health.
  • 87 Eisenberg DM. Advising patients who seek alternative therapies. Ann Intern Med 1997; 127: 61-69.
  • 88 Mashour NH, Lin I G, Frishman WH. Herbal medicine for the treatment of cardiovascular disease. Arch Intern Med 1998; 158: 2225-34.

Correspondence to:

Dr. Noah Samuels
130 Rachmilevich Street
Jerusalem 97791, Israel
Telefon: 972–2–5850371   
Fax: 972–2–5849825   

  • References

  • 1 Eisenberg DM, Davis RB, Ettner SL. et al Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 1998; 280: 1569-75.
  • 2 Kaufman DW, Kelly JP, Rosenberg L. et al Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 2002; 287: 337-44.
  • 3 Gulla J, Singer AJ. Use of alternative therapies among emergency department patients. Ann Emerg Med 2000; 35: 226-7.
  • 4 De Smet PAGM. Herbal remedies. N Engl J Med 2002; 347: 2046-56.
  • 5 Schulman S. Care of patients receiving long-term anticoagulant therapy. N Engl J Med 2003; 349: 675-83.
  • 6 Schulman S. Oral anticoagulation. In Butler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U. eds Williams Hematology. 6th ed.. New Yok: McGraw-Hill; 2001: 1777-92.
  • 7 Burnham BE. Garlic as a possible risk for postoperative bleeding. Plastic Recon Surg 1995; 95: 213.
  • 8 Rose KD, Croissant PD, Parliament CF. et al Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurgery 1990; 26: 880-2.
  • 9 German K, Kumar U, Blackford HN. Garlic and the risk of TURP bleeding. Br J Urol 1995; 76: 518.
  • 10 Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of ginkgo biloba extract. N Engl J Med 1997; 336: 1108.
  • 11 Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology 1996; 46: 1775-6.
  • 12 Gilbert GJ. Ginkgo biloba. Neurology 1997; 48: 1137.
  • 13 Matthews MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998; 50: 1933-4.
  • 14 Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet 1998; 352: 36.
  • 15 Wong ALN, Chan TYK. Interaction between warfarin and the herbal product Quilinggao. Ann Pharmacother 2003; 37: 836-8.
  • 16 Hogan RP. Hemorrhagic diathesis caused by drinking an herbal tea. JAMA 1983; 249: 2679-80.
  • 17 Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997; 54: 692-3.
  • 18 Hopkins MP, Androff L, Benninghoff AS. Ginseng face cream and unexplained vaginal bleeding. Am J Obstet Gynecol 1988; 159: 1121-2.
  • 19 Greenspan EM. Ginseng and vaginal bleeding. JAMA 1983; 249: 2018.
  • 20 Yu CM, Chan JCN, Sanderson JE. Chinese herbs and warfarin potentiation by ‘Danshen’. J Int Med 1997; 241: 337-9.
  • 21 Tam LS, Chan TYK, Leung WK. et al Warfarin interactions with Chinese traditional medicines: danshen and methyl salicylate medicated oil. Aust N Z J Med 1995; 25: 258.
  • 22 Izzat MB, Yim AP, El-Zufari MH. A taste of Chinese medicine. Ann Thorac Surg 1998; 66: 941-942.
  • 23 Shaw D, Leon C, Kolev S. et al Traditional remedies and food supplements: a 5-year toxicological study (1991–1995). Drug Saf 1997; 17: 342-56.
  • 24 Norred CL, Brinker F. Potential coagulation effects of preoperative complementary and alternative medicines. Alt Ther Health Med 2001; 7: 58-67.
  • 25 Heck AM. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000; 57: 1221-30.
  • 26 Hoult JRS, Paya M. Pharmacological and biochemical actions of simple coumarins: Natural products with therapeutic potential. Gen Pharmac 1996; 27: 713-22.
  • 27 Lindberg RL, Negishi M. Alteration of mouse cytochrome P450cho substrate specificity by muation of a single amino-acid residue. Nature 1989; 339: 632-4.
  • 28 Gong X, Sucher NJ. Stroke therapy in traditional Chinese medicine (TCM): prospects for drug discovery and development. Trends Pharmacol Sci 1999; 20: 191-6.
  • 29 Mashour NH, Lin I G, Frishman WH. Herbal medicine for the treatment of cardiovascular disease: clinical considerations. Arch Intern Med 1998; 158: 2225-34.
  • 30 Chan K, Lo ACT, Yeung JHK. et al The effects of Danshen ( Salvia miltiorrhiza) on warfarin pharmacodynamics and pharmacokinetics of warfarin enantiomers in rats. J Pharm Pharmacol 1995; 47: 402-6.
  • 31 Chan TY. Interaction between warfarin and danshen ( Salvia miltiorrhiza). Ann Pharmacother 2001; 35: 501-4.
  • 32 Li BQ, Fu T, Yan YD. et al Inhibition of HIV infection by baicalin – a flavonoid compound purified from Chinese herbal medicine. Cell Mol Biol Res 1993; 39: 119-24.
  • 33 Kubo M, Matsuda H, Tani T. et al Studies on Scutellariae radix XII. Anti-thrombic actions of various flavonoids from Scutellariae radix. Chem Pharm Bull 1985; 33: 2411-5.
  • 34 Dong H, Chen SX, Kini RM. et al Effects of tannins from Geum japonicum on the catalytic activity of thrombin and factor Xa of blood coagulation cascade. J Nat Prod 1998; 61: 1356-60.
  • 35 Teng CM, Ko FN, Wang JP. et al Antihaemostatic and antithrombotic effect of some antiplatelet agents isolated from Chinese herbs. J Pharm Pharmacol 1991; 43: 667-9.
  • 36 Ackerman RT, Mulrow CD, Ramirez G. et al Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med 2001; 161: 813-24.
  • 37 Stevinson C, Pittle MH, Ernst E. Garlic for treating hypercholesterolemia. A meta-analysis of randomized clinical trials. Ann Intern Med 2000; 133: 420-9.
  • 38 Bordia A. Effect of garlic on human platelet aggregation in vitro. Atherosclerosis 1978; 30: 355-60.
  • 39 Bordia A, Bansal HC, Arora SK. et al Effect of the essential oils of garlic and onion on alimentary hyperlipemia. Atherosclerosis 1975; 21: 15-19.
  • 40 Bordia A, Verma SK. Srivastava KC. Effect of garlic ( Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1998; 58: 257-63.
  • 41 Mohammad SF, Woodward SC. Characterization of a potent inhibitor of platelet aggregation and release reaction isolated from allium sativum (garlic). Thromb Res 1986; 44: 793-806.
  • 42 Makheja AN, Vanderhoek JY, Bailey JM. Inhibition of platelet aggregation and thromboxane synthesis by onion and garlic. Lancet 1979; 1: 781.
  • 43 Lawson LD, Ransom DK, Hughes BG. Inhibition of whole blood platelet-aggregation by compounds in garlic clove extracts and commercial garlic products. Thromb Res 1992; 65: 141-56.
  • 44 Apitz-Castro R, Cabrera S, Cruz MR. et al Effects of garlic extract and of three pure components isolated from it on human platelet aggregation, arachidonate metabolism, release reaction and platelet ultrastructure. Thromb Res 1983; 32: 155-69.
  • 45 Rahman K, Billington D. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr 2000; 130: 2662-65.
  • 46 Makheja AN, Bailey JM. Antiplatelet constituents of garlic and onion. Agents Actions 1990; 29: 360-3.
  • 47 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.
  • 48 Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2003; 4: CD 000145.
  • 49 Srivastava KC. Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids 1989; 35: 183-5.
  • 50 Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1997; 56: 379-84.
  • 51 Srivastava KC. Isolation and effects of some ginger components of platelet aggregation and eicosanoid biosynthesis. Prostaglandins Leukotr Med 1986; 25: 187-98.
  • 52 Vogler BK, Pittler MH, Ernst E. Feverfew as a preventive treatment for migraine: a systematic review. Cephalgia 1998; 18: 704-8.
  • 53 Pittler MH, Vogler BK, Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev 2000; 3: CD002286.
  • 54 Ernst E, Pittler MH. The efficacy and safety of feverfew (Tanacetum parthenium L.): an update of a systematic review. Public Health Nutr 2000; 3: 509-14.
  • 55 Makheja AN, Bailey JM. The active principle in feverfew. Lancet 1981; 2: 1054.
  • 56 Heptinstall S, Groenewegen WA, Spangenberg P. et al Extracts of feverfew may inhibit platelet behaviour via neutralization of suphydryol groups. J Pharm Pharmacol 1987; 39: 459-65.
  • 57 Biggs MJ, Johnson ES, Persaud NP. et al Platelet aggregation in patients using feverfew for migraine. Lancet 1982; 2: 776.
  • 58 Groenewegen WA, Heptinstall S. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity invitro. J Pharm Pharmacol 1990; 42: 553-7.
  • 59 Collier HO, Butt NM, McDonald-Gibson WJ. et al Extract of feverfew inhibits prostaglandin biosynthesis. Lancet 1980; 2: 922-3.
  • 60 Dragland S, Senoo H, Wake K. et al Several culinary and medicinal herbs are important sources of dietary antioxidants. J Nutr 2003; 133: 1286-90.
  • 61 Srivastava KC. Antiplatelet principles from a food spice clove (Syzygium aromaticum L). Prostaglandins Leukot Essent Fatty Acids 1993; 48: 363-72.
  • 62 Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci 2001; 58: 1234-45.
  • 63 Morita AH, Uchida DA, Taussig SJ. et al Chromatogographic fractionation and characterization of the active platelet aggregation inhibitory factor from bromelain. Arch Int Pharmacodyn Ther 1979; 239: 340-50.
  • 64 Tawata M, Yoda Y, Aida K. et al Anti-platelet action of GU-7, a 3-arylcoumarin derivative, purified fro Glycyrrhizae radix. Planta Med 1990; 56: 259-63.
  • 65 Tawata M, Aida K, Noguchi T. et al Anti-platelet action of isoliquiritigenin, an aldose reductase inhibitor in licorice. Eur J Pharmacol 1992; 25: 87-92.
  • 66 Wang Z, Roberts JM, Grant PG. et al The effects of a medicinal Chinese herb on platelet function. Thromb Haemost 1982; 48: 301-6.
  • 67 Murray MT. Panax ginseng. In The Healing Power of herbs. Prima Publishing; 1995. USA: pp 265-279.
  • 68 Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomized clinical trials. Eur J Clin Pharmacol 1999; 55: 567-75.
  • 69 Yun YP, Do JH, Ko SR. et al Effects of Korean red ginseng and its mixed prescription on the high molecular weight dextran-indced blood stasis in rats and human platelet aggregation. J Ethnopharm 2001; 77: 259-64.
  • 70 Pittler MH, Ernst E. Gingko biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med 2000; 108: 276-81.
  • 71 Canter PH, Ernst E. Ginkgo biloba: a smart drug? A systematic review of controlled trials of the cognitive effects of ginkgo biloba extracts in healthy people. Psychopharmacol Bull 2002; 36: 108-23.
  • 72 Le Bars PL, Katz MM, Berman N. et al A placebocontrolled, double-blind randomized trial of an extract of Ginkgo biloba for dementia. JAMA 1997; 278: 1327-32.
  • 73 Chung KF McCusker, Page CP. et al Effect of a ginkgolide mixture (BN 52063) in antagonizing skin and platelet responses to platelet activating factor in man. Lancet 1987; 1: 248-51.
  • 74 Halat KM, Dennehy CE. Botanicals and dietary supplements in diabetic peripheral neuropathy. J Am Board Fam Pract 2003; 16: 47-57.
  • 75 Wang JP, Hsu MF, Teng CM. Antiplatelet effect of capsacain. Thromb Res 1984; 36: 497-507.
  • 76 Wasantapruek S, Poolsuppasit S, Pibolnukarintr O. Enhanced fibriolytic activity after capsicum ingestion. N Engl J Med 1974; 290: 1259-60.
  • 77 Bensky D, Barole R. Chinese Herbal Medicine: Formulas and Strategies. Eastland Press; 1990. Seattle WA: pp 3-27.
  • 78 Makino T, Wakushima H, Okamoto T. et al Pharmacokinetic interactions between warfarin and kangen-karyu, a Chinese traditional hebal medicine, and their synergistic action. J Ethnopharmacol 2002; 82: 35-40.
  • 79 Makino T, Wakushima H, Okamoto T. et al Effects of Kangen-karyu on coagulation system and platelet aggregation in mice. Biol Pharm Bull 2002; 25: 523-5.
  • 80 Makino T, Wakushima H, Okamoto T. et al Pharmacokinetic and pharmacological interactions between ticlopidine hydrochloride and Kangen-Karyu – Chinese traditional herbal medicine. Phytother Res 2003; 17: 1021-4.
  • 81 Gou YL, Ho ALS, Rowlands DK. et al Effects of Bak Foong pill on blood coagulation and platelet aggregation. Biol Pharm Bull 2003; 26: 241-6.
  • 82 Gaudineau C, Beckerman R, Welbourn S. et al Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem Biophys Res Commun 2004; 318: 1072-8.
  • 83 Sugiyama T, Kubota Y, Shinozuka K. et al Gingko biolbab extract modifies hypoglycemic action of tolbutamied via hepatic cytochrome P450 mediated mechanism in aged rats. Life Sci 2004; 75: 1113-22.
  • 84 Engelsen J, Nielsen JD, Winther K. Effect of Coenzyme Q 10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomized, double blind, placebo-crossover trial. Thromb Haemost 2002; 87: 1075-6.
  • 85 Cui J, Garle M, Eneroth P. et al What do commercial ginseng preparations contain?. Lancet 1994; 344: 134.
  • 86 National Center for Complementary and Alternative Medicine (NCCAM): Get the facts: Herbal supplements: consider safety, too nccam.nih.gov/ health.
  • 87 Eisenberg DM. Advising patients who seek alternative therapies. Ann Intern Med 1997; 127: 61-69.
  • 88 Mashour NH, Lin I G, Frishman WH. Herbal medicine for the treatment of cardiovascular disease. Arch Intern Med 1998; 158: 2225-34.