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Ginkgo bilobo, Bleeding,
Anticoagulants, and Surgery

This article was written by Eric Yarnell, ND, RH(AHG) and is protected by copyright, 2021.
Last updated 10 Feb 2021 

Misleading Review Articles

These reviews state ginkgo potentiates anticoagulants or cause bleeding after surgery, but their conclusions are based on a theoretical extrapolation from in vitro and animal studies and/or human case studies. Since these were published, numerous human clinical trials (documented below) have shown that their predictions were wrong and there is no interaction (with one minor exception, as noted below).

Izzo AA, Ernst E (2001) "Interactions between herbal medicines and prescribed drugs: A systematic review" Drugs 61:2163–75.

Ang-Lee MK, Moss J, Yuan CS (2001) "Herbal medicines and perioperative care" JAMA 286(2):208–16. 

Williamson EM (2003) "Drug interactions between herbal and prescription medicines" Drug Saf 26:1075–92.

These reviews were published after several human trials showed no interactions, and yet still report that ginkgo interacts with anticoagulants or surgery (these might be called politics-based, rather than evidence-based, reviews):

Izzo AA, Ernst E (2009) "Interactions between herbal medicines and prescribed drugs: An updated systematic review" Drugs 69(13):1777–98.

Tsai HH, Lin HW, Simon Pickard A, et al. (2012) "Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: A systematic literature review" Int J Clin Pract 66(11):1056–78.
    Cites two human clinical trials (ignoring/missing several others) which showed no interactions, yet then goes on to cite 20+ review articles that do not consider the clinical trials, concluding erroneously that ginkgo interacts harmfully with anticoagulants.

Evidence-Based Review Articles

Bone KM (2008) "Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: What is the evidence?" Mol Nutr Food Res 52(7):764–71.
      This cites the published human clinical trial evidence to date and concludes accurately that there are no clear interactions between ginkgo and anticoagulants.

Table Summarizing Human Clinical Trials

 

Anti-Clotting Drug

n

GBE dose

Outcome

Ref

Warfarin mix dose

24 European adults

100 mg

No effect

Engelsen 2003

Warfarin 25 mg

12 healthy Asian and European men

120 mg qd

No effect

Jiang 2005

Warfarin 5 mg

12 healthy Asian adults

?

No effect

Zhou 2011

Aspirin 325 mg

55 European adults w/ PAD

300 mg qd

No effect

Gardner 2007

Ticlopidine 250 mg

24 healthy Asian men

80 mg qd

No effect

Kim 2010

Ticlopidine 250 mg

127 Asian men with strokes

80 mg bid

No effect

Hong 2013

Cilostazol 100 mg

34 healthy Asian men

80 mg qd

No effect

Kim 2014

Cilostazol 100 mg

10 healthy Asian men

120 mg qd

Prolonged bleeding time

Aruna 2007

Clopidogrel 75 mg

10 healthy Asian men

120 mg qd

No effect

Aruna 2007

 

Warfarin

Systematic review of clinical trials showing no interactions: 
Choi S, Oh DS, Jerng UM (2017) "A systematic review of the pharmacokinetic and pharmacodynamic interactions of herbal medicine with warfarin" PLoS One 12(8):e0182794.

n=24 Danish adults on long-term stable warfarin therapy (one of the few real-world studies as a result)
Double-blind, randomized, crossover trial.
Participants cycled between adding gingko extract 100 mg, CoQ10 100 mg, or placebo each for 4 wk with 2 wk wash-out between treatments.
No change in INR or warfarin dosing was needed with ginkgo or CoQ10.
Engelsen J, Nielsen JD, Hansen KF (2003) "Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial" Ugeskr Laeger 165(18):1868–71 [in Danish].
    This appears to be an English version of this study: Engelsen J, Nielsen JD, Winther K (2003) "Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial" Thromb Haemost 87(6):1075–6.
    
N=6 Chinese women and 6 Chinese men, all healthy
Standardized ginkgo extract vs placebo tid x 5 wk, then single-dose warfarin 5 mg on day 29.
No change in PT, APTT, or pharmacokinetics,
Zhou Y, Zeng R (2011) “Effects of Ginkgo biloba extract on anticoagulation and blood drug level of warfarin in healthy volunteers” Zhongguo Zhong Yao Za Zhi 36(16):2290–3 [in Chinese].

n=24 healthy Australian men (ethnic/racial information not provided)
Randomized, open-label trial.
Ginkgo extract (of an unstated dose) caused no pharmacokinetic or pharmacodynamic interaction with a single 25 mg dose of warfarin.
Jiang X, Blair EY, McLachlan AJ (2006) "Investigation of the effects of herbal medicines on warfarin response in healthy subjects: A population pharmacokinetic-pharmacodynamic modeling approach" J Clin Pharmacol 46(11):1370–8.

N=12 men (half Asian, half European)
Open label, cross-over trial.

Ginkgo biloba extract (GBE) 120 mg tid or Zingiber officinale (ginger) 1200 mg tid x 1 wk
After one week on either herb, they took a single 25 mg dose of warfarin, continued herbs for 1 more week, then crossed over to the other herb.
No change in clotting status or pharmacokinetics with either herb.
Jiang XM, Williams KM, Liauw WS, et al. (2005) “Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects” Br J Clin Pharmacol 59(4):425–32.

Case study of bleeding associated with warfarin apparently (details not available)
Matthews MK Jr (1998) "Association of Ginkgo biloba with intracerebral hemorrhage" Neurology 50:1933–4.

Aspirin

 n=55 US adults with peripheral artery disease (another real-world study)
All were taking 325 mg aspirin qd.
Double-blind, randomized trial lasting 4 weeks.

Ginkgo extract 300 mg qd vs. placebo: no difference in two measures of platelet function, no difference in bruising or bleeding between the groups.
Gardner CD, Zehnder JL, Rigby AJ, et al. (2007) “Effect of Ginkgo biloba (Egb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: A randomized clinical trial” Blood Coag Fibrinolysis 18:787–93.

Case study: 70-yo man (ethnicity/race not stated) on aspirin 325 mg qd x 3 yr after CABG surgery.
Started on ginkgo extract 40 mg bid, two days later had hyphema (bleeding into the anterior chamber from the iris). Case studies like this cannot prove a causative connection between events.
Rosenblatt M, Mindel J (1997) "Spontaneous hyphema associated with ingestion of Ginkgo biloba extract" N Engl J Med 336:1108 [letter].

Ibuprofen

Case study: 71-yo man (ethnicity/race not stated) with a history of BPH and hip replacement who didn't drink alcohol was on ginkgo extract 40 mg bid x ~2.5 yr. Started on ibuprofen 600 mg qd for hip pain, 4 weeks later died of massive, non-traumatic intracerebral hemorrhage. Correlation does not equal causation.
Meisel C, Johne A, Roots I (2003) "Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen" Atherosclerosis 167(2):367. 

Ticlopodine

N=24 Korean men
Ticlopidine 250 mg alone or with GBE 80 mg x 1 wk then crossover
No difference in platelet inhibition between groups
Kim BH, Kim PK, Lim KS, et al. (2010) “Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: An open-label, randomized, two-period, two-treatment, two-sequence, single-dose crossover study in healthy korean male volunteers” Clin Ther 32(2):380–90.

n=41 on ticlopidine 250 mg qd alone, n=43 on ticlopidine 250 mg qd and GBE 80 mg bid x 3 mon
All subjects were Korean adults
No better or worse outcomes in the combination group (no evidence of synergy, no evidence of increased toxicity) vs. single drugs
Note: An additional group with n=43 on clopidogrel 75 mg qd alone (no clopidogrel + ginkgo group was included) was also involved in the study
Hong JM, Shin DH, Lim YA, et al. (2013) "Ticlopidine with Ginkgo biloba extract: A feasible combination for patients with acute cerebral ischemia" Thromb Res 131(4):e147–53.

Cilostazol

n=34 healthy Korean men
Randomized, double-blind clinical trial.
Cilostazol 100 mg + ginkgo extract 80 mg or cilostazol + placebo (all doses bid) x 7 days
No pharmacokinetic interaction and no statistically significant difference in platelet inhibition between the groups occurred.
Kim HS, Kim GY, Yeo CW, et al. (2014) "The effect of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of cilostazol and its active metabolites in healthy Korean subjects" Br J Clin Pharmacol 77(5):821–30.

n=10 healthy East Indian men
Randomized, open-label, cross-over study.
Various doses and combinations tested in random order: ginkgo extract 120 mg, ginkgo extract 240 mg, cilostazol 100 mg, cilostazol 200 mg, clopidogrel 75 mg, clopidogrel 150, ginkgo extract 120 mg + cilostazol 100 mg, ginkgo extract 120 mg + clopidogrel 75 mg.
Bleeding time was prolonged only in the ginkgo + cilostazol group (clotting time and and platelet counts unchanged). This is only example from any clinical trial of ginkgo and anticoagulants showing a synergistic interaction. And of course the larger, more rigorous study noted above did not confirm its findings.
Aruna D, Naidu MU (2007) "
Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects" Br J Clin Pharmacol 63(3):333–8.
​

Clopidogrel

See study description under cilostazol above. This study found no interaction of ginkgo with clopidogrel.
Aruna D, Naidu MU (2007) "Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects" Br J Clin Pharmacol 63(3):333–8.

Surgery

n=15 French adults undergoing aortic valve replacement
Randomized to gingko extract 320 mg or placebo daily for 5 days before surgery.
There was reduced oxidative stress in the ginkgo group during and after surgery.
There was no difference in adverse effects, including bleeding, or recovery time between the groups.
​Pietri S, Séguin JR, d'Arbigny P, et al. (1997) "Ginkgo biloba extract (EGb 761) pretreatment limits free radical-induced oxidative stress in patients undergoing coronary bypass surgery" Cardiovasc Drugs Ther 11(2):121–31.

n=60 Chinese adults with vertebrobasilar artery insufficiency undergoing total hip replacement
Randomized to receive intravenous ginkgo extract 1 mg/kg or placebo during surgery
There was some improved cerebral oxygenation with ginkgo over placebo.
There was no difference in adverse effects between the groups. One patient in the ginkgo group had a cerebral hemorrhage; this difference was not statistically significantly different from the placebo group.
Xu L, Hu Z, Shen J, McQuillan PM (2015) "Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia" Complement Ther Med 23(2):220–5.

n=57 elderly Chinese adults undergoing cancer surgery
Randomized to oxygen and "appeasement therapy" (not described) with or without ginkgo liquid (equal to 80 mg extract three times per day) from day of surgery until 6 days after. No placebo was used.
There was a significant reduction in postoperative delirium with ginkgo vs. the control group.
Adverse effects were not reported. Presumably if there was a significant increase in bleeding or any problem with ginkgo, it would have been noted.
Xie KJ, Zhang W, Yuan JB, et al. (2018) "Therapeutic effect of Ginkgo biloba extract on postoperative delirium in aged patients" Zhonghua Yi Xue Za Zhi 98(18):1430–3 [in Chinese].

n=60 Chinese adults with rheumatic heart disease undergoing mitral valve replacement
Randomized to get IV ginkgo extract (dose unknown) or normal saline before surgery
There was better cerebral oxygenation and less oxidative damage with ginkgo vs. saline.
There was no increase in bleeding with ginkgo vs. saline.
Deng YK, Wei F, Zhang DG (2006) "Brain protective effects of Ginkgo biloba leaf extract (ginaton) in patients undergoing hypothermic cardiopulmonary bypass" Zhongguo Zhong Xi Yi Jie He Za Zhi 26(9):795–8 [in Chinese].

n=40 Chinese patients (age unknown) undergoing repair procedures for congenital cardiac anomalies
Randomized to ginkgo extract (0.5 mg/kg) or no ginkgo added to the cardioplegic solution given via the abdominal aorta. No placebo was used.
The ginkgo group had signs of improved myocardial health after surgery compared to controls.
There was no increase in bleeding with ginkgo.
Deng YK, Wei F, An BQ (2006) "Effects of Ginaton on the markers of myocardial injury during cardiopulmonary bypass" Zhongguo Zhong Xi Yi Jie He Za Zhi 26(4):316–8 [in Chinese].

Blood Coagulation in Health People

n=11 Canadian children and adults (age 12–35 yr) with vitiligo taking ginkgo standardized extract 60 mg bid x 12 weeks
​No significant change in platelet count, activated partial thromboplastin time, or international normalized ratio from baseline to twelve weeks.
​Szczurko O, Shear N, Taddio A, Boon H (2011) "Ginkgo biloba for the treatment of vitilgo vulgaris: An open label pilot clinical trial" BMC Complement Altern Med 11:21.

Conclusion

Small clinical trials in healthy adults and children, as well as two larger trials in patients taking anticoagulants for health conditions, have found no interaction between ginkgo and these drugs, and in particular, no increased risk of bleeding. The only exception is a potential increased platelet inhibition between ginkgo and cilostazol found in one clinical trial (though a more rigorous trial failed to confirm this finding). Similarly, clinical trials of ginkgo in surgery find no adverse effects and no increased risk of bleeding.

Much of the concern about ginkgo and bleeding appears to come from a handful of case studies suggesting a link between ginkgo and bleeding in people taking anticoagulants. To use these as the pre-eminent evidence in the face of overwhelmingly opposite conclusions from far more rigorous studies is absurdly anti-scientific.

People taking anticoagulant and antiplatelet drugs have minor and serious bleeding effects all the time regardless of herb intake, so of course by chance there will periodically be people taking these drugs and herbs and have bleeding. This does not prove the herbs caused the problem by any stretch of the imagination.

he best evidence does not support that people on anticoagulants or undergoing surgery need to avoid taking ginkgo (in the case of surgery, the best evidence actually supports a benefit from ginkgo in surgery), and should have the same levels of monitoring anyone has while taking such anticoagulants.
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