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Ginkgo biloba

An ornamental tree & the oldest species of tree. Medicinal use has been traced back to the Chinese Materia Medica from 2800 BC. The German physician Engelbert Kaempfer was the 1st European to catalog Ginkgo in the late 17th century. It was brought to the US in 1784. Ginkgo is the most resistant of all trees to infection & pollution. Uses: Current uses: 1) symptomatic treatment of cognitive impairment* due to organic brain disease a) Alzheimer's disease - no benefit in prevention of Alzheimer's disease [13] b) multi-infarct dementia c) prevention of cognitive decline post ischemic stroke [17] 2) peripheral arterial disease* 3) headache 4) vertigo 5) asthma 6) tinnitus 7) macular degeneration [12] 8) no memory benefit for healthy elderly* [7,9,11] 9) anxiety (GRS9) [14]; not FDA-approved * of questionable benefit for cognitive impairment peripheral arterial disease (data conflicting) [16] Contraindications: Caution: 1) discontinue use prior to surgery (1-2 weeks prior) 2) avoid in patients with bleeding disorder 2) avoid in patients with seizure disorder Dose: 1) standard extract is 24% flavonoid glycosides a) cognitive impairment: - 120 to 240 mg of dry leaf extract in 2-3 doses b) peripheral arterial disease - 120 to 1600 mg of dry leaf extract in 2-3 doses c) prevention of cognitive decline post ischemic stroke 450 mg QD [17] 2) capsules 40 mg 3) usual dose 40 mg TID 4) range 80-240 mg/day 5) gingi fluid extract 1:1, 25% alcohol: 1-2 mL TID 6) start with low dose & titrate upward to avoid headache 7) discontinue 36 hours before surgery [12] Pharmacokinetics: 1) at least 8 weeks of treatment for cognitive impairment 2) at least 6 weeks of treatment for peripheral vascular disease 3) Ginkgo probably induces CYP2C19 Adverse effects: 1) increase risk for bleeding - case reports of subarachnoid hemorrhage & hyphemas 2) GI distress (common) a) nausea b) diarrhea 3) headache (common) - use a low dose & titrate upward 4) no data on safety during pregnancy 5) no toxicity reported with leaf 6) skin contact with fruit can cause a poison ivy type syndrome 7) seizures (case reports); reduces seizure threshold [10] 8) anxiety [12]; used for anxiety (GRS9) [14] Drug interactions: 1) potential interaction with anticoagulants* a) warfarin (coumadin) b) heparin 2) potential interactions with antiplatelet agents* - non-steroidal anti-inflammatory agents (NSAIDs) - SSRI (fluoxetine) [16] 3) anticonvulsive agents 4) possible interaction with drugs that lower seizure threshold [6,8] - antipsychotics, antidepressants, cholinesterase inhibitors, decongestants, sedating antihistamines, systemic steroids, methylphenidate, fentanyl, theophylline, cyclosporine 5) tricyclic antidepressants (TCA) 6) trazodone (Desyrel) in combination may cause CNS depression by overstimulation of GABA receptors [5] 7) diminished levels of drugs metabolized by CYP2C19 [8] - ginkgo decreases omeprazole levels & probably other proton pump inhibitors [8] 8) MAO inhibitors increase effect & toxicity of ginkgo [12] 9) possible interactions with alprazolam, buspirone, efavirenz [16] * discontinue 36 hours before surgery [12] Mechanism of action: 1) active ingredients: a) Ginkgo flavone glycosides & heterosides 1] quercetin 2] kaempferol 3] isorhamnetine b) terpenes c) organic acids d) the leaves are extracted with acetone:water, the organic solvent removed & the extract dried & processed 2) membrane stabilizing 3) free radical scavenger 4) enhances cellular uptake & utilization of glucose & O2 5) make enhance action of Na+/K+ ATPase 6) vasodilation via nitric oxide & prostacyclin 7) may enhance venous tone 8) inhibits platelet activation, adhesion & degranulation due to direct membrane & antioxidant effects 9) increased synthesis of prostacyclin 10) antagonist of platelet activating factor (PAF) 11) improved rheological properties of blood 11) improvement of hypoxic tolerance

Interactions

drug interactions

General

pharmaceutical herb; medicinal herb; herbal supplement; botanical

References

  1. Victoria Rand, UCSF Fresno Lecture, 10/7/98
  2. Le Bara et al, JAMA October 1997
  3. Kleijnen et al, British J Clinical Pharmacology, 1992
  4. Kaiser Permanente, Northern California Regional Pharmacy & Therapeutics Committee
  5. Prescriber's Letter 7(9):53 2000
  6. Prescriber's Letter 9(2):9 2002
  7. Journal Watch 22(18):140, 2002 Prescriber's Letter 9(9):53-54 2002 Solomon PR, Adams F, Silver A, Zimmer J, DeVeaux R. Ginkgo for memory enhancement: a randomized controlled trial. JAMA. 2002 Aug 21;288(7):835-40. PMID: 12186600
  8. Prescriber's Letter 12(9): 2005 Drug Interactions with Ginkgo Detail-Document#: 210910 (subscription needed) http://www.prescribersletter.com
  9. DeKosky ST et al Ginkgo biloba for Prevention of Dementia JAMA. 2008;300(19):2253-2262 PMID: 19017911
  10. Prescriber's Letter 16(1): 2009 Ginkgo for Prevention of Dementia Detail-Document#: 250103 (subscription needed) http://www.prescribersletter.com
  11. Snitz BE et al Ginkgo biloba for Preventing Cognitive Decline in Older Adults. JAMA. 2009;302(24):2663-2670 PMID: 20040554 http://jama.ama-assn.org/cgi/content/full/302/24/2663
  12. Geriatrics at your Fingertips, 13th edition, 2011 Reuben DB et al (eds) American Geriatric Society
  13. Vellas B, Coley N, Ousset PJ et al Long-term use of standardised ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial Lancet Neurol. 2012 Oct;11(10):851-9. PMID: 22959217 http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2812%2970206-5/abstract
  14. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
  15. Hirsch C. Ginkgo biloba extract did not reduce risk for Alzheimer disease in elderly patients with memory complaints. Ann Intern Med. 2013;158(2):JC7 PMID: 23318341
  16. Medical Knowledge Self Assessment Program (MKSAP) 17, 18 American College of Physicians, Philadelphia 2015, 2018.
  17. Li S, Zhang X, Fang Q et al Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial. Stroke Vasc Neurol. 2017 Dec 18;2(4):189-197 PMID: 29507779 Free PMC Article http://svn.bmj.com/content/early/2017/11/08/svn-2017-000104