Ginkgo: What to Remember

1. History

Ginkgo biloba, also known as the maidenhair tree, is a species of tree native to China that is considered a living fossil. The species dates back to around 250 million years ago, surviving through the extinction of dinosaurs and the Ice Age.1 Ginkgo trees are known for their resilience, with trees located within 1-2km of the Hiroshima atomic bomb explosion still growing today. Ginkgo has been used medicinally for quite some time; records from 5000 years ago describe using ginkgo for asthma and bronchitis. In traditional Chinese medicine, it has been used to increase sexual drive, decrease urination frequency, and to treat cancer and infections.2 Currently, ginkgo leaf extract is the most common form used medicinally.

2. Medicinal use

To improve memory and concentration, treat dementia, confusion, ringing in the ears, premenstrual syndrome (PMS), blood circulation problems, vision problems, and vertigo

Non-medicinal use

Ginkgo nuts are used in Chinese and Japanese cooking and are served at special occasions.

3. Major components hypothesized to be the active ingredients.

Flavonoid glycosides (myricetin and quercetin) and terpenoids (ginkgolides, bilobalides)3

4. Theorized mechanism of action

It is thought to cause effects by improving blood flow throughout the body, but especially in the brain. It also has antioxidant and antiplatelet effects attributed to flavone and terpene lactones.3

5. Clinical issues; DDIs, suggested dose, adverse effects, PK, overdose, use in special populations

Ginkgo may induce or inhibit certain CYP 450 enzymes, such as 2C9 and 2C19. It may also interact with warfarin, trazodone, buspirone, alprazolam, ibuprofen, efavirenz, and fluoxetine.

Ginkgo is not to be used during pregnancy due to potential early induction of labor or prolonged bleeding. There is not enough data on breastfeeding to recommend it. Ginkgo may make diabetes management more difficult, cause seizures, reduce fertility, and prolong bleeding.

The suggested starting dose is no more than 120 mg daily of leaf extract. The dose varies depending on the indication, but the highest recommended dose is 600 mg daily. The leaf extract should be given in two or three divided doses.4

6. Efficacy vs. safety

Ginkgo leaf extract is safe to take by mouth, but may cause stomach upset and dizziness. The pulp and fruit may cause allergic reactions of the skin. The roasted seeds are possibly unsafe to take by mouth, potentially causing a weak pulse or difficulty breathing. The fresh seeds are poisonous. Meta-analysis of randomized, double-blind trials comparing ginkgo to placebo concluded that ginkgo use appears to be safe, with no major side effects compared to placebo. However, the authors felt that “the evidence that Ginkgo has predictable and clinically significant benefit for people with dementia or cognitive impairment is inconsistent and unconvincing.”5 Evidence showing that ginkgo can slow progression of Alzheimer’s dementia seems controversial.

7. Information about standard of the various preparations available

Standardized ginkgo extracts are available and often used in clinical trials. They contain 24 percent ginkgo flavonoid glycosides, 6 percent terpene lactones, and no more than 5 parts per million ginkgolic acids.6 However, ginkgo products available on the market can contain different doses and amounts of ingredients. Since it is regulated as a dietary supplement, not all products are tested for purity and efficacy.

8. Cost (compare to prescription medication)

~$12-18 for 200 capsules of ginkgo extract 60mg

~$100 for 60 capsules of rivastigmine 1.5mg

~$55 for 100 tablets of trimetazidine 35mg

9. Prevalence of use

One of the ten best-selling herbals in the U.S.6

Among healthy elderly (60-94 years old) in one study: 15.3%

Prescribing among nursing home residents diagnosed with epilepsy or seizures: 61.9%

10. Evidence-based studies

The National Toxicology Program did a study on whether ginkgo was carcinogenic in mice. They found an increase in liver and thyroid cancers. The NIH did a study on 75 year-old adults and found no improvement in preventing dementia or reducing blood pressure.7

11. Comparable prescription or non-prescription medications

Rivastigmine for treating Alzheimer’s related dementia - study found that rivastigmine should be preferred over ginkgo.8

Trimetazidine, betahistin, and ginkgo for reducing tinnitus symptoms - study found that all three significantly reduce symptoms, but trimetazidine is most effective.9

12. Any regulatory issues

It is regulated by the FDA as food rather than a drug, which means less stringent regulation.

References:

1. Nelson, B. (2000). History of ginkgo biloba. Retrieved 02/04, 2014, from http://www.herballegacy.com/Nelson_Ginkgo_History.html

2. Das, D. (2013). Ginkgo. Retrieved 02/04, 2014, from http://www.britannica.com/EBchecked/topic/233931/ginkgo

3. Diamond BJ, B. M. (2013). Ginkgo biloba: Indications, mechanisms, and safety. Psychiatric Clinics of North America, 36(1)

4. Ginkgo. (2013). Retrieved 02/04, 2014, from http://www.nlm.nih.gov/medlineplus/druginfo/natural/333.html

5. Birks, J., & Grimley Evans, J. (2007). Ginkgo biloba for cognitive impairment and dementia. Cochrane Dementia and Cognitive Improvement Group, 10(2)

6. Blumenthal M. German Federal Institute for Drugs and Medical Devices. Commission E. The complete  

       German Commission E monographs: therapeutic guide to herbal medicines. Austin, Tex.: American      

       Botanical Council, 1998:11–12.

7. National Toxicology Program. (2013). Ginkgo. (). NC: National Institute of Environmental Health Sciences.

8. Nasab, N., Bahrammi, M., Nikpour, M., Rahim, F., & Naghibis, S. (2012). Efficacy of rivastigmine in comparison to ginkgo for treating alzheimer's dementia. Journal of Pakistan Medical Association, 62(7)

9. Orhan, I., Aydın, S., Altın, G., & Yılmaz, F. (2013). An efficacy comparison of betahistin, trimetazidine and ginkgo biloba extract in patients with tinnitus. Journal of Ear, Nose, and Throat, 23(3)