Ginkgo – much more than a herb for cognition – part 2.

Ginkgo istock3Apart from possible benefits in the management of conditions such as dementia, stroke, diabetic neuropathies, macular degeneration and glaucoma, the cardioprotective and neuroprotective properties of ginkgo suggest potential applications in other situations in which there is exposure to various drugs or substances with a risk of adverse events.

Adjunct with neurotoxic drugs

Concomitant use of ginkgo may be useful when taking or exposed to other drugs or chemical toxins(1, 2). Animal studies have reported protective actions of ginkgo against ototoxicity (inner ear and auditory nerve damage) from the antibiotic drug gentamycin(3), kidney (nephro) toxicity, liver (hepato) toxicity and genotoxicity from the herbicide glyphosate(4), and nerve damage from the herbicide paraquat(1).

These studies suggest that patients being prescribed gentamycin or other aminoglycoside antibiotics which have a risk of causing hearing or kidney damage, or people regularly using or exposed to herbicides such as glyphosate or paraquat, may benefit from taking ginkgo at the same time.

 

Supporting liver function:

Ginkgo leaf is a very bitter herb, and some would say that it is therefore hardly surprising that it is a useful agent for liver conditions. In fact there are now numerous studies showing it has protective actions on the liver.

These hepatoprotective effects have been reported in rodent studies against a wide range of liver toxins. They include alcohol, paracetamol, rifampicin & other chemicals(5-11). Improvements have been shown to occur in several liver abnormalities including malondialdehyde levels, glutathione levels, superoxide dismutase, elevated liver enzymes (LFT’s), and histological damage.

Hepatoprotective effects similar to those of silymarin were reported in a 2011 study involving treatment of rats with silymarin or ginkgo for a week prior, or 4 weeks post administration of nitrosodiethylamine, a known liver carcinogen(12). Other rodent studies have revealed potential antitumour effects against liver cancer for ginkgo(13, 14).

These studies suggest ginkgo could be a useful adjunct to take during treatment with the common analgesic paracetamol, as well as other drugs sometimes associated with liver adverse events, such as azathioprine, isoniazid, statins, ketoconazole and nitrofurantoin.

 Ginkgo when given in larger than usual doses to rats, has protective actions against both acute and chronic alcohol-induced liver damage, effects associated with its antioxidant actions, and improvement in hepatic microcirculation(15-18). Those whose alcohol intake is excessive, may do well to consider taking ginkgo to help ameliorate some of its negative effects on the liver.

Adjunct with chemotherapy:

Adverse events to chemotherapy are common, and use of cytotoxic drugs such as doxorubicin and cisplatin can lead to infertility, kidney damage (nephrotoxicity) and damage to the heart (cardiotoxicity) in some cancer patients.

Pre-treatment or concomitant treatment with large doses of oral or intraperitoneal ginkgo in rats has been shown to help protect against chemotherapy-induced adverse effects on other organs. These include protection against cisplatin-induced peripheral neuropathy(19), protection against cisplatin and doxorubicin cardiotoxicity, and cisplatin nephrotoxicity and ototoxicity(20-25).

Other studies have reported protective effects for ginkgo against the damaging effects of doxorubicin & cisplatin on testicular function in male rats(26, 27), and against against oxidative and genotoxic damage in patients with differentiated thyroid cancer during 90 day radio-iodine treatment(28). These results suggest possible benefits of ginkgo if taken during chemotherapy or radiotherapy treatment, by patients wanting to have children in the future.

While few human clinical trials have investigated these promising findings from animal studies, a Chinese clinical trial has reported a lower incidence of ECG abnormalities and cardiotoxicity in 60 breast cancer patients being treated with doxorubicin, when ginkgo was prescribed concurrently(29). Adjunctive Ginkgo also slightly improved overall survival in a small trial involving 27 patients with advanced hepatocellular cancer, compared to previous sorafenib monotherapy(30).

Adjunct with antipsychotics:

The response of schizophrenia patients to antipsychotic drug medications is often less than ideal, and the frequency of adverse events to these associated with low levels of compliance. Findings from a Chinese clinical trial involving 12 weeks of ginkgo and haloperidol or placebo and haloperidol administration in a group 109 schizophrenia patients and previously treated with antipsychotic medications for at least 6 months, are therefore of interest(31).

At the end of the 12 week study, 57% of the ginkgo treated group were rated as responders, versus only 38% of the haloperidol only treatment group, which in itself is highly significant. Additionally however, a lower incidence of extrapyramidal side effects, a major problem with haloperidol and other older generation antipsychotic drugs, was also seen in the ginkgo-treated group(31, 32).

Improvement in some schizophrenia symptom scores was also reported in a subsequent study involving adjunctive ginkgo treatment in patients taking olanzapine, a newer generation antipsychotic drug(33).

Potential applications of ginkgo in the management of other psychiatric conditions including depression and ADHD, have also been suggested(34, 35), though further clinical studies are needed.

 

Dosage:

A concern is the use of relatively large doses in most animal studies, yet those used in human clinical studies are often much lower, and sometimes probably less than what they should have been. Also given that most neurodegenerative conditions such as dementia, diabetic neuropathies, glaucoma and macular degeneration are slow to develop but tend to be progressive, unless clinical trials involve large participant numbers and continue for a long period of time, their ability to statistically detect clinically significant outcomes , is limited.

Despite these challenges and the cost of long term clinical trials, given the hugely debilitating nature of all of these conditions, and their large burden on both patients and the health care system, further trials to validate promising findings from in vitro and animal studies, and determine optimal dosage and treatment protocols in humans are needed.

 

And finally:

New Zealand is an excellent country for growing ginkgo, and locally harvested ginkgo leaves have been shown to contain high levels of ginkgo flavone glycosides and terpene lactones.

While it is sometimes claimed that ginkgolic acid, a minor component of ginkgo leaves, is associated with allergic reactions, the evidence basis for this is unconvincing. In fact research is increasingly showing that this compound probably contributes to ginkgo’s cognitive benefits(36), and exhibits a wide range of other useful pharmacological properties. These include anti-diabetic(37), anti-fibrotic(38) and potential anticancer properties, including against pancreatic (39), liver, colon and gastric cancers (40-42).

 

References:

  1. Silva AM et al, Plants (Basel). 2019 Nov 29;8(12):556.
  2. Rasmussen PL, 2017. Ginseng, Ginkgo and Ginger – the 3 G’s, paper presented to NHAA International Conference on Herbal Medicine, Brisbane, Australia, 17-19 March 2017.
  3. Yang TH et al, J Nutr Biochem 2011; 22(9):886-894.
  4. Cavusoglu K et al, J Med Food 2011; 14(10):1263-1272.
  5. Shenoy KA et al, Indian J Physiol Pharmacol 2002 Apr;46(2):167-74
  6. Luo YJ et al, World J Gastroenterol 2004; 10(7):1037-1042.
  7. He SX et al, World J Gastroenterol 2006; 12(24):3924-8.
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  9. Naik SR et al, Liver Int. 2007 Apr;27(3):393-9.
  10. Yang L et al, Fitoterapia. 2011 Sep;82(6):834-40.
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  12. El Mesallamy HO et al, Cancer Cell Int 2011; 11(1):38.
  13. Dias MC et al, Chem Biol Interact. 2008 May 9;173(1):32-42.
  14. Ahmed HH et al, Acta Biochim Pol. 2017;64(1):25-33.
  15. Yao P et al, Food Chem Toxicol 2007 Aug;45(8):1333-42.
  16. Yuan Q et al, J Ethnopharmacol 2017 Jan 4;195:1-9.
  17. Rasmussen PL, Protective effects of ginkgo against alcohol-induced liver damage Phytonews 27, 2007. June. Published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand. ISSN 1175-0251.
  18. Rasmussen PL, Ginkgo: beneficial effects in liver disease? Phytonews 19, 2004. Published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand. ISSN 1175-0251.
  19. Ozturk G et al, Toxicol Appl Pharmacol. 2004 Apr 1;196(1):169-75
  20. Naidu MUR et al, Indian J Exp Biol. 2002 Aug;40(8):894-900
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  22. Cakil B. et al, J Laryngol Otol. 2012 Nov;126(11):1097-101
  23. Song J et al, Evid Based Complement Alternat Med 2013; 2013:846126.
  24. Dias MA et al, Int Tinnitus J. 2015;19(2):12-9
  25. Esen E et al, J Int Adv Otol 2018 Apr;14(1):22-26.
  26. Yeh YC et al, Br J Pharmacol. 2009 Jan;156(1):48-61
  27. Amin A et al, J Biomed Biotechnol. 2012;2012:362049.
  28. Dardano A et al, Thyroid 2012; 22(3):318-324.
  29. Yi SY et al, Zhongguo Zhong Xi Yi Jie He Za Zhi 28(1):68-70, Jan 2008.
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  32. Chen X et al, Psychiatry Res 2015; 228(1):121-127.
  33. Atmaca M et al, Psychiatry Clin Neurosci 2005; 59(6):652- 656.
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  36. Mango D et al, Front Pharmacol. 2016 Oct 26;7:401
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  38. Qiu F et al, Toxicol Appl Pharmacol 2018; 15:345:1-9
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  41. Li H et al, Oncol Rep. 2019 Jan;41(1):369-376.
  42. Liang JR et al, Biomed Pharmacother. 2020 May;125:109585

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