Ginkgo – much more than a herb for cognition (part 1).

Extracts made from leaves of the ginkgo tree (Ginkgo biloba) are a widely used herbal medicine, mostly due to a reputation to help support cognitive functions in both healthy young(1,2) and middle-aged(3,4) people. However, numerous other potential applications exist for the bitter leaves of this beautiful tree, which has actions as a strong antioxidant and microcirculatory enhancer(5).

Neuroprotective:

More than 400 of the 4000 papers on ginkgo published in the peer-reviewed scientific literature, relate to protective effects against nerve damage or degeneration, in in vitro and animal studies. These include reduced neurodegeneration and oedema in animal models of brain ischaemia(6-8), implicating potential applications of ginkgo to help prevent or reduce ischaemia-induced damage in stroke prone patients(9).

Clinical studies in humans show improved neurological and cognitive outcomes when ginkgo is taken in the immediate period following a stroke(10-12), without increasing the incidence of vascular events. The largest of these was a Chinese multicentre study where 450mg ginkgo extract was given daily together with 100mg aspirin for a 6 month period, in 348 post-stroke patients(11). While these results are promising, further trials involving greater patient numbers and longer treatment durations, are needed.

Parkinson’s disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and is associated with oxidative stress, neuroinflammation and apoptosis. Studies in animal models of Parkinsons disease have implicated beneficial actions of ginkgo or its constituents(13-18). These include a reduction in elevated oxidative stress markers and inflammatory cytokines, reduced locomotion impairment(13), clearance of the alpha-synuclein (α-syn) protein by ginkgolic acid(17), and regulation of brain copper levels(19).

Two small trials involving a daily dosage of 240mg extract have investigated ginkgo’s effects on patients with multiple sclerosis, but with mixed results(20, 21).

Potential applications exist also for ginkgo to help protect against neurodegenerative retinal diseases such as macular degeneration or glaucoma, and diabetes.

Glaucoma is primarily a condition of raised intraocular pressure, but even successful intraocular pressure reduction does not stop the progression of glaucoma in all patients. As vascular dysregulation, reduced microcirculation, oxidative stress and inflammation are contributory to its development, ginkgo has relevant pharmacological actions that may be useful(22-25).

Ginkgo pretreatment and early post-treatment has been shown to protect retinal ganglion cells from damage in a rat model of chronic glaucoma(26). Few clinical trials have taken place apart from a Korean trial involving 99 patients given ginkgo for 2 years, which reported improved visual function in some patients with normal tension glaucoma(27). Given the limited treatment options for this increasingly common condition, the use of ginkgo as an adjuvant or preventive therapy should be further explored(24).

Similar potential benefits would seem to exist for age-related macular degeneration (AMD), the leading cause of irreversible blindness in adults over 50 years of age. Two trials involving a total of 119 people have reported some positive effects of ginkgo on vision in AMD patients, for doses of 160mg or 240mg per day taken over a 6 month period(28). A Russian trial involving 240mg ginkgo extract together with lutein, zeaxanthin, vitamins C, E, A and B2, rutin, zinc, selenium and bilberry in diabetic patients with initial stages of diabetic retinopathy or combined diabetic retinopathy and AMD, also found evidence of both preventive and treatment benefits(29). Again however, larger trials and for longer treatment periods, are needed.

Potential benefits in diabetes:

Type 2 Diabetes mellitus is one of the major diseases of the 21st century, and is putting an increasing burden on health care budgets. While dietary education and interventions and exercise can assist, and oral hypoglycaemic drugs or insulin are often prescribed, other interventions to reduce drug medication needs and/or improve patient outcomes can have huge benefits.

Diabetes is primarily a condition of poor blood glucose control, but vascular dysfunction often develops and long term outcomes can include development of conditions such as retinal neuropathy and blindness, peripheral vascular disease leading to leg ulcers, and glomerulonephritis leading to deterioration in kidney function.

Various studies in animals suggest a possible role for ginkgo in protecting against such neuropathies. One in diabetic rats found that 4 weeks treatment with ginkgo and magnetised water protected type 2 diabetic rat kidneys from nephrotoxic damages, effects associated with reduced hyperlipidemia, uraemia, oxidative stress, and renal dysfunction(30). Another found ginkgo pretreatment improved neurological scores, and reduced cerebral infarct volume and acute cerebral ischemia‑reperfusion injury in diabetic rats(31). Improvement in cognitive function has been reported in elderly diabetic mice(32), as has reduced plaque lipid deposition and aorta atherosclerosis, and reduced expressions of cytokines and other inflammatory markers (33). Doses used in these animal studies, however, were generally significantly higher than those normally recommended in humans.

Few clinical trials have been undertaken to date and patient numbers were relatively small. Various trials involving a combined treatment of diabetic patients with a particular combination of various Chinese herbs and ginkgo reported improved outcomes, although the contribution of the relatively low dose of 24mg ginkgo extract used in these studies is unknown(34-36).

Another trial found an improved response through adding ginkgo to the oral hypoglycaemic drug metformin for 90 days(37). Blood levels of fasting glucose, insulin, and HbA1c (glycated haemoglobin), whose elevation is linked to risks of diabetic complications, showed a greater reduction in the combined ginkgo-metformin treatment group, than with metformin treatment alone.

Ginkgo would seem to offer various relevant potential benefits in the prevention and management also of Metabolic syndrome(38). This is an insidious cluster of conditions including high blood pressure, diabetes, obesity and high blood lipids, and associated with an increased risk of cardiovascular disease events. Given the increasing prevalence of Metabolic syndrome including in up to a third of American adults, herbal agents such as ginkgo with diverse but relevant pharmacological actions, should receive greater attention.

 

References:

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  22. Doozandeh A et al, J Ophthalmic Vis Res. Apr-Jun 2016;11(2):209-20.
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  24. Cybulska-Heinrich AK et al, Mol Vis. 2012;18:390-402.
  25. Bungau S et al, Oxid Med Cell Longev. 2019 Feb 12;2019:9783429.
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