Indications
There is no FDA approved indication, and there is insufficient evidence to support non-FDA approved use of Ginkgo biloba.
Dementia/ Cognitive Impairment
In terms of treatment for existing dementia, data has been contradictory regarding the efficacy of Ginkgo biloba extract (EGb). A 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 309 patients in 1997 concluded that EGb was safe and though modestly, it appeared to stabilize and improve the cognitive performance as well as social functioning of dementia patients for six months to 1 year.[1] Similarly, another 24-week randomized controlled trial with 410 outpatients found that treatment with EGb 761 using a once-daily dose of 240 mg was safe and demonstrated a statistically significant improvement in cognition, psychopathology, functional status and quality of life of patients and caregivers.[2] On the other hand, a randomized control trial of 513 outpatients with mild to moderate dementia of the Alzheimer type did not support the efficacy of ginkgo extract.[3] A systematic review of 36 trials in 2009 and another review of 38 trials in 2018, though demonstrated that Ginkgo biloba was relatively safe, but did not support its clinical benefit for patients with cognitive impairment and dementia.[4][5] Conversely, a 2015 systematic review of 9 trials concluded that EGb761 at 240 mg/day was able to decelerate decline in cognition, function, behavior, and global change at 22 to 26 weeks in patients with dementia, especially for those with neuropsychiatric symptoms.[6] A 2017 study of 12 systematic reviews also suggested that at doses greater than 200mg/day for at least five months, EGb had potentially beneficial effects for patients with dementia.[7]
In terms of preventing dementia, there is also insufficient evidence to support the use of ginkgo. The Ginkgo Evaluation of Memory (GEM) Study showed that Ginkgo biloba at 120 mg twice a day was not effective in reducing both all-cause dementia incidence and Alzheimer dementia incidence in elderly patients with normal cognition or with mild cognitive impairment.[8] Similarly, the GuidAge clinical trial conducted in patients aged 70 years or older who spontaneously reported memory complaints to their primary care physician in France. This trial randomized patients with either 120 mg standardized Ginkgo biloba extract or matching placebo and did not support the benefit of long-term use of standardized EGb in reducing the risk of progression to Alzheimer disease throughout five years.[9] A meta-analysis of two trials involving 5889 participants showed no significant difference in the rate of developing dementia between Ginkgo biloba and the placebo in late-life.[10] A 2012 meta-analysis did not find support for the use of Ginkgo biloba in enhancing cognitive function in healthy adults.[11]
Cardiovascular disease (CVD)/ Cardiovascular Risk Factors Reduction
Effects of ginkgo on cardiovascular disease and risk factors, including hypertension and diabetes, have been the topic of many studies. However, there has been a lack of large evidence-based, well-designed randomized controlled trials/studies to support its use in treating or preventing the incidence of cardiovascular disease. Though Ginkgo biloba extract has often been an option in the treatment of acute ischemic stroke in China, a systemic review in 2005 did not show the benefit of improving mortality or neurological recovery in the post-stroke period.[12] On the other hand, a randomized, open-label, blinded, controlled clinical trial in 2018 suggested that ginkgo, in combination with aspirin treatment lessened cognitive and neurological impairment after acute ischemic stroke without increasing the incidence of vascular events.[13] A small randomized controlled trial of eighty patients with coronary artery disease showed that the use of EGb correlated with an increase in blood flow of left anterior descending coronary artery as measured by Doppler echocardiography as well as an increase in nitric oxide and a decrease in endothelin-1 level.[14]
A randomized controlled trial in 2010 that monitor CVD as a preplanned secondary outcome of the GEM study showed no evidence that ginkgo reduced CV mortality or CVD events though it reported a smaller number of peripheral vascular disease events in ginkgo arm.[15] A systemic review, however, suggested that that Ginkgo biloba had no statistical or clinically significant benefit for patients with peripheral arterial disease.[16] Data from the GEM study also demonstrated that EGb did not reduce blood pressure or the incidence of hypertension in elderly patients with a mean age of 79 years old.[17] Ginkgo biloba research has also shown it to decrease plasma lipoprotein(a) level - a known risk factor for atherosclerotic diseases.[18] A small randomized controlled trial in 2018 showed that adjunct use of EGb along with metformin was more effective than metformin alone in improving outcomes in patients with type 2 diabetes mellitus as measured by blood HbA1c, fasting glucose, insulin level, BMI, waist circumference and visceral adiposity index without negatively affecting the liver, kidney, or hematopoietic functions.[19]
Overall, due to the lack of strong evidence, the use of Ginkgo biloba extract is not indicated at this point for treatment or prevention of CVD.
Psychiatric disorders:
Studies have examined the role of Ginkgo biloba in treating depression and other psychiatric disorders. A small randomized controlled trial with 136 subjects suggested that EGb, as an adjunctive treatment along with citalopram, could improve depressive symptoms and cognitive function as measured by Hamilton Depression Rating Scale (HAMD) and Wisconsin Card Classification Test (WCST), respectively; it also decreased the expression of serum S100B, a marker of brain injury.[20] A randomized controlled trial of 157 patients with DSM-IV-diagnosed schizophrenia and tardive dyskinesia (TD) suggested EGb could help reduce the symptoms of TD.[21] A meta-analysis of four trials involving 1628 patients showed treatment with EGb improved behavioral and psychological symptoms of dementia and also caregiver distress associated with such symptoms.[22]
Sexual Dysfunction
Many small studies have explored the role of EGb in treating sexual dysfunction. A triple-blind, placebo-controlled trial of 24 patients with sexual dysfunction due to antidepressant drugs showed no statistically significant differences in responses and side-effect profiles between the EGb group and the placebo group.[23] A randomized control trial of 108 patients showed that a nutritional supplement containing L-arginine, ginseng, ginkgo, damiana, multivitamins, and minerals, helped increase the level of sexual desire in premenopausal, perimenopausal, and postmenopausal women compared to placebo.[24]
Vertigo
A multicenter double-blinded randomized control trial that followed 70 patients throughout three months showed that Ginkgo biloba extract could reduce the intensity, frequency, and duration of vertiginous syndrome compared (47% in the EGb group compared to 18% in the placebo group).[25] Another randomized controlled trial in 2014 showed that there was no statistically significant difference in vertigo treatment outcomes between Ginkgo biloba versus betahistine group though EGb had a better tolerance profile.[26] Again due to the lack of strength of the evidence, more studies are necessary to establish the efficacy of Ginkgo biloba in treating vertigo.
Tinnitus
A Cochrane review in 2013, which included four trials with a total of 1543 participants, demonstrated that there was no evidence that Gingko biloba was effective in patients with a primary complaint of tinnitus.[27] Similarly, a 2018 study that extracted data from systematic reviews concluded the use of Ginkgo biloba did not alleviate the severity of tinnitus or improve the quality of life of patients.[28]
Vitiligo
A double-blind placebo-controlled trial of 52 vitiligo patients showed that treatment with Ginkgo biloba correlated with a statistically significant cessation of active progression of depigmentation.[29] Despite such a promising result, more studies are to validate ginkgo's role as a potential therapy of choice for vitiligo.
Macular Degeneration
A 2012 systematic review identified one study of 20 patients with macular degeneration conducted in France, randomly allocated to Gingko Biloba extract EGb 761 80 mg twice daily or placebo and another study of 99 patients performed in Germany randomly assigned to two different doses of Ginkgo biloba extract EGb 761 (240 mg per day and 60 mg per day). Researchers followed the patients for six months in both trials. Their results could not be pooled, but both experiments demonstrated some beneficial effects of Ginkgo biloba on vision.[30]
Glaucoma
A 2019 systematic review suggested that flavonoids, often found in Ginkgo biloba, had a beneficial impact on glaucoma, particularly in terms of increasing ocular blood flow and potentially halting the progression of visual field loss.[31] More quality research is warranted to determine the role of Gingko biloba in treating glaucoma.
Altitude Sickness
The Prevention of High Altitude Illness Trial (PHAIT) that followed 614 healthy western trekkers showed that ginkgo was not effective at preventing acute mountain sickness when compared to placebo.[32] Besides, a 2017 systematic review demonstrated that Ginkgo biloba, neither used alone or as an adjunct to acetazolamide, was beneficial for altitude sickness.[33]