Ginkgo biloba improves ocular blood flow

Brenna Hendrick

American College of Healthcare Sciences HERB 504

Dr. Nolan Noska

Abstract

Ginkgo, Ginkgo biloba, is one of Germany's most commonly prescribed herbal medicines; Ginkgo is also a highly used over-the-counter herbal supplement in the United States (Diamond et al., 2000). Clinical trials support the effectiveness of this herbal remedy. This literature review aims to evaluate if Ginkgo biloba can improve ocular blood flow. There are clinical trials that support Ginkgo biloba increasing ocular blood flow.

The potential use of the herbal remedy, Ginkgo biloba, to improve ocular blood flow was evaluated by reading and assessing primary and secondary peer-reviewed scholarly journals. The clinical trials evaluated ocular blood flow using Doppler modalities, confocal scanning, and ultrasound. The evidence suggests that Ginkgo biloba can improve ocular blood flow.

Keywords: Ginkgo biloba, Ginkgo, Phytotherapy, Ocular Blood Flow, Glaucoma, Eye Health, Herbal Remedies, Natural Medicine.

Introduction

Ginkgo biloba has the potential to improve ocular blood flow and, as a result, ignite hope for a breakthrough in the battle against glaucoma, a pathogenesis that threatens vision. Research indicates that impaired ocular blood flow is correlated to the development of glaucoma (Maram et al., 2017). Because of this, assessing the impact of Ginkgo biloba on the rate of ocular blood flow could be invaluable for the early detection and treatment of glaucoma. This research offers hope for glaucoma patients seeking solace as the research indicates that the tree Ginkgo biloba can be an effective phytotherapy for increasing ocular blood flow.

Ginkgo is of interest as it contains flavonoid glycosides which can dilate blood vessels, decrease blood viscosity, and act as an antioxidant scavenging free radicals (Park et al., 2007). This tree is a long-lived deciduous tree in the Ginkgoaceae family native to China (Hohmann et al., 2018). Ginkgo biloba has been around for 390,000 years, with earlier varieties showing fossil evidence of existence a million years ago (Hohmann et al., 2018). Some of the trees in China are approximately 3,000 years old and are found close to human settlements. The proximity to human settlement indicates that the tree may have been used for food and medicine for thousands of years (Hohmann et al., 2018). This ancient herbal tree has made an indelible mark in human history.

The research explores Ginkgo biloba as a treatment for improving ocular blood flow. The clinical studies evaluated Ginkgo biloba and measured ocular blood flow before and after treatment. Peer-reviewed journal articles were accessed through PubMed and the American College of Health Care Sciences University's library databases. The clinical studies reviewed were assessed in detail and looked at pre-treatment and post-treatment blood flow before and after administering Ginkgo biloba. The clinical evaluations varied in dosage and duration of time. Improving ocular blood flow could be a therapy option for patients experiencing glaucoma (Park et al., 2007). Normal tension glaucoma is described as optic nerve damage, and glaucomatous visual field loss occurs when optical pressure is within the normal range (Park et al., 2007). The diagnosis of glaucoma is often by intraocular pressure and tissue ischemia from decreased blood flow (Park et al., 2007). Studying the impact of Ginkgo on ocular blood flow is essential as these patients with normal tension glaucoma can continue to struggle with visual field defects even when intraocular pressure is normal (Park et al., 2007). The research presented here shows the impact of this ancient herb on ocular blood flow, presenting a compelling case for its therapeutic potential.

Results

Chung et al. (1999) looked into decreased peripapillary blood flow and the link to disease development in patients with glaucoma. A total of 12 mix-gender individuals around 54 years of age (+/- 3 years standard deviation) with normal eye examinations participated in the study as a control group. A group of 12 patients with early-stage normal tension glaucoma were recruited from the Indiana University Hospital Glaucoma Service to participate in the clinical trial. All recruited patients had intraocular pressure less than 21 mm Hg, averaging 16 mm Hg. Before the study began, written consent was provided, and the institutional review board reviewed and approved the study. The study was performed following the Declaration of Helsinki. The patients and controls were evaluated once. A confocal scanning laser Doppler flowmetry and flow histograms were used to evaluate blood flow. Two-tailed paired t-tests were used to evaluate statistical comparisons. Anything with a P-value greater than 0.05 was not considered statistically significant. A pixel-by-pixel data analysis showed that the blood flow for patients with glaucoma was significantly less than the control group (0.006). The research directly documents a reduction in blood flow in the peripapillary retina for patients with early-stage normal tension glaucoma. This data does not prove that the reduction in blood flow is the cause of glaucoma; it just shows that patients with glaucoma experience reduced blood flow. No conflicts of interest were presented in this study.

Another clinical study by Chung et al. (1999) looked at Ginkgo biloba extract as a treatment option for glaucoma patients. A total of 11 mix-gender, healthy participants aged around 34 years (+/-3 years standard deviation) volunteered to be part of the study at the Indiana University Medical Center. Before the study began, written consent was provided, and the institutional review board reviewed and approved the study. The study was performed following the Declaration of Helsinki. The study was a randomized, prospective, double-masked cross-over trial with placebo control. The Ginkgo extract administered was a trademarked Ginkoba® (Pharmaton, Ridgefield CT). The dosage was 40 mg orally 3 times a day for 2 days. Ginkoba® is standardized to 24% flavonoid glycosides and 6% terpenes. The placebo was fructose. The capsules that were given were identical in appearance. The control group (placebo) included 5 individuals, and the experimental group (ginkgo extract) included 6 individuals. A baseline measurement of ocular blood flow was taken using color Doppler imaging. No participants dropped out of the study. Post-study, the exact measurement was taken. Because this was a double-masked study, a 2-week washout occurred, and baseline measurements were retaken. In this round, the control group (placebo) included the 6 individuals that previously took the ginkgo extract, and the experimental group (ginkgo extract) included the 5 individuals that previously were administered the placebo. No participants dropped out of the study, and post-study measurements were retaken. Two-tailed paired t-tests were used to evaluate statistical comparisons. Anything with a P-value greater than 0.05 was not considered statistically significant. The mean end-diastolic velocity results (p=0.070) were not statistically significant but showed improvements in the ophthalmic, central retinal, and short posterior ciliary arteries. The ophthalmic artery individually showed a statistically significant improvement in the end-diastolic velocity (p=0.023). No conflicts of interest were found in this clinical trial.

Harris et al. (2018) conducted a clinical trial with Ginkgo biloba extract for patients with open-angle glaucoma. The study focused on ocular blood flow before and after treatment. A total of 45 mix-gender participants aged 30 years and older diagnosed with open-angle glaucoma participated in the study at the Glaucoma and Diagnostic Center within the Eugene and Marilyn Glick Eye Institute at Indiana University School of Medicine. The average age of participants was 67 (+/- 11 standard deviation). During the clinical study, 3 patients dropped out, and 42 out of the 45 completed the study. Before the study began, written consent was provided, and the institutional review board reviewed and approved the study. The study was performed following the Declaration of Helsinki. The Ginkgo was part of a dietary supplement blend (Optic Nerve Formula, ScienceBased Health, Houston, TX). The Ginkgo dosage was 120 mg, standardized to 24% flavonoid glycosides. The other dietary supplement components were vitamins, minerals, USP-verified fish oil, and more. The placebo was identical in appearance and made up of sunflower oil, calcium carbonate, lecithin, and beeswax. Baseline measurements were taken for intraocular pressure, ocular perfusion pressure, and retinal capillary blood flow. The article did not mention the daily frequency for the month the dietary supplement was taken. After a month of treatment, post-treatment measurements were obtained. Because this was a double-masked study, a 3-week washout occurred, the placebo and experimental groups were switched, and the study was repeated. Ultrasound and laser Doppler modalities were used to measure the baseline and post-treatment values, and measurements by the same operator occurred to limit variability. Single-paired t-tests were used to evaluate statistical comparisons. Anything with a P-value greater than 0.05 was not considered statistically significant. Before the study started, pretreatment data for the group treated with the dietary supplement had statistically lower peak systolic velocity and end-diastolic velocity in the central retinal and ophthalmic arteries. After the month of treatment, the group taking the dietary supplement had a statistically significant increase in peak systolic velocity and end diastolic velocity central retinal artery and the ophthalmic artery. The results also showed a statistically significant decrease in vascular resistance for the experimental group. No conflicts of interest were found in this clinical trial (Harris et al., 2018).

Park et al. (2007) evaluated the impact of blood flow by Ginkgo biloba extract on individuals with normal tension glaucoma. This clinical trial evaluated if Ginkgo could aid in increasing ocular blood flow and ultimately improve the symptoms of individuals experiencing normal tension glaucoma. A total of 30 mix-gender patients between the ages of 18-80 diagnosed by the Gangman Severance Hospital participated in the study. Before the study began, written consent was provided, and the institutional review board reviewed and approved the study. Ocular examination occurred before the trial started and immediately after. Visual field, Heidelberg retina flowmeter, and systemic evaluations occurred. Confocal scanning laser Doppler flowmetry was used for blood flow measurements. The study was a randomized, double-masked, placebo-controlled clinical trial. The dosage was 80 mg of Ginkgo biloba extract (19.2 mg of flavonoid glycosides) twice daily for 4 weeks. There were 15 participants in the experimental study group and 15 in the control group. None of the participants dropped out of the study. After completion of treatment, the results showed a statistically significant improvement for the temporal peripapillary retina area, temporal neuroretina rim area, and the neuroretinal rim area. The results showed no statistical significance for the superior nasal peripapillary and optic cup areas. No conflicts of interest were presented in this study (Park et al., 2007).

Wimpissinger et al. (2007) looked at a single dosage of Ginkgo biloba and its impact on ocular blood flow. Fifteen healthy males aged 25 (+/-3 years standard deviation) participated in this study at the Medical University of Vienna. Before the study began, written consent was provided, and the institutional review board reviewed and approved the study. The study was performed following the Declaration of Helsinki. The study was a randomized, double-masked, placebo-controlled, two-way cross-over clinical trial. The Ginkgo extract administered was standardized EGB761. The dosage administered was 240 mg orally once. The dosage administered of the Ginkgo biloba extract EGB761 is equivalent to 57.6 mg ginkgo flavonoid glycosides and 14.4mg terpene lactones. The placebo used was not shared. Baseline measurements were taken before treatment and up to three hours after dosage. Intraocular pressure was measured using laser Doppler flowmetry, laser Doppler velocimetry, a retinal vessel analyzer, laser interferometry, and applanation tonometry. Because this was a double-masked study, a 4-day washout occurred, the placebo and experimental groups were switched, and the study was repeated. A two-way repeated measure ANOVA model was used to evaluate statistical comparisons. Anything with a P-value greater than 0.05 was not considered statistically significant. The data showed no statistical difference between the placebo and the Ginkgo extract. The authors conclude that this is not a result of underdosing because the dose administered is at the upper end of the therapeutic range. No conflicts of interest were found in this clinical trial (Wimpissinger et al., 2007).

Discussion

Ginkgo biloba contains flavonoid glycosides which can dilate blood vessels, decrease blood viscosity, and act as an antioxidant scavenging free radicals (Park et al., 2007). The first clinical trial presented did not directly measure ocular blood flow. This trial was conducted by Chung et al. (1999). This article was included to demonstrate a potential link between a reduction in blood flow and early tension glaucoma. The data does not prove that the reduction in blood flow is the cause of glaucoma; it just shows that patients with glaucoma experience reduced blood flow (Chung et al., 1999). The benefit of Ginkgo biloba as a preventative or treatment option should be evaluated further, as 3 of the 4 clinical studies discussed below show a significant improvement in ocular blood flow (Chung et al., 1999), (Harris et al., 2018), and (Park et al., 2011).

Chung et al. (1999) showed a statistically significant improvement in blood flow in the ophthalmic artery and end-diastolic velocity. Harris et al. (2018) showed a statistically significant increase in peak systolic velocity and end-diastolic velocity in the central retinal and ophthalmic arteries. The results also showed a statistically significant decrease in vascular resistance for the experimental group (Harris et al., 2018). This research indicates that Ginkgo can improve peak systolic and end diastolic velocity, which could benefit glaucoma patients (Harris et al., 2018). Park et al. (2011) showed that Ginkgo biloba extract could improve peripapillary blood circulation and be a favorable treatment option for patients with normal tension glaucoma (Park et al., 2011).

The studies varied in length of time and dosage. Chung et al. (1999) administered 40 mg 3 times a day for 2 days dosage of Ginkgo biloba. This Ginkgo extract was standardized to 24% flavonoid glycoside and 6% terpenes. Harris et al. (2018) used other vitamins and minerals and a 120 mg Gingko biloba dosage for 1 month. This Ginkgo extract was standardized to 24% flavonoid glycosides. Park et al. (2007) used an 80 mg dosage of Ginkgo twice daily for 4 weeks. This extract was standardized to 19.2 mg of flavonoid glycosides. Currently, there is a lack of consistency in the percentage of flavonoid glycosides and terpenes present in Gingko biloba products (Mei et al., 2017). Of 29 products evaluated in a study only 1 matched the percentage of glycoside flavonoids and terpene lactones expected (Mei et al., 2017). This variability can make it challenging to evaluate clinical results.

The study that did not show any statistically significant improvements had the highest dosage of 240 mg standardized to 57.6% flavonoids. This trial by Wimpissinger et al. (2007) concluded that Ginkgo extract does not improve ocular blood flow. The difference between this study and the other clinical evaluations is that this clinical trial administered an extract of Ginkgo biloba only once (Wimpissinger et al., 2007). This data indicates that a high dosage may not be the most critical factor when using Ginkgo biloba. However, the frequency and duration of administration play a role in the potential therapeutic benefit. The study should be repeated with an increased length of administration.

The data presented used various tools to assess how to evaluate ocular blood flow, as there is no standard for assessing ocular blood flow. The lack of standard measurement can result in inconsistencies in results which can be a shortcoming when evaluating treatment options (Harris et al., 2020). Even though all the results demonstrated significant improvements, there is variability in assessments and dosage. More research is needed to determine a standardized amount of the flavonoid glycosides in Ginkgo biloba to provide therapeutic benefits. The current data could have varying results for treatment efficacy if the symptoms assessment tools were different.

The data suggest that the Ginkgo improves ocular blood flow (Chung et al., 1999) (Park et al., 2011) and (Harris et al., 2018). More data must be collected on the minimum acceptable dose, length of time, and percentage of flavonoid glycosides and terpenes needed to understand Ginkgo biloba’s potential for improving ocular blood flow and if this could benefit glaucoma patients.

Conclusion

This literature review aimed to evaluate if Ginkgo biloba can result in improved ocular blood flow. The evidence suggests that Ginkgo biloba has the potential to improve ocular blood flow (Chung et al., 1999), (Harris et al., 2018), and (Park et al., 2011) when taken for longer than a day. The data indicated that a single dose of Ginkgo biloba was ineffective (Wimpissinger et al., 2007). More research is needed to understand how long the patient must dose to experience therapeutic actions. For length of time, Chung et al. (1999) did show effectiveness 3 times a day for 2 days. For dosage, the controls are lacking to ensure standardization of formulas (Mei et al., 2017); however, Chung et al. (1999) did see a benefit with 40 mg dosage 3 times a day, which is equivalent to the 120 mg dose Harris et al. (2018) saw a benefit with during the clinical trial. The data indicates it is not the high dosage but the length of time taking Ginkgo biloba that provides a therapeutic benefit for ocular blood flow. Ginkgo biloba as a treatment for improving ocular blood flow unveils a realm of possibilities for ocular health and glaucoma management. Continued research could revolutionize the management of glaucoma and provide a promising outlook for patients experiencing visual field defects despite normal pressure levels (Park et al., 2007). Ginkgo biloba and its benefit on ocular blood flow is far from reaching its final conclusion, more research is needed to unlock the possibilities of nature's wisdom for the betterment of ocular health.

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