Ginkgo biloba extracts bring benefits

Subjective cognitive decline (SCD) is an important predictor of memory deterioration in old age.
There is evidence that SCD may be the first symptomatic manifestation of Alzheimer’s disease (AD), but is also a common condition in old age independently. Given the proportional increase in the ageing population, this represents a major challenge for today’s healthcare system. As a result, there is growing interest in substances that improve cognitive function.

SCD has been identified as a precursor to mild cognitive impairment (MCI) and may represent the earliest clinical manifestation of Alzheimer’s disease. SCD can be seen as an early stage of dementia, followed by a long developmental process that can extend over more than a decade. Although not everyone with SCD shows progression, people with SCD are ideal candidates for preventive measures aimed at delaying and/or preventing the onset of Alzheimer’s disease. However, despite the clinical value of SCD, there are still significant limitations in SCD research due to the heterogeneity of definitions and the different approaches to measuring SCD.

Ginkgo biloba as a source of many ingredients

Ginkgo biloba L., also known as maidenhair tree, is used in China as a traditional remedy for various diseases. Ginkgo biloba products are available in various specifications. In Europe, the standardized extract of Ginkgo biloba leaves (GBE) is a herbal medicinal product for the symptomatic treatment of age-related cognitive decline/impairment, including memory and concentration problems, as well as tinnitus, dizziness and intermittent claudication. In Switzerland, GBE is available as a drug approved by the Swiss Health Service and is reimbursed by basic health insurance.

According to the EU Pharmacopoeia, the dry extract of the ginkgo leaf is standardized to 22-27% flavonoids expressed as flavone glycosides, 2.6-3.2% bilobalides, 2.8-3.4% ginkgolides A, B and C and a content of ginkgolic acids below 5 ppm. The mechanism of action is linked to the different components of the extract. These constituents are involved in restoring impaired mitochondrial function by improving neuronal energy supply, reducing the amount of free oxygen radicals called reactive oxygen species (ROS), inhibiting amyloid-β (Aβ) protein aggregation and toxicity, and improving synaptic function and plasticity. Only a few effects appear to be independent of the improvement in mitochondrial function, such as the increase in local cerebral blood flow, the reduction in blood viscosity and the modification of neurotransmitter systems. GBE can therefore be considered a multi-target drug.

Currently, most available review articles focus on the effects of GBE on MCI and dementia, but not on SCD and its specific cognitive effects. Dr. Jörg Grünwald, Analyze & Realize GmbH, Berlin, and colleagues from the University of Basel conducted a review of information on the effectiveness of standardized GBE in SCD [1]. The researchers collected clinical data on the effects of standardized GBE on early stages of cognitive decline in middle-aged adults. The search was based on the available literature from the main randomized clinical trials (RCTs), systematic reviews and meta-analyses on standardized GBE in people with cognitive impairment. In addition, information was obtained from the selected studies on the duration of treatment, the daily dose of GBE used, the average age of participants and the parameters assessed in each clinical trial.

The number of available GBE studies on SCD is small, as the review showed. The authors emphasize that since SCD was first described more than 20 years ago, different terminologies have been used in clinical studies, e.g. subjective cognitive impairment, subjective memory loss, memory complaints. Therefore, the selection of studies for this review was challenging. Comparison between the studies was also difficult, as the studies differed in terms of the doses used, the criteria, the duration and the outcomes measured.

240 mg GBE/day could be beneficial for SCD

Of the 8 randomized clinical trials, 6 studies provided evidence of efficacy for GBE in the treatment of SCD with respect to at least one cognitive parameter. One study was inconclusive, but a post-hoc analysis showed efficacy in preventing Alzheimer’s disease when taken for 4 years.

Half of the included studies used a specific standardized GBE at a dose of 240 mg/day, but the duration of treatment ranged from weeks to years. When GBE was administered over a short period of time (3 weeks to 2 months) to people with SCD, it showed positive effects on cognitive flexibility.

The extract improved cognitive flexibility without significant changes in brain activation, implying that there was no increased recruitment of neural systems and/or resources. In addition, there was a trend towards a trade-off between speed and accuracy in the Go/NoGo task. According to the authors, GBE might induce mild prefrontal dopaminergic potentiation, but further additional testing is needed to assess this effect on dopaminergic systems. At higher doses, the same standardized GBE (320 and 600 mg/day) improved information processing speed in the elderly. Medium-term treatment (3 to 6 months) with standardized GBE at a dose of 240 mg/day also led to improvements in cognitive domains such as concentration, visual and verbal memory, and aspects of subjective well-being (physical health) in middle-aged adults (45 to 65 years).

With regard to the safety aspects of the standardized GBE, no serious side effects occurred. Treatment with doses of up to 240 mg/day proved to be safe and well tolerated and led to an improvement in cognitive abilities and daily activities. In all studies, the extracts had the same safety profile as the placebo treatments. Even long-term administration of standardized GBE (240 mg daily) had no effect on vital signs, physical or neurological function. Thus, the use of standardized GBE is safe and well tolerated even over long periods of time. The results also showed that a dose of more than 200 mg/day of GBE over a period of at least 5 months was required to support the beneficial effects in people with dementia.

The age of the participants could also play a role in the results of the clinical studies. According to the authors, the results suggest that GBE may have a positive effect in preventing, improving or delaying SCD in the 50 and older generation. Two studies reported an improvement in cognitive function and aspects of subjective well-being in SCD participants in the 45-65 age group. In both studies, the same dose of GBE (240 mg/day) was used for short- to medium-term treatments (2 to 3 months). Positive cognitive effects were also observed in participants with an average age of 69 years (55-86 years), including visual short-term memory and improvement in information speed. However, the studies used different standardized GBE (320 and 600 mg/day) and low doses for short- to medium-term treatments (3 weeks and 6 months, respectively). As Grünwald et al. emphasize, larger, well-defined RCTs with SCD criteria are therefore needed to further demonstrate this effect in SCD patients.

Literature:

1. Grünwald J, et al: The Effects of Standardized Ginkgo Biloba Extracts (GBE) on Subjective Cognitive Decline (SCD) in Middle-Aged Adults: A Review. Advances in Aging Research 2020; 9: 45-65; doi: 10.4236/aar.2020.93005.

HAUSARZT PRAXIS 2024; 19(8): 42-43
InFo NEUROLOGY & PSYCHIATRY 2024; 36-37