Ginkgo Biloba

Ginkgo biloba in Alzheimer’s disease: a systematic review.
Janssen IM, Sturtz S, Skipka G, Zentner A, Velasco Garrido M, Busse R.
Wien Med Wochenschr. 2010 Dec;160(21-22):539-46.

 This systematic review determines the benefit of treatment with Ginkgo biloba (Ginkgo) in Alzheimer’s disease (AD) concerning patient-relevant outcomes. Bibliographic databases, clinical trial and study result registries were searched for randomized controlled trials (RCTs) in patients with AD (follow-up ≥16 weeks) comparing Ginkgo to placebo or a different treatment option. Manufacturers were asked to provide unpublished data. If feasible, data were pooled by meta-analysis. Six studies were eligible; overall, high heterogeneity was shown for most outcomes, except safety aspects. Among studies administering high-dose Ginkgo (240 mg), all studies favour treatment though effects remain heterogeneous. In this subgroup, a benefit of Ginkgo exists for activities of daily living. Cognition and accompanying psychopathological symptoms show an indication of a benefit. A harm of Ginkgo is not evident. An estimation of the effect size was not possible for any outcome. Further evidence is needed which focuses especially on subgroups of AD patients. PMID: 21170694

 Ginkgo biloba extract ameliorates oxidative phosphorylation performance and rescues abeta-induced failure.
Rhein V, Giese M, Baysang G, Meier F, Rao S, Schulz KL, Hamburger M, Eckert A.
PLoS One. 2010 Aug 24;5(8):e12359.

 Energy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer’s disease (AD). Recently, we demonstrated that chronic exposure to amyloid-beta (Abeta) in human neuroblastoma cells over-expressing human wild-type amyloid precursor protein (APP) resulted in (i) activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS) and in (ii) a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE) is able to rescue Abeta-induced defects in energy metabolism. We used a high-resolution respiratory protocol to evaluate OXPHOS respiratory capacity under physiological condition in control (stably transfected with the empty vector) and APP cells after treatment with GBE. In addition, oxygen consumption of isolated mitochondria, activities of mitochondrial respiratory enzymes, ATP and reactive oxygen species (ROS) levels as well as mitochondrial membrane mass and mitochondrial DNA content were determined. We observed a general antioxidant effect of GBE leading to an increase of the coupling state of mitochondria as well as energy homeostasis and a reduction of ROS levels in control cells and in APP cells. GBE effect on OXPHOS was even preserved in mitochondria after isolation from treated cells. Moreover, these functional data were paralleled by an up-regulation of mitochondrial DNA. Improvement of the OXPHOS efficiency was stronger in APP cells than in control cells. In APP cells, the GBE-induced amelioration of oxygen consumption most likely arose from the modulation and respective normalization of the Abeta-induced disturbance in the activity of mitochondrial complexes III and IV restoring impaired ATP levels possibly through decreasing Abeta and oxidative stress level. Although the underlying molecular mechanisms of the mode of action of GBE remain to be determined, our study clearly highlights the beneficial effect of GBE on the cellular OXPHOS performance and restoration of Abeta-induced mitochondrial dysfunction. PMID: 20808761

  Ginkgolide B complex efficacy for brief prophylaxis of migraine in school-aged children: an open-label study.”
Esposito M, Carotenuto M.
Neurol Sci. 2011 Feb;32(1):79-81

 Primary headaches (migraines and tension-types headaches) are very common in school-aged children. Ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, was considered as a promising pharmacological aid for the treatment of migraine in adult patients because of its modulation of the glutamatergic transmission in the CNS and on antiplatelet activating factor (PAF). The aim of study is to verify the effectiveness and safety of association of Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium complex for brief prophylaxis in a population of school-aged children with migraine. In our sample after 3 months of treatment with association of Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium complex, the mean frequency per month of migraine was significantly decreased (9.71 ± 4.33 vs. 4.53 ± 3.96 attacks; p < 0.001). Our findings suggest that in childhood headache management, the use of alternative treatments must be considered not to evoke a placebo effect, but as soft therapy without adverse reactions. PMID: 20872034

  Effects of Ginkgo biloba in dementia: systematic review and meta-analysis.
Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN.
BMC Geriatr. 2010 Mar 17;10:14.

 The benefit of Ginkgo biloba has been discussed controversially. The aim of this review was to assess the effects of Ginkgo biloba in Alzheimer’s disease as well as vascular and mixed dementia covering a variety of outcome domains. We searched MEDLINE, EMBASE, the Cochrane databases, CINAHL and PsycINFO for controlled trials of ginkgo for Alzheimer’s, vascular or mixed dementia. Studies had to be of a minimum of 12 weeks duration with at least ten participants per group. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as risk ratios or standardized mean differences (SMD) in scores. Nine trials using the standardized extract EGb761(R) met our inclusion criteria. Trials were of 12 to 52 weeks duration and included 2372 patients in total. In the meta-analysis, the SMDs in change scores for cognition were in favor of ginkgo compared to placebo (-0.58, 95% confidence interval [CI] -1.14; -0.01, p = 0.04), but did not show a statistically significant difference from placebo for activities in daily living (ADLs) (SMD = -0.32, 95% CI -0.66; 0.03, p = 0.08). Heterogeneity among studies was high. For the Alzheimer subgroup, the SMDs for ADLs and cognition outcomes were larger than for the whole group of dementias with statistical superiority for ginkgo also for ADL outcomes (SMD = -0.44, 95% CI -0.77; -0.12, p = 0.008). Drop-out rates and side effects did not differ between ginkgo and placebo. No consistent results were available for quality of life and neuropsychiatric symptoms, possibly due to the heterogeneity of the study populations. Ginkgo biloba appears more effective than placebo. Effect sizes were moderate, while clinical relevance is, similar to other dementia drugs, difficult to determine. PMID: 20236541

  Protective effects of extract of Ginkgo biloba on adriamycin-induced heart failure and its mechanism: role of ghrelin peptide.
Xu Z, Wu W, Lan T, Zhang X.
Zhongguo Zhong Yao Za Zhi. 2009 Nov;34(21):2786-9.

 To explore the protective effects of extract of Ginkgo biloba (EGB) in adriamycin (ADR)-induced heart failure (HF) and the mechanism of ghrelin peptide.Wistar rats were randomly divided into three groups: control group, HF group and EGB group. ADR was injected in the rats of HF group and EGB group by caudal vein. After the last injection, the rats in EGB group were given intra-gastric administration of EGB solution (100 mg x kg(-1) x d(-1)). Three weeks later, cardiac function was detected; Ghrelin levels in plasma and myocardium were measured by radio-immunology assay (RIA); High energy phosphates (HEP) contents in myocardium were measured by HPLC; Myocardial gene expression of ghrelin was measured by RT-PCR. Compared with control group, HF group had obviously decreased index of cardiac function, and these indexes such as +/- dp/dt max in EGB group were higher than those in ADR group. Plasma ghrelin level in HF group was higher than that in control group while myocardial ghrelin level was significantly lower than that in control group. Myocardial ATP content and gene expression of ghrelin mRNA in HF group were significantly lower than those in control group; Plasma ghrelin level in EGB group was significantly increased. Myocardial ATP content and gene expression of ghrelin mRNA in EGB group were significantly higher than those in HF group, and were closed to those of control group. Myocardial energy dysfunction is an important reason of ADR-induced HF. EGB therapy can improve cardiac function and energy metabolism in HF rats, partly because it might increase the expression and production of ghrelin, which can promote positive energy metabolism.  PMID: 20209916

  Effectiveness of standardized ginkgo biloba extract on cognitive symptoms of dementia with a six-month treatment: a bivariate random effect meta-analysis.
Wang BS, Wang H, Song YY, Qi H, Rong ZX, Wang BS, Zhang L, Chen HZ.
Pharmacopsychiatry. 2010 May;43(3):86-91

 The objective of this study is to take into consideration the influence of baseline risk on the treatment effect and evaluate the effectiveness of standardized GINKGO BILOBA extract (GbE) on cognitive symptoms of dementia with the treatment period of approximately 6 months. We systematically searched the literature to identify all randomized placebo-controlled clinical trials (English language) of GbE in the treatment of dementia. Data were extracted from selected trials and combined with standard meta-analysis methods. A bivariate meta-analysis was carried out to further estimate the effect size of GbE. The random effect estimate of standard mean difference (SMD) between GbE and placebo groups of 6 selected trials was -0.89 (95% CI -1.82 to 0.04) in the assessment of cognitive function. Bivariate random effect estimate of difference of change in ADAS-cog scores was -2.65 (95% CI –4.53 to -0.76), which showed a significant difference in favor of GbE. Considering baseline risk in the assessment of treatment effect, GbE was found to be effective for cognitive functions in dementia with the treatment of 6 months. PMID: 20104449
Copyright Georg Thieme Verlag KG Stuttgart New York.

  Ginkgo biloba: specificity of neuropsychological improvement–a selective review in search of differential effects.
Kaschel R.
Hum Psychopharmacol. 2009 Jul;24(5):345-70.

 Extracts of Ginkgo biloba are widely used for the treatment of cognitive impairment. Whereas reviews have focused on the question whether ginkgo is effective to enhance cognition in general, little is known about specificity of improvement. This might be crucial for future trials, thus enabling hypotheses about sensitive outcome measures. Therefore, this article summarizes such information, i.e. neuropsychological effects of chronic administration of ginkgo in healthy and cognitively impaired subjects of any age. Objective psychometric test results were considered if they reflected distinct cognitive functions from randomized controlled group-studies (RCT). We reviewed 29 RCTs yielding 209 placebo-drug comparisons of psychometric scores in four different cognitive domains comprising 14 sub-functions. Whereas little specific information can be obtained from trials for treatment of dementia, a pattern of pharmacological actions on cognitive processes emerges here from studies for mild cognitive impairment (MCI), depression, multiple sclerosis and healthy young and elderly subjects. There is consistent evidence that chronic administration improves selective attention, some executive processes and long-term memory for verbal and non-verbal material. Further trials should be more comprehensive as there are few data available on some cognitive functions and psychometric flaws in the selection of tests and the interpretation of their results favouring predominantly beta-errors. Thus, though this pattern is encouraging it also asks for a cautious interpretation to date. PMID: 19551805

  Modulation of cognitive performance following single doses of 120 mg Ginkgo biloba extract administered to healthy young volunteers.
Kennedy DO, Jackson PA, Haskell CF, Scholey AB.
Hum Psychopharmacol 2007 Dec;22(8):559-66..

 Previous research from our laboratory demonstrated that administration of single doses (120, 240, 360 mg) of standardised Ginkgo biloba extract (GBE) had linear, dose-dependent, positive effects on the speed of performing attention tasks in comparison to placebo. However, whilst the lowest dose, which is typical of a recommended daily dose, had no effect on the speed of attention task performance it did engender mild improvements in secondary memory performance. The current study presents a reanalysis of data from three methodologically identical studies that each included a treatment of 120 mg GBE and matched placebo. All three studies were of a multiple dose, placebo-controlled, double-blind, balanced-crossover design, employing four or five treatment arms in total. Across the studies 78 healthy young participants received 120 mg GBE and placebo in randomly counterbalanced order, separated by a wash-out period of at least 7 days. On each study day participants’ performance on the Cognitive Drug Research (CDR) computerised cognitive assessment battery was measured immediately prior to dosing and at 1, 2.5, 4 and 6 hr following treatment, with scores collapsed into the six measures (speed of attention, accuracy of attention, secondary memory, working memory, speed of memory, quality of memory) which have previously been derived by factor analysis of the data from CDR subtests. The results showed that 120 mg of Ginkgo engendered a significant improvement on the ‘quality of memory’ factor that was most evident at 1 and 4 hr post-dose, but had a negative effect on performance on the ‘speed of attention’ factor that was most evident at 1 and 6 hr post-dose. The current study confirmed the previous observation of modestly improved memory performance following 120 mg of GBE, but suggests that acute administration of this typical daily dose may have a detrimental effect on the speed of attention task performance which is opposite to that seen previously following higher doses. PMID: 17902186