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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Complementary and Alternative Medicine 1/2018

Clinical and genomic safety of treatment with Ginkgo biloba L. leaf extract (IDN 5933/Ginkgoselect®Plus) in elderly: a randomised placebo-controlled clinical trial [GiBiEx]

BMC Complementary and Alternative Medicine > Ausgabe 1/2018
Stefano Bonassi, Giulia Prinzi, Palma Lamonaca, Patrizia Russo, Irene Paximadas, Giuseppe Rasoni, Raffaella Rossi, Marzia Ruggi, Salvatore Malandrino, Maria Sánchez-Flores, Vanessa Valdiglesias, Barbara Benassi, Francesca Pacchierotti, Paola Villani, Martina Panatta, Eugenia Cordelli
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12906-018-2080-5) contains supplementary material, which is available to authorized users.



Numerous health benefits have been attributed to the Ginkgo biloba leaf extract (GBLE), one of the most extensively used phytopharmaceutical drugs worldwide. Recently, concerns of the safety of the extract have been raised after a report from US National Toxicology Program (NTP) claimed high doses of GBLE increased liver and thyroid cancer incidence in mice and rats. A safety study has been designed to assess, in a population of elderly residents in nursing homes, clinical and genomic risks associated to GBLE treatment.


GiBiEx is a multicentre randomized clinical trial, placebo controlled, double blinded, which compared subjects randomized to twice-daily doses of either 120-mg of IDN 5933 (also known as Ginkgoselect®Plus) or to placebo for a 6-months period. IDN 5933 is extracted from dried leaves and contains 24.3% flavone glycosides and 6.1% of terpene lactones (2.9% bilobalide, 1.38% ginkgolide A, 0.66% ginkgolide B, 1.12% ginkgolide C) as determined by HPLC. The study was completed by 47 subjects, 20 in the placebo group and 27 in the treatment group. Clinical (adverse clinical effect and liver injury) and genomic (micronucleus frequency, comet assay, c-myc, p53, and ctnnb1 expression profile in lymphocytes) endpoints were assessed at the start and at the end of the study.


No adverse clinical effects or increase of liver injury markers were reported in the treatment group. The frequency of micronuclei [Mean Ratio (MR) = 1.01, 95% Confidence Intervals (95% CI) 0.86–1.18), and DNA breaks (comet assay) (MR = 0.91; 95% CI 0.58–1.43), did not differ in the two study groups. No significant difference was found in the expression profile of the three genes investigated.


None of the markers investigated revealed a higher risk in the treatment group, supporting the safety of IDN 5933 at doses prescribed and for duration of six months.

Trial registration Identifier: NCT03004508, December 20, 2016. Trial retrospectively registered.
Additional file 1: Certificate. Analysis Certificate of IDN 5933/Ginkgoselect®Plus and placebo [LM42506]. Indena S.p.A. declares all components used for the preparation of products. (PDF 622 kb)
Additional file 2: Questionnaire. GiBiEx QUESTIONNAIRE. The English version of the questionnaire administered to all participants to the GiBiEx study is reported. (PDF 10 kb)
Additional file 3: Comet Assay Raw data. Individual data relative to comet assay. For each donor data are shown as before (T0) and after (T1) placebo or IDN 5933 administration. (PDF 425 kb)
Additional file 4: Gene expression Raw data. Data were analyzed in each sample in terms of increase/decrease of the specific gene expression at T1 compared to T0, with a cut-off value ≥2-fold change (The values reported represent the excel conversion of the original raw data (average Ct calculated out of four replicates loaded onto the 48-wells PCR plate); the raw data are produced as “.csv” file by the EcoIllumina software and need to be converted into excel file for delta delta Ct analysis). (PDF 163 kb)
Additional file 5: Micronucleus Assay Raw data. Individual data relative to the MN Assay. Data are reported as before (T0) and after (T1) placebo or IDN 5933 administration. (PDF 683 kb)
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