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 Complement Altern Med. 2018 Jan 22;18(1):22. doi: 10.1186/s12906-018-2080-5. Bonassi S1,2, Prinzi G3, Lamonaca P3, Russo P3, Paximadas I3, Rasoni G4, Rossi R5, Ruggi M6, Malandrino S7, Sánchez-Flores M8, Valdiglesias V8, Benassi B9, Pacchierotti F9, Villani P9, Panatta M9, Cordelli E9. Author information 1 Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, San Raffaele University, Via di Val Cannuta 247, 00166, Rome, Italy. stefano.bonassi@sanraffaele.it. 2 Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Via di Val Cannuta 247, 00166, Rome, Italy. stefano.bonassi@sanraffaele.it. 3 Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, San Raffaele University, Via di Val Cannuta 247, 00166, Rome, Italy. 4 RSA San Raffaele Rocca di Papa, Via Ariccia, 16, 00040, Rocca di Papa (RM), Italy. 5 RSA San Raffaele Sabaudia, via Borgo Nuovo, 04010, Sabaudia (LT), Italy. 6 RSA San Raffaele Montecompatri, Via San Silvestro, 67, 00077, Montecompatri (RM), Italy. 7 Indena S.P.A., viale Ortles, 12, 20141, Milan, Italy. 8 DICOMOSA Group, Department of Psychology, Universidade de A Coruña, A Coruña, Spain. 9 Laboratory of Biosafety and Risk Assessment, ENEA CR Casaccia, Via Anguillarese, 301, 00123, Rome, Italy. Abstract BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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: ClinicalTrials.gov Identifier: NCT03004508 , December 20, 2016. Trial retrospectively registered. KEYWORDS: DNA cell maintenance; Genomic stability; Ginkgo biloba Extract; Safety PMID: 29357859 PMCID: PMC5778811 DOI: 10.1186/s12906-018-2080-5 [Indexed for MEDLINE] Free PMC Article