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]

• Published in: BMC complementary and alternative medicine 2018-01, Vol.18 (1), p.22-12, Article 22
• Main Authors: Bonassi, Stefano, Prinzi, Giulia, Lamonaca, Palma, Russo, Patrizia, Paximadas, Irene, Rasoni, Giuseppe, Rossi, Raffaella, Ruggi, Marzia, Malandrino, Salvatore, Sánchez-Flores, Maria, Valdiglesias, Vanessa, Benassi, Barbara, Pacchierotti, Francesca, Villani, Paola, Panatta, Martina, Cordelli, Eugenia
• Format: Article
• Language: English
• Subjects: Aged; Bilobalide; Bioassays; c-Myc protein; Cancer therapies; Cardiovascular disease; Clinical trials; Comet assay; Confidence intervals; Damage detection; Dementia; Deoxyribonucleic acid; Dietary supplements; DNA; DNA cell maintenance; DNA damage; Drug dosages; Evidence-based medicine; Flavone glycosides; Gene expression; Genetic aspects; Genomic stability; Genomics; Geriatrics; Ginkgo; Ginkgo biloba; Ginkgo biloba Extract; Glycosides; Health aspects; Herbal medicine; High-performance liquid chromatography; Lactones; Leaves; Liquid chromatography; Liver; Liver cancer; Lymphocytes; Markers; Materia medica, Vegetable; Medicine; Micronuclei; Mutagenesis; Myc protein; Nursing homes; Older people; p53 Protein; Physiological aspects; Plant extracts; Properties; Safety; Seeds; Thyroid; Thyroid cancer; Toxicity; Toxicology
• ISSN: 1472-6882; 1472-6882
• DOI: 10.1186/s12906-018-2080-5

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. ClinicalTrials.gov Identifier: NCT03004508 , December 20, 2016. Trial retrospectively registered.