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]

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article number22
JournalBMC Complementary and Alternative Medicine
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 22 2018

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Ginkgo biloba
Randomized Controlled Trials
Placebos
Safety
ginkgolide B
flavone
Comet Assay
Confidence Intervals
DNA Breaks
Liver
Terpenes
Wounds and Injuries
Insurance Benefits
Lactones
Therapeutics
Liver Neoplasms
Glycosides
Nursing Homes
Transcriptome
Thyroid Neoplasms

Keywords

  • DNA cell maintenance
  • Genomic stability
  • Ginkgo biloba Extract
  • Safety

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

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]. / 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.

In: BMC Complementary and Alternative Medicine, Vol. 18, No. 1, 22, 22.01.2018.

Research output: Contribution to journalArticle

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. / 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]. In: BMC Complementary and Alternative Medicine. 2018 ; Vol. 18, No. 1.
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T1 - Clinical and genomic safety of treatment with Ginkgo biloba L. leaf extract (IDN 5933/Ginkgoselect®Plus) in elderly

T2 - A randomised placebo-controlled clinical trial [GiBiEx]

AU - Bonassi, Stefano

AU - Prinzi, Giulia

AU - Lamonaca, Palma

AU - Russo, Patrizia

AU - Paximadas, Irene

AU - Rasoni, Giuseppe

AU - Rossi, Raffaella

AU - Ruggi, Marzia

AU - Malandrino, Salvatore

AU - Sánchez-Flores, Maria

AU - Valdiglesias, Vanessa

AU - Benassi, Barbara

AU - Pacchierotti, Francesca

AU - Villani, Paola

AU - Panatta, Martina

AU - Cordelli, Eugenia

PY - 2018/1/22

Y1 - 2018/1/22

N2 - 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.

AB - 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.

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KW - Genomic stability

KW - Ginkgo biloba Extract

KW - Safety

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