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Commentary

Herbal therapy: a new pathway for the treatment of Alzheimer's disease

Jinzhou Tian*, Jing Shi, Xuekai Zhang and Yongyan Wang

Alzheimer's Research & Therapy 2010, 2:30  doi:10.1186/alzrt54

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Ginkgo biloba has a proven benefit

Siegfried Kasper   (2010-12-07 14:04)  Medical University of Vienna email

Tian et al. arrive at a negative conclusion with regard to Ginkgo biloba for the treatment of Alzheimer's disease by relying on a Cochrane Review [1] and a study that did not really address the question they were trying to answer [2]. Unfortunately, the cited Cochrane review is flawed in that it lumps together studies using different Ginkgo products that can by no means be considered bioequivalent as well as studies in patients with different diseases or ailments (merely subjective memory complaints, mild cognitive decline, overt dementia). Obviously, it does not make sense to estimate a common effect size for 0.57 mg flavone glycosides and 0.97 mg ginkgolides per day in subjective cognitive complaints [3] and 58.8 mg flavone glycosides and 14.4 mg terpene lactones per day in dementia [4], as done in Birks' analysis no. 1.15. Furthermore, it is not true that three of the four most recent trials showed no difference between Ginkgo and placebo: the trials by Napryeyenko [4] and Mazza [5] showed significant superiority of Ginkgo biloba extract over placebo. The DIGGER trial [6] was an attempt to address two questions at the same time and was seriously underpowered after repeated downward calculation of the sample size due to recruitment problems.
Finally, Snitz et al. [2] reported on a prevention trial in elderly people who were cognitively healthy or had MCI. It is not possible to draw any conclusions with respect to efficacy of Ginkgo biloba extract in the treatment of Alzheimer's disease from a prevention trial. It is also inappropriate to conclude from this trial that Ginkgo extract does not reduce cognitive decline, since there was no cognitive decline to be reduced, neither in the Ginkgo group nor in the control group.
Recent meta-analyses that adequately considered inclusion diagnoses, extract type and dosing confirmed the efficacy of Ginkgo biloba leaf extracts standardized according to the European Pharmacopoeia at a daily dose of 240 mg in dementia and Alzheimer's disease [7,8,9,10].


References
1. Birks J, Grimley Evans J: Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2009, 1:CD003120.
2. Snitz BE, O'Meara ES, Carlson MC, Arnold AM, Ives DG, Rapp SR, Saxton J, Lopez OL, Dunn LO, Sink KM, DeKosky ST; Ginkgo Evaluation of Memory Study: Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA 2009, 302:2663-2670.
3. Brautigam MRH, Blommaert FA, Verleye G, Castermans J, Jansen Steur ENH, Kleijnen J: Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double blind placebo-controlled study. Phytomedicine 1998, 5:425-434.
4. Napryeyenko O, Borzenko I; GINDEM-NP Study Group: Ginkgo biloba special extract in dementia with neuropsychiatric features. A randomized, placebo-controlled, double-blind clinical trial. Arzneimittelforschung 2007, 57:4-11.
5. Mazza M, Capuano A, Bria P, Mazza S: Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study. Eur J Neurol 2006, 13:981-985.
6. McCarney R, Fisher P, Iliffe S, van Haselen R, Griffin M, van der Meulen J, Warner J: Ginkgo biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo-controlled trial. Int J Geriatr Psychiatry 2008, 23:1222-1230.
7. IQWiG Institute for Quality and Efficiency in Health Care. IQWiG Reports �� Commission No. A05-19B, Ginkgo in Alzheimer's disease. Executive Summary. K��ln: IQWiG, 2008: http://www.iqwig.de/download/A05-19B_Executive_Summary_Ginkgo_in_Alzheimers_disease.pdf.
8. Kasper S, Schubert H: Ginkgo biloba extract EGb 761�� in the treatment of dementia: Evidence of efficacy and tolerability [Ginkgo-Spezialextrakt EGb 761�� in der Behandlung der Demenz: Evidenz f��r Wirksamkeit und Vertr��glichkeit]. Fortschr Neurol Psychiat 2009; 77: 494-506.
9. Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN: Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr 2010, 10:14.
10. Wang BS, Wang H, Song YY, Qi H, Rong ZX, Wang BS, Zhang L, Chen HZ: Effectiveness of Standardized Ginkgo biloba Extract on Cognitive Symptoms of Dementia with a Six-Month Treatment: A Bivariate Random Effect Meta-Analysis. Pharmacopsychiatry 2010, 43:86-91.

Competing interests

Dr. Kasper has received grant/research support from Bristol Myers-Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Organon, Sepracor and Servier; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Merck Sharp and Dome (MSD), Novartis, Organon, Pfizer, Schwabe, Sepracor, and Servier; and has served on speakers�� bureaus for Angelini, AstraZeneca, Bristol Myers-Squibb, Eli Lilly, Janssen, Lundbeck, Pfizer, Pierre Fabre, Schwabe, Sepracor, and Servier.

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