HerbalEGram: Volume 5, Number 11, November 2008

A vast body of research supports numerous health benefits for ginkgo extracts, particularly for treating various symptoms and conditions associated with declining cognitive performance and poor circulation, says the American Botanical Council, an independent nonprofit research and education organization.

A new six-year clinical trial will be published Wednesday, November 19, in the Journal of the American Medical Association.¹ In the Ginkgo Evaluation of Memory (GEM) trial, a leading ginkgo extract was not effective in preventing the development of dementia in older adults. The ginkgo failed to reduce the overall incidence rate of dementia in a total of 3069 elderly individuals (minimum 75 years; average age 79) with normal cognition or those with mild cognitive impairment (MCI).

Researchers used the world’s most tested ginkgo extract (EGb 761®; made by W. Schwabe of Karlsruhe, Germany). The dosage used by 1545 subjects was 240 mg per day (120 mg twice daily) of the ginkgo tablets or a matching placebo (for 1524 people).

Described as a randomized, double-blind, placebo-controlled trial conducted from 2000 to 2008,^1,2 Steven T. DeKosky, M.D., currently dean of the University of Virginia School of Medicine (at the University of Pittsburgh, PA during the time of the study) and colleagues evaluated 2587 cognitively intact adults plus 482 adults with MCI. They were assessed every 6 months for dementia in 5 academic centers for 6.1 years.

The authors acknowledge that one of possible shortcomings of this trial is “because the delay from initial brain changes to clinical dementia is known to be long, it is possible that an effect of G. biloba, positive or negative, may take many more years to manifest.”¹

In an accompanying editorial, Lon S. Schneider MD of the University of Southern California, Los Angeles, “Despite 2 decades of research with standardized extracts of Ginkgo biloba, considerable uncertainty about its pharmacology and clinical effects remains.”³

ABC’s Response to the GEM trial

“There is a significant body of scientific and clinical evidence supporting the safety and efficacy of ginkgo extract for both cognitive function and improved circulation,” said Mark Blumenthal, the founder and executive director of ABC.

In addition to the issue of a longer duration raised by the authors, ABC noted that another potential weakness of this trial is the lack of an active control, i.e., a potential third arm of the trial in which patients would have used a pharmaceutical medication with known efficacy, to determine to what extent the particular population being tested would respond. This was not possible for this trial since no conventional pharmaceutical drug has ever demonstrated the ability to prevent the onset of dementia or diminish its progression.

Further, the trial notes that only about 60% of the patients were in compliance with their use of the ginkgo or placebo by the end of the trial. It is unclear whether the poor adherence to the assigned treatment might have had a negative effect on the trial’s results.

According to ABC’s Blumenthal, “Ginkgo’s benefits must be viewed in the context of the entirety of the published clinical data,” – a reference to numerous controlled clinical trials that support the use of ginkgo extract for treating symptoms of MCI and even early stage Alzheimer’s disease, as well as the circulatory benefit of increasing the ability of older people to walk distances with less leg pain (a condition known as peripheral arterial occlusive disease or intermittent claudication).

Veteran Maryland psychopharmacologist Jerry Cott, PhD, a member of the ABC Advisory Board, stated in an e-mail to CNN that due to the extreme difficulty and expense in generating useful life-style type clinical research data he often places more value in the basic science, i.e., “the pharmacology, rather than controlled clinical trials. The science for ginkgo says that it has physiological and biochemical effects in human and animal tissues that would surely be beneficial for many chronic illnesses, especially those that have a vascular component.”⁴

ABC also emphasized that the GEM trial is only 1 of about 5 clinical trials that are being conducted to try to determine if ginkgo extract can have a preventive effect on elderly adults and lessen the potential progression to dementia. Another large trial is currently underway with the results not expected for at least one year.⁵

ABC emphasized that ginkgo extract has been shown to be effective in treating symptoms of dementia in numerous controlled clinical trials as well as in population-based (epidemiological) studies. For example, 2 epidemiological studies conducted in France (known as the EPIDOS & PAQUID studies) have demonstrated a positive effect of the Schwabe EGb 761® ginkgo extract on the onset of Alzheimer’s dementia⁶ and the length of patients’ survival.⁷ These trials suggest that this ginkgo extract may be beneficial and appropriate therapy for elderly adults.

Further, an NIH sponsored study in the United States in 2008 demonstrated a beneficial effect of a standardized ginkgo extract on the risk of developing dementia in only the trial subjects taking the ginkgo on a regular basis.⁸

In addition to being tested for cognitive impairment, at least 16 controlled clinical trials have demonstrated benefits of various ginkgo extracts for healthy, non-cognitively impaired adults. A comprehensive review has shown that in 11 of these trials, the ginkgo increased short-term memory, concentration and time to process mental tasks.⁹

ABC also noted that ginkgo extract has been shown to be effective in controlled clinical for treating patients with peripheral arterial occlusive disease (PAOD), a condition in older people characterized by pain in the legs while walking due to inadequate circulation. A systematic review of 9 controlled clinical trials found that in at least 7 trials the ginkgo extract exhibited safe and effective benefits compared to placebo.¹⁰

About Ginkgo Extract

Ginkgo (Ginkgo biloba) is the world’s oldest living tree, dating back about 250 million years. Ginkgo leaves have been used in traditional Chinese medicine for about 500 years. For about the past 30 years the leaves of ginkgo have been made into a highly concentrated (50:1) extract, chemically standardized to compounds unique to ginkgo (ginkgolides and bilobalide) as well as other compounds. The leading German ginkgo extract has been subjected to a vast range of clinical trials documenting its ability to improve peripheral circulation and cognitive function, particularly in patients with early stages of mild cognitive impairment, senile dementia, Alzheimer’s disease, and memory loss. Clinical trials also support the use of ginkgo extract in assisting elderly patients in walking longer distances without leg pain (PAOD, also known as intermittent claudication). Standardized ginkgo extracts are approved for use as medicines in Germany and numerous other countries.

References

1. DeKosky ST, Williamson J, Fitzpatrick A, Kronmal RA, Ives DG, Saxton J, Lopez O, Burke G, Carlson M, Fried L, Kuller LH, Robbins J, Tracy RP, Woolard NF, Dunn L, Snitz BE, Nahin RL, Furberg CD for the GEM Study Investigators. Ginkgo biloba for primary prevention of dementia: Results of the Ginkgo Evaluation of Memory (GEM) Study. JAMA Nov 19, 2008;300(19):2253-2262.

2. American Medical Association. Ginkgo biloba does not appear to prevent dementia, Alzheimer’s disease [press release]. Chicago, IL: Nov. 13, 2008.

3. Schneider L. Ginkgo biloba extract and preventing Alzheimer’s disease. JAMA Nov 19, 2008; 300(19):2306-2308.

4. Cott J e-mail to Elizabeth Cohen (CNN), Nov. 16, 2008 

5. Andrieu S, Ousset PJ, Coley N, Ouzid M, Mathiex-Fortunet H, Vellas B, GuidAge Study Group. GuidAge study: a 5-year double-blind, randomized trial of EGb 761 for the prevention of Alzheimer’s disease in elderly subjects with memory complaints. I Rationale, Design and baseline data. Curr Alz Res 2008;5:406-415.

6. Andrieu S, Gillette S, Amouyal K, Nourhashemi F, Reynish E, Ousset PJ, Albarede JL, Vellas B, Grandjean H. Association of Alzheimer’s disease onset with Ginkgo biloba and other symptomatic cognitive treatments in a population of women aged 75 years and older from the EPIDOS study. J Gerontol Med Sci 2003;58A:372-377.

7. Dartigues JF, Carcaillon L, Helmer C, Lechevallier N, Lafuma A, Khoshnood B. Vasodilators and Nootropics as Predictors of Dementia and Mortality in the PAQUID Cohort. J Am Geriatr Soc 2007; 55:395–399.

8. Dodge HH, Zitzelberger T, Oken BS, Howieson D, Kaye J. A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline. Neurology 2008;70:1809-1817.

9. Crews W, Harrison DW, Griggin ML, Falwell KD, Crist T, Longest L, Hehemann L, Rey ST. The neuropsychological efficacy of ginkgo preparations in healthy and cognitively intact adults; A comprehensive review. HerbalGram 2005;67:42-62.