Ginkgo biloba …what is it good for?

Holland and Barrett have recently taken the opportunity to pitch me the idea, via an e-mail, that Ginkgo Biloba “helps the maintenance of good cognitive function.”   Their web page contains a more detailed and specific claim: 

“Today nutritionists are taking a closer look at this wonderful herb because it has been used for many years throughout Europe. Supports the maintenance of good cognitive function and healthy circulation which helps to maintain memory with age decline.”

Interestingly the UK’s Advertising Standards Authority (ASA) tells me that they have, “… accepted that this particular product can, in the short term, help with the maintenance of memory in healthy individuals.”  This acceptance seems, to me to extend beyond the “age decline” claim of Holland and Barrett.

So, curious about the evidence, I decided to search for something to convince me that Ginkgo Biloba supports the, “maintenance of good cognitive function” or, “memory in healthy individuals”.

As always, my first port of call was the respected Cochrane Library.  I searched this resource for “Ginkgo Biloba” and found only one potentially relevant Cochrane review.  As it is, this looks at the effects of this herb on people with dementia, rather than the general population that the ASA are happy to accept can be helped.

Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD003120. DOI: 10.1002/14651858.CD003120.pub2.

There is no convincing evidence that Ginkgo biloba is efficacious for dementia and cognitive impairment.

Overall, evidence that Ginkgo has predictable and clinically significant benefit for people with dementia or cognitive impairment is inconsistent and unconvincing. Two of the best most recent trials, which are also among the largest trials, found no difference between placebo and Ginkgo.

This is a familiar theme when dealing with CAM: the better the trial the less positive the result.

(There is a Cochrane protocol listed, “Ginkgo biloba for cognitive improvement in healthy individuals (November 2003)”.  This would be directly relevant, hopefully it will soon come to fruition.)

My search did turn up some other reviews.

Oken B S,Storzbach D M,Kaye J A.The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Archives of Neurology.1998;55(11):1409-1415.

“Based on a quantitative analysis of the literature there is a small but statistically significant effect of 3- to 6-month treatment with 120 to 240 mg of Ginkgo biloba extract on objective measures of cognitive function in AD.”

The CRD commentary on this review offers some cautionary observations:

“The quality of the included studies was not assessed and the authors have not reported on how the articles were selected, or how many of the reviewers were involved in the data extraction.

The studies were combined using effect size statistics but there is no discussion of how the interpretation of those effect sizes translate quantifiably to the cognitive assessment measures included in the review. The authors do not report any tests for homogeneity but the heterogeneity of studies is discussed in the text. It appears that heterogeneity may have been significant and so pooling may have been inappropriate. The authors acknowledge several drawbacks about the quality and design of the individual studies.”

Each Holland and Barrett pill contains, according to the label (see below), a dose of 60 mg Ginkgo Biloba leaf Extract (Standardised for a minimum of 24% Ginkgo Flavone Glycosides, 14.4mg and 6% terpenes, 3.6mg).  

The dosage directions on the label are, “Take one or two tablets daily, preferably with meals. Do not exceed stated dose.”  This is recommending a maximum daily intake of 120 mg, which would seem to make the effectiveness of this product marginal, even in the sub-group of people who may benefit; if efficacy can be inferred from this study.

Ernst E,Pittler M H.Ginkgo biloba for dementia: a systematic review of double-blind, placebo-controlled trials. Clinical Drug Investigation.1999;17(4):301-308.

The majority of randomised controlled trials available to date support the notion that Ginkgo biloba is efficacious in delaying the clinical deterioration of patients with dementia or in bringing about symptomatic improvement. Unfortunately none of the current studies is flawless and ultimately convincing.

 Bandoiler made the following observations on this review:

 “There is no convincing evidence to show that lower doses of ginkgo bilboa extract improve dementia. However, oral ginkgo 240 mg and intravenous ginkgo 200 mg did produce significantly greater improvements than placebo. The superiority of the intravenous dose was based on only 40 patients, so the result is not robust. One problem in these trials is their ability to demonstrate a difference between study treatments, since patients with mild dementia were included. If patients with only moderate or severe dementia had been included the internal sensitivity of the studies would have been greater. This is an important measure of study validity. Another problem in these trials is that different outcomes, doses and durations of treatment were assessed. The studies were clinically heterogeneous and patient information could not be pooled in a meta-analysis.”

A similar observation can be made about the dosage recommended for the Holland and Barrett product (120 mg daily maximum) and the dosage for which this study provides at least some evidence of efficacy: 240 mg orally for people with dementia. 

Not very impressive so far.  Next, I wondered what the NHS National Library of Health had to say.  This turned up nothing new or relevant; aside from a pretty poor document from the Royal College of Nursing entitled, “Complementary approaches to Menopausal symptoms.”  This document is probably worth a short post in itself.  [Edit 18/11/08: actually I’ll be covering it in two posts. The first installment is here and deals mainly with what it has to say about herbs.] It had this to say about Gingko biloba:

“It is suggested that Gingko has a beneficial effect on cognitive impairment and dementia. One randomised trial looking at the effects of Gingko on mood and cognition in post-menopausal women showed better non-verbal memory and sustained attention with Gingko (Hartley, 2003).”

The trial referenced seems to be Hartley et al. “Effects on cognition and mood in postmenopausal women of 1-week treatment with Ginkgo biloba.” Pharmacol Biochem Behav. 2003 Jun;75(3):711-20.  What the RCN document fails to mention is that this was a one week trial with only 31 subjects.  It also used 120 mg/day of Ginkgo: the maximum dose Holland and Barrett direct. 

The same lead author appears to have followed up this work with a longer (12 weeks) larger (n=57) trial of a supplement (Gincosan) containing both Ginkgo biloba (120 mg) Panax ginseng (200 mg).  The conclusion was: 

“There were no significant effects of Gincosan treatment on ratings of mood, bodily symptoms of somatic anxiety, menopausal symptoms, or sleepiness or on any of the cognitive measures of attention, memory or frontal lobe function. Thus, after chronic administration, Gincosan appeared to have no beneficial effects in post-menopausal women.”

Some of the same authors reported, “Limited cognitive benefits in Stage +2 postmenopausal women after 6 weeks of treatment with Ginkgo biloba” in 2005.  This was an explicit follow-up to the trial reported in 2003.  The summary states:

“We have previously found that 1 week of treatment with ginkgo improved attention, memory and mental flexibility in post-menopausal women, but the evidence for any beneficial effects of longer treatment is less well-established. The present study aimed to determine whether cognitive benefits, similar to those previously found after 1 week of treatment, would persist after 6 weeks of treatment, and whether those with poorer cognitive performance would benefit more.”

The trial was the largest of the three I have commented on (n=87).  Again it was a, “placebo-controlled, double-blind study” of, “postmenopausal women”.  These were, “randomly allocated to receive a standardized extract of ginkgo … (one capsule/day of 120 mg, n = 45) or matching placebo (n = 42) for 6 weeks.”  The result:

“… The beneficial effects of ginkgo were limited to the test of mental flexibility and to those with poorer performance.” 

And this was only one of, what appears to be eight outcomes measured.  So, in the end: no evidence for improvement of memory in this population.  This is a series of small studies with inconsistent results.  The initial study showed benefits for, “…non-verbal memory and sustained attention …” whilst the follow-up trial showed significant benefit for, “mental flexibility” only. 

(It is also a little disturbing that the RCN document, published in September 2006, only cites the smallest, shortest duration trial.) 

Even the pro-CAM “Complementary and Alternative Medicine Specialist Library” section of NLH contained nothing new or particularly relevant (it did link to an interesting report reviewing a study published this year in the International Journal of Geriatric Psychiatry.  It found that, “Ginkgo biloba does not improve mental function or quality of life in people with dementia.”) 

Looking at Bandolier, in 1995 it commented favourably on this herb, but only for people with specific medical conditions, “The main indications for gingko are peripheral vascular disease such as intermittent claudication and “cerebellar insufficiency“. This latter is an imprecise term that describes a collection of symptoms, especially in elderly people.” This is not evidence for the improvement of cognitive function or memory in healthy individuals.

On a positive note, Singh and Ernst also judge that there is “good” evidence for the efficacy of Ginkgo for, “dementia, poor circulation in the leg.” [Trick or Treatment, p.203].

Finally, a directly relevant trial.  R Barker Bausell, in his review of high quality CAM trials contained in Snake Oil Science [p. 188] cites a paper from the Journal of the American Medical Association:

P R Solomon et al. “Ginkgo for memory enhancement: a randomized controlled trial.” JAMA 288 (2002) 835-840.

This was a six-week randomized, double-blind, placebo-controlled, parallel-group trial testing an over the counter supplement. The participants were, “randomly assigned to receive ginkgo, 40 mg 3 times per day (n = 115), or matching placebo (n = 115). ”  This is the upper limit of the directed dose for the Holland and Barrett product. 

At 230 participants, this is one of the larger trials I’ve found.  Of these 88% (203) completed the trial.

“Analysis of the modified intent-to-treat population (all 219 participants returning for evaluation) indicated that there were no significant differences between treatment groups on any outcome measure. Analysis of the fully evaluable population (the 203 who complied with treatment and returned for evaluation) also indicated no significant differences for any outcome measure.” 

“The results of this 6-week study indicate that ginkgo did not facilitate performance on standard neuropsychological tests of learning, memory, attention, and concentration or naming and verbal fluency in elderly adults without cognitive impairment. The ginkgo group also did not differ from the control group in terms of self-reported memory function or global rating by spouses, friends, and relatives. These data suggest that when taken following the manufacturer’s instructions, ginkgo provides no measurable benefit in memory or related cognitive function to adults with healthy cognitive function.”

So, what is it good for?  It looks like a generous answer would be: not much.  Perhaps there just might be something to be said for this herb treating some conditions in some populations; but I haven’t found anything that would lead me to be suspicious about the Cochrane Review published just last year, which stated:

There is no convincing evidence that Ginkgo biloba is efficacious for dementia and cognitive impairment.

As far as I can tell, there is even less evidence that healthy individuals may benefit – as the ASA seem happy to accept.  Neither can I see that the evidence is strong enough to support the promotion of a product to the general population, as Holland and Barrett are.  The evidence suggests that if there are benefits to be had the dose directed on this product is too small (note: I am definitely not encouraging anyone to take this supplement, let alone take it in doses above that which is directed on the label.)

However, this is not a field in which I have any particular knowledge or skills: I could be wrong.  I have written to the ASA asking them to tell me what evidence their view is based on – I await their reply with interest!

[BPSDB]

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