Table 3a.
(continued)
| References | Test methods (PASSCLAIM criteria 3 + 4) | Effect size (per dosing or time) (PASSCLAIM criteria 2H + 5) | Remarks |
|---|---|---|---|
| Nicolai et al. (23) | Absolute claudication distance (ACD) at end of study (available in 11 trials (N=477). | Increase of 64.5 metres (−1.8–130.7, non-significant) of GB treatment vs. placebo at the end of the study periods. | Conclusion authors: the clinical relevance of a non significant improvement of 64.5 metres in ACD is questionable. It was concluded that Ginkgo biloba has no significant effect on walking distance in people with intermittent claudication. |
| Horsch and Walther (21) | Ratio of the walking distance between EGb761 and placebo | Duration studies: 6 months, as required by guidelines (8); 3 months and 6 weeks (1): Pooled estimator of the ratio = 1.23 (1.16–1.31) improvement in pain-free walking distance 34 and 33 m; this equals an increase of at least 30% compared to man values at baseline, results are clinically relevant according to study guidelines. | Conclusion authors: this review confirms the efficacy of EGb761. It demonstrates statistical significance of the difference with respect to placebo and clinical relevance for the treatment of PAOD patients. |
| Comment: high variability between study designs, study conditions and centers within each study. | |||
| Pittler and Ernst (22) | Pain-free walking distance: defined using devices that forced the patients to walk at a set speed. | Duration of studies: 6–24 weeks 7/8 trials: weighted mean differences that favored GB compared to placebo, 4/8 trials significant differences. | Conclusion authors: results suggest that Ginkgo biloba extract is superior to placebo in the symptomatic treatment of intermittent claudication. |
| Statistical pooling: significant difference in the increase in pain-free walking distance GB compared to placebo: weighed mean difference 34 meters (95% CI 26–43) | Overall effects seem modest, of uncertain clinical relevance, no final judgment on the efficacy of this treatment. | ||
| Comment: only one trial reported the randomization procedure that was used. | |||
| Hopfenmuller (82) | Symptom improvement ginkgo compared to placebo. Symptoms among others: headache, tinitus, concentration, dizziness, fear, bad memory, forgetfulness | For all analyzed single symptoms: sign differences, superior of ginkgo. | Conclusion authors: Therapeutical effectiveness of Ginkgo biloba regarding the clinical symptoms complex confirmed. |
| Total of clinical symptoms: seven studies confirmed effectiveness of ginkgo, one study inconclusive. | |||
| Kleijnen and Knipschild (24) | Different per study, a.o. symptoms, overall assessment doctor/patient, cognitive test battery, behavioral rating scale. | All but one trial (of eights investigated) showed positive effects of Ginkgo biloba compared with placebo on the symptoms; significant improvements after 12 weeks/3 months. | Conclusion authors: therapy is warranted for patients with mild to moderate cerebral insufficiency, but further studies are needed, with larger numbers of patients; treatment must be for 4–6 weeks before positive effects can be expected. Differences are large enough to be clinically relevant. |
| Dose: 112–160 mg/day. | Comment: only 8 out of 40 studies were well performed. | ||
| Canter and Ernst (87) | Objective and/or subjective outcome measures of cognitive function (excl studies which measure only neurophysiological parameters such as EEG). Different outcome measures, e.g. Sternberg, Critical Flicker Fusion, Choice Reaction Time, LARS, Image recognition, Image free-recall, CDR test battery, speed of attention, immediate word recall, Stroop test. | In the single-dose and medium-term studies stat sign positive effects are largely confined to one or at most two tests from a larger battery of tests. All of these trials failed to report subjective effects of the extract. A positive subjective effect was reported only in the longest trial. | Conclusion authors: there is no sufficient evidence to advocate Ginkgo for cognitive enhancement in healthy populations, the effects reported in these trials are few and inconsistent. Need for long-term trials with healthy subjects. The use of Ginkgo biloba as a ‘smart’ drug cannot be recommended on the basis of the evidence available to date. |
| Birks et al. (28) (updated in 2007 and 2009 (30, 32) |
|
CGI scale (dichotomized) | Conclusion authors: overall there is promising evidence of improvement in cognition and function with ginkgo. However, three more modern trials show inconsistent results. There is need for more trials to confirm the efficacy |
| Benefits associated with Ginkgo biloba at dose <200 mg/day, duration <12 weeks: OR 15.32 (5.90–39.80) p= < 0.0001; and dose >200 mg/day, duration 24 weeks: OR 2.16 (1.11–4.20) p=0.02. | *new preparation, Geriaforce, was used, ethanolic extract of ginkgo leaves (1:4), contains 0.20 mg/ml flavone glycosides, 0.34 mg/ml ginkgolides. | ||
| Cognition | Update 2009: three more trials included. Conclusion authors: ‘Many of the early trials used unsatisfactory methods, were small, and publication bias cannot be excluded. The evidence that Ginkgo biloba has predictable and clinically significant benefit for people with dementia or cognitive impairment is inconsistent and unreliable.’ | ||
| Benefit for ginkgo compared with placebo at 12 weeks (<200 mg and >200 mg), 24 weeks (all doses), 52 weeks (<200 mg/day). | |||
| ADL | |||
| Benefit for ginkgo compared with placebo at <12 weeks (dose <200), 24 weeks (dose <200), 52 weeks (dose <200) | |||
| Mood and emotional function | |||
| Benefit for ginkgo at <12 weeks, dose <200 mg/day | |||
| 12 weeks, dose <200 mg/day | |||
| 24 weeks, dose < 200 mg/day | |||
| Oken et al. (98) | Objective measures of cognitive function in Alzheimer disease. | Overall significant effect size of 0.40, p<0.0001. This modest effect size translated into a 3% difference in the ADAS-cog. | Conclusion authors: small but significant effect of 3–6-month treatment with 120–240 mg of Ginkgo biloba extract. The clinical significance of this effect size is less clear. |
| SKT (syndrome-Kurztest), choice reaction time, ADAS-cog, 10-item battery (incl Benton Visual Retention Test, digit symbol, word list recall, and reaction time), mini-mental state examination (MMSE), kendrick digit copying and object learning tasks, digit recall, classification task. | Further research in the area will need to determine if there are functional improvements and to determine the best dosage. | ||
| Comment: only four studies met inclusion criteria, out of 57. Almost all studies reported positive effects, majority for ‘cerebral insufficiency,’ if this diagnosis was not further specified, article was not included. |