Ginkgo has been used in the treatment of intermittent claudication, Raynaud's syndrome and chilblains (Pittler & Ernst 2000, Mouren et al 1994). Intermittent claudication In 2000, a meta-analysis of eight clinical trials found a significant difference in the increase in pain-free walking distance in favour of G. biloba over placebo in intermittent claudication (Pittler & Ernst 2000). An earlier randomised study measuring transcutaneous partial pressure of oxygen during exercise showed that a dose of 320 mg/day EGb 761 taken for 4 weeks significantly decreased the amount of ischaemic area by 38% compared with no change with placebo (Mouren et al 1994).
A more recent 2004 meta-analysis confirmed that ginkgo is more effective than placebo in intermittent claudication (Horsch & Walther 2004). Nine double-blind studies of EGb 761 for intermittent claudication were assessed in a total of 619 patients. A sensitivity analysis of a homogeneous sample in terms of design, treatment duration, inclusion and exclusion criteria and methods of measurement confirms these findings. Most studies have used a dose of 120 mg/day taken in divided doses, although one trial found 240 mg/day gave better results. It should be recommended as long-term therapy and as an adjunct to exercise for the best results.
Commission E approved the use of standardised ginkgo extract for intermittent claudication (Blumenthal et al 2000).
Clinical note— Peripheral arterial disease
Peripheral arterial disease (PAD) is the chronic obstruction of the arteries supplying the lower extremities. The most frequent symptom is intermittent claudication, which results from poor oxygenation of the muscles of the lower extremities and is experienced typically as an aching pain, cramping, or numbness in the calf, buttock, hip, thigh, or arch of the foot. Symptoms are induced by walking or exercise and are relieved by rest. Presently, medical treatment revolves around lifestyle changes, such as increased exercise, and surgery as a final option.
Raynaud's syndrome A standardised G. biloba extract (Seredrin) taken over a 10-week period significantly reduced the number of attacks per week (from 13.2 to 5.8) compared with placebo, according to a randomised study (Muir et al 2002).
VERTIGO, TINNITUS AND SUDDEN DEAFNESS
Ginkgo is used to treat these and other symptoms of vestibule-cochlear disorders.
In 1999, a systematic review of five RCTs testing standardised G. biloba extracts in people whose primary complaint was tinnitus concluded that treatment with G. biloba may result in significant improvements in tinnitus (Ernst & Stevinson 1999). Three years later, a review of eight controlled trials in tinnitus confirmed these findings, stating that ginkgo is significantly superior to placebo or reference drugs when used for periods of 1 -3 months (Holstein 2001).
However, results of two double-blind studies conducted more recently have shifted the evidence against the use of G. biloba in tinnitus. The first was a large, double-blind, placebo-controlled study involving 1121 people aged between 18 and 70 years with tinnitus and 978 matched controls, which found that 12 weeks of treatment with ginkgo extract, LI 1370 (Lichtwer Pharma, Berlin, Germany), 50 mg, three times daily resulted in no significant differences when subjects assessed their tinnitus in terms of loudness and how troublesome it was (Drew & Davies 2001). A more recent double-blind, placebo-controlled, randomised study of 66 subjects with tinnitus failed to show benefits with active treatment using a dose of 120 mg extract daily over 12 weeks (Rejali et al 2004). The primary outcome measures used were the Tinnitus Handicap Inventory, The Glasgow Health Status Inventory and the average hearing threshold at 0.5, 1, 2 and 4 kHz. In 2004, Rejai et al conducted a metaanalysis of clinical trials and found that 21.6% of patients with tinnitus reported benefit from G. biloba versus 18.4% of patients who reported benefit from a placebo.
A 2004 Cochrane systematic review came to a similar conclusion, reporting that the limited evidence currently available does not support the use of ginkgo in tinnitus; Ginkgo biloba 532
however, the authors also pointed out that if a greater level of understanding and
diagnostic accuracy could be reached about the different aetiologies of tinnitus, this may naturally highlight subgroups of patients in whom further controlled trials of G. biloba are worth considering (Hilton & Stuart 2004).
Salicylate-induced tinnitus One in vivo study investigating the effects of ginkgo in salicylate-induced tinnitus found a statistically significant decrease in the behavioural manifestation of tinnitus for ginkgo in doses of 25, 50 and 100 mg/kg/day (Jastreboff etal 1997).
Sudden deafness Ginkgo extract was as effective as pentoxifylline in the treatment of sudden deafness, according to one randomised double-blind study (Reisser & Weidauer 2001). Both treatments equally reduced associated symptoms of tinnitus and produced the same effects on the return to normal of speech discrimination. Subjective assessment suggested that G. biloba extract was more beneficial than pentoxifylline. EGb 761 (240 mg/day) has also been shown to accelerate and secure recovery of acute idiopathic sudden sensorineural hearing loss, observable within 1 week of treatment under randomised double-blind test conditions (Burschka et al 2001).
Commission E approves the use of standardised ginkgo extract in these conditions when of vascular origin (Blumenthal et al 2000).
MACULAR DEGENERATION, GLAUCOMA AND RETINOPATHY
In regard to these opthalmological conditions, ginkgo has numerous properties that should theoretically make it a useful treatment, such as increasing ocular blood flow, antioxidant and platelet-activating factor inhibitor activity, NO inhibition and neuroprotective abilities.
Macular degeneration Although some positive evidence exists, a 2000 Cochrane review has suggested overall there is insufficient evidence currently available to conclude that Ginkgo biloba treatment is effective in macular degeneration, with further testing required (Evans 2000).
Glaucoma In regard to glaucoma, the little research conducted so far appears promising.
Researchers using colour Doppler imaging have observed significantly increased end-diastolic velocity in the ophthalmic artery after treatment with EGb (120 mg/day) in a placebo-controlled, randomised crossover study (Chung et al 1999). A randomised, double-blind crossover study found that EGb 761 (120 mg/day) taken for 4 weeks produces positive effects in normal tension glaucoma (Quaranta et al 2003). Furthermore, ginkgo treatment did not significantly alter intraocular pressure, blood pressure or heart rate and was well tolerated.
Chloroquine retinopathy In vivo tests using electroretinography have identified protective effects against the development of chloroquine-induced retinopathy using Ginkgo biloba (Droy-Lefaix et al 1992). This has been observed in both acute and chronic chloroquine toxicity of the retina (Droy-Lefaix et al 1995).
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