Benefits
Cognition and daily function
In people already diagnosed with dementia, 240 mg a day improved cognition, daily function and global ratings versus placebo over 22 to 26 weeks, and two meta-analyses of those trials agree. Overall the evidence gives mixed results: in healthy older adults or those with mild memory problems, large trials found no slowing of decline, and a review of 36 ginkgo trials judged the benefit inconsistent.
Mood, apathy and irritability
In two trials of 22 and 24 weeks with about 810 people who had dementia and marked behavioral symptoms, 240 mg a day improved Neuropsychiatric Inventory scores, which cover apathy, anxiety, irritability and low mood, more than placebo. In the 24-week trial the score improved by 4.6 points versus 2.1. These results come from people with dementia, not healthy adults.
Anxiety and tension
In one 4-week trial of 107 people diagnosed with generalized anxiety disorder or adjustment disorder with anxious mood, Hamilton Anxiety scores fell by 14.3 points on 480 mg a day and 12.1 points on 240 mg, versus 7.8 on placebo. This is a single short trial in diagnosed patients and is not a reason to stop or replace prescribed care.
Blood flow and circulation
Ginkgolides block platelet-activating factor, and the flavonoids neutralize free radicals in laboratory studies. In people, a Cochrane review of 14 trials (739 people) with leg pain on walking found no clinically significant gain in walking distance, and over 5 years strokes were similar on ginkgo and placebo (65 vs 60).
Mechanism of action
Platelet-Activating Factor Inhibition & Microcirculation
Ginkgolides, particularly ginkgolide B, antagonize platelet-activating factor (PAF), reducing platelet aggregation and blood viscosity while promoting nitric-oxide-mediated vasodilation. These are pharmacology findings, not measured clinical benefits: randomized trials in intermittent claudication found no clinically significant gain in walking distance. The same platelet-activating-factor effect is why ginkgo carries a bleeding-interaction warning.
Antioxidant / Free-Radical Scavenging
In laboratory studies the flavonol glycosides (quercetin, kaempferol, isorhamnetin) scavenge reactive oxygen species and bind pro-oxidant metals, protecting nerve and blood vessel cells from oxidative stress.
Neuroprotection & Mitochondrial Stabilization
In laboratory studies bilobalide stabilizes mitochondrial membranes, supports energy production and may limit nerve cell damage when oxygen supply is low.
Neurotransmitter Modulation
In laboratory studies the extract influences acetylcholine, serotonin and dopamine signaling and may mildly inhibit monoamine oxidase. How much these effects explain the trial results in people is not known.
Clinical trials
Placebo-controlled double-blind randomized trial of EGb 761 120 mg a day for 52 weeks in outpatients with mild to severe Alzheimer's disease or multi-infarct dementia (North American EGb Study Group). (Le Bars et al. 1997, JAMA)
309 patients with Alzheimer's or multi-infarct dementia. 52-week intervention.
EGb 761 was 1.4 points better than placebo on the ADAS-Cog (P=0.04) and 0.14 points better on the caregiver-rated GERRI (P=0.004); clinician global impression did not differ. 27% versus 14% improved by at least 4 ADAS-Cog points. Only 202 of the 309 patients provided evaluable data at 52 weeks.
Ginkgo Evaluation of Memory Study: randomized double-blind placebo-controlled trial of EGb 761 120 mg twice daily (registry NCT00010803), median follow-up 6.1 years. (DeKosky et al. 2008, JAMA)
3,069 community volunteers aged 75 or older with normal cognition (2,587) or mild cognitive impairment (482).
Dementia developed in 277 people on ginkgo and 246 on placebo: hazard ratio 1.12 for all-cause dementia (P=0.21) and 1.16 for Alzheimer's disease (P=0.11), neither significant. Ginkgo also did not slow progression to dementia in those with mild cognitive impairment. A later report from this cohort found no slowing of decline in any thinking domain.
Randomized double-blind placebo-controlled trial of EGb 761 120 mg twice daily for 5 years, funded by Ipsen. (Vellas et al. 2012, Lancet Neurol)
2,854 adults aged 70 or older who had reported memory complaints to their doctor.
Probable Alzheimer's disease was diagnosed in 61 people on ginkgo and 73 on placebo (hazard ratio 0.84, P=0.306), not a significant difference. Deaths (76 vs 82), strokes (65 vs 60) and other bleeding or cardiovascular events did not differ.
24-week multicenter randomized double-blind placebo-controlled trial of EGb 761 240 mg once daily. (Herrschaft et al. 2012, J Psychiatr Res)
410 outpatients with mild to moderate Alzheimer's or vascular dementia and neuropsychiatric symptoms.
The SKT cognitive score improved by 2.2 points on EGb 761 versus 0.3 on placebo, and the NPI behavioral score by 4.6 versus 2.1 (both P<0.001). Most secondary measures, including daily function and quality of life, also favored EGb 761.
Systematic review and meta-analysis of 9 placebo-controlled randomized trials of EGb 761 lasting 22 to 26 weeks, with 2,561 patients in total. (Tan et al. 2015, J Alzheimers Dis)
People with cognitive impairment or dementia across 9 trials.
Cognition, activities of daily living and clinician global rating all favored EGb 761 over placebo, mainly at 240 mg a day, with no important safety concerns. In people with neuropsychiatric symptoms the benefit was larger, while results in the Alzheimer's disease subgroup were much the same as in the whole group.