ginkgo biloba

Authors:

Talal Alzahrani, Tran Nguyen

Findings:

This review summarizes evidence for Ginkgo biloba's diverse pharmacological properties (antioxidant, anti-inflammatory, neuroprotective, anticancer, antidiabetic, cardiovascular benefits, etc.) attributed to its bioactive components like flavonoids and terpenoids. Both preclinical and clinical studies support its potential therapeutic applications for conditions including dementia, respiratory diseases, metabolic syndrome, and tardive dyskinesia. However, the review also highlights potential adverse effects (especially with high doses/long-term use or seeds), drug interactions, and toxicity concerns, emphasizing the need for more rigorous, standardized research to confirm efficacy and safety for medicinal use.

Participants:

Review covers numerous preclinical (in vitro cell lines like A549, HepG2, HUVECs, neuroblastoma; animal models including mice, rats, rabbits, fish) and clinical studies (human patients with HCC, dementia, T2DM [N=60], schizophrenia with TD, GAD [N=25-30/group], vitiligo [N=12], depression [N=136], ADHD [N=50]).

Dosage:

Review covers a wide range of dosages across studies: Preclinical doses vary greatly (e.g., 5 mg/kg/day ginkgolide B in rats, 100-1225 mg/kg/day EGb 761 in mice, various µM/mg/mL concentrations in vitro). Clinical trials often used standardized extracts like EGb 761, typically ranging from 80-720 mg/day, with common doses being 120 mg/day (T2DM study) or 240 mg/day (dementia, TD studies). Specific examples include 60 mg BID (vitiligo), 19.2 mg TID (depression), 80-120 mg/day (ADHD). High doses or long-term use are associated with adverse effects.

Study Quality Assessment:

The review cites preclinical and clinical studies, including randomized controlled trials (RCTs), double-blind, placebo-controlled trials (e.g., N=60 T2DM study over 3 months; GAD study over 4 weeks), meta-analyses (e.g., for TD), and observational studies. Methods mentioned include HPLC-MS, LC-MS, flow cytometry, and microarray analysis. The review notes limitations such as heterogeneity in study methodologies complicating comparisons, potential for toxicity (genotoxicity, hepatotoxicity in rodents at high doses/long duration) and adverse effects (e.g., bleeding risk, seizures from seeds), drug interactions (e.g., with CYP substrates, warfarin), and the need for further verification of safety and efficacy, especially regarding dose-response and long-term effects.

All Effects:

Authors:

Noor-E-Tabassum, Rajib Das

Study Quality Assessment:

Type: review

Authors:

Kate McKeage

Findings:

EGb 761® showed positive effects on cognition, behaviour, and global change compared to placebo in randomized trials and meta-analyses involving adults with mild-to-moderate dementia, although results varied across studies and outcomes (e.g., significant improvement in SKT/ADAS-cog/NPI in some trials but not all). Effects may be more marked in patients with neuropsychiatric symptoms. Limited data suggests efficacy may be comparable to donepezil, and adding EGb 761® to AChEIs might offer additional benefits. EGb 761® is generally well tolerated.

Participants:

Adults with mild-to-moderate dementia (including Alzheimer's disease (AD) and/or vascular dementia (VD)), some specifically with neuropsychiatric symptoms (NPS). Also mentioned are elderly volunteers with subjective memory impairment, healthy males, healthy volunteers, elderly patients with peripheral artery disease or at risk of cardiovascular disease. Animal studies involved rats, gerbils, mice, and cats. Specific trial sample sizes are mentioned in tables (e.g., N=205 vs N=203).

Dosage:

Usual dosage discussed is 120–240 mg/day, divided into 2 or 3 doses, taken with meals. Specific RCTs evaluated 120 mg/day, 160 mg/day, 240 mg/day, or 160/240 mg/day. Other studies mentioned used 300 mg/day or 120, 240, and 480 mg/day.

Study Quality Assessment:

The review discusses findings from randomized, placebo-controlled clinical trials (RCTs), meta-analyses, and double-blind studies. Specific methodologies mentioned include intent-to-treat (ITT) analysis, trial durations (22-52 weeks), specific assessment scales (SKT, ADAS-cog, CGI-2, GERRI, NPI, ADCS-CGIC, NAB, NAA, VFT, TE4D, CDT, MMSE, DEMQOL-Proxy, GBS), subgroup analyses, and comparison with active controls (AChEIs). Sample sizes for individual trials are provided in tables. High heterogeneity (I2 scores 62-100%) is noted for several meta-analyses. One RCT [50] was criticized as potentially underpowered. The review mentions it received no external funding, authors are employees of Adis/Springer, and the marketing-authorization holder (Ipsen Pharma) reviewed data for scientific accuracy.

All Effects:

Authors:

Nan Mei

Findings:

This review summarizes evidence on Ginkgo biloba toxicity from experimental studies and human reports. Ginkgo seeds contain the neurotoxin MPN (ginkgotoxin), causing poisoning (convulsions, vomiting). Ginkgo leaf extract showed carcinogenic activity (liver, thyroid) in NTP rodent studies and is classified as a possible human carcinogen (IARC Group 2B). Large clinical trials (GuidAge, GEM) found standardized extracts (EGb761) ineffective for preventing Alzheimer's disease, cognitive decline, dementia, or cardiovascular events in older adults, contradicting some earlier smaller studies. Adverse effects reported in humans include seizures, spontaneous bleeding (especially with anticoagulants like warfarin), potential drug interactions (via CYP enzyme induction/inhibition), and allergic reactions. Significant variability in chemical composition, quality control issues, and adulteration exist in commercial Ginkgo products.

Participants:

Review covers in vitro studies, in vivo animal studies (rats including F344/N, Wistar, SH, SD; mice including B6C3F1/N, Swiss albino, CD-1, ICR, C57B1I/6), human case reports, and human clinical trials (healthy volunteers, elderly individuals with/without cognitive impairment, patients with various conditions like Alzheimer's risk, peripheral arterial disease, macular degeneration, tinnitus, cognitive decline, stroke, epilepsy, schizophrenia). Specific trial populations mentioned include GuidAge (N=2854, mean age 76.8, 67% female) and GEM Study (N=3069, age >=75, mean age 79, 46% female, normal cognitive or mild cognitive impairment).

Dosage:

Clinical trials: Standardized extract EGb761 at 120 mg twice daily (GuidAge, GEM); other trials used 60–240 mg daily. Case reports/Interaction studies: 120 mg/day, 280 mg/day (two 70-mg tablets twice daily), 360 mg/day (e.g., 60 mg tablets 3 times daily). NTP rodent studies: 100, 300, or 1000 mg/kg (rats); 200, 600, or 2000 mg/kg (mice) daily via gavage. Other animal studies used various doses (e.g., 3.5-14 mg/kg/day, 25-100 mg/kg/day, 100-1225 mg/kg/day). Ginkgo seed poisoning reported after consuming ~50-80 nuts or 1 kg.

Study Quality Assessment:

Review synthesizes data from experimental studies (in vitro, in vivo including NTP 3-month and 2-year toxicity/carcinogenicity gavage bioassays in rats/mice), human case reports, systematic reviews (Cochrane), and large randomized controlled trials (RCTs) like GuidAge (N=2854, double-blind, placebo-controlled, 5 yrs) and GEM (N=3069, placebo-controlled, avg 6 yrs). Mentions specific methods (e.g., HPLC/MS, HPLC-UV, TLC, Comet assay, γ-H2A.X phosphorylation, Topo II inhibition assays, neutral red assay, bacterial gene mutation assays, mouse lymphoma assay, microarray analysis, Western blot, LD50 tests, histopathology, popliteal lymph node assay), IARC classification (Group 2B), NTP conclusions ('clear evidence of carcinogenic activity...in mice'). Use of standardized extract EGb761 in some trials is noted. Acknowledges limitations like inconsistent trial results (especially older/smaller trials vs newer/larger ones), variability/adulteration in commercial products, insufficient follow-up time for cancer endpoint in GEM study, and controversy over some findings (e.g., bleeding risk). Disclaimers regarding NLM/NIH endorsement and FDA position are present.

All Effects:

Findings:

The meta-analysis found that Ginkgo biloba extract EGb761, compared to placebo, showed favorable effects on cognition, activities in daily living (ADLs), and Clinicians' Global Impression of Change (CGIC), particularly at a dose of 240 mg/day. EGb761 at 240 mg/day was concluded to stabilize or slow decline in cognition, function, behavior, and global change over 22-26 weeks, especially in patients with neuropsychiatric symptoms. No important safety concerns were identified.

Participants:

Patients with cognitive impairment and dementia (N=2,561 total across included trials). Subgroup analyses conducted for patients with neuropsychiatric symptoms and patients with Alzheimer's disease.

Dosage:

Benefits mainly associated with standardized Ginkgo biloba extract EGb761 at a dose of 240 mg/day.

Study Quality Assessment:

Systematic review and meta-analysis of nine randomized controlled trials. Trials were placebo-controlled and of 22-26 weeks duration. Databases searched include MEDLINE, EMBASE, Cochrane. Total sample size N=2,561. Statistical methods mentioned: weighted mean differences, standardized mean differences, Peto OR, subgroup analysis.

All Effects: