Ginkgo Biloba

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For healthy persons using Gingko Biloba as a cognitive enhancer, a one time dose of 120-240mg of the EGb-761 extract (or a 50:1 concentrated extract) taken 1-4 hours before performance appears to be the most reliable dose.

For alleviation of cognitive decline in older adults, a thrice daily dose of 60-120mg Gingko Biloba EGb-761 extract (or a 50:1 concentrated extract) taken with meals appears to be the most reliable method of administration.

This may be the definition of a compound that "works for you" or whatnot. If using as a nootropic (brain enhancer) and it works, great. If not, I wouldn't bother repurchasing.

There are more reliable nootropics out there, this one just has a bunch of nice side-benefits to do with circulation (like Vinpocetine)

Kurtis Frank

Edit1. Sources and Components

Gingko biloba is a compound derived from the Maidenhair tree, from the genus of Ginkgo from which the supplement Gingko Biloba derives the first part of its name. The latter part (Biloba) is derived from the shape of the leaves, consisting of two lobes.

1.1. Components

There are various components in extracts from Maidenhair, including:

• Quercetin^[1]
• Kaempferol^[1][2]
• Isorhamnetin^[1]
• D-Glucaric^[1]
• Proanthocyanidins^[1]
• Gingkolic acids^[1]

Additionally, there are compounds unique to Maidenhair (and thus Gingko Biloba), the terpene lactones, known as:

• Gingkolide A, B and C;^[3] all totaling around 3-3.6% dry weight^[4]
• Gingkolide J, at around 0.3-0.6% dry weight^[4]
• Gingkolide M,^[5] which can also be synthesized^[6]
• Bilobalide, totalling 2.6-3.4% dry weight^[4]

1.2. EGb-761

There is a standardized extract of Ginkgo Biloba called EGb-761, which is produced only from the ground up leaves of Maidenhair and consists of 24% flavone glycosides and 6% terpene lactones by total dry weight.^[1]

The Gingkolide content of EGb-761 is standardized to 2.8-3.4% of Gingkolides A, B and C combined and standardized to 2.6-3.2% Bilobalides.^[1] There is no standardization for ginkgolides J or M.

The extract itself is sometimes referred to as Tanakan, Tebonin, or Rökan. Another name, Kaveri (LI 1370), is similar but with 25% flavone glycosides.^[7]

There are two other possible extracts of Maidenhair, Cp202 which is free of all terpenoid structures and BN52063 which is free of all flavonoid structures.^[8]

Edit2. Effects on Neurology

2.1. Effects on Neural Tissue

The EGb-761 extract seems to, in mouse models, to alleviate cognitive damage and excitotoxicity if preloaded before the insult; which is due to bilobalides and gingkolides.^[9][10] This neuroprotection is mediated wholly through heme-oxygenase 1^[11] which is upregulated in a dose and time dependent manner in cells with no apparent toxicity level.^[12]

Gingko Biloba can increase cerebral blood flow when measured overall, which is mostly due to increasing blood flow to the left-parietal occipital region.^[13] 60mg/kg bodyweight in rats is slightly more effective than 40mg/kg bodyweight Bacopa Monnieri.^[14] Due to a combination of its effects on neural blood flow and being a vasomodulatory compound, rat models suggest that Gingko Biloba can also attenuate changes in blood pressure after subarachnoid haemorrhage.^[15]

Gingko Biloba has also been implicated, in a rat model, with neuronal proliferation of AChE and NOS positive neurons in the forebrain.^[16]

2.2. Tolerance and Adaptation

At least one study has noted that effects were seen acutely, but not at the end of the trial, and suggested adaptation.^[17]

2.3. Dosing

Effects seen with Gingko Biloba appear to be relatively dose dependent in some regards^[18] although not in a linear 'more is better' sense.^[19] That being said, the 'speed of attention' appears to be dulled with 120mg of Gingko Biloba (a dose that is effective at slightly increasing working memory) while enhanced at 240-360mg acute dosages.^[18][20]

Word recollection appears to be more beneficially affected at a once taken dose of 120mg rather than 240mg or thrice daily lower dosages.^[19]

2.4. Human Trials - Cognitive impairment

At 240mg daily of the EGb-761 extract, some benefit is seen with functional impairment of Alzheimers and Multi-infarct dementia over 24 weeks^[21] and has also been noted to have similar effects at 120mg for 52 weeks.^[22] Shorter times at the lower dose may not be as significant.^[23] These benefits may translate into a better quality of life in those with neurological functional impairments.^[24]

It has been suggested that the effects of Ginkgo Bilboa supplementation are potentiating when cognitive decline just starts, but merely become a 'slowing' of decline in worse stages of dementia.^[25] Although it benefits all parameters of cognitive decline to a degree, it seems to improve visual-constructive impairments.^[26]

A recent (2009) Cochrane report suggest that, for the purpose of alleviating cognitive decline, that Gingko Biloba has benefit in numerous trials but the results of the benefits are inconsistent; Gingko Biloba supplementation doesn't seem to have any risks relative to other methods of preventing cognitive decline, however.^[7]

In models of cognitive decline, Gingko Bilboa seems to be effective at alleviating the rate of decline or otherwise improving symptoms. That being said, its effects are highly variable and do not benefit all parameters. Definitely bioactive, possibly effective, not reliable.

2.5. Human Trials - Healthy Persons

A trial in healthy adults over the age of 60 with 120mg Ginkgo daily for 26 months failed to find a difference between treatment and placebo.^[27] This is the same dose (120mg) that was found to be ineffective at improving working memory and mood, but increased pattern-recognition memory and attention.^[17] However, other studies do note benefits to working memory at this dose in healthy persons.^[28]

Shorter term studies find cognitive improvement in otherwise healthy older adults at 180mg daily^[29][30] which is a dose used with limited success for dementia.^[31] Higher dosages (240mg EGb-761) are effective in improving recall performance in healthy volunteers,^[32] and very high doses (600mg) still appear to be effective over the short-term.^[33]

As noted in one review,^[34] the use of Gingko Biloba in healthy persons for the use of cognitive enhancement is inconsistent.

In healthy persons, Gingko Biloba definitely appears to be bioactive. That being said, its practical results are highly variable. A dose of 240mg taken 1-4 hours before testing for the purpose of enhancing working memory appears to be the best guess at this moment in time.

Edit3. Effects on Circulation

3.1. Regulation

The EGb-761 extract, at 240mg daily in healthy persons, appears to have a regulatory effect on blood flow.^[35] Traditional medicine and select reviews^[8][36] note that Ginkgo Biloba may have vasomodulatory actions, and one study in healthy volunteers noted an increase in forearm blood flow with 7.2mg active terpenoids and 28.8 active flavonoids (Brand: Gibidyl Forte) over 6 weeks.^[37]

One study noted that those subjects with highest baseline bloodflow and highest values after occlusion noted the most significant decreases, while lesser effects were seen with less dramatic baseline stats; lending credence to the 'regulatory' aspect of Ginkgo Biloba.^[35]

The effects on blood flow do not appear to be related to age.^[35]

These effects are seen both by enhancing the neuronal release of endogenous relaxing factors, and via inhibiting the COMT enzyme.^[38]

3.2. On arousal

Gingko Biloba, due to its ability to enhance blood flow and eNOS, has been implicated in potentiating non-contact erections; erections caused by non-physical sensory stimuli.^[39]

It is being looked at to alleviate sexual side-effects of some anti-depressants like SSRIs^[40] due to increasing availability of NO.^[41] In a triple blind study, it seems to have efficacy in some persons but not consistent enough to be statistically significant.^[42] Repeats of this trial done over 2 months note an improvement, but not statistically different than placebo.^[43] The evidence is preliminary, but it doesn't seem to be overly effective at this goal.

3.3. With Aspirin

Ginkgo Biloba has been investigated in being paired with aspirin for heart health.

The combination of Ginkgo Biloba and Aspirin does not seem to further increase bleeding time or coagulation, suggesting they are a safe combination.^[44][45]

Edit4. Synergism

4.1. Phosphatidylserine

Ginkgo Bilboa has its bioavailability enhanced when complexed with Phosphatidylserine, and can make low doses more effective at the same measures.^[46]

4.2. Panax Ginseng

Gingko and Ginseng, in a 60:100mg ratio, were effective at improving scores on the 'serial sevens' arithmatic task at combined doses of 320mg and 640mg where gingko or ginseng in isolation were unable to differ from placebo.^[47] Gingko alone, however, was able to improve scores in the 'serial threes' arithmatic task at dosages of 240mg and 360mg.

Edit5. Safety and Toxicity

Possibly due to the compound Gingkolide B, which is an inhibitor of platlet activating factors, Ginkgo Bilboa has been associated with case studies of subdural hematomas.^[48][49] This compound may also be responsibly for a case of hyphema associated with the combination therapy of Ginkgo Biloba and Aspirin^[50] at 80mg of a 50:1 concentrated extract of Ginkgo with 325mg Aspirin.

References

1. [No authors listed. EGb 761: ginkgo biloba extract, Ginkor. Drugs R D. (2003)
2. Sloley BD, et al. Identification of kaempferol as a monoamine oxidase inhibitor and potential Neuroprotectant in extracts of Ginkgo biloba leaves. J Pharm Pharmacol. (2000)
3. Kaur P, et al. Optimization of extraction technique and validation of developed RP-HPLC-ELSD method for determination of terpene trilactones in Ginkgo biloba leaves. J Pharm Biomed Anal. (2009)
4. Ekman L, et al. Development of an alternative method for determination of terpene lactones in ginkgo dry extract. Pharmeur Bio Sci Notes. (2009)
5. Scholtyssek H, et al. Antioxidative activity of ginkgolides against superoxide in an aprotic environment. Chem Biol Interact. (1997)
6. Bolshakov S, et al. A concise synthesis of ginkgolide M, a minor component of a terpene trilactone fraction from ginkgo biloba roots. J Nat Prod. (2006)
7. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. (2009)
8. Diamond BJ, et al. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil. (2000)
9. Lee EJ, et al. Acute administration of Ginkgo biloba extract (EGb 761) affords neuroprotection against permanent and transient focal cerebral ischemia in Sprague-Dawley rats. J Neurosci Res. (2002)
10. Nada SE, Shah ZA. Preconditioning with Ginkgo biloba (EGb 761®) provides neuroprotection through HO1 and CRMP2. Neurobiol Dis. (2012)
11. Saleem S, et al. Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury. Stroke. (2008)
12. Zhuang H, et al. Induction of heme oxygenase 1 by Ginkgo biloba in neuronal cultures and potential implications in ischemia. Cell Mol Biol (Noisy-le-grand). (2002)
13. Mashayekh A, et al. Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative MR perfusion imaging: a pilot study. Neuroradiology. (2011)
14. Kamkaew N, et al. Bacopa monnieri Increases Cerebral Blood Flow in Rat Independent of Blood Pressure. Phytother Res. (2012)
15. Sun BL, et al. Effects of extract of ginkgo biloba on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in a rat model of subarachnoid haemorrhage. Int J Neurosci. (2007)
16. Jin GH, et al. Effects of Ginkgolide on the development of NOS and AChE positive neurons in the embryonic basal forebrain. Cell Biol Int. (2006)
17. Elsabagh S, et al. Differential cognitive effects of Ginkgo biloba after acute and chronic treatment in healthy young volunteers. Psychopharmacology (Berl). (2005)
18. Kennedy DO, Scholey AB, Wesnes KA. The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. Psychopharmacology (Berl). (2000)
19. Rigney U, Kimber S, Hindmarch I. The effects of acute doses of standardized Ginkgo biloba extract on memory and psychomotor performance in volunteers. Phytother Res. (1999)
20. Kennedy DO, et al. Modulation of cognitive performance following single doses of 120 mg Ginkgo biloba extract administered to healthy young volunteers. Hum Psychopharmacol. (2007)
21. Kanowski S, et al. Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry. (1996)
22. Le Bars PL, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA. (1997)
23. Le Bars PL, Kieser M, Itil KZ. A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract EGb 761 in dementia. Dement Geriatr Cogn Disord. (2000)
24. A double-blind placebo-controlled trial of tanakan in the treatment of idiopathic cognitive impairment in the elderly
25. Le Bars PL, et al. Influence of the severity of cognitive impairment on the effect of the Gnkgo biloba extract EGb 761 in Alzheimer's disease. Neuropsychobiology. (2002)
26. Le Bars PL. Response patterns of EGb 761 in Alzheimer's disease: influence of neuropsychological profiles. Pharmacopsychiatry. (2003)
27. Solomon PR, et al. Ginkgo for memory enhancement: a randomized controlled trial. JAMA. (2002)
28. Stough C, et al. Neuropsychological changes after 30-day Ginkgo biloba administration in healthy participants. Int J Neuropsychopharmacol. (2001)
29. Mix JA, Crews WD Jr. An examination of the efficacy of Ginkgo biloba extract EGb761 on the neuropsychologic functioning of cognitively intact older adults. J Altern Complement Med. (2000)
30. Mix JA, Crews WD Jr. A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings. Hum Psychopharmacol. (2002)
31. Mazza M, et al. Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study. Eur J Neurol. (2006)
32. Kaschel R. Specific memory effects of Ginkgo biloba extract EGb 761 in middle-aged healthy volunteers. Phytomedicine. (2011)
33. Subhan Z, Hindmarch I. The psychopharmacological effects of Ginkgo biloba extract in normal healthy volunteers. Int J Clin Pharmacol Res. (1984)
34. Canter PH, Ernst E. Ginkgo biloba is not a smart drug: an updated systematic review of randomised clinical trials testing the nootropic effects of G. biloba extracts in healthy people. Hum Psychopharmacol. (2007)
35. Boelsma E, et al. Evidence of the regulatory effect of Ginkgo biloba extract on skin blood flow and study of its effects on urinary metabolites in healthy humans. Planta Med. (2004)
36. McKenna DJ, Jones K, Hughes K. Efficacy, safety, and use of ginkgo biloba in clinical and preclinical applications. Altern Ther Health Med. (2001)
37. Mehlsen J, et al. Effects of a Ginkgo biloba extract on forearm haemodynamics in healthy volunteers. Clin Physiol Funct Imaging. (2002)
38. Auguet M, et al. Pharmacological bases of the vascular impact of Ginkgo biloba extract. Presse Med. (1986)
39. Yeh KY, et al. Ginkgo biloba extract enhances noncontact erection in rats: the role of dopamine in the paraventricular nucleus and the mesolimbic system. Neuroscience. (2011)
40. Cohen AJ, Bartlik B. Ginkgo biloba for antidepressant-induced sexual dysfunction. J Sex Marital Ther. (1998)
41. McKay D. Nutrients and botanicals for erectile dysfunction: examining the evidence. Altern Med Rev. (2004)
42. Wheatley D. Triple-blind, placebo-controlled trial of Ginkgo biloba in sexual dysfunction due to antidepressant drugs. Hum Psychopharmacol. (2004)
43. Kang BJ, et al. A placebo-controlled, double-blind trial of Ginkgo biloba for antidepressant-induced sexual dysfunction. Hum Psychopharmacol. (2002)
44. Wolf HR. Does Ginkgo biloba special extract EGb 761 provide additional effects on coagulation and bleeding when added to acetylsalicylic acid 500 mg daily. Drugs R D. (2006)
45. Gardner CD, et al. Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial. Blood Coagul Fibrinolysis. (2007)
46. Kennedy DO, et al. Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine. Hum Psychopharmacol. (2007)
47. Scholey AB, Kennedy DO. Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand. Hum Psychopharmacol. (2002)
48. Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology. (1996)
49. Miller LG, Freeman B. Possible subdural hematoma associated with Ginkgo biloba. J Herb Pharmacother. (2002)
50. Spontaneous Hyphema Associated with Ingestion of Ginkgo biloba Extract

(Common misspellings for Ginkgo Biloba include ginko, jinko, gingo, jingo, bilboa, bilbo, biloa, bloba)

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