Monday, November 30, 2015

Pro's and Con's of Ginkgo Biloba Extracts / Products for Alzheimer's Disease / Dementia (Includes the 'Hard Science')





Ginkgo; a chinese herb noted for it's brain-health promoting activities - is also an inexpensive remedy for neurodegenerative disorders. Many 'natural health doctors' advocate for specific preservation of forests containing Ginkgo in order to accommodate the marketing of high-quality extracts. 

Despite it being a common , and abundant plant - many companies assert their ginkgo is cultivated in the best area's, ''has the best ratio of active components' etc.... and yet there is still debate as to the actual criteria one must fit into for Ginkgo to be effective and even whether it is actually that effective overall.

Some studies cast serious doubt that Ginkgo even has a benefit in neurodegenerative disorders and elderly Dementia. While others show significant benefit in comparison to placebo.

In order to understand why there is contrasting results, we need to take a look at the pharmacology of the substance ; as it is clear that each extract used in both studies is the same - and thus the issue is not one of purity.



 PHARMACOLOGY / MECHANISM(S) OF ACTION OF GINKGO BILOBA

  • Ginkgo acts to preserve certain brain receptors; notably the 5-HT(1)A and muscarinic acetylcholine receptors (1) (2).
  • Ginkgo appears to stimulate histamine neurons (3).
  • Ginkgo appears to be a strong norepinephrine reuptake inhibitor (4).
  • Ginkgo's constitute's selectively block GABAergic neurotransmission.
  • Ginkgo seems to downregulate 5-HT2A receptors (5).
  • Ginkgo appears to downregulate or decrease the responsiveness of serotonergic 5-HT1 receptor family. (6)
  • Ginkgo has glycine-site antagonistic properties (7)
  • Ginkgo decreases beta-amyloid plaques slightly. (8)
  • Ginkgo thins the blood and boosts blood flow (9)
  • Ginkgo enhances nitric oxide and blocks degradative enzymes. (10) (11)
  • Ginkgo can modulate alpha-2-receptors (can agonize or antagonize) (12)
  • Ginkgo may faciliate dopamine release (13)
  • Ginkgo may decrease aldosterone and cortisol (14) 

A couple notations : 
Ginkgo's properties ; the majority of which are beneficial - also, from a pharmacological point of view contradict themselves . For example - one of the goals of blocking serotonergic neurons from a memory perspective - is to facilitate glutamatergic (of glutamate) and cholinergic (of acetylcholine) neurotransmission, and glycine is a partition of the strongest glutamate receptor (NMDA-complex) - so Ginkgo, by blocking glycine sites - reduces some of the benefits of it's other actions of reducing serotonergic receptors and activity. 

With respect to the 5-HT1A promoting effects of Ginkgo - this is an interesting bit - as both agonists and antagonists of the receptor have shown differential memory-improving effects (15) (16) (17) (18).



(Summary : Ginkgo's properties seem to move things in the right direction =-= but some properties are contradicting)


THE 'HARD SCIENCE'


There are a few reasons why Ginkgo erk's me - and to be clear - it's not a bad herb. It's actually very beneficial, but I need to expand on the above points. 

First of all - Ginkgo's differential effects on different systems may provoke unwanted side-effects; and it may not be ideal for those with anxiety and / or temperament issues. This is in part due to it's GABA-antagonism but also due to it's Glycine antagonism - which we will get to next as a primary (and reinforcing) point.



 GLYCINE RECEPTOR SITE ANTAGONISM BY GINKGO BILOBA 
( The Low Point of Ginkgo's Function ; and not a Pretty Sight )

I'  like to reiterate again before we proceed - that I am not , have not , and never will be (most likely) against Ginkgo products. However, this glycine-antagonism component of Ginkgo (!) should be taken for what it is - the 'dark side' of ginkgo's mechanism of action.

Why?

Well first and foremost - because glycine is a necessary anti-aging component to the {human} brain and also is necessary for sanity (literally). Those with low levels of glycine; ESPECIALLY limbic and cortical levels - are prone to both obsessive-compulsive-behavior and Psychotic features...as well as cognitive deficits {see-here} {and here} {and HERE}


Interesting then, how Ginkgo may be promoted as a brain-booster but yet - one mechanism is highly contradictory to this effect.




        THE GOOD GUY IN GINKGO 

~!~ ~!~ It's still a GodSend ~!~ ~!~


Don't let the above dishearten you too much about Ginkgo....


The majority of Ginkgo's components are still very much so a plausible union of notable and advantageous compounds - and for healthy individuals - Ginkgo can help keep you healthy! (!)

It may also Prove to be an effective brain-tonic for studies in College; for exam's and such - more so to be taken daily/in the long-run - but can provide benefits before a test as well! {~!~}

Ginkgo may help alleviate the negative cognitive side-effects of blood-brain-penetrating antihistamines and thus reduce remarkably, the lethargy and memory issues whilst on these drugs ~(!)~

The net effect of Ginkgo extracts is still increased acetylcholinergic neurotransmission, enhanced norepinephrine activity (especially locus coreulus) and thus enhanced awareness, cognitive performance and a slightly increased intellectual capacity by some ends.

The histaminergic aspect is also very Enlightening and Promising. :)












3 comments:

  1. Antagonizing the glycine receptors will actually be beneficial after chronic use. Most likely increasing the density of glycine receptors and the amount of glycine floating around.

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    1. Got a study to prove that? I have no problem with your theory. Its just we have so many people that claim "antagonizing" will upregulate where this is thrown as a *General Rule* of sorts...Some receptors downregulate in response to Antagonism/Blockade AND stimulation/agonism i.e 5-HT2AR. Just sayin'.

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    2. ***5-HT2A Research***
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362472/
      https://www.ncbi.nlm.nih.gov/pubmed/11750789
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110590/

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