Green Tea Extract: EGCG & The Benefits It Has for Down Syndrome

EGCG, which stands for Epigallocatechin-3-gallate, is an extract from Green Tea. EGCG is the major polyphenolic compound found in green tea. Green Tea has been known to have lots of health benefits for awhile, but about two years ago it came to the attention of people in the Down syndrome world.

I’ve been watching it over the last couple years. But, when I saw some new research come out about EGCG a couple weeks ago, I decided it was time to jump on the bandwagon and start supplementing with EGCG. As usual though, I needed to have all my ducks in a row, so to speak, have all the research and facts lined up, so I can definitively know why we are using EGCG. Of course, this helps others as well, which is also why I’ve typed it all up.

Original research with EGCG that sparked the attention of those in the DS world was research for Alzheimer’s disease. Let’s look at some of this initial research to lay the groundwork.

EGCG prevents certain apoptotic (pre-programmed) cell death through inhibiting the elevation of Abeta (a protein involved with Alzheimer’s and also involved with DS) via inhibition of beta and gamma-secretases. This, therefore, reduces neuroinflammation that’s associated with the progression of Alzheimer’s disease (1). We also know that neuroinflammation is involved with DS.

Alzheimer’s Disease & Down syndrome have the increased amyloid-beta protein (Abeta), which causes plaques & tangles in the brain. The processes & increases which Abeta cause are reduced by EGCG. EGCG improves memory function, as well as reducing harmful levels of increased Abeta and its associated functions (2).

So, we have EGCG which prevents cell death, reduces the elevated levels of amyloid beta, reduces Beta Secretase expression, reduces APP (Amyloid Precursor Protein – overexpressed in DS) and reduces neuroinflammation. All of this will help improve neurogenesis. That’s all great stuff, but there’s still more amazing benefits to EGCG – specifically for Down syndrome.

There’s an annoying little gene that is over expressed in Down syndrome called – get ready for this long word - dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A, also known as DYRK1A. We’ll use the abbreviated word, since it’s a lot easier to say and remember! DYRK1A causes cognitive & learning impairments in DS and is highly involved in the neurodegenerative process in the Down syndrome brain (3-6). It also plays a role in the Alzheimer-like pathway that is seen in Down syndrome (3).
The good thing about DYRK1A is research has shown that it can be inhibited. If DYRK1A is inhibited, then the harmful effects of the gene won’t be able to function.  Remember, the over expressed aspect of this gene is what is the problem – not just the gene in and of itself.

EGCG is a safe DYRK1A inhibitor and there has been very successful research done in individuals with Down syndrome. The Jerome Lejeune Foundation has a program designed to research what will inhibit this gene. Professor Mara Dierssen, from the Jerome Lejeune Foundation, has had a very successful clinical trial (10) with individuals with Down syndrome using EGCG. Professor Dierssen is also now recruiting for a second clinical trial (11).

EGCG is also a GABA antagonist (7-9). An antagonist is a substance that acts within the body to reduce the physiological activity of another substance. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter.

Now that we have the definitions down, let’s get on to the problem with GABA. GABA is a good thing when it is not in excess, because it creates the perfect balance between neuronal excitation and inhibition to allow for efficient learning. But, there appears to be too much GABA-related inhibition in Down syndrome and therefore it “turns off” too many neurons in the brain and makes it more difficult to process information.

So, EGCG being a GABA antagonist, namely blocking the GABA(A) receptor (recombinant alpha1beta2gamma2L GABA(A) receptor), is a very beneficial thing for individuals with DS.  Having an antagonist which can reduce GABA, will greatly help the brain and learning in Down syndrome.

Mitochondrial dysfunction has been well established in Down syndrome. EGCG prevents oxidative deficit in the mitochondria, reduces oxidative stress and actually promotes mitochondrial biogenesis in Down syndrome (12).  This is amazing, because there has never before, to my knowledge, been a way to efficiently combat the mitochondrial dysfunction in Down syndrome.

EGCG is also an iron-chelator, which can be beneficial for individuals with DS, due to the oxidation issues that come with high levels of iron. Now, if an individual with DS already has low levels of iron, this would be something to keep in mind and monitor the iron levels while supplementing with EGCG.
So, to recap, EGCG helps improve memory, reduce the learning impairment seen in individuals with DS, reduce oxidative stress, is a potent antioxidant, promotes mitochondrial biogenesis, is a GABA antagonist, is an iron-chelator, inhibit DYRK1A, prevents cell death, reduces neuroinflammation, reduces Beta Secretase & APP expression, and causes a reduction in Abeta and the problems it causes.

With all this, one may ask, is there anything negative about EGCG? There is one thing to keep an eye on, but I wouldn’t necessarily call it a “negative.”

EGCG inhibits or reduces DHFR, which is an enzyme involved in the methylation and folate cycle. So, ultimately, it may reduce folate. We already know that folate is reduced in Down syndrome and many people use additional supplements to increase folate in Down syndrome. As long as a sufficient amount of folate or folinic acid is supplemented, I would not be too concerned about this aspect of EGCG. There are some other questions regarding DHFR and some genes that it is involved in regulating – whether it is good to stop that or not.

But, for now, look at all the benefits for EGCG above and think about all the problems which DYRK1A (and others) cause. The answer is simple for me, at the moment: Supplement with additional folate/folinic acid, or supplements to support the methylation cycle, as you are using EGCG.

Now, the question comes down to, what is the recommended dosage and what are the best brands.

The recommended dosage is 9mg/kg (kg=2.5lbs) of EGCG. This is the dosage that the clinical trials in Down syndrome are using. This is also the dosage that many parents are using with their children.

One important note on the dosage: that is NOT 9mg/kg of Green Tea. This is important to note, as most products will be Green Tea that you are giving. You will have to calculate the amount of EGCG in the product to give the correct amount. You will be giving more Green Tea, but the recommended dosage of 9mg/kg.

Because EGCG is still in the early stages of use and development, it can be a little tricky to get a brand that is bioavailable. A good brand of just EGCG is Teavigo. The problem with Teavigo is that it is not in a liposomal encapsulation (a fatty acid), to make it bioavailable enough to cross the blood-brain-barrier (which is where it is needed).

GreenSelect Phytosomes made by a company named Indena, has been found by some to be a good bioavailable form of EGCG. This has the phospholipid bound to it. There are several companies which use GreenSelect as their base. One example is VitaCost GreenSelect. Another example is Swanson's Ultra GreenSelect Green Tea Phytosome.

Another liposomal brand which some families use with their children is Enzymatic Therapy Green Tea Elite with EGCG. You can view it here and here.

We will be using the Swanson's Ultra GreenSelect Green Tea Phytosome, as is mentioned above. The cost is $14.99 for 60 capsules. Each capsule contains the following:

GreenSelect® Phytosome™

(green tea extract Camellia sinensis leaves/ Glycine max soybeans) -600 mg

Standardized to:  

19-25% polyphenols - 114-150 mg  

13% epigallocatechin 3-0 gallate (EGCG) - 78 mg

The dosage can be a little tricky with the GreenSelect Green Tea. VitaCost's GreenSelect Extract which is mentioned above contains the following per 1 capsule:

“Green Tea Extract (Camellia sinensis leaves/Glycine max soybeans) [standardized to 60% polyphenols 180mg, 40% epigallocatechin 3-0 gallate (EGCG) 120 mg]”

Originally we were going to use the VitaCost brand. But, Richard on the DSTNI list pointed out that VitaCost doesn't calculate the dosage accurately. Yes, it can be a little confusing. But, they miss the dosage part of the fatty acids in the mix. So, the dosage above for Swanson's GreenSelect is accurate and not as confusing. The VitaCost dosage is not accurate.

For a child that is O’s weight – 50 lbs – that would calculate out to 180mg/day of EGCG. With the Swanson GreenSelect EGCG, that would mean approximately 2 & 1/2 capsules. With the VitaCost brand, the dosage is almost doubled.

So, there’s a LONG explanation of why EGCG is good and everything that goes with it. I will keep notes of how O does on the EGCG and any changes we see.

*Note (Update 8/20/15): I realized that it is not mentioned about giving the child the 9mg/kg dosage of EGCG twice a day. That IS the recommended thing to do. It is best to give the 9mg/kg dosage TWICE a day, as then it is in child's body at all times. We do this with O. Some have had problems giving the dosage at night, because it has kept their child awake. Others have not had this problem. We have not experienced this problem at all.

References:
1. Brain Res. 2009 Jan 23;1250:164-74 (-)-Epigallocatechin-3-gallate prevents lipopolysaccharide-induced elevation of beta-amyloid generation and memory deficiency. Lee YK, Yuk DY, Lee JW, Lee SY, Ha TY, Oh KW, Yun YP, Hong JT.
2. Nutr. 2009 Oct;139(10):1987-93. Green tea (-)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice. Lee JW, Lee YK, Ban JO, Ha TY, Yun YP, Han SB, Oh KW, Hong JT.
3. Ageing in Down Syndrome: DYRK1A As a Candidate Gene for Cognitive Decline
http://www.sciencedirect.com/science/article/pii/S2171974808700394
4. Dyrk1A Overexpression Inhibits Proliferation and Induces Premature Neuronal Differentiation of Neural Progenitor Cells. http://www.jneurosci.org/content/30/11/4004.full
5. DYRK1A in normal brain development and Down syndrome. http://www.nature.com/nrn/journal/v13/n12/fig_tab/nrn3314_F2.html 
6. Green Tea Polyphenols Rescue of Brain Defects Induced by Overexpression of DYRK1A http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004606
7. http://sydney.edu.au/medicine/pharmacology/adrien-albert/images/pdfs/RefsPDFs/367.pdf 
8. Reducing GABAA α5 Receptor-Mediated Inhibition Rescues Functional and Neuromorphological Deficits in a Mouse Model of Down Syndrome. http://www.jneurosci.org/content/33/9/3953.full
9. Implications for treatment: GABAA receptors in aging, Down syndrome and Alzheimer's disease. http://www.ncbi.nlm.nih.gov/pubmed/21388375
10. http://clinicaltrials.gov/ct2/show/NCT01394796?term=EGCG+and+down+syndrome&rank=1
11. http://clinicaltrials.gov/ct2/show/NCT01699711?term=EGCG+and+down+syndrome&rank=2
12. Epigallocatechin-3-gallate prevents oxidative phosphorylation deficit and promotes mitochondrial biogenesis in human cells from subjects with Down's syndrome http://www.sciencedirect.com/science/article/pii/S092544391200302X
13.  A few helpful websites:
https://sites.google.com/site/superdownsyndrome/supplements/green-tea-extract
http://changingmindsaboutdownsyndrome.blogspot.com (search EGCG)
http://dsdaytoday.blogspot.com/2011/03/egcg-green-tea-extract.html
http://dstoner.net/Math_Science/Downs.html

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