Sunday, March 20, 2011

EGCG Green Tea Extract For Memory

I had been giving Jett green tea extract for a while and didn't see any change. Turns out, I had missed the fact that the dosage on the bottle was for TWO capsules. So, I was only giving him a half a dose for the longest time (5mg/per kg) twice a day! But, once I increased the dosage to 10mg/per kg twice a day, I saw huge increases in cognition in just three days. At age 3, he went up from an Auditory Processing level of 2-3 to a solid 3. (For explanation of AP, see My Strategy for Good Behavior.) I took him off for a while and when I restarted, he went from 5 word sentences to using his first 6 and 7 word sentences in a couple of days as well! It's not just Jett who responds positively to this supplement. I know a lot of moms who are seeing great benefits from giving it to their child with Down syndrome. Needless to say, I'm a big fan. At five years old, Jett weighs 32 lbs and gets one capsule of Teavigo twice a day. For those of you who don't know Jett, at age 4, he tested as reading on a 5th grade level and his speech is very good.

Learn more about Green Tea Extract in the Down syndrome population at the 2016 Down Syndrome Innovations Conference on September 16-17 in Little Rock, Arkansas.  

Overview of Benefits

Green Tea, and especially the component epigallocatechin gallate (EGCG), provide potent neuroprotective effects to the brain as well as improved learning abilities. But I prefer supplementing with green tea as a whole rather than just the EGCG since studies show the benefits are greater in the whole, more synergistic form. Other parents agree that their child does better on the whole extract as well.

Source: http://www.memoryaction.com/content/Ingredient_Research.htm
Improved memory learning ability. In laboratory animals, administration of green tea catechins (including EGCG) showed improved spatial memory and learning ability of the animals in maze navigation studies. The animals receiving the green tea had much less oxidative stress activity in the hippocampus (memory) area of the brain. According to the researchers, the improved memory is most likely due to significant antioxidant protection provided by the green tea.

Neuroprotective for neurogenerative diseases. EGCG has a protective effect on neurons. One study showed the ability of EGCG to protect dopaminergic neurons against a herbicide known to be toxic to these cells. Further studies have shown that EGCG is protective to neurons injured due to neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases.

Neuro Rescue role as an iron-chelator and antioxdant. Neurodegeneration in Parkinson’s and Alzheimer’s disease are characterized by the accumulation of iron at the location where neuron cell death occurs. Iron increases levels of oxidative stress at the site, and is believed to be a major factor in the neurodegenerative process. EGCG is an iron chelator, and can remove the iron, thereby eliminating a significant source of oxidative stress. In addition, EGCG is an potent antioxidant, which further mitigates the oxidative stress of the neuron.

Greatly improves levels of antioxidant enzymes and antioxidants in the brain. The brain is very susceptible to oxdiative stress related damage because of its high content of polyunsaturated acids. EGCG has been shown, in lab animals, to improve the activity of antioxidant enzymes such as superoxide dismutase, as well as support increased levels of the antioxidants tocopherol, ascorbic acid and glutathione. EGCG is therefore a good neuroprotective agent (from oxidative stress) for the aging brain.

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There's a lot of information about EGCG on the Changing Minds About Down Syndrome Blog Start reading at the beginning of the DYRK1A and DSCR posts.
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There is a possible clinical trial underway concerning EGCG and Down syndrome.
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Green Tea May Cut Alzheimer’s Risk…

Excerpt from: http://www.memoryaction.com/content/Ingredient_Research.htm

Green tea...contains a compound called EGCG that appears to reduce the formation of beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer’s disease…....Many researchers believe that by blocking formation of beta-amyloid, memory loss and other troubling symptoms may be slowed or halted. “The findings suggest that a concentrated component of green tea can decrease brain beta-amyloid plaque formation,” says researcher Jun Tan, M.D., Ph.D., director of the Neuroimmunology Laboratory at the University of South Florida. “If beta-amyloid pathology in this Alzheimer’s mouse model is representative of Alzheimer’s disease pathology in humans, EGCG dietary supplementation may be effective in preventing and treating the disease.”


Sipping Tea Not Enough...

But drinking green tea or taking green tea supplements rich in antioxidants may not be enough to cut Alzheimer’s risk. The researchers showed that other flavonoids in green tea actually block EGCG’s ability to prevent the harmful buildup of beta-amyloid. “This finding suggests that a green tea extract selectively concentrating EGCG would be needed to override the counteractive effect of other flavonoids found in green tea,” says Doug Shytle, Ph.D., of the University of South Florida….


By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


Source
Rezai-Zadeh K, et al: “Green Tea Epigallocatechin-3-Gallate (EGCG) Modulates Amyloid Precursor Protein.” Journal of Neuroscience, Volume 25. September 21, 2005, pages 8807-8814.

Source: http://www.memoryaction.com/content/Ingredient_Research.htm

References
Chen LW, et al. Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson's disease. CNS Neurol Disord Drug Targets. 2007 Aug;6(4):273-81.
Tohda C, et al. Search for natural products related to regeneration of the neuronal network. Neurosignals. 2005;14(1-2):34-45.
Haque AM, et al. Long-term administration of green tea catechins improves spatial cognition learning ability in rats. J Nutr. 2006 Apr;136(4):1043-7.
Hou RR, et al. Neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) on paraquat-induced apoptosis in PC12 cells. Cell Biol Int. 2007 Sep 1
Avramovich-Tirosh Y, et al. Neurorescue activity, APP regulation and amyloid-beta peptide reduction by novel multi-functional brain permeable iron- chelating- antioxidants, M-30 and green tea polyphenol, EGCG. Curr Alzheimer Res. 2007 Sep;4(4):403-11
Weinreb O, et al. The application of proteomics for studying neurorescue activity of the polyphenol (-)-epigallocatechin-3-gallate. Arch Biochem Biophys. 2008 Jan 13
Srividhya R, et al. Attenuation of senescense-induced oxidative exacerbations in aged rat brain by (-)-epigallocatechin-3-gallate. Int J Dev Neurosci. 2008 Apr;26(2):217-23

Video on EGCG & Down syndrome & Alzheimer's disease


Prof. Jacqueline London "Therapeutical Approach for Trisomy 21 & Alzheimer disease

AD/DS links start at 3:03, For EGCG jump to 7:22 and it stops at 14:50
http://www.youtube.com/watch?v=TXKcvBCOz7A

For my Product recommendations, see the DS Day to Day amazon Store

NSI GreenSelect Green Tea Extract features GreenSelect Phytosome® , a standardized, caffeine-free green tea extract complexed with soy phospholipids for enhanced bioavailability and efficacy. Like the enhanced bioavailability, but don't like the soy, though...

GreenSelect Green Tea Phytosome

More info on GreenSelect

Decaffeinated and fluoride-free liquid: bodyecology.com $20, or 3 for $16.96 each or 4 for $15.96 each.
It contains 80 mg of polyphenols per 20 drops, 100 mg of polyphenols per 30 drops. This actually may be discontinued.

Green Tea Elite with EGCG

Teavigo is a good brand.


Dosage


EGCG may be given every 4-6 hours. As for dosage, an adult is advised to take no more than 500 mg in a 24 hour period. Please read about possible side effects of high doses before deciding how much to give.

Former dosage suggestion: 9mg/per kg of EGCG. This is the dose they used in the clinical trial done in Spain by Dierson, see www.clinicaltrials.gov for details.

New dosage suggestion: Up to 15-20mg/per kg of EGCG. This is the dose they used in a new EGCG study to be published in August 2013. I have a copy and can email it to you if you'd like.

With this new dosage info, I increased Jett's dose to 10mg/per kg and saw huge increases in just three days. He went up from an Auditory Processing level of 2-3 to a solid 3. I took him off for a while and when I restarted, he went from 5 word sentences to using his first 6 and 7 word sentences!

Jett weighs 27 lbs/12.24 kg x 10mg = 122mg of EGCG. The brand I have (Vitacost green tea select with Phytosome) contains 120mg of EGCG per capsule so he gets one capsule, three times a day and will slowly increase his dose to 15mg/per kg and then to 20mg/per kg to see how it goes.

That would be 27 lbs/12.24 kg x 15mg = 183mg of EGCG. So that would be 1 1/2 capsules, three times a day (120 + 60).

And then 27 lbs/12.24 kg x 20mg = 244mg of EGCG. So that would be 2 capsules, three times a day (120 + 120). At four years old, 28.8 lbs, this is the dose Jett gets, but I only give it twice a day. Once in the am and then again in the late afternoon.


Here is a website that a dad started about giving EGCG to his son with DS it has dosage info (that's probably outdated now).
Side Effects

EGCG is an iron chelator, which is great for most of our kids. But if your child's iron is low, make sure you are giving him plenty of sources of iron. Jett's iron (at an early blood test) was on the low side of normal. So I have added extra vitamin C to help his body better use iron and will soon introduce organic liver from grass fed cows.

EGCG decreases the absorption of folate and our children need it, so you have to supplement with calicium folinate (folinic acid) or l-5-methlyfolate. (See explanation below.)
To address this, I increased Jett's folinic and folinate intake and always give B12. I also give EGCG four hours after I give Jett the other supplements to give the folate and folinic acid some time to absorb.

From mom to 3 year old with DS, Linley Lyerly: 
EGCG blocks DHFR enzymes which converts folate in to folinic acid. So if you give folinic acid, then you bypass this problem.  I however, recently came across another role for DHFR in the methylation/folate/methionine-homocysteine cycle (and all the trillions of things connected to this complex thingy).  I read that DHFR is involved in recycling BH4.  I will add the link for the study, but here is the gist from what I understand.  So BH4 is critical for making nitric oxide.  But under times of high oxidation (which occurs in DS) then it tends to be converted to BH2 rather than BH4. BH2 is not a good thing because it uncouples NOS (nitric oxide synthase), an enzyme critical for NO production.  DHFR is a cool player, because it can come along and convert some of that BH2 being made, back into BH4.  This is great....it helps to regulate proper BH2:BH4 ratios, and it says particularly when there is low biopterin available, which often is the case in DS. Also, if you have the a1298c MTHFR mutation, which my kiddo has, then you already have trouble making adequate BH4.  so, this unfortunately seems like a pretty critical role for DHFR and thus inhibition by EGCG may not be ideal.  This being said, Dyrk1a (whose gene product EGCG inhibits) plays a role in the methionine-homocysteine conversion part of that cycle.  So....which one do you "fix" and which one do you "sacrifice"?  This is what I have been wrestling with lately in regards to EGCG use.

Here are the two studies:

Critical Role for Tetrahydrobiopterin Recycling by Dihydrofolate Reductase in Regulation of Endothelial Nitric-oxide Synthase Couplinghttp://www.jbc.org/content/284/41/28128.full

DYRK1A, a Novel Determinant of the Methionine-Homocysteine Cycle in Different Mouse Models Overexpressing this Down-Syndrome-Associated Kinasehttp://www.plosone.org/article/info:doi/10.1371/journal.pone.0007540

From mom, Christy:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1964900/
Here are some excerpts from the article about "too much of a good thing can be harmful" referring to nine case reports of liver toxicity caused by ingesting too much EGCG.:
  • laboratory research with both rodents and dogs has shown that high doses of the most heavily studied green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), cause liver, kidney, and gastrointestinal toxicities.
  • “To date, there have been nine anecdotal case reports of liver toxicity in humans associated with consumption of high doses [700–2,000 mg/day] of green tea from dietary supplements,” says lead author Joshua Lambert,
    an assistant research professor in the Department of Chemical Biology
    at Rutgers University.
  • “In some cases, the subject stopped taking the supplement and the symptoms resolved, and then the subject started taking the supplement again and liver toxicity returned.” Such observations, albeit anecdotal,
    suggest that green tea supplements are not without risk.
  • “People who take less than 500 mg [of green tea concentrate or preparation] per day and spread the dose out over the course of the day are unlikely to have toxic side effects,” says Yang.
  • Yang adds that some Japanese publications report beneficial effects for the consumption of 10 cups of green tea a day with no apparent harmful effects.
  • Yang and Lambert hypothesize that people with oxidative stress–related liver diseases such as hepatitis or cirrhosis may be at greater risk of toxic side effects from ingesting high doses of green tea polyphenols.
    “When a person’s liver is already under stress, toxic effects tend to
    become amplified,” Yang says.
  • Conversely, he notes there are data showing that low or moderate amounts of green tea have a protective effect against both toxicity and carcinogenesis in target organs—once again supporting the adage
    “everything in moderation, nothing to excess.”
Additionally, this study suggests that 600mg total catechins (50% egcg), given in 3 daily divided 200mg doses over the course of 2 years, is perfectly safe and quite beneficial. 

One thing I would take from this article if I were giving EGCG to my child is to spread the dose out throughout the day (like your body would get it if you were drinking green tea throughout the day). You wouldn't sit down and drink 10 cups of green tea at once - thus your body wouldn't get 10 cups worth of EGCG at once. Also, the statement about "those taking less than 500 mg EGCG at once are less likely to have toxic side effects" - I assume they are referring to adults, so keep that in mind when trying to convert the dose to a safe level for children.

Watch out for these:
Folic Acid Deficiency Symptoms

Folic acid deficiency causes very general symptoms such as:
  • Fatigue and weakness
  • Headaches and difficulty concentrating
  • Palpitations
  • Diarrhea
  • In the early stages, the tongue may be red and painful leading to a smooth shiny surface in the chronic stages of deficiency.
The Three Stages of Folic Acid Deficiency 
At the first stage of deficiency the plasma folate levels fall. If the diet does not contain adequate folate, the red blood cell (RBC) folate levels drop after three to four months. With continuing deficiency, the bone marrow cells and other cells become affected. This is stage three, the clinical stage of folic acid anemia. It occurs after approximately four to five months of deficiency. Folic acid anemia is called megaloblastic anemia. 
Folic acid functions in DNA synthesis and therefore cell division. Without this important vitamin, cells such as red blood cells produced in the bone marrow, fail to divide properly. RNA continues to form and build up producing excess haemoglobin. The RBC becomes an immature enlarged non-functioning cell often containing excess haemoglobin. This is megaloblastic anemia. 
Certain factors confuse the diagnosis of folic acid deficiency anemia. The folic acid anemia is identical to the anemia of vitamin B12 deficiency. Therefore, it is very important to rule out vitamin B12 deficiency before taking folic acid supplements for anemia; otherwise, the megaloblastic anemia of vitamin B12 may go on unnoticed. In addition, the factors that lead to folate deficiency, such as poor diet, malabsorption and alcoholism, affect other nutrients as well, so singling out folic acid as the cause is often difficult. 
Testing for Folic Acid Deficiency 
Serum folate levels reflect recent changes in folate intake whereas RBC folate measures the folate stored in the body. RBC folate is a more reliable test. These tests are available through a standard blood test from the doctor. 
High homocysteine levels may also reflect low folate status but it may also be indicative of vitamin B12 and vitamin B6 deficiency. [Our kids usually have a B12 deficiency and an overabundance of B6.- Andi]

Resources
Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ. Modern Nutrition in Health and Disease. 10 ed. Maryland: Lippincott Williams & Wilkins; 2006.
Gropper S, Smith JL, Groff JL. Advanced nutrition and human metabolism. Belmont, CA: Thomson Wadsworth; 2005.
Johnson LE. Folate [monograph on online] 2007 April [cited 2008 November]
Gentili A. Folic Acid Deficiency. [monograph online] 2007 19 September [cited 2008 November]

Read more at Suite101: Folic Acid Deficiency: The Causes, Symptoms, and Stages of Folate Deficiency and Anemia http://www.suite101.com/content/folic-acid-folate-deficiency-a79897#ixzz1GuI87ODM

Related Posts

Folic Acid Cuts Alzheimer’s Risk in Half
Why B12 & Folinic Acid for Down syndrome?

Gingko: The Hows and Whys for Down Syndrome
Why Rhodiola Rosea?
Jett's Supplement List
Longvida Curcumin
Anemia: Causes and Cures


9 comments:

Anonymous said...

the phospholipid in Longvida is also soy derived

Andi Durkin said...

Yes... I'm looking into a replacement... Maybe just eating some sort of fat with the curcumin will help to cross the blood brain barrier? Will post when I find one! Any ideas for an alternative?

Anonymous said...

combine your curcuma with
sunflower lecithine
coconut oil
white pepper

it will encrease the absorption and i will cross the blood/brain barrier.

thats what i found in my reaserchs.

Anonymous said...

how do you give the egcg to your child.
the taste is very bitter..
i mixed it up with orange juice but my daughter spitted it out.

Andi Durkin said...

I put it in a nut butter like peanut, sunflower or pumpkin. Masks the flavor nicely. You can also add a little all-fruit spread.

Pri GuimarĂ£es said...

Hi Andi! My baby have 2 months and I want to know if ECGC can be offer in this age! Tks!

Andi Durkin said...

Hi Pri!

If you are nursing, take the EGCG yourself -- 10 mg per kg -- just make sure you don't take more than the max amount. If you're not nursing, you can try one of the nonalcohol liquid green tea extracts and put a drop in formula to see what kind of reaction you get. I would then very very slowly increase the dose to get to 10 mg per kg and then at 8 months or so slowly increase to the 15mg per kg. Watch for symptoms. I would add some sort of natural vitamin C (like camu camu or amla) to protect iron stores. If iron gets low, read my post on anemia. It's best to increase vitamin C rather than to give straight iron.

Anonymous said...

Hi Andi,
are you aware of any studies that EGCG is in the nursing mothers milk ?

10 mg per kg for nursing mother is related to infant weight or mother's ?

Andi Durkin said...

Hi! I don't know of any published research. I am in contact with researchers who are working on this and related issues. For whatever reasons, they are recommending 10 mg/kg for the nursing mother.