Risk of chromosomal aberration induced by EGCG

[Miee]

Everyone

;

I found many valuable information and discussion on effects of EGCG, surprised to hear that a large amount of EGCG uptake may have a risk of DNA damage, because I did not know it.

healthunlocked.com/cllsuppo...

I am taking 2g EGCG/day (1g in the morning, and 1g in the afternoon), so I am afraid that chromosomal aberration occur in the CLL cells to evolve toward aggressive clone. I have read several articles on the effects of EGCG on cultured cell chromosomes. I summarized my understanding obtained from papers.

(1)Hydrogen peroxide (a kind of active oxygen) generates due to EGCG, and it is related with chromosomal aberration.

(2)When EGCG greater than 100 micromolar/L is added to culture medium, chromosomal aberration occurs in cultured cells. However, hydrogen peroxide is not detected and chromosomal aberration does not occur in the presence of 10 micromolar/L EGCG.

(3)Below 1 micromolar/L EGCG, chromosomal aberration induced by another drug (or active oxygen?) seems to be suppressed.

(4)When 1g EGCG is taken, plasma EGCG concentration reach in 4 hr, and the concentration is 1 micromolar/L. Thereafter, the plasma EGCG concentration decrease in several hours.

(5)In general, the cancer cells may not contain catalase, so they are sensitive to hydrogen peroxide. In some paper, it is described that the CLL cells have enough catalase which is scavenger of hydrogen peroxide. I expect that hydrogen peroxide may be destroyed by catalase if small amount of hydrogen peroxide is produced by 1 micromolar/L EGCG.

References

Mutagenesis　26 : 489-498 (2011)

J. BUON.15 : 330-336 (2010) ( ncbi.nlm.nih.gov/pubmed/206... ）

Food Chem. Toxicol. 46:2190-2200 (2008)（ ncbi.nlm.nih.gov/pubmed/183... ）

J. Nutrition 132: 1836-1839 (2002)（ jn.nutrition.org/content/13... ）

Miee

(Modified reference links so this site will create the links. HU won't do this if any non-white space character is adjacent to a link - Admin)

[ikahan]

According to the data that you showed above if you take 2 g EGCG per day , 2 times per day your concentration during the day will never be say above 2 micromole/L which is safe.

[Miee in reply to ikahan]

ikahan

If you take 2g EGCG each in a day (maybe in the morning and afternoon) (4g/day), your plasma EGCG concentration reach max level of 2 micromole/L. I guess (hope) that this value may be safe. But, this is an average value, so someone may go 4~5 micromole/L.

Miee

[ikahan in reply to Miee]

Hello Miee and thank you for the interesting articles that you found and interpreted for us. Sorry if I was not clear but I was talking about taking a total of 2g per day but even if you take 4g per day and you get even to 6 micromole /L at some time during the day, you probably would be safe, i.e. under 10, based on this research. However we have to keep in mind that this research is based on in vitro cell culture and it may not apply to the whole human body.

Moreover there could be other mechanisms than mutagenisis through which EGCG can act. For example the mechanism that Chris is talking about, of killing more B cells that are very fragile and would have died anywhy and thus contributing to evolution of harder to kill clones of B cells.

[Miee in reply to ikahan]

Hi ikahan

Thank you for your reply and explaining kindly. I am also keeping in mind on the EGCG effects on CLL cells leading to the growth of aggressive clones (if clonal evolution toward aggressive clone is caused without DNA mutation or chromosomal aberration). EGCG kills CLL cells by activating signaling pathway to leading apoptosis (although reported that EGCG acts other pathways). If aggressive clones become rapidly growing by killing fragile clones, drugs leading to apoptosis by targeting signaling pathways such as iburtinib, ABT-199, idelalisib --- maybe all of them would cause clonal evolution. I do not have information of clonal evolution or transforming to aggressive CLL caused by the treatment with these drugs. So I am optimistic on the clonal evolution by EGCG without genetic alteration. But I am not sure---.

Miee

[Miee in reply to Miee]

ikahan

In my last reply to you, my answer was not enough to reply to your question.

• Taking EGCG of 1 g twice per day. Is it safe?

I think that it probably safe with respect to chromosomal aberration. Not definitely, although the possibility is low.

• EGCG may have risks causing adverse outcome in vivo.

(1)When one signaling pathway is inhibited by EGCG, CLL cells may become use another pathway to survive. Thereby, not only CLL cells acquire tolerance against EGCG, CLL progression speed is possibly promoted (conversion toward aggressive clone).

(2)EGCG may cause a slight bone marrow suppression. (This is my experience but not sure)

(3)EGCG may have a slight suppressing effect of blood coagulation. (My experience)

(4)Stop of EGCG taking causes an abrupt increase of ALC. (reported in the paper, and also my experience)

Several months ago, my WBC suddenly increased twice (from 25000 to 45000) despite I continued to take EGCG every day. So I have increased EGCG (2g/day), and an increase of WBC seemed to stop or go slowly for several months. Such a response is possibly related to EGCG, or is just accidental.

Although I can not avoid from some adverse effects of drugs (including EGCG) if continue to take, I really hope to avoid from the chromosomal aberration risk. In a large number of CLL patients, a chromosome having tumor suppressor gene is lack. If you may lose another chromosome loading other tumor suppressor gene, or genetic mutation to promote cell proliferation, it is fatal. This is the reason why I have specially concerned to the risk of genetic damage especially chromosomal aberration.

Miee

[ikahan in reply to Miee]

Thank you this is very interesting and gives me a lot to think about

[WillieG]

I'm glad you found and posted that, I was wondering the same sort of thing that you were. I take just 1600mg of Curcumin and 1200mg of EGCG and it works pretty good, twice a week knocks my numbers down by 50%. I have Trisomy 12 with no genetic mutations (considered intermediate.) *Note: I also take pepperine to increase absorption of Curcumin)

The comment about hydrogen peroxide some what made me perk up on the idea of clonal mutation and the possibility. I know with FCR the mutation rate for Trisomy 12 is 3%/treatment, with hydrogen peroxide I would only assume it to be less since over coming it with catalase is such a simple matter and doesn't really involve a lot.

Most cells have the ability to protect themselves form oxygen and many bacteria do as well. It just happens that a lot of the dangerous bacteria have problems with it but can over come it simply by activating dormant genes or through transgenic means (aka obtaining genetic material from dead cells and incorporating it into their own make up.)

I really don't think curcumin and EGCG would do so much in the way of generating dangerous mutations. Chromosomal aberrations are generally deadly to the cell, well over 90% of 'healthy' cells die from it. Can't say about cancerous ones though but I wouldn't think they were would be better at recover but more likely worst. If anything they would simply become dormant. I could be wrong though, haven't see any studies on it, just basing it on what I learned and saw in college.

[ulkunneusser in reply to WillieG]

Hi WillieG . I wanted to ask you. How many grams of which supplement do you take on a daily basis? and does it still work. Currently I take less than a gram EGCG Ganoderma reishi extract vitamin C and Vitamin D on a daily basis. I can say it makes me feel fitter than before. If you dont mind, I would like to know what you are taking beacuse you are taking curcumin and EGCG together.Thanks and best wishes.Işık

[AussieNeil Partner Administrator]

Interesting research Miee. Phagocytes (which include neutrophil and monocyte white blood cells), use hydrogen peroxide to kill bacteria and our body cells also have mechanisms to control the level of hydrogen peroxide:

sciencedaily.com/releases/2...

washington.edu/research/pat...

en.wikipedia.org/wiki/Phago...

I guess it shouldn't come as a surprise that this is one of the ways by which EGCG is toxic to CLL cells, particularly if you appreciate that 'natural' compounds that are active against cancer and drugs made for the same purpose are likely to use the same mechanisms to kill off cancer cells if they are to be effective. This just further reinforces my oft made point that we need to carefully consider how anything we take works; natural isn't necessarily good. With cancer cells only very subtly different from healthy cells, trying to kill off cancer cells without causing some damage to good cells is very hard to accomplish.

You might like to try spreading your EGCG dose more throughout the day, rather than just taking 1g twice a day if you are overly concerned.

How are you going with your CLL by the way?

Neil

[Miee]

Ikahan, Willieg and Neil:

Thank you for comments and further information. I was encouraged hearing that EGCG and curcumin worked very well. In my case, plasma EGCG concentration may temporarily reach 1 micromolar/L twice in a day, because I takes 1 g EGCG in the morning and in the afternoon each. Only 0.5 micromolar/L of EGCG has been reported to be effective in the presence of vitamin A (maybe contained in plasma). In this case, mechanism of killing CLL cells may not be due to hydrogen peroxide. The EGCG bind to some receptor on plasma membrane of CLL cells, and thereby intracellular signaling pathway leading to apoptosis of cells is activated.

journals.plos.org/plosone/a...

(It has been reported that EGCG also affects other signaling pathways)

I started only 300mg EGCG in a day a year ago. My WBC (also ALC) decreased or kept steady for a couple of months. Unfortunately, thereafter WBC became to increase, so I increased EGCG dose a little, but a couple of months later, WBC became to increase again. Thus I increased EGCG dose step by step, and now reached 2 g/day. Fortunately this dose seems to stop WBC increase for recent 6 months, although I am not sure whether EGCG really stopped WBC increase or just accidentally. Recent my WBC is around 45,000. Others (such as neutrophill, platelet number etc.) are not so worse.

Miee