24 replies to this topic

[nameless]

Although I don't think this particular issue has been studied in detail, I was wondering: if a certain amount of polyphenols (from food or supplements) would be considered healthy, at what point would they become detrimental to health?

I realize if someone consumes mega doses of green tea, for instance, their liver will begin to cry. But what about polyphenols from various sources?

For instance, I take a grapeseed extract, and recently started a green tea extract (although my belly is still not so happy about it). Both are at reasonable doses. I sometimes (when I take it) get citrus bioflavanoids from Ester C. I also eat a lot of blueberries, a small amount of pomegranate juice and dark chocolate daily. Plus include the random other fruit: berries, apple, etc.

Is this too much? At what point does a person consume too many polyphenols?

Edited by nameless, 17 May 2009 - 03:01 AM.

[tunt01]

it's a very good question and i wish i knew the answer. i've read through several studies and reviews of existing literature on polyphenols. i will go back and check this issue tomorrow, to see if i can find anything specific in the notes I had printed out on the subject.

I think the key is moderation, similar to how the data in resveratrol and other hormetic substances has come in. low dose and not high/bombastic amounts is probably the best guideline anyone can give at this point.

if you have any data on green tea causing a bad outcome in the liver, i would like to see it. i probably drink 5+ cups of green tea a day, and have done so for years.

[nameless]

if you have any data on green tea causing a bad outcome in the liver, i would like to see it. i probably drink 5+ cups of green tea a day, and have done so for years.

You have nothing to worry about at 5 cups/daily, assuming caffeine doesn't cause you any issues. It's only if you megadose green tea supplements, or drink like 50 cups daily, that your liver has problems.

http://pubs.acs.org/....1021/tx7000515

Although I'm not specifically interested in liver issues and polyphenol intake, but more overall health.

[2tender]

I have read that you actually have to drink at least that much green tea to get any of the benefits it provides. I dont think you have to worry about any damage drinking green tea, not the same with extracted supplements they may have toxic by-products as the tea was commercially grown and some batches were contaminated. New GT products are appearing as certified organic and may be worth a try. People stopped using green tea extracts for this reason, their popularity increased its rapid growth and harvest resulting in tainted products .

Edited by 2tender, 17 May 2009 - 11:59 AM.

[nameless]

I think the key is moderation, similar to how the data in resveratrol and other hormetic substances has come in. low dose and not high/bombastic amounts is probably the best guideline anyone can give at this point.

Yeah, I agree there, but what is the cumulative effect from multiple polyphenol sources? Ex. 5-10 cups of green tea should be fine. But what happens if you have 5-10 cups green tea, several glasses of wine, 2 glasses of pomegranate juice, several fruits, 2 cups of blueberries, several cups of cocoa, etc.?

What may be a moderate dose of a single polyphenol source, sort of balloons into an awful lot when you have moderate doses from several sources all in the same day.

Are there any population studies where they study several polyphenol sources, by one group of people? The only ones I know of are single sources. I'm not sure if there are even any population groups that would match exactly... as it's pretty unlikely Kuna indians (cocoa people) drink lots of green tea and wine too, or French/Italians drink as much green tea as Japanese, or... well, you get the idea.

[tunt01]

this is clearly an issue. i think it will be an interesting topic for researchers in 5-10 years, once we understand the inter-workings of the human body in a more profound way.

I will tell you how I think about it with 0 evidence

- we know that low dose is clearly preferable to high dose based on the research
- we know that there are synergistic effects between different polyphenols based on the research



From David Sinclair's Article in Cell journal: http://juvenon.com/j...no12_update.pdf

- i *think* that a lot of polyphenols end up inhibiting NF-kB, which plays a key role in inflammatory/ROS response pathways.
- i *think* this is a very good thing when it comes to atherosclerosis/heart disease and some types of cancers that are more associated with diet.
- i *think* this is a very bad thing when it comes to some cancers/bacteria/pathogens/etc., where you need the persistent immune response to hold the pathogen in check.

- we know that certain viruses compound the effects of atherosclerosis, likely due to the inflammatory nature of the body's immune response to the virus.
- we know that certain viruses cause mutations which lead to cancer.


this issue cropped up during the discussion of TheFirstImmortal, where some people thought resveratrol was making his situation worse rather than better (I was one of those people).

One way to think about it is how long these substances are bioavailable. I don't have a good list handy, but it would be great if someone could chart out how long these things last in the body, so that we are constantly creating a window for the body to go back to turning on NF-kB.

I think the best answer at this point is to cycle on/off. i'm using Wednesday and Saturday as my "off" days, where I take nothing.

I also always take these substances with a meal and treat the situation as sort of a "hyper-healthy" food approach (if this makes any sense). I personally think it's better to take significant doses of things like resveratrol with food, and based on the complaints over tendonitis (megadosing on empty stomachs??) it seems to be born out in the anecdotal facts. Most importantly, I think the circadian rhythm functions better when we take these substances with food and not on an empty stomach.

- part of my own personal plan is to actually get a PCR antibody assay test for several obscure viruses like CMV, HPV, EBV, etc. to see what I have floating around in my body. I know I have the chicken pox virus from childhood (a herpes family virus).

It would be interesting to see if there were any studies of humans who took resveratrol and has some sort of shingles outbreak... I think that's the kind of thing we'd want to be looking for, based on the question you are posing. If we are inhibiting parts of the immune system so much that we are upping our risk of cancers and other types of pathogens to run wild, there would be some sort of phenotype response in the form of cancer/viral/fungal/bacterial outbreaks.


btw: this 2005 compilation of 97 polyphenol studies may be of interest to you

http://www.ajcn.org/.../full/81/1/230S

Edited by prophets, 18 May 2009 - 01:49 AM.

[nameless]

Wow, excellent reply... thanks. Great article too, just glanced over, but will read it in detail later.

What will be interesting to determine, if it's even possible, at what dosages specific polyphenols begin affecting inflammation, or suppressing the immune system in a negative way. And as you mentioned, in certain cases it'd be a balancing act... don't want to suppress the immune system so much that cancers/bacteria, etc become a problem -- but enough to reduce risks of atherosclerosis/heart disease.

And I don't take resveratrol for many of the reasons you stated. Nobody knows yet what dose is optimal, or even what effects (good and bad) it'll have in the majority of people.

And antibody testing can produce some interesting results. I recently found out I have plenty of EBV antibodies, and exposure to a couple of odd tick diseases, for instance.

[tunt01]

EBV is associated with multiple sclerosis. The prevailing thought on the MS forums I've read seems to be that high doses of vitamin D help the immune system hold it in check.

I hadn't given it much thought until you mentioned it, but being aware of how hormones like growth hormone, vitamin D help promote a healthy immune system is probably critical in this equation.

the interplay between hormones vs. polyphenols might be an interesting subject to dig into further. subject to be looked into at a later date, perhaps.

[bgwithadd]

That's like the people here who group 'vitamins' together like they are all one thing. All of them are going to have some effect you don't like if you take enough, I am sure, but it's likely going to be completely different in each case.

[edward]

I posed this question awhile back and I don't think there was any consensus. I feel there is an additive or even synergistic effect when taking multiple polyphenol and polyphenol like substances, I have reduced my dosages across the board because of this and may reduce even futher. Just a quick list of all the supplements rich in polyphenol like substances I take: grape seed, pine bark, bilberry, resveratrol, green tea, pomegranate, cocoa, ginkgo, coffee, fruits and vegetables including lots of berries and lots of other plant extracts that may overlap: rhodiola, ashwagandha, bacopa, curcumin etc etc etc.

Edit: Of course I also take two days off of most "supplements", however I will take nootropic/mood supplements on these off days.

Edited by edward, 18 May 2009 - 05:34 PM.

[malbecman]

I generally agree with all of these statements. I don't try to megadose on polyphenolics but do try to have a diet and/or supplements to make my daily ingestion polyphenolic-rich. I realize that is a bit of a moving target and if you ask ten different people, you will get ten different answers but
I really don't think we know the exact optimum level of any of these, especially when you include inter-individual variability which is really THE wild card in all of medicine and health. And I usually cycle off the supplements over the weekend.

[4eva]

Some people can have a sensitivity to phenols. This might indicate the person under methylates.

There are enzymes and the failsafe diet for those with this problem. The enzymes are usually called No Phenol or something like that.

But the most common symptom of sensitivity is a rash. It doesn't sound like this is an issue for you.

Polyphenols can chelate iron and copper.

[tunt01]

4eva:

do you have any good links/studies on this issue? polyphenols and methylation?

i read some of your other posts on under methylators. any links to papers you recommend on this subject? thx.

[4eva]

From a nutritional journal.
http://www.jbnat.com...methylation.pdf

This site has interesting info. It explains the two phases of liver detox which is generally related to phenols and sulfation.
http://www.canarys-e.../sulfation.html

Failsafe is usually for autistic children with neurological problems or other kinds of foods issues.
http://www.nourishin...y_sulfatio.html

http://www.enzymestu...methylation.htm

Terms defined mostly
http://www.absolutea...imethyl_sulfate

Papers sounds like studies to me. The Journal of Ortho Medicine is the best source at orthomeculor.org. (I can't read the JOM on my PDA because the archives are in PDF. JOM studies are not indexed on pubmed because the journal is considered controversial.)

Undermethylation or overmethylation is explained on sites that are geared toward holistic approaches, orthomolecular treatment, metabolic typing, and nutritonal info.

[Lufega]

I keep reading that polyphenols chelate copper. There is an enzyme called Diamine oxidase that is needed to degrade polyphenols. This enzyme is copper dependent. Maybe what's happening is that an increase in dietary polyphenols also increases the need for copper.

I got this info. from "The Handbook of minerals as Nutritional Supplements"

[tunt01]

I carefully read through geddarkstorm's "resveratrol / tendonitis: can we explain it?" entire thread last night and spent some time thinking about this copper chelation theory.

I think the copper chelation by resveratrol and polyphenols is almost conclusively the driver of the tendonitis problem.

This PM, I am going to read on this issue further.

Thanks v. much 4eva. I greatly appreciate the links.

Edited by prophets, 18 May 2009 - 06:46 PM.

[kenj]

I carefully read through geddarkstorm's "resveratrol / tendonitis: can we explain it?" entire thread last night and spent some time thinking about this copper chelation theory.

I think the copper chelation by resveratrol and polyphenols is almost conclusively the driver of the tendonitis problem.

This PM, I am going to read on this issue further.

Thanks v. much 4eva. I greatly appreciate the links.

Prophets,

I've given this a thought, too. Would appreciate if you could look more into this, thx.

[4eva]

In some ways it seems to me that "chelating copper" seems inaccurate. But I think that if polyphenols use up diamine oxidase then that is how copper is lost (probably excreted with diamine oxdase). So maybe chelating is accurate.

I stopped reading that thread on resv and joint problems when geddarkstorm said there was no evidence that polyphenols chelated copper.

[niner]

I keep reading that polyphenols chelate copper. There is an enzyme called Diamine oxidase that is needed to degrade polyphenols. This enzyme is copper dependent. Maybe what's happening is that an increase in dietary polyphenols also increases the need for copper.

I got this info. from "The Handbook of minerals as Nutritional Supplements"

I don't see how this would work, Lufega. Diamine oxidase oxidizes amines, but polyphenols don't generally have amine functionality. The enzyme is copper dependent, so I suppose if polyphenols chelated enough copper, assuming that's something they could do, then you might see a reduction in your ability to oxidize amines. This could include degrading histamine, among other things. Are you thinking of polyphenol oxidase?

[maxwatt]

Aspirin chelates copper several times as effectively as resveratrol, yet I've never heard of it "causing" joint pain.

[4eva]

I don't see how this would work, Lufega. Diamine oxidase oxidizes amines, but polyphenols don't generally have amine functionality. The enzyme is copper dependent, so I suppose if polyphenols chelated enough copper, assuming that's something they could do, then you might see a reduction in your ability to oxidize amines. This could include degrading histamine, among other things. Are you thinking of polyphenol oxidase?

Those who have a phenol sensitivity have high histamine levels. The problem is about a build up of biogenic amines. Those sensitive to phenols can, if severe enough, have symptoms similar to the symptoms of the cheese effect from certain MAO inhibitors and bad diet choices (like aged cheese, wine, most alcohol I think, etc).

Quote
then you might see a reduction in your ability to oxidize amines.

That's exactly right. Biogenic amines build up. That's why this sensitivity is likely an indication of undermethylation. UMs already have high histamine levels.

[tunt01]

Prophets,

I've given this a thought, too. Would appreciate if you could look more into this, thx.

In some ways it seems to me that "chelating copper" seems inaccurate. But I think that if polyphenols use up diamine oxidase then that is how copper is lost (probably excreted with diamine oxdase). So maybe chelating is accurate.

I stopped reading that thread on resv and joint problems when geddarkstorm said there was no evidence that polyphenols chelated copper.

as a follow-up. i went through a few resveratrol studies. a couple of them seem to cite this paper:

Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage : A putative mechanism for anticancer properties
http://cat.inist.fr/...cpsidt=17408177

and one of these citing papers says point blank that, "resveratrol mobilizes endogenous copper"

so i guess the chelating effect is cited for the basis of an anti-cancer property by resveratrol, but too much would probably be a bad thing. maybe lead to effects like tendonitis or aneurysms ?

i'm not sure exactly. it'd be nice if someone could pull that copper/polyphenol paper, as it may elucidate the issue a bit ?

anyway, I did not see this paper cited before as it relates to resveratrol, probably because it doesn't discuss resveratrol in the abstract specifically, but i found other resveratrol papers which cite its work directly.

[4eva]

Yeah, that makes sense to me. Reducing copper would be beneficial in some people. But moderation is key. I wouldn't be surprised if there were a lot of people who have too much stored copper. Its a common environmental toxin.

High copper is associated with a risk of cancer and/or heart disease. High copper can also mean high calcium, which means tissue calcificiations.

[tunt01]

i wish i knew the ratio of how much resveratrol vs. copper depletion exists in the body. if anyone had that kind of data, it would be fantastic. maybe bill sardi knows, he's commented on it before.

Edited by prophets, 25 May 2009 - 03:39 AM.

[VespeneGas]

As was mentioned higher up in the thread, Geddarkstorm concluded that resveratrol cannot chelate copper from the body, and that resv induced tendinitis was probably related to aromatase inhibition or disruption of the circadian rhythm or...