Re: Re: Polyphenols -- good or bad?

[Guest guest]

Emma,

> > Well, you have to get from a distant cell to the liver somehow, and

> > usually you do that through the blood, which is made out of water.

> > So, while you could transfer fat-soluble free radicals to the liver

> > via lipoproteins, I'm not sure the polyphenols play no role in such

> > transport, and I'm not sure they wouldn't play a role in the liver

> > either.

> But this says that lipophilic and hydrophilic can interact directly:

> " When the radicals were generated in the lipid compartment,

> {alpha}-tocopherol and the carotenoids acted together as the first

> line of defense against oxidative damage, followed by the oxidation of

> uric acid. In contrast to uric acid, ascorbic acid was rapidly

> consumed in the presence of MeO-AMVN, suggesting an active interaction

> between ascorbic acid and {alpha}-tocopherol, as reported earlier

> (29,30).

All they showed was that ascorbic acid, despite being water-soluble,

is depleted by lipid oxidation. They did not show any direct action

between ascorbic acid and alpha-tocopherol, and certainly didn't show

that this interaction *wasn't* mediated by polyphenols.

> So you're not saying they're required, just that they're helpful?

I don't know whether they are " required " or not, and I'm not sure how

useful trying to assess the question is. If they are beneficial, then

they would be " required " for maximum lifespan and optimal health.

> In

> which case, how helpful are they? As I say, the only way they can stay

> in the body long enough to do anything is by actively inhibiting PST,

Although I got over 800 hits for " PST enzyme, " when I searched

pubmed.com for " polyphenol PST " I got zero. When I searched for

" polyphenol clearance, " I did not turn anything up on the PST enzyme.

I did, however, find that they stimulate Phase II detox enzymes. It

is not clear to me whether or not they have to be oxidized first to

carry out this effect based on the article. Their excretion would, as

I understand it, rest on their stimulation of phase III enzymes, which

they do not seem to directly affect, and even still, some phase III

enzymes will send them from the liver to the blood rather than from

the liver into the bile.

==============

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dopt=Abstra\

ctPlus & list_uids=15832810 & query_hl=1 & itool=pubmed_docsum

For the phase II DMEs, phase II gene inducers such as the phenolic

compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone

(tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate

(EGCG) and the isothiocyanates (PEITC, sulforaphane) generally appear

to be electrophiles. They generally possess electrophilic-mediated

stress response, resulting in the activation of bZIP transcription

factors Nrf2 which dimerizes with Mafs and binds to the

antioxidant/electrophile response element (ARE/EpRE) promoter, which

is located in many phase II DMEs as well as many cellular defensive

enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction

of the expression of these genes.

==============

> and while they're present they cause all kinds of other metabolic

> effects (like inhibiting or stimulating enzymes) apart from catching

> some free radicals.

The question, of course, is whether or not those metabolic effects are

health-promoting or are health-damaging. Since there are a number of

tropical peoples who consume a massive amount of fresh, virgin coconut

fat, sometimes up to 30%-50% of total calories, and these peoples are

extremely healthy, I suggest that the polyphenols in coconut oil are

health-promoting.

> > I don't care about the French Paradox -- although, are there any very

> > healthy populations that *don't* eat lots of polyphenols? Even the

> > Inuit, North American Indians and Masai must have been getting all

> > kinds of interesting polyphenolic compounds from tree barks and so on,

> > no?

> That's something that's hard to quantify though, and it depends what

> the polyphenols are doing and whether they are antioxidants. It's not

> hard to get polyphenols - oats, wheat, potatoes, and other unexpected

> sources.

The polyphenols in tree bark are antioxidants, and the polyphenols in

coconut oil are also antioxidants. Not all polyphenols are equal.

The polyphenols in virgin coconut oil are much more potent

antixoidants than those in coconut oil made from copra, which are in

turn much more potent than those in peanut oil. I haven't seen virgin

coconut oil polyphenols compared to those from grains or potatoes.

> As I say, ketones are pretty effective antioxidants. Fasting and

> low-carbing seem like good ways to reduce oxidative stress.

Coconut oil is also rich in medium-chain fatty acids, which, according

to a review on ketones I have (VanItallie and Nufert, Ketones:

Metabolism's Ugly Duckling, Nutrition Reviews, 2003), exert a

ketogenic effect that is independent of carbohydrate restriction.

> > I'm not sure why you'd think that a benzene ring should ipso facto

> > lead to carcinogenicity. It's my understanding that benzene is

> > carcinogenic because it has no functional groups attached to it that

> > can mediate its modfication.

> Ok, I think it's up for debate, but this paper says it isn't the

> benzene, but the metabolites created from it when it is oxidated to -

> wait for it - phenolic compounds. The paper says the reason phenols

> don't show up as carcinogens is because when they are administered

> instead of benzenes, they are deactivated as soon as they go through

> the liver, whereas benzenes are oxidated into phenols and have to go

> around again.

> http://www.ehponline.org/docs/1996/Suppl-6/smith.html

I don't see anything in the paper suggesting that any chemcial with a

phenol group is ipso facto carcinogenic. It is certainly an

interesting hypothesis, and if every phenolic compound had the same

effect on free radical production and enzyme disruption that these

several specific benzene metbolites have, it might meaningfully

reflect on the antioxidant polyphenols found in various foods, but

they are each different.

> > Well there's no blood supply to thin in cell culture, so how do you

> > explain salicylate-mediated anti-carcinogenic effects in vitro?

> It could be because there's evidence salicylates are cytotoxic - like

> most chemotherapeutic drugs - they kill all cells indiscriminately.

> They also impair mitochondrial Ca+ uptake, which prevents cells from

> proliferating:

> It's sort of a " we'll break it to fix it " approach. At least in the

> case of salicylates, we know they aren't beneficial antioxidants.

I wasn't defending the use of salicylates to prevent cancer or the

general approach, but you had said their cancer prevention effect was

due only to blood thinning, whereas that appears to be contradicted by

cell experiments showing a direct apoptosis-stimulating effect.

In the case of coconut polyphenols, resveratrol, and some others, we

know they *are* beneficial antioxidants.

> It

> > doesn't seem to me entirely unreasonable that something could be

> > beneficial *because* it is excreted.

> Yes, I think that's how uric acid works as the body's main antioxidant

> (good reason to eat protein).

Then the argument that we excrete them, therefore we do not need them

and consider them toxic, does not hold.

> The trouble is that the phase I liver detox (oxidation), frequently

> produces toxic/carcinogenic metabolites in the body. These then have

> to be conjugated by the phase II detox to make them water soluble -

> i.e. through either/or glutathione conjugation, amino acid (glycine)

> conjugation, methylation, sulphation, glucuronidation, acetylation.

And the food polyphenols stimulate phase II enzymes.

> Often whether you are susceptible to cancer or not depends on how well

> phase II can keep up with phase I - those with an overactive phase I

> system and/or an underactive phase II system are at risk. Smoking,

> incidentally, stimulates specific pro-carcinogenic phase I CYP

> enzymes, so it's not just a case of getting some free radicals in the

> smoke.

That sounds like an awfully good reason to eat polyphenol-rich foods then.

> The fact that salicylates and a number of " wonderful " polyphenols and

> antioxidants like quercetin and others actively suppress and/or hog

> PST and glucuronidation enzymes makes me pretty nervous about the

> overall cancer risk in vivo, as opposed to direct antioxidant and/or

> DNA damage effects of polyphenols in vitro, because of the wider

> impact on the body's ability to get rid of benzenes and phenols.

Everything I'm reading says that polyphenols increase glucuronidation.

Apparently, sulfation is not unequivocally a good thing, so

inhibition of the enzyme might not be an unequivocally bad thing:

=================

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dopt=Abstra\

ctPlus & list_uids=16289744 & query_hl=15 & itool=pubmed_docsum

The cytosolic sulfotransferases (SULTs) catalyze the sulfate

conjugation of many hormones, neurotransmitters, and xenobiotic

compounds (Coughtrie et al., 1998). They are involved in the Phase II

detoxification of xenobiotics, as well as in the inactivation of

endogenous compounds such as steroid and thyroid hormones,

catecholamines and bile acids (Coughtrie et al., 1998). In contrast to

this protective function, sulfation is also a key step in the

bioactivation of a host of pro-mutagens and pro-carcinogens (Glatt,

2000, et al., 2000 and Yamazoe et al., 1999). Sulfation

activates carcinogens such as hydroxymethyl polycyclic aromatic

hydrocarbons, allylic alcohols, benzylic alcohols, and

N-hydroxyarylamines, since their sulfate esters are electrophiles that

covalently bind to nucleic acids and other macromolecules (Glatt, 2000

and Meerman et al., 1994).

===========

Although the actual effect of quercetin in humans may be insignificant:

===========

Quercetin has been shown to inhibit the catalytic activity of P-PST

using cell-free enzyme preparations in vitro with an IC50 value as low

as 0.1 ìM. In the intact human hepatoma cell line HepG2, the potency

of quercetin as an inhibitor of P-PST decreased about 25-fold,

yielding an IC50 value of 2.5 ìM (Eaton et al., 1996).

=============

> If the polyphenols hog PST thereby increasing

> phenol/benzene/salicylate levels in the body, they are indirectly

> contributing to cell damage and injury, which produces oxidative stress...

But they have the opposite effect through the upregulation of the

other phase II enzymes.

> I wonder if there are any phase II stimulators in coconut though?

> Glycine? Betaine? Sulphate?

Polyphenols?

> > It's my understanding that experiments show

> > life-lengthening, and it seems that traditional cultures have taken in

> > plenty of polyphenols even when they were meat-heavy cultures, and

> > that a coconut fat, which is loaded with polyphenols that have

> > powerful antioxidant activity, is very widespread in the tropics, and

> > the people who eat the most of it are remarkably healthy.

> > Is there evidence to the contrary?

> I guess it depends whom the onus is on to prove what.

Whether or not there is evidence to the contrary does not depend on

where the burden of proof lies. There either is or there isn't. If

traditional diets were rich in polyphenols, whether from tree bark

teas or massive amounts of coconut fat, then I think even in the

absence of absolute proof of their essentiality, they should be

considered an important part of traditional diets, unless there is

some evidence against it.

===========

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dopt=Abstra\

ctPlus & list_uids=16441844 & query_hl=19 & itool=pubmed_docsum

Blueberry polyphenols increase lifespan and thermotolerance in

Caenorhabditis elegans.

==========

It seems the balance of the evidence would lie in favor of polyphenols

-- or at least certain polyphenols that are abundant in a variety of

health-promoting, traditional foods.

Chris

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