• N&PD Moderators: Skorpio | thegreenhand

plant polyphenols lacking bioavailability

allone

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Jun 20, 2020
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All the plant polyphenols i have ever been extracting were through simple methods like brewing them as tea aka extraction method WATER.
OK SO, i researched this a bit and found out they are hardly bioavailable in the human, first of all because they are hardly extracted to begin with, and second of course is the supposed quick metabolism and clearance. BUT second one is not actually that much of a problem. You can always research and add inhibitors to the mix as to slow down absorption and dispersion. One example can be black pepper or just plain piperine. I believe there are many, but I dont expect any of you guys to know them because this isnt herbal healing forum etc. BUT, if you can think of any, PLEASE DO ADD, THANKS.
Anyway, back to number one problem I believe is the main issue, the extraction method. I have been reading about plant polyphenols for a very long time now and their solubility is almost never water based. I would say, probably 90% of polyphenols are not soluble in water to at least an important extent. So, one would need to acquire many other solvents in order to get their benefits. I checked them all, and none of them are widely available to the general public. Now, what does one do then in such case? The only two solvents that are easy to acquire are Acetic acid and of course, Ethanol. But both are not very practical really. Acetic acid is corrosive. I was wonder if I can replace it with Vinegar? But the percent is only 5%, what do you guys think about this? And Ethanol, its kind of defeats its purpose to use ethanol to extract herbs that I need to use to actually quit alcohol.
So anyway, this is what I need help with from you guys. What other solvents can you recommend that are easy to acquire. How does one use pure ethanol to extract herbs. Can you please explain it to me? And very importantly, how much ethanol residue will be left in the final product, as I try to avoid alcohol for the most part. But I guess thats my only solution. Just please guide me through using Ethanol as solvent to extract polyphenols. That including which type of alcohol, as there are many! Definitely no methanol, no thanks! Please give me some guide, thank you!
 
I would say, probably 90% of polyphenols are not soluble in water to at least an important extent.

based on what data, last I checked they are indeed water soluble, how else do they have measurable amounts of cachetin in tea?
 
based on what data, last I checked they are indeed water soluble, how else do they have measurable amounts of cachetin in tea?

i couldnt find any reliable data. i came to this conclusion based on reading on about i dunno like 100s of polyphenols or so? but it does sound a bit excessive i suppose. i remembered catechins in tea are indeed water soluble. but they are also pretty much even more soluble in ethanol and other solvents so water is just cheap easy way to get some of them. i assume its not the whole package. green tea extracts for example use harsher solvents to get ALL the catechins therefore causing side effects like liver problems. SO i suppose maybe more polyphenols i dunno about CAN BE soluble in water but arent really extracted to their fullest? but good point about green tea and its full extract being detrimental. maybe its best not to extract all the polyphenols in herbs. and harsh solvents probably leave residues which might contribute to side effects. BUT thats why im looking for some simple non toxic solvent beyond water. i suppose i can figure out something with ethanol. but because i lack chemistry knowledge, im not sure how to extract them properly using ethanol without the final product being there. that was one of my main questions too and i sure hope someone can answer me!?
 
Polyphenols are plenty soluble in hot water, there's nothing to gain by using ethanol.

green tea extracts for example use harsher solvents to get ALL the catechins therefore causing side effects like liver problems.
The solvents used are by no means "harsher", I believe supercritical CO2 is common, they are just different. And as far as I know the whole liver thing is not a concern. There are no obvious cases of liver damage from green tea extract, maybe some enzyme variations, but it's nothing to be scared of. The solvent used would not matter at all either, what matters is the cachetins (supposedly).

i suppose maybe more polyphenols i dunno about CAN BE soluble in water but arent really extracted to their fullest?
If you use a sufficient volume of hot water, they should be completely extracted.

and harsh solvents probably leave residues which might contribute to side effects.
This is chemophobic nonsense, unless you are using crude oil as a solvent, it's trivially easy to get high purity solvents that are removed completely and easily.

thats why im looking for some simple non toxic solvent beyond water.
There aren't any of those, really. Ethanol and DMSO and a few others are not super toxic but nothing comes close to water in safety.

im not sure how to extract them properly using ethanol without the final product being there.
Use a Soxhlet extractor and a flask of ethanol, and afterwards evaporate the ethanol off, preferably under vacuum.

Consider this though: for thousands of years cachetins and polyphenols have been extracted with little more than boiling water. Think of tea, coffee, chicory, etc...
 
All of the hydroxyl groups (poly - phenol) make these compounds water soluble.

They are basically non - drugs based on their piss poor kinetics though.
 
"All of the hydroxyl groups (poly - phenol) make these compounds water soluble. " uhm i recommend you look into some of them. you clearly havent done much research. im not talking about the basics like tea and coffee or cocoa. there are thousands of polyphenols. i probably checked on at least 50 of them and it usually says the same shit "sparingly soluble or not soluble in water". top of my head right now, turmeric, ginger, chamomile, kava, milk thistle, fenugreek, magnolia (honokiol & magnolol) on and on list can keep going. ill start adding as i remember all.
IN FACT, ill form a database and post it here so you guys see what i mean. obviously none of you cares enough to research those. as skorpio put it, they are generally piss poor in absorption. but you missed on my first post where i mentioned things like black pepper or piperine which are proven and shown to enhance absorption to most vitamins, and polyphenols. did you ever read on this a bit more?
anyway, thats my goal, use better solvent than water, add black pepper or piperine and see if there is much difference.

sekio, you obviously drink tea so thats why you feel uncomfortable with what is said about the liver issues. well, you drink it and you only get a fraction of the catechins because water is not the best solvent, but if you have researched this a bit more you will find out green tea extracts sold as high standardization catechins have used different solvents. those different solvents, in an article i read once, can be blamed as residue leftover and possible liver issues. OR the really high, unnatural amount of catechins can be blamed for that too. dozen of articles are out there mentioning the liver issues. somehow you completely dismiss it as if its all a haux or something. its very strange to me.

and what about acetic acid as safe non toxic solvent besides water or ethanol? BUT thanks for that last information on the extraction with ethanol. problem is, its hard for me to grasp on this unless shown in step by step or maybe a video? can you help me with some website or some video going through the process, thanks!
 
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All the plant polyphenols i have ever been extracting were through simple methods like brewing them as tea aka extraction method WATER.
OK SO, i researched this a bit and found out they are hardly bioavailable in the human, first of all because they are hardly extracted to begin with, and second of course is the supposed quick metabolism and clearance. BUT second one is not actually that much of a problem. You can always research and add inhibitors to the mix as to slow down absorption and dispersion. One example can be black pepper or just plain piperine. I believe there are many, but I dont expect any of you guys to know them because this isnt herbal healing forum etc. BUT, if you can think of any, PLEASE DO ADD, THANKS.
Anyway, back to number one problem I believe is the main issue, the extraction method. I have been reading about plant polyphenols for a very long time now and their solubility is almost never water based. I would say, probably 90% of polyphenols are not soluble in water to at least an important extent. So, one would need to acquire many other solvents in order to get their benefits. I checked them all, and none of them are widely available to the general public. Now, what does one do then in such case? The only two solvents that are easy to acquire are Acetic acid and of course, Ethanol. But both are not very practical really. Acetic acid is corrosive. I was wonder if I can replace it with Vinegar? But the percent is only 5%, what do you guys think about this? And Ethanol, its kind of defeats its purpose to use ethanol to extract herbs that I need to use to actually quit alcohol.
So anyway, this is what I need help with from you guys. What other solvents can you recommend that are easy to acquire. How does one use pure ethanol to extract herbs. Can you please explain it to me? And very importantly, how much ethanol residue will be left in the final product, as I try to avoid alcohol for the most part. But I guess thats my only solution. Just please guide me through using Ethanol as solvent to extract polyphenols. That including which type of alcohol, as there are many! Definitely no methanol, no thanks! Please give me some guide, thank you!

I wrote about this topic on two other threads. Here is what I said:

"Just because a molecule shows activity "in vitro" at extremely high concentrations(micromolar to millimolar range) doesn't mean that it will have any in situ effects on our cells. The oral bioavailabiltiy of most flavonoids is 1% or less, with some having BV of 0.2% or less. We evolved with plants for millions of years, and our bodies are designed physiologically to not absorb most plant molecules, and the little that gets absorbed gets quickly destroyed and removed by the body through hepatic metabolism. The reason for this is that these molecules, if absorbed, would disturb metabolism, and the body really hates that because one of the keys to optimum health is homoestasis. Usually, plant molecules that show desirable activities in vitro are modified by medicinal chemistry to make them 100 to 1,000 X more potent and at least 50 X more orally active. The few molecules that are not modified need to be designed with special carrier system to make them orally active. A good example of this would be silibinin from milk thistle. It has strong anti-inflammatory actions. However, silibinin is not orally active, being mostly hydrolized in the gut and the little that gets absorbed is quickly conjugated and glucorinated in the liver and excreted. So they created an emulsified version using phospholipids in a special matrix of long-chained dextrose polymers that allows silibinin to have much higher oral activity, and silimarin produces plasma levels of silibinin 7 X higher than the same equivalent dose of silibinin taken from milk thistle. Another example is cycloastragenol, which is a potent activator of telomerase in vitro. The oral biovailability is 1-3% at normal doses, and increases to 25% at massive doses due to non-linear pharmacokinetics. There is a special formulation of CA called TA-65 which utilizes micronized CA in layers of hypromellose of different molecular weights in a hard shell and bioperine. The hypromellose layers allows the CA to reach the gut intact, and the micronization allows it to diffuse through the cell membranes of the intestines. Then, bioperine significantly inhibits the two livr enzymes that breaks down CA. TA-65 results in plasma levels of CA roughly 60 X greater than CA taken alone. It took ten years and cost millions of dollars to be developed because making most phytochemicals orally bioavailable is quite a bitch.

In general, the plant compounds that are most orally active tend to be alkaloids. There are exceptions, of course. For instance, berberine is an alkaloid and has poor oral bioavailability. But, in general, alklaoids unlike most phytochemicals have very good oral bioavailability. The classic example is caffeine, which is the prototypical orally bioavailable molecule with an oral bioavailability of 99%, which puts to shame most pharmaceutical drugs. Caffeine is so bioavailable because of it's high solubility and the fact that it has both hydrophilic and lipohilic pockets, allowing it to readily cross cellular membranes. The reason why alkaloids have such good oral bioavailability is not because plants want to help us, but because they want to kill us. Plants don't make alkaloids to heal us, but because they don't want us to eat them. They are poisons that the plant develops specifically to bypass all the enzymatic and cellular barriers of our body and produce high plasma concentratons so that it is effective at killing us.

Taking bioperine doesn't help that much because the problem with polyphenols is their multiple polar rings, which result in them being hydrolized in the gut before even reaching the liver. What makes polyphenols not orally bioactive is not so much that they do not survive liver first bypass metabolism - although that is a big part too, yes - but the problem is that that they are too polar. Also, they are not lipophilic, so they do not cross cellular membranes very effectively. Our cell membranes are mostly phospholipids, and molecules that are lipophobic do not penetrate cells properly.

So only between 1% to 10% of them gets through the gut, and then they undergo hepatic first by-pass metabolism and only 0.2% to 1% of the dose you took actually makes it to the plasma unchanged. And then, because these molecules are just a step or two from being small enough to be excreted, their half-lives are only 1 or 2 hours so that tiny amount that made through is glucorinated and completely gone in 3-5 hours. Polyphenols are garbage as potential drugs. Consider, for instance, resveratrol. Tests using resevratrol in vitro in large doses indicates that it is a SIRTUIN-1 inducer. Because of the huge potential health benefits of this, which would allow you to reap the benefits of caloric restriction without starving, they tried to use resveratrol as a drug. The problem is that only 0.5% makes it into the bloodstream unchanged, and that is broken and expelled from the body completely. The doses used in cell assays are in the oder of 10-50 uMOL. That would translate into oral doses of 5-20 grams to obtain the same effect observed in vitro. But that is assuming a 100% bioavailability. The actual dose is 200 X greater than that. Because that is completely impractical and even impossible, pharmaceutical companies tried to work the issue to increase the bioavailability. Sirtris Pharmaceutical tried to design a bucal delivery system, but there were many drawbacks. Another company tried to develop an emulsified version in an encapsulation of polyethylene glycol esters, but that still produced blood levels of RV about 100 X lower than needed even when they gave the subject multi-gram doses. After spending millions of Dollars they gave up."
 
so i guess the polyphenols in the medicinal plants were never making them medicinal in the first place. are medicinal plants a huge hoax, giant scheme? come to think of it, there is not a single mention of anyone being cured using medicinal plants ever. which is weird they are so popular now, isnt that strange? medicinal plants have not been as popular as they are now, ever previously in their existence. which is so ironic when we are actually finally realizing they are useless, they are in fact becoming even more economically valuable. just check out the multi-billion dollar supplement industry. enough said!
 
so i guess the polyphenols in the medicinal plants were never making them medicinal in the first place. are medicinal plants a huge hoax, giant scheme? come to think of it, there is not a single mention of anyone being cured using medicinal plants ever. which is weird they are so popular now, isnt that strange? medicinal plants have not been as popular as they are now, ever previously in their existence. which is so ironic when we are actually finally realizing they are useless, they are in fact becoming even more economically valuable. just check out the multi-billion dollar supplement industry. enough said!

Of course it's not a "hoax". Some of the most useful medicines we have come from plants. Where do you think morphine comes from? Or atropine? Also, a lot of the precursors for the synthesis of potent pharmaceuticals come from plants, like safrole for MDMA and piperine from pepper.

The point is, some phytochemicals are not orally active, and among those the phenols and chalcones are up the list. Even taking mult-gram doses of them would only have an effect "in vivo" if you took it with specila carrier systems to increase their ability to survive hydrolisis in the gut and absorption through the GI tract. That's what they did with silibinin and cycloastragenol.

Among plant extracts that are sold freely, the only ones that contain potent orally active molecules that I have seen are Caapi, Syrian rue and St.John's Wort. The former two contain harmala alkaloids, which are potent MAO-A inhibitors and orally active. And the latter contains hyperforin, which is a fairly potent reuptake inhibitor of serotonin, norepinephrine and dopamine - unfortunately, it is also a potent reuptake inhibitor of glutamate and glycine, which makes it very toxic.

In the case of Caapi, morphine and atropine, it proves my point: the most orally active molecules from plants tend to be alkaloids.
 
i meant all those herbal supplements out there, not the illegal alkaloids or MAIOs plants might have as bioactive. the whole supplement industry is a multi billion dollar industry. so there must be a reason, that it probably works. i was very curious about polyphenols but it seems its dead end. of particular interest was quercetin. its enormously studied polyphenol. dozen of research on it! but its common issue; weak bioavailability of only 2 hours.
there is something else you havent considered though. polyphenols get metabolized by gut bacteria and in turn become different molecules and therefore more bioavilable but we cannot detect them simply because we dont know what to look for. we just check plasma levels for what we assume is one polyphenol the original being consumed. this is very interesting area of research and some hope that polyphenols might actually be beneficial, just not in their original form. you should also look into this, because you understand more than me in this area. and its definately something i recommend to sekio to look into as he is a tea lover. it appears those EGCGs are very low bioavailabiltiy BUT somehow gut bacteria plays a significant role in their beneficial effect.

mind me asking this; are you taking any supplements Bravoncious, and is it ok to share which ones and if they do anything for you?
 
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i meant all those herbal supplements out there, not the illegal alkaloids or MAIOs plants might have as bioactive. the whole supplement industry is a multi billion dollar industry. so there must be a reason, that it probably works. i was very curious about polyphenols but it seems its dead end. of particular interest was quercetin. its enormously studied polyphenol. dozen of research on it! but its common issue; weak bioavailability of only 2 hours.
there is something else you havent considered though. polyphenols get metabolized by gut bacteria and in turn become different molecules and therefore more bioavilable but we cannot detect them simply because we dont know what to look for. we just check plasma levels for what we assume is one polyphenol the original being consumed. this is very interesting area of research and some hope that polyphenols might actually be beneficial, just not in their original form. you should also look into this, because you understand more than me in this area. and its definately something i recommend to sekio to look into as he is a tea lover. it appears those EGCGs are very low bioavailabiltiy BUT somehow gut bacteria plays a significant role in their beneficial effect.

mind me asking this; are you taking any supplements Bravoncious, and is it ok to share which ones and if they do anything for you?

You are very poorly informed about many things. Most polyphenols are not metabolized by gut bacteria, but rather by the liver. Gut bacteria metabolize mostly insolube fibers and sugar alcohols by the process of fermentation.

The short half life of polyphenols is not really the issue in their bioavailability. For instance, the antidepressant, agomelatine, has a short half life of 1 hour, and yet it is bioavailable and effective. The problem with polyphenols are the multiple polar rings that result in hydrolises in the gut and the very extensive first by-pass hepatic metabolism. Then, there is the issue of potency: most of the studies showing polyphenol activity in vitro indicate potencies in the high micromolar to low milimolar range of 100 Umol to 10 mMOL. That is very, very weak and even with multi-gram doses you would only achieve any effect in vivo if the oral bioavailabiltiy was very high, over 75%, which is not the case. In fact, it is a good thing that polyphenols have such crap bioavailability, because polyphenols are much stronger topoimerase inhibitors than they are MAO inhibitors, or COX-1 inhibitors or whatever. If they had high bioavailability, you would be risking death every time you had more than a couple cups of tea.

As for why the the supplement industry is a multi-billion Dollar industry, it boils down to marketing. They have thousands of people working around the clock to convince you to give them your hard earned money. Then, there is the placebo effect. Humans can convince themselves they are experiencing gains, when they are not. People under hypnosis can be convinced that they are being burned with cigarettes even when they are not, and they will even develop strong inflammation in the area. This goes to show how strong the placebo effect is. And this is why genuine pharmaceutical frugs need to be tested for effectiveness in double-blind, placebo-controlled trials, to show that they are not placebos.

This is not to say that all supplements are crap. For instance, HMB(beta-hydroxy beta-methylbutyric acid) is a genuine anabolic compound. It potently stimulates the MTORC-1 pathway, increasing muscle and bone protein synthesis, and it is converted into cholesterol directly inside muscle tissues and added to the cellular membrane(cholesterol is veery important in all anabolic reactions as it composes almost 40% of all cell membranes). Of course, activating MTORC-1 is absolutely terrible for your health and longevity, but it's definitely effective for building muscle.

Another example of an effective supplement is NAC(n-acetyl-cysteine). It reliably increases glutathione levels in vivo. It was originally developed as a genuine medicine, as an antidote for acetaminophen posoning. It eventually got clearance to be sold as a supplement due to a legal loohole(it is a derivative of a naturally occuring amino acid)

Both HMB and NAC are not only potent but highly orally bioavailable, as you would expect from amino acid derivatives - we evolved to absorb amino acids from foods since 9 amino acids are essential. But HMB and NAC are exceptions, and both of them were the result of serious scientific research, and were developed to treat illnesses and not to be used as supplements. Like I said, NAC was originally developed as an antidote, and HMB was originally developed to treat sarcopenia in people with third degree burns and HIV infection. They are genuinelly potent and orally active molecules that started being sold as supplements due to legal loppholes. . But they are exceptions. 99% of supplements are crap, placebos that have little more than marketing to them and do nothing. Vitamins and minerals, of course, are not placebos, but unless you have a very shitty diet where you eat not only exclusively processed foods and only one or two types of processed foods, vitamins and minerals are waste of money since the body uses what it needs and pisses away the excess. Even if you eat a diet of McDonald's and pizza, you probably don't need vitamin and mineral supplements since Federal law requires foods to be fortified. Also, excessive vitamins and minerals can be toxic. Vitamin A in it's active form(retinol) is highly toxic in excess and so is Iron, which can dramatically increase oxidative stress in mitochondrian.
 
Bravoncious, you didnt even research what I asked you to. Simple google search indeed shows dozen of results that polyphenols are indeed metabolized by gut bacteria and turned into various other molecules.
I mean, just the tip of the begining of such google search already states; Polyphenols are usually hydrolysed by intestinal enzymes or by gut microbiota. These modifications produce metabolites completely different from those present in food. In this form they reach blood, tissues and brain where exert biological activities. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199944/

Then you scroll through the search and you see another and another and another study etc. https://www.google.com/search?client=firefox-b-1-d&q=polyphenols+metabolized+by+gut+bacteria

Also, you didnt answer me what supplemens are you taking, or perhaps its a secret? I assume you take NAC and HMB as those are the ones you discussed in length. NAC has a lot of serious side effects that need further research. Ive also tried HMB and it was absolutely useless for me. Maybe its placebo as you said. Because I believe I probably got more benefit from a polyphenol than HMB...
 
Bravoncious, you didnt even research what I asked you to. Simple google search indeed shows dozen of results that polyphenols are indeed metabolized by gut bacteria and turned into various other molecules.
I mean, just the tip of the begining of such google search already states; Polyphenols are usually hydrolysed by intestinal enzymes or by gut microbiota. These modifications produce metabolites completely different from those present in food. In this form they reach blood, tissues and brain where exert biological activities. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199944/

Then you scroll through the search and you see another and another and another study etc. https://www.google.com/search?client=firefox-b-1-d&q=polyphenols+metabolized+by+gut+bacteria

Also, you didnt answer me what supplemens are you taking, or perhaps its a secret? I assume you take NAC and HMB as those are the ones you discussed in length. NAC has a lot of serious side effects that need further research. Ive also tried HMB and it was absolutely useless for me. Maybe its placebo as you said. Because I believe I probably got more benefit from a polyphenol than HMB...

These studies are worthless. Try doing a meta-analysis. Little polyphenols actually reach the gut, since most is hydrolized in the stomach. And even if they did, the metabolic products of them are not absorbed either, and lack completely the chemical properties seen in vitro since they are different molecules. In fact, this makes the case worse for you, since changing the molecules mean they are not the same as the ones that showed activity in vitro, and you want those to reach your bloodstream unchanged.

NAC does not have serious side effects except for heart burn in some people. If it had serious side effects, it wouldn't be used to treat people poisoned with acetaminophen since you don't give dangerous drugs to someone who is already weakened. The same for HMB, which is a natural product of leucine metabolism. The fact that you have not responded to it is 100% irrelevant. Maybe you have shitty genetic, or maybe you didn't work out at all.

Anyway, I have said all I wanted to on this topic and I am not interested in continuing further.
 
here, another one im quite interested in with positive results regarding absorption; https://www.sciencedirect.com/science/article/pii/S131901641000040X - Bioavailability of oleuropein. Phenolic compounds from virgin olive oil have been demonstrated to be highly bioavailable. ... It was supported by their finding that 15% of an oleuropein-glycoside supplement administered to healthy human subjects was excreted in urine as hydroxytyrosol and tyrosol

I can probably keep going and going with many others but your unwillingness to bother and take some time to research this better, is such a waste of your mind.
 
let's keep this thread civil, arguing over polyphenols is stupid

the whole supplement industry is a multi billion dollar industry. so there must be a reason, that it probably works

scientology is a multi billion dollar religion but it doesn't work at all. see also: homeopathy, alternative medicines, etc

It was supported by their finding that 15% of an oleuropein-glycoside supplement administered to healthy human subjects was excreted in urine as hydroxytyrosol and tyrosol

15% ba is stupid low
 
oh yeah? i see dozen of studies and articles that continue to claim high absorption of olive polyphenols. i suppose you will say its only the healthy fats in olive oil that contribute to health, but dont you think there is more to it than simply this?

here is more uses for polyphenols as what i posted wasnt a lot already; https://www.ergo-log.com/cistus.html
 
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here is more on how "useless" polyphenols are, YET, can have dramatic effect on the human being by binding to various minerals, including vital iron. PLUS severe interactions with medications; https://academic.oup.com/ajcn/article/81/1/326S/4607649
it also talks about why green tea extracts became toxic to the liver, something you have been denying in earlier posts while i was persistent and i am right.
a lot of talk of how detrimental they are in fact, and probably the reason why we shouldnt consume high doses.
 
seperate from this article, i also read this based on google search; Heat-stable thiamine antagonists occur in several plants; ferns, tea, betel nut. They include polyphenols; these and related compounds are found in blueberries, red currants, red beets, brussel sprouts, red cabbage, betel nuts, coffee and tea

i suffer from low thiamine and i guess those harmless "useless" polyphenols have nothing to do with it, right Bravoncious, you smart guy you

somehow i have a feeling i can stretch this thread into 12 pages all by myself finding new information about polyphenols. so i will try to slow down for a bit so the rest catch up and then ill only post very new information that comes available, thanks.
 
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