Talk:Antioxidant effect of polyphenols and natural phenols

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++Lar: t/c 01:22, 16 June 2006 (UTC)

Some General Concerns and A Possible Clarification

I have raised a similar concern about the Wikipedia section on antioxidants, but some of these concerns are worth repeating here. The fundamental issue is the confusion or conflation of the totality of polyphenol effects with a simple reduction of reactive oxygen species. Even more seriously, the author(s) conflate failure of the antioxidants vitamins and selenium with cautions about effects of polyphenols, suggesting a major lack of sophistication about basic distinctions between vitamins and polyphenols. This page needs a real expert to pitch in and write something. This is not a professional effort.

It is clear that numerous classical polyphenol antioxidants have a host of other effects on cellular mechanisms beyond reduction of reactive oxygen species, including what appears to be a common down-regulation of nuclear factor kappa B (a transcription factor widely regarded as a fundamental link between chronic inflammation and the eventual generation of cancer). It may turn out that numerous phytochemicals protect us from cancer not primarily because of reduction of reactive oxygen species and associated damage to DNA but also because of their inhibitory effects on NF kappa B, and their associated promotion of apoptosis in damaged cells. Additionally, the classic polyphenol antioxidant resveratrol (one of the hottest molecules in the anti-aging business) may have its most biologically protective effects mediated through mechanisms that have little or nothing to do with the reduction of oxidative stress. For example, resveratrol appears to activate surtuins, and about 20 other cellular pathways (including COX-2, iNOS, JNK, MEK, AP-1, p53, Bax, caspases, survivin, cyclins, Bcl-2, CIAP, Egr-1, PKC, PKD, casein kinase II, 5-LOX, VEGF, IL-1, IL-6, IL-8, just to name a partial list). (see Aggarwal 2006 in Biochemical Pharmacology for an excellent review). Turmeric appears even more complicated in its effects.

Indeed after reading some of the recent molecular work on antioxidant phytochemicals, one has to genuinely wonder if the term antioxidant really does them justice. It seems like they are more very complex cellular physiology modulators affecting transcription pathways, energy metabolism pathways, inflammatory pathways, apoptotic mechanisms, and a dizzying array of cellular signaling processes. However the term "cell physiology modulators" obviously is not going to catch on or replace the term "antioxidants". indeed this whole collection of other effects of classic polyphenols may explain why they appear to have far greater efficacy in relationship to the diseases of aging than classic antioxidant vitamins, which have been a complete bust in relationship to heart disease, Alzheimer's disease, and cancer.

However, Wikipedia should more accurately reflect some of these considerations.

DFW April 8, 2008 —Preceding unsigned comment added by 207.180.129.233 (talk) 01:39, 9 April 2008 (UTC)

Jargon

Jargon can be dealt either by linking to an appropriate article, using a more common term or defining the technical word.

• "phytonutrient" do not "contain" Polyphenol antioxidants. Foodstuff do. Blueberries are not phytonutrients, but flavones are.

• comment addressed in text edit on 6/14/6 Anlace 04:54, 14 June 2006 (UTC)

• The regulation chemistry consists of a polyphenol antioxidant’s ability to scavenge free radicals and up-regulate certain metal chelation reactions.
  • this entire sentence is pure jargon, even with the link. Much more details need to be added for it to be comprehensible by the layman.

• the sentence as written is precise, correct concise biochemical description, well wiki linked to relevant terms. i have added a following sentence in the text on 6/14/6 to assist in reading Anlace 04:54, 14 June 2006 (UTC)

• Since reactive oxygen species are linked to mobilization of ion transport systems[...]
• Reduction in inflammatory effects such as coronary artery disease including specific medical research into the pathways of improved endothelial health via downregulation of oxidative LDL.
  • the two elements liked by "including" have no apparent relation. THe resulting sentence is confusing at best
• Reactive oxygen species are important markers for inflammatory diseases.

• this is an ironic one. the term "marker" is the watered down version of the proper term biomarker. i had chosen the more approachable term already. the word marker is commonly used by physicians in their discussions with patients. in any case i have edited the article to provide the wiki link...a very good outcome you stimulated. Anlace 05:44, 14 June 2006 (UTC)

• For some of the ancillary benefits,
  • Also, a specific example of such a benefit would be nice

• most people would think the word ancillary is a common English word, not jargon. in any case ive given a wiki linked example as requested...probably more words you dont like :) Anlace 05:31, 14 June 2006 (UTC)
  • I replaced it with the much simpler "side-benefits", which is clear to any reader. "Secondary"is an acceptable, and certainly more universal synonym of "ancillary" Circeus 16:36, 14 June 2006 (UTC)

• Wine, although nonessential, has a high polyphenol content
  • Nonessential in regard to what?? Regular diet? Research?

• Nonessential is a common term used in medicine and food science (see for example the wikipedia article Essential amino acid Anlace 05:00, 14 June 2006 (UTC)
  • "Essential/nonessential" are normally applied to nutrients, not foodstuff, AFAIK. Saying that Wine is "nonessential" is confusing in this regard. Circeus 16:36, 14 June 2006 (UTC)

• The polyphenol content of wines is usually evaluated by the Folin reagent

• reagent is a very common chemical term...i have provided a wikilink to it. Anlace 05:18, 14 June 2006 (UTC)

• Statistical least squares analysis has been conducted to demonstrate the Folin method correlates
  • This would need a proper wikilink ASAP, as it can obviously not be explained inline.

• this comment is right on target. thank you. wiki links have been added in the article Anlace 05:07, 14 June 2006 (UTC)

• There is debate regarding the total body absorption of dietary intake of polyphenolic compounds.
  • This sentence give the impression that the debate is about the amount absorbed, while the rest of the paragraph males it obvious that the issued relates to the effects. Maybe "Intake" is jargon-ish here.
• there is evidence that some combinations of foods may inhibit full bloodstream uptake of certain polyphenol antioxidants

• article edited to reflect comment and avoid use of biochemical term "uptake"Anlace 00:55, 19 June 2006 (UTC)

• various exogenous sources of oxidative stress

• good english word, this is. ive provided a wikilink to the article exogenousAnlace 00:55, 19 June 2006 (UTC)

• responsible for the extrinsic type of skin aging

• another good english word, not even specialized to biology. ive added the wikilinkAnlace 00:55, 19 June 2006 (UTC)

Circeus 03:29, 14 June 2006 (UTC)

Proper terminology

the above comments are thoughtful and im sure are meant in a very constructive way. it is unfortunate that the editor chose an emotionally charged, pejorative word "jargon" to initiate the discussion. in any case i am responding to each comment and assuming it is meant in good faith. this article is by its nature dealing with a complex biochemical subject and a balance must be struck here between good descriptive science and approachable text by the informed layman. i shall work with the above editor and any other commenters to achieve the best outcome for our readers. i do not think the answer is to water down the science and emasculate the essence of the discussion. i have responded to many of the above comments with substantive responsive article edits and will continue to work through the remainder as i have time. regards. Anlace 05:44, 14 June 2006 (UTC)

Diluting the science has never been the answer on Wikipedia. - Samsara (talk • contribs) 11:25, 14 June 2006 (UTC)

Most of the times these can be dealt very easily (e.g. linking or using a synonym) or would probably gain in being expanded upon anyway. I do not request a dumbing down of any sort, which is actually the very last thing I wish for. I just think that the average reader should be able to comprehend the article as straightforwardly as possible.

Saying that a word like "up-regulate" is common in the field does nothing to help the unacquainted reader in understanding the topic being discussed and is likely to throw him out completely.

I have made a few vocabulary-related edits myself, but in the cases where expansion would be preferable, or where the term was out of my sphere of knowledge, I avoided making any more edits because I know I am not knowledgeable enough in the topic. Circeus 20:01, 14 June 2006 (UTC)

Am I missing something

This article appears to be entirely about flavonoids, but is talking about them using the term "Polyphenol antioxidant" which seems to have arisen in the medical literature, and is not really based in the organic chemistry of the molecules. Shouldn't this article be merged into the flavonoid article or the antioxidant article? It should at least be made clear for the non-biochemists that the undescribed antioxiadants that this article is talking about are flavonoids, since the article never mentions that fact directly (twice in passing). --Peta 12:16, 16 June 2006 (UTC)

The article appears to describe a specific class of antioxidants. The flavonoid cat I cannot tell whether is appropriate. However, The mention of the chemical class comes in at half the article and looks out of place. The lack of specific examples of Polyphenol antioxidants in the article makes it practically impossible to know whether they are all flavonoids, or only some. Circeus 14:20, 16 June 2006 (UTC)

perhaps these facts will help

• there are many antioxidants that are not polyphenols, such as zinc and many other inorganic substances. thus merging this article with antioxidants is absurd.

• not all polyphenols have been demonstrated to have antioxidant properties, so the name "polyphenol antioxidants" is a meaningful and useful distinction designating an important class of chemicals.

• flavonoids have a specific structure which must include one or more phenylbenzopyrone rings. some, but not all, polyphenols have such a structure. thus polyphenols and flavonoids are two distinct classes of chemicals, which happen to have some of the same members. thus merging "polyphenol antioxidants" with "flavonoids" is chemically incorrect, besides being absurd. Anlace 20:21, 16 June 2006 (UTC)

• The article fails to make all of those distinctions.--Peta 04:47, 21 June 2006 (UTC)

Class?

From the first sentence:

A polyphenol antioxidant is a member of a class of multi-phenolic compounds known for their free radical scavenging abilities.

What class is this? 81.76.99.188 14:27, 16 June 2006 (UTC)

Indeed that sentence is not ideal, as the class is obviously that of polyphenol antioxidants themselves, which are a type of antioxidant. Circeus 14:49, 16 June 2006 (UTC)

sentence has been edited to read more clearly Anlace 00:56, 19 June 2006 (UTC)

DFW's concerns apparently not yet addressed, and distinctions between mid-MW phenolics and true polyphenolics apparently not yet respected

I see no concerted effort to address DFW's early critique, which is well-informed and I think, first rate. Clearly a biologist with expertise. Perhaps someone can search the literature and identify and invite him/her back, after some attention has been given to the concerns. **A good advisor-editor is critical to becoming a good science writer, and if one has one but does not listen to them, you will lose them.** We should respond (but I am a chemist, and so not qualified, there.)

In keeping with that earlier critique, as well, no one seems to have gone over this article, asking whether the title is accurate to the content, and vice-versa, with regard to the polyphenol chemical structure class referenced.

If one wants the article to be about general phenolic involvement in antioxidant-associated cellular processes, the title should not say polyphenol, but should be more generic. **I would propose this title change approach.** Some of you know the mid-MW phenol literature fairly well (flavanoids, chalcones, etc.) and want to write about these. Let's not kill ourselves. Write about them, just don't call all of the phenols which have this antioxidant activity, what only a subset truly, structurally are (polyphenols). Change the title, please.

Otherwise, a careful read needs to be done, with each citation being checked as to the structure being referred to, and text on properties of compounds **removed** that are not about polyphenols -- but rather are ill-defined as to structure, or are simpler phenylpropanoids or flavanoids or other low to mid-MW phenolics. If the title stays, the article is misleading as is. Non-polyphenol references and comments need to be eliminated and/or substantially rephrased to indicate less that complete relatedness to the title subject. This is arduous work, and as a chemist, I can do it eventually. But I would rather allow those having done the initial writing to check statements for true relevance to the title (or alternatively, to have the title changed). Prof D. — Preceding unsigned comment added by 98.193.10.59 (talk) 20:47, 15 December 2011 (UTC)

Please also see Peta's "Am I Missing..." comments above, in comparison to closing paragraph to earlier Prof D comment

These issues of what are and are not polyphenols are not insignificant, and are mostly not subtle; the distinctions are recognized broadly by people trained in natural products chemistry, biochemistry, and pharmacology, and so should be respected. As Peta implies, flavanoid and polyphenol are NOT interchangeable / synonymous. Any substance discovered having more than one phenolic is simply not a polyphenol (e.g., see recent phlorogluinol-koala edit at polyphenols page), and a component part of a chemical structure cannot be equated to the whole of the structure, vis-a-vis its properties, therapeutic benefits, etc. (see vancomycin example in text of polyphenol article).

Bottom line, the distinction between classes of molecules -- here between polyphenols such as raspberry ellagitannin and the small molecule phenols (simple and dimeric to mid-molecular weight phenols such as gallic acid, phloroglucinol, and classes such as chalcones, phenylpropanoids, flavones and isoflavones) that compose them -- has to be respected. Otherwise, these articles on phenolics will lack long term meaning, and so, long term value. **More broadly and bluntly put, In my view, we need to get this right, or it makes a mockery of this site being an authoritative, encyclopedic source of chemical information.**

Finally, I reiterate a matter stated more fully elsewhere: These articles simply cannot reproduce errors in the literature. The case of the Japanese group polymerizing simple phenols and producing polyphenylenes **devoid of ANY phenolic groups** (except for a stray one at the end), and terming the oxygen-poor product a "polyphenol" is a nomenclature misstep, understandable given the language barrier. (See current "chemical synthesis" section in the Polyphenol article, and compare to what appeared before the 15 Dec major edit there.) To reproduce the error in an encyclopedia simply because the title of the Japanese article uses the term polyphenol is poor scholarship. Please, **read the articles you cite** (because a look at an image of the product just described, in the original paper, would make clear it is not the polyphenol of these articles). Discuss content about which you are unsure -- if ones knowledge of the field doesn't allow detection of such errors, please, consider making consultations or having discussion before making edits. There is simply not enough time in the day for one with experience to keep correcting mistakes, when they can just be reiterated or reverted. Prof D Meduban (talk) 18:00, 22 December 2011 (UTC)

In light of the Growing Scientific Concensus on the Mechanisms behind Polyphenols As Antioxidants, Is it time to Rename This Article?

Citing "Hormetics: Dietary Triggers of an Adaptive Stress Response" by Marc Birringer

After the introduction of the “Free Radical Theory of Ageing” by Denham Harman in 1956, reactive oxygen species (ROS) were considered one of the main reasons for the ageing process, including the development of age-related diseases [Citation: Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11:298–300.] The desire to cure cancer, cardiovascular diseases, or diabetes mellitus by the use of antioxidants was nothing more than wishful thinking. Today, more than 50 years later, current meta-analyses of intervention studies with antioxidants reveal a devastating picture [Park Y, Hunter DJ, Spiegelman D, Bergkvist L, Berrino F, van den Brandt PA, et al. Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies. JAMA. 2005;294:2849–57.] [Jiang L, Yang KH, Tian JH, Guan QL, Yao N, Cao N, et al. Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials. Nutr Cancer. 2010;62:719–27.] Antioxidant supplementation has no beneficial effect on age-related diseases; it furthermore may cause side effects and even increase mortality [Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and metaanalysis. JAMA. 2007;297:842–57.] How can the discrepancies between Harman’s hypothesis and clinical outcomes be explained, since the amount of ROS positively correlates with the incidence of neurodegeneration, cardiovascular events, diabetes mellitus, and cancer? Whether the appearance of increased ROS levels is a consequence of or a reason for the disease is the question to be answered. Nowadays, ROS change their attributes, and a more differentiated view is advisable to answer this question.

Classical polyphenols are antioxidants by definition; they are able to scavenge free radicals. This property was demonstrated in a series of in vitro studies but was scarcely seen in vivo. However, polyphenols' overall antioxidative benefit were clearly demonstrated in cell culture and animal studies. A recent review by Siow and Mann propagates polyphenols as hormetic effectors [citation: Siowand RC, Mann GE. Dietary isoflavones and vascular protection: activation of cellular antioxidant defenses by SERMs or hormesis? Mol Aspects Med. 2010;31:468–77.)] [citation: Mann GE, Bonacasa B, Ishii T, Siow RC. Targeting the redox sensitive Nrf2-Keap1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones. Curr Opin Pharmacol. 2009;9:139–45.] This discussion is better elucadated by Marc Birringer article entitled "Hormetics: Dietary Triggers of an Adaptive Stress Response" According to Birringer, Some Polyphenols listed in his Table VII are structurally related to polyphenols from Table II but are not Michael acceptors at first glance. But most interestingly, they induce ROS formation, GSH depletion, as well as Nrf2 activation. Less is known about how polyphenols increase intracellular ROS levels. Several . A series of dietary ingredients and metabolites are able to induce an adaptive stress response either by generation of reactive oxygen species (ROS) and/or via activation of the Nrf2/Keap1 stress response network. Most of the molecules belong to activated Michael acceptors, electrophiles capable to S-alkylate redox sensitive cysteine thiols. This review summarizes recent advances in the research of these compounds and classifies them into distinct groups. More than 60 molecules are described that induce the Nrf2 network, most of them found in our daily diet. Although known as typical antioxidants, a closer look reveals that these molecules induce an initial mitochondrial or cytosolic ROS formation and thereby trigger an adaptive stress response and hormesis, respectively. This, however, leads to higher levels of intracellular glutathione and increased expression levels of antioxidant enzymes such as glutathione peroxidase, thioredoxin reductase, and superoxide dismutase. According to this principle, polyphenols as antioxidants are just one of many dietary hormetics resulting in indirect antioxidant activity. Are polyphenols responsible for reducing ROS? Are they another calorie restriction mimetics via Nrf2/Keap1 Pathway inducing the Antioxidant Enzyme Response(ARE) - This is an important distinction.

How should one describe and document polyphenols as antioxidants? As they classic hydrogen donating antioxidants, or are they yet another signaling molecule (xenohormesis) triggering Nrf2/Keap1 pathway known to induce the Antioxidant Enzyme Response(ARE)? Perhaps polyphenols as ARE inducers and antioxidants, and they are simply being confused with chalcones, phenylpropanoids, flavones and isoflavones, since they often occur together in nature. This article is too confusing as written, and much of the problem may begin with the title. Is the title limiting/driving the information? Would renaming it to "Polyphenols and Phytochemicals as Antioxidants Inducers," (terrible, I know, add some suggestions for me here) help broaden the subject discussion to include a growing consensus of evidence that the Nrf2/Keap1 pathway may play an important role in mitigating oxidative stress in classic, polyphenol rich foods? Someone with more experience who can clearly consolidate/expand this wikipedia subject matter needs to review this article. It's good information, but is appropriate to try to discuss dietary "Polyphenol Antioxidants" alone without the larger conversation that includes epigenetic triggers from phytochemical, the concepts of hormesis and xenohormesis, calorie restriction mimetics, so called survival genes etc. RGK (talk) 19:44, 31 July 2012 (UTC) RGK (talk) 21:13, 31 July 2012 (UTC)

Outdated medical sources

I noticed that many of the sources used to support medical information are too old to meet WP:MEDRS. Can someone replace them with newer references? --Ronz (talk) 19:41, 3 December 2014 (UTC)

This article is confounded science

The "natural phenols" effort here at wikipedia is an unsubstantiated, non-standard thrust of writing that defies both the preponderance of solid primary and secondary scientific writing, as well as clear, scholarly chemical thinking. The fact that web sources will use language loosely does not support the comparable practice at Wikipedia (WP). WP reports on the best science from secondary sources, not the trends in language use on the web.

In the best scientific sources, words have meaning that remain somewhat static over long periods of time, so that complex scientific/chemical concepts can be communicated in short textual space. When a term in chemical nomenclature is used, it means what the standard chem nomenclature agencies say that it means (IUPAC and the like), otherwise, at very least, what the citable, best secondary sources consistently report.

This lumping together of all phenols of interest to a subset of wikipedia editors by those editors flies in the face of the way that these classes of molecules are discussed in the literature. While it is clear that there is debate among the experts in the field whether or not to remain with the original, restrictive nomenclature for polyphenols, it is also completely clear that no one of scientific repute proposes in the literature that any phenol that can be found in nature (that is, any "natural phenol"—and these include poisonous C₆H₅OH phenol itself, which is a metabolite in some microbial systems)—should be considered in same breath or category as traditional polyphenols.

This polyphenol-natural phenol obfuscation has to end. A polyphenol antioxidant is precisely what the name implies, an antioxidant whose activity has been (rightly or wrongly) associated with a polyphenol structure. Readers will not grasp the central therapeutic concept of SAR, the relationship between polyphenol structure and bioactivities (or between any other class of phenols and their characteristic bioactivities) if the underlying, fundamental concept of structural classes defined by accepted nomenclature ceases to exist.

Please, begin to deconvolute this. Only an article on phenols should contain all categories. After that, there should—for the sake of the lay readers—be articles on polyphenols, lignans, etc. (literature-substantiated, clearly established structure classes). These relatively distinct subgroups should not be convoluted in lists or other articles, that downplay their distinctives (and therefore can only serve to bewilder lay readers). 71.239.87.100 (talk) 06:35, 12 February 2015 (UTC)

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