Talk:Polyphenol
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Merge proposal
[edit]As we deal with this complicated article, it is timely to consider merging it with tannins. They are the same compounds. Both polyphenol and tannin are in need to clean up, but that challenge should be undertaken only after we deal with the overlap. If we decide not to merge, then we can at least figure out the distinctions.--Smokefoot (talk) 22:24, 29 October 2020 (UTC)
- Oppose - although the precise chemical definitions of the two large categories should prevail, it seems safe to conclude that all tannin variants (ellagitannins, gallotannins, condensed tannins, among other subcategories) are within the general polyphenol category, whereas not all polyphenol compounds are tannins. In simple terms, tannins are a subclass of polyphenols, similar to the separate subclassification of flavonoids and other smaller polyphenols. Per WP:OVERCAT and WP:MEDMOS, I prefer to see individual topics maintained as separate to keep organization and navigation between related articles as simple as possible for the common, non-science user. My opinion is that it would be more effective to clarify the tannin article to maintain the distinction. Zefr (talk) 15:19, 30 October 2020 (UTC)
- Comment. Well I am no expert but here is my analysis: Tannin seems mostly about polyphenols, the big review (ACIE) indicates that tannins and polyphenols are the same thing or are used interchangeably, "Structure and classes of tannins 1.1 Pseudo tannins" [lousy refs, probably misleading or undue weight], History section is name dropping and vacuous, "Cellular localization" [yet a new attempt to define the topic], "Presence in soils "The convergent evolution of tannin-rich plant communities has occurred on nutrient-poor acidic soils throughout the world...." [really??]. We are doing a disservice to readers by providing this hodgepodge of misleading factoids. IMHO. --Smokefoot (talk) 14:14, 5 November 2020 (UTC)
Weak review on blood pressure effects in the journal, Nutrients
[edit]There are too many problems with this review published in the dubious MDPI journal Nutrients to include its results in the article.
First, concerning the quality of the studies reviewed, the authors themselves make the case for weak clinical research designs and evidence from the observational and prospective studies reviewed, leading to their discussion of limitations: "small number of studies or participants, involvement of manufacturers, and scarce clinical relevance of some significant results (not enough variation in blood pressure); (i) large variability of polyphenol content in plant-derived foods (depending on cultivar, preservation, temperature, sun exposure, and other factors) as well as in absorption of polyphenols among humans; (ii) dietary sources of polyphenols are typically rich in other compounds that may exert cardioprotective effects, including fiber or monounsaturated fatty acids; thus, disentangling the unique effects of polyphenols is rather difficult when studying food groups; (iii) mechanistic studies conducted on cells and animals often do not take into account the cooking processes, which may lead to a loss in total polyphenol or transformation of specific molecules into others with different biological activities; and (iv) discrepancy between in vitro and in vivo doses (in vitro doses often lead to unrealistic dietary intake in humans).
There are too many negative and doubtful factors of experimental design and interpretation to state in the article that polyphenols in food help to improve blood pressure when the overall blood pressure effect in healthy normal people and those with cardiovascular disease was only on average about 3 mmHg for systolic pressure and 1.5 mmHg for diastolic pressure (Figure 2), i.e., physiologically minimal changes which cannot be ascribed with certainty only to polyphenol consumption.
Second, Nutrients is a dubious publication for discussing physiological effects of foods because a) it has a history of publishing low-quality articles and poor editorial practices, which led to the collapse of its editorial board in 2018, as summarized in Science; b) after such a tarnished recent editorial history, what rigorous academic editor would want to be associated with the journal now, and how do we as Wikipedia medical editors view publications in Nutrients?; see the disclaimer to WP:CITEWATCH; c) predatory publishing by Nutrients may also indicate that the authors paid the publisher, MDPI, to have their article published, further creating doubt about using such a journal as a WP:SCIRS or WP:MEDRS source; and d) high-quality reviews on factors affecting blood pressure are not published in a food journal, like Nutrients, but rather would appear in a reputable clinical journal, if the quality of studies and effects reviewed were convincing, which are not the case here. Although the Nutrients impact factor has improved since the editorial board resignation, this is likely due to the MDPI practice of open access and speed of publishing, as stated in the Science article.
The article's section on health effects is adequately stated that the fate of dietary polyphenols in vivo and potential physiological effects are unknown, as there are no definitive studies or reputable reviews to show otherwise. Zefr (talk) 16:12, 16 March 2022 (UTC)
- Thanks Zefr, for this comprehensive comment. I am not ready for a final verdict on Nutrients, even after reading the controversies. Some European universities demand that you publish your work as open access, which plays into MDPI's hands. And while the peer-review process is certainly not comparable to high-impact journals like Science or Nature I see it as any other entry-level journal for younger academics or those who start publishing their first papers. Anyways, in my view the study in question shows that we do know at least a little about in vivo effects and that could have added some balance to the current section that very boldly claims "we don't know nuttin". However, I am okay with stopping the discussion here because in the end the paper isn't worth spending too much time on it and I respect your assessment on it. CarlFromVienna (talk) 07:03, 17 March 2022 (UTC)
- I came across the following today on Twitter. So just for the fun of it, this well-designed RCT with a very clear positiv result came out these days. I know that it cannot be used as it is a primary study. But in the light of it I find the strong language of „we don’t know nothing“ even more inappropriate. CarlFromVienna (talk) 17:39, 18 March 2022 (UTC)
- There are facts we do know that reflect on the supposed health benefits of polyphenols: 1) there are no dietary reference intake recommendations by regulatory agencies (such as for vitamins and minerals, for which label decisions are based on the available literature), e.g., there are no Daily Values for any polyphenol appearing on food labels in major western countries; 2) the FDA and European Commission prevent food manufacturers from making health (or anti-disease) claims about polyphenols on food labels; 3) EFSA has acknowledged lab evidence for effects of 200 mg/day of cocoa extract and olive polyphenols having benefits, but what manufacturers are making use of such extract amounts to produce food products having common value?; and 4) "the possible functions of polyphenols in vivo remain unknown" because there are no existing methods to track and define their mechanisms and actions specifically in vivo. As with all research attempting to define a relationship between food and health, the clinical research is burdened by the numerous uncontrolled factors of people and their daily diets, and by the unknown fate and nutritional value of other food components complicating any interpretation specifically about polyphenols. Zefr (talk) 19:16, 18 March 2022 (UTC)
- Thanks, Zefr, I understand. BTW, the study I linked above on cocoa flavanols, has just come back to bite me :-) CarlFromVienna (talk) 08:38, 22 March 2022 (UTC)
- There are facts we do know that reflect on the supposed health benefits of polyphenols: 1) there are no dietary reference intake recommendations by regulatory agencies (such as for vitamins and minerals, for which label decisions are based on the available literature), e.g., there are no Daily Values for any polyphenol appearing on food labels in major western countries; 2) the FDA and European Commission prevent food manufacturers from making health (or anti-disease) claims about polyphenols on food labels; 3) EFSA has acknowledged lab evidence for effects of 200 mg/day of cocoa extract and olive polyphenols having benefits, but what manufacturers are making use of such extract amounts to produce food products having common value?; and 4) "the possible functions of polyphenols in vivo remain unknown" because there are no existing methods to track and define their mechanisms and actions specifically in vivo. As with all research attempting to define a relationship between food and health, the clinical research is burdened by the numerous uncontrolled factors of people and their daily diets, and by the unknown fate and nutritional value of other food components complicating any interpretation specifically about polyphenols. Zefr (talk) 19:16, 18 March 2022 (UTC)
- I hope I might interject here as well. The problem is that "Polyphenols" is - outside of research - more a marketing hype than a useful definition. Some compounds and groups have a lot of research, others don't - so any summary statement beyond "it's complicated" needs clarification. In observational studies, they're usually linked to some health benefits - but that's (in my opinion) mainly due to the fact that one can't really consume a diet with a lot of polyphenols without consuming a "healthy" diet (i.e. lots of fruits and vegetables).
- I think an entry for Polyphenols is important, because of the hype around them - but I think it is important to distinguish between the group and individual compounds and classes, and not to assign any benefit (or lack thereof) to the group.
- Regarding Nutrients - a lot of journals require authors now to pay for articles to be published (e.g. the massive open access online journals, but also when opting for 'gold open access'.Ggux (talk) 07:12, 16 May 2022 (UTC)
- I came across the following today on Twitter. So just for the fun of it, this well-designed RCT with a very clear positiv result came out these days. I know that it cannot be used as it is a primary study. But in the light of it I find the strong language of „we don’t know nothing“ even more inappropriate. CarlFromVienna (talk) 17:39, 18 March 2022 (UTC)
In vivo biomarkers?
[edit]This edit summary suggested that biomarkers exist for metabolized polyphenols. There is no reliable source used in the article for that measurement, which would be a significant breakthrough for assessing the fate of digested polyphenols. This seems impossible for compounds that are rapidly digested and metabolized to smaller compounds changed and distributed among body organs, then are excreted by the kidneys within minutes. Zefr (talk) 19:32, 15 May 2022 (UTC)
- Polyphenol metabolites are routinely used as biomarkers of polyphenol intake - and have been for a very long time. For example isoflavnone metabolites were used as biomarker of isoflavone intake [[1]]. A more recent review expands this to a much larger range of compounds [[2]] and biomarkers of flavan-3-ol intake have been applied to a larger cohort study [[3]].
- Here [[4]] is a review of ADME for flavonoids - "excreted within minutes" would be an exception. There is one study with radio-tracers (14C) which is probably the most reliable, and t1/2 for epicatechin metabolites is about 1h - for the microbial metabolites around 6h [[5]].
- The compounds are not rapidly digested - a large proportion ends up in the large intestine and is metabolised by the gut microbiome [[6]] and enter (and leave) the body much later. But this is not new - that has been known since the early 2000s (see literature by Crozier or Rice-Evans). Ggux (talk) 22:10, 15 May 2022 (UTC)
- All those sources explain the limitations which leave the issue of polyphenol biomarkers dicey at best. I believe the only thing we can say is that measurement attempts have been made, with little evidence of accuracy for fate, biological activity, and quantitative evidence of effect. The first paragraph of the health effects section seems to accurately explain what is a relatively poor "state of the art". Zefr (talk) 22:35, 15 May 2022 (UTC)
- There are very good data for some of them - but obviously not for all of them. There is very good evidence of the fate of those that have been investigated. It depends on whether polyphenols are seen as a single entity or whether they are seen as a group with many different members. I would distinguish between different parts and state that for some, there are very good data whereas for others there are very little. Ggux (talk) 05:33, 16 May 2022 (UTC)
- All those sources explain the limitations which leave the issue of polyphenol biomarkers dicey at best. I believe the only thing we can say is that measurement attempts have been made, with little evidence of accuracy for fate, biological activity, and quantitative evidence of effect. The first paragraph of the health effects section seems to accurately explain what is a relatively poor "state of the art". Zefr (talk) 22:35, 15 May 2022 (UTC)
iron absorption and erythropoiesis
[edit]Could you elaborate zefr ? thanks.Atchoum (talk) 17:07, 8 December 2022 (UTC)
Cancer
[edit]As of 2019, there is little evidence that dietary flavonoids lower the risk of cancer.
The reference was retrieved in 2019, but the Linus Pauling Institute article cited is from 2016 and is a survey of even older publications. Is the really the best and most current citation to put here? ThreeRocks (talk) 23:04, 9 March 2023 (UTC)
- I have raised that issue before but it is the best overview to date even it was last reviewed in 2016. Unfortunately if you go looking for systematic reviews on polyphenols it is just garbage published in the unreliable MDPI journals such as [7], [8]. There are no good reviews to date and much more research needs to be done. Psychologist Guy (talk) 00:04, 10 March 2023 (UTC)
I think to balance this section one must not search for "polyphenols" in general, because that would really be a tough claim to make, that all polyphenols or most of them or whatever subset (like flavonoids) reduce cancer risk. If you look for specific polyphenols like soy isoflavones there are studies on PubMed to be found and I just added one of them. As soy is a staple in Asia there are also prospective cohort studies and meta analysis of these. CarlFromVienna (talk) 13:50, 10 March 2023 (UTC)
I have also changed the summary of the LPI that was clearly wrong. Reading the actual text, it states: "...found an overall 11% reduced risk of breast cancer with the highest versus lowest intake of soy isoflavones..." for Asian woman and "...results suggested that intakes of flavonols and flavones may also be inversely associated with the risk of breast cancer" and "a pooled analysis of four case-control studies that stratified by menopausal status showed inverse associations between breast cancer and intakes of flavonols, flavones, or flavan-3-ols in postmenopausal women only" and "Finally, a meta-analysis of four prospective cohort studies found an overall 16% reduced risk of breast cancer recurrence in women with high versus low isoflavone intakes" and "A meta-analysis of 13 observational studies also suggested an inverse relationship between prostate cancer risk and consumption of soy products, especially tofu" and "suggesting that isoflavones may reduce prostate cancer incidence" whatever you make of this, claming that the LPI sees "no evidence" is wrong. They do say that "whether supplementation with specific flavonoids could benefit cancer prevention or treatment" needs research, but now we're talking supplements! CarlFromVienna (talk) 13:57, 10 March 2023 (UTC)
Iron chelation and accumulation
[edit]I recently cited an article which states:
- The iron-chelating effects of EGCG, curcumin, myricetin, ginsenosides, and ginkgetin are thought to be an underlying mechanism through which polyphenols prevent neurotoxicity, leading to a neuroprotective effect against neurodegenerative diseases like Parkinson's Disease, Alzheimer's Disease, and Huntington's Disease.
and
- the iron-chelating and inhibitory effects on absorption of iron associated with polyphenols may lead to poor iron status
Both of these are referenced to review articles, for instance. This review article they cite states:
- In fact, these compounds have been known to have neuroprotective effects due to their iron-chelating properties [154, 156, 269–271].
Additionally, a review of 34 randomized controlled trials "showed that dietary polyphenol supplementation restricts iron absorption".
Based on this I edited in the following:
- While the chelation of iron by polyphenols may help prevent the buildup of iron in the brain, protecting against some neurodegenerative diseases, this chelation also inhibits the absorption of iron in the small intestines, which can contribute to iron deficiency.
In hindsight, I would change "can contribute" to "may contribute". However, I intentionally qualified the language of the sources to "the chelation of iron ... may help prevent" to make the language less certain than what was used in the sources cited. @User:Zefr, please explain what you believe was an "exaggerated interpretation" and please cite the text from WP:MEDRS that you believe disqualifies the usage of this source. Photos of Japan (talk) 08:12, 31 August 2024 (UTC)
- The reverted text was
"While the chelation of iron by polyphenols may help prevent the buildup of iron in the brain, protecting against some neurodegenerative diseases, this chelation also inhibits the absorption of iron in the small intestines, which can contribute to iron deficiency"
, cited by this report mostly of lab research. - Discussion of each of the three concepts is just conjecture: a) iron chelation by polyphenols prevents buildup in the brain, b) such chelation protects against neurodegenerative diseases, and c) chelation inhibits intestinal iron absorption. None of this is established fact, and none of this is supported by a WP:MEDRS review or a clinical guideline proposing such use of polyphenols as an approved therapy, WP:MEDORG. Zefr (talk) 16:16, 31 August 2024 (UTC)
- Comment: phenols, especially catechol and pyrogallol derivatives, (which includes polyphenols) will no doubt bind Fe (hence the evolution of catechol-based siderophores such as enterobactin). Binding Fe(III) is just what they do regardless of the location of polyphenols. I guess sequestering Fe could be relevant or possibly the Fe-polyphenol complex has the correct shape for some binding. --Smokefoot (talk) 17:55, 31 August 2024 (UTC)
- "such use of polyphenols as an approved therapy"
- Please note that the edit in question was made to the "Toxicity and adverse effects" section. Polyphenols have been substantially looked at for potential neuroprotective benefits, and many people take them for that reason. I wanted to point out that, one of the proposed mechanisms for this effect, their iron-chelating ability, can itself have deleterious effects. The purported health benefits of polyphenols are often touted, but there is inadequate discussion of their potential harm.
- Zefr has stated that the statment "chelation inhibits intestinal iron absorption" is not "supported by a WP:MEDRS review". This is a systematic review that was published in perhaps the most influential nutritional journal of the last 100 years. I'm not even mentioning the effects of erythropoiesis that that review found (which Zefr previously reverted), just the mundane claim that polyphenols chelate iron and that this can inhibit intestinal absorption (which can contribute to iron deficiency).
- With regards to protection against neurodegenerative diseases, I am not stating that "It is an established fact that polyphenols prevent neurodegenerative disorders", just that they may help prevent some of them (or they may not). We don't even know if the iron accumulation we see in many neurodegenerative disorders is a cause or effect of them. The sources I quoted use much stronger language:
- "In fact, these compounds have been known to have neuroprotective effects due to their iron-chelating properties"
- I do not know that there is sufficient evidence to make such a strong assertion, but the sources provided demonstrate that, at the least, their chelating effect may help prevent neurodegenerative diseases.
- I didn't spend a long time mulling over my original wording, and I am open to changes, for instance:
- While the chelation of iron by some polyphenols may help prevent the buildup of iron in the brain, which may help protect against some neurodegenerative diseases, this chelation also inhibits the absorption of iron in the small intestines, which may contribute to iron deficiency.(citing above sources)
- But without really understanding what part of WP:MEDRS Zefr believes these sources do not meet, I cannot suggest wording changes to address their concerns. Photos of Japan (talk) 20:31, 31 August 2024 (UTC)
- The Xu review is 3 years old, and has not since been substantiated by any further quality review, regulatory authority (such as EFSA or FDA) or clinical organization, which leads the concept of in vivo chelation by polyphenols to WP:UNDUE as a non-mainstream issue. WP:MEDSCI encourages following the prevailing scientific consensus, for which there is no evidence of widely-held endorsement of this presumed effect as an issue of concern or benefit to the public.
- A critical point is the presumption that polyphenol parent compounds are intact after ingestion when the chelating capability seen in vitro could apply. They are not intact, but rather rapid metabolism breaks them into multiple small units with unknown fates in vivo and rapid excretion (i.e., negligible bioavailability), making the whole story of potential physiological benefit or adverse effect moot, as explained in the article.
- To consider citing the Xu review under Research in the article, it's difficult to propose useful wording. The authors discuss extensive limitations of the studies reviewed, giving pause about the certainty of presumed effects, and conclude that polyphenol ingestion only "may" affect erythropoiesis or serum iron.
- For a minor topic receiving no regulatory or clinical attention, I don't feel it would be useful to say
"A 2021 review of preliminary research found that ingesting polyphenols may affect erythropoiesis or serum iron."
That doesn't impress as conclusive enough for the encyclopedia, MEDMOS, Writing for the wrong audience. Zefr (talk) 22:07, 31 August 2024 (UTC)
- Comment: phenols, especially catechol and pyrogallol derivatives, (which includes polyphenols) will no doubt bind Fe (hence the evolution of catechol-based siderophores such as enterobactin). Binding Fe(III) is just what they do regardless of the location of polyphenols. I guess sequestering Fe could be relevant or possibly the Fe-polyphenol complex has the correct shape for some binding. --Smokefoot (talk) 17:55, 31 August 2024 (UTC)
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