Talk:Antioxidant/Archive 2

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Archive 1 Archive 2

Glutathione Levels

The values for glutathione levels in serum, provided in the table are wildly off. Normal values are as much as a hundred times less than the value in the chart, at ~3-6uM. See http://www.ncbi.nlm.nih.gov/pubmed/8353942 and http://www.circ.ahajournals.org/cgi/reprint/100/22/2244 for references. —Preceding unsigned comment added by 70.233.173.122 (talk) 11:08, 10 March 2009 (UTC)

Yes, those references do give a very different value than the reference I quoted and the new value agrees better with the Meister Annual review that states "micromolar levels are found in blood plasma". I've substituted one of the references you cited. Thanks for finding this mistake. Tim Vickers (talk) 15:18, 10 March 2009 (UTC)

Unreferenced table

The new table in the section on "Measurement and levels in food" is unreferenced. I can't find any evidence in the literature that eating eggs or milk actually changes the levels of glutathione or melatonin in the body. Unless this material is referenced with a reliable source that establishes the link with antioxidants, this material does not belong in the article about antioxidants. Tim Vickers (talk) 16:17, 26 May 2009 (UTC)

I found a source that discusses this (link to full text) PMID 15213035. A low-protein diet produces a transient change in serum GSH, but this is restored after a few days when the body adapts. Tim Vickers (talk) 19:58, 26 May 2009 (UTC)
Antioxidant compounds Foods provide highest level of these antioxidants' building block[citation needed]
Glutathione Milk, Cheese, Egg (methionine, precursor of cysteine), Whey Protein
Melatonin Milk, Cheese (Tryptophan, precursor of serotonin)

Curious effects of ACE inhibition on EC-SOD (SOD3)

Both the inhibitor and the angiotensin receptor blocker seem to drastically upregulate the antioxidant enzyme: PMID 11171786 (2001) and review in PMID 16601572 (2006) --CopperKettle 14:18, 1 June 2009 (UTC)

this article is total crap

This article fails to point out that anti-oxidants are created by microbiology for the purpose of microbiology.. and these systems would be particulary distant and unaffected by the consumption of food and beverage that its pointless to consider "eating" anti-oxidants... except if they are there to stop the apple turning brown.

the term 'anti-oxidant' is so poorly defined, and there is so many nonsensical claims about anti-oxidants and "oxidative stress".. I suspect that failing to include a strong definition leads this article to dance a dance of "consensus" and not address the subject at hand with any solid fact. The solid fact is that "anti-oxidant" is a notional property of a substance in microbiology and is not proved to be a topic relevant to nutrition... See an antioxidant may keep dying cells of apples from turning brown, but so far they escape observation of having any affect on healthy cells...leading one to believe that healthy cells need no outside meddling for optimal life.

I'd recommend PMID 8660387 and PMID 9129943 as good general references on the science, and possibly PMID 15153272 as a recent review on the importance of antioxidants in human health. Tim Vickers (talk) 17:17, 28 January 2010 (UTC)
I share the frustration of 202.92.40.8 (Unfortunately, TimVickers seems to have replied before the bot could sign the strongly negative contribution of 202.92.40.8). The article appears to be validating the widespread health claims about eating "antioxidants". In part this appearance is magnified by mentioning vitamins (A, C, E) which a human can, by definition, only obtain through the diet. Although these substances may have some antioxidant activity, this activity is slight at at the levels which prevent the deficiency diseases. The important effects of these substances are their vitamin activities. (In the case of vitamin C, or ascorbic acid, the ascorbic effect results from its ability to oxidize certain molecules, and not from its ability to prevent oxidation. Trying to understand the importance of vitamin C to human nutrition by calling it an antioxidant therefore is not just silly, it is counterproductive). Many of the important antioxidants (not reducing agents) are produced in the human body, and can use the standard reducing agents — food energy molecules like sugar and fat — without needing any special dietary antioxidants. Many other highly-touted antioxidants, such as the polyphenols (tannins), tend to react with protein (that's how they tan skin into leather) in the digestive system and be eliminated through the colon, making them unavailable through the diet.     Jay L09 (talk) 16:00, 27 May 2010 (UTC)
Although it would not be necessary in the best of all possible worlds, I think that this article could be improved by clarifying the difference between the importance of a chemical in vivo, and the utility of consuming it in the diet.     Jay L09 (talk) 16:00, 27 May 2010 (UTC)

Antioxidants Explained Easy

An easy way to explain antioxidants and free radicals is think of a 5 lane highway. Each lane has cars traveling smoothly with no traffic. The highway represents your body or major organ. The cars represent cells in your body. A crack develops in lane #1. The car in lane #1 hits the crack, spins out of control and runs into the car in lane #2. The car in lane #2 then collides in the car in lane #3 and so on. Soon all the cars are colliding into each other causing all sorts of issues. The crack represents a free radical and the best way to get rid of the crack on the lane is to repair it or fill it in. An antioxidant is the molecule which would fill in the crack, allowing the cars/cells in lane #1 to get back to normal which would also allow the other cars/cells in the subsequent lanes be relatively normal again. This is how antioxidants and free radicals work.

The Antioxidant Detective 04:25, 26 May 2010 (UTC) —Preceding unsigned comment added by NeemaF (talkcontribs)

Well, that was certainly and easy and compelling explanation. I am left wondering, however, whether it has anything to do with reality, or is simply a sales pitch for a useless or perhaps dangerous product.     Jay L09 (talk) 14:43, 27 May 2010 (UTC)

I tell ya, this discussion would be a LOT easier to follow if Wikipedia had a bot that went around and just crossed out anything that had weasel words in it. I can tell you this: ALL of this baloney about antioxidants would be gone in a flash. It's ALL so full of "may" and "might" and "indicates that it may be" and "appears to" and all that. Richard8081 (talk) 03:31, 29 May 2012 (UTC)

Uric Acid

I, for one, find myself unconvinced of the importance of uric acid as an antioxidant. (Perhaps I need to be educated. Oh! Perhaps that's why I read the Wikipedia article.) When I read the uric acid section, there was only one reference, a 40-year-old letter to the editor, with a question as its title. I found the source of the claim about the relative importance of uric acid antioxidant activity in the blood, and was also not completely convinced. Would someone who is more expert in biochemistry than I am address these two points:

  • Uric Acid Substituting for Ascorbic Acid in Humans: Is there more recent information than Peter Proctor's 40-year-old letter to the editor, either yea or nay? ("Similar Functions of Uric Acid and Ascorbate in Man?" Nature 228 (1970)868
  • Relative Importance of Uric Acid as an Antioxidant in Human Blood Serum: The "more than half" value derives from a paper by S. R. J. Maxwell et al. ("Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus" European Journal of Clinical Investigation (1997)27, 484-490) about a study of diabetic and normal persons. Assays of in vitro blood serum antioxidant activity were linearly regressed against the concentrations of several antioxidants. The correlation coefficients were multiplied by the concentrations, and the results expressed as percentages, normalized to 100%. Uric acid came up as 65.1% Although this is the most obvious method, I question whether it is valid. Thoughts from an expert?

Jay L09 (talk) 06:20, 17 June 2010 (UTC)

This is a very interesting question, thanks for bringing it up! The best review of the literature I found is in the introduction of PMID 8325534, although this is a rather old paper. It cites several papers to support their statement "It has been estimated that urate comprises 30-65% of the peroxyl radical-scavenging capacity of blood plasma." including this Ames paper. The interaction with ascorbate is reviewed in this 1991 paper I think it is well-established that urate can act as an antioxidant, although there is recent controversy surrounding its possible role as a pro-oxidant in stroke, reviewed in PMID 18617849. Tim Vickers (talk) 16:51, 17 June 2010 (UTC)
I've had a go at reworking this section. Tim Vickers (talk) 16:59, 17 June 2010 (UTC)

is it damaged by heat —Preceding unsigned comment added by 123.200.11.6 (talk) 06:43, 28 November 2010 (UTC)

I don't understand this concept.

The first sentence in this article is "An antioxidant is a molecule that inhibits the oxidation of other molecules.". As far as I know, our metablolism relies on the oxidating potential from oxygen in the air. If antioxidants prevented oxygen from oxidating glucose molecules they would be highly toxic. Fortnately it doesn't really seem like antioxidants inhibit the oxidation of glucose molecules. Rather it seems like these antioxidants capture radicals. Shouldn't your definition of an antioxidant rather be "a molecule that captures radicals"?

An oxidizing agent is defined as a molecule that captures electrons from other molecules. Radicals aren't neccessarily oxidazing agents, but from reading this article I get the impression that "free radicals" are oxidizing agents. 152.94.59.5 (talk) 16:10, 7 April 2013 (UTC)

History section

Once a coherent narrative can be developed, the article should give high points in the history of antioxidant science. Once such point is that Antioxidant use in rubber was pioneered by Sidney M. Cadwell at the United States Rubber Company. AresLiam (talk) 12:44, 29 December 2013 (UTC)

Science

I have heard information from various sources saying that antioxidants are unhealthy. I want some clarification on the current scientific consensus on antioxidants. — Preceding unsigned comment added by 180.200.145.196 (talk) 00:59, 3 August 2014 (UTC)

Chain Reaction

The article's intro currently states: "Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When the chain reaction occurs in a cell, it can cause damage or death to the cell."

This appears to be referring to antioxidants preventing a specific type of oxidation known as lipid peroxidation, which is a chain reaction, but it is not the only type of oxidation reaction inhibited by antioxidants. Thus the definition in the lead is inaccurate and should be modified accordingly. A definition that more closely follows that of Halliwell & Gutteridge (1989), cited in the article in the lead,[2] should be used instead. Rhode Island Red (talk) 16:48, 16 February 2015 (UTC)

Commercialization

Blythwood proposed using the following file as an example of discredited antioxidant products. I removed it per WP:NOT, i.e., inappropriate to draw attention to a commercial product, good or bad, and not a reliable WP:SECONDARY source. Up for discussion/re-evaluation. --Zefr (talk) 18:00, 10 November 2015 (UTC)

Proposed text and illustration: Despite the fact that they have been widely discredited, dietary supplements containing antioxidants continue to be promoted. An example preparation, ReversAge, was billed in 2013 as containing antioxidants that 'fight free radical damage at the cellular level' to 'address aging'.[3]

Pedantic point, but WP:SECONDARY is not relevant here. The source is being solely cited a source as to what the company is claiming. On that front it is a primary source. If a company claims that their drug cures cancer, you can absolutely cite them as evidence that they say their drug cures cancer. So the only issue is WP:NOT: whether people mind having an image showcasing the kind of claims altmed companies make. I thought this was an interesting example to showcase since the image is official to the company, it's CC-licensed so can be widely disseminated without issue, and it makes upfront claims to treat aging. (Often altmed people are surprisingly unwilling to say exactly what their product does, especially here in the UK where false advertising is actionable.) If you like I have no objection to removing the name of the product so they aren't getting google hits out of this. (By the way, sorry about reverting instantly - I couldn't see discussion of commercial policy on this talk page and thought you assumed I was plugging this stuff.) Blythwood (talk) 22:52, 10 November 2015 (UTC)

Hello Blythwood: As there are countless similar products purporting antioxidant benefits, a WP:SECONDARY review by a reputable source is what I intended for our collective consideration. But I am unaware of such a document, and feel singling out ReversAge gives it WP:UNDUE attention, is potentially misleading to lay users and is also WP:OR if we were to display it as an example. I propose bypassing this as an example. --Zefr (talk) 01:44, 11 November 2015 (UTC)
It is just a can with branding on it. I do not see that it is needed. Doc James (talk · contribs · email) 01:58, 11 November 2015 (UTC)


Order of material

Puzzled as to why "Health effects" are being put first. Unlike compounds with purely medical relevance, such as antibiotics, antioxidants as a large group of enzyme systems and metabolites, similar to DNA repair systems or cell signalling systems. Dietary antioxidants are a sub-set of the total, so the effects of these compounds on human health can't really be the main focus of this top-level article. Tim Vickers (talk) 21:52, 17 December 2015 (UTC)

Health effects are definitely one main focus. If one searches for antioxidants this is definitely a major focus of most of the top hits. Doc James (talk · contribs · email) 23:44, 17 December 2015 (UTC)
I also share concerns about having this particular version of the 'health effects' section upfront. The problem as I see it is that the section shifts the focus exclusively on the effects of supplementation when it should be more general, discussing how physiology/pathology are impacted by endogenous antioxidants like SOD, catalase, glutathione peroxidase, etc., in addition to vit A/C/E, irrespective of supplementation. Basically, it's a distinction between (1) the role of antioxidants in health and disease versus (2) the effects of antioxidant supplementation on health and disease; and it makes sense that #1 would precede #2 in the article. As it stands, I'd say it's more or less an issue of WP:BALANCE and WP:UNDUE, and a somewhat misleading title. Rhode Island Red (talk) 02:59, 18 December 2015 (UTC)
Not super clearcut priority to me. Health is probably the top hit because we are all wondering about our mortality. But in the industrial world, anti-oxidants are also very important additives, e.g. in foods and plastics. So it would be misleading if such application were not mentioned in early on. One advantage of mentioning these non-biological apps is that they provide the reader with context.--Smokefoot (talk) 03:19, 18 December 2015 (UTC)
That's a good point too -- antioxidants are important in food and chemical preservation as well. What I would hope to avoid here is the reader walking away with the impression that antioxidants are merely substances that people take as supplements (or drugs) to prevent oxidative stress and diseases, when the impression should be more general: e.g., that antioxidants are substances that donate electrons to alter redox reactions; that they are produced naturally by biological organisms (from bacteria to animals) to regulate a variety of redox reactions (cell signaling as well as oxidative stress), used in industry to prevent oxidation, and, lastly, studied experimentally as potential therapeutic agents (mostly without positive results to date). I'm not so much concerned by what people are searching for on Google. If that logic were to be applied to guiding article content, Kim Kardashian would probably be the first line in the WP article on Armenia. Rhode Island Red (talk) 16:22, 18 December 2015 (UTC)
Valid points and good discussion by all, but I think about the general lay public (think first-time users in a high school biology class) accessing this article, looking for a concise overview about what's in the encyclopedia about antioxidants in the diet. The lede is too long and detailed as is, and is conspicuously bloated with WP:OVERCITE, but is no doubt the section most read. Like reading a news article, the lay user would quickly scan the lede and TOC for content. For these reasons, I favor having the health section high in order as arguably the most lay-relevant information, leaving the more detailed scholarly body for specialists' needs. Specific points: 1) to best serve lay users on a complex topic, what order is more preferred and why? 2) let's take a stab at reducing lede verbosity and sourcing. There also is misinformation in the lede, mentioning polyphenols as reducing agent antioxidants (only in vitro, no human relevance) and pharmacological antioxidants as validated tools in treating stroke and neurodegenerative disorders (no such approved drugs). I'm removing these statements as a first-pass lede revision. --Zefr (talk) 16:58, 18 December 2015 (UTC)
I'm broadly with Tim on this one (good to see you, Tim) - an encyclopedic treatment of the topic does not begin with health and dietary supplements. If anything, we're contributing to laypeople's common misunderstandings about antioxidants and their health effects by featuring that subtopic so prominently, and before any meaningful background has been provided for the chemistry. I do agree that the lead could be simplified, though I think the revision that dropped the "oxidation reactions are crucial for life" paragraph might be going a little too far. Opabinia regalis (talk) 18:02, 18 December 2015 (UTC)
I agree that we should discuss all aspects. We should however present what people most likely are looking for first.
Health information is also often easier to prevent in easy to understand language while the discussion of metabolites gets rather complicated rather quickly. Doc James (talk · contribs · email) 18:31, 18 December 2015 (UTC)
There is a major problem however in talking about the health effects of antioxidants before we've discussed what they are and how they work. If this basic introductory material is covered at too high a level, we could either simplify it, or add an "Overview" section, like I did with Oxidative phosphorylation (Good to see you too Opabinia) Tim Vickers (talk) 23:34, 23 December 2015 (UTC)
Echoing Tim and Opabinia, given that the health benefits of antioxidants are not so clear cut, I think it makes more sense to first discuss how they work. This puts the potential health effects in better perspective and will make the discussion of health effects more meaningful. Also it is important to point out that roughly half of the current lead discusses health. Boghog (talk) 00:30, 24 December 2015 (UTC)
Trying to thinking of a way around this problem. If we were to move the health section further down in the article, is there a way we could present the health aspect more clearly in the lead, so that people searching on a major health topic could be quickly satisfied with a basic summary and not have to wade into the rest of the article? Tim Vickers (talk) 20:53, 30 December 2015 (UTC)

Measurement -

Some content from hot chocolate : "In a single serving of cocoa, the researchers found 611 milligrams of gallic acid equivalents (GAE) and 564 milligrams of epicatechin equivalents (ECE), compared with 340 milligrams of GAE and 163 milligrams of ECE in red wine, and 165 milligrams of GAE and 47 milligrams of ECE in green tea.[1]" could usefully go here ? - Rod57 (talk) 22:24, 24 February 2016 (UTC)

  1. ^ Friedlander Jr., Blaine P. (December 3, 2003). "Ahhhh! Better than red wine or green tea, cocoa froths with cancer-preventing compounds, Cornell food scientists say". Cornell News. Retrieved July 5, 2008.
I don't see where it would fit. Rhode Island Red (talk) 00:53, 25 February 2016 (UTC)

Might food sources be good and supplements harmful?

I've been reading medical sources about the benefits of antioxidant-rich foods, and then I come here and 95% of the article is about how antioxidants are useless or harmful.

This article cites a heap of studies, but so do the doctors who wrote the articles with a seemingly contradictory conclusion.

In trying to solve this contradiction, I noticed that I'd been reading about foods, not supplements.

For example, Michael Greger points out here that the study "Lancet 2004; 364: 1219-28" concluded that supplements of B-carotene vitamins A, C, and E seem to increase overall mortality. But the study "Int. J. Cancer: 131, E544-E554 (2012)" found that dietary antioxidant intake from plant foods is associated with a reduction of risk of stomach cancer.

I checked a dozen of the citations from this article and they were either about:

  • supplements
  • meta-analyses which don't specify whether dietary sources were supplements or foods
  • or I couldn't tell because the citation is a paywalled study and the contributor didn't quote anything from the study (does Wikipedia not have rules saying citations should be as verifiable as possible?)

Now, I know this is only a starting point. (Questions remain, such as: how do we know it was the antioxidants of those plants that is associated with reducing stomach cancer, and not the fiber or something else?) My question: Am I right in saying that this article doesn't actually show that antioxidants are useless or harmful, but rather that isolated antioxidant supplements are useless or harmful?

Thanks. Great floors (talk) 14:31, 2 March 2016 (UTC)

Featured article prose?

Diets containing foods high in antioxidants have been shown to improve health. However, in supplement form, the prevention of diseases such as cancer or coronary heart disease and the general promotion of health has not been confirmed experimentally. Trials including supplements of beta-carotene, vitamin A, and vitamin E singly or in different combinations found no effect on mortality or might increase it.

Is there much more like this? --John (talk) 19:20, 13 May 2016 (UTC)

The first sentence John quotes is uncited and, as best as I know, a mistake. No diet high in vitamins A-C-E, the only confirmed dietary antioxidants, has been shown to improve health. The section under Health effects, Relation to diet (which is poorly organized around intake of supplements, not food), does not discuss any diet with positive health effects. Neither is there any quantitative proof that a polyphenol-rich diet improves health: polyphenols are not accepted as dietary or in vivo antioxidants, as their bioavailability is poor, their fate in vivo cannot be measured and they are rapidly excreted, i.e., the body doesn't want them in the same way it does vitamin C (water soluble, widely dispersed in high retained content) and vitamins A and E (stored in lipids). --Zefr (talk) 19:44, 13 May 2016 (UTC)
Yes, the science is wrong and the writing sub-literate. If there is a lot like this in the article it had better be improved or we would need to consider reviewing its status. --John (talk) 19:50, 13 May 2016 (UTC)

hmm..i will try.. Garg himanshu (talk) 18:10, 15 May 2017 (UTC)

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Antioxidants for schizophrenia

Hello everybody, I got some feedback on my post about antioxidants as add-on treatment for schizophrenia (it was a table summarising evidence from a Cochrane review on the topic). In my opinion it did fit well into the "Drug candidate" section of the article and it complies with the pages high quality standard (Systematic review), but I was not aware of the fact that some people might disagree, sorry for this. Below you find the table, maybe we can discuss this: Lena08041993 (talk) 10:04, 20 July 2017 (UTC)

Add-on antioxidants for schizophrenia versus placebo[1]
Summary
Although 22 trials provide some limited evidence, the data are limited with short duration follow-up and mostly not relevant to clinicians or consumers. There is a need for larger trials with longer periods of follow-up and outcomes meaningful for people with schizophrenia.[1]
Good source. I think it can be summarized as "Evidence is insufficient as of 2016 to determine if antioxidants have an effect on schizophrenia".[4] Not convinced this needs a whole table.

References

  1. ^ a b Magalhães, P; Dean, O; Andreazza, A (2016). "Antioxidant treatments for schizophrenia". Cochrane Database of Systematic Reviews. 1: CD008919.pub2. doi:10.1002/14651858.CD008919.pub2.
--Doc James (talk · contribs · email) 10:02, 20 July 2017 (UTC)
Issues with the edit, in no order of importance: 1) it was entered in the section, "Drug candidates", but Gingko biloba (stated by the authors as one of the most promising agents) is neither a drug nor a proven antioxidant; 2) vitamins A and E are dietary antioxidants and are not typically discussed as "drugs"; 3) the antioxidant theory as a factor in schizophrenia has no systematic review or meta-analysis of high-quality clinical research to support it - the literature shows a lot of speculation, but this is primary research not meeting WP:MEDRS quality; 4) the authors stated, "However, overall, the trials suffered from a lack of real-world outcomes, such as clinical response, rates of relapse, quality of life, functioning, safety and satisfaction or acceptability of treatment", indicating overall a weak base of research and therefore a weak source; a review of the full article here, shows that for each of the agents studied, only 1-4 trials with small subject numbers and multiple study concerns were analyzed; 6) there is no justification to include a table for such vague or negative results that do not provide encyclopedic clarity. --Zefr (talk) 14:16, 20 July 2017 (UTC)
Agree, in an article like acupuncture where we have zealots we are forced to report on waste of time reviews like this, on things that have almost no chance of doing anything. There is no need to bother with this here. If we do summarize it there is no reason to give it much weight, as it is a yawner. Jytdog (talk) 03:33, 21 July 2017 (UTC)

Summary of health effects

Were moved out of the lead so I have moved them back. Doc James (talk · contribs · email) 02:57, 24 January 2018 (UTC)

Appropriate mentioning of terms: Anthocyanin

The terms that are thrown around in the discussion of antioxidants need to be prominently featured on the page. "Polyphenol" and "anthocyanin" are the ones I'm thinking of. The article I'm reading specifically mentions anthocyanins as fueling the craze to buy antioxidant foods like Pom Wonderful. Even if anthocyanins have been shown not to have any effect in humans, the confusion and resolution must be addressed. Bod (talk) 20:12, 10 June 2018 (UTC)

First, the predominant polyphenols in pomegranate peels and Pom Wonderful juice are ellagitannins. The current TV and display ads for Pom Wonderful pomegranate juice highlighting its supposed "antioxidant benefits" are a contradiction in several ways. 1) the ads appear to violate the FDA and FTC sanctions against the manufacturer for blatantly false claims of health benefits; those sanctions appear to remain in effect, yet Pom Wonderful has been running "antioxidant benefit" ads for several years. 2) on the Pom Wonderful website under Our Products/Learn More/Nutritional Facts, there are no dietary antioxidants (vitamins A-C-E) shown in significant content. 3) the prevailing scientific opinion on possible biological effects of ingested anthocyanins is based on the EFSA review which states that anthocyanins have not been confirmed as safe when added to foods beyond colorant amounts, indicating that for the EU and North America, food labels cannot contain statements about anthocyanins (or generally for any polyphenols which have no proven effects in vivo). It's not clear what could be said in the article beyond what we have now. --Zefr (talk) 21:07, 10 June 2018 (UTC)

This compound is a natural product in a subset of the human population which is synthesized by a very small number of bacterial species that can colonize the human GI tract; it's not produced by human enzymes, so it doesn't naturally occur in all humans, just those who are colonized by bacteria like Clostridium sporogenes. It's also an experimental drug that's currently being tested in clinical trials under the brand name "Oxigon"; it's not commercially available as a dietary supplement. Given its relationship to melatonin as an antioxidant, which is mentioned in this article, and the fact that it is a natural product in humans, should content on this compound be added? Seppi333 (Insert ) 02:30, 21 June 2018 (UTC)

Areas for Improvement

There are many areas in which this featured article can be improved. I am a new wikipedian but, in my opinion, this article would not pass a Featured Article review in this state. For example:

  • The first lede paragraph states: "[antioxidants are] natural chemicals found in [...] body tissue which are said to have beneficial health effects". This is not correct, as antioxidants are physiologically essential.
  • Also in the lede: "Antioxidant dietary supplements do not improve health nor are they effective in preventing diseases." Vitamin A improves health and is effective in preventing Vitamin A deficiency. More to the point, the essential nature of dietary antioxidants is not mentioned.
  • The second sentence of the lede is too narrow in scope, applying only to antioxidants in biology.
  • The second paragraph ("To balance the oxidative...) is awkward and somewhat unclear.
    • Are organisms using "glutathianine and enzymes" and "vitamins A, C, and E" mutually exclusive?
    • Does this apply to all plants and animals? Does this apply to other kingdoms of life such as fungi or bacteria?
  • More broadly, at times it is difficult to distinguish what parts of the article apply to antioxidants at large vs antioxidants in biology at large vs antioxidants in human biology.

I would be happy to help with these issues, but can see that this page is patrolled with vigilance and I have already been reverted once. Is anyone willing to step in and help address these issues? Perhaps user:Girth Summit, User:Project Osprey, user:Zefr can offer advice? Dag330 (talk) 19:42, 20 June 2018 (UTC)

Re: "Antioxidant dietary supplements do not improve health nor are they effective in preventing diseases." I attempted to clarify this in my last edit. Seppi333 (Insert ) 02:14, 21 June 2018 (UTC)
Hi Seppi333. I've put the sentence in the lead back to the way it was. My concern is that the alternative phrasing that you reinstated implies that it is the antioxidant properties of the vitamins in question that are beneficial. We undoubtedly need Vitamin A, but it's not because it is 'an antioxidant vitamin' - we specifically need Vitamin A. Diets rich in fruit and veg are likely to be good for you for a whole host of reasons - I don't think that we need to invoke the antioxidant properties of their constituents and tacitly suggest that they are the reason. Would be interested to hear other people's perspective.Girth Summit (talk) 07:51, 21 June 2018 (UTC)
Thank you user:Seppi333 and user:Girth Summit for your input! Girth, your comments about Vitamin A make perfect sense, thanks for explaining. Apologies also if my original post came off as rude. Which areas of the article do you think are most in need of attention? --Dag330 (talk) 03:34, 22 June 2018 (UTC)
I suppose it's fine. Seppi333 (Insert ) 23:44, 23 June 2018 (UTC)

First Sentence

I am proposing to clarify that an antioxidant is not a specific molecule, but a broad class of compounds, as follows:

An antioxidant is a class of organic compounds that inhibit the oxidation of other molecules.

Let me know what you all think of the change. --Dag330 (talk) 18:32, 21 June 2018 (UTC)

I made first sentence plural. IMO, vitamin A not an antioxidant, and anyway, preventing vitamin A deficiency is not an antioxidant function. The "or" in the second paragraph has nothing to do with mutually exclusive, rather, it is an attempt to distinguish between endogenously produced antioxidants and dietary. I do agree the article needs improving, but suggest you get down into the body rather than the lead. David notMD (talk) 02:19, 22 June 2018 (UTC)
Hi user:David notMD, Thanks for making the change and clarifying the role of Vitamin A. I will try to move on to edits to the article proper. Regarding the second paragraph, the phrase, "to balance the oxidative state," may need a little more context for lay readers. What areas of the body would you like to see improved? --Dag330 (talk) 04:45, 22 June 2018 (UTC)

Physical Exercise

What is written for physical exercise is an embarrassment. I suggest deleting it and starting anew. A PubMed search on antioxidant exercise, limited to only meta-analyses and systematic reviews, yielded dozens of citations, some of which appeared useful in this context. It is possible that the conclusion will be no benefit for exercise performance, or for post-exercise soreness/pain, but that is worth summarizing for the article. You may want to look at the Vitamin E, Vitamin C and Polyphenol antioxidant articles to see how these topics are being addressed and referenced David notMD (talk) 14:10, 22 June 2018 (UTC)

Thanks David notMD! I didn't know this was an area of research. Here are some of those links to systematic reviews:

References

  1. ^ Candia-Luján, Ramón; De Paz Fernández, José Antonio; Costa Moreira, Osvaldo (2014-10-05). "[Are antioxidant supplements effective in reducing delayed onset muscle soreness? A systematic review]". Nutricion Hospitalaria. 31 (1): 32–45. doi:10.3305/nh.2015.31.1.8171. ISSN 1699-5198. PMID 25561096.
  2. ^ Myburgh, Kathryn H. (2014-5). "Polyphenol supplementation: benefits for exercise performance or oxidative stress?". Sports Medicine (Auckland, N.Z.). 44 Suppl 1: S57–70. doi:10.1007/s40279-014-0151-4. ISSN 1179-2035. PMC 4008802. PMID 24791917. {{cite journal}}: Check date values in: |date= (help)
  3. ^ Camiletti-Moirón, D.; Aparicio, V. A.; Aranda, P.; Radak, Z. (2013-8). "Does exercise reduce brain oxidative stress? A systematic review". Scandinavian Journal of Medicine & Science in Sports. 23 (4): e202–212. doi:10.1111/sms.12065. ISSN 1600-0838. PMID 23495801. {{cite journal}}: Check date values in: |date= (help)
  4. ^ Sties, Sabrina Weiss; Andreato, Leonardo Vidal; de Carvalho, Tales; Gonzáles, Ana Inês; Angarten, Vitor Giatte; Ulbrich, Anderson Zampier; de Mara, Lourenço Sampaio; Netto, Almir Schmitt; da Silva, Edson Luiz (2018-3). "Influence of exercise on oxidative stress in patients with heart failure". Heart Failure Reviews. 23 (2): 225–235. doi:10.1007/s10741-018-9686-z. ISSN 1573-7322. PMID 29497889. {{cite journal}}: Check date values in: |date= (help)
  5. ^ Shields, Nora; Downs, Jenny; de Haan, Judy B.; Taylor, Nicholas F.; Torr, Jennifer; Fernhall, Bo; Kingsley, Michael; Mnatzaganian, George; Leonard, Helen (2018-6). "What effect does regular exercise have on oxidative stress in people with Down syndrome? A systematic review with meta-analyses". Journal of Science and Medicine in Sport. 21 (6): 596–603. doi:10.1016/j.jsams.2017.10.015. ISSN 1878-1861. PMID 29103914. {{cite journal}}: Check date values in: |date= (help)

I think these sources can get us on the right track. Maybe we can make this less of an "embarassment!" A search of the current article showed no mention of "exercise" at all. I am thinking this could be a new subsection between "drug candidates" and "adverse effects" called "relation to exercise." Let me know if I am missing something. --Dag330 (talk) 19:46, 22 June 2018 (UTC)

(edit conflict) None of these references is a MEDRS-quality review. Antioxidant biomarkers and assessment of exercise effects on oxidation status are not reliably measurable; I think we should avoid getting into guesswork and not discuss exercise at all. --Zefr (talk) 19:57, 22 June 2018 (UTC)
I would not throw it all out. However, for an article "Antioxidant," the effects of exercise on oxidative status not relevant. That means not your last three references. I suggest crafting text and references in your sandbox, then creating a new section here in Talk and copying that in. That will give me and Zefr and others something to comment. Alternative would be to drop it into the article, but then the whole thing might get reverted, and then to be hashed out in Talk anyway. David notMD (talk) 22:16, 22 June 2018 (UTC)
Thanks for the feedback. I will put something together in the sandbox and post a link here. --Dag330 (talk) 00:05, 23 June 2018 (UTC)

U.S. IOM definition of antioxidant

Perhaps a bit out of date (2000), but the Institute of Medicine definition is "A dietary antioxidant is a substance in foods that significantly decreases the adverse effect of reactive species, such as reactive oxygen and nitrogen species, on normal physiological functions in humans." Thie IOM DRI text went on to include vitamin C, vitamin E, selenium (functioning through selenoproteins) but excluded carotenoids. Did not address dietary phenols - or melatonin. I continue to be in favor of not including melatonin in this article. Endogenous quantities appear to function as a hormone. Orally consumed as a dietary supplement, even for the high end of what is sold (10 mg), evidence that it effects normal physiological function in humans via countering reactive species, i.e., free radicals, is not sufficient.

See also Giorgio M. Oxidative stress and the unfulfilled promises of antioxidant agents. Ecancermedicalscience. 2015 Jul 23;9:556. PMID 26284120 for lack of mention of melatonin. David notMD (talk) 18:08, 24 June 2018 (UTC)

I think the IOM definition of a dietary antioxidant is a good one; not too worried about the source being old (from 2000) in that context since basic definitions don't usually change all that much over time. But the list of antioxidants it mentions is more problematic given the advances in antioxidant biochemistry in the past 18 years. I also think it would be ideal to draw a consensus based on several good sources (recent reviews) rather than relying on any single source.
The Giorgio article is underwhelming for me, mostly because the journal itself is an obscure open-access journal and the article is written by a single author from an experimental oncology group in Milan; although he's credible, his slant and the focus of the article is from the oncology perspective, so failing to mention melatonin could just mean that it has limited applicability in oncology, not that it's biologically irrelevant.
I'm definitely OK with not mentioning melatonin in the article as it stands now. It isn't a noteworthy enough detail that melatonin has been reported by some sources to have antioxidant properties. The issue is whether its biological importance as an antioxidant is sufficient to warrant mentioning it alongside other well established biologically important antioxidants without violating WP:UNDUE, and I have seen no evidence to support that yet. IMO two conditions would have to be met before including it: (1) it would have to be featured in several reliable and fairly recent general review articles from superior sources as being among the list of biologically important antioxidants; (2) it should not be listed ahead of other important antioxidants that are not currently included, i.e., the section would have to be expanded to include several other compounds ahead of melatonin. Lastly, there's reason to be extra vigilant about this issue to avoid WP:PROMO with respect to melatonin supplement products. Seem reasonable? Rhode Island Red (talk) 20:49, 26 June 2018 (UTC)
Agreed. David notMD (talk) 02:36, 27 June 2018 (UTC)

'Adverse Effects' recent additions

184.55.99.202 - You indicated that you would be monitoring the page, so I want to explain why I reverted the changes you made. Claims about biomedical information need to be sourced in compliance with WP:MEDRS. The source you used for your main claim about adding onions and garlic to food was the 'NutraIngredients' website - it does not meet MEDRS. I also had some stylistic concerns about the writing - see WP:MOS, particularly WP:YOU. I don't think that the article is suggesting anywhere that legumes are to be avoided in any way; if you think there is an issue with the way this section is worded, please discuss here. Girth Summit (talk) 13:36, 29 June 2018 (UTC)

Melatonin?

On principle, I am not happy with any of this section. If endogenous synthesis is on the order of one mg/day, and not clear that any of its functions are as antioxidant, then evidence for administered melatonin at non-physiological amounts functioning as an antioxidant smacks of being promotional for dietary supplements. Keep in mind that a no-dose peak of 50-100 pg/ml is VERY different from the 10,000 to 15,000 pg/ml resulting from an oral dose of 10 mg. David notMD (talk) 22:31, 22 June 2018 (UTC)

I agree. The article includes sections on only 5 antioxidants, of which melatonin is one: (i.e., uric acid, vitamin C, glutathione, melatonin, and vitamin E). The list seems arbitrary; the title of the grouping "metabolites" makes no sense; and including melatonin in the list smacks of WP:UNDUE. Rhode Island Red (talk) 23:10, 22 June 2018 (UTC)
I support RIR's change to the section title and deletion of the melatonin sub-section. David notMD (talk) 02:13, 23 June 2018 (UTC)
Why is the use of melatonin as a dietary supplement even relevant to this discussion? I don't see why melatonin should not be included given that it's the most potent naturally occurring scavenger of hydroxyl radicals in humans. Moreover, HMDB ([5]) lists two of its biological roles as "Antioxidant" and "Free radical scavenger". Seppi333 (Insert ) 23:43, 23 June 2018 (UTC)
The supplement aspect isn't really the crux of the matter. The issue is that melatonin is lumped in with other widely recognized biologically important antioxidants in a list that ends up seeming randomly cobbled together. I see it as a two-fold issue of assigning undue weight to melatonin and WP:OR in randomly creating a list without any sources that include that same list. For the section in question, a list based on consensus from a few high quality recent review articles (and not cherry-picked) would be the way to go. The HMDB isn't useful as a source. For one thing, it's simply a metabolomics database rather than a refereed journal article or some other form of optimal WP:MEDRS that reviews biological antioxidants, and secondly, the database lists other compounds as antioxidants (e.g., beta-carotene, CoQ10, etc.) that are not included in the article's current list, which again takes us back to the WP:UNDUE issue (i.e., why include melatonin and not other antioxidants that are equally if not more important biologically). Rhode Island Red (talk) 00:10, 24 June 2018 (UTC)
I'm also rather skeptical about the claim that melatonin is the "most potent naturally occurring scavenger of hydroxyl radicals in humans". No source was presented to back that up and I'm pretty sure that it's not a consensus POV. It smacks of WP:PROMO. Rhode Island Red (talk) 00:15, 24 June 2018 (UTC)
Are you suggesting I’m trying to promote dietary supplement sales? Statements on talk pages don’t require citations. I was simply giving context. There’s no point in me citing that claim if it’s not going to be added to the article. Seppi333 (Insert ) 00:35, 24 June 2018 (UTC)
Also, what you’re calling WP:OR isn’t relevant to that policy. Lists can be cited piecewise; many tables cite rows/columns independently. Seppi333 (Insert ) 00:37, 24 June 2018 (UTC)
The argument you presented was that melatonin should be included (i.e., deleted text about melatonin restored) because, according to your assertion, “it's the most potent naturally occurring scavenger of hydroxyl radicals in humans”. While it’s technically true that no source is required to backup that statement on the talk page, it was the crux of your argument as to why melatonin should be included in the article. Thus, in the absence of reliable supporting sources (and in seeming defiance of reality), the argument carries no weight.
By citing WP:PROMO I wasn’t suggesting that you are hawking dietary supplements (are you?); if I were I would have cited WP:COI. Something can be promotional without it necessarily being a COI. Hope that makes things clearer.
As for the general argument that lists can be created piecemeal, I disagree. It’s akin to arguing for a list of US presidents that arbitrarily includes the names of some presidents but not others. I hope you can see that this would constitute WP:OR. Furthermore, general arguments about what may or may not be in other WP articles isn’t the issue. We have to be context specific, and in this context, there is no justification for elevating melatonin’s biological importance beyond what the collective sources (i.e., recent review articles on biologically important antioxidants) indicate.
To clarify further, I am not arguing that melatonin is not an antioxidant nor that it is not biologically relevant but rather that the details and choice of antioxidants to list seems to have been cobbled together somewhat randomly without relying on guidance from good sources. In other words, if a list is included, it should be a complete one. That would mean drawing a basic distinction between enzymatic and non-enzymatic antioxidants, and the former would include thioredoxin, lipoic acid, NAC, carotenoids, flavonoids, etc. It’s easy enough to resolve; it just will take a bit of extra work. Rhode Island Red (talk) 17:40, 24 June 2018 (UTC)
As an example, here is a fairly recent review article in a fairly decent journal that breaks down the broad classes of biologically important antioxidants as follows: A) Carotenoids, B) Cathecholamines, C) Phospholipids, D) Chalcones, E) Coumarins, F) Phenolic acids, G) Flavonoids, H) Lignans, and I) Tannins.[6] A few more sources like that would be useful in guiding the construction of the section in question. Rhode Island Red (talk) 17:50, 24 June 2018 (UTC)
Here is another example -- not exactly recent but the article gives a good idea of the broad range of biologically important antioxidants (however, it doesn't mention melatonin).[7] — Preceding unsigned comment added by Rhode Island Red (talkcontribs) Seppi_was_too_lazy_to_check_the_timestamp (UTC)

@Rhode Island Red: Sigh. I stopped editing for over a week after my last reply on this page, so I haven't been able to follow-up on this until today. These are refs from another article (I'm too lazy to do a pubmed search to find rate constants for other endogenous antioxidants right now):

  1. Primary source[1]
  2. IUPHAR review from 2016 on melatonin and its GPCR targets[2]
    • Outdated review from 2000 on melatonin – I only included this because it includes a table of rate constants for reactions between melatonin and hydroxyl radicals[3] – Full text: sci-hub.tw/10.1159/000025480

Here's a few reviews from a cursory Pubmed searches on "melatonin" and pairs of relevant terms (e.g., "mitochondria", "free radical", "antioxidant", etc.) in the title/abstract:

  1. Review from 2017 about melatonin transport across plasma/mitochondrial membranes and free radical scavenging[4] (there's a large amount of relevant text from the review in this citation's quote) – Full text: http://sci-hub.tw/10.1007%2Fs00018-017-2616-8
  2. A few other reviews that were published within the last 2 years;[5][6][7][8] the full text of each is on sci-hub. I only the quoted the abstracts here. The scope of all of these reviews pertains to the role of melatonin as a mitochondrial free radical scavenger
  3. Other recent review articles: Look here
Reflist for these citations
Reflist with long quotations/excerpts (emphasis added via bold/italics/underline/big/highlight)
  1. ^ Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA (July 1999). "Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid". J. Biol. Chem. 274 (31): 21937–21942. doi:10.1074/jbc.274.31.21937. PMID 10419516. [Indole-3-propionic acid (IPA)] has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. ... In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  2. ^ Jockers R, Delagrange P, Dubocovich ML, Markus RP, Renault N, Tosini G, Cecon E, Zlotos DP (September 2016). "Update on melatonin receptors: IUPHAR Review 20". British Journal of Pharmacology. 173 (18): 2702–25. doi:10.1111/bph.13536. PMC 4995287. PMID 27314810. Hence, one melatonin molecule and its associated metabolites could scavenge a large number of reactive species, and thus, the overall antioxidant capacity of melatonin is believed to be greater than that of other well‐known antioxidants, such as vitamin C and vitamin E, under in vitro or in vivo conditions (Gitto et al., 2001; Sharma and Haldar, 2006; Ortiz et al., 2013).
  3. ^ Reiter RJ, Tan DX, Osuna C, Gitto E (2000). "Actions of melatonin in the reduction of oxidative stress. A review". Journal of Biomedical Science. 7 (6): 444–58. doi:10.1159/000025480. PMID 11060493.
  4. ^ Mayo JC, Sainz RM, González-Menéndez P, Hevia D, Cernuda-Cernuda R (November 2017). "Melatonin transport into mitochondria". Cellular and Molecular Life Sciences : CMLS. 74 (21): 3927–3940. doi:10.1007/s00018-017-2616-8. PMID 28828619. [Excerpt from abstract]
    In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. ... The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where [melatonin] is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for [melatonin]'s protective actions. Melatonin's mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of [melatonin] functions reported to date. ... Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell. ...

    [Excerpts from review]
    Since then, many publications have reported either the ability of melatonin to scavenge free radicals thereby protecting cells from radicals insults; also, melatonin functions to increase antioxidant enzymes and then alter the redox signaling in different types of cells [108–110]. As a consequence of its antioxidant function, melatonin protects lipids, reducing lipid peroxidation and preserving the fluidity of the membranes [109, 111, 112]; as well as proteins, preserving them from oxidative degradation [113], and also nuclear and mitochondrial DNA from oxidative damage [36, 114, 115]. Melatonin's antioxidant activity is mediated by a cascade pathway that implies the reaction of melatonin with free radicals to form cyclic 3-hydroxymelatonin (C3-OHM) [116], as well as other kynuramines including N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) [117] and N1-acetyl-5-methoxykynuramine (AMK) [118], which, in turn, can react with other free radicals [119, 120]. In this way, each melatonin molecule can presumably scavenge up to 10 ROS/RNS in a reaction cascade through which the structurally different metabolites of melatonin also exhibit free radical scavenging activities. This scavenging cascade makes melatonin highly effective as a free radical scavenger and antioxidant [38, 121]. The discovery of some of these metabolites in vivo as potential biomarkers of melatonin's antioxidant activity in murine models by Tan and co-workers [116] confirmed that antioxidant activity might be a primary action; this has been proposed as the most ancient and evolutionary-conserved function of melatonin [37, 110]. Melatonin modulates intracellular redox signaling by increasing antioxidant cellular defense, either enzymatic or non-enzymatic [37, 122, 123] or by protecting key redox proteins such as Trx1 from oxidation [124]. In vitro, cell-free studies have shown that these melatonin-mediated direct scavenging reactions do not require any receptor [118, 125–127] though some of the antioxidant effects could also be receptor-mediated [128, 129]. As a result, free radical scavenging actions have been associated with many of the protective effects exerted by [melatonin] in different models, particularly as an oncostatic agent [100, 130–132] or in the nervous system [38, 133, 134]. ...
    Melatonin is known to protect against oxidative damage and preserve mitochondrial function in different culture cells and in in vivo models [160–163]. Melatonin has been considered by different authors as a critical modulator of mitochondrial integrity and physiology [164, 165] and this assumption has been proven in several mitochondrial-related disorders including murine models of Parkinson's disease [166–168]. This experimental evidence and the abovementioned data in prokaryotes and unicellular organisms identify mitochondria as a likely original site of melatonin synthesis, placing [melatonin] as a strategic molecule during the evolution of aerobic eukaryotes [139]. ...

    Concluding remarks
    Melatonin is a very effective agent in reducing ROS-derived consequences at both the cellular and the organism levels and in both cases mitochondria have been proposed as its major target. For many of these direct protective actions, the presence of the mitochondria themselves is required, so [melatonin] must be 'at the right time in the right place'. Direct passive diffusion has been the method classically used to explain the presence of melatonin within any subcellular organelle, but recent evidence from analytical chemistry suggests otherwise that either melatonin would be localized mainly at the membrane or the passive diffusion process itself would be highly limited. However, new transport systems, namely GLUT/SLC2A and PEPT1/2, have been shown to have an active role in facilitating melatonin transport across membranes. Furthermore, the localization of these two transport systems in the mitochondria strongly suggests the participation of both in mitochondrial transport of melatonin. The role of these and other transporters in different cell types as well as their use as potential therapeutic targets for different diseases should be further investigated.
  5. ^ Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre-Jimenez M, Qin L (October 2016). "Melatonin as an antioxidant: under promises but over delivers". Journal of Pineal Research. 61 (3): 253–278. doi:10.1111/jpi.12360. PMID 27500468. Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack).
  6. ^ Reiter RJ, Rosales-Corral S, Tan DX, Jou MJ, Galano A, Xu B (November 2017). "Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas". Cellular and Molecular Life Sciences : CMLS. 74 (21): 3863–3881. doi:10.1007/s00018-017-2609-7. PMID 28864909. Melatonin is an ancient antioxidant. After its initial development in bacteria, it has been retained throughout evolution such that it may be or may have been present in every species that have existed. Even though it has been maintained throughout evolution during the diversification of species, melatonin's chemical structure has never changed; thus, the melatonin present in currently living humans is identical to that present in cyanobacteria that have existed on Earth for billions of years. Melatonin in the systemic circulation of mammals quickly disappears from the blood presumably due to its uptake by cells, particularly when they are under high oxidative stress conditions. The measurement of the subcellular distribution of melatonin has shown that the concentration of this indole in the mitochondria greatly exceeds that in the blood. Melatonin presumably enters mitochondria through oligopeptide transporters, PEPT1, and PEPT2. Thus, melatonin is specifically targeted to the mitochondria where it seems to function as an apex antioxidant. In addition to being taken up from the circulation, melatonin may be produced in the mitochondria as well.
  7. ^ Sharafati-Chaleshtori R, Shirzad H, Rafieian-Kopaei M, Soltani A (2017). "Melatonin and human mitochondrial diseases". Journal of Research in Medical Sciences : the Official Journal of Isfahan University of Medical Sciences. 22: 2. doi:10.4103/1735-1995.199092. PMC 5361446. PMID 28400824. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ Manchester LC, Coto-Montes A, Boga JA, Andersen LP, Zhou Z, Galano A, Vriend J, Tan DX, Reiter RJ (November 2015). "Melatonin: an ancient molecule that makes oxygen metabolically tolerable". Journal of Pineal Research. 59 (4): 403–19. doi:10.1111/jpi.12267. PMID 26272235. Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant ... We hypothesize that the initial and primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5-3.2 billion years ago, was as an antioxidant. The evolution of melatonin as an antioxidant by this organism was necessary as photosynthesis is associated with the generation of toxic-free radicals. The other secondary functions of melatonin came about much later in evolution. We also surmise that mitochondria and chloroplasts may be primary sites of melatonin synthesis in all eukaryotic cells that possess these organelles. This prediction is made on the basis that mitochondria and chloroplasts of eukaryotes developed from purple nonsulfur bacteria (which also produce melatonin) and cyanobacteria when they were engulfed by early eukaryotes. Thus, we speculate that the melatonin-synthesizing actions of the engulfed bacteria were retained when these organelles became mitochondria and chloroplasts, respectively. That mitochondria are likely sites of melatonin formation is supported by the observation that this organelle contains high levels of melatonin that are not impacted by blood melatonin concentrations. Melatonin has a remarkable array of means by which it thwarts oxidative damage. It, as well as its metabolites, is differentially effective in scavenging a variety of reactive oxygen and reactive nitrogen species. Moreover, melatonin and its metabolites modulate a large number of antioxidative and pro-oxidative enzymes, leading to a reduction in oxidative damage. The actions of melatonin on radical metabolizing/producing enzymes may be mediated by the Keap1-Nrf2-ARE pathway. Beyond its direct free radical scavenging and indirect antioxidant effects, melatonin has a variety of physiological and metabolic advantages that may enhance its ability to limit oxidative stress.

I assume the combined significance of high concentrations of melatonin in mitochondria and its high potency for radical scavenging is obvious; if not, it's due to the fact that mitochondria are the site of OXPHOS, which generates free radicals. Free radicals travel very, very, very short distances before reacting with another molecule, so the utility of an endogenous antioxidant is determined by both its concentration in fluid compartments where free radicals are produced and its potency as a free radical scavenger.

Re: We have to be context specific, and in this context, there is no justification for elevating melatonin’s biological importance beyond what the collective sources (i.e., recent review articles on biologically important antioxidants) indicate. I agree. The vast majority of review articles on antioxidants are naturally going to focus on the body's oxidation–reduction system of enzymes, their oxidized substrates, and their reduced analogs which participate in a repeating cycle of redox reactions with free radicals and reducing enzymes. In other words, most are likely to only cover the set of recycled antioxidants and their metabolites that this article exclusively covers as of right now. Melatonin would not be included in any typical academic review of the oxidation-reduction system in mammalian cells given that it's not an enzymatically reduced/recycled antioxidant.

The minimal NPOV-scope of this article (within the context of WP:MCB) includes all antioxidant biomolecules for which there's significant coverage of a functionally important/necessary role as an antioxidant in some or all cell types; consequently, ignoring a high-potency free radical scavenging biomolecule that participates in redox reactions under physiological conditions within mitochondrial and other subcellular compartments simply because it isn't recycled like most others is – IMO – really asinine and a rather arbitrary decision rule; it's also a non-neutral POV given how much coverage there is of one such biomolecule (i.e., melatonin) in relevant review articles. Whether or not melatonin is a "high-potency free radical scavenging biomolecule that participates in redox reactions under physiological conditions within mitochondrial and subcellular compartments" depends entirely upon what fairly recent WP:SCIRS-quality reviews say about it; in contrast, it's a rather non-NPOV editorial decision to filter out content on certain aspects of the topic on which there's extensive coverage in recent RS. Seppi333 (Insert ) 23:06, 7 July 2018 (UTC)

Recycling isn't a common feature of the various compounds I referred to above, so that's a red herring if I'm not mistaken. Incidentally, it's interesting that the WP article on melatonin says: "Melatonin is a poor direct antioxidant, it is, however, a highly efficient direct free radical scavenger and indirect antioxidant due to its ability to stimulate antioxidant enzymes.[76][77][78]" If it is in fact a poor antioxidant, that would further argue for caution when considering including it here. My position still stands: if fairly recent and comprehensive reviews on biologically relevant antioxidants typically list melatonin, then it would be reasonable to include it in the list in this article with due weight relative to other antioxidant compounds mentioned in those same review articles. The issue is about context and due weight, which can't be addressed by simply cherry-picking selective articles exclusively about melatonin. Rhode Island Red (talk) 22:12, 8 July 2018 (UTC)

@Rhode Island Red: If all you want is a review on antioxidants that mention melatonin in the text but not the title, then all you need to do is run this pubmed search: [8]. Why you would want to cite an unfocused review is beyond me, but that satisfies what you asked for. Seppi333 (Insert ) 21:39, 10 July 2018 (UTC)

Conjectural and unencyclopedic. Not one of those sources is definitive about an antioxidant role for melatonin in vivo. --Zefr (talk) 21:51, 10 July 2018 (UTC)
If you say so. Your assertion about melatonin is conjecture; so is your conjecture about the sources being conjectural. I'll rewrite the melatonin section sometime in the next few days. Seppi333 (Insert ) 22:07, 10 July 2018 (UTC)
Feels like a game of 52 pickup. What are we supposed to glean from the PubMed article list? Is there any specific content in any of those articles that is relevant to what we've been discussing? To think that the link comes close to satisfying what I asked for suggests that maybe you didn't WP:LISTEN. Rhode Island Red (talk) 23:45, 10 July 2018 (UTC)

Also, I don't know why you're quoting a Wikipedia article as evidence of what melatonin is or isn't. Wikipedia is not a reliable source. As for antioxidant recycling, I haven't read this entire article, but every compound listed in the section on biomolecules (e.g., glutathione, Vitamin C, etc.) forms a reactive oxidized intermediate upon reaction with ROS/RNS which needs to be enzymatically reduced before regaining its function as an antioxidant. Antioxidants don't have an infinite reducing capacity. Seppi333 (Insert ) 21:57, 10 July 2018 (UTC)

Unless you mean to suggest that the details about melatonin (i.e., being a poor direct antioxidant) and the sources cited in the WP article are inaccurate/unreliable, then your point is moot. Kind of funny in a circular way to be editing here and arguing that WP is unreliable, aside from dodging a fairly obvious fact-based reliably sourced statement about melatonin being a poor antioxidant. Not sure what point you were trying to make about recycling. Is it related to any editorial suggestion/issue? Rhode Island Red (talk) 23:56, 10 July 2018 (UTC)
(edit conflict) Why don't I just WP:V-check the statement then and tell you what a "poor direct antioxidant" means (or delete it if it fails WP:V)? Seppi333 (Insert ) 00:20, 11 July 2018 (UTC)
@Rhode Island Red: I don't see the statement you quoted – "Melatonin is a poor direct antioxidant, it is, however, a highly efficient direct free radical scavenger and indirect antioxidant due to its ability to stimulate antioxidant enzymes.[76][77][78]" – anywhere in the melatonin article. Where did you see this? Nevermind, you deleted it since it failed to comply with content policy. I find it extremely amusing that you're using content+references that you deleted from another article for failing to adhere to content policy to suggest that it's a poor antioxidant. Seppi333 (Insert ) 00:27, 11 July 2018 (UTC)
5 general-purpose reviews on antioxidants/oxidative stress that cover melatonin
After going through the search above and the first page of a more refined search, I came across 5 general-purpose reviews: PMID 29731617, 27482198, 25992214, 20716905, 7737461 (ordered chronologically).
  • The 5th review compares melatonin to other endogenous antioxidants in the abstract (I didn't skim through the review since the abstract established notability).
  • The 4th includes a list of antioxidants by type according to a proposed classification system. This is probably the most useful review for context due to the utility of a classification system (NB: there's no official/widely-adopted "antioxidant classification system"; most of the sources I've read in the last week just call antioxidants "natural", "synthetic", or "dietary" and often conflate this terminology for compounds that belong to more than 1 of those groups - e.g., virtually all dietary antioxidants are "natural"). Seppi333 (Insert ) 00:19, 11 July 2018 (UTC)
  • The 3rd covers melatonin in its own level 2 section (i.e., a relatively large proportion of the review is dedicated exclusively to melatonin).
  • The 2nd is probably the least relevant since its coverage lacks context (i.e., it's covered in its own level 3 section under an irrelevant level 2 section) and it fails to mention anything about an effect upon mitochondria.
  • The 1st covers melatonin in a massive wall of text which spans the majority of the section under which it's located. I didn't bother reading reading it because it's a poorly formatted wall of text. I don't think the authors ever learned the purpose of a paragraph in writing.

The only reason I've listed reviews 5 here is that I was interested in reading how others put melatonin's antioxidant function into context. I don't really care as much about the inclusion of this content anymore since this article will no longer be FA-class in ~6 weeks. I'll write the section within the next few days nonetheless. I'd probably only cite at most 2 (more likely just 1 or none) of these 5 if I did because general-purpose reviews are generally useless for detailed topical coverage. Seppi333 (Insert ) 00:19, 11 July 2018 (UTC)

The search you employed was inconsistent with the strategy I was advising. To reiterate once again, the suggestion was to employ an unbiased approach by surveying a random sampling of fairly recent, high-quality general review articles on biologically important antioxidants and see (a) whether a majority/many/a consensus mention melatonin and (b) if so, weight that content relative to other antioxidants that are mentioned in those reviews so as not to create a problem with WP:UNDUE or WP:PROMO. The goal was not to search specifically for review articles that mention melatonin as a bio-antioxidant, which is the approach you took. Interestingly, that cherry-pick search generated a total of 28 hits;[9] however, specifically excluding melatonin from that same search yields 5220 hits.[10] In other words, general reviews on endogenous antioxidants that don’t include melatonin outnumber those that do by a 186:1 ratio. For review articles specifically, the ratio was 60:1 (851 vs 14); the gap widened to 74:1 (588 vs 8) when limited to reviews published in the last 10 years and rocketed to 127:1 (380 vs 3) when limited to reviews published in the past 5 years. That pretty much clinches the issue about WP:UNDUE. It also shows a trend of decreasing relative importance of melatonin over time.
Not that it’s really necessary to go further down the rabbit hole, but of the 5 articles highlighted from the list of 28, none appear to be particularly compelling or high quality. One was 23 years old, a couple mentioned melatonin in passing as a therapy (i.e., not as an endogenous biomolecule), and I gave up after that as it seemed fruitless – as though spaghetti was thrown at the wall to see if something would stick. Rhode Island Red (talk) 03:35, 11 July 2018 (UTC)
LOL. Quote the specific content policy on WP that backs up your notion that you need to implement an "unbiased search strategy" to determine content inclusion. Your argument is utter bullshit given that no one ever needs to show what fraction of high-quality reviews are relevant relative to a total number; the only reason I used that particular search string was to easily find general-purpose reviews that mentioned it. Seppi333 (Insert ) 03:55, 11 July 2018 (UTC)
I'm serious though, quote me the text in a content policy that you think (lol) actually supports your absurd assertion. Seppi333 (Insert ) 03:57, 11 July 2018 (UTC)
Obviously there is no policy that explicitly states that an “unbiased search strategy” should be used. It’s supported directly by basic commonsense and indirectly by various sections in WP:MEDRS, like WP:MEDSCI, which refers to summarizing scientific consensus (“Wikipedia policies on the neutral point of view and not publishing original research demand that we present prevailing medical or scientific consensus, which can be found in recent, authoritative review articles”); WP:MEDASSESS, which refers to evidence quality, and WP:MEDDATE, which specifies using up to date evidence.
To establish a consensus viewpoint, we obviously have to look at a broad sweep of recent review articles on the topic and see whether or not melatonin is typically included in such sources. Using the search parameters you laid out, it is clear that melatonin is typically not mentioned in recent reviews – a mere 3 reviews out of 380 published in the last 5 years mention it. As such, one could reasonably argue that WP:FRINGE applies. Anyhow, certainly can’t cherry-pick to make the point. Rhode Island Red (talk) 15:00, 11 July 2018 (UTC)
I agree that the endogenous antioxidants discussed here (or the members of any class) should be based on what reviews of the class highlight. To the extent this is just describing normal biochemistry or cell biology, this is not medicine per se but should be based on textbooks or reviews of antioxidant systems. I will do some looking. Jytdog (talk) 15:30, 11 July 2018 (UTC)
Great. I agree that some good recent textbooks would be useful for this exercise. The research literature, even the reviews, tends to be disease-specific, which isn't ideal, while the textbooks would approach antioxidant biochemistry more broadly. Rhode Island Red (talk) 15:58, 11 July 2018 (UTC)

FA Review

Given that (1) this article is a featured article which must constantly adhere to WP:FACR and (2) all of the reviews I've cited here which elaborate on the physiological function of melatonin as a mitochondrial antioxidant, I intend to nominate this article at WP:FAR to delist it as an FA if the physiological role of melatonin isn't mentioned. The article is clearly NOT comprehensive with a significant omission like this given both the relative notability and physiological significance of melatonin's antioxidant function.
As someone who has written two, here's some advice on how to write an featured article: when you want to comprehensively cover a topic, you don't look to general-purpose reviews for detailed information on one relatively general aspect of the topic, information on very specific subtopics, and certainly not for detailed information on those subtopics. Rather, you look to reviews that focus on that particular subtopic. Seppi333 (Insert ) 23:22, 7 July 2018 (UTC)
I would be fine with delisting this. It has fallen way out of date and is incomplete. Jytdog (talk) 00:01, 8 July 2018 (UTC)
Given that it was promoted 11 years ago, you're probably right. Nominating an article at FAR requires listing specific (not necessarily all) problems with the article in relation to the FA criteria though. Seppi333 (Insert ) 01:03, 8 July 2018 (UTC)
Due to the opposition to fixing the problem with WP:FACR, I've nominated this article for review at Wikipedia:Featured article review/Antioxidant/archive1. Since I don't expect anyone to be able to fix the problems in this article, it's going to end up being downgraded to B-class in 6 weeks. Seppi333 (Insert ) 22:36, 10 July 2018 (UTC)

At the very least, is anyone interested/willing to fix the issues that this article has with WP:LEAD? Seppi333 (Insert ) 01:06, 11 July 2018 (UTC)

Reviews on endogenous antioxidants from past 10 years: [1]PMID 26501252, 24580561, 21130758, 20232751, 26151600


Significant omissions:

  1. Transcriptional regulation of cellular antioxidant proteins / transcriptional responses by this system's master regulator: Nrf2[2][3]PMID 26151600 is listed in the nonspecific pubmed search from above ([1]); the textbook chapter[2] was listed on the first page of a google search of "endogenous antioxidants". I would've opposed this article at its FAC on the basis of this omission alone.
  2. Endogenous antioxidants, including melatonin (re: the previous section) – covered in a general review article (PMID 26501252) that was listed in the nonspecific pubmed search from above ([1])
  3. Adequate coverage of dietary antioxidants (specification of notable omissions pending assessment of the review abstracts listed in [12])

Seppi333 (Insert ) 01:29, 15 July 2018 (UTC)

References

  1. ^ a b c [1]
  2. ^ a b c Aguilar TA, Navarro BC, Pérez JA (December 2016). "Endogenous Antioxidants: A Review of their Role in Oxidative Stress". A Master Regulator of Oxidative Stress - The Transcription Factor Nrf2. InTechOpen. doi:10.5772/62743. ISBN 9789535128380. Retrieved 15 July 2018.
  3. ^ Vomund S, Schäfer A, Parnham MJ, Brüne B, von Knethen A (December 2017). "Nrf2, the Master Regulator of Anti-Oxidative Responses". International Journal of Molecular Sciences. 18 (12): 2772. doi:10.3390/ijms18122772. PMC 5751370. PMID 29261130.{{cite journal}}: CS1 maint: unflagged free DOI (link)

I'm certain others at WT:MCB would agree with my assertion that, ignoring all other issues in this article, the lack of coverage of this transcription factor (Nrf2) constitutes a lack of compliance with WP:FACR 1b. It's like failing to cover Antioxidant#Examples of bioactive antioxidant compounds or Antioxidant#Enzyme systems in this article.

If anyone is interested in taking on the challenge of preserving this article's FA-class rating, this needs to be added; ideally, the section on this should include a table analogous to the one for ΔFosB in Addiction#Reward sensitization with rows for Nrf2's transcriptional target genes which encode an antioxidant protein and columns that specify the target gene, effect on target expression, and something like target function or cellular effects. Seppi333 (Insert ) 01:48, 15 July 2018 (UTC)

Mentioning NRF2 doesn't seem unreasonable but the proposed table on gene targets sounds like it might be unnecessary duplication of material in the NRF2 article and excessive detail for this article. It would seem that a wikilink might suffice. Rhode Island Red (talk) 23:53, 15 July 2018 (UTC)
Nrf2#Target genes isn't a comprehensive list of its gene targets and, more relevant to this article, it's not a comprehensive list of its antioxidant gene targets. Conveying a gene target, effect on target expression, and the cellular effect of a change in target expression is more suited to a data table than prose, hence why I said that's the ideal format. Seppi333 (Insert ) 03:55, 17 July 2018 (UTC)
I'm not quite understanding. Are you proposing to have a list (i.e., a table) of NRF2 gene targets in this article that's more comprehensive than the one in the article on NRF2 (i.e., Nrf2#Target genes)? Bear in mind that NRF2 isn't an antioxidant but rather a regulator of antioxidant gene expression, which is why I opined that it was reasonable to mention it here but not to go overboard with detail. The proposed table sounds like excessive detail to me, at least for this article; perhaps not for the NRF2 article. Also, are there one or more good sources that include such a list or table or is this something that would be cobbled together using a number of primary sources? That could again be a WP:SYNTH issue. Rhode Island Red (talk) 15:45, 17 July 2018 (UTC)
This article isn’t comprehensive if it doesn’t explain why and how Nrf2 is a “master regulator” of cellular antioxidant responses to oxidative stress. Hence, this article’s coverage of Nrf2’s transcriptional targets needs to cover every gene target which encodes an antioxidant protein. Nrf2#Target genes lists just 7 groups of transcriptional targets and several of them aren’t even relevant to cellular redox activity.
I can’t imagine that a primary source would cover all of Nrf2’s transcriptional targets. There’s a textbook and a review article on Nrf2 cited in one of the sections above. Could start there. Could alternatively use a gene DB. I don’t intend to look for additional sources on this or write about it. Seppi333 (Insert ) 16:08, 17 July 2018 (UTC)
Again, I don't disagree with summarizing the why/how aspect but I am not convinced that this article necessarily needs to cover every gene target in a table with the level of detail proposed, given issues with excessive detail, synth, WP:OR etc. That might be more appropriate for the NRF2 article rather than this one; or at least, that would be the logical place to start, no?
To which textbook/review article on NRF2 were you referring? Creating the proposed table de novo from a gene database could be thorny with respect to WP:OR/WP:SYNTH/WP:MEDRS. But again, I'd say that the NRF2 article would be the best place to start with that before tackling it here. Rhode Island Red (talk) 22:13, 17 July 2018 (UTC)
Your argument seems no different than arguing that a drug's medical uses should be covered in the disease articles and its pharmacodynamics in its biomolecular targets' articles ... because too much detail and WP:OR/WP:SYNTH (I don't really follow you on that last part). Your argument about fleshing out Nrf2 first would be reasonable if it weren't for the fact that this article is (nominally) a featured article. In any event, there's only 1 other section on this page that mentions Nrf2, so search that word and you'll find it.
A table of Nrf2 gene targets and the encoded antioxidant proteins is just a "Table of antioxidant proteins". Examine how an actual FA-quality article on a set of proteins covers relevant proteins: Serpin#Human. Seppi333 (Insert ) 22:45, 17 July 2018 (UTC)
So far no one is contesting removal from FA, so ringing that alarm bell is not necessary. I agree however, that this page should discuss nrf2; the content here should probably just be a copy/paste of the lead of that page, with refs added, WP:SUMMARY/WP:SYNC. The place for detailed information about its functions and the various transduction pathways should be there, not here. Jytdog (talk) 22:26, 17 July 2018 (UTC)
To be fair, I'd be satisfied as long as the word "Nrf2" is somewhere in the article provided that it's demoted to a B-class article. An article with a in the top right corner, however, should go into far more detail on literally every major subtopic than would be expected of a typical Wikipedia article. I don't think the Nrf2 article will ever contain a comprehensive list of its targets given that it regulates over 1000 genes in mice (per [13]); it's just not feasible to cover them all in that article. Per PMID 23294312 (specifically, the supplemental file: [14]), there's only about 2-3 dozen antioxidant protein coding gene targets though. Seppi333 (Insert ) 19:44, 18 July 2018 (UTC)

@Rhode Island Red: I wrote my reply on my phone yesterday and wasn't prompted with an edit conflict. Frankly, I had no idea that Jytdog replied before me and wouldn't have removed it intentionally (that should be obvious given that he's agreeing with me about this article in the reply above). I don't know why you assumed the errant deletion was intentional, but I figure I'll just template you the same way you did me. Facepalm Facepalm Seppi333 (Insert ) 14:23, 18 July 2018 (UTC)

Apology accepted but do try to b more careful in the future. FYI, he was agreeing with me not you (i.e., include a very brief summary of NRF2 but not the table you proposed). How you could have come to the opposite conclusion suggests that you're either not paying attention of being WP:TE for the hell of it. Rhode Island Red (talk) 15:09, 18 July 2018 (UTC)
The only reason I created this section on the talk page is to emphasize that this article isn't FA-quality if Nrf2 isn't mentioned. If this article isn't an FA, I'm not particularly inclined to continue arguing about including a table of gene targets because its quality rating doesn't necessitate its inclusion. That's why I said he's agreeing with me. Seppi333 (Insert ) 18:54, 19 July 2018 (UTC)

Reverted edit of 04:53, 20 March 2022‎

The Harvard source is basically a summary of NIH’s publication on antioxidants. That source is in line with WP:MEDRS. (1)

There is an abundance of evidence in the literature supporting the fact that a diet rich in antioxidant-rich natural, plant-based foods has a positive effect on disease risk and all-cause mortality. At the same time, research has found no clear benefit of antioxidant supplements on disease risk.

It may seem perplexing to people, especially laypeople, that an antioxidant-rich diet and antioxidant supplementation have such discrepant effects on health outcomes. It might even misinform people about the merits of a diet rich in fruits and vegetables. The added text tries to elucidate why antioxidant supplements don’t work (of which the current article offers no explanation) and clearly reflects the current scientific consensus in this area. Based on this, the suggested edit is clearly an improvement of the article (however, as I come to think of it, it might not belong to the lede). 98.192.82.105 (talk) 03:25, 22 March 2022 (UTC)

Although a respected organization, the Harvard Chan School of Public Health is not a secondary MEDRS source, and does not carry equal weight to the NIH lay summary, a national government source meeting WP:MEDSCI. The NIH source already used in the article saying, "Research has shown that people who eat more vegetables and fruits have lower risks of several diseases; however, it is not clear whether these results are related to the amount of antioxidants in vegetables and fruits, to other components of these foods, to other factors in people’s diets, or to other lifestyle choices," has more detail and summarizes the state of science for this issue. Your statement above, "There is an abundance of evidence in the literature supporting the fact that a diet rich in antioxidant-rich natural, plant-based foods has a positive effect on disease risk and all-cause mortality", is not proof of dietary antioxidant effects, but merely a correlation sufficiently discussed in the article. Zefr (talk) 04:56, 22 March 2022 (UTC)
I believe we agree on most things here. I have never claimed that there was proof of dietary antioxidant effects and if that phrasing made it seem like I did that was not my intention. Clearly that is not what is stated in the aforementioned sources. Having said that, the phrasing in the NIH source is a lot more straightforward and less confusing than the phrasing in the current article. The article states that "there is still considerable debate on whether antioxidant-rich foods (...) have anti-disease activity". Contrast this with NIH's statement of "Vegetables and fruits are healthy foods and rich sources of antioxidants (...) Several decades of dietary research findings suggested that consuming greater amounts of antioxidant-rich foods might help to protect against diseases.") This statement clearly does not indicate causation just like you said, but it elucidates the fact the vegetables and fruits (which contain antioxidants) are healthy. Whether antioxidants have any role in fruits and vegetables' anti-disease effects is disputed. This should be stated more clearly, maybe in line with the phrasing in the NIH source, along with the hypothesized reasons of why study results show stark differences in the effectiveness between diets rich in vegetables and fruits and antioxidant supplementation. (e.g. "Most clinical studies of antioxidant supplements have not found them to provide substantial health benefits. Researchers have suggested several reasons for this (...) The beneficial health effects of a diet high in vegetables and fruits or other antioxidant-rich foods may actually be caused by other substances present in the same foods, other dietary factors, or other lifestyle choices rather than antioxidants" (...) "Differences in the chemical composition of antioxidants in foods versus those in supplements may influence their effects." (...) "The antioxidant supplements may not have been given for a long enough time to prevent chronic diseases"). Some of these hypotheses I might not personally agree with, but it is still important to mention at least a small variety of them until scientific consensus is reached in this area. 98.192.82.105 (talk) 00:12, 24 March 2022 (UTC)
As stated in the lede and other sections, the only established dietary antioxidants are vitamins A (from carotenes), C and E, which have science-based dietary recommendations and are sufficiently discussed, including the foods that contain them. Zefr (talk) 00:28, 24 March 2022 (UTC)
Yes, that is widely understood and not doubted by me or any of the sources I have quoted from. The relation to diet section that you previously mentioned is in agreement, however tersely phrased, with the NIH source as well. That section is useful and informative although I feel it could explain things in a little more detail, in line with the medical sources. That being said, I am fine with leaving the section and its topic as is without additional details if you are so adamant about keeping everything succinct. After all, it does convey the consensus. What I am advocating for is a short mention of the fact that "diets high in vegetables and fruits, which are good sources of antioxidants, have been found to be healthy", or something along these lines, in the lede. This is already mentioned in the body of the article and is one of the major points of the NIH source which summarizes the state of science well. The lede, in it current form, is somewhat misleading in the sense that it does not convey the scientific consensus in full detail. Current evidence does not support the fact that antioxidant supplementation has beneficial health effects but it also does not disprove the fact that diets rich in fruits and vegetables, which are rich sources of antioxidants, have beneficial effects. 98.192.82.105 (talk) 23:21, 24 March 2022 (UTC)
Noting that I support Zefr's amendment to my amendment - that looks reasonable. Girth Summit (blether) 18:37, 29 March 2022 (UTC)

Too much focus on biological/physiological effects?

As novice, I don't want to make any changes, but as this touches my research area, I would like to make suggestion: I wonder whether there is too much focus on biological/physiological effects. Antioxidants have quite important roles in industrial applications (as is mentioned very far down) - and this is still their main use (the Oxford English Dictionary doesn't mention other applications in their examples). Their popularity in particular in nutrition dates from much later and has resulted in a lot of controversial claims for health effects - this is all well documented here. But isn't this giving way too much emphasis to one aspect that might receive more popular interest but is not as relevant?

My suggestion would be to make the lede much more balanced (i.e. mention industrial/chemical uses more prominently) and move industrial uses to the top of the article. The biology of oxidative stress, ROS and RNS are interesting, but in my opinion they simply duplicate what can be found e.g. under Reactive oxygen species and could perhaps be more succinct. The discussion about dietary antioxidants beyond vitamins describes effects that are not really based on radical scavenging but other effects of individual compounds and could be directed to the individual compounds where this is (or could be) described much better and in much better detail. Ggck2 (talk) 18:53, 22 October 2022 (UTC)

WP:BEBOLD with WP:SCIRS reviews. Zefr (talk) 19:30, 22 October 2022 (UTC)
Thank you for the encouragement - I have tried to keep most of the references and rearranged. I assume it is easy to revert if it was too much.Ggck2 (talk) 07:38, 23 October 2022 (UTC)

Wiki Education assignment: CHEM 300

This article was the subject of a Wiki Education Foundation-supported course assignment, between 9 January 2023 and 28 April 2023. Further details are available on the course page. Student editor(s): Lapurete (article contribs).

— Assignment last updated by Lapurete (talk) 02:59, 22 January 2023 (UTC)

Bibliography

1. Vashishth, Amit; Ram, Sewa; Beniwal, Vikas. "Cereal phytases and their importance in improvement of micronutrients bioavailability". PubMed Central. 7 (1): 42

  • This is a journal article published by 3 Biotech, so this is a reliable source. It covers phytases in cereal and their importance as micronutrients, which is helpful information to refer to when discussing adverse effects of antioxidants.
The journal name is 3Biotech not PubMed Central.

2. Lewandowski, Marcin (Nov 22, 2017). "Nitroxides as Antioxidants and Anticancer Drugs". International Journal of molecular sciences. 18 (11)

  • This is a journal article from International Journal of molecular sciences, thus it comes from a reliable source. It discusses properties and applications of nitroxides as antioxidant and anticancer medications.

3. Singh, Kanchanlata; Bhori, Mustansir; Kasu, Yasar; Bhat, Ganapathi (Dec 19, 2017). "Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity – Exploring the armoury of obscurity". National Library of Medicine. 26 (2)

  • This article comes from a journal of National Library of Medicine, thus the source is reliable. This is useful information to add in "Health Research" section of the article, as some antioxidants are known to interfere with the function of anticancer medication.
The journal name is Saudi Pharmaceutical Journal, not National Library of Medicine.
PubMed Central is a publication digital database, not a journal, and National Library of Medicine is not a journal, but the National Library of Medicine on the campus of the US National Institutes of Health in Bethesda, Maryland.

4. Cory, Hannah; Passarelli, Simone; Szeto, John; Tamez, Martha; Mattei, Josiemer (Sep 21, 2018). "The Role of Polyphenols in Human Health and Food Systems: A Mini-Review". Frontiers in Nutrition

  • This article is a reliable source as it comes from a journal called "Frontiers in Nutrition"and covers the role of polyphenols in depth. This will help improve notability in terms of the relationship between polyphenols and disease treatment.

Lapurete (talk) 01:18, 12 March 2023 (UTC)

Numbers 1 and 3 are obscure, low-quality journals not indexed in Medline, so are not used on Wikipedia for medical content. Numbers 2 and 4 are highly speculative reports based on lab or preliminary research in MDPI and Frontiers media journals listed on WP:CITEWATCH as suspicious for predatory publishing practices, and are not usable as WP:MEDRS sources. Zefr (talk) 02:32, 12 March 2023 (UTC)

Improvement

To further improve this article, I think for the health research, plant-derived antioxidants can be added to explain their relation to diet. Biomolecules such as melatonin are also good example of antioxidants other than polyphenol. Also, I think in health research section, introducing a debate about whether antioxidants disrupt anticancer drugs and reduce efficacy of them or not would be good too. If it interferes, then one should mention a reason, including briefly how anticancer drugs work in human body. For the industrial uses, specifically how synthetic phenolic and aminic antioxidants cause potential human and environmental hazards could be mentioned.   Lapurete (talk) 01:57, 14 March 2023 (UTC)

These 3 molecules are the only antioxidants?

According to this article vitamin A, C, E, these 3 molecules are the only antioxidants that exist in the human diet. Seems a bit a silly doesn't it?

Alphalipoic acid, quercetin, curcumin, anthocyanins, etc, have in-vivo evidence of antioxidant activity. In fact the antioxidants found in blueberries are much stronger than ascorbic acid.

This misleading nonsense needs to be changed: "The only dietary antioxidants are vitamins A, C, and E, but the term antioxidant has also been applied to numerous other dietary compounds that only have antioxidant properties in vitro, with little evidence for antioxidant properties in vivo.[1]"

Also the source study [1] is withdrawn and doesn't exist!

65.94.168.132 (talk) 12:45, 17 March 2023 (UTC)

The theme is very broad, ill-defined, and infused with pseudoscience. Thousands of hydrocarbons can serve as antioxidants, for example. Please feel free to edit.--Smokefoot (talk) 14:43, 17 March 2023 (UTC)
There is a lot of misinformation in the public, such as referring to blueberries as a source of antioxidants (yes, some, but only for vitamin C in fresh berries; see nutrition table here), but not for anthocyanins or other polyphenols which are altered by digestion becoming small derivatives destined for rapid excretion, as discussed under "Health research-Relation to diet" and more completely in the Polyphenol article.
The comment made by the IP user, "Alphalipoic acid, quercetin, curcumin, anthocyanins, etc, have in-vivo evidence of antioxidant activity. In fact the antioxidants found in blueberries are much stronger than ascorbic acid" refers only to test tube experiments where supraphysiological doses of test compounds are used. There is no evidence that eating foods that contain these non-vitamin compounds have any antioxidant properties on human health.
If there was scientific evidence of physiological antioxidant effects in humans eating such foods, there would be dietary guidelines - like the Dietary Reference Intake - for each compound, and a food label guide - like the Daily Value - which do not exist, as they do for vitamins A-C-E. Zefr (talk) 17:48, 17 March 2023 (UTC)
"There is no evidence that eating foods that contain these non-vitamin compounds have any antioxidant properties on human health."??? are you serious
Example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694612/
"Curcumin has therefore been proven to be an antioxidant." :::https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664031/
"The authors concluded that short-term supplementation with a curcuminoid-piperine combination significantly improves oxidative and inflammatory status in patients with MetS. Curcuminoids could therefore be regarded as natural, safe, and effective CRP-lowering agents"
"Curcumin has been shown to improve systemic markers of oxidative stress [23]. There is evidence that it can increase serum activities of antioxidants such as superoxide dismutase (SOD) [24,25,26]. A recent systematic review and meta-analysis of randomized control data related to the efficacy of supplementation with purified curcuminoids on oxidative stress parameters—indicated a significant effect of curcuminoids supplementation on all investigated parameters of oxidative stress including plasma activities of SOD and catalase, as well as serum concentrations of glutathione peroxidase (GSH) and lipid peroxides [23]."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918523/
"In humans, curcumin bioavailability was increased by 2,000% at 45 minutes after co-administering curcumin orally with piperine, whereas in rats, it has been found that concomitant administration of piperine 20 mg/kg with curcumin 2 g/kg increased the serum concentration of curcumin by 154% for a short period of 1-2 hours post drug. The study shows that in the dosages used, piperine enhances the ser:um concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects [95]." 65.94.168.132 (talk) 22:08, 17 March 2023 (UTC)
Note: Some of the studies I listed above use purified curcumin extract, which I understand might not be considered as a "food source". Although it would be silly to claim that eating raw turmeric with a little bit of black pepper (which counts as "food") has absolutely no antioxidant effect compared to the extracts.
Our article on curcumin is up to date and accurate: "Laboratory and clinical research have not confirmed any medical use for curcumin. It is difficult to study because it is both unstable and poorly bioavailable. It is unlikely to produce useful leads for drug development." Both sources you provide are from MDPI journals which are unreliable as likely influenced by predatory publishing practices. They are not acceptable as WP:MEDRS sources. Further, they do not prove antioxidant efficacy in humans consuming curcumin (a result for which no good sources exist). Zefr (talk) 01:06, 18 March 2023 (UTC)
Here's a study on humans eating blueberries:
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/effect-of-wild-blueberry-vaccinium-angustifolium-consumption-on-postprandial-serum-antioxidant-status-in-human-subjects/DB819F101A80A1125FC6AE871A48B84B
"The aim of the present study was to determine whether the consumption of wild blueberries (Vaccinium angustifolium), a concentrated source of non-nutritive antioxidant phytochemicals, would enhance postprandial serum antioxidant status in healthy human subjects."
"Serum antioxidant status was determined using the oxygen radical absorbance capacity (ORAC) assay and the total antioxidant status (TAS) assay. The wild-blueberry treatment was associated with a significant treatment effect as determined by the ORAC assay (water-soluble fraction ORACperchloric acid (PCA), P=0·04). Significant increases in serum antioxidant status above the controls were observed at 1 h (ORACPCA (8·5 % greater), P=0·02; TAS (4·5 % greater), P=0·05), and 4 h (ORACtotal (15·0 % greater), P=0·009; ORACacetone (16·0 % greater), P=0·007) post-consumption of the high-fat meal. In conclusion, the consumption of wild blueberries, a food source with high in vitro antioxidant properties, is associated with a diet-induced increase in ex vivo serum antioxidant status. It has been suggested that increasing the antioxidant status of serum may result in the reduced risk of many chronic degenerative diseases." 65.94.168.132 (talk) 22:30, 17 March 2023 (UTC)
Note: You might complain for the above blueberry study that it's just the Vitamin C in the berries that's responsible for the effect.
I have full access to the paper, and the authors added this:
"The design of the present study does not allow us to determine what compounds within the blueberry are responsible for the increase in serum antioxidant status observed in this trial. However, it is most likely that anthocyanins within the blueberry are the major contributing phenolic compounds responsible for this effect. Anthocyanins comprise the highest concentration of all phenolic subgroups in the blueberry (Wang & Lin, 2000). Previous research has determined that the ORAC value of the blueberry corre- lates more strongly with anthocyanins than with total phenolics in the berry (Mazza & Oomah, 2000). Furthermore, the antioxidant properties of anthocyanins have been validated using other systems of oxidation such as their ability to prevent LDL oxidation in vitro (Laplaud et al. 1997). Therefore, although we have not proven directly that anthocyanins are responsible for the observed antioxidant effect in the blueberry-treatment group, studies have shown that the in vitro antioxidant properties of wild blueberries are mainly a result of their high concentration of anthocyanins (along with other phenolics) and not their concentrations of antioxidant vitamins, minerals or fibre (Bushway et al. 1983; Prior et al. 1998; Kalt et al. 1999)." 65.94.168.132 (talk) 22:53, 17 March 2023 (UTC)
This lab study from 16 years ago is not a MEDRS review. In 2007, it was just conjecture about the fate of anthocyanins in vivo. ORAC is a dismissed measurement that was used only to estimate in vitro antioxidant status, as stated in the article here. Zefr (talk) 01:05, 18 March 2023 (UTC)
The problem with many of these claims is that while compounds might be antioxidants in vivo, they are not once they are absorbed as they are metabolised. For example (-)-epicatechin (which has been labelled antioxidant before) has no free catechol group in the human body as it becomes methylated (see e.g. [15]). The same applies to most other compounds. Curcumin is also metabolised by [[16]]. Here [17] is an extensive review of the metabolism of the compounds you mentioned.
ORAC (and similar measures like FRAP) are useful to get an overall estimate of polyphenol content (as many polyphenols have catechol groups), but that does not mean that they act as antioxidant in vivo. The scientific consensus at least in the field of polyphenols is largely what has been written almost 20 years ago [18].
One can of course debate whether the activation of antioxidant systems in the body would justify calling compounds antioxidants, but the consensus is that this is not appropriate.
Ggck2 (talk) 20:45, 18 March 2023 (UTC)

Wiki Education assignment: CHEM 300

This article was the subject of a Wiki Education Foundation-supported course assignment, between 9 January 2023 and 28 April 2023. Further details are available on the course page. Student editor(s): Lapurete (article contribs). Peer reviewers: R123J456.

— Assignment last updated by RS UBC800 (talk) 21:15, 2 April 2023 (UTC)

editing

I have edited some parts of this article. I posted the draft in my sandbox, and my edit falls into the health research section. I want some feedback from Wikipedia users about my edit on that section, especially about chemo/radiation therapy, anticancer drugs, and melatonin. I focused on writing more about free radical formation rather than mentioning much about medicinal content, but I am not so sure. Would you guys mind reading it in my sandbox and giving me some feedback? Lapurete (talk) 07:04, 7 April 2023 (UTC)

Most sources look weak and may be contested on Wikipedia. Saudi or Turkish journal? The one ref that stands out is Nature Reviews Drug Discovery. The Nature series are prestigious (competitive, peer reviewed, edited by globally savvy staff) journal and a WP:SECONDARY source. You could probably just rely on this one source to complete your homework assignment. The opinions expressed are just that, opinions by one editor.--Smokefoot (talk) 12:35, 7 April 2023 (UTC)

Results

Here are the new refs from this hard working student's homework:

--Smokefoot (talk) 21:54, 15 April 2023 (UTC)