Talk:Thiamine/GA1

GA Review

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Reviewer: Mertbiol (talk · contribs) 16:00, 1 October 2022 (UTC)

I will take on this review. Here are some comments on the first part of the article. I will add more in due course. Best wishes Mertbiol (talk) 16:00, 1 October 2022 (UTC)

Lead section

• I suggest changing "which" to "that" in the first sentence.
• I suggest moving "Thiamine is required for metabolism including that of glucose, amino acids, and lipids." so that it becomes the third sentence of this section.
• I suggest rephrasing "Thiamine is required for metabolism..." to "Phosphorylated forms of thiamine are required for metabolism..."
• I suggest starting a new paragraph with "Food sources of thiamine include..."

Infobox

• I suggest rephrasing the figure caption so that it reads "Skeletal formula and ball-and-stick model of the thiamine cation".
• Please link "cation" to Ion#Anions_and_cations.

Definition

• I suggest rephrasing the first sentence so that it reads "Thiamine is one of the B vitamins and is also known as vitamin B₁."
• I know what you are trying to say when you write " thiamine is only one chemical compound", but you may confuse lay readers later in the page, when you discuss the different phosphorylated forms of thiamine.
• Please link folate, vitamin B6 and vitamer.
• I suggest moving the content of the "Chemistry" section to this section. (Please merge the content so that discussion of thermal stability and the chloride salt are not repeated.)

Deficiency

• Would "symptoms" be better than "signs" in the first sentence? Or perhaps rephrase as "Thiamine deficiency may be accompanied by malaise, weight loss, irritability and confusion."
• Would the second sentence be better placed as the first?
• Please avoid repeating "Thiamine deficiency" in the first two sentences.
• "In Western countries, chronic alcoholism is a secondary cause." Secondary cause of what?
• Please link HIV/AIDS and diabetes.

Chemistry

• Please combine this section with the "Definition" section.

Functions

• I suggest renaming this section to "Biological functions"
• Some of this section is difficult to read for non-specialists. It might be worth trying to reformat some of this material into a table.
• Would it be possible to provide skeletal formulae for the phosphorylated forms? Perhaps @Michael D. Turnbull: might be able to help out here?

 Done. Gallery could be tweaked to make the diagrams more consistent. For now I've just taken the images from the respective articles. Alternative versions would be easy to draw: or could just use ROP(=O)(OH)₂ type of drawing, although readers may be less confused with the full images. Mike Turnbull (talk) 19:43, 1 October 2022 (UTC)

Medical uses

• Please remove the subsection heading "Prenatal supplementation".
• Please link fetus, placenta.
• Please link "third trimester" to Pregnancy#Third_trimester, "lactating" to lactation, "mitochondrial membrane" to mitochondrion and "synaptosomal membrane" to synaptosome.
• Would "synaptic membrane" be better than "synaptosomal membrane"?
• I suggest rephrasing "It has also been suggested that thiamine deficiency plays a role in the poor development of the infant brain that can lead to sudden infant death syndrome (SIDS)" to read "It has also been suggested that thiamine deficiency hinders brain development in infants and may be a cause of sudden infant death syndrome (SIDS)" or similar.

Dietary recommendations

• Please decide if you are going to abbreviate United States as "US" or "U.S."
• Please link National Academy of Medicine.
• I suggest linking "Reference Daily Intake" to Reference Daily Intake or to Dietary Reference Intake.
• Please expand the acronym "IOM" and link to National Academy of Medicine. Why is "IOM" used and not "NAM"?
• Please change "In the case of Riboflavin" to read "In the case of Thiamine".
• Please link Dietary Reference Intake and remove "(DRIs)", which is not used elsewhere.
• Please change "The EFSA" to "EFSA".

Table

• Please move the table up to the top of the Dietary recommendations section.
• Please change "United States" to identify the body responsible for determining the RDAs (I presume that this is the US National Academy of Medicine).
• Please use a small "i" for "intake" in "Adequate Intake".
• I suggest removing the "tolerable upper intake" column and adding a note to the bottom of the table to say "neither NAM nor EFSA have determined the tolerable upper intake for thiamine" or similar.

Safety

• I suggest rewriting "Rarely, adverse side effects have been reported..." as "There are rare reports of adverse side effects..."

Labeling

• Please decide if you are going to abbreviate United States as "US" or "U.S.".
• Please add a comma after "For US food and dietary supplement labeling purposes".
• I suggest rephrasing "For thiamine labeling purposes 100% of the Daily Value was 1.5 mg, but as of May 27, 2016, it was revised to 1.2 mg to bring it into agreement with the RDA." to "Since May 27, 2016, the Daily Value has been 1.2 mg, in line with the RDA."

Sources

• Please delete "To aid with adequate micronutrient intake, pregnant women are often advised to take a daily prenatal multivitamin."
• Please delete "among different vitamins" from "While micronutrient compositions vary among different vitamins, a typical daily prenatal vitamin product contains around 1.5 mg of thiamine."

Antagonists

• Please rename this subsection to "Degredation"
• I suggest moving this subsection to either the "Absorption, metabolism and excretion" or to the "Synthesis" section.

Food fortification

• I suggest combining this subsection with the first part of the "Sources" section.

I will add further comments in due course. Best wishes Mertbiol (talk) 12:05, 2 October 2022 (UTC)

Status of the review

Hi @David notMD: I am a little concerned that you have not responded to any of the points raised above or edited the Thiamine article since I started the review. I appreciate that you have been unwell with COVID, but since 1 October you have made over 500 edits to other pages on Wikipedia. Could you let me know where things stand please? If you are unable to work on the Thiamine article, then I will have to fail the review. Best wishes Mertbiol (talk) 17:34, 7 November 2022 (UTC)

As I mentioned on David's Talk Page, I'm happy to work through the suggestions made, if he can't do so for any reason. Mike Turnbull (talk) 18:25, 7 November 2022 (UTC)

Mertbiol and Michael D. Turnbull - due to many circumstances, I have not returned to this task. I welcome Mike's offer to attack the suggestions made so far. I may be able to join the process, but do not promise. My non-response to date should not be taken to infer that I disagreed with any of the suggestions. David notMD (talk) 15:42, 8 November 2022 (UTC)

Hi @David notMD: I'm sorry that you're not able to continue to work on the article. In that case I would like to take up Michael D. Turnbull's offer to respond the review. Perhaps I can let Mike work through the article and my comments, and when he's ready, I can provide more feedback? Best wishes Mertbiol (talk) 18:18, 8 November 2022 (UTC)

Yes, I'll start on that tomorrow and look forward to dealing with any further suggestions. Mike Turnbull (talk) 18:29, 8 November 2022 (UTC)

@Mertbiol, @David notMD All done, I think, except to remove column from table, which I'm not technically confident enough to do! Please check my edits and make any new suggestions. Mike Turnbull (talk) 17:15, 9 November 2022 (UTC)

Thanks @Michael D. Turnbull: I'll have a thorough look through the article tomorrow. Best wishes, Mertbiol (talk) 20:28, 9 November 2022 (UTC)

Further feedback

Lead section

• I suggest changing "Thiamine and some of its phosphorylated forms are required for metabolism including that of glucose, amino acids, and lipids" to "In the body, phosphorylated forms of thiamine are required for some metabolic reactions, including the breakdown of glucose and amino acids." (Lipids are not mentioned in the rest of the article, so should be removed from the lead section.)
• Please change "Grain processing removes much of the thiamine content…" to "Grain processing removes much of the vitamin content…" or similar, to avoid repetition of "thiamine".
• Please change "Other uses include the treatment..." to "They are also used to treat..."

Definition

• I suggest deleting "Unlike other B vitamins including folate and vitamin B6, which occur in several chemically related forms known as vitamers".
• Please change "Within the body..." to "In the body..."
• I suggest deleting "The amino group can form additional salts with further acids."
• Please change "It is stable at acidic pH…" to "Thiamine is stable at acidic pH…".

Biological functions

• This is beyond the scope of a GA review, but I wonder if it would be possible to modify the images of the skeletal formulae of the thiamine derivatives, so that the thiamine moiety and the phosphates are highlighted in different colours? (I’m thinking perhaps a yellow circle under the phosphates and then to use another colour under the thiamine?)
• Could you redraw the ThMP, ThDP and AdThP so that the ionisation of the phosphate groups is the same please? Perhaps use the ThTPP drawing as the starting point, so that the thiamine moiety is in the same orientation and position in all five images?
• Please change "are all important in carbohydrate metabolism" to "are important in carbohydrate metabolism".
• Please change "which is a major form of energy for the cell" to "which is the major energy currency of the cell" or similar.
• Please link acetylcholine.
• Please rephrase: "ThTP was long considered a specific neuroactive form of thiamine, playing a role in chloride channels in the neurons of mammals and other animals, although this is not completely understood.[19] However, it was shown that ThTP exists in bacteria, fungi, plants and animals suggesting a much more general cellular role. In particular in E. coli, it seems to play a role in response to amino acid starvation." to "ThTP was long considered a neurone-specific form of thiamine. It is implicated in chloride channel activation in mammals and other animals, although its precise role is not completely understood. Recently, ThTP has been found in bacteria, fungi and plants, suggesting that it also has a much more general cellular role. In E. coli, it is implicated in the response to amino acid starvation." or similar.
• Please delink Escherichia coli in the AThTp section.

Medical uses

• "Pregnant women require more thiamine..." More thiamine than who? This sentence might be better rephrased as "During pregnancy, thiamine is sent to the fetus via the placenta. Pregnant women have a greater requirement for the vitamin than other adults, especially during the third trimester."
• Please switch the order of the current second and third sentences, so that the sentences about thiamine in pregnancy is together.

Dietary recommendations

• I will alter the table to remove the third column at the end of the GA review.
• Please delete "As for safety".
• Please delete "Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes." as this is not specific to thiamine and not appear to be required for a reader to understand the data.
• I suggest that the lack of a UL from both the US National Academy of Medicine and the European Food Safety Authority is moved to form a separate, third paragraph.

Sources

• "and is important in maintaining plant health" – this does not appear to fit in this section. I suggest deleting it or moving it to the Biological Functions section.
• Please link "Indian government" to Government of India

Synthesis

• Please change "…and then combined to form…" to "…and are then combined to form…".
• I suggest changing "These are assembled by the action..." to "The ring is assembled by..."
• Please change "...pyrophosphate derivative of the phosphomethylpyrimidine..." to "...pyrophosphate derivative of phosphomethylpyrimidine..."
• I suggest changing "...the only riboswitch identified.." to "...the only known riboswitch found..."
• Please split the sentence "The ethoxy group was then converted..." into two, so that "ready for the final stage..." starts the second sentence as "In the final stage...".
• I suggest rephrasing "The 1936 laboratory-scale synthesis was developed by Merck & Co., allowing them to manufacture thiamine in Rahway in 1937." to "Merck & Co. adapted the 1936 laboratory-scale synthesis method, allowing them to begin large-scale manufacture of thiamine in Rahway in 1937." or similar.

Stopping here for now

I will aim to provide more feedback on the rest of the article on Saturday. Best wishes Mertbiol (talk) 21:04, 10 November 2022 (UTC)

Thanks, Mertbiol. I'll tackle these suggestions but probably not until Sunday, which will give you time to add anything more. While doing the first batch of changes, it occurred to me that the article says very little on how ThDP acts as a coenzyme. As an organic chemist, this seems quite important to me. It is covered, including poor diagrams, at Thiamine pyrophosphate#Reaction mechanisms. Should some of that be included here, especially the ability to form a ylide, which is crucial? I agree with you that the gallery of structures needs to be improved and I'll try out some colour schemes as you suggest. Mike Turnbull (talk) 11:13, 11 November 2022 (UTC)

Absorption, metabolism and excretion

• I think the distinction between pre- and post-consumption degradation is not very helpful, so I suggest renaming the current first subsection to "degradation".

Degradation prior to consumption

• The writing in this subsection doesn't really seem to flow very well – there are too many short sentences. The second half is unreferenced, so it may need a bit of a rethink. (It may be worth combining the two subsections.)
• I suggest rephrasing "Sulfites, which are added to foods usually as a preservative..." to "Sulfites, added to foods as a preservative..."
• I suggest deleting "in the structure" – anyone who understands an "attack at the methylene bridge" will know that this is a molecular reaction and "in the structure" does not help clarify for those that don't!
• I suggest deleting "Some thiaminases are produced by bacteria."
• Please link "acidotic conditions" to acidosis and "reduce" to redox.
• I suggest rephrasing "can have thiamine-antagonistic activities" to "can reduce the uptake of thiamine" or similar.
• Does the action degradation of thiamine by thiaminase in the rumen not take place after consumption?

After consumption

• I suggest renaming this subsection to "absorption and excretion" and then making this the first subsection of this section.
• I suggest rephrasing the first two sentences of this section to read "Some phenols found in plants, including caffeic acid, chlorogenic acid and tannic acid, degrade thiamine."
• I am not clear whether the discussion of phenols in plants relates to degradation of thiamine in the plant or to its degradation in the human body. (If the former, then this may not belong in the "after consumption" subsection.)
• I suggest rephrasing the first sentence of the current first paragraph to read "In the upper small intestine, thiamine phosphate esters released from food are hydrolyzed by alkaline phosphatase enzymes." or similar.
• I suggest switching the order of the third and fourth sentences of the second paragraph, so that discussion of active transport of thiamine is in one place.
• I suggest moving the paragraph beginning "The majority of thiamine in serum..." to a new subsection entitled "circulation in the blood and uptake by cells" or similar.
• Please change "coded by the genes SLC19A2 and SLC19A3" to "encoded by the genes SLC19A2 and SLC19A3".
• Please change "soluble thiamine transporter that is dependent on Na+" to " Na+-dependent transporter".

History

• Please delete "in 1910" from the first sentence.
• Please replace, "Prior to that..." with "Before its isolation..."
• Please delete "a disease" from the second sentence and the quotation marks around "beriberi".
• Navy should probably have a capital "N" in "Japanese navy".
• Please change "hypothesized" to "proposed" or "suggested".
• Please delete "substances" from "unknown substances at the time."
• Please change "so expensive a program" to "an expensive program" or "such an expensive program".
• Please split the final sentence of the second paragraph in two.
• Please link "Dutch Indies" to Dutch East Indies.
• Please link starch.
• I suggest rephrasing "He described the compound is not only anti beriberi factor but also essential nutrition to human in the paper" to "He described the compound as not only an anti-beriberi factor, but also as being essential to human nutrition."
• "However" should be preceded either by a full stop or a semi-colon.
• Please link "Oxford" to Oxford University.
• I suggest changing "introduced thiamine-deprived pigeons as a model for understanding how thiamine deficiency can lead to the pathological-physiological symptoms..." to "used pigeons to understand how thiamine deficiency results in the pathological-physiological symptoms..." or similar.
• I suggest changing "Indeed, feeding the pigeons upon polished rice leads to an easily recognizable behavior of head retraction, a condition called opisthotonos" to "Pigeons fed exclusively on polished rice developed opisthotonos, a condition characterized by head retraction."
• I am not sure how helpful it is to use the term "biological lesion" as it is not commonly used by research scientists today.
• Please correct the spelling of "Lohmann" - it has two "n"s!
• Please correct the spelling of "oxidative"
• I suggest rephrasing the final sentence of the final paragraph to read "In 1937, Lohmann and Schuster showed that the diphosphorylated thiamine derivative (thiamine diphosphate, ThDP) was a cofactor required for the oxidative decarboxylation of pyruvate."

Research

• This section is very short and doesn't seem to fit where it is. It might be better to move it to the "Synthesis" section, possibly as a new subsection called "Synthetic analogs" or similar.

Stopping here after the second read through

That's all for now. Best wishes Mertbiol (talk) 11:52, 12 November 2022 (UTC)

@Mertbiol All now done (except column removal from table), including updating the chemical diagrams and adding a bit about the ylide form. I think it would be helpful if you and David notMD could read through and reappraise. Mike Turnbull (talk) 13:39, 15 November 2022 (UTC)

Thanks @Mike Turnbull. I have removed the third column from the table, tweaked the layout of the images and given the text a light copyedit. I have also used thiamine pyrophosphate (TPP) in preference to thiamine diphosphate (ThDP) as this seems to be the preferred usage in the sources and on wikipedia. Perhaps both you and @David notMD: could take a quick look.

Assuming that all is well, I will read through for a final time tomorrow (Wednesday) evening. Best wishes Mertbiol (talk) 18:35, 15 November 2022 (UTC)

Yes, that ThDP versus TPP is a pain. I was inclined to use the former in this article only because it gives more internal consistency (ThMP, ThDP and ThTP) for the three derivatives. As you say, the pesky biochemists seem to prefer TPP, so let's go with that. Mike Turnbull (talk) 18:42, 15 November 2022 (UTC)

A new IP editor has recently attempted to fix one of my edits but seems to have ended up with duplicated content at Sources/Thiamin [sic] Antagonists and Absorption, metabolism and excretion / Degradation. I've left a message on their Talk Page asking them to engage with us here to reach a consensus on what the article should contain, as it currently seems incorrect to stay as-is. I moved the antagonist subsection to the degradation one following Mertbiol's suggestion here at Talk:Thiamine/GA1#Antagonists. Mike Turnbull (talk) 12:46, 16 November 2022 (UTC)

Hi @Mike Turnbull. Thanks for your message. I’ve had a look at the anonymous editor's changes. It seems to me that there are three separate issues with their edits:

• Use of "Thiamin" instead of "Thiamine" — The spelling has been discussed on the talk page and the clear consensus is for the latter to be used here on Wikipedia. It seems to me that this consensus reflects the overwhelming (but not universal) trend in the recent literature to use the "Thiamine" spelling.
• Use of the terms "anti-thiamine factors" and "thiamine antagonists" as synonyms. I have had a quick look at the recent literature and, from my reading, it is clear that these two terms do not refer to the same phenomenon. An antagonist is a molecule that competes with an agonist (in this case thiamine) for a receptor binding site whereas an "anti-thiamine factor" is responsible for the biochemical degradation of thiamine. My feeling is that the version of the article before the anonymous editor's changes reflected this position very clearly. I cannot see the justification for the current version which conflates the two terms.
• Organisation of the article. It would appear the anonymous editor would like to see the degradation of thiamine in food by "anti-thiamine factors" discussed in the "Sources" section. While there is merit in this layout, it does have the effect of splitting the degradation of thiamine between two sections (the "Sources" and the "Absorption, metabolism and excretion" section). On balance my feeling is that it is better to keep discussion of degradation in one place, again as in the version before the anonymous editor's changes.

It would be good if the anonymous editor could engage with this discussion and could explain the rationale for their changes more fully. Perhaps also @David notMD: could provide some input as the nominator. Clearly we are all anxious to avoid an edit war, which would derail the GA review process.
Best wishes Mertbiol (talk) 20:04, 16 November 2022 (UTC)

sorry to join the discussion so late. Your second point is a very good one, and I had not been aware of this distinction. ("A _thiamine_antagonist_ may be defined as a compound that can compete with thiamine, or thiamine precursors or derivatives, in enzyme reactions. "--E F Rogers)

My opinion is that the previous structure (anti-thiamine factors and thiamine antagonists being contained in the food sources section). This structure of the Thiamine page had been stable in this way for years, and my view is that there are good reason for this.

Final point, if we have a separate section for Thiamine Degradation, then one should at least link this section to the Thiamine food sources with a paragraph or sentence.

In my second edit I removed the redundant content, and did link the two sections together. To me this seemed to flow fairly well, and the structure was satisfactory. My final opinion is that all that remains to be done is to make changes to make the distinction between thiamine antagonists and anti-thiamine factors clear. 38.49.92.7 (talk) 22:16, 16 November 2022 (UTC)

sorry I didn't proofread before post; 2nd paragraph should instead start out with ""My opinion is that the previous structure (anti-thiamine factors and thiamine antagonists being contained in the food sources section) made for more informative and better flowing reading. 38.49.92.7 (talk) 22:19, 16 November 2022 (UTC)

Is it possible that Thiamine Antagonists are a broader category that includes both Agonists and ATF's.

Below is the paragraph from the original earlier November 9 version ( en.wikipedia.org/w/index.php?title=Thiamine&oldid=1120934845#Antagonists ) :

"Plant thiamine antagonists are heat-stable and occur as both the ortho- and para-hydroxyphenols. Some examples of these antagonists are caffeic acid, chlorogenic acid, and tannic acid. These compounds interact with the thiamine to oxidize the thiazole ring, thus rendering it unable to be absorbed. Two flavonoids, quercetin and rutin, have also been implicated as thiamine antagonists.

With an oxidized thiazole ring, would one consider the thiamine degraded? 38.49.92.7 (talk) 23:09, 16 November 2022 (UTC)

I think that earlier versions of the article have not used the word "antagonist" in its strict sense mentioned by Mertbiol. It is in that sense of "active site competitor" that I'm accustomed to using it. A recent article Wilson, Robert Beaumont (2020). "Pathophysiology, prevention, and treatment of beriberi after gastric surgery". Nutrition Reviews. 78 (12): 1015–1029. doi:10.1093/nutrit/nuaa004. PMC 7666909. PMID 32388553. is helpful in that it confirms that all the named chemicals caffeic acid, chlorogenic acid, tannic acid, quercetin and rutin are NOT antagonists in that sense but act to degrade the thiamine in various chemical ways. Indeed, the only true antagonist mentioned by Wilson is omeprazole, which is clearly not relevant for our article as it is a drug that most people would not be exposed to. The way forward, I think, is to use this review reference for all the statements we make about individual chemicals but to make it clear we mean "anti-thiamine", not "antagonist". I prefer to place whatever wording we agree in one subsection together at "Absorption, metabolism and excretion / degradation" because by if the thiamine is degraded by an anti-thiamine, then it can't be a source! Nevertheless, I don't mind if 38.49.92.7's logic feels it is better in the sources section. Maybe this is something where David notMD can help as he hadn't yet been heard on this issue? Mike Turnbull (talk) 11:54, 17 November 2022 (UTC)

Mertbiol, Michael D. Turnbull, 38.49.92.7 - My life complications have cleared. I will look at all the progress made toward achieving closure on the GA review, and see if I can make useful contributions. Deep appreciation to all the work done in my absence. David notMD (talk) 02:39, 17 November 2022 (UTC)

Hi All. I think the best thing to do now is for Mike Turnbull and @David notMD: to work together to propose a new wording for the "Sources" and "Absorption, metabolism and secretion" sections, using additional references. Once they've done that, perhaps 38.49.92.7 could suggest any amendments. Once consensus is reached, I can take a final look as the GA reviewer. Does this work for everyone? Best wishes Mertbiol (talk) 21:15, 17 November 2022 (UTC)

Works for me. I will be looking at it Friday morning. David notMD (talk) 04:37, 18 November 2022 (UTC)

I really don't follow this logic: "I prefer to place whatever wording we agree in one subsection together at "Absorption, metabolism and excretion / degradation" because by if the thiamine is degraded by an anti-thiamine, then it can't be a source! "

As long as there's a short paragraph within the Sources section that summarizes anti-thiamine factors (including caffeic acid, which is a very common one diets) then I don't mind if there is a section added in Metabolism and Degredation where there can be a subsection Degradation, where biochemists can elaborate and expand on the topic in great detail (substances that alter thiamine and the details). The summary paragraph in the sources section can then link to the more detailed discussion in the Degradation section. (I think I may have tried to finish it in this way in my final edit yesterday.)

I think possibly this might be the best of both worlds; a short summary paragraph on ATF's (and how it affects absorption and availability of dietary thiamine) in the food Sources and Nutrition part of the page, which the reader then can click through to follow up on much more detailed biochemistry and categories of anti thiamine factors a dedicated section on the topic elsewhere on the page. 38.49.92.7 (talk) 05:52, 18 November 2022 (UTC)

OK, let's see how David notMD gets on with a redraft (presumably here on the GA review page at first). The version in the live article is still as you had it. Mike Turnbull (talk) 12:25, 18 November 2022 (UTC)

First return to Thiamine after the start of the GA review

First, an appreciation to the editors who moved this forward in my absence. (My life had become very complicated for a longish while.) Second, my vitamin involvement history - I've been editing this article since 2016, intensively since January 2022, leading to my GA nomination in July 2022. Previously, I have raised ten vitamin articles to GA, leaving only Thiamine, Vitamin E and Vitamin D. Third, while I acknowledge that academic credentials and career experience do not perforce favor the opinion of any one editor over another, a long time ago I earned a doctorate in nutritional biochemistry, followed by a 40-year career in medical nutrition R&D and vetting scientific accuracy of health claims for functional foods, sports nutrition products and dietary supplements (now retired).

The issue at hand appears to be the subsection "Antagonists and Anti-thiamine factors" in the Sources section. Copied here: "The potential of thiamine in foods to be absorbed and utilized may be affected by antagonists contained naturally within the food, synthetic food additives, or thiamin degradation within the food by microorganisms prior and during food consumption. Plant thiamine antagonists are heat-stable and occur as both the ortho- and para-hydroxyphenols. Some examples of these antagonists are caffeic acid, chlorogenic acid, and tannic acid. These compounds interact with the thiamine to oxidize the thiazole ring, thus rendering it unable to be absorbed. Two flavonoids, quercetin and rutin, have also been implicated as thiamine antagonists." Ref is Combs (2008).

There is also an unreferenced sentence "Some plant phenols found in foods, including caffeic acid, chlorogenic acid, and tannic acid act as thiamin antagonists, or anti-thiamine factors." added to the Degradation subsection, with a Wikilink back to the previous content.

I do not have access to the Combs ref. I tried several PubMed approaches to the concept of thiamine antagonists and thiamine antivitamins. The most promising was "Thiamine and selected thiamine antivitamins - biological activity and methods of synthesis." (Tylicki 2018 PMID:29208764). It covered known chemical antagonists such as oxythiamine, but had no mention of any of the compounds in dispute here. As a different approach, I searched for thiamine and each of the proposed food or supplement compounds. I found little primary or secondary literature in support of the proposed content. For example, "Evidence against the reported antithiamine effect of caffeic and chlorogenic acids" (Horman, 1981 PMID:7327861) was negative. "Antithiamins of plant origin: their chemical nature and mode of action" (Hilker 1982 7044222) identified caffeic acid as an antagonist, based on high consumption of caffeic containing plants but only in animal models.

As the named acids are present in coffee and tea, I searched the scientific literature on thiamine x coffee or tea to little avail. This is important, because coffee and tea consumption is common, and includes a subset of people who consume LOTS of these beverages. In contrast, there are non-journal mentions of coffee and tea as thiamine antagonists. For example: "Causes of thiamine deficiency - Cornell University" at http://thiamine.dnr.cornell.edu/Thiamine_causes.html. The weakness is that websites like this refer back to the same weak and very old journal articles.

In conclusion, albeit unable to see Combs or what Combs referenced, in my opinon the scientific literature does not support naming caffeic, chlorogenic and tannic acids as thiamine antagonists, as the literature does not achieve WP:MEDRS. The disputed content sould be deleted. Even if some of the evidence is scientifically true (which I find very weak), the amounts consumed by humans from foods is not clinically relevant. David notMD (talk) 13:31, 19 November 2022 (UTC)

Hello, I have access to the Combs reference, albeit the fifth edition rather than the third edition as cited in the article. I can paraphrase the relevant section here if you'd like, but the quote you provided above has the same information with the exception that hemin apparently also binds thiamine, sequestering it.

However, what is most notable is that the book widely does not have any inline citations, so nothing can be easily traced to a source and verified. There are many footnotes adding context notes and sometimes citations, but the claims at debate here do not have them.

I recently noticed the thiamine good article review from the WikiProject Molecular Biology page, and wanted check what the process looked like since thiamine is a favourite enzyme cofactor of mine. Let me know if you want to discuss the reference (I'm not exactly clear with what I'm allowed to share under my university's permissions), and I'm a little interested in recreating the chemical diagrams to have a consistent style. Synpath (talk) 20:20, 22 November 2022 (UTC)

@Synpath All but two of the chemical diagrams (in the drugbox and of the ylide) were done by me using Biovia Draw then Inkscape to convert to .svg. I tried to make them as consistent as possible, for example in orientation. Was there something specific you think should be changed? Mike Turnbull (talk) 16:15, 23 November 2022 (UTC)

@Michael D. Turnbull Thanks for your work, especially the ThiC reaction diagram - seeing that got me into reading about the conversion after I skimmed the article. My main issue was that the diagrams should follow the ACS style per MOS:CDSG, and it would benefit my reading (at least on my browser/computer) as several of the diagrams not in that style are difficult to read since they are scaled down. There's also a nit picky issue with a bolded nitrogen in the thiazole synthase substrate. I'm not sure what Biova Draw is like to use, and I hope it's possible to import ACS style settings and resave the images without having to go to through the trouble of redrawing everything. If that's the case and you don't have time, I can pick that up. Synpath (talk) 18:16, 23 November 2022 (UTC)

@Synpath Interesting comments. I'm very well aware of MOS:CDSG (I wrote some of it!) and my defaults in Biovia Draw are indeed ACS style. The "problem" is that the guide is written with the assumption that, for example, text should be rendered as 10pt Arial. Everything else scales with that. In practice, using .svg files, the diagrams scale according to the space available on individual browsers (which can be influenced by using a specified pixel width for some images). If you scaled any of my diagrams to have exactly 10pt text, all the rest will be as the ACS guideline. However, that's NOT what happens in practice in articles. To see what I mean, click on a diagram and look at it full-size: it will fill your browser window, not just scale up to 10pt text. So I'm not sure what can or should be done. Well done for spotting the "bolded" nitrogen: I made a mistake there with a double nitrogen and I've fixed that. Mike Turnbull (talk) 18:39, 23 November 2022 (UTC)

For what its worth I was linking CDSG just to show I wasn't trying to impose a personal preference for ACS style, and I'm a little embarrassed to quote it to one of its authors. That being said I kinda don't understand the issue as I thought the ACS style prescribed a certain ratio between heteroatom letter size and bond length among other minutia, rather than point sizes of fonts (though it might define those ratios with a default point size). That ratio should be preserved in an SVG. I realize I'm making an assumption here, and I think I'll look into it this evening. The essence of my first point stands: some of the scaled down diagrams are hard to read. Bumping up the point size of the heteroatoms could be a solution. Synpath (talk) 20:00, 23 November 2022 (UTC)

Found the relevant point in the style guide, and it's basically "a benzene ring should be ~3.5 times as wide as a letter is tall" except using absolute measurements. For whatever reason the ratio isn't being preserved in a link in the chain to create the .svg (what even is a .emf file?), and I'm convinced if I were to figure that out by downloading those programs I could just redraw the diagrams instead. Not pinging as I don't think what I've written here is terribly useful. Synpath (talk) 06:24, 24 November 2022 (UTC)

I'll take this up on your Talk page, as it isn't really relevant to the GA review but is worth discussing as a general issue. Mike Turnbull (talk) 12:40, 24 November 2022 (UTC)

Quercetin and rutin - thiamine antagonists?

This statement "Two flavonoids, quercetin and rutin, are also considered to be thiamine antagonists." was found at Medigoo https://www.medigoo.com/articles/vitamin-b1-thiamine-deficiency/ without references (along with mention of coffee, tea and betal nut chewing). The concept is of interest because in addition to being compounds in foods, in some countries these compounds are sold as dietary supplements. Various searches did not find confirmation that quercetin or rutin act as thiamine antagonists. Mention of such should be deleted unless WP:MEDRS-compliant references can be provided. David notMD (talk) 14:16, 19 November 2022 (UTC)

Reviews?

@David notMD The article I mentioned above, doi:10.1093/nutrit/nuaa004, looked WP:MEDRS-compliant to me and has all the named compounds in its Table 3. I thought that the issue was the use of the word "antagonist" and where to place these statements. See all comments after "Stopping here after the second read through" above. Mike Turnbull (talk) 13:32, 20 November 2022 (UTC)

My concern continues to be that this and other "reviews" are citing inadequate primary research for caffeic chlorogenic and tannic acids, rutin and quercetin. (A referenced case can be made for foods that contain thiaminases, which can be inactivated with the heat of cooking.)

See: https://lpi.oregonstate.edu/mic/vitamins/thiamin This is the Linus Pauling Institute article on Thiamin. "Anti-thiamin factors (ATF): The presence of anti-thiamin factors (ATF) in foods contributes to the risk of thiamin deficiency. Certain plants contain ATF, which react with thiamin to form an oxidized, inactive product. Consuming large amounts of tea and coffee (including decaffeinated), as well as chewing tea leaves and betel nuts, have been associated with thiamin depletion in humans due to the presence of ATF (34, 35). ATF include mycotoxins (molds) and thiaminases that break down thiamin in food. Individuals who habitually eat certain raw fresh-water fish, raw shellfish, or ferns are at higher risk of thiamin deficiency because these foods contain thiaminase that normally is inactivated by heat in cooking (1, 6). In Nigeria, an acute, neurologic syndrome (seasonal ataxia) has been associated with thiamin deficiency precipitated by a thiaminase in African silkworms, a traditional, high-protein food for some Nigerians (36)." Ref 34 is Vimokesant (1975) PMID 803009, which presents evidence for fermented fish (thiaminase source) and betel nut chewing. Ref 35 is Ventura (2013) PNID 22436368, which presents a case study of one woman with high tea intake. REf 36 is Mishimune (2000) PMID 10827220), which presents the consequences of season consumption of silkworm larvae (thiaminase source).

The doi you mention is to Wilson RB (2020). It covers antithiamine factors on page 1020 and lists caffeic and tannic acids in coffee and tea, also quercetin and rutin, in Table 3. Thiaminases are described and referenced. The text's food refs are a WHO report and Vimokesant (1982) PMID 7044221. In the table, except for the WHO report, none of the referencs address the polyphenols or flavonoids. The WHO report (1999) https://apps.who.int/iris/bitstream/handle/10665/66139/WHO_NHD_99.13.pdf?sequence=1&isAllowed=y addresses anti-thiamine factors on pages 30-32. Again, thiaminases are presented. Vimokesant is cited as presenting evidence that tea drinking and tea leaf chewing [my bold] in Thailand was associated with thiamine deficiency. Hilker (1971) is cited in support of tannins, but that is an in vitro study, as are the evidences cited in Hilker (1982) PMID 7044222 for caffeic acid and other compounds. Table 15 of the WHO report - like in Wilson - lists polyphenols and flavonoids with no references. To summarize, Vimokesant 1975 and 1982 appear to present human evidence from Thailand for betel nut chewing and tea leaf chewing. Nowhere is there human evidence for caffeic acid, chlorogenic acid or the flavonoids, or for coffee or other polyphenol foods as having clinically relevant anti-thiamine activity. My opinion is that the two subsections I addressed in my previous comment be deleted and a subsection about food thiaminases be added. I am willing to write the latter if there is concensus on that.

Thus, after chasing the literature down the rabbit hole, my findings are that there are "reviews" based on old literature, mostly in vitro, and not strong enough to support the current text on anti-thiamine activity. David notMD (talk) 02:39, 21 November 2022 (UTC)

Thanks for doing the deep dive, David_notMD. I'm happy to have you amend the text in the live article as you propose. Then 38.49.92.7 can comment if they wish and that should allow Mertbiol to complete the GA review. Mike Turnbull (talk) 12:00, 21 November 2022 (UTC)

I will proceed to edit the article based on my assessment of the literature. Briefly, remove all content about polyphenols and flavonoids as antagonists, and chose one place to add referenced content about thiaminases. I state here that I do not have access to the Combs ref that is cited in support of the aforementioned putative antagonists, so if that ref in turn references credible clinical research, the situation can be reopened here at Talk. David notMD (talk) 12:06, 21 November 2022 (UTC)

Actually, thiaminases are already mentioned in the article, referenced, under Degradation and there is a thiaminase article. I will see what can be added that adds value to thiamine. David notMD (talk) 13:04, 21 November 2022 (UTC)

Hello, anon editor here, I've just created a handle, as I think this is looking like it may be a long term effort to improve and improve to a satisfactory state.

Only to mention thiaminases as antagonists of thiamine would be incredibly inaccurate. Also, it is not justified to make this change (including removing the long standing section of Antagonists within the Thiamin article) simply because the potency of the anti-thiamine effect in caffeic/chlorogenic and various polyphenols is much smaller (maybe an order of magnitude or almost two) than in those ATF's found in certain exotic foods (eg betel nuts and certain ferns). The latter can cause incredibly serious health issues (including beriberi and death) in certain populations. Instead, a statement should be made that effects vary greatly, and if possible to roughly quantify the degree these might impact a person's nutrition.

Low thiamine and B levels are not uncommon in the populations. This is probably especially the case for vegan and some vegetarian diets that are below or near the threshold given by officially recommended guidelines. David notMD, like many other males in my country, I drink a full pot of coffee over the day; can you be confident to predict that the ATF effects of the resulting caffeic and chlorogenic acids I'm consuming every day would not significantly impact my health if I were on a typical vegan diet (without specific supplements) skimming the threshold for suggested dietary B vitamin intake?

Lastly, if you cannot find population studies supporting measured clinical effects of various common ATF's, it may be because it is difficult (with so many other factors in subjects that might affect results), expensive, and very time consuming to conduct such studies. You can simply say that there is no conclusive evidence that consumption of thse ATFs in the general population results in clinical thiamine deficiency. PecanSequoiaForests (talk) 20:40, 25 November 2022 (UTC)

Once more into the breach

Notifying Mertbiol, Michael D. Turnbull and 38.49.92.7. To PecanSequoiaForests: I agree that it is possible that certain polyphenols and flavonoids inactivate thiamine. My reason for deleting the content is lack of evidence. As to "long-standing", the text and Combs ref was added on 28 April 2008, and remained unchanged until I recently removed it. When I reviewed and revised the article prior to nominating it for GA, I let it stand untouched, which was an error. While I do not have access to the Combs ref, in the extended discussion above, Synpath does, and states that information about these antagonists is in Combs WITHOUT INLINE CITATIONS. So that is one more 'review' type article that fails to present human evidence. In my own literature searches, nowhere in the literature did I find WP:MEDRS quality literature in support. Nor did I find useful human literature aside from the very old and limited lit be Vimokesant. I am not saying that these compounds may not interfere with thiamine, i.e., "antagonists" or whatever they may be called, only that published evidence is absent.

You (PSF) propose that the article contain a "...statement should be made that effects vary greatly, and if possible to roughly quantify the degree these might impact a person's nutrition." There is no evidence that any of the foods (coffee, tea, chocolate, etc.) mentioned in the 'reviews' listed above (Combs, Cornell, Linus Pauling Institute, Wilson, Medigoo) act as clinically relevant antagonists to any degree. All of that is speculation. My opinion is that speculation is not good enough to be in this article. Naming these compounds and foods that contain them as ATFs is a disservice to the readers. David notMD (talk) 07:02, 26 November 2022 (UTC)

Another 'review' example with no references: MedlinePlus at https://medlineplus.gov/druginfo/natural/965.html#FoodInteractions "Chemicals in coffee and tea called tannins can react with thiamine, converting it to a form that is difficult for the body to take in. This could lead to thiamine deficiency. Interestingly, thiamine deficiency has been found in a group of people in rural Thailand who drink large amounts of tea (>1 liter per day) or chew fermented tea leaves long-term. However, this effect hasn't been found in Western populations, despite regular tea use. Researchers think the interaction between coffee and tea and thiamine may not be important unless the diet is low in thiamine or vitamin C. Vitamin C seems to prevent the interaction between thiamine and the tannins in coffee and tea."

Non-human lit

Hilker (PMID 7044222) reviewed the in vitro and animal literature that appears to be the root reason for mention of these compounds as having antithiamine activity "ANTITHIAMINS OF PLANT ORIGIN: THEIR CHEMICAL NATURE AND MODE OF ACTION D. Hilker, J. Somogyi Published 1 March 1982 Chemistry, Medicine Annals of the New York Academy of Sciences. The existence of non-enzymatic thiamin inactivating factors in plant material was first observed by Weswig et al. in 1946, roughly ten years after the structure of this vitamin was established. This short note stated that rats fed bracken fern as 40% of the diet lost weight and developed symptoms suggestive of thiamin deficiency. The term “antithiamine activity” was used in describing this action and the possible relation to “fern poisoning” in cattle was discussed. Three years later, Evans and Evans2 confirmed these findings using rats fed a standard diet plus bracken leaves. Subsequently, Kundig and Somogyi analyzed a number of fruit and vegetables for antithiamin activity (ATA) and found highest activity in blueberries, red chicory, black currants, red beetroot, brussel sprouts, and red cabbage. The activity appeared to be associated with colored plants. Plant antithiamin activity was also studied by Japanese workers: Thai: and Indian investigators.6 The next investigations concerned the chemical nature of the antithiamin substances in plants. It was soon concluded that the activity was connected with phenolic compounds. Matsukawa and Kawakami determined the ATA of a number of phenols, quinones, catechol, and tannic acid: the optimal conditions for activity; as well as products of thiamin decomposition. They noted that (a) the ATA in plants was associated with phenol compounds having two OH groups, (b) the optimal pH was above 7.0 (c) the optimal temperature was above 5OoC, (d) the reaction required oxygen, (e) the reaction was inhibited by cysteine, and (f) thiochrome and thiamin disulfide appeared as reaction products of thiamin decomposition. After analyzing over 30 phenolic compounds for ATA, Somogyi and Bonicke postulated that the number and position of OH groups is of primary importance for antithiamin activity. Compounds having only one OH group had no activity, those with ortho OH groups had the highest activity, those with para OH groups had medium activity, and those having the OH in the meta position had no activity. Caffeic acid (3,4-dihydroxycinnamic acid) was isolated from fern’ and blueberries’” as one the the antithiamin factors in these plants. Sarkar and Chaudhuri” isolated and characterized an antithiamin factor from cotton seed as 3,5-dimethoxy salicylic acid. A more complex substance containing glucose and an ortho-hydroxy phenol group with CH3 and COOH radicals has been partially characterized from rice bran.” Williams in 1927 described experiments in which pigeons were fed rice mill by-products and developed..." From this article we have specific mention of caffeic acid and polyphenols for in vitro and animal research, but nothing subsequent in the lit for humans. David notMD (talk) 07:59, 26 November 2022 (UTC)

Final verdict

GA review (see here for what the criteria are, and here for what they are not)

1. It is reasonably well written.

   a (prose, spelling, and grammar): b (MoS for lead, layout, word choice, fiction, and lists):

2. It is factually accurate and verifiable.

   a (reference section): b (citations to reliable sources): c (OR): d (copyvio and plagiarism):

3. It is broad in its coverage.

   a (major aspects): b (focused):

4. It follows the neutral point of view policy.

   Fair representation without bias:

5. It is stable.

   No edit wars, etc.:

6. It is illustrated by images and other media, where possible and appropriate.

   a (images are tagged and non-free content have non-free use rationales): b (appropriate use with suitable captions):

7. Overall:

   Pass/Fail:

This is a very interesting article. Congratulations to @David notMD: for the original nomination and to @Michael D. Turnbull: for doing much of the work to address the points raised during the review. Thank you also to @Synpath: and @PecanSequoiaForests: for their thoughtful input. I am happy now to promote the article. Congratulations to all. Best wishes Mertbiol (talk) 18:44, 5 December 2022 (UTC)