Wikipedia:Featured article candidates/Beta-Hydroxy beta-methylbutyric acid/archive4

The following is an archived discussion of a featured article nomination. Please do not modify it. Subsequent comments should be made on the article's talk page or in Wikipedia talk:Featured article candidates. No further edits should be made to this page.

The article was promoted by Sarastro1 via FACBot (talk) 21:53, 23 March 2018 [1].

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Beta-Hydroxy beta-methylbutyric acid

Nominator(s): Seppi333 (Insert 2¢) & Boghog (talk) 07:28, 20 January 2018 (UTC)

Notified WT:WikiProject Medicine, WT:WikiProject Pharmacology, and WT:WikiProject Molecular and Cell Biology.

This article is about a natural product in humans which is used as a medical food ingredient and dietary supplement; it has medical and athletic performance-enhancing applications for preventing/reversing muscle wasting and improving body composition respectively. My previous nomination of this article was archived approximately one year ago. Since then, this article has received minor updates and gone through a thorough GA review (Talk:Beta-Hydroxy beta-methylbutyric acid/GA1).

This is the second pharmacology article that I've worked on for FA status. My first pharmacology FA was amphetamine, so this article's layout and formatting mirror that article. Like amphetamine, this article includes citations in the lead that are grouped in a citation note at the end of each paragraph. I will not remove the lead references since they cite medical claims.

The section names and the organization of the sections in the article follow MOS:PHARM and MOS:MED#Drugs, treatments, and devices. Per WP:MEDRS, all medical claims in this article must be cited by recent reviews, meta-analyses, or systematic reviews. Most of the paywalled medical reviews that are cited in the article are temporarily available in this link for viewing/downloading. The file names (without the .pdf extension) of the papers listed in this link reflect the reference names (i.e., <ref name="...">) used in the source code of the HMB article. Seppi333 (Insert 2¢) 07:28, 20 January 2018 (UTC)

@Soupvector, Barbara (WVS), Jo-Jo Eumerus, Lingzhi, Tom (LT), Galobtter, and Evolution and evolvability: This article's nomination is now near the end of the FAC nomination list at WP:FAC, so there isn't much time left to review this article. Do any of you have any further comments/concerns about this article which still need to be addressed before you're willing to support promotion of this nomination? Seppi333 (Insert 2¢) 23:57, 19 March 2018 (UTC)

Nothing new. Have updated my comments. --Tom (LT) (talk) 08:56, 20 March 2018 (UTC)

@Jo-Jo Eumerus, Lingzhi, Galobtter, and Evolution and evolvability: I'm guessing there's only a day or two left before this nomination is closed. If any of you have further comments/concerns or are willing to support this nomination as is, please follow up soon. Seppi333 (Insert 2¢) 23:25, 21 March 2018 (UTC)

@FAC coordinators: Do you feel there's a consensus for promoting this article? I only ask because I don't want to badger reviewers who have only left comments w/o a clear statement of support or opposition if doing so is completely unnecessary. Seppi333 (Insert 2¢) 01:18, 20 March 2018 (UTC)

@FAC coordinators: I think this nomination has pretty much run its course. I've addressed all the comments/concerns that I can from the four reviewers that have remained neutral (Galobtter, Lingzhi, Jo-Jo Eumerus and DePiep); the other six reviewers (Evolution and evolvability, Tom (LT), Soupvector, Barbara (WVS), Dudley Miles and Dank) have indicated their support for promotion to FA status. Barring a very-last-minute review, there's nothing left for me to action.except the very last comment/bullet in #Comments by Dudley; I'm not sure how long it will take me to find those patent expiry dates, but I intend to continue searching when time permits. In any event, please close this nomination at your convenience. Seppi333 (Insert 2¢) 06:58, 22 March 2018 (UTC)

Comments by Galobtter

Some points (adding as I review the article):

1. Very minor point but in Beta-Hydroxy_beta-methylbutyric_acid#Available_forms "blood" links to blood plasma - either should be blood plasma or just not linked per WP:EGG
2. The metabolism of HMB is initially catalyzed by an uncharacterized enzyme which converts it to HMB-CoA. The metabolism is initially catalyzed?
3. "HMB is sold worldwide.." source only says commercially available as such
4. 30-50$ per month for 3 grams - shouldn't there be a location given?; also the citation "PEDS in sports" (currently [19]) doesn't seem to support that sentence from quick looking and searching through the article; addendum: hmm, according to the lead it is worldwide sold at that range of price? Unsure how that can be determined
5. Metabolic Technologies, Inc., the company that grants licenses to include HMB in dietary supplements, advises pregnant and lactating women not to take HMB due to a lack of safety studies conducted with this population. Seems somewhat repetitive and redundant to the sentence No clinical testing with supplemental HMB has been conducted on pregnant women and not very pertinent; I suggest combining or removal
6. Unsure why the chemistry section does not use the acronym HMB but instead the full form
7. In #Detection in body fluids:
   • adequate dietary source of HMB for what? e.g HMB doesn't seem necessary for a normal human's diet
   • Without any real commentary or analysis, writing out in prose all the measurements done in blood plasma, urine, intramuscular and what concentration was found is mostly redundant to the table..
8. As MOS:CHEM says The structures of many organic compounds are obvious - the chemical structure section seems to not say much and could be removed:
   • β-Hydroxy β-methylbutyric acid and β-hydroxy β-methylbutyrate are structural analogs of butyric acid and butyrate that have a hydroxy group and methyl group attached to the beta carbon of these compounds. not sure why the butyrate is necessary to be mentioned, and it doesn't say much that a structural diagram doesn't; however it is the more useful sentence
   • By extension, β-hydroxybutyric acid and β-methylbutyric acid are also parent compounds of β-hydroxy β-methylbutyric acid. β-Hydroxy β-methylbutyric acid is the conjugate acid of β-hydroxy β-methylbutyrate, while β-hydroxy β-methylbutyrate is the conjugate base of β-hydroxy β-methylbutyric acid. Entirely unnecessary - the first sentence is really "so what?" and the second sentence repeats itself twice with no real meaning or relevance

- Galobtter (pingó mió)

1. Fair point. I've cut the pipe or removed the wikilink. diff
2. Fixed (diff). That only would've made sense to say if it were written as "HMB metabolism" instead of "The metabolism of HMB".
3. I've changed "sold" to is "commercially available" (diff), although I don't think there's much of a difference between the old/new statement TBH; the newer version is just longer.
4. Good catch. After looking at the ref quote and what it cited in the article, it's pretty obvious that it was meant to cite the first sentence in that paragraph (per the part about being available OTC). Until about a month ago, the 1st sentence immediately preceded the statement about the cost of $30-50/month. Seems like I placed that ref after the wrong sentence. I fixed it in this edit: diff.
5. This was added following my discussion with two other medical editors at Talk:Beta-Hydroxy beta-methylbutyric acid#Comment about safety. The statement "Metabolic Technologies, Inc., the company that grants licenses to include HMB in dietary supplements, advises pregnant and lactating women not to take HMB due to a lack of safety studies conducted with this population." is a contraindication, and technically should be placed under a level 2 heading titled "Contraindications" per MOS:MED#Drugs, treatments, and devices; however, since that section would only have 1 sentence under it, it was juxtaposed with the related sentence under safety. I can create the contraindications section and move it there if you'd like; however, I don't think it would be prudent to omit that sentence from the article because that is a clinically relevant contraindication.
6. This issue came up in the GA review, so it might be worthwhile to read my explanation there: Talk:Beta-Hydroxy_beta-methylbutyric_acid/GA1#Linked from FAC.
7. Changed the sentence to: "This concentration is far too low to be an adequate dietary source of HMB for obtaining pharmacologically active concentrations of the compound in blood plasma, ..." in this diff. I agree that there's a lot of redundancy between the 1st paragraph and the table, although the the text includes slightly more information (e.g., a specific gender is specified in two instances). The reason it was done this way is that some people prefer text over data tables and vice versa for this type of information. IMO, it's more useful to list that material in a table since it is data; however, given that the units of measurement and abbreviations listed in the table are not something I'd expect most of our readers to know, covering those in the article text helps to clarify what the units and abbreviations in the table are.
8. In light of what I mentioned in the bulleted response below, would you like me to delete one or more of the sentences that you specified above?
   • The entire chemistry section was significantly expanded following the discussion in the first FAC at Wikipedia:Featured article candidates/Beta-Hydroxy beta-methylbutyric acid/archive1#Comments by Nergaal; if he were to return to comment, I'm not sure how he would feel about the deletion of the entire structure subsection. Also, I think the average reader of this article is unlikely to have a significant chemistry background simply due to the fact that this compound is notable (and hence likely to be searched) for reasons unrelated to its chemistry; hence, intuitively, the average reader likely isn't going to have a chemistry background. In contrast, I suspect that most people reading the page acetic acid would be reading it due to an interest in its chemical properties, synthesis, etc. and would therefore have some relevant background knowledge of the structural properties of compounds (e.g., how acetate relates to acetic acid). So, in a nutshell, unless this article explicitly states that beta-hydroxy beta-methylbutyric acid and beta-hydroxy beta-methylbutyrate are two distinct albeit related compounds, and not simply synonyms as implied in the lead, then our readers are probably not going to understand that "HM-butyric acid" and "HM-butyrate" are not the same thing.
   • Butyric acid, butyrate, β-hydroxybutyric acid, and β-methylbutyric acid were all mentioned because I think structural analogs of pharmacologically active substances (and even a few biologically inert compounds) are interesting things to mention/know. In pharmacology, the relation between a compound's biological activity and its chemical structure is known as a structure–activity relationship or "SAR" for short. Interestingly, the pharmacodynamics of butyric acid, beta-hydroxybutyric acid, and HMB are different; however, I have yet to read an article that states that and covers the differences in their biological activity, so I can't cover this in the article right now. For comparison with the HMB article, in a similar drug FA that I wrote (amphetamine), there is much more coverage of its stuctural analogs and derivatives in the amphetamine#Related endogenous compounds and Amphetamine#Substituted derivatives sections.

Seppi333 (Insert 2¢) 08:41, 21 January 2018 (UTC)

Regarding point 3, I was referring to the "worldwide" part, not the sold - does the source say worldwide? Galobtter (pingó mió) 08:46, 21 January 2018 (UTC)

Oh, my bad. No cited ref states that it's available "worldwide", "globally", or "internationally"; the refs that are cited state that it is a commercially available substance, but do not state a region for its availability. Some of the refs do state that it's not regulated as a drug though (i.e., the one which indicates that it's an OTC dietary supplement). Its global availability simply follows from the fact that non-regulated goods can generally be freely imported to/exported from most countries. In other words, an individual in another country could import it from the United States about as freely as if it were a cotton T-shirt. Based upon a cursory check of a few websites that sell a branded HMB product via the internet, I found https://www.bodybuilding.com/store/met-rx/hmb-1000.html, which appears to offer shipping of that product in over 100 countries (per that website's information page on their shipping policy, if you click the flag in the top right corner, a list of countries where it ships to appears).

In any event, I don't particularly care about specifying the region, so if you'd like me to simply state that it's a "commercially available substance" instead of "commercially available (in such-and-such region)", I'm ok with that. Seppi333 (Insert 2¢) 09:34, 21 January 2018 (UTC)

I think better to stick to the source. Galobtter (pingó mió) 09:38, 21 January 2018 (UTC)

Changed "commercially available worldwide" to just "sold" in this diff. Also, since I wrote my first 4 responses yesterday, I didn't actually respond to the part of #4 that you added afterward. As is evident from the example website that I linked above, that product is sold internationally, but the cost of that product is listed in US dollars. That's the currency that an international customer would be paying for that product in if they purchased it from that vendor. While it's possible that local vendors in other countries sell it for a different amount (if adjusted to USD through the FOREX market), there's nothing preventing an international customer from buying the product from a US website in USD. A financial intermediary (e.g., bank or credit card company) would simply process the transaction using the current foreign exchange rate in order to convert their currency to USD. Since we're not specifying a location and just going with what the refs says, is the listed price range still a concern for you? Seppi333 (Insert 2¢) 09:54, 21 January 2018 (UTC)

Fine with me. Galobtter (pingó mió) 10:03, 21 January 2018 (UTC)

Regarding the amphetamine, it seems rather more interesting because substituted amphetamines are important class of drugs in of themselves, while HMB's relation to butyric acid seems rather trivial and unimportant. Thinking over, the first sentence about structural analogs explains the diagrams to the right; but I think "By extension, β-hydroxybutyric acid and β-methylbutyric acid are also parent compounds of β-hydroxy β-methylbutyric acid." can be cut; and also "β-Hydroxy β-methylbutyric acid is the conjugate acid of β-hydroxy β-methylbutyrate" as redundant. Galobtter (pingó mió) 07:08, 24 January 2018 (UTC)

I didn't see that in the lead and elsewhere butyrate version was referred too; since it is, does make sense to mention it. If "β-methylbutyric acid" is mentioned somewhere/(addendum: or is used pharmacologically - basically has some importance) then it makes sense to mention it being parent compound. Also suggest replacing "β-Hydroxy β-methylbutyric acid and β-hydroxy β-methylbutyrate are structural analogs of butyric acid and butyrate that have a hydroxy group and methyl group attached to the beta carbon of these compounds" with "β-Hydroxy β-methylbutyric acid is butyric acid with a hydroxy group and methyl group attached to the beta carbon." for clarity for non-chemists. Galobtter (pingó mió) 07:14, 24 January 2018 (UTC)

I made the changes you listed above in this diff, although I did slightly modify the sentence on butyric acid (i.e., mentioned it being a structural analog) relative to what you wrote above. If you have any further suggestions for changes, let me know!

To my knowledge, β-methylbutyric acid is biologically inert, but potentially toxic in high concentrations. Outside the structure section, it's only mentioned in the synthesis section and depicted in the corresponding reaction/pathway the diagram.

β-Hydroxybutyric acid is a biologically/pharmacologically-active compound (it's a class I histone deacetylase inhibitor, similar to butyric acid). Butyric acid, β-hydroxybutyric acid, and HMB are all natural products in humans, but they're each synthesized through different metabolic pathways (butyric acid: bacterial metabolism of dietary fiber in the colon; β-hydroxybutyric acid: ketogenesis; HMB: Leucine#Metabolism in humans; technically, HMB could be metabolized into β-hydroxybutyric acid via the pathway HMB→HMB-CoA→HMG-CoA→acetoacetate→beta-hydroxybutyrate - that might be worth depicting in the svg version of {{Leucine metabolism in humans}}). Seppi333 (Insert 2¢) 08:06, 24 January 2018 (UTC)

Lead Prose

1. ingredient in some medical foods. It is added to certain medical foods that are intended to provide nutritional support for people with muscle wasting due to cancer or HIV/AIDS and to promote wound healing. Can't it be combined to "ingredient in some medical foods that are intended.."
2. "muscle size" is another EGG link
3. speed recovery from exercise "quicken" than "speed" - speed isn't used as a verb like that very often which confused me
4. No issues with safety safety is another EGG link and this phrasing is awkward - what about no side-effects?
5. HMB is a metabolite of l-leucine that is produced in the body through oxidation of the ketoacid of l-leucine (α-ketoisocaproic acid). "and is produced" would be clearer; or can even cut "a metabolite of l-leucine that"
6. A healthy adult produces approximately 0.3 grams adding "of HMB" after that would make it clearer

- Galobtter (pingó mió)

1. Done (diff). Seppi333 (Insert 2¢) 08:18, 24 January 2018 (UTC)
2. Hmm. "Muscle size" was used here in place of "muscle hypertrophy" because the term "hypertrophy" is somewhat jargony. The term "increased muscle size" is synonymous with the term "muscle hypertrophy", but "exercise-induced gains in increased muscle size" sounds a bit odd. In any event, I've removed the pipe, so this now says and links "muscle hypertrophy". (diff) Seppi333 (Insert 2¢) 08:27, 24 January 2018 (UTC)
3. I've changed "speed" (and "speed up" in the body) to "expedite", which is the term I originally used (diff). Doc James changed this to simplify the language in the lead, although I think it's likely that the majority of our readers know the meaning of the term "expedite". Seppi333 (Insert 2¢) 08:32, 24 January 2018 (UTC)
4. Changed to "No adverse effects..." in diff (NB: beneficial/desirable side effects on cholesterol and blood pressure have been reported, but I didn't think they were notable since IIRC they were only found in 1 or 2 studies). Seppi333 (Insert 2¢) 09:16, 24 January 2018 (UTC)
5. Done: diff Seppi333 (Insert 2¢) 09:07, 24 January 2018 (UTC)
6. Done: diff Seppi333 (Insert 2¢) 09:10, 24 January 2018 (UTC)

Regarding 2, I think it'd be better to keep muscle size and not include a link to hypertrophy - "increase exercise-induced gains in muscle hypertrophy" doesn't make sense, right? Galobtter (pingó mió) 08:33, 24 January 2018 (UTC)

Actually you're right. It should either read as "... shown to increase exercise-induced muscle hypertrophy" or "... shown to increase exercise-induced gains in muscle size"; the only issue here is that the phrase "gains in" also applies to the phrase "muscle strength, and lean body mass" that follows "muscle size" (In healthy adults, supplementation with HMB has been shown to increase exercise-induced gains in muscle hypertrophy, muscle strength, and lean body mass ...). Seppi333 (Insert 2¢) 08:42, 24 January 2018 (UTC)

I've changed it back to muscle size in the lead and made an analogous change in the body. Seppi333 (Insert 2¢) 09:00, 24 January 2018 (UTC)

Expedite is indeed a common word. Galobtter (pingó mió) 08:34, 24 January 2018 (UTC)

Biosynthesis section

On the biosynthesis section, according to MOS:CHEM the biosynthesis should be in the synthesis section, which makes more sense than pharmacokinetics to me. That biosynthesis section is confusing and needs major reworking/cutting. It appears mostly lifted from Leucine? There's a lot of irrelevant material about metabolic pathways that don't lead to HMB - A small fraction of l-leucine metabolism – less than 5% in all tissues except the testes where it accounts for about 33% – is initially catalyzed by leucine aminomutase, producing β-leucine, which is subsequently metabolized into β-ketoisocaproate (β-KIC), β-ketoisocaproyl-CoA, and then acetyl-CoA by a series of uncharacterized enzymes. and other sentences in that big paragraph in the middle. The large image squishes the text too much for my taste. If that image could be made smaller but more focused on HMB I think that'd help. Galobtter (pingó mió) 08:30, 20 January 2018 (UTC)

May still want to keep it in pharmacology by I don't think biosynthesis is really part of pharmacokinetics. Galobtter (pingó mió) 08:36, 20 January 2018 (UTC)

As previously discussed, I also think biosynthesis does not belong in the pharmacokinetics section. I would suggest that it be moved to the chemistry section just before synthesis section and the synthesis heading be renamed to "Laboratory synthesis" to distinguish it from biosynthesis. This would also mean that File:ISSN HMB statement Fig 1.jpg would need to split into two figures, biosynthesis and metabolism so that they can be placed next to the text that talks about them. As mentioned above the present figure is too large and complex. Splitting the figure into two figures would solve that problem. Boghog (talk) 08:59, 20 January 2018 (UTC)

@Galobtter and Boghog: That's a fair point. It would actually be very easy to cut the entire image into 2 parts using template:annotated image 4's cropping functionality; however, I'd like to get additional feedback on how to redraw this image in SVG at WT:MCB#Template:Leucine metabolism in humans. I invite you two to comment in that thread if either of you have any comments/suggestions on either technical changes to the diagram (e.g., whether or not cofactors should be indicated and how to illustrate cofactors/inputs to each reaction if they're included) or cosmetic changes to this image when it's redrawn in svg.

@Boghog & Galobtter: Also, which of the two following two solutions do each of you prefer?

1. Use the full image (Template:Leucine metabolism in humans) which spans two adjacent sections (the level 4 heading "Metabolism", located under the level 3 "Pharmacokinetics" heading, which would be followed by a level 3 "Biosynthesis" heading) in the "Pharmacology" section (see this link for an illustration of how this would look), or
2. Split the diagram into 2 images, placing the metabolic pathway in the "Metabolism" section and the biosynthetic pathway in the "Biosynthesis" section (which could be located under "Pharmacology" as a level 3 heading or under the "Chemistry" section as a level 3 heading)

FWIW, I think the biosynthesis and metabolism sections should be kept together in "Pharmacology" (i.e., option 1) because it's more cohesive to discuss the entire metabolic pathway of leucine within the same level 2 heading compared to splitting it and covering it in completely different parts of the article. Given that the biosynthetic and metabolic pathways partially overlap along 1 route (specifically, the HMB↔HMB-CoA↔MC-CoA pathway), using 1 image and keeping these sections close together would help convey to readers that this portion of the pathway serves as both a route of HMB metabolism (under physiological conditions) and HMB biosynthesis (during biotin deficiency). Seppi333 (Insert 2¢) 08:29, 21 January 2018 (UTC)

@Galobtter: I've changed your bulleted entries above so that I can easily reply below in a point-by-point manner; I think using a numbered list format will make it easier to identify which point I'm responding to when you/others read my reply or when I'm rereading it at a later time. I hope that's ok with you. If not, feel free to revert my changes to the bulleted list. Seppi333 (Insert 2¢) 08:28, 21 January 2018 (UTC)

@Galobtter: In relation to what you mentioned about the information in the biosynthesis and metabolism sections being copied from leucine: the content in leucine was actually copy/pasted verbatim from HMB, not the other way around (NB: I am the editor that copy/pasted it). As of a few hours ago, I actually just deleted the entire Leucine#Metabolism in humans section and selectively transcluded the same content in from the HMB article. In relation to that minor pathway involving β-leucine metabolism, the reason it was mentioned in the HMB article is that the cited source stated that HMB might be biosynthesized from the metabolites along that pathway; however, due to the fact that the associated reactions/enzymes aren't not well characterized, this is not known for certain. I can cut that part in the HMB article (while still transcluding it to the leucine article) if you think it's not useful contextual information for the HMB article. Seppi333 (Insert 2¢) 08:37, 21 January 2018 (UTC)

Well, as someone who doesn't know about all that, that minor pathway seems like irrelevant information. Galobtter (pingó mió) 08:43, 21 January 2018 (UTC)

@Galobtter: See diff. That paragraph still appears in the Leucine article despite its removal from the HMB article. Seppi333 (Insert 2¢) 08:55, 21 January 2018 (UTC)

@Galobtter: Now that I've finished redrawing the diagram in svg and annotating it, I can crop it fairly easily to show only the biosynthesis and only the metabolism pathways; if I were to do this, I could place each annotated diagram below the article text in the corresponding section as a centered image. Centering the diagrams beneath the article text would avoid the text-squashing issue that you mentioned above. I could also move the biosynthesis section under the "Chemistry" heading if I split the image like this. If you'd like me to split the image and move the biosynthesis section – or you'd prefer an entirely different solution – let me know! I'm willing to work this.

Also, have I adequately addressed all of the other issues that you pointed out in the sections above? If I haven't, please let me know which ones still require my attention. Seppi333 (Insert 2¢) 01:57, 31 January 2018 (UTC)

​ In the biosynthesis section can also cut this "Around 40% of dietary l-leucine is converted to acetyl-CoA, which is subsequently used in the synthesis of other compounds." I think. Issues have been addressed; 50-50 on whether it should be moved honestly. Galobtter (pingó mió) 07:57, 1 February 2018 (UTC)

Hmm. I figured that would give the reader some context on how much leucine ends up as other metabolites, although that statement is partially relevant to HMB's metabolism because acetyl-CoA is a metabolite of HMB; assuming the isovaleryl-CoA and HMB pathways contribute to that 40% value equally, then based upon the 2–10% range for HMB biosynthesis specified in the article text, the metabolism of HMB would yield between .8% to 4% of that 40%.
I'll cut it if you think it's not useful information for the readers though. Seppi333 (Insert 2¢) 03:07, 2 February 2018 (UTC)

If all this isn't explained/important, I don't think it is overly helpful. Galobtter (pingó mió) 06:42, 2 February 2018 (UTC)

Removed it in this diff. Seppi333 (Insert 2¢) 07:52, 2 February 2018 (UTC)

Comments by Tom (LT)

I did the GA review and find this article to be of very high quality and certainly worth consideration. I think it has the potential to be amongst Wikipedia's finest works. I had a few concerns noted at the end of the review which I will paste down here. I think it would be a real shame if this review falls down because of insufficient attention (again).

"Some small additional concerns. I don't think these are enough to prevent a successful GA nomination, and they have been discussed with Seppi333 during the nomination and we have reached a loggerheads. I note these with a view to a (1) FA nomination and (2) MEDRS compliance:

1. I still think some work could be done paring down references
2. I think information relating to the lack of effects of overdose should be included in text
3. I am concerned that primary sources are used to make medical claims, which is not something recommended by our WP:MEDRS
   • "One clinical trial with Juven for AIDS also demonstrated improvements in immune status, as measured by a reduced HIV viral load relative to controls and higher CD3+ and CD8+ cell counts"
   • "The efficacy of Juven for the treatment of cancer cachexia was also examined in a phase 3 clinical trial which found a strong trend (i.e., p=.08) for an improvement in lean body mass relative to controls"
4. I do not think that the article needs so many notes (I think most could be removed without damaging the article's integrity)"

Some of the comments above are fairly general and I'd be interested to know what other reviewers think (I haven't done a FA review before). I'll follow the commentary and will definitely be leaning support if the above are addressed. --Tom (LT) (talk) 10:40, 20 January 2018 (UTC)

I'll work on addressing these soon. Sorry for the delay in my initial response. Seppi333 (Insert 2¢) 05:46, 24 January 2018 (UTC)

@Tom (LT): My itemized responses are below. Seppi333 (Insert 2¢) 01:19, 31 January 2018 (UTC)

1. Are there any sentences in particular that you feel should/needs to have the reference count reduced? The featured article criteria do not include a requirement for limiting the number of references used to cite article content, although they do require articles to fully adhere to the WP:Manual of style, including its guidance on the use and formatting of references. Nonetheless, I realize that FAC is a place for consensus; so, if others feel similarly about the number of citations used to support the sentences in the article beyond those that are required for WP:V, I'm willing to delete all of those. Again, per our discussion at the GA review, I think that would be a really bad idea if applied to the sentences that include medical claims relating to efficacy or safety though.
2. At present, I haven't come across a reference that I can use to explicitly state that there are no potential adverse effects that may arise from overdosing on HMB. The only thing I can explicitly state based upon the sources I've cited in the article, as well as other sources I've read that aren't currently cited, is that no adverse effects were reported by a single clinical study which involved the use of 15 grams of HMB/day (NB: 15 grams/day does constitute an "overdose" relative to the typical 3–6 gram doses used in the vast majority of clinical studies). If you want me to mention that in the article, please let me know.
3. All of the medical claims made in this article are fully supported by one or more medical reviews. At the moment, there are no primary sources that cite a statement about this compound's treatment efficacy or safety profile anywhere in the article; since all of the primary sources with a PMID number (i.e., primary medical sources) in the article are marked as "primary source" via a parameter in their citation templates, you can easily verify this by examining the sentences cited by the references that are marked as "primary source".
   • The sentence "One clinical trial with Juven for AIDS also demonstrated improvements in immune status, as measured by a reduced HIV viral load relative to controls and higher CD3+ and CD8+ cell counts" does refer to a primary source, but the two references citing that sentences (PMID 24072740 and PMID 24057808) are a medical review and a systematic review of randomized controlled trials. Those two references are clearly WP:MEDRS compliant given the publication type of those sources and the their publication dates (2013 and 2014) being compliant with WP:MEDDATE. Given that every single medical claim in this article is ultimately based upon primary research which is summarized in the secondary medical sources that support+cite those claims, I don't see how removing this statement simply due to its basis in primary research would be any different than removing every medical claim in the article for the same reason. However, if others feel the same way that you do about the inclusion of that sentence, I will remove it per consensus.
     • @Tom (LT): On reconsideration, I've decided to delete this sentence: diff. I didn't cover the non-adverse side effects of lower LDL cholesterol and slightly lower blood pressure associated with long-term HMB use simply because they were documented in 1 trial, despite being covered in very recent reviews from the past few months. Given that this was my justification for not including that material and given that you're making a similar argument here, I think it's reasonable to apply the same inclusion criterion for all medical statements. Seppi333 (Insert 2¢) 03:00, 2 February 2018 (UTC)
4. Which notes in particular are you referring to?
   • Edit: I just noticed that I deleted one note when I cut the sentence you specified above about AIDS and immune status. Seppi333 (Insert 2¢) 06:33, 2 February 2018 (UTC)

Seppi333 (Insert 2¢) 01:19, 31 January 2018 (UTC)

@Tom (LT): Re – the following sentences:

The efficacy of Juven for the treatment of cancer cachexia was also examined in a phase 3 clinical trial which found a strong trend (i.e., p=.08) toward improvement in lean body mass relative to controls;[18][34] however, the trial did not adequately test the ability of Juven to prevent or reverse the loss of lean body mass in individuals with cancer cachexia since the majority of participants did not complete the study.[18]

How would you feel about rewording this material as follows:

The efficacy of Juven for the treatment of cancer cachexia was also examined in a phase 3 clinical trial that assessed improvements in lean body mass relative to controls;[18][34] however, since the majority of participants did not complete the study, the trial was unable to adequately test the ability of Juven to prevent or reverse the loss of lean body mass in individuals with cancer cachexia.[18]

Seppi333 (Insert 2¢) 06:57, 7 February 2018 (UTC)

References

Update

Thanks Seppi333 and sorry for the delay - I have been travelling and busy with work. Update:

1. This is a general comment about the whole article as we discussed in the good article review. Lots of relatively noncontroversial statements such as "The safety profile of HMB in adult humans is based upon evidence from clinical trials in humans and animal studies", "The metabolism of HMB is catalyzed by an uncharacterized enzyme which converts it to β-hydroxy β-methylbutyryl-CoA (HMB-CoA" and so on. I don't feel that there is a need to provide so many citations and it makes the article harder for editors to verify. On the other hand, I don't think this should block your nomination to FA status.
2.  Done Overdose - happy here with your no adverse effect dose. I also like your thorough note attached about how this was identified.
3.  Doing... thank you for removing the first instance. The second instance is still directly quoting a primary source to make a medical claim, even rewording it. The whole sentence should be removed in my opinion, because it is a single study and presenting the results in this fashion is misleading. I believe WP:MEDRS supports me here.
4.  Doing... Notes - thanks for removing one. Other notes I think should be removed are, as they are also quoting single studies. I also think original research may be relevant here.
   • " Approximately equal doses of pure HMB-FA (2.42 grams) and L-leucine "
   • "In one study, ingestion of a 1 gram dose of HMB-Ca "
   • "In one study, ingestion of a 1 gram and 3 gram HMB dose resulted "

At present I am leaning support this is a high quality article and Seppi333 has addressed many of my concerns.--Tom (LT) (talk) 00:08, 11 February 2018 (UTC)

Update: finally, claim removed. Striking out first comment as this is a matter of taste and difficult to address. Would still prefer if notes regarding single studies could be removed. Support nomination. Overall a great article.--Tom (LT) (talk) 08:58, 20 March 2018 (UTC)

Comments by Lingzhi

1. Coffman DD, Cramer R, Mochel WE (June 1958) Missing year (that would be 2015).
2. Mochamat, Cuhls H, Marinova M, Kaasa S, Stieber C, Conrad R, Radbruch L, Mücke M (July 2016) Missing first name for Mochamat.
3. Is this "Reference notes" section standard practice for your field? It seems that it could be made a bit more accessible than a huge list of bracketed numbers. Lingzhi ♦ (talk) 23:48, 30 January 2018 (UTC)

I've converted the bulleleted list above to a numbered list so I can address each item in the corresponding numbered list below; I hope that's fine with you.

1. I don't seem to be able to find the year 2015 listed anywhere in this article or the article's publication date on the website where it's hosted (https://dx.doi.org/10.1021/ja01544a072). Where did you see that year listed for this journal article?
2. Oops. For some reason the citation template generator I used doesn't initialize Mochamat's first name; it normally initializes the first names of all authors. In any event, I've fixed this issue in this edit.
   • I've restored the original authors list since my previous edit didn't address this problem. Per my discussion with Boghog at User talk:Boghog#Bug in the citation template filling tool, "Mochamat" appears to be this author's first and only name; he doesn't seem to have a surname. A pubmed search for "Mochamat" shows that he doesn't include a second name in any of his publications. Seppi333 (Insert 2¢) 06:26, 31 January 2018 (UTC)
3. The "Reference notes" section is for the ^{[sources #]} notes in the article, which are used to group sets of 4+ references together in 1 citation; the purpose of grouping 4+ references together is to improve readability in the article, since some people (not me) find that a large string of references makes article prose harder to read. I've used those "sources" notes and a corresponding "Reference notes" section in roughly a dozen articles since I first started editing (NB: I've edited thousands of articles); in general, I don't think it's a useful section to include in an article since most articles don't need several references to support a single sentence. In the case of medical articles, it is sometimes necessary to include several citations when multiple medical claims are made in a single sentence or a group of non-medical claims in 1 sentence are only individually supported by a set of references. Also, since some objected to the inclusion of citations in the lead of this article, the references in each lead paragraph were moved to the end of the paragraph and grouped into a reference note; refnotes #1–3 in Beta-Hydroxy beta-methylbutyric acid#Reference notes correspond to the groups of references for the 3 lead paragraphs.

   Edit: The practice of grouping references like this to improve the readability of article prose is covered in Wikipedia:Citing sources#Bundling citations.

Seppi333 (Insert 2¢) 00:25, 31 January 2018 (UTC)

@Lingzhi: Sorry, I meant to ping you in my last edit. Seppi333 (Insert 2¢) 00:28, 31 January 2018 (UTC)

(←) If I may ask, do you use a tool to add references to the text, or do you do them by hand? If the former, which tool? ... OH OOPS I copy/pasted the wrong title for the article that's missing a year (mentioned above); that would be ""3-OH-isovaleric acid". ChemSpider. Royal Society of Chemistry. Retrieved 10 August 2016. Experimental Boiling Point" Lingzhi ♦ (talk) 08:08, 31 January 2018 (UTC)

• The citation template generator that I use is [2], which is maintained by Boghog (my co-nominator for this article). I really only use that script to generate citation templates for pubmed-indexed articles since the templates it generates for those are always perfectly formatted; all it requires is a PMID number for an input. For websites and textbooks, I manually fill out the citation templates. Seppi333 (Insert 2¢) 14:46, 1 February 2018 (UTC)
• Added the year 2015 to the ChemSpider ref in this edit. Seppi333 (Insert 2¢) 14:46, 1 February 2018 (UTC)
  • That's an excellent tool. More later. Lingzhi ♦ (talk) 16:08, 1 February 2018 (UTC)

Another couple of comments on the "reference notes" issue: The inline links say ^{[sources #]}, whereas the section at the bottom is titled "Reference notes". The disconnect between these adds a bit of confusions/. One solution that I've seen in some chemistry journals like ChemBioChem is to nest the references e.g.: my references are this, this, these, and this. (which uses the code {{refn|Reference set: <ref name="ref1"/><ref name="ref2"/><ref name="ref3"/>}}. It at least puts all the references into the same list so are easier to read. T.Shafee(Evo&Evo)^talk 12:21, 9 February 2018 (UTC)

Replied in your comments section below. Seppi333 (Insert 2¢) 01:06, 20 February 2018 (UTC)

• Am confused by the "reference Notes" section. What is that? Are there many cites for any given assertion, and if so, why? I doubt much of this article is controversial....Could it be made less cryptic? Lingzhi ♦ (talk) 00:00, 22 March 2018 (UTC)
  • @Lingzhi: By it, do you mean the section title? "Reference notes" is just a header for the list of bundled references in the article. I created a separate section for those since it looks odd to juxtaposed bundled references and actual citations in the "References" section. I can rename that section heading to "Grouped references" or something similar if you think that would help clarify the type of content (i.e., a series/list of bundled references) that's located beneath that heading.
    In any event, the reason some sentence have many citations is that multiple claims are included that require several citations to fully support the assertion. Also, the first 3 entries in that list cite the entirety of the 3 corresponding lead paragraphs, which is why they include many refs. Seppi333 (Insert 2¢) 00:08, 22 March 2018 (UTC)
• It's not the name; it's the format. It's confusing to the point of distraction. People complain about my bundled links when I have 3; you have umpteen. Why do you need so many? Is this a raging controversy in the white coat world? Are people waving their arms and screaming? And if those are bundled cites, what cite referes to what assertion? And what is "Proteins in Human Health and PerformanceLucene image - May 16-17, 2013"? It's a link for a conference? how can you cite a link to a conference. It has no text to back any assertions. And all that after five seconds of looking. I feel very Oppose-ful at this moment based on just this; please persuade me otherwise. Lingzhi ♦ (talk) 00:13, 22 March 2018 (UTC)

Copy/pasting from that section:

1. [2][8][9][10][11][12][13][14][15][16][17][18][19] ← This set of references cites every sentence in the 1st lead paragraph.
2. [1][8][14][18][20][21][22][23][24][25][26][27] ← This set of references cites every sentence in the 2nd lead paragraph.
3. [8][20][28][29][30][31][32][33] ← This set of references cites every sentence in the 3rd lead paragraph.

   The three bundled references above could be deleted, but all three of the lead paragraphs would be uncited. Doing this would likely cause other medical editors to revert me, but I can do so if you strongly oppose citing it.

4. [2][8][9][10] ← This set of references cites the following sentence in the body of the article: "Some branded products that contain HMB (i.e., certain formulations of Ensure and Juven) are medical foods that are intended to be used to provide nutritional support under the care of a doctor in individuals with muscle wasting due to HIV/AIDS or cancer, to promote wound healing following surgery or injury, or when otherwise recommended by a medical professional."

   One ref cites the inclusion of HMB in Juven, a second cites its inclusion in Ensure, the remaining 2 references cite the medical conditions for which these medical foods are used to provide nutritional support. Omitting any of them would result in an issue with WP:V.

5. [1][11][12][15][16][20] ← This set of references cites the following sentence in the body of the article: "With an appropriate exercise program, dietary supplementation with 3 grams of HMB per day has been shown to increase exercise-induced gains in muscle size, muscle strength and power, and lean body mass, reduce exercise-induced skeletal muscle damage,[note 3] and expedite recovery from high-intensity exercise."

   Note that this sentence contains 6 distinct medical claims. Omitting any of the citations for them would result in an issue with WP:V.

@Lingzhi: I hope this clarifies things. If I'm missing the point about what you're asking, please let me know. Seppi333 (Insert 2¢) 00:25, 22 March 2018 (UTC)

Edit: that specific reference you asked about cites the following statement in that source "... Juven®, which is a nutritional beverage that is clinically shown to promote healing after injury or surgery." It's used to support the following article text (copied from #4 above) "Some branded products that contain HMB... are medical foods that are intended to be used ... to promote wound healing following surgery or injury ...". Sorry for not mentioning that when I pinged you. Seppi333 (Insert 2¢) 00:38, 22 March 2018 (UTC)

Nevermind. I've deleted that reference from the sentence and unbundled the citation (diff) since I really don't feel like arguing about including it. This introduces a problem with WP:V for the underlined portion of the struck-out text above though. I deleted the clause that became unsupported. Seppi333 (Insert 2¢) 01:19, 22 March 2018 (UTC)

• Either you're missing completely everything I said, or I am missing what you said, or else we are completely misunderstanding each other. Look, in principle, you should try to:

1. use the very best sources for every assertion; no need to cite every paper that repeats an assertion;
2. try to avoid cites in the WP:LEDE, unless your assertion is challenged or challengeable;
3. try to link each cite up with the actual assertion it is verifying.

• I have been working for almost two years now I think on a history article, and people are screaming at me for violating 1) and 3) above (but pushing me to add more cites in the lede, since assertions are allegedly controversial or whatever). So the article I'm working on has the same potential concerns that this does, but this one is multiple times worse. So:

1. How many cites match with each assertion? If it's more than 2, go to Google Scholar, find the ones that are closest in relevance to your assertion and with the most real world, off-wiki cites, eg " Cited by 310", and use those.
2. Do we really need any cites at all in the lede? Keep only the smallest amount you can without arousing the ire of "medical people", eg, support only controversial assertions
3. I love bundled cites, you love bundled cites, but I bundle cite only a few sources and only for one or at most two sentences. You bundle cite for the whole paragraph. Even I, the guy who loves bundled cites, think that's unacceptable. Try to match the supporting cite with the assertion it supports. If the assertion is non-controversial, it doesn't need to be supported in the lede, but almost certainly does need to be supported in body text. Does that make sense? Lingzhi ♦ (talk) 00:49, 22 March 2018 (UTC)

Yes. I've deleted every citation in the lead (this seems like a very bad idea to me, but whatever) and unbundled the 1 citation that I mentioned above. The only citation that I can't unbundle is the 1 remaining one with 6 references since I previously pruned that one down as much as possible when the issue of multiple citations arose at the GA review. Seppi333 (Insert 2¢) 01:19, 22 March 2018 (UTC)

@Lingzhi: Would you like me to make any other changes? Seppi333 (Insert 2¢) 01:39, 22 March 2018 (UTC)

• But I certainly didn't say delete every cite in the lede. I said choose them well and choose them carefully, and match the cite to the specific assertion it supports, and in the lede cite only those things that medical editors would dispute.
• Has someone checked your sources for WP:RS? I mentioned above that you cite a link to a conference (as just one example!), even tho that link offers no supporting text. Are there similar problems elsewhere in the text? Lingzhi ♦ (talk) 01:43, 22 March 2018 (UTC)
  • You stated Do we really need any cites at all in the lede? The simplest solution to your objection is to delete them all.
  • A number of medical editors have checked the medical sources for WP:MEDRS – which most of the statements in the article require – a number of times over the course of all 4 FAC nominations. As for the handful (10-ish) refs that only require WP:RS for citing only non-medical claims, I don't think so. In any event, that "conference" reference you're referring to is not citing a conference. It's citing text on a webpage which is about a conference. It cites nothing from the conference itself because I have no clue what was discussed in said conference. Seppi333 (Insert 2¢) 01:52, 22 March 2018 (UTC)

    If you'd like, I can ping some of those editors who reviewed the sources against WP:MEDRS if you want their input. Seppi333 (Insert 2¢) 01:53, 22 March 2018 (UTC)

    • You don't need to ping anyone. You just need to assert that your cites have been checked. if you do that, it relieves me of the responsibility of worrying about it.. But BTW, if you "have no clue what was discussed in said conference", then why the heck are you citing it???? Lingzhi ♦ (talk) 02:08, 22 March 2018 (UTC)
      • Sounds good. After going through the list of references, it doesn't look like I added any new non-medical sources since the last FAC, so I'm pretty sure all of them have been manually checked for WP:RS. I know for certain that all medical sources have been checked for WP:MEDRS compliance. As for that citation about a conference, it's not a citation to a conference; it's a citation to a webpage. This webpage discusses a conference. I'm not sure why you keep saying it's a citation to a conference. The quote parameter in the corresponding citation template for that reference only contains text from the webpage. FWIW, this particular citation was mentioned at a previous FAC in this link when Jytdog and I were discussing how to phrase the coverage of HMB-containing medical foods and their uses as well as what references should be used to cite that content. Seppi333 (Insert 2¢) 02:21, 22 March 2018 (UTC)
• How can you cite.. a webpage announcing a conference... when 1) that website contains zero supporting text for any assertion in the article, and 2) You have no idea what was said in the conference??? is that more clear? Lingzhi ♦ (talk) 02:24, 22 March 2018 (UTC)

  What do you mean by that website contains zero supporting text for any assertion in the article? The only text from that webpage which is being used to support any statement in the article is the text in the citation's quote parameter. For simplicity, I'll re-quote that text here: "Dr. Nissen and his collaborator Dr. Naji N. Abumrad, Professor and Chair, Department of Surgery, Vanderbilt University, discovered beta-hydroxy-beta-methylbutyrate (HMB) and its beneficial effects on human health and performance. HMB is currently marketed nationally by Abbott Laboratories as Revigor™, which is a component of Ensure® Muscle Health, and Juven®, which is a nutritional beverage that is clinically shown to promote healing after injury or surgery." Seppi333 (Insert 2¢) 02:28, 22 March 2018 (UTC)

• Let me summarize, unfortunately at length: 1) I use bundled cites, so you may accuse me of hypocrisy, but I think your use of bundled cites is way overboard. Choose the very best sources available, and match the cite to the corresponding assertion. You can't add eight or nine cites to the end of an entire paragraph when the eight cites are covering seven different assertions. 2) You didn't need to delete everything, most especially if you think medical editors would complain about the deletion. [Please mentally add an exclamation point after that statement]. You needed to choose the very best sources available, and match the cite to the corresponding assertion. 3) In general, when some reviewer complains about something and the nominator "suddenly deletes everything", it makes me nervous. That response doesn't seem carefully thought out at all.... if you can suddenly delete it without harming the article, then why was it in there in the first place? 4) I find it difficult to believe that any non-Wikipedia publication would accept text from "a webpage announcing a conference, with a two-sentence blurb about its history" as a WP:RS or WP:MEDRS source. 5) When I see one source that I think is very shaky, and it's cited four times, that makes me wonder, "Are there more such?" 6) But if all the WP:MED editors are OK with all of that, then I will take their word for it. Lingzhi ♦ (talk) 02:56, 22 March 2018 (UTC)

  Fair enough. The reason I didn't mind deleting the end-of-paragraph references is that each sentence in the lead is fully cited in the source of the article (you'll see what I mean if you examine the source of the lead). Fully re-citing the lead only requires that I decensor those censored refs (note that after the last sentence of each paragraph, I censored the bundled reference markup in the source - I wouldn't decensor that if I decensored the sentence-by-sentence refs). I can decensor those lead refs once I'm back on my laptop in a couple of hours if you'd prefer that sentence-by-sentence citation approach (please let me know if so!). TBH, I prefer citing each lead sentence over citing each lead paragraph; I only cited it by paragraph because other reviewers have complained about sentence-by-sentence lead citations in the past. Seppi333 (Insert 2¢) 03:26, 22 March 2018 (UTC)

  • Do whatever medical articles typically do. I find it difficult to believe that medical articles bundle many cites at the end of a paragraph, even though different cites/sources in the bundle refer to different sentences and different assertions... but if they do, then do so. Heck, the dinosaur people seem to cite to a 50-page range and say "yawn, whatever", which I find quite literally shocking (except in a few cases). But if they say whatever, then hell, whatever. And if the medical people think it's OK to cite to a webpage announcing a conference, then whatever... And if the cites in the lede are covered in body text, then delting them from the lede is the correct thing to do unless they are controversial. Lingzhi ♦ (talk) 03:41, 22 March 2018 (UTC)

    Most medical articles cite the medical claims in lead and use sentence-by-sentence citations as opposed to the grouped end-of-paragraph citations that was being used here. I dislike the end-of-paragraph method. The only reason I used that method is that every other time I nominate an article at FAC and cite individual lead sentences in the nominated article, a reviewer comes along and opposes solely on the basis of the lead's non-compliance with their preference for no lead citations. Neither the FA criteria, nor MOS:LEADCITE, say "don't fully cite the lead" or "don't cite every lead sentence". But, since FAC is based upon consensus, I end up making compromises that result in awkward citation styles like end-of-paragraph citations.

    Anyway, I doubt anyone will come around to object to the sentence-by-sentence format before this nomination closes if I restore it now, so I'll go ahead and do that shortly.

    FWIW, I agree that citing a 50-page range is absurd. Seppi333 (Insert 2¢) 05:31, 22 March 2018 (UTC)

    @Lingzhi: Done. Please let me know if you find the current lead citation format acceptable. I'm open to removing the citations to non-medical claims, although I would prefer to fully cite the lead. Seppi333 (Insert 2¢) 06:03, 22 March 2018 (UTC)

• Nolo contendere I give up. The problem is not that I don't know what I'm doing; the problem is that Wikipedia has no fucking idea what it's doing. And things "work" only because there really is nothing that says what works or doesn't work, so only the loudest voice or voices always win (not naming names from personal experience, for fear of being blocked, but here I am not talking about the dinosaur editors), which is the same thing as saying it doesn't actually work at all, it just pretends to work, and everyone goes along and pretends it does work. Lingzhi ♦ (talk) 06:12, 22 March 2018 (UTC)

References

Comments by Jo-Jo Eumerus

Image review:

1. File:Beta-Hydroxy beta-methylbutyric acid.svg: License and use seem fine for me.
2. File:Calcium β-hydroxy β-methylbutyrate monohydrate.jpg: License and use seem fine for me. I wonder where the caption comes from.
3. File:Muscle protein synthesis signaling cascades.jpg: License and use seem fine for me, and caption is reasonably sourced. I wonder though, is it mammalian target of rapamycin or mechanistic target of rapamycin? My impression is that "mammalian" is much more widely used, despite our article title thinking otherwise.
4. File:ISSN HMB statement Fig 2.jpg: License and use seem fine for me.
5. File:HMB biosynthesis and metabolism diagram - no labels.svg: Use and factual accuracy seem fine for me; I wonder if it's correct to license a work derived from a CC-BY2.0 image under CC-BY4.0.
6. File:Butyric acid carbons.svg: License and use seem fine for me.
7. File:Hydroxymethylbutyric acid.png: License and use seem fine for me.
8. File:HMB synthesis historical.svg and File:HMB synthesis 2.svg: License and use seem fine for me; may want to consider to copy part of the article text into the file page so that the image is sourced there as well.

The chemical diagrams don't have ALT text, I presume for complexity reasons? Jo-Jo Eumerus (talk, contributions) 10:05, 2 February 2018 (UTC)

2. The caption is based upon my measurement of the capsule size (NB: I uploaded this image) and the ingredients listed on the supplement bottle.
3. mammalian-TOR and mechanistic-TOR are unofficial synonyms for the currently accepted UNIPROT name of "Serine/threonine-protein kinase mTOR"; per MOS:MCB, article titles should be listed under the current UNIPROT name. Based upon a pubmed search, most sources use "mammalian" as opposed to "mechanistic", however most of the sources in the article use "mechanistic" when referring to the protein or protein complexes (i.e., mTORC1/mTORC2), so I chose to use this term instead.
5. Given that I had to manually redraw every line in this image in inkscape (NB: I didn't use an automated trace module on the original image file), shifted a number of lines in subsequent uploads (~20 based upon the file history), and completely redrew the bottom half of this diagram, I think it would be difficult for the original author to claim that it's a derivative work. E.g., if you superimposed the original diagram on top of this diagram and set its opacity to 50%, you would see that the line segments in these diagrams don't align. Frankly, I think it's more likely that this image falls within the public domain given that it is literally just a graphic containing rather arbitrarily placed line segments.

• I've drawn a labeled version of this diagram, however I need to make a few adjustments to it since its conversion to png looks terrible at the moment. I had the original file that I uploaded under the file name Commons:File:HMB biosynthesis and metabolism diagram.svg deleted for that reason. Seppi333 (Insert 2¢) 17:29, 3 February 2018 (UTC)

Will do this soon and respond here once this has been done.

• Done – I've added the corresponding paragraphs from the HMB article to the file description templates in Commons:File:HMB synthesis historical.svg and Commons:File:HMB synthesis 2.svg. Seppi333 (Insert 2¢) 18:23, 3 February 2018 (UTC)

Re – the image alt text: all of the images in this article actually have alt text and captions; if you were looking at the alt text link in the FA toolbox, it wouldn't show this because most of the images in the article are displayed in templates ({{infobox drug}}, {{multiple image}}, or {{Annotated image 4}}) that bork the altviewer tool. The chemical structure diagrams in the infobox have alt text but not individual captions (NB: they do have a footer caption though). The chemical structure and chemical synthesis diagrams in the chemistry section are displayed using {{Multiple image}}, which doesn't display alt text captions in the altviewer tool. All 4 of those images do have alt text and captions though. Seppi333 (Insert 2¢) 17:29, 3 February 2018 (UTC)

Regarding 5, Since it is BY only (not sharealike) can license it under whatever as long as attribution is given.. (but anyhow older versions of CC licenses can be relicensed into newer versions) Galobtter (pingó mió) 17:42, 3 February 2018 (UTC)

Seems like it's all set then. Jo-Jo Eumerus (talk, contributions) 14:42, 4 February 2018 (UTC)

@Jo-Jo Eumerus: I've uploaded File:HMB biosynthesis and metabolism diagram.png and used the template caption as the description on the file page. I also mentioned a third metabolic pathway that I didn't depict due to the fact that most of the associated enzymes are not known. This png version is currently only used in ja:3-ヒドロキシイソ吉草酸 and d:Q223081. I intend to upload an SVG version that contains image text within the next week. Seppi333 (Insert 2¢) 05:24, 8 February 2018 (UTC)

There is a template for Wikimedia screenshots that should probably be applied, but I can't find it now... Jo-Jo Eumerus (talk, contributions) 09:37, 8 February 2018 (UTC)

​ c:Template:Wikimedia-screenshot - google works well enough; I'm not sure if it is necessary though Galobtter (pingó mió) 09:46, 8 February 2018 (UTC)

Haha. I hadn't even considered that; text on WP is indeed licensed under CC-BY-SA-3.0, although it seems sort of odd to change the licensing in this case because the relevant text is really just a bunch of nouns (+1 adjective and verb+preposition). Since I'm the sole author of everything depicted in the PNG image though, I'm pretty sure I can just implicitly multi-license the WP text that I wrote in that image as public domain (see Wikipedia:Multi-licensing) by listing only that copyright license for the SVG background file as the license for that PNG file (i.e., the text is PD and the background is CC-BY-4.0, so the whole image is CC-BY-4.0). That said, this will be a moot issue in a week since I intend to save the PNG conversion of the SVG image and reupload it over the current PNG image file. Seppi333 (Insert 2¢) 10:23, 8 February 2018 (UTC)

Comments by DePiep

• The infobox says: Molar mass 118.131 g/mol

Wikidata beta-hydroxy beta-methylbutyric acid (Q223081) says 118.063 dalton, (from PubChem).

If you have a source for the infobox value, that would be best. I have reasons to doubt the PubChem calculations, since their atomic weights differ from the standard ones (compared). -DePiep (talk) 19:00, 2 February 2018 (UTC)

• About licence (US, EU).

On the FDA site I found no hits (trying variants of Beta-Hydroxy beta-methylbutyric acid): FDA

On the EMA site I found no hits (trying variants of Beta-Hydroxy beta-methylbutyric acid): EMA (should hit by INN, INN variants like 'acid' might be relevant).

An Y then for: no FDA and EMA presence. (Others do check me). -DePiep (talk) 23:07, 2 February 2018 (UTC)

Thanks for reviewing DePiep. HMB is not currently licensed as a pharmaceutical, so I wouldn't expect it to have an entry on the FDA or EMA websites.

PubChem lists a molar mass of 118.132, ChemSpider lists 118.131, and HMDB lists 118.1311 (4 sig figs). It would seem that the molecular weight, rounded to 3 significant figures, is probably 118.131. Seppi333 (Insert 2¢) 16:46, 3 February 2018 (UTC)

So the infobox best uses ChemSpider + add its ref. PubChem values and Wikidata values are fishy (so outside of this FAC, if not used). And I suggest: no more time spending on this. -DePiep (talk) 18:32, 3 February 2018 (UTC)

I've added the chemspider ref to that drugbox field. Seppi333 (Insert 2¢) 20:31, 3 February 2018 (UTC)

Comments from Dank

• I haven't usually been doing prose reviews for biochem articles, and there's some question in my mind whether I have anything useful to add to the process. I occasionally follow biophysics (not the same thing, I know). But biochemistry articles are sometimes failing for lack of support; I see this one is on its 4th go-around. A prose review can help with that problem ... provided I can come up with something useful to say, and I don't embarrass myself in the process. We'll see.
• I made a couple of edits that got rid of "however"; see if those edits make sense to you, and feel free to discuss.
• "KIC dioxygenase": I'm not following why that's italicized.
• "This concentration is far too low to be an adequate dietary source of HMB for obtaining pharmacologically active concentrations of the compound in blood plasma, but milk products could be fortified with HMB to confer benefits to skeletal muscle.": The last sentence of the abstract says "fortification of milk and dairy products with HMB and/or HICA appears to be justified." Recommending that bovine milk be fortified with HMB, presumably for some medical food or even for general consumption, is quite a jump from "there's not much HMB in bovine milk". Do they justify that recommendation in the article?
• "which subsequently acquired six HMB-related patents": What does "subsequently" mean here?
• I'm personally on board with the frequent use of "e.g.", but others may have a different view.
• Support on prose per my standard disclaimer. Well done. As always, feel free to revert my copyediting. These are my edits. - Dank (push to talk) 16:09, 4 February 2018 (UTC)

Thanks for taking on a review of the prose!

• I've removed the italics from KIC dioxygenase. I don't remember why I originally italicized it.
• I'll look into the source about food fortification and respond back when I've done so.
  • Re - the paper about food (milk) fortification w/ HMB: the introduction describes the clinical effects of HMB on muscle protein metabolism (NB: the coverage of this is a brief summary of what was covered in Beta-Hydroxy beta-methylbutyric acid#Medical and Beta-Hydroxy beta-methylbutyric acid#Enhancing performance) and then states: "The presence of naturally occurring levels of HMB and HICA in milk and fermented dairy products has not been reported to date. Because milk and fermented dairy products are widely consumed, they are potentially suitable media for fortification with HMB and/or HICA in order to deliver the above-described physiological benefits."
    In the last section ("Results and discussion"), the paper says, "On the basis of existing clinical studies and largely musculoskeletal outcome measures, the endogenous concentrations of HMB and HICA found by this study are insufficient by large margins to deliver any physiological benefits. Hence the opportunity arises for the fortification of milk, milk-based nutritional products, and fermented dairy products with HMB and/or HICA."
    You can view the full-text of this article by following this link. Seppi333 (Insert 2¢) 03:41, 5 February 2018 (UTC)
    • Thanks, I skimmed it, and then deleted "but milk products could be fortified with HMB to confer benefits to skeletal muscle" ... the safety and benefits of HMB aren't addressed by this study at all, so it's not a basis for recommending that milk ought to be fortified with HMB (which is the conclusion some readers would be left with). - Dank (push to talk) 03:55, 5 February 2018 (UTC)
      • That seems reasonable. Seppi333 (Insert 2¢) 04:27, 5 February 2018 (UTC)
• which subsequently acquired six HMB-related patents – A synonym for that context would be "later". It's just being used to say that the company wasn't established at the same time that all of the patents were acquired.

FWIW, I appreciate the edits you made to the article. Seppi333 (Insert 2¢) 02:44, 5 February 2018 (UTC)

Great, glad I could help. I'll ping you when I get stuck on a biophysics article. - Dank (push to talk) 02:54, 5 February 2018 (UTC)

Comments by Soupvector

Overall, I think this is a well-written, well-referenced, very interesting article. My comments here will focus on the medical uses section.

Regarding the first sentence of Uses / Medical (also reflected in the lede) Some branded products that contain HMB (i.e., certain formulations of Ensure and Juven) are medical foods that are intended to be used to provide nutritional support under the care of a doctor in individuals with muscle wasting due to HIV/AIDS or cancer, to promote wound healing following surgery or injury, or when otherwise recommended by a medical professional.[sources 4] - the cited sources don't appear to be MEDRS. The Nature Medicine ref (Khamsi 2013) has the superficial appearance of being substantial, but is just a news item. The Iowa State ref (Linn 2013) is an Abbott-sponsored conference proceeding; the other 2 refs under ref note 4 are Abbott-produced documents. Surely this is insufficient for medical claims, particularly in the Uses/Medical section of a FAC? There are other references that note the benefits of HMB+glutamine+arginine - but do any of them attribute the benefits to HMB itself?

Overall, the Uses / Medical reads (and is sourced) like an article about Juven and Ensure - but we have those already. Is there biomedical consensus that HMB, specifically, has efficacy for these medical uses? If not, this might be a stronger FAC if the medical claims were pared back to what the MEDRS support - that products containing HMB have evidence of safety and benefit for fat-free mass (with links to the Ensure, Juven, etc articles), but the specific benefits of HMB for these applications are not known (are they?). One potential mitigation: refer to "HMB-containing supplements" rather than "supplementation with HMB" - especially in the lead - unless the latter has MEDRS support. — soupvector (talk) 03:18, 11 February 2018 (UTC)

@Jytdog: I think you may want to comment on this since you worked with me in the 1st/2nd FACs to expand the content on this. Seppi333 (Insert 2¢) 05:20, 14 February 2018 (UTC)

As for the article on Juven, that was created after this content was added to the HMB article simply because it was readily apparent that the topic was notable from the refs that were cited in the HMB article. Seppi333 (Insert 2¢) 05:22, 14 February 2018 (UTC)

Will follow up on this tomorrow; sorry for the delay in responding. Seppi333 (Insert 2¢) 09:26, 16 February 2018 (UTC)

Sorry about the late follow-up!

I figured Jytdog would comment, but I'll just go ahead and summarize the reasoning behind why the medical food-related content was worded/cited as it is at the moment:

• In the United States and EU, medical foods are regulated differently relative to food and dietary supplements. In the US, medical foods have 3 requirements; they must be: (1) a product that can be ingested or administered via a feeding tube, (2) labeled for the dietary management of a specific medical disorder, disease or condition for which there are distinctive nutritional requirements, and (3) intended to be used under medical supervision.
• The sentence "Some branded products that contain HMB (i.e., certain formulations of Ensure and Juven) are medical foods that are intended to be used to provide nutritional support under the care of a doctor in individuals with muscle wasting due to HIV/AIDS or cancer, to promote wound healing following surgery or injury, or when otherwise recommended by a medical professional" isn't actually making any claims about the efficacy of Juven and certain Ensure formulations for the listed uses; if you compare this sentence to requirements (2) and (3) listed above, you'll notice that it's worded in a manner that reflects the definition of a medical food in the context of Juven and "Ensure Enlive". In other words, this sentence was very precisely worded in a manner that states only the aspects of those two products (Juven and Ensure Enlive) that cause them to be regulated as a medical food. Consequently, this sentence is really just making a regulatory claim about a medical use.
  If you still take issue with the wording in that sentence though, I'm fine with cutting the clause that lists the factors that cause those products to be regulated as medical foods. In other words, the sentence would be written as: "Some branded products that contain HMB (i.e., certain formulations of Ensure and Juven) are medical foods."
• As for MEDRS-compliant source which support the efficacy of the uses which are listed in that sentence:
  • to promote wound healing following surgery or injury – I have come across a handful of reviews that mentioned Juven's use/efficacy for wound healing; but, given that the underlying clinical trials of Juven for wound healing are limited to a small number of trials that each involved a distinct type of wound (e.g., surgery, a burn, an ulcer, etc.), the results of these trials can't be aggregated. In other words, I'd essentially have to summarize the results of individual clinical trials by wound type. I'd prefer not to do that since it'd require an entire paragraph of coverage, which would be excessive given the comparatively small amount of research on this use relative to the other uses that are listed in that section (i.e., Juven for AIDS/HIV & cancer and HMB for sarcopenia).
  • ... in individuals with muscle wasting due to HIV/AIDS or cancer – the efficacy of Juven for these uses is covered in the 1st paragraph of the "Medical" section; all of those efficacy statements are cited by a review, systematic review, or meta-analysis.
• To clarify what research has been conducted with Juven vs HMB alone to assess their efficacy for preserving lean body mass in a particular condition:
  • Juven – most of the clinical research involves individuals with cachexia (e.g., cachexia due to cancer, HIV/AIDS, and other causes)
  • HMB alone – most of the clinical research involves older adults with sarcopenia; virtually all of the studies that assessed the efficacy of HMB in healthy individuals for the uses listed in Beta-Hydroxy beta-methylbutyric acid#Enhancing performance have used HMB by itself, not Juven or a combination product.
  • In the "Medical" section, Juven's efficacy for various conditions is covered only in the 1st paragraph, whereas the efficacy of HMB alone for various conditions is covered only in the 2nd paragraph.

I hope that clarifies things. If you'd like me to make the changes I described in the 2nd bullet above, let me know. Seppi333 (Insert 2¢) 10:38, 18 February 2018 (UTC)

Does the article provide support for HMB itself for these conditions? Setting aside performance, which was not the focus of my concern, is there a scientific consensus (to which we can point) stating that HMB is the active ingredient to which the benefit can be ascribed, or is it just one of the ingredients? I would guess that we won't ascribe, in articles for each of the ingredients of Juven, all of the benefits attributed to Juven? You again cite support for Juven, but Juven isn't the subject of this FAC. — soupvector (talk) 14:41, 18 February 2018 (UTC)

Does the article provide support for HMB itself for these conditions? ... is there a scientific consensus (to which we can point) stating that HMB is the active ingredient to which the benefit can be ascribed, or is it just one of the ingredients? Yes, provided that the sentence refers to "HMB" and not "Juven". If a sentence about efficacy mentions "Juven" and not "HMB", then it has not been established that HMB alone has efficacy for treating the listed condition. All of the reviews/meta-analyses in "Medical" have reference quotes containing the relevant statements from the ref which support the assertions about treatment efficacy for a given condition, so you'll be able to verify this quite easily; however, statements like "more research is needed to determine efficacy for XYZ" don't have corresponding quotes in their citations since I didn't think that was necessary. To be clear, dozens of studies have examined the efficacy of HMB alone for various medical conditions and roughly 20 studies have examined the efficacy of Juven for various conditions.

The reason that Juven was mentioned at all in this article is that a number of reviews on the medical uses of HMB have discussed Juven at length (i.e., they usually include several paragraphs on studies that were conducted with Juven). In other words, Juven is notable in relation to HMB; if that weren't true, reviews about HMB wouldn't mention Juven or "HMB/ARG/GLN" mixtures. It's not unusual for articles on drugs to cover the treatment efficacy of combination products which contain them; e.g., bupropion is a featured article that contains a dedicated subsection – Bupropion#Obesity – about the use of bupropion/naltrexone for treating obesity (NB: bupropion is not FDA-approved for treating obesity or even commonly prescribed off-label for that purpose). Seppi333 (Insert 2¢) 17:24, 18 February 2018 (UTC)

I continue to have the sense that this is about Juven and not HMB. Neither the article nor your responses here demonstrate to me that HMB itself is the active agent. Are we going to add all of these claims to the ARG and GLN articles as well, or should we reserve medical claims for the combinations that are actually supported in the MEDRS? I don't want to wade too far into WP:OSE, but your reference to bupropion is illustrative: the first sentence in that section cites a MEDRS that states (as a specific conclusion) that bupropion is effective as a treatment for obesity. Can we do the same for HMB? — soupvector (talk) 18:15, 18 February 2018 (UTC)

Sorry, I thought you were asking for my assessment of the sources that are cited in the medical section, not links to them. One of the sources cited in the 2nd paragraph is PMID 26169182 - the abstract alone sufficiently answers your second question.

As for the first question, I don't see why Juven shouldn't be covered in the glutamate and arginine articles. Adding coverage of medical foods in relevant WP articles isn't a priority for me though. Seppi333 (Insert 2¢) 05:14, 19 February 2018 (UTC)

That's what I needed - it's not a top-line finding in that review, but they do mention cancer and AIDS wasting as specific conditions that are ameliorated by HMB. Thanks. — soupvector (talk) 13:21, 19 February 2018 (UTC)

• I support this FAC nomination. — soupvector (talk) 00:01, 20 March 2018 (UTC)

Comments by T.Shafee

I've only minor comments, since others have mentioned everything else I'd noticed.

• Some of the quotes in the references may be overly long,, but I don't think it's a big problem.
• The image pair of File:Butyric_acid_carbons.svg and File:Hydroxymethylbutyric_acid.png should both be a little smaller in order to better match the text size elsewhere.
• The greek letters in image File:Butyric_acid_carbons.svg should probably be a little larger.
• I noted above, but will repeat here for easier reading, that the "References" and "Reference notes" sections should probably be merged. For example: my references are this, this, these, and this. (which uses the code {{refn|Reference set: <ref name="ref1"/><ref name="ref2"/><ref name="ref3"/>}}. It at least puts all the references into the same list so are easier to read.

References

Overall, a very clear and well-written article. T.Shafee(Evo&Evo)^talk 05:58, 11 February 2018 (UTC)

HMB with larger Greek letters

Would this version be responsive? — soupvector (talk) 05:58, 14 February 2018 (UTC)

I slightly revised File:Butyric acid carbons 2.svg and uploaded a version of the HMB structure diagram (File:Beta-Hydroxy beta-methylbutyric acid 2.svg) with line sizes that are identical to the butyric acid carbons diagram. I replace both of the images that were in that section with these two images since File:Butyric acid carbons 2.svg looks better than File:Butyric acid carbons.svg and has enlarged greek letters.

With respect to the size of the letters "OH"/"HO" in these diagrams: after looking at all the svg files used in the article, I noticed that the size of the letters relative to the lines in those 2 structure diagrams is actually very similar to the other structure/synthesis diagrams; so, I think it might look awkward if those diagrams had smaller letters if I don't make a similar change in the other structure/synthesis diagrams. I did reduce the size of these images from 250px to 235px though; if I reduce it any further, the captions will end up wrapping to a new line (NB: it looks awkward), which is something I'd like to avoid.

As for the references, the main reason I separated the grouped references from the reference list is that the references section doesn't appear well-formatted IMO when they're combined. As an alternative, I could change ^{[sources #]} to ^{[ref note #]} if you think that would remove the potential for confusion that you mentioned above. Seppi333 (Insert 2¢) 09:23, 16 February 2018 (UTC)

Good work with the diagrams. These sorts of referencing situations are always tricky, so I'm happy to stick with your solution. I support the current version for FA. T.Shafee(Evo&Evo)^talk 01:11, 22 March 2018 (UTC)

Comments by Barbara Page

I'm helping to review this article and have a tendency to simply fix an issue rather than leave megabytes of comment on the review page. I will list the things that I have noted about the article and have or have not edited.

• one of the templates on the bottom of the article displayed in its fully expanded form; I have it now displaying in the collapsed form to be consistent with the other templates.
• these foods are mentioned but not linked to articles- alfalfa, asparagus, avocados, cauliflower, grapefruit, and catfish. Is there a reason for this?
• I added more categories. If there is a problem, let me know.
• There are many duplicate links. Since I am not heavily experienced in the FA process, perhaps there is a reason for so many duplicates. Can you explain that? (not my inexperience but the many duplicate links)
• Did you take a quick look at the article in the other languages to see if there other references that could be used in this article? I don't think that is required, I am only curious.

Barbara (WVS) ✐  ✉ 13:16, 2 March 2018 (UTC)

@Barbara (WVS): Sorry for the long-delayed reply. I've been very busy off-wiki lately.

• Collapsing that navbox seems fine.
• I don't really think it's useful to wikilink to those. Wikilinking catfish is potentially useful simply because it's comparatively less common in Western diets.
• The two ageing-related categories probably aren't that relevant here, but I think the other three you added are apt.
• Normally, there should be at most 1 link per term in the lead prose and 1 link per term in the body prose; that doesn't apply to wikilinked terms in infoboxes, tables, and captions though - just the prose.
• The last time I looked at the HMB articles in non-English Wikipedias, they were all very short and most cited outdated sources. If one of the HMB articles on a non-English Wikipedia were GA/FA-class (or similarly rated for quality), it probably would've been a good idea to go through them though.

Seppi333 (Insert 2¢) 18:06, 14 March 2018 (UTC)

I am quite satisfied with your responses and would be very pleased to see this article promoted to Featured Article status. It is certainly the best that Wikipedia has to offer. It now exists as the best resource online on this topic. The Best of Regards to you, Barbara ✐  ✉ 01:16, 20 March 2018 (UTC)

Thanks for your support Barbara. Seppi333 (Insert 2¢) 01:33, 20 March 2018 (UTC)

Comments by Dudley

• Support and minor suggestions.
• I would wikilink sarcopenic, hypercatabolic, cachexia.
  • Linking those sounds fine to me. I'll add them tomorrow when I'm on my laptop since I'm on my phone right now. Seppi333 (Insert 2¢) 03:52, 18 March 2018 (UTC)\
    • Done. Seppi333 (Insert 2¢) 01:30, 20 March 2018 (UTC)
• p=.08 Is it possible to explain this simply - 8% probability that the result was due to chance?
  • Given this is not statistically significant and from a primary source, I've proposed this should just be removed, especially given there are lots of high quality secondary sources used in the article, and that we are talking about FA. What do you think @Dudley Miles? --Tom (LT) (talk) 19:21, 15 March 2018 (UTC)
    • I agree. Dudley Miles (talk) 19:28, 15 March 2018 (UTC)
      • @Tom (LT): Fair enough. I've removed those sentences (see diff). Seppi333 (Insert 2¢) 03:52, 18 March 2018 (UTC)
• Information about when HMB related patents expire would be helpful. Dudley Miles (talk) 15:40, 15 March 2018 (UTC)
  • I'll look tomorrow and add this info if I can find it. Seppi333 (Insert 2¢) 03:52, 18 March 2018 (UTC)
    • I looked yesterday, but couldn't seem to find anything from google. I'm certain that the patent expiry information is available somewhere, but I'm not sure how to find it. Seppi333 (Insert 2¢) 00:42, 22 March 2018 (UTC)
      • I'll try again later when I have more time - the US patent office's website probably includes it somewhere. I agree that this is relevant & notable information that's worth adding to the article. Seppi333 (Insert 2¢) 06:20, 22 March 2018 (UTC)
      • @Boghog: Do you have any thoughts on where I might find the expiry dates for the six HMB-related patents that are mentioned in the article? Seppi333 (Insert 2¢) 07:24, 22 March 2018 (UTC)
        • The short answer: In the US, granted date + 17 years. I will try to find an explicit source that talks about the expiration dates of these specific patents. If we can't find explicit source, we will have to rely on WP:CALC. Boghog (talk) 08:57, 22 March 2018 (UTC)
          • Absent a compelling need to invent patent expiration dates, I would avoid adding them if not apparent in RS; that they "would be helpful" might be true, but only if accurate. Patent expiration is a process, not a carved-in-stone event; often subject to vagaries of patent law and litigation. — soupvector (talk) 13:06, 22 March 2018 (UTC)

• OK, as far as I can tell, the patents in question have not even been granted yet:

• "19 results found in the Worldwide database for: Metabolic Technologies as the applicant". Espacenet patent search.
• WO application 2015094925, White TO, "Stable liquid filled hard capsule comprising beta-hydroxy-beta-methylbutyric acid", published 25 June 2015, assigned to Capsugel Belgium Nv 
• WO application 2012140276, Noti C, Schmid L, Rittiner B, Hanselmann P, Bierstedt A, "Process for the preparation of 3-hydroxy-3-methylbutyric acid or its calcium salts", published 10 January 2013, assigned to Lonza Ltd 

• There is no guarantee that any of these patent applications will be granted, hence it way too premature to talk about expiration dates. Boghog (talk) 20:49, 22 March 2018 (UTC)
  • Thanks for looking into that Boghog. Since that's the case, I suppose it's best to leave the history section as is. Seppi333 (Insert 2¢) 22:59, 22 March 2018 (UTC)
    • If the patents have not been granted, the history section is wrong to say that MTI acquired patents and should be amended. Dudley Miles (talk) 23:47, 22 March 2018 (UTC)
      • The source that supports the statement about six patents says ""Metabolic Technologies took out six patents on HMB and licensed the right to manufacture it and to cite Nissen's research to several sports supplement brands."; if "took out" means "applied for", I suppose this can be addressed by just tweaking the verb in that sentence. However, based upon Boghog's patent search results link, there appears to now be 10 patent applications by Metabolic Technologies which include HMB in the patent title. I can't seem to find an indication on that website of whether or not those patents were approved/granted though. Seppi333 (Insert 2¢) 00:03, 23 March 2018 (UTC)
      • The Metabolic Technologies website indicates that they currently hold and enforce multiple HMB-related patents. [3][4] It doesn't indicate the exact number, but it's more than 3 based upon the first link. Seppi333 (Insert 2¢) 00:21, 23 March 2018 (UTC)
        • In digging further, it does appear that the following patents have been granted to Metabolic Technologies:

• US patent 8815280, Rathmacher J, Fuller J, Baier S, Nissen S, Abumrad N, "Nutritional intervention for improving muscular function and strength", issued August 26, 2014, assigned to Metabolic Technologies. 
• US patent 9259430, Rathmacher J, Fuller J, Baier S, Nissen S, Abumrad N, "Nutritional intervention for improving muscular function and strength", issued February 16, 2016, assigned to Metabolic Technologies. 
• US patent 9539224, Rathmacher J, Fuller J, Baier S, Nissen S, Abumrad N, "Nutritional intervention for improving muscular function and strength", issued January 10, 2017, assigned to Metabolic Technologies. 
• US patent 9707241, Rathmacher J, Fuller J, Baier S, Nissen S, Abumrad N, "Nutritional intervention for improving muscular function and strength", issued July 18, 2017, assigned to Metabolic Technologies. 
• US patent 9770424, Rathmacher J, Fuller J, Baier S, Nissen S, Abumrad N, "Nutritional intervention for improving muscular function and strength", issued September 26, 2017, assigned to Metabolic Technologies. 

Boghog (talk) 04:24, 23 March 2018 (UTC)

Closing comment: This has had a very thorough review and I shall be promoting shortly. After promotion, I'd be grateful if someone could check for duplinks. We seem to have quite a few and I can't really see that we need them all. This tool will highlight any duplication. But that isn't worth delaying promotion over. Sarastro (talk) 21:52, 23 March 2018 (UTC)

• Closing note: This candidate has been promoted, but there may be a delay in bot processing of the close. Please see WP:FAC/ar, and leave the {{featured article candidates}} template in place on the talk page until the bot goes through. Sarastro (talk) 21:53, 23 March 2018 (UTC)

The above discussion is preserved as an archive. Please do not modify it. No further edits should be made to this page.