Talk:Β-Hydroxy β-methylbutyric acid

message: *Review of HMB's effects on skeletal muscle, pharmacodynamics, and pharmacokinetics from January 2016
*Systematic review on supplements for cachexia from 2016
Seppi333 (Insert 2¢) 19:15, 5 December 2016 (UTC)
thread_title: December 2016

message: *Covers HMB's effects on protein synthesis in brain cells, neurite outgrowth, and age-related dendritic remodeling in the brain of various nonhuman animals: 
**Evidence that HMB is a (non-protein small molecule) neurotrophic factor in the brain of nonhuman animals (mice - in vitro/rats - in vivo)
**Increases protein synthesis in the mouse brain (in vitro) and pig brain (in vivo)
Seppi333 (Insert 2¢) 03:19, 28 May 2016 (UTC)
thread_title: Recent preclinical research

message: Leaving this here for personal reference.
*Has a detailed mTOR signaling cascade diagramFigure 2: The mTOR Signaling Pathway 
*Discusses and includes a diagram of signaling cascades involved in MPS/MPB hosted here temporarily
Seppi333 (Insert 2¢) 08:51, 1 June 2016 (UTC)
thread_title: mTOR signaling cascades

message: *HMB-CoA HMDB entry
*HMB-CoA KEGG entry
** 3-Hydroxyisovaleryl-CoA ⇔ 3-Methylcrotonyl-CoA + H2O – 
** 3-Hydroxyisovaleryl-CoA ⇔ 3-Hydroxyisovalerate – "unclear reaction"
* alpha-Ketoisocaproate + O2 ⇒ 3-Hydroxy-3-methylbutyrate + CO2 – ; 4-hydroxyphenylpyruvate dioxygenase = KIC dioxygenase per 
Should be able to write a comprehensive biosynthesis/metabolism section using these 5 refs:
# (covers α-KIC → HMB reaction)
# (covers most of the metabolic pathway; has another diagram)
# (covers HMB-CoA → HMB)
# (covers most of the metabolic pathway; includes the same metabolic pathway graphic as the ISSN review)
#ISSN review -  (review with the article's current metabolic pathway graphic)
Seppi333 (Insert 2¢) 00:10, 7 June 2016 (UTC)
thread_title: Metabolic pathway links

message: ;WADA and NCAA refs
*allowed by WADA and the NCAA 
*WADA banned substances list 
;Physical/Chemical properties and classification refs
*Chemical taxonomy - http://www.hmdb.ca/metabolites/HMDB00754#taxonomy (already defined as ) 
*Parent compounds and the relationship between the acid/base 
;Primary clinical research involving Juven (3 g HMB + 14 g arginine + 14 g glutamine)
* - 2002 trial of Juven for cancer cachexia
* - 2002 trial examining the effect of Juven on collagen deposition 
* - 2007 trial examining the effects of Juven in critically ill trauma patients.
* - 2008 Phase 3 clinical trial of Juven w/o exercise for cancer cachexia
* - 2015 trial of Juven for postoperative recovery of quadriceps muscle strength after total knee arthroplasty
* - 2016 trial with Juven examining the effect on vascular endothelial function in older adults after 6 months
;Reviews covering clinical trials with Juven
* - 2013 review that probably covers the phase 3 + other trials w/ Juven for cachexia (need to obtain this review)
* - 2014 review of Juven for diabetic foot ulcers
*  / #cite_note-Nutrition_supplements_for_athletes_2014_review-14 - covers the effects of Juven on lean body mass+immune function in individuals w/ AIDS and lean body mass in individuals w/ cancer cachexia 
* / #cite_note-Systematic_review_December_2013-5 - relevant section quoted below
*
Seppi333 (Insert 2¢) 00:55, 25 August 2016 (UTC)
thread_title:  FAC-related references 

message: "Beta-hydroxy-beta-methylbutyrate free acid improves resistance training-induced muscle mass and function: a systematic review" - anticipated completion (publication?) date: September 2016
:Research question: What is the effect of HMB-FA on resistance training-induced muscle mass and function?
:Primary outcomes:
:*Effects on skeletal muscle in sedentary, active and recreationally-trained subjects and HMB-supplemented compared with placebo.
:*Change in lean mass from baseline to final intervention.
:*Change in strength and biochemical parameters from baseline to final intervention.
Seppi333 (Insert 2¢) 11:45, 31 July 2016 (UTC)
thread_title: Upcoming systematic review

message: Thanks for doing a literature search and posting these sources here; I really appreciate it!  I'll read through and use them to write new content when I get a chance later today or tomorrow. Seppi333 (Insert 2¢) 21:26, 9 September 2016 (UTC)
replies: text: I've been busier than I expected off-wiki over the past few days.  I should have time to follow-up on this tomorrow night. Seppi333 (Insert 2¢) 22:48, 12 September 2016 (UTC)
replies: text:  My bad for not doing this yet; I'm going to stop trying to give myself further deadlines that I can't meet due to how busy I've been this past week.  I will, however, use the sources that you linked below to add content before I look for sources to cite for adding a statement on the calcium content of HMB-Ca. Seppi333 (Insert 2¢) 23:40, 16 September 2016 (UTC)
replies: text: That's OK - the fitzpatrick book is already used and there is not much else here that is useful. I was mostly recording my work actually trying to track down sales.. Jytdog (talk) 23:43, 16 September 2016 (UTC)
replies: text:  Oh.  Well, I'll still look through them anyway - might have something worth adding.  Also, one of the refs that you linked to at FAC mentioned something you might be interested in (see the bold+underlined text below). As of when this ref was published, all of MTI's products contained HMB, as stated in the quote.  As of now, they also sell or license one product which contains no HMB: an adenosine triphosphate (ATP) supplement which they call "betaATP". Seppi333 (Insert 2¢) 00:44, 17 September 2016 (UTC)
replies: text: FWIW, based upon the prices of currently available HMB-Ca and HMB-FA supplements and the relative efficacy in primary studies between HMB-FA and HMB-Ca, I really doubt MTI is making close to $10,000,000 annually on HMB-FA alone. Seppi333 (Insert 2¢) 00:51, 17 September 2016 (UTC)
thread_title: New sources

message: am looking for sources for this, will record what I find here.  others are free to add of course...
This is really hard as MTI is a private company so have no obligation (and don't) report sales.  
*   -- says that 10,300 athletes at the 2000 Summer Olympics were tested for doping, and of them, 2758 were surveyed about their use of supplements.   24 of them said they used HMB.  (for comparison, 1996 used some kind of vitamin)
*   (not a great ref, but guy who runs it seems to be not insignificant in world of lifers, see here).   Has a blog entry focused on primary sources  published in 2014 and the followup  published this July and their remarkable results, and writes: "A supplement that’s been around for a long time, but which isn’t all that popular, works better than steroids?".   "which isn't all that popular".   Not much but something.
*   again really slim.  From 1999.  One of roundtable participants says: "HMB sales declined rapidly after it was introduced because it had no perceived effect on muscle mass and was expensive."  Same person also said: "Likewise, HMB has not lived up to its marketing hype as an anabolic agent"  Another, " Among athletes who want to gain muscle mass, protein and creatine supplements are popular, especially in football, wrestling, and track and field. HMB and the banned substances DHEA and the “andros” are used by few or none" 
This is all I found in a google search 10 pages out.  Will check my library... Jytdog (talk) 21:10, 9 September 2016 (UTC)
thread_title:  sources for extent of  use of HMB 

message: *   -- has a passage describing the origin of Metabolic Technologies.  Also discusses the science a bit - says early research was hyped, and notes the 2009 review that found it had some benefit for people just starting a training regimen but not for people who have been at it longterm. 
*  --  "hook" was launch of Ensure Muscle Health;  discusses that HMB is marketed to older/middle aged folks who want to start getting into shape, because that is who benefits the most (citing the 2009 review again)
*  - a trade rag, notes that HMB is marketed for horses but there is "little to no data to support its use in horses".
Same search as above. Jytdog (talk) 21:10, 9 September 2016 (UTC)
thread_title: sources on business background and marketing

message: Need to find a WP:RS-quality source for this, since I think it's worth covering.  Probably should be mentioned in the article since the  navbox links here and most HMB-Ca brands don't appear to list this information on the supplement bottles. Seppi333 (Insert 2¢) 23:40, 16 September 2016 (UTC)
thread_title: Mg of ionic calcium per gram of pure HMB from HMB-Ca

message: Biosynthesis is currently a subsection pharmacology/pharmacokinetics.  Pharmacokinetics is what the body does to the drug, not how the body synthesizes it. Also some bugs and I assume many other "critters" synthesize HMB. Hence logically biosynthesis should not be a subsection of pharmacokinetics, but rather the chemistry (or possibly a new biochemistry) section.  The reason I ask is that MC-CoA is used in the biosynthesis of a tetrasaccharide produced by  Bacillus anthracis (anthrax  bacteria) and HMB itself has been used in the laboratory synthesis of this tetrasaccharide (see ). This new material would not be appropriate to add to the pharmacokinetics section but would be appropriate in a new biochemistry section. Thoughts? Boghog (talk) 09:13, 25 September 2016 (UTC)
replies: text: I'm okay with moving it. I recognized that it wasn't really relevant to the PK section when I created it under that heading, but I put it there anyway simply because the HMB metabolism diagram also illustrates HMB biosynthesis. Seppi333 (Insert 2¢) 10:33, 25 September 2016 (UTC)
thread_title:  Placement of biosynthesis section 

message: With thanks to  for supplying database searches, I have expanded the synthesis section.  There are several more syntheses that could be added, but most of these are obscure reactions or reactions where HMB is a side product.  Hence I question the notability of these.  Also there were some early syntheses reported (and associated physical data of the synthesized HMB) based on an aldol condensation without dehydration between acetone and ethyl acetate.  However I think this would be highly unlikely since the dehydration is the driving force for the reaction. As far as physical data, there is not much more that could (or should) be added.  By far, the most notable aspect of HMB is that is a naturally produced metabolite and a food additive .  Much less has been published about its chemistry.  Hence per WP:DUE, it is appropriate that the chemistry section of this article is significantly shorter than some of the other sections. Boghog (talk) 09:35, 25 September 2016 (UTC)
replies: text: you should probably post this in Nergaal's review section to discuss with him what should or could be added about to HMB's chemistry. He's the only reviewer who has commented on the chemistry section thus far. Seppi333 (Insert 2¢) 17:52, 26 September 2016 (UTC)

text: Yes.  I was thinking of doing something similar.  Thanks for taking care of that. Boghog (talk) 17:32, 9 November 2016 (UTC)
thread_title:  Expansion of chemistry section 

message: I split part of the material that you added to the history section to the synthesis section and re-added a slightly duplicate statement about its very first reported synthesis to the history section in this edit.  Is that okay with you? Seppi333 (Insert 2¢) 16:52, 9 November 2016 (UTC)
replies: text: Yes.  I was thinking of doing something similar.  Thanks for taking care of that. Boghog (talk) 17:32, 9 November 2016 (UTC)
thread_title: History → Synthesis section split 

message: #  I just did a literature search and found one new review: ; it was published online on May 10, 2017.  Also, I contacted the corresponding author of this prospective systematic review a few weeks ago; he told me that it has been submitted to an academic journal and is currently being peer-reviewed, so I suspect that it will be published within the next 1–3 months. Once it's published, I intend to add a summary of its findings on the effects/efficacy of HMB in healthy individuals.
As for this review, I intend to use it to cite existing statements and possibly add new material which is relevant to clinical uses (e.g., HMB supplementation in elderly/sarcopenic individuals). These are the sections from the review that are relevant to its clinical uses:
: 
: 
Also, check for new pharmacology content to add from these sections of the review: 
*Effects on protein metabolism in skeletal muscle
*Effects on leucine metabolism
*Effects on cholesterol metabolism
*Exercise performance and effects of HMB supplementation
Most of the quoted material above is already covered to some extent in the article at the moment, but the commentary from this review isn't reflected in the current article text.  Should new content be added, or should this reference just be appended to existing text that it supports? Do any of you have any proposed revisions to the article in mind?  @Doc James: I'm directing that last question mainly at you since you took issue with how some of the medical statements were worded during the most recent FAC nomination. Seppi333 (Insert 2¢) 04:27, 3 June 2017 (UTC)
thread_title: 1st

message: #"A systematic review on β-hydroxy-β-methylbutyrate free acid supplementation suggests improvements in measures of muscle recovery, performance, and hypertrophy following resistance training."
 The "#Upcoming systematic review" was finally published in an academic journal in September.  Boghog, do you think we should renominate the article for FA or continue with GAN once I add coverage of this review and the other reviews listed below to the article? Seppi333 (Insert 2¢) 04:48, 9 November 2017 (UTC)
replies: text: FYI: I'm waiting to get ref #5 below () from WP:RX before I update the article with the content from all of the reviews cited in this section (i.e., the ones in #Section reflist). Seppi333 (Insert 2¢) 01:13, 19 November 2017 (UTC)
thread_title: 2nd

message: # This is a primary source which examines the same pharmacodynamic and pharmacokinetic parameters for HMB-CA as the ones that were examined in the study on HMB-FA and leucine which is currently cited in the article – October 2017 primary study. Seppi333 (Insert 2¢) 06:12, 9 November 2017 (UTC)
thread_title: Pharmacodynamics and pharmacokinetics of HMB-CA in humans ''in vivo''

message: From this search:
Meta-analyses from 2018
* ; meta-analysis: performance-enhancement literature  
* ; meta-analysis + systematic review: healthy adults - presumably mostly athletes (effect on exercise-induced muscle damage)  
----
Systematic reviews from 2018
*  - systematic review: elderly/clinical 
*  - systematic review: clinical population - post-surgical recovery 
----
Other reviews from 2017–2018
*  - review by Cruz-Jentoft that I missed earlier 
Add these when time permits:
#  - review: athletes
#  - (narrative?) review: elderly ("aging neuromuscular junction")
#  - sports pharmacology review
#  - review: athletes
#  - review
Seppi333 (Insert 2¢) 21:36, 23 October 2018 (UTC)
thread_title:  Updates - recent (post-FA) reviews and meta-analyses 

message: This is what the beginning of the article looks like in desktop view on my Huawei P20 Pro: https://i.imgur.com/zyevlQK.jpg
Is it necessary to put the conjugate base in a ? The full, acid name is not in a nowrap. Cheers, Manifestation (talk) 10:49, 26 February 2019 (UTC)
replies: text: That's a good point. I support nowrap or other methods to keep each beta with its next word, but no need to keep separate words together. I changed it to allow breaking at the whitespace, as the acid itself is, as you note. DMacks (talk) 15:34, 26 February 2019 (UTC)
replies: text:  Great! It works. Thanks a lot, Manifestation (talk) 16:25, 27 February 2019 (UTC)
thread_title:  Lead breaks on mobile phones in desktop view 

message: This article mentions the supplement Myoplex three times: once in the lead, once under "Use", and once under "History". However, the brand under which the formulation was distributed, EAS, has been discontinued as of June 2018 by its parent, Abbott Laboratories (see here and here). Therefore, I assume Myoplex is no longer being produced. Many shops still have it in stock, but I guess they will run out eventually. Cheers, Manifestation (talk) 17:09, 27 February 2019 (UTC)
replies: text: Removed it Seppi333 (Insert 2¢) 20:27, 1 August 2023 (UTC)
thread_title:  Myoplex 

message: There is little to no information about where companies are sourcing HMB for human consumption. Where is the compound coming from? Animals? Plants? Mining? 2603:6011:5840:77:E883:6958:855B:D2FC (talk) 14:51, 29 May 2023 (UTC)
replies: text: There’s an entire section on chemical synthesis … Seppi333 (Insert 2¢) 20:27, 1 August 2023 (UTC)
thread_title:  Sources of HMB 

message: There are scores of very recent secondary reviews in PubMed, and yet most of the sourcing in the Uses section of this article are dated. SandyGeorgia (Talk)  13:39, 1 August 2023 (UTC)
replies: text: Where is supplements purged, under what brand name. 67.4.0.15 (talk) 19:30, 1 August 2023 (UTC)

text: Might update it in a year or two. Seems fine right now. Seppi333 (Insert 2¢) 20:14, 1 August 2023 (UTC)
thread_title:  Source update