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Most of these articles are currently available here. The file names reflect the ref names defined in the source code below. Seppi333 ( Insert 2¢) 19:05, 23 May 2016 (UTC)
References
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Seppi333 ( Insert 2¢) 20:36, 29 April 2016 (UTC)
@ Jytdog: Hey, sorry to bother you again with this request, but would you be willing to send me these 5 reviews? [3] [4] [5] [6] [7] They're paywalled and I don't have access. I'd really appreciate it. Seppi333 ( Insert 2¢) 22:28, 23 May 2016 (UTC)
Seppi333 ( Insert 2¢) 19:15, 5 December 2016 (UTC)
References
Molecular Aspects of Medicine 2016 review
was invoked but never defined (see the
help page).PEDs in sports 2015 review
was invoked but never defined (see the
help page).HMB for cancer cachexia 2013 review
was invoked but never defined (see the
help page).Effects of amino acid derivatives 2015 review
was invoked but never defined (see the
help page).Nutrition supplements for athletes 2014 review
was invoked but never defined (see the
help page).Seppi333 ( Insert 2¢) 03:19, 28 May 2016 (UTC)
References
In conclusion, we have shown for the first time that HMB promoted neurite outgrowth through PI3K/Akt and ERK1/2 signaling pathways in Neuro2a cells. Its effect in neuron differentiation is concomitant with higher levels of glucose transporters, the activation of mTOR by mTORC2 and consequently an increase in protein synthesis. Moreover, HMB is involved in promoting MEF2 activity and expression of members of this family of transcriptional factors. We believe that HMB may have great potential as [a neurotrophic] factor promoting neuron differentiation and plasticity. Our results indicated a novel effect of HMB on neurite outgrowth and call to further studies to reveal its positive influences on cognitive outcomes.
The fractional rates of protein synthesis in the brain were greater in the piglets supplemented with HMB 40 and 80 or fed the HP diet compared to feeding the LP diet alone or the fasting condition (P < 0.05, Fig. 5, G).
Leaving this here for personal reference.
Seppi333 ( Insert 2¢) 08:51, 1 June 2016 (UTC) Updated 00:42, 27 August 2016 (UTC)
References
Should be able to write a comprehensive biosynthesis/metabolism section using these 5 refs:
Seppi333 ( Insert 2¢) 00:10, 7 June 2016 (UTC)
References
Figure 8.57: Metabolism of L-leucine
{{
cite book}}
: External link in |quote=
(
help)
Reduced activity of MCC impairs catalysis of an essential step in the mitochondrial catabolism of the BCAA leucine. Metabolic impairment diverts methylcrotonyl CoA to 3-hydroxyisovaleryl CoA in a reaction catalyzed by enoyl-CoA hydratase (22, 23). 3-Hydroxyisovaleryl CoA accumulation can inhibit cellular respiration either directly or via effects on the ratios of acyl CoA:free CoA if further metabolism and detoxification of 3-hydroxyisovaleryl CoA does not occur (22). The transfer to carnitine by 4 carnitine acyl-CoA transferases distributed in subcellular compartments likely serves as an important reservoir for acyl moieties (39–41). 3-Hydroxyisovaleryl CoA is likely detoxified by carnitine acetyltransferase producing 3HIA-carnitine, which is transported across the inner mitochondrial membrane (and hence effectively out of the mitochondria) via carnitine-acylcarnitine translocase (39). 3HIA-carnitine is thought to be either directly deacylated by a hydrolase to 3HIA or to undergo a second CoA exchange to again form 3-hydroxyisovaleryl CoA followed by release of 3HIA and free CoA by a thioesterase.
For Nergaal's review
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For Jytdog's review
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For Nergaal+Axl's reviews (History section content)
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References
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Seppi333 ( Insert 2¢) 00:55, 25 August 2016 (UTC)
"Beta-hydroxy-beta-methylbutyrate free acid improves resistance training-induced muscle mass and function: a systematic review" - anticipated completion (publication?) date: September 2016
Seppi333 ( Insert 2¢) 11:45, 31 July 2016 (UTC)
I'd like to start off by stating that I hope my commenting here does not turn away any potential GA reviewers since I believe these concerns can be addressed quickly, so much so that I'm tempted to go ahead and make them myself rather than post here, but I believe the prose will be more consistent if these changes are made by those who have written the majority of the article already.
In the opening there is a stand-alone sentence discussing HMB's safety in "young or old individuals", but to me that is a little unclear. The first source cited for that statement says "Chronic consumption of HMB is safe in both young and old populations", so I looked through it to see what they consider young. It appears they are referring to young adults as later in the paper they state that no research has been carried out on infants and very little research has been carried out on adolescents. Additionally no research appears to have been carried out on pregnant women.
With this in mind I would suggest further clarifying in the lead the lower bound of the age of individuals for which HMB supplementation appears safe. In addition the description of its safety in humans in the side effects section should be qualified so that it excludes human sub-populations that HMB hasn't been well studied in. Lastly the first sentence of that section implies that safety for animals in general has been established—"the safety profile of HMB in humans and animals"—this should be reworded/expanded to convey either which animals it has been found to be safe for, and/or to describe how animal models have been used to help establish the safety profile in humans. M. A. Bruhn ( talk) 05:13, 3 August 2016 (UTC)
the utility of HMB supplementation in animals has been shown in numerous studies, which have demonstrated enhanced body weight gain and carcass yield in slaughter animals", but I'm going to look for other sources that cover its use in livestock for this purpose before covering it in the article since I don't know how common/notable this practice is. Seppi333 ( Insert 2¢) 09:24, 3 August 2016 (UTC); edited at 14:17, 3 August 2016 (UTC)
@ M. A. Bruhn: How would you feel about the addition of this statement to the paragraph on pregnancy?
As of 2016 [update], 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. [1]
I'm hesitant to add this, although I think it's notable since this is the company that grants licenses to allow the inclusion of HMB in dietary supplements. The reference is a primary source for the statement, but the statement itself is advisement as opposed to a medical claim. Seppi333 ( Insert 2¢) 02:45, 23 August 2016 (UTC)
References
Pregnant or lactating women are advised against taking HMB because safety studies have not yet been conducted for these populations.
The page name doesn't seem to be the most obvious choice to be. Thinking about WP:NAMINGCRITERIA I might suggest as alternatives (in rough order of preference):
Thoughts? If there is a decision for no change, then I think the last 2 terms should also be redirects here. Klbrain ( talk) 18:38, 3 August 2016 (UTC)
@ Jytdog: 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)
Metabolic Technologies 2011 sales + 5-year sales projections
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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.
This is all I found in a google search 10 pages out. Will check my library... Jytdog ( talk) 21:10, 9 September 2016 (UTC)
Same search as above. Jytdog ( talk) 21:10, 9 September 2016 (UTC)
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 {{
mineral supplements}}
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)
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 PMID 15152001, 20614885). 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)
With thanks to Sizeofint 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)
@ Boghog: 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)
The content in this tab has been moved again; it's now located at
Wikipedia:Featured article candidates/Beta-Hydroxy beta-methylbutyric acid/archive3#Comments by Doc James.
Please continue this discussion there. | ||
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The review you are using comes to three sentences of conclusions "HMB contributed to preservation of muscle mass in older adults." which says it help keep mm mass, does not comment on those with sarcopenea. "HMB supplementation may be useful in the prevention of muscle atrophy induced by bed rest or other factors." A decrease of uncertainty "Further studies are needed to determine the precise effects of HMB on muscle strength and physical function in older adults." Means it is unclear if HMB affects str or function. Doc James ( talk · contribs · email) 03:04, 17 December 2016 (UTC)
@
Doc James: What is your concern with that sentence, specifically, if the population samples included in the RCTs from that meta-analysis (
link here) wasn't the issue?
Seppi333 (
Insert 2¢) 00:00, 20 December 2016 (UTC)
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Checked for updates on November 9th, 2017 (my birthday, yay). Seppi333 ( Insert 2¢) 05:33, 9 November 2017 (UTC)
Added (partially) - more potential material to go through and add if deemed encyclopedic; see collapse tab below
As for this [1] 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:
Excerpts of the sections on Elderly populations, Toxicity + adverse effects, and Conclusions
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Also, check for new pharmacology content to add from these sections of the review:
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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)
@ Boghog, Jytdog, and Doc James: The " #Upcoming systematic review" was finally published in an academic journal in September. [2] 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)
Seppi333 ( Insert 2¢) 05:19, 9 November 2017 (UTC) – Updated 06:12, 9 November 2017 (UTC)
- HMB increases myofibrillar protein synthesis by upregulation via the mTOR pathway. - HMB modulates protein degradation by inhibiting the ubiquitin-proteasome proteolytic pathway in muscle cells. Ubiquitin is induced by immobilization and by catabolic conditions, inducing proteasome expression through the activation of nuclear factor kappa B (NK-κB), thus promoting muscle wasting. HMB may inhibit the activity of NK-κB, attenuating muscle loss in wasting conditions. - The integrity of cell membranes depends on cholesterol synthesis from acetyl-CoA. HMB is converted to ß-hydroxyß- methylglutaryl-coenzyme A (HMG-CoA), which is turned into cholesterol by the HMG-coenzyme A reductase, the rate-limiting enzyme to cholesterol synthesis. Thus, HMB supplementation may stabilize cell membranes. HMB itself seems to be a component of cell membranes. - HMB may prevent cell apoptosis and enhance muscle satellite cell survival. - HMB increases proliferation and differentiation of muscle stem cells, via the MAPK/ERK and PI3K/Akt pathways. - HMB up-regulates transcription and expression of the IGF-I gene in skeletal muscle and liver. IGF exerts an anabolic action and causes hypertrophy of skeletal muscle fibers. |
References
HMB's mechanisms of action are generally considered to relate to its effect on both muscle protein synthesis and muscle protein breakdown (Figure 1) [2, 3]. HMB appears to stimulate muscle protein synthesis through an up-regulation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), a signaling cascade involved in coordination of translation initiation of muscle protein synthesis [2, 4]. Additionally, HMB may have antagonistic effects on the ubiquitin–proteasome pathway, a system that degrades intracellular proteins [5, 6]. Evidence also suggests that HMB promotes myogenic proliferation, differentiation, and cell fusion [7]. ... Exogenous HMB-FA administration has shown to increase intramuscular anabolic signaling, stimulate muscle protein synthesis, and attenuate muscle protein breakdown in humans [2].
Clinical trials performed in older adults confirm that HMB can attenuate the progression of sarcopenia in elderly subjects. HMB supplementation results in an increase in skeletal muscle mass and strength in the elderly and its effect is even greater when combined with physical exercise.
HMB is widely used as an ergogenic supplement by young athletes.
No serious side effects have been reported with leucine, EAA, or HMB supplementation; and the health risks associated with these supplements are few and predictable.
Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 μM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < [0.001]) and suppressions in MPB (PA: 7.6 ± 1.2 μmol Phe per leg min-1, Ca-HMB: 5.2 ± 0.8 μmol Phe per leg min-1, p < 0.01). ... During the first 2.5 h period we gathered postabsorptive/fasted measurements, the volunteers then consumed 3.42 g of Ca-HMB (equivalent to 2.74 g of FA-HMB) ... It may seem difficult for one to reconcile that acute provision of CaHMB, in the absence of exogenous nutrition (i.e. EAA's) and following an overnight fast, is still able to elicit a robust, perhaps near maximal stimulation of MPS, i.e. raising the question as to where the additional AA's substrates required for supporting this MPS response are coming from. It would appear that the AA's to support this response are derived from endogenous intracellular/plasma pools and/or protein breakdown (which will increase in fasted periods). ... To conclude, a large single oral dose (~3 g) of Ca-HMB robustly (near maximally) stimulates skeletal muscle anabolism, in the absence of additional nutrient intake; the anabolic effects of Ca-HMB are equivalent to FA-HMB, despite purported differences in bioavailability (Fig. 4).
The stimulation of MPS through mTORc1-signalling following HMB exposure is in agreement with pre-clinical studies (Eley et al. 2008). ... Furthermore, there was clear divergence in the amplitude of phosphorylation for 4EBP1 (at Thr37/46 and Ser65/Thr70) and p70S6K (Thr389) in response to both Leu and HMB, with the latter showing more pronounced and sustained phosphorylation. ... Nonetheless, as the overall MPS response was similar, this cellular signalling distinction did not translate into statistically distinguishable anabolic effects in our primary outcome measure of MPS. ... Interestingly, although orally supplied HMB produced no increase in plasma insulin, it caused a depression in MPB (−57%). Normally, postprandial decreases in MPB (of ~50%) are attributed to the nitrogen-sparing effects of insulin since clamping insulin at post-absorptive concentrations (5 μU ml−1) while continuously infusing AAs (18 g h−1) did not suppress MPB (Greenhaff et al. 2008), which is why we chose not to measure MPB in the Leu group, due to an anticipated hyperinsulinaemia (Fig. 3C). Thus, HMB reduces MPB in a fashion similar to, but independent of, insulin. These findings are in-line with reports of the anti-catabolic effects of HMB suppressing MPB in pre-clinical models, via attenuating proteasomal-mediated proteolysis in response to LPS (Eley et al. 2008).
Ongoing GA review
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Reviewer: Tom (LT) ( talk · contribs) 05:47, 28 November 2017 (UTC)
Assessment
Discussion
@ Tom (LT): I finished going through the points below. I just need your feedback on my responses about some of the statements in the medical and pharmacodynamics sections in order to proceed with addressing those issues. Seppi333 ( Insert 2¢) 23:12, 21 December 2017 (UTC) Review of textHappy to discuss any of the below. These suggestions are not intended to be prescriptive & only intended to illustrate my concerns about the 'well-written' point. They don't all need to be addressed for the review to pass. Hope it is helpful. -- Tom (LT) ( talk) 22:59, 3 December 2017 (UTC)
Lead
UsesMedical
Side-effects
Pharmacology
Chemistry
History
In general
I hope this review helps. Will start working through your replies in the next day or so. Cheers -- Tom (LT) ( talk) 22:50, 8 December 2017 (UTC) @ Tom (LT): I combed through the references and compiled the list below that includes every primary source cited in the article which has a PMID number (the handful of other primary sources cite statements in chemistry, history, etc., so they're all covered by WP:RS). Primary sources with a PMID # that were cited in this article – the sections in the body where these are cited are listed in parentheses:
Seppi333 ( Insert 2¢) 00:02, 9 December 2017 (UTC) COMMENT: Under the rubric of "less is more," I find it unnecessary and annoying that so many of the references include extended quotation of material from the abstracts or articles. Some exceeding 150 words and containing mention of references in the cited article. If the information is essential to the article it belongs in the article. If not, it does not belong anywhere. I've rarely seen reference bloat of this nature, and this is a particularly egregious example. David notMD ( talk) 15:45, 12 December 2017 (UTC)
ConclusionThanks for your patience, Seppi333. This is a great article that you've put a lot of effort into. With your many changes I feel the article has improved to meet GA criteria. I have one or two concerns that I feel we are at loggerheads here with and will pop on the article's talk page, but nothing that would mean this article shouldn't become a GA. Thanks for your responsiveness; Merry Christmas! -- Tom (LT) ( talk) 22:26, 25 December 2017 (UTC) |
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:
It would be useful if a third editor could comment on these; Seppi333 makes some good points and it may be useful if a third or fourth editor could offer their opinion on the above. Have a lovely festive season, -- Tom (LT) ( talk) 22:53, 25 December 2017 (UTC)
β-Hydroxy β-methylbutyric acid is a member of the carboxylic acid family of organic compounds and like them, it is a weak acid.
@ EdChem: Would you happen to know of a source that can be used to cite this statement? Seppi333 ( Insert 2¢) 09:56, 17 April 2018 (UTC)
β-Hydroxy β-methylbutyric acid is a weak acid and a member of the carboxylic acid family of organic compounds."
β-hydroxy β-methylbutyric acid is a member of the carboxylic acid family of organic compounds. It is a structural analog...
@ Seppi333: I don't really think any citation was needed as the fact that it is a carboxylic acid and a weak acid is utterly uncontroversial and unlikely to be challenged by anyone. Nevertheless, I also agree with DMacks that the pKa value confirms that it is a weak acid, and the form of words proposed and implemented from your discussion is accurate. Sorry for the delay in responding. EdChem ( talk) 12:04, 20 July 2018 (UTC)
There appears to be disagreement on whether Beta-Hydroxy beta-methylbutyrate should be described like an alternate name of Beta-Hydroxy beta-methylbutyric acid in the lead. While the two are closely related (They're each other's conjugate acid/base.), I think that the article needs to recognize that they're not exactly the same molecule. Care to differ or discuss with me? The Nth User 02:10, 1 June 2018 (UTC)
Most of the content in the introduction is repeated literally word-for-word in the article body. In my revisions I removed all the duplicate info], repeated word for word in the body. I read other bioactive chemical pages and they don’t have the extreme repetitiveness of this article. The intro almost reads as an advertisement for HMB, let your customers read the article first. Anyway, I saw no reason given for undoing my copyedits, why were they removed? Dogshu ( talk) 13:04, 29 August 2018 (UTC)
From this search:
Meta-analyses from 2018
Systematic reviews from 2018
Other reviews from 2017–2018
Add these when time permits:
Seppi333 (
Insert 2¢) 21:36, 23 October 2018 (UTC)
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 {{ nowrap}}? The full, acid name is not in a nowrap. Cheers, Manifestation ( talk) 10:49, 26 February 2019 (UTC)
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)
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)
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)
This is the
talk page for discussing improvements to the
Β-Hydroxy β-methylbutyric acid article. This is not a forum for general discussion of the article's subject. |
Article policies
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Find medical sources: Source guidelines · PubMed · Cochrane · DOAJ · Gale · OpenMD · ScienceDirect · Springer · Trip · Wiley · TWL |
Archives: 1 |
This article is written in American English, which has its own spelling conventions (color, defense, traveled) and some terms that are used in it may be different or absent from other varieties of English. According to the relevant style guide, this should not be changed without broad consensus. |
Β-Hydroxy β-methylbutyric acid is a featured article; it (or a previous version of it) has been identified as one of the best articles produced by the Wikipedia community. Even so, if you can update or improve it, please do so. | ||||||||||||||||||||||||||||
This article appeared on Wikipedia's Main Page as Today's featured article on May 28, 2018. | ||||||||||||||||||||||||||||
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This article is rated FA-class on Wikipedia's
content assessment scale. It is of interest to multiple WikiProjects. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Ideal sources for Wikipedia's health content are defined in the guideline
Wikipedia:Identifying reliable sources (medicine) and are typically
review articles. Here are links to possibly useful sources of information about Β-Hydroxy β-methylbutyric acid.
|
The contents of the Calcium beta-hydroxy-beta-methylbutyrate page were merged into Β-Hydroxy β-methylbutyric acid. For the contribution history and old versions of the redirected page, please see its history; for the discussion at that location, see its talk page. |
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Diagrams and reviews
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Most of these articles are currently available here. The file names reflect the ref names defined in the source code below. Seppi333 ( Insert 2¢) 19:05, 23 May 2016 (UTC)
References
|
Seppi333 ( Insert 2¢) 20:36, 29 April 2016 (UTC)
@ Jytdog: Hey, sorry to bother you again with this request, but would you be willing to send me these 5 reviews? [3] [4] [5] [6] [7] They're paywalled and I don't have access. I'd really appreciate it. Seppi333 ( Insert 2¢) 22:28, 23 May 2016 (UTC)
Seppi333 ( Insert 2¢) 19:15, 5 December 2016 (UTC)
References
Molecular Aspects of Medicine 2016 review
was invoked but never defined (see the
help page).PEDs in sports 2015 review
was invoked but never defined (see the
help page).HMB for cancer cachexia 2013 review
was invoked but never defined (see the
help page).Effects of amino acid derivatives 2015 review
was invoked but never defined (see the
help page).Nutrition supplements for athletes 2014 review
was invoked but never defined (see the
help page).Seppi333 ( Insert 2¢) 03:19, 28 May 2016 (UTC)
References
In conclusion, we have shown for the first time that HMB promoted neurite outgrowth through PI3K/Akt and ERK1/2 signaling pathways in Neuro2a cells. Its effect in neuron differentiation is concomitant with higher levels of glucose transporters, the activation of mTOR by mTORC2 and consequently an increase in protein synthesis. Moreover, HMB is involved in promoting MEF2 activity and expression of members of this family of transcriptional factors. We believe that HMB may have great potential as [a neurotrophic] factor promoting neuron differentiation and plasticity. Our results indicated a novel effect of HMB on neurite outgrowth and call to further studies to reveal its positive influences on cognitive outcomes.
The fractional rates of protein synthesis in the brain were greater in the piglets supplemented with HMB 40 and 80 or fed the HP diet compared to feeding the LP diet alone or the fasting condition (P < 0.05, Fig. 5, G).
Leaving this here for personal reference.
Seppi333 ( Insert 2¢) 08:51, 1 June 2016 (UTC) Updated 00:42, 27 August 2016 (UTC)
References
Should be able to write a comprehensive biosynthesis/metabolism section using these 5 refs:
Seppi333 ( Insert 2¢) 00:10, 7 June 2016 (UTC)
References
Figure 8.57: Metabolism of L-leucine
{{
cite book}}
: External link in |quote=
(
help)
Reduced activity of MCC impairs catalysis of an essential step in the mitochondrial catabolism of the BCAA leucine. Metabolic impairment diverts methylcrotonyl CoA to 3-hydroxyisovaleryl CoA in a reaction catalyzed by enoyl-CoA hydratase (22, 23). 3-Hydroxyisovaleryl CoA accumulation can inhibit cellular respiration either directly or via effects on the ratios of acyl CoA:free CoA if further metabolism and detoxification of 3-hydroxyisovaleryl CoA does not occur (22). The transfer to carnitine by 4 carnitine acyl-CoA transferases distributed in subcellular compartments likely serves as an important reservoir for acyl moieties (39–41). 3-Hydroxyisovaleryl CoA is likely detoxified by carnitine acetyltransferase producing 3HIA-carnitine, which is transported across the inner mitochondrial membrane (and hence effectively out of the mitochondria) via carnitine-acylcarnitine translocase (39). 3HIA-carnitine is thought to be either directly deacylated by a hydrolase to 3HIA or to undergo a second CoA exchange to again form 3-hydroxyisovaleryl CoA followed by release of 3HIA and free CoA by a thioesterase.
For Nergaal's review
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For Jytdog's review
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For Nergaal+Axl's reviews (History section content)
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References
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Seppi333 ( Insert 2¢) 00:55, 25 August 2016 (UTC)
"Beta-hydroxy-beta-methylbutyrate free acid improves resistance training-induced muscle mass and function: a systematic review" - anticipated completion (publication?) date: September 2016
Seppi333 ( Insert 2¢) 11:45, 31 July 2016 (UTC)
I'd like to start off by stating that I hope my commenting here does not turn away any potential GA reviewers since I believe these concerns can be addressed quickly, so much so that I'm tempted to go ahead and make them myself rather than post here, but I believe the prose will be more consistent if these changes are made by those who have written the majority of the article already.
In the opening there is a stand-alone sentence discussing HMB's safety in "young or old individuals", but to me that is a little unclear. The first source cited for that statement says "Chronic consumption of HMB is safe in both young and old populations", so I looked through it to see what they consider young. It appears they are referring to young adults as later in the paper they state that no research has been carried out on infants and very little research has been carried out on adolescents. Additionally no research appears to have been carried out on pregnant women.
With this in mind I would suggest further clarifying in the lead the lower bound of the age of individuals for which HMB supplementation appears safe. In addition the description of its safety in humans in the side effects section should be qualified so that it excludes human sub-populations that HMB hasn't been well studied in. Lastly the first sentence of that section implies that safety for animals in general has been established—"the safety profile of HMB in humans and animals"—this should be reworded/expanded to convey either which animals it has been found to be safe for, and/or to describe how animal models have been used to help establish the safety profile in humans. M. A. Bruhn ( talk) 05:13, 3 August 2016 (UTC)
the utility of HMB supplementation in animals has been shown in numerous studies, which have demonstrated enhanced body weight gain and carcass yield in slaughter animals", but I'm going to look for other sources that cover its use in livestock for this purpose before covering it in the article since I don't know how common/notable this practice is. Seppi333 ( Insert 2¢) 09:24, 3 August 2016 (UTC); edited at 14:17, 3 August 2016 (UTC)
@ M. A. Bruhn: How would you feel about the addition of this statement to the paragraph on pregnancy?
As of 2016 [update], 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. [1]
I'm hesitant to add this, although I think it's notable since this is the company that grants licenses to allow the inclusion of HMB in dietary supplements. The reference is a primary source for the statement, but the statement itself is advisement as opposed to a medical claim. Seppi333 ( Insert 2¢) 02:45, 23 August 2016 (UTC)
References
Pregnant or lactating women are advised against taking HMB because safety studies have not yet been conducted for these populations.
The page name doesn't seem to be the most obvious choice to be. Thinking about WP:NAMINGCRITERIA I might suggest as alternatives (in rough order of preference):
Thoughts? If there is a decision for no change, then I think the last 2 terms should also be redirects here. Klbrain ( talk) 18:38, 3 August 2016 (UTC)
@ Jytdog: 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)
Metabolic Technologies 2011 sales + 5-year sales projections
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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.
This is all I found in a google search 10 pages out. Will check my library... Jytdog ( talk) 21:10, 9 September 2016 (UTC)
Same search as above. Jytdog ( talk) 21:10, 9 September 2016 (UTC)
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 {{
mineral supplements}}
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)
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 PMID 15152001, 20614885). 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)
With thanks to Sizeofint 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)
@ Boghog: 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)
The content in this tab has been moved again; it's now located at
Wikipedia:Featured article candidates/Beta-Hydroxy beta-methylbutyric acid/archive3#Comments by Doc James.
Please continue this discussion there. | ||
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The review you are using comes to three sentences of conclusions "HMB contributed to preservation of muscle mass in older adults." which says it help keep mm mass, does not comment on those with sarcopenea. "HMB supplementation may be useful in the prevention of muscle atrophy induced by bed rest or other factors." A decrease of uncertainty "Further studies are needed to determine the precise effects of HMB on muscle strength and physical function in older adults." Means it is unclear if HMB affects str or function. Doc James ( talk · contribs · email) 03:04, 17 December 2016 (UTC)
@
Doc James: What is your concern with that sentence, specifically, if the population samples included in the RCTs from that meta-analysis (
link here) wasn't the issue?
Seppi333 (
Insert 2¢) 00:00, 20 December 2016 (UTC)
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Checked for updates on November 9th, 2017 (my birthday, yay). Seppi333 ( Insert 2¢) 05:33, 9 November 2017 (UTC)
Added (partially) - more potential material to go through and add if deemed encyclopedic; see collapse tab below
As for this [1] 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:
Excerpts of the sections on Elderly populations, Toxicity + adverse effects, and Conclusions
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Also, check for new pharmacology content to add from these sections of the review:
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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)
@ Boghog, Jytdog, and Doc James: The " #Upcoming systematic review" was finally published in an academic journal in September. [2] 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)
Seppi333 ( Insert 2¢) 05:19, 9 November 2017 (UTC) – Updated 06:12, 9 November 2017 (UTC)
- HMB increases myofibrillar protein synthesis by upregulation via the mTOR pathway. - HMB modulates protein degradation by inhibiting the ubiquitin-proteasome proteolytic pathway in muscle cells. Ubiquitin is induced by immobilization and by catabolic conditions, inducing proteasome expression through the activation of nuclear factor kappa B (NK-κB), thus promoting muscle wasting. HMB may inhibit the activity of NK-κB, attenuating muscle loss in wasting conditions. - The integrity of cell membranes depends on cholesterol synthesis from acetyl-CoA. HMB is converted to ß-hydroxyß- methylglutaryl-coenzyme A (HMG-CoA), which is turned into cholesterol by the HMG-coenzyme A reductase, the rate-limiting enzyme to cholesterol synthesis. Thus, HMB supplementation may stabilize cell membranes. HMB itself seems to be a component of cell membranes. - HMB may prevent cell apoptosis and enhance muscle satellite cell survival. - HMB increases proliferation and differentiation of muscle stem cells, via the MAPK/ERK and PI3K/Akt pathways. - HMB up-regulates transcription and expression of the IGF-I gene in skeletal muscle and liver. IGF exerts an anabolic action and causes hypertrophy of skeletal muscle fibers. |
References
HMB's mechanisms of action are generally considered to relate to its effect on both muscle protein synthesis and muscle protein breakdown (Figure 1) [2, 3]. HMB appears to stimulate muscle protein synthesis through an up-regulation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), a signaling cascade involved in coordination of translation initiation of muscle protein synthesis [2, 4]. Additionally, HMB may have antagonistic effects on the ubiquitin–proteasome pathway, a system that degrades intracellular proteins [5, 6]. Evidence also suggests that HMB promotes myogenic proliferation, differentiation, and cell fusion [7]. ... Exogenous HMB-FA administration has shown to increase intramuscular anabolic signaling, stimulate muscle protein synthesis, and attenuate muscle protein breakdown in humans [2].
Clinical trials performed in older adults confirm that HMB can attenuate the progression of sarcopenia in elderly subjects. HMB supplementation results in an increase in skeletal muscle mass and strength in the elderly and its effect is even greater when combined with physical exercise.
HMB is widely used as an ergogenic supplement by young athletes.
No serious side effects have been reported with leucine, EAA, or HMB supplementation; and the health risks associated with these supplements are few and predictable.
Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 μM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < [0.001]) and suppressions in MPB (PA: 7.6 ± 1.2 μmol Phe per leg min-1, Ca-HMB: 5.2 ± 0.8 μmol Phe per leg min-1, p < 0.01). ... During the first 2.5 h period we gathered postabsorptive/fasted measurements, the volunteers then consumed 3.42 g of Ca-HMB (equivalent to 2.74 g of FA-HMB) ... It may seem difficult for one to reconcile that acute provision of CaHMB, in the absence of exogenous nutrition (i.e. EAA's) and following an overnight fast, is still able to elicit a robust, perhaps near maximal stimulation of MPS, i.e. raising the question as to where the additional AA's substrates required for supporting this MPS response are coming from. It would appear that the AA's to support this response are derived from endogenous intracellular/plasma pools and/or protein breakdown (which will increase in fasted periods). ... To conclude, a large single oral dose (~3 g) of Ca-HMB robustly (near maximally) stimulates skeletal muscle anabolism, in the absence of additional nutrient intake; the anabolic effects of Ca-HMB are equivalent to FA-HMB, despite purported differences in bioavailability (Fig. 4).
The stimulation of MPS through mTORc1-signalling following HMB exposure is in agreement with pre-clinical studies (Eley et al. 2008). ... Furthermore, there was clear divergence in the amplitude of phosphorylation for 4EBP1 (at Thr37/46 and Ser65/Thr70) and p70S6K (Thr389) in response to both Leu and HMB, with the latter showing more pronounced and sustained phosphorylation. ... Nonetheless, as the overall MPS response was similar, this cellular signalling distinction did not translate into statistically distinguishable anabolic effects in our primary outcome measure of MPS. ... Interestingly, although orally supplied HMB produced no increase in plasma insulin, it caused a depression in MPB (−57%). Normally, postprandial decreases in MPB (of ~50%) are attributed to the nitrogen-sparing effects of insulin since clamping insulin at post-absorptive concentrations (5 μU ml−1) while continuously infusing AAs (18 g h−1) did not suppress MPB (Greenhaff et al. 2008), which is why we chose not to measure MPB in the Leu group, due to an anticipated hyperinsulinaemia (Fig. 3C). Thus, HMB reduces MPB in a fashion similar to, but independent of, insulin. These findings are in-line with reports of the anti-catabolic effects of HMB suppressing MPB in pre-clinical models, via attenuating proteasomal-mediated proteolysis in response to LPS (Eley et al. 2008).
Ongoing GA review
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Reviewer: Tom (LT) ( talk · contribs) 05:47, 28 November 2017 (UTC)
Assessment
Discussion
@ Tom (LT): I finished going through the points below. I just need your feedback on my responses about some of the statements in the medical and pharmacodynamics sections in order to proceed with addressing those issues. Seppi333 ( Insert 2¢) 23:12, 21 December 2017 (UTC) Review of textHappy to discuss any of the below. These suggestions are not intended to be prescriptive & only intended to illustrate my concerns about the 'well-written' point. They don't all need to be addressed for the review to pass. Hope it is helpful. -- Tom (LT) ( talk) 22:59, 3 December 2017 (UTC)
Lead
UsesMedical
Side-effects
Pharmacology
Chemistry
History
In general
I hope this review helps. Will start working through your replies in the next day or so. Cheers -- Tom (LT) ( talk) 22:50, 8 December 2017 (UTC) @ Tom (LT): I combed through the references and compiled the list below that includes every primary source cited in the article which has a PMID number (the handful of other primary sources cite statements in chemistry, history, etc., so they're all covered by WP:RS). Primary sources with a PMID # that were cited in this article – the sections in the body where these are cited are listed in parentheses:
Seppi333 ( Insert 2¢) 00:02, 9 December 2017 (UTC) COMMENT: Under the rubric of "less is more," I find it unnecessary and annoying that so many of the references include extended quotation of material from the abstracts or articles. Some exceeding 150 words and containing mention of references in the cited article. If the information is essential to the article it belongs in the article. If not, it does not belong anywhere. I've rarely seen reference bloat of this nature, and this is a particularly egregious example. David notMD ( talk) 15:45, 12 December 2017 (UTC)
ConclusionThanks for your patience, Seppi333. This is a great article that you've put a lot of effort into. With your many changes I feel the article has improved to meet GA criteria. I have one or two concerns that I feel we are at loggerheads here with and will pop on the article's talk page, but nothing that would mean this article shouldn't become a GA. Thanks for your responsiveness; Merry Christmas! -- Tom (LT) ( talk) 22:26, 25 December 2017 (UTC) |
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:
It would be useful if a third editor could comment on these; Seppi333 makes some good points and it may be useful if a third or fourth editor could offer their opinion on the above. Have a lovely festive season, -- Tom (LT) ( talk) 22:53, 25 December 2017 (UTC)
β-Hydroxy β-methylbutyric acid is a member of the carboxylic acid family of organic compounds and like them, it is a weak acid.
@ EdChem: Would you happen to know of a source that can be used to cite this statement? Seppi333 ( Insert 2¢) 09:56, 17 April 2018 (UTC)
β-Hydroxy β-methylbutyric acid is a weak acid and a member of the carboxylic acid family of organic compounds."
β-hydroxy β-methylbutyric acid is a member of the carboxylic acid family of organic compounds. It is a structural analog...
@ Seppi333: I don't really think any citation was needed as the fact that it is a carboxylic acid and a weak acid is utterly uncontroversial and unlikely to be challenged by anyone. Nevertheless, I also agree with DMacks that the pKa value confirms that it is a weak acid, and the form of words proposed and implemented from your discussion is accurate. Sorry for the delay in responding. EdChem ( talk) 12:04, 20 July 2018 (UTC)
There appears to be disagreement on whether Beta-Hydroxy beta-methylbutyrate should be described like an alternate name of Beta-Hydroxy beta-methylbutyric acid in the lead. While the two are closely related (They're each other's conjugate acid/base.), I think that the article needs to recognize that they're not exactly the same molecule. Care to differ or discuss with me? The Nth User 02:10, 1 June 2018 (UTC)
Most of the content in the introduction is repeated literally word-for-word in the article body. In my revisions I removed all the duplicate info], repeated word for word in the body. I read other bioactive chemical pages and they don’t have the extreme repetitiveness of this article. The intro almost reads as an advertisement for HMB, let your customers read the article first. Anyway, I saw no reason given for undoing my copyedits, why were they removed? Dogshu ( talk) 13:04, 29 August 2018 (UTC)
From this search:
Meta-analyses from 2018
Systematic reviews from 2018
Other reviews from 2017–2018
Add these when time permits:
Seppi333 (
Insert 2¢) 21:36, 23 October 2018 (UTC)
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 {{ nowrap}}? The full, acid name is not in a nowrap. Cheers, Manifestation ( talk) 10:49, 26 February 2019 (UTC)
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)
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)
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)