Lihat sumber Asam beta-hidroksi beta-metilbutirat

{{Distinguish|asam β-hidroksibutirat}}
{{DISPLAYTITLE:Asam ''beta''-hidroksi ''beta''-metilbutirat}}
{{Infobox drug
| Verifiedfields    =
| Watchedfields     =
| verifiedrevid     = 718190677
| drug_name         = asam β-hidroksi β-metilbutirat
| INN               = tidak ada
| IUPAC_name        = asam 3-hidroksi-3-metilbutanoat
| image             = Beta-Hydroxy beta-methylbutyric acid 2.svg
| width             =
| alt               = Rumus struktur, asam konjugasi
| image2            = Beta-Hydroxy beta-methylbutyrate 2.svg
| width2            =
| alt2              = Rumus struktur, basa konjugasi
| caption           = Atas: Asam β-hidroksi β-metilbutirat<br />Bawah: β-hidroksi β-metilbutirat
<!-- Clinical data -->
| pronounce         =
| Drugs.com         =
| MedlinePlus       =
| licence_EU        = <!-- EMA requires brand name -->
| licence_US        = <!-- FDA may use generic name -->
| pregnancy_AU      = <!-- A/B1/B2/B3/C/D/X -->
| pregnancy_AU_comment =
| pregnancy_US      = <!-- A / B / C / D / X / N -->
| pregnancy_US_comment =
| pregnancy_category=
| routes_of_administration = [[Oral]]<ref name="ISSN position stand 2013" /><!--This ref refers to "ingestion" of HMB a number of times--> atau [[Pipa makanan#Jenis|nasogastris]]<ref name="Ensure and Juven" />
| legal_AU          = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_AU_comment  =
| legal_CA          = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment  =
| legal_DE          = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment  =
| legal_NZ          = <!-- Class A, B, C -->
| legal_NZ_comment  =
| legal_UK          = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment  =
| legal_US          = Suplemen makan
| legal_US_comment  =
| legal_UN          = Tak terjadwal
| legal_UN_comment  =
| legal_status      = 
<!-- Pharmacokinetic data -->
| bioavailability   =
| protein_bound     =
| metabolism        =
| metabolites       = [[HMB-KoA]], [[HMG-KoA]], [[mevalonat]], [[kolesterol]], [[asetil-KoA]], [[asetoasetat]], [[β-hidroksibutirat]]
| onset             = {{abbr|HMB-FA|asam β-hidroksi β-metilbutirat}}: 30–60&nbsp;menit<ref name="ISSN position stand 2013"/><br />{{abbr|HMB-Ca|kalsium β-hidroksi β-metilbutirat monohidrat}}: 1–2&nbsp;jam<ref name="ISSN position stand 2013"/>
| elimination_half-life = {{abbr|HMB-FA|asam β-hidroksi β-metilbutirat}}: 3&nbsp;jam<ref name="ISSN position stand 2013"/><br />{{abbr|HMB-Ca|kalsium β-hidroksi β-metilbutirat monohidrat}}: 2.5&nbsp;jam<ref name="ISSN position stand 2013"/>
| duration_of_action =
| excretion         = [[Ginjal]] (10–40% diekskresikan)<ref name="ISSN position stand 2013">{{cite journal | vauthors = Wilson JM, Fitschen PJ, Campbell B, Wilson GJ, Zanchi N, Taylor L, Wilborn C, Kalman DS, Stout JR, Hoffman JR, Ziegenfuss TN, Lopez HL, Kreider RB, Smith-Ryan AE, Antonio J | title = International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB) | journal = Journal of the International Society of Sports Nutrition | volume = 10 | issue = 1 | pages = 6 | date = February 2013 | pmid = 23374455 | pmc = 3568064 | doi = 10.1186/1550-2783-10-6 | quote = The [International Society of Sports Nutrition] has concluded the following.  1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations.&nbsp;... 4. Thirty-eight mg·kg·BM<sup>−1</sup> daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized.&nbsp;... 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations. }}</ref><ref name="HMB athletic performance-related effects 2011 review" />
<!-- Identifiers -->
| CAS_number        = 625-08-1
| CAS_supplemental  =
| CAS_number_Ref    = {{cascite|correct|}}
| ATC_prefix        = none
| PubChem           = 69362
| IUPHAR_ligand     =
| DrugBank          =
| DrugBank_Ref      =
| ChemSpiderID      = 62571
| ChemSpiderID_Ref  = {{chemspidercite|correct|chemspider}}
| UNII              = 3F752311CD
| UNII_Ref          = {{fdacite|correct|FDA}}
| KEGG              = C20827
| KEGG_Ref          = {{keggcite|correct|kegg}}
| ChEBI             = 37084
| ChEBI_Ref         = {{ebicite|correct|}}
| ChEMBL            =
| NIAID_ChemDB      =
| synonyms          = Bentuk [[Asam konjugat dan basa konjugat|asam konjugasi]]:<br />asam β-hidroksiisovalerat<br />asam 3-hidroksiisovalerat<br />Bentuk [[Asam konjugat dan basa konjugat|basa konjugasi]]:<br />hidroksimetilbutirat
<!-- Chemical data -->
| C=5 | H=10 | O=3
| SMILES            = CC(C)(CC(=O)O)O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C5H10O3/c1-5(2,8)3-4(6)7/h8H,3H2,1-2H3,(H,6,7)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AXFYFNCPONWUHW-UHFFFAOYSA-N
| density           = ~1.1
| density_notes     = pada 20&nbsp;°C<ref name="HMB MSDS" />
| solubility        =
| melting_point     = −80
| melting_high      =
| melting_notes     = (kaca)<ref name = "Coffman_1958"/>
| boiling_point     = 128
| boiling_notes     = pada 7&nbsp;[[Milimeter raksa|mmHg]]<ref name="HMB MSDS">{{cite web|title=Safety data sheet: 3-Hydroxy-3-methyl butyric acid|url=http://www.alfachina.cn/AlfaAesarApp/getpdf?contentId=EN_US_MSDS_42722|publisher=Alfa Aesar|accessdate=9 November 2016|date=23 March 2005|deadurl=no|archiveurl=https://web.archive.org/web/20160917215449/http://www.alfachina.cn/AlfaAesarApp/getpdf?contentId=EN_US_MSDS_42722|archivedate=17 September 2016}}</ref><ref name="ChemSpider">{{cite encyclopedia | title=3-OH-isovaleric acid | url=http://www.chemspider.com/Chemical-Structure.62571.html | work=ChemSpider | date=2015 | publisher=Royal Society of Chemistry | accessdate=10 August 2016 | quote=Experimental Boiling Point:&nbsp;... 128&nbsp;°C / 7&nbsp;mm&nbsp;...<br />Experimental solubility:<br />Soluble in water | deadurl=no | archiveurl=https://web.archive.org/web/20160811095753/http://www.chemspider.com/Chemical-Structure.62571.html | archivedate=11 August 2016 }}</ref>
}}

'''Asam β-hidroksi β-metilbutirat'''{{#tag:ref|Sinonim dan ejaan lain termasuk: '''asam {{nowrap|''beta''-hidroksi}} {{nowrap|''beta''-metilbutirat}}''', '''asam {{nowrap|3-hidroksi-3-metilbutanoat}}''' (nama [[International Union of Pure and Applied Chemistry|IUPAC]]), '''asam {{nowrap|3-hidroksiisovalerat}}''', dan '''asam {{nowrap|''beta''-hidroksiisovalerat}}'''.<ref name="PubChem HMB">{{cite encyclopedia | title = beta-Hydroxyisovaleric acid | url = https://pubchem.ncbi.nlm.nih.gov/compound/69362 | work = PubChem Compound | publisher = United States National Library of Medicine&nbsp;– National Center for Biotechnology Information | accessdate = 6 February 2018 | date = 3 February 2018 | quote = Chemical Names: Beta-Hydroxyisovaleric acid; 3-Hydroxy-3-methylbutanoic acid;&nbsp;... 3-Hydroxyisovaleric acid; 3-Hydroxy-3-methylbutyric acid | deadurl = no | archiveurl = https://web.archive.org/web/20180206190322/https://pubchem.ncbi.nlm.nih.gov/compound/69362 | archivedate = 6 February 2018}}</ref>| group = "catatan" }} ('''HMB'''), atau yang dikenal dengan [[Asam konjugat dan basa konjugat|basa konjugatnya]], '''{{nowrap|β-hidroksi}} {{nowrap|β-metilbutirat}}''', adalah suatu senyawa [[produk alami|yang dihasilkan secara alami]] dalam tubuh manusia yang digunakan sebagai [[suplemen makanan]] serta sebagai bahan dalam beberapa [[makanan medis]] yang diperuntukkan bagi [[penyembuhan luka]] serta menyediakan dukungan nutrisi bagi individu dengan [[atrofi otot]] akibat [[kanker]] atau [[HIV/AIDS]].{{#tag:ref|<ref name="ISSN position stand 2013" /><ref name="Iowa State University" /><ref name="Medical foods" /><ref name="PR Newswire" />|group="sumber"}} Pada orang dewasa yang sehat, suplementasi dengan HMB telah terbukti meningkatkan ukuran otot yang diinduksi olahraga, kekuatan otot, dan perampingan [[massa tubuh]], mengurangi kerusakan [[otot rangka]] saat olahraga, meningkatkan latihan kinerja aerobik, dan mempercepat pemulihan dari olahraga.<ref name="Enhancing performance" group="sumber" /> [[Tinjauan pustaka|Tinjauan medis]] dan [[meta-analisis]] menunjukkan bahwa suplementasi HMB juga membantu menjaga atau meningkatkan massa tubuh dan kekuatan otot pada individu yang mengalami [[sarkopenia|kehilangan otot akibat usia]].<ref name="Meta-analysis of efficacy in older adults" group="catatan" /><ref name="Meta-analytic systematic review September 2015" /><ref name="August 2017 supplementation review" /><ref name="HMB for sarcopenia and sarcopenic obesity – October 2017 review" /> HMB menghasilkan efek ini sebagian dengan merangsang [[sintesis protein|produksi protein]] dan menghambat [[pemecahan protein]] di [[Otot|jaringan otot]].<ref name="Meta-analytic systematic review September 2015" /><ref name="Pimentel 2017 systematic review on HMB">{{cite journal | vauthors = Silva VR, Belozo FL, Micheletti TO, Conrado M, Stout JR, Pimentel GD, Gonzalez AM | title = β-hydroxy-β-methylbutyrate free acid supplementation may improve recovery and muscle adaptations after resistance training: a systematic review | journal = Nutrition Research | volume = 45 | issue = | pages = 1–9 | date = September 2017 | pmid = 29037326 | doi = 10.1016/j.nutres.2017.07.008 | quote = 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].&nbsp;... Exogenous HMB-FA administration has shown to increase intramuscular anabolic signaling, stimulate muscle protein synthesis, and attenuate muscle protein breakdown in humans [2]. <!--Therefore, the anabolic and anti-catabolic properties of HMB-FA offer an appealing nutritional supplement for athletes participating in high-intensity, muscle damaging exercise.-->}}</ref><ref name="Pharmacology of HMB-FA in humans in vivo" /> Tidak ada [[efek samping]] dari penggunaan jangka panjang senyawa ini sebagai suplemen makanan pada orang dewasa yang telah ditemukan.<ref name="Molecular Aspects of Medicine 2016 review">{{cite journal|vauthors=Brioche T, Pagano AF, Py G, Chopard A|date=August 2016|title=Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention|url=|journal=Molecular Aspects of Medicine|volume=50|issue=|pages=56–87|doi=10.1016/j.mam.2016.04.006|pmid=27106402|quote=<!--HMB can decrease apoptosis, judging by a dramatic decrease in the number of TUNEL-positive nuclei in the soleus and plantaris of hindlimb-unloaded old rats treated with HMB, as compared to a placebo group.&nbsp;... Similar data were obtained in muscle cell cultures (Kornasio et al., 2009).&nbsp;...--> In conclusion, HMB treatment clearly appears to be a safe potent strategy against sarcopenia, and more generally against muscle wasting, because HMB improves muscle mass, muscle strength, and physical performance. It seems that HMB is able to act on three of the four major mechanisms involved in muscle deconditioning (protein turnover, apoptosis, and the regenerative process), whereas it is hypothesized to strongly affect the fourth (mitochondrial dynamics and functions). Moreover, HMB is inexpensive (~30– 50 US dollars per month at 3 g per day) and may prevent osteopenia (Bruckbauer and Zemel, 2013; Tatara, 2009; Tatara et al., 2007, 2008, 2012) and decrease cardiovascular risks (Nissen et al., 2000). For all these reasons, HMB should be routinely used in muscle-wasting conditions especially in aged people.&nbsp;... 3&nbsp;g of CaHMB taken three times a day (1&nbsp;g each time) is the optimal posology, which allows for continual bioavailability of HMB in the body (Wilson et al., 2013)|via=}}</ref><ref name="Systematic review December 2013" /><ref name="Efficacy and safety of leucine + HMB consumption" />

== Penggunaan ==

=== Bentuk yang tersedia ===

HMB dijual sebagai [[suplemen makanan]] yang dijual bebas dalam bentuk [[asam]] bebasnya, ''asam β-hidroksi β-metilbutirat'' (HMB-FA), dan sebagai [[garam]] kalsium [[monohidrat]] dari basa konjugatnya, ''kalsium {{nowrap|β-hidroksi β-metilbutirat}} monohidrat'' (HMB-Ca, CaHMB).<ref name="PEDs in sports 2015 review">{{cite journal | vauthors = Momaya A, Fawal M, Estes R | title = Performance-enhancing substances in sports: a review of the literature | journal = Sports Medicine | volume = 45 | issue = 4 | pages = 517–531 | date = April 2015 | pmid = 25663250 | doi = 10.1007/s40279-015-0308-9 | quote = Currently, HMB is available as an over-the-counter supplement. The drug is not tested for nor banned by any sporting organization.&nbsp;... Wilson et al. [91] demonstrated that when non-resistance trained males received HMB pre-exercise, the rise of lactate dehydrogenase (LDH) levels reduced, and HMB tended to decrease soreness. Knitter et al. [92] showed a decrease in LDH and creatine phosphokinase (CPK), a byproduct of muscle breakdown, by HMB after a prolonged run.&nbsp;... The utility of HMB does seem to be affected by timing of intake prior to workouts and dosage [97]. Further, chronic consumption of HMB appears safe [97].&nbsp;... No serious adverse effects from HMB consumption have been reported. }}</ref><ref name="HMB-FA commercial availability as of 2015">{{cite journal | vauthors = Fuller JC, Sharp RL, Angus HF, Khoo PY, Rathmacher JA | title = Comparison of availability and plasma clearance rates of β-hydroxy-β-methylbutyrate delivery in the free acid and calcium salt forms | journal = The British Journal of Nutrition | volume = 114 | issue = 9 | pages = 1403–1409 | date = November 2015 | pmid = 26373270 | doi = 10.1017/S0007114515003050 | department = primary source | quote = Recently, the free acid form of HMB (HMB-FA) has become commercially available in capsule form (gelcap). The current study was conducted to compare the bioavailability of HMB using the two commercially available capsule forms of HMB-FA and Ca-HMB.&nbsp;... In conclusion, HMB-FA in capsule form improves clearance rate and availability of HMB compared with Ca-HMB in capsule form. }}</ref> Karena hanya sebagian kecil dari prekursor [[metabolisme]] HMB, {{nowrap|{{smallcaps all|L}}-leusin}}, dimetabolisme menjadi HMB, konsentrasi aktif senyawa dalam [[plasma darah]] dan otot hanya dapat dicapai dengan menambahkan HMB secara langsung.<ref name="ISSN position stand 2013" /><ref name="Skeletal muscle crosstalk 2016 review">{{cite journal | vauthors = Argilés JM, Campos N, Lopez-Pedrosa JM, Rueda R, Rodriguez-Mañas L | title = Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease | journal = Journal of the American Medical Directors Association | volume = 17 | issue = 9 | pages = 789–796 | date = September 2016 | pmid = 27324808 | doi = 10.1016/j.jamda.2016.04.019 | url = http://www.jamda.com/article/S1525-8610(16)30113-X/fulltext | quote = Studies suggest dietary protein and leucine or its metabolite β-hydroxy β-methylbutyrate (HMB) can improve muscle function, in turn improving functional performance.&nbsp;... These have identified the leucine metabolite β-hydroxy β-methylbutyrate (HMB) as a potent stimulator of protein synthesis as well as an inhibitor of protein breakdown in the extreme case of cachexia.&nbsp;... A growing body of evidence suggests HMB may help slow, or even reverse, the muscle loss experienced in sarcopenia and improve measures of muscle strength.&nbsp;... However, dietary leucine does not provide a large amount of HMB: only a small portion, as little as 5%, of catabolized leucine is metabolized into HMB.&nbsp;... Thus, although dietary leucine itself can lead to a modest stimulation of protein synthesis by producing a small amount of HMB, direct ingestion of HMB more potently affects such signaling, resulting in demonstrable muscle mass accretion.&nbsp;... Indeed, a vast number of studies have found that supplementation of HMB to the diet may reverse some of the muscle loss seen in sarcopenia and in hypercatabolic disease.&nbsp;... The overall treatment of muscle atrophy should include dietary supplementation with HMB, although the optimal dosage for each condition is still under investigation.&nbsp;...<br />[http://www.jamda.com/cms/attachment/2060482578/2062671998/gr4_lrg.jpg Figure 4: Treatments for sarcopenia.] It is currently recommended that patients at risk of or suffering from sarcopenia consume a diet high in protein, engage in resistance exercise, and take supplements of the leucine metabolite HMB. }}</ref><ref name="HMB clinical evidence 2016 review">{{cite journal | vauthors = Landi F, Calvani R, Tosato M, Martone AM, Ortolani E, Savera G, D'Angelo E, Sisto A, Marzetti E | title = Protein Intake and Muscle Health in Old Age: From Biological Plausibility to Clinical Evidence | journal = Nutrients | volume = 8 | issue = 5 | pages = 295 | date = May 2016 | pmid = 27187465 | pmc = 4882708 | doi = 10.3390/nu8050295 | quote = HMB is an active leucine metabolite which activates the mTOR signaling pathway in muscle. Following its absorption, dietary leucine is converted into α-ketoisocaproate (KIC), which is further metabolized into either isovaleryl-CoA or HMB. Under normal conditions, the majority of KIC is converted into isovaleryl-CoA, while only approximately 5% of leucine is metabolized to HMB. This implies that, in order to reach pharmacological levels of HMB, this compound needs to be administered directly, rather than via increasing leucine dosage.&nbsp;... HMB exerts its effects through protective, anticatabolic mechanisms and directly influences protein synthesis. HMB has also been shown to stabilize the muscle cell membrane, to modulate protein degradation and to up-regulate protein synthesis [68].<!--&nbsp;... More recently, Deutz and colleagues [13]—in a multicenter, randomized, placebo-controlled, double-blind trial—demonstrated that the early administration (within 72 h of hospitalization) of a nutrient-dense oral nutritional supplement containing high concentrations of protein and HMB was associated with decreased post-discharge mortality and improved nutritional status in malnourished older adults [13].--> }}</ref> Orang dewasa yang sehat menghasilkan sekitar 0.3&nbsp;gram per hari, sedangkan HMB tambahan biasanya dikonsumsi dalam dosis {{nowrap|3–6}}&nbsp;gram per hari.<ref name="Systematic review December 2013">{{cite journal | vauthors = Molfino A, Gioia G, Rossi Fanelli F, Muscaritoli M | title = Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials | journal = Amino Acids | volume = 45 | issue = 6 | pages = 1273–1292 | date = December 2013 | pmid = 24057808 | doi = 10.1007/s00726-013-1592-z | quote = Normally, an individual metabolizes 60&nbsp;g of L-LEU to obtain 3&nbsp;g of HMB but a 70&nbsp;kg person produces 0.2–0.4&nbsp;g of HMB per day, depending on the dose of LEU in the diet (Van Koevering and Nissen 1992).&nbsp;... The usual dose of 3&nbsp;g/day may be routinely recommended to maintain or improve muscle mass and function in health and disease. The safety profile of HMB is unequivocal.&nbsp;... These results show that HMB/ARG/GLN can be safely used to treat AIDS- and cancer-related muscle wasting }}</ref> HMB dijual dengan harga sekitar {{nowrap|{{currency|30|USD}}–50}} per bulan ketika dikonsumsi dengan dosis 3&nbsp;gram per hari.<ref name="Molecular Aspects of Medicine 2016 review" /> HMB juga terkandung dalam beberapa produk nutrisi dan makanan medis yang dipasarkan oleh [[Abbott Laboratories]] (sepeti, formulasi tertentu [[Goldsure]], [[Juven]], dan [[Myoplex]]),<ref name="Iowa State University">{{cite web|vauthors=Linn J|title=Proteins in Human Health and Performance|url=http://www.fshn.hs.iastate.edu/proteins-in-human-health-and-performance/|archive-url=https://web.archive.org/web/20160827191643/http://www.fshn.hs.iastate.edu/proteins-in-human-health-and-performance/|archive-date=27 August 2016|publisher=Iowa State University|accessdate=31 July 2016|date=13 May 2013|quote=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 Goldsure® Muscle Health, and Juven®, which is a nutritional beverage that is clinically shown to promote healing after injury or surgery.|deadurl=yes}}</ref><ref name="Abbott Nutrition product overview">{{cite web|title=Abbott Nutrition Overview|url=http://prod3.dam.abbott.com/en-us/documents/pdfs/media-center/nutrition-fact-sheet.pdf|website=Abbott|publisher=Abbott Laboratories|accessdate=3 September 2016|deadurl=yes|archiveurl=https://web.archive.org/web/20160903081517/http://prod3.dam.abbott.com/en-us/documents/pdfs/media-center/nutrition-fact-sheet.pdf|archivedate=3 September 2016}}</ref> serta hadir dalam jumlah yang tidak signifikan dalam makanan tertentu, seperti [[alfalfa]], [[asparagus]], [[alpukat]], [[kembang kol]], [[limau gedang]], dan [[ikan lele]].<ref name="2008rev">{{cite journal | vauthors = Wilson GJ, Wilson JM, Manninen AH | title = Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review | journal = Nutrition & Metabolism | volume = 5 | issue =  | pages = 1 | date = Januari 2008 | pmid = 18173841 | pmc = 2245953 | doi = 10.1186/1743-7075-5-1 }}</ref><ref name="HMB in animals 2015 review">{{cite journal | vauthors = Szcześniak KA, Ostaszewski P, Fuller JC, Ciecierska A, Sadkowski T | title = Dietary supplementation of β-hydroxy-β-methylbutyrate in animals – a review | journal = Journal of Animal Physiology and Animal Nutrition | volume = 99 | issue = 3 | pages = 405–417 | date = June 2015 | pmid = 25099672 | doi = 10.1111/jpn.12234 | quote = Cholesterol is a major component of the cell membrane, and sarcolemma is the one that relies mainly on de novo synthesis of cholesterol. This is important under stressful conditions when muscle cells may lack the capacity to produce adequate amounts of the cholesterol that is essential to proper functioning of cell membranes. Many biochemical studies have shown that HMB may be a precursor of cholesterol synthesis (Bachhawat et al., 1955; Bloch et al., 1954; Coon et al., 1955; Adamson and Greenberg, 1955; Gey et al., 1957). According to pertinent literature, HMB carbon is incorporated into cholesterol. Therefore, increased intramuscular HMB concentrations may provide readily available substrate for the cholesterol synthesis that is needed to form and stabilize the sarcolemma.&nbsp;... It is known that HMB supplementation decreases post-exercise levels of enzymes, indicating muscle damage, such as creatinine phosphokinase (CK) and lactate dehydrogenase (LDH), which suggests an enhancement of the muscle cell membrane function. This was shown in numerous studies in humans undergoing both resistance and endurance training (Wilson et al., 2013)&nbsp;... In theory, HMB use as a precursor to cholesterol could aid in stabilizing muscle cell membranes; however, this has not been confirmed by research studies. The effect of HMB on protein metabolism may in fact help stabilize muscle structure more than any effect HMB may have on cholesterol metabolism in the cell. }}</ref>

=== Kedokteran ===
HMB tambahan telah digunakan dalam [[uji klinis]] sebagai pengobatan untuk menjaga massa tubuh tanpa lemak dalam kondisi pengecilan otot, khususnya [[sarkopenia]], dan telah dipelajari dalam uji klinis sebagai [[terapi tambahan]] bersamaan dengan [[Latihan kekuatan|latihan ketahanan]].<ref name="Meta-analytic systematic review September 2015" /><ref name="Molecular Aspects of Medicine 2016 review" /><ref name="Skeletal muscle crosstalk 2016 review" /> Berdasarkan dua ulasan medis dan [[meta-analisis]] dari tujuh [[uji acak terkendali]], suplementasi HMB dapat mempertahankan atau meningkatkan massa otot dan kekuatan otot pada orang dewasa yang lebih tua.{{#tag:ref|Meta-analisis menemukan bahwa peningkatan rata-rata massa otot akibat suplementasi HMB pada orang dewasa yang lebih tua adalah {{convert|0.35|kg|lbs}}.<ref name="Meta-analytic systematic review September 2015" /> Dengan [[Selang kepercayaan|selang kepercayaan 95%]] untuk perkiraan peningkatan massa otot karena suplementasi HMB sebesar {{convert|0.11|–|0.59|kg|lb}}.<ref name="Meta-analytic systematic review September 2015" /><br />Tujuh uji acak terkendali yang dimasukkan dalam meta-analisis berisi total 147 orang dewasa yang lebih tua dalam kelompok perlakuan HMB dan 140&nbsp;orang dewasa yang lebih tua dalam kelompok kontrol.<ref name="Meta-analytic systematic review September 2015" /> Tujuh uji berdurasi 2–11&nbsp;bulan dan durasi rata-rata studi ini, ditimbang dengan ukuran sampel, sekira 6&nbsp;bulan.<ref name="Meta-analytic systematic review September 2015" />|name="Meta-analysis of efficacy in older adults"|group="catatan"}}<ref name="Meta-analytic systematic review September 2015">{{cite journal | vauthors = Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, Li C, Huang G, Niu K | title = Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis | journal = Archives of Gerontology and Geriatrics | volume = 61 | issue = 2 | pages = 168–175 | date = September 2015 | pmid = 26169182 | doi = 10.1016/j.archger.2015.06.020 | quote = Overall, this meta-analysis indicates that HMB can prevent lean body mass loss in older adults. But the effects of HMB on muscle strength and physical function appears to vary in different populations. Additional well-designed clinical studies are necessary to confirm the effectiveness of HMB in the prevention of loss of muscle strength and physical function.&nbsp;... Mechanisms underlying the role of HMB in muscle regeneration have also been explored: results indicated that HMB enhances protein synthesis via upregulation of anabolic signaling pathways and attenuate proteolysis via downregulation of catabolic signaling pathways (Wilkinson et al., 2013). }}</ref><ref name="August 2017 supplementation review">{{cite journal | vauthors = Holeček M | title = Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions | journal = Journal of Cachexia, Sarcopenia and Muscle | volume = 8 | issue = 4 | pages = 529–541 | date = August 2017 | pmid = 28493406 | pmc = 5566641 | doi = 10.1002/jcsm.12208 | quote = The reports summarized here indicate that HMB provides a number of benefits to subjects involved in strength-power and endurance sports. The effects on muscle mass and strength, particularly during resistance training, are likely related to the suppression of proteolysis and a positive effect on protein synthesis. Its benefits in aerobic performance are probably more associated with improved mitochondrial biogenesis and fat oxidation. Favourable effects on the recovery from exercise-induced damage may be related to the role of HMB as a precursor of cholesterol, which modulates membrane fluidity and affects ion channels, and membrane excitability.&nbsp;... Studies have demonstrated that HMB can prevent the development of sarcopenia in elderly subjects and that the optimal action of HMB on muscle growth and strength occurs when it is combined with exercise. }}</ref><ref name="HMB for sarcopenia and sarcopenic obesity – October 2017 review">{{cite journal | vauthors = Rossi AP, D'Introno A, Rubele S, Caliari C, Gattazzo S, Zoico E, Mazzali G, Fantin F, Zamboni M | title = The Potential of β-Hydroxy-β-Methylbutyrate as a New Strategy for the Management of Sarcopenia and Sarcopenic Obesity | journal = Drugs & Aging | volume = 34| issue = 11| pages = 833–840| date = October 2017 | pmid = 29086232 | doi = 10.1007/s40266-017-0496-0 | quote = 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.}}</ref>

Beberapa produk bermerek yang mengandung HMB (yaitu, formulasi tertentu dari Ensure dan Juven) merupakan [[makanan medis]] yang dimaksudkan untuk digunakan untuk memberikan dukungan nutrisi di bawah perawatan dokter pada individu dengan [[atrofi otot]] akibat [[HIV/AIDS]] atau [[kanker]], untuk mempromosikan [[penyembuhan luka]] setelah pembedahan atau cedera, atau ketika direkomendasikan oleh profesional medis.{{#tag:ref|<ref name="Ensure and Juven">{{cite web|title=Product Information: Ensure Enlive Advanced Therapeutic Nutrition Shake|publisher=Abbott Nutrition|url=http://static.abbottnutrition.com/cms-prod/abbottnutrition.com/img/Ensure-Enlive-Advanced-Therapeutic-Nutrition-Shake.pdf|accessdate=22 August 2016|date=9 August 2016|quote=<br />{{•}}Use under medical supervision.<br />{{•}}HMB + protein for muscle health.|deadurl=no|archiveurl=https://web.archive.org/web/20161012132214/http://static.abbottnutrition.com/cms-prod/abbottnutrition.com/img/Ensure-Enlive-Advanced-Therapeutic-Nutrition-Shake.pdf|archivedate=12 October 2016}}<br /><br />{{cite web|title=Product Information: Juven|publisher=Abbott Nutrition|url=http://static.abbottnutrition.com/cms-prod/abbottnutrition.com/img/Juven.pdf|date=7 May 2016|accessdate=22 August 2016|quote=<br />{{•}}Administer orally or as a modular via feeding tube&nbsp;...<br />{{•}}Use under medical supervision.<br />{{•}}Nutravigor® (CaHMB, calcium β-hydroxy-β-methylbutyrate)|deadurl=no|archiveurl=https://web.archive.org/web/20161012132216/http://static.abbottnutrition.com/cms-prod/abbottnutrition.com/img/Juven.pdf|archivedate=12 October 2016}}</ref><ref name="Iowa State University" /><ref name="Medical foods">{{cite journal | vauthors = Khamsi R | title = Rethinking the formula | journal = Nature Medicine | volume = 19 | issue = 5 | pages = 525–529 | date = May 2013 | pmid = 23652097 | doi = 10.1038/nm0513-525 | quote = The questions about what defines a medical food will likely grow as the market does—and that market now extends far beyond PKU and other inherited metabolic disorders.&nbsp;... Abbott Nutrition's Juven provides nutrients to people with HIV or AIDS experiencing excessive weight loss due to disease }}</ref><ref name="PR Newswire">{{cite web|title=JUVEN Added to Abbott Laboratories' Nutritional Product Line for People With Cancer, HIV/AIDS and Wounds/Pressure Ulcers|url=http://www.prnewswire.com/news-releases/juven-added-to-abbott-laboratories-nutritional-product-line-for-people-with-cancer-hivaids-and-woundspressure-ulcers-72059102.html|website=PR Newswire|publisher=Abbott Laboratories|accessdate=11 December 2016|date=12 March 2004|deadurl=yes|archiveurl=https://web.archive.org/web/20161220105220/http://www.prnewswire.com/news-releases/juven-added-to-abbott-laboratories-nutritional-product-line-for-people-with-cancer-hivaids-and-woundspressure-ulcers-72059102.html|archivedate=20 December 2016}}</ref>|group="sumber"}}

=== Peningkatan performa ===
Dengan program olahraga yang tepat, suplementasi makanan dengan 3&nbsp;gram HMB per hari telah terbukti meningkatkan peningkatan ukuran otot yang diinduksi oleh olahraga, kekuatan dan ketahanan otot, dan massa tubuh tanpa lemak, mengurangi kerusakan otot rangka yang disebabkan oleh olahraga,{{#tag:ref|Efek HMB pada kerusakan otot rangka telah dinilai dalam penelitian pada manusia menggunakan empat [[Biomarker (obat)|biomarker]] berbeda dari kerusakan otot atau pemecahan protein: [[serum darah|serum]] [[kreatin kinase]], serum [[laktat dehidrogenase]], [[nitrogen urea]] urin, and {{nowrap|[[3-metilhistidin]]}} urin.<ref name="ISSN position stand 2013" /><ref name="PEDs in sports 2015 review" /><ref name="Effects of amino acid derivatives 2015 review" /> Ketika intensitas dan volume latihan cukup untuk menyebabkan kerusakan otot rangka, seperti selama [[lari jarak jauh]] atau [[kelebihan beban progresif]], suplementasi HMB telah ditunjukkan untuk melemahkan peningkatan biomarker ini sebesar 20–60%.<ref name="ISSN position stand 2013" /><ref name="PEDs in sports 2015 review" /><ref name="Exercise-Induced Muscle Damage Meta-analysis" />|group="catatan"|name="biomarkers"}} dan mempercepat pemulihan dari latihan dengan intensitas tinggi.{{#tag:ref|<ref name="ISSN position stand 2013" /><ref name="Meta-analytic systematic review September 2015" /><ref name="August 2017 supplementation review" /><ref name="Pimentel 2017 systematic review on HMB" /><ref name="PEDs in sports 2015 review" /><ref name="Effects of amino acid derivatives 2015 review">{{cite journal | vauthors = Luckose F, Pandey MC, Radhakrishna K | title = Effects of amino acid derivatives on physical, mental, and physiological activities | journal = Critical Reviews in Food Science and Nutrition | volume = 55 | issue = 13 | pages = 1793–1807 | date = 2015 | pmid = 24279396 | doi = 10.1080/10408398.2012.708368 | quote = HMB, a derivative of leucine, prevents muscle damage and increases muscle strength by reducing exercise-induced proteolysis in muscles and also helps in increasing lean body mass.&nbsp;... HMB is converted to HMB-CoA which is then used for the synthesis of cholesterol in muscle cells (Nissen and Abumrad, 1997). Cholesterol is needed for the growth, repair, and stabilization of cellular membranes during exercise (Chen, 1984).&nbsp;... The meta analysis studies and the individual studies conducted support the use of HMB as an effective aid to increase body strength, body composition, and to prevent muscle damage during resistance training. }}</ref><ref name="Exercise-Induced Muscle Damage Meta-analysis">{{cite journal | vauthors = Rahimi MH, Mohammadi H, Eshaghi H, Askari G, Miraghajani M | title = The Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Recovery Following Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis | journal = Journal of the American College of Nutrition | volume = 37 | issue = 7 | pages = 640–649 | date = 2018 | pmid = 29676656 | doi = 10.1080/07315724.2018.1451789 | quote = The current evidence revealed a time-dependent effect of HMB in reducing LDH and CK serum levels among adults. HMB, therefore, may be seen as a priority muscle damage recovery agent in interventions.}}</ref>|group="sumber"|name="Enhancing performance"}}

== Farmakologi ==

=== Farmakodinamika ===

Beberapa komponen [[transduksi sinyal|kaskade persinyalan]] yang memediasi peningkatan yang diinduksi oleh HMB dalam sintesis protein otot rangka manusia telah diidentifikasi secara ''[[in vivo]]''.<ref name="Pimentel 2017 systematic review on HMB" /><ref name="Pharmacology of HMB-FA in humans in vivo">{{cite journal | vauthors = Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Etheridge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ | title = Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism | journal = The Journal of Physiology | volume = 591 | issue = 11 | pages = 2911–2923 | date = June 2013 | pmid = 23551944 | pmc = 3690694 | doi = 10.1113/jphysiol.2013.253203 | quote = The stimulation of MPS through mTORc1-signalling following HMB exposure is in agreement with pre-clinical studies (Eley et al. 2008).&nbsp;... 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.&nbsp;...  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.&nbsp;... 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&nbsp;μU&nbsp;ml<sup>−1</sup>) while continuously infusing AAs (18&nbsp;g&nbsp;h<sup>−1</sup>) 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).}}</ref>

=== Biosintesis ===

Mayoritas metabolisme {{nowrap|{{smallcaps all|L}}-leusin}} mulanya dikatalisis oleh enzim [[asam amino rantai samping aminotransferase]], menghasilkan {{nowrap|[[α-ketoisokaproat]]}} (α-KIC).<ref name="HMB athletic performance-related effects 2011 review">{{cite journal | vauthors = Zanchi NE, Gerlinger-Romero F, Guimarães-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, Seelaender M, Lancha AH | title = HMB supplementation: clinical and athletic performance-related effects and mechanisms of action | journal = Amino Acids | volume = 40 | issue = 4 | pages = 1015–1025 | date = April 2011 | pmid = 20607321 | doi = 10.1007/s00726-010-0678-0 | quote = HMB is a metabolite of the amino acid leucine (Van Koverin and Nissen 1992), an essential amino acid. The first step in HMB metabolism is the reversible transamination of leucine to [α-KIC] that occurs mainly extrahepatically (Block and Buse 1990). Following this enzymatic reaction, [α-KIC] may follow one of two pathways. In the first, HMB is produced from [α-KIC] by the cytosolic enzyme KIC dioxygenase (Sabourin and Bieber 1983). The cytosolic dioxygenase has been characterized extensively and differs from the mitochondrial form in that the dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981, 1983). Importantly, this route of HMB formation is direct and completely dependent of liver KIC dioxygenase. Following this pathway, HMB in the cytosol is first converted to cytosolic β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which can then be directed for cholesterol synthesis (Rudney 1957) (Fig. 1). In fact, numerous biochemical studies have shown that HMB is a precursor of cholesterol (Zabin and Bloch 1951; Nissen et al. 2000).<!--<br /><br /> In the second pathway, after transamination, [α-KIC] in liver generates isovaleryl-CoA through the enzymatic action of branched-chain ketoacid dehydrogenase (BCKD) and after several steps, there is production of HMG-CoA through the enzyme HMG-CoA synthase (Fig. 1). Under normal conditions the majority of KIC is converted into isovaleryl-CoA, in which approximately 5% of leucine is metabolized into HMB (Wilson et al. 2008; Van Koverin and Nissen 1992). However, Nissen and Abumrad (1997) provided evidence that the primary fate of HMB is probably conversion to HMG-CoA in the liver, for cholesterol biosynthesis.--> }}</ref><ref name="Leucine metabolism">{{cite book | vauthors=Kohlmeier M | title=Nutrient Metabolism: Structures, Functions, and Genes | date=May 2015 | publisher=Academic Press | isbn=978-0-12-387784-0 | pages=385–388 | edition=2nd | section-url=https://books.google.com/books?id=aTQTAAAAQBAJ&pg=PA387&q=beta-hydroxy%20beta-methylbutyrate%20HMB#v=onepage | url=https://books.google.com/books?id=aTQTAAAAQBAJ&printsec=frontcover#v=onepage | accessdate=6 June 2016 | section=Leucine | quote=Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours&nbsp;... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds | deadurl=no | archiveurl=https://web.archive.org/web/20180322000056/https://books.google.com/books?id=aTQTAAAAQBAJ&printsec=frontcover#v=onepage | archivedate=22 March 2018}}<br />[https://books.google.com/books?id=aTQTAAAAQBAJ&pg=PA386#v=onepage&q&f=false Figure 8.57: Metabolism of {{smallcaps all|L}}-leucine] {{webarchive|url=https://web.archive.org/web/20180322000056/https://books.google.com/books?id=aTQTAAAAQBAJ&pg=PA386 |date=22 March 2018 }}</ref> α-KIC utamanya dimetabolisme oleh enzim [[mitokondria]]l [[asam alfa-keto rantai cabang dehidrogenase|{{nowrap|asam α-keto}} rantai cabang dehidrogenase]], yang mengubahnya menjadi [[isovaleril-CoA]].<ref name="HMB athletic performance-related effects 2011 review" /><ref name="Leucine metabolism" /> Isovaleril-KoA selanjutnya dimetabolisme oleh [[isovaleril-KoA dehidrogenase]] dan dikonversi menjadi {{nowrap|MC-KoA}}, yang digunakan dalam sintesis asetil-KoA dan senyawa lainnya.<ref name="Leucine metabolism" /> Selama [[defisiensi biotin]], HMB dapat disintesis dari {{nowrap|MC-KoA}} melalui [[enoil-KoA hidratase]] dan enzim [[tioesterase]] yang tidak diketahui,<ref name="HMB-CoA ⇔ HMB">{{cite web|title=KEGG Reaction: R10759|url=http://www.genome.jp/dbget-bin/www_bget?rn:R10759|website=Kyoto Encyclopedia of Genes and Genomes|publisher=Kanehisa Laboratories|accessdate=24 June 2016|deadurl=no|archiveurl=https://web.archive.org/web/20160701140720/http://www.genome.jp/dbget-bin/www_bget?rn:R10759|archivedate=1 July 2016}}</ref><ref name="pmid21918059" /><ref name="HMB-CoA ⇔ MC-CoA">{{cite web|title=KEGG Reaction: R04137|url=http://www.genome.jp/dbget-bin/www_bget?rn:R04137|website=Kyoto Encyclopedia of Genes and Genomes|publisher=Kanehisa Laboratories|accessdate=24 June 2016|deadurl=no|archiveurl=https://web.archive.org/web/20160701144143/http://www.genome.jp/dbget-bin/www_bget?rn:R04137|archivedate=1 July 2016}}</ref> yang mengubah {{nowrap|MC-KoA}} menjadi {{nowrap|HMB-KoA}} dan {{nowrap|HMB-KoA}} menjadi HMB berturut-turut.<ref name="pmid21918059">{{cite journal | vauthors = Mock DM, Stratton SL, Horvath TD, Bogusiewicz A, Matthews NI, Henrich CL, Dawson AM, Spencer HJ, Owen SN, Boysen G, Moran JH | title = Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans | journal = The Journal of Nutrition | volume = 141 | issue = 11 | pages = 1925–1930 | date = November 2011 | pmid = 21918059 | pmc = 3192457 | doi = 10.3945/jn.111.146126 | department = primary source | quote = 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.}}</ref> Sejumlah kecil α-KIC dimetabolisme di [[hati]] oleh enzim [[sitosol]]ik [[4-hidroksifenilpiruvat dioksigenase]] (KIC dioksigenase), yang mengubah α-KIC menjadi HMB.<ref name="HMB athletic performance-related effects 2011 review" /><ref name="Leucine metabolism" /><ref name="KIC dioxygenase">{{cite web|title=Homo sapiens: 4-hydroxyphenylpyruvate dioxygenase reaction|url=http://www.biocyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-13640|website=MetaCyc|publisher=SRI International|accessdate=6 June 2016|date=20 August 2012}}</ref> Pada individu sehat, jalur minor ini&nbsp;– yang melibatkan konversi {{nowrap|{{smallcaps all|L}}-leusin}} menjadi α-KIC dan kemudian HMB&nbsp;– adalah jalur utama sintesis HMB.<ref name="HMB athletic performance-related effects 2011 review" /><ref name="Leucine metabolism" />

== Efek samping ==

[[Keamanan obat|Profil keamanan]] HMB pada manusia dewasa didasarkan pada bukti dari [[uji klinis]] pada manusia dan penelitian pada [[hewan]].<ref name="Molecular Aspects of Medicine 2016 review" /><ref name="Efficacy and safety of leucine + HMB consumption">{{cite journal | vauthors = Borack MS, Volpi E | title = Efficacy and Safety of Leucine Supplementation in the Elderly | journal = The Journal of Nutrition | volume = 146 | issue = 12 | pages = 2625S–2629S | date = December 2016 | pmid = 27934654 | pmc = 5118760 | doi = 10.3945/jn.116.230771 | quote = One study tested the safety of HMB for long-term use in rats. Fuller et al. (50) conducted a 91-d study with the use of Sprague-Dawley rats that tested the safety of β-hydroxy-β-methylbutyric free acid (HMBFA). This new form of HMB results in higher HMB serum concentrations than CaHMB. In this study, rats were administered an HMBFA intervention of 0%, 0.8%, 1.6%, or 4% of the diet by body weight. The highest dose is the equivalent of ~400&nbsp;mg ⋅ kg<sup>−1</sup> ⋅ d<sup>−1</sup> for humans. No adverse advents were observed for any treatment group. Similarly, blood and urine analyses were within the normal range in all groups, with no group differences. The authors concluded that HMBFA was safe for consumption in a rat model.&nbsp;... 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.}}</ref> Pada manusia, tidak ada [[efek samping]] pada orang dewasa muda atau orang dewasa yang lebih tua yang telah dilaporkan ketika HMB dikonsumsi dalam dosis 3 gram per hari hingga satu tahun.<ref name="Molecular Aspects of Medicine 2016 review" /><ref name="Systematic review December 2013" /><ref name="Efficacy and safety of leucine + HMB consumption" />

== Kimia ==
{{multiple image
<!--Layout parameters-->
 | align             = right
 | direction         = vertical
<!--Image 1-->
 | image1            = Butyric acid carbons 2.svg
 | width1            = 235
 | alt1              = Rumus kerangka asam butirat dengan karbon alfa, beta, dan gamma ditandai
 | caption1          = Rumus kerangka [[asam butirat]] dengan karbon alfa, beta, dan gamma ditandai
<!--Image 2-->
 | image2            = Beta-Hydroxy beta-methylbutyric acid 2.svg
 | width2            = 235
 | alt2              = Rumus kerangka asam β-hidroksi β-metilbutirat
 | caption2          = Rumus asam {{nowrap|β-hidroksi β-metilbutirat}}
}}
Asam {{nowrap|β-hidroksi}} {{nowrap|β-metilbutirat}} adalah suatu [[asam β-hidroksi]] [[asam karboksilat|monokarboksilat]] serta [[produk alami]] dengan [[rumus molekul]] {{chemical formula|C|5|H|10|O|3}}.<ref name="HMDB">{{cite web | title=3-Hydroxyisovaleric acid | url=http://www.hmdb.ca/metabolites/HMDB00754 | work=HMDB Version&nbsp;4.0 | publisher=Human Metabolome Database | accessdate=26 December 2017 | date=7 December 2017 | deadurl=no | archiveurl=https://web.archive.org/web/20171205103122/http://www.hmdb.ca/metabolites/HMDB00754 | archivedate=5 December 2017}}</ref><ref name="3-Hydroxyisovalerate ChEBI entry">{{cite web|title = 3-hydroxyisovalerate|url = https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:82957|website = Chemical Entities of Biological Interest|publisher = European Bioinformatics Institute|accessdate = 20 Agustus 2016|date = 16 September 2014|deadurl = no|archivedate = 1 Desember 2017|archiveurl = https://web.archive.org/web/20171201032101/https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:82957}}</ref> Pada suhu ruangan, asam {{nowrap|β-hidroksi}} {{nowrap|β-metilbutirat}} terdapat sebagai cairan transparan, tak berwarna hingga kuning terang yang larut dalam air.<ref name="ChemSpider" /><ref name="Patent #WO2015094925 A1">{{cite patent| country = WO| number = 2015094925| status = application| title = Stable liquid filled hard capsule comprising beta-hydroxy-beta-methylbutyric acid | pubdate = 25 Juni 2015 | fdate = 11 Desember 2014 | pridate = 18 Desember 2013| inventor = White TO| assign1 = Capsugel Belgium Nv}}</ref><ref name="ChemicalBook HMB">{{cite web | title = Beta-Hydroxyisovaleric acid | url = http://www.chemicalbook.com/ProductChemicalPropertiesCB3213104_EN.htm | website = ChemicalBook | accessdate = 20 Agustus 2016 | deadurl = no | archiveurl = https://web.archive.org/web/20160821184418/http://www.chemicalbook.com/ProductChemicalPropertiesCB3213104_EN.htm | archivedate = 21 Agustus 2016}}</ref> Asam {{nowrap|β-hidroksi}} {{nowrap|β-metilbutirat}} adalah suatu [[asam lemah]] dengan [[pKa|p''K''<sub>a</sub>]] 4.4.<ref name = "Coffman_1958"/> [[Indeks refraksi]] (<math>\mathit{n}_\text{25°C}^\mathrm{\lambda=589nm}</math>) senyawa ini adalah 1.42.<ref name = "Coffman_1958"/>

=== Struktur kimia ===
Asam {{nowrap|β-hidroksi}} {{nowrap|β-metilbutirat}} merupakan anggota keluarga [[senyawa organik]] [[asam karboksilat]].<ref name="HMDB" /> Senyawa ini adalah analog struktural dari [[asam butirat]] dengan [[gugus fungsi]] [[gugus hidroksi|hidroksil]] dan suatu [[substituen]] [[gugus metil|metil]] yang berlokasi pada [[karbon alfa dan beta|karbon beta]].<ref name="HMDB" /><ref name="3-Hydroxyisovaleric acid ChEBI entry">{{cite web|title = 3-hydroxyisovaleric acid|url = https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:37084|website = Chemical Entities of Biological Interest|publisher = European Bioinformatics Institute|accessdate = 20 Agustus 2016|date = 23 Oktober 2015|deadurl = no|archivedate = 12 Maret 2016|archiveurl = https://web.archive.org/web/20160312153637/http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:37084}}</ref> Dengan perpanjangan, analog struktur lainnya diantaranya [[asam β-hidroksibutirat|asam {{nowrap|β-hidroksibutirat}}]] dan [[asam β-metilbutirat|asam {{nowrap|β-metilbutirat}}]].<ref name="HMDB" /><ref name="3-Hydroxyisovaleric acid ChEBI entry" />

=== Sintesis ===
Berbagai jalur sintesis asam {{nowrap|β-hidroksi}} {{nowrap|β-metilbutirat}} telah dikembangkan. Pendekatan [[sintesis kimia]] HMB yang pertama dilaporkan mendekati HMB dengan oksidasi [[alkena]], [[diol]] [[visinal (kimia)|visinal]], dan prekursor [[alkohol]]:
* pada tahun 1877, [[kimiawan]] Rusia Michael dan [[Alexander Mikhaylovich Zaytsev|Alexander Zaytsev]] melaporkan preparasi HMB oleh oksidasi 2-metilpent-4-en-2-ol dengan [[asam kromat]] (H<sub>2</sub>CrO<sub>4</sub>);<ref name="First synthesis">Sitiran pertama bagi sintesis asam β-hidroksi β-metilbutirat dalam basis data kimia [[Reaxys]] sejak September 2016 adalah:<br />{{cite journal|last1=Saytzeff|first1=Michael|last2=Saytzeff|first2=Alexander|author-link2=Alexander Mikhaylovich Zaytsev|date=1877|title=Synthese des Allyldimethylcarbinols|trans-title=Synthesis of allyldimethylcarbinols|journal=Justus Liebig's Annalen der Chemie|language=de|volume=185|issue=2–3|pages=151–169|doi=10.1002/jlac.18771850204|name-list-format=vanc}}</ref>
* pada tahun 1880 dan 1889, Schirokoff dan Reformatsky (masing-masing) melaporkan bahwa pembelahan oksidatif diol visinal 4-metilpentana-1,2,4-triol dengan [[kalium permanganat]] (KMnO<sub>4</sub>) dalam suasana asam menghasilkan HMB<ref>{{cite journal | last1 = Schirokoff | first1 = Alexius | name-list-format = vanc | title = Ueber die β-Dipropyl- und β-Diäthyläthylenmilchsäure und über die Oxydation des Allyldimethylcarbinols und Diallylcarbinols mit übermangansaurem Kalium | trans-title = On the β-dipropyl- and β-diethylenyl-lactic acid, and on the oxidation of the allyl dimethylcarbinol and diallylcarbinol with excess potassium | language = de | journal = Journal für Praktische Chemie | date = January 1881 | volume = 23 | issue = 1 | pages = 196–208 | doi = 10.1002/prac.18810230115 }}</ref><ref>{{cite journal | last1 = Reformatzky | first1 = Bergius | name-list-format = vanc | title = Synthese einiger Glycerine mittelst unterchloriger Säure | trans-title = Synthesis of some glycerol by hypochlorous acid | language = de | journal = Journal für Praktische Chemie | date = 30 October 1889 | volume = 40 | issue = 1 | pages = 396–419 | doi = 10.1002/prac.18890400137}}</ref> – hasil ini paling mendekati terkait dengan sintesis pertama karena KMnO<sub>4</sub> encer dan dingin mengoksidasi alkena menjadi diol-''cis'' visinal yang lebih lanjut dioksidasi oleh KMnO<sub>4</sub> panas dalam suasana asam menjadi senyawa yang mengandung karbonil, serta zat antara diol tidak diperoleh kita kondisi asam dan panas digunakan bagi [[oksidasi alkena]].<ref>{{cite book|title = Fundamentals of Organic Chemistry|edition = 7th|first = John E.|last = McMurry|authorlink = John E. McMurry|pages = 124–126, 142|chapter = Oxidation of Alkenes: Epoxidation, Hydroxylation, and Cleavage|isbn = 9781439049716|publisher = [[Cengage Learning]]|year = 2010|chapter-url = https://books.google.com/books?id=3_4oLh-OWEcC&pg=PA142&dq=oxidation+alkene+KMnO4}}</ref> Dengan kata lain, [[rasemat]] 4-metilpentana-1,2,4-triol adalah turunan 2-metilpent-4-en-2-ol dan asam β-hidroksi β-metilbutirat adalah turunan keduanya; serta,
* pada tahun 1892, Kondakow melaporkan preparasi HMB oleh oksidasi 3-metilbutana-1,3-diol dengan permanganat.<ref>{{cite journal | vauthors = Kondakow J | title = On the action of mineral acids on dimethylallyls <!-- Surely this is a trans-title... what was the title? --> | date= 1892 | language = Russian | journal = Zhurnal Russkago Fiziko-Khimicheskago Obshchestva (Journal of the Russian Physico-Chemical Society) | volume = 1 <!-- Is this volume correct?  Volume 1 of the journal was in 1869, volume 38 was in 1906, so shouldn't 1892 be volume 24?  From 1907, the journal split into A / B sections for physics and chemistry, both starting at volume 39 --> | pages = 508–513 }} abstrak oleh {{cite journal | author = Grosset | title = Ueber die Einwirkung von Mineralsauren auk Dimethylallen | language = German | trans-title = On the action of mineral acids on dimethylallyls | journal = Berichte der Deutschen Chemischen Gesellschaft | date = 1893 | volume = 26 | issue = 4| page = 96 | doi = 10.1002/cber.18930260412 }}</ref>
[[Berkas:HMB synthesis historical.svg|600px|pus|jmpl|alt=Gambar jalur sintesis asam β-hidroksi β-metilbutirat pertama|Jalur sintesis asam {{nowrap|β-hidroksi}} {{nowrap|β-metilbutirat}} pertama]]

Bergantung pada kondisi eksperimen, [[sikloadisi]] dari [[aseton]] dan [[ketena]] menghasilkan {{nowrap|β-isovalerolakton}} atau 4,4-dimetiloksetan-2-on,<ref>{{cite journal | vauthors = Gresham TL, Jansen JE, Shaver FW, Beears WL | title = β-Propiolactone. XIV. β-Isovalerolactone | journal = Journal of the American Chemical Society | date = January 1954 | volume = 76 | issue = 2 | pages = 486–488 | doi = 10.1021/ja01631a045 }}</ref><ref>{{cite patent | country = WO | number = 2012140276 | status = application | title = Process for the preparation of 3-hydroxy-3-methylbutyric acid or its calcium salts | pubdate = 10 January 2013 | gdate = | fdate = 19 August 2012 | pridate = 17 November 2011 | inventor = Noti C, Schmid L, Rittiner B, Hanselmann P, Bierstedt A | assign1 = Lonza Ltd | url = }}</ref> keduanya [[Hidrolisis|terhidrolisis]] dalam kondisi basa untuk menghasilkan basa konjugat dari HMB. [[Reaksi haloform]] menyediakan jalur lain ke HMB yang melibatkan halogenasi lengkap dari wilayah metil-keton [[alkohol diaseton]] dengan [[natrium hipobromit]] atau [[natrium hipoklorit]];<ref name = "Coffman_1958">{{cite journal | vauthors = Coffman DD, Cramer R, Mochel WE | title = Syntheses by Free-radical Reactions. V. A New Synthesis of Carboxylic Acids | journal = Journal of the American Chemical Society | date = June 1958 | volume = 80 | issue = 11 | pages = 2882–2887 | doi = 10.1021/ja01544a072 }}</ref><ref name = DiacetoneAlcohol>{{cite journal | last1 = Kohn | first1 = Moritz | name-list-format = vanc | title = Zur Kenntnis des Diacetonalkohols und des Mesityloxyds | trans-title = Knowledge of diacetone alkohols and mesityl oxide | journal = Monatshefte für Chemie und Verwandte Teile Anderer Wissenschaften | date = September 1903 | volume = 24 | issue = 9 | pages = 765–772 | doi = 10.1007/BF01526057 }}</ref><ref>{{cite book | vauthors = Doraiswamy LK | title = Organic Synthesis Engineering | date = February 2001 | publisher = Oxford University Press | location = New York | isbn = 978-0-19-509689-7 | chapter-url = https://books.google.com/books?id=_0rnCwAAQBAJ&pg=PA103#v=onepage | pages = 102–124 | chapter = Example 5.2 }}</ref>

== Catatan ==
{{Reflist|group="catatan"}}

== Catatan referensi ==
{{Reflist|group="sumber"}}

== Referensi ==
{{Reflist}}

== Pranala luar ==
{{Commons category|Beta-Hydroxy beta-methylbutyrate|Beta-Hidroksi beta-metilbutirat}}
* {{MeshName|Beta-Hydroxyisovaleric acid}}

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