β-Hydroxy β-methylbutyric acid (HMB), otherwise known as its
conjugate base, , is a
naturally produced substance in humans that is used as a
dietary supplement
A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
and as an ingredient in certain
medical foods that are intended to promote
wound healing and provide nutritional support for people with
muscle wasting due to
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
or
HIV/AIDS. In healthy adults, supplementation with HMB has been shown to increase exercise-induced gains in
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
size, muscle strength, and
lean body mass, reduce
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
damage from exercise, improve aerobic exercise performance, and expedite recovery from exercise.
Medical reviews and
meta-analyses indicate that HMB supplementation also helps to preserve or increase lean body mass and muscle strength in individuals experiencing
age-related muscle loss.
HMB produces these effects in part by stimulating the
production of proteins and inhibiting the
breakdown of proteins in muscle tissue.
No
adverse effect
An adverse effect is an undesired harmful effect resulting from a Pharmaceutical drug, medication or other Surgery#Definitions, intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main ...
s from long-term use as a dietary supplement in adults have been found.
HMB is sold as a dietary supplement at a cost of about per month when taking 3 grams per day.
HMB is also contained in several nutritional products, including certain formulations of
Ensure,
Juven, and
Myoplex
EAS (formerly Experimental & Applied Sciences) was a distributor of creatine nutritional supplements with approximately 300 staff, annual sales exceeding $300 million, and offices/distributors in 54 countries.
History
EAS was founded in Pacif ...
.
HMB is also present in insignificant quantities in certain foods, such as
alfalfa,
asparagus,
avocados,
cauliflower,
grapefruit
The grapefruit (''Citrus'' × ''paradisi'') is a subtropical citrus tree known for its relatively large, sour to semi-sweet, somewhat bitter fruit. The interior flesh is segmented and varies in color from pale yellow to dark pink.
Grapefruit is ...
, and
catfish
Catfish (or catfishes; order Siluriformes or Nematognathi) are a diverse group of ray-finned fish. Named for their prominent barbels, which resemble a cat's whiskers, catfish range in size and behavior from the three largest species alive, ...
.
The effects of HMB on human skeletal muscle were first discovered by Steven L. Nissen at
Iowa State University in the .
HMB has not been banned by the
National Collegiate Athletic Association,
World Anti-Doping Agency, or any other prominent national or international athletic organization.
In 2006, only about 2% of college
student athlete
A student is a person enrolled in a school or other educational institution.
In the United Kingdom and most commonwealth countries, a "student" attends a secondary school or higher (e.g., college or university); those in primary or elementar ...
s in the United States used HMB as a dietary supplement.
As of 2017, HMB has found widespread use as an
ergogenic supplement
Performance-enhancing substances, also known as performance-enhancing drugs (PEDs), are substances that are used to improve any form of activity performance in humans. A well-known example of cheating in sports involves doping in sport, where bann ...
among young athletes.
Uses
Available forms
HMB is sold as an
over-the-counter dietary supplement
A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
in the
free acid
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of database
In c ...
form, ''β-hydroxy β-methylbutyric acid'' (HMB-FA), and as a
monohydrated calcium
salt of the
conjugate base, ''calcium monohydrate'' (HMB-Ca, CaHMB).
Since only a small fraction of HMB's metabolic precursor, , is metabolized into HMB, pharmacologically active concentrations of the compound in
blood plasma and muscle can only be achieved by supplementing HMB directly.
A healthy adult produces approximately 0.3 grams per day, while supplemental HMB is usually taken in doses of grams per day.
HMB is sold at a cost of about per month when taken in doses of 3 grams per day.
HMB is also contained in several nutritional products and medical foods marketed by
Abbott Laboratories (e.g., certain formulations of
Ensure,
Juven, and
Myoplex
EAS (formerly Experimental & Applied Sciences) was a distributor of creatine nutritional supplements with approximately 300 staff, annual sales exceeding $300 million, and offices/distributors in 54 countries.
History
EAS was founded in Pacif ...
),
and is present in insignificant quantities in certain foods, such as
alfalfa,
asparagus,
avocados,
cauliflower,
grapefruit
The grapefruit (''Citrus'' × ''paradisi'') is a subtropical citrus tree known for its relatively large, sour to semi-sweet, somewhat bitter fruit. The interior flesh is segmented and varies in color from pale yellow to dark pink.
Grapefruit is ...
, and
catfish
Catfish (or catfishes; order Siluriformes or Nematognathi) are a diverse group of ray-finned fish. Named for their prominent barbels, which resemble a cat's whiskers, catfish range in size and behavior from the three largest species alive, ...
.
Medical
Supplemental HMB has been used in
clinical trials as a treatment for preserving lean body mass in muscle wasting conditions, particularly
sarcopenia, and has been studied in clinical trials as an
adjunct therapy in conjunction with
resistance exercise.
Based upon two medical reviews and a
meta-analysis of seven
randomized controlled trials, HMB supplementation can preserve or increase lean muscle mass and muscle strength in
sarcopenic
Sarcopenia is a type of muscle loss (muscle atrophy) that occurs with aging and/or immobility. It is characterized by the degenerative loss of skeletal muscle mass, quality, and strength. The rate of muscle loss is dependent on exercise level, c ...
older adults.
HMB does not appear to significantly affect fat mass in older adults.
Preliminary clinical evidence suggests that HMB supplementation may also prevent
muscle atrophy
Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakness ...
during
bed rest.
A growing body of evidence supports the efficacy of HMB in nutritional support for reducing, or even reversing, the loss of muscle mass,
muscle function, and
muscle strength that occurs in
hypercatabolic
Hypermetabolism is defined as an elevated resting energy expenditure (REE) > 110% of predicted REE. Hypermetabolism is accompanied by a variety of internal and external symptoms, most notably extreme weight loss, and can also be a symptom in itself ...
disease states such as cancer
cachexia;
consequently, the authors of two 2016 reviews of the clinical evidence recommended that the prevention and treatment of sarcopenia and muscle wasting in general include supplementation with HMB, regular resistance exercise, and consumption of a
high-protein diet.
Clinical trials that used HMB for the treatment of muscle wasting have involved the administration of 3 grams of HMB per day under different dosing regimens.
According to one review, an optimal dosing regimen is to administer it in one 1 gram dose, three times a day, since this ensures elevated plasma concentrations of HMB throughout the day;
however, the best dosing regimen for muscle wasting conditions is still being investigated.
Some branded products that contain HMB (i.e., certain formulations of Ensure and Juven) are
medical foods that are intended to be used to provide nutritional support under the care of a doctor in individuals with
muscle wasting due to
HIV/AIDS or
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
, to promote
wound healing following surgery or injury, or when otherwise recommended by a medical professional. Juven, a nutrition product which contains 3 grams of , 14 grams of
-arginine, and 14 grams of
-glutamine per two servings,
has been shown to improve
lean body mass during clinical trials in individuals with AIDS and cancer, but not
rheumatoid cachexia.
Further research involving the treatment of cancer cachexia with Juven over a period of several months is required to adequately determine treatment efficacy.
Enhancing performance

With an appropriate exercise program, dietary supplementation with 3 grams of HMB per day has been shown to increase exercise-induced gains in muscle size, muscle strength and power, and lean body mass, reduce exercise-induced skeletal muscle damage, and expedite recovery from high-intensity exercise. Based upon limited clinical research, HMB supplementation may also improve aerobic exercise performance and increase gains in
aerobic fitness when combined with
high-intensity interval training.
These effects of HMB are more pronounced in untrained individuals and athletes who perform high intensity resistance or aerobic exercise.
In resistance-trained populations, the effects of HMB on muscle strength and lean body mass are limited.
HMB affects muscle size, strength, mass, power, and recovery in part by stimulating
myofibrillar muscle
protein synthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
and inhibiting muscle
protein breakdown through various mechanisms, including the activation of
mechanistic target of rapamycin complex 1
mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis.
mTOR Complex 1 (mTORC1) is compo ...
(mTORC1) and inhibition of
proteasome
Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
Proteasomes are part of a major mechanism by w ...
-mediated
proteolysis
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...
in skeletal muscles.
The efficacy of HMB supplementation for reducing skeletal muscle damage from prolonged or high-intensity exercise is affected by the time that it is used relative to exercise.
The greatest reduction in skeletal muscle damage from a single bout of exercise has been shown to occur when is ingested hours prior to exercise or is ingested minutes prior to exercise.
In 2006, only about 2% of college
student athlete
A student is a person enrolled in a school or other educational institution.
In the United Kingdom and most commonwealth countries, a "student" attends a secondary school or higher (e.g., college or university); those in primary or elementar ...
s in the United States used HMB as a dietary supplement.
As of 2017, HMB has found widespread use as an
ergogenic supplement
Performance-enhancing substances, also known as performance-enhancing drugs (PEDs), are substances that are used to improve any form of activity performance in humans. A well-known example of cheating in sports involves doping in sport, where bann ...
among athletes.
HMB has not been banned by the
National Collegiate Athletic Association,
World Anti-Doping Agency, or any other prominent national or international athletic organization.
Side effects
The
safety profile
Term Given By Tushar Sharma (UPES Batch 2025)
Pharmacovigilance (PV, or PhV), also known as drug safety, is the pharmaceutical science relating to the "collection, detection, assessment, monitoring, and prevention" of adverse effects with pharma ...
of HMB in adult humans is based upon evidence from
clinical trials in humans and
animal studies.
In humans, no
adverse effect
An adverse effect is an undesired harmful effect resulting from a Pharmaceutical drug, medication or other Surgery#Definitions, intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main ...
s in young adults or older adults have been reported when HMB is taken in doses of 3 grams per day for up to a year.
Studies on young adults taking 6 grams of HMB per day for up to 2 months have also reported no adverse effects.
Studies with supplemental HMB on young, growing rats and livestock have reported no adverse effects based upon
clinical chemistry or observable characteristics;
for humans younger than 18, there is limited data on the safety of supplemental HMB.
The
human equivalent dose The term human equivalent is used in a number of different contexts. This term can refer to human equivalents of various comparisons of animate and inanimate things.
Animal models in chemistry and medicine
Animal models are used to learn more abou ...
of HMB for the
no-observed-adverse-effect level (NOAEL) that was identified in a rat model is approximately 0.4 g/kg of
body weight per day.
Two animal studies have examined the effects of HMB supplementation in pregnant pigs on the offspring and reported no adverse effects on the fetus.
No clinical testing with supplemental HMB has been conducted on pregnant women,
and pregnant and lactating women are advised not to take HMB by
Metabolic Technologies, Inc.
Metabolic Technologies, Inc is an American life sciences company that sells dietary supplements and analytical services. Metabolic Technologies is headquartered in Ames, Iowa.
The company has sponsored a number of clinical trial
Clinical tria ...
, the company that grants licenses to include HMB in dietary supplements, due to a lack of safety studies.
Pharmacology
Pharmacodynamics
Several components of the
signaling cascade
A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that ...
that mediates the HMB-induced increase in human skeletal muscle protein synthesis have been identified ''
in vivo''.
Similar to HMB's
metabolic precursor, , HMB has been shown to increase protein synthesis in human skeletal muscle via
phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
of the
mechanistic target of rapamycin (mTOR) and subsequent activation of , which leads to
protein biosynthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...
in cellular
ribosome
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
s via phosphorylation of mTORC1's immediate targets (i.e., the
p70S6 kinase and the
translation repressor protein
4EBP1).
Supplementation with HMB in several non-human animal species has been shown to increase the
serum
Serum may refer to:
*Serum (blood), plasma from which the clotting proteins have been removed
**Antiserum, blood serum with specific antibodies for passive immunity
* Serous fluid, any clear bodily fluid
* Truth serum, a drug that is likely to mak ...
concentration of
growth hormone and
insulin-like growth factor 1 (IGF-1) via an unknown mechanism, in turn promoting protein synthesis through increased mTOR phosphorylation.
Based upon limited clinical evidence in humans, supplemental HMB appears to increase the secretion of growth hormone and IGF-1 in response to resistance exercise.
, the signaling cascade that mediates the HMB-induced reduction in muscle protein breakdown has not been identified in living humans, although it is well-established that it attenuates
proteolysis
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...
in humans ''in vivo''.
Unlike , HMB attenuates muscle protein breakdown in an
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
-independent manner in humans.
HMB is believed to reduce muscle protein breakdown in humans by inhibiting the
19S and
20S
Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
Proteasomes are part of a major mechanism by w ...
subunits of the
ubiquitin–proteasome system
Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
Proteasomes are part of a major mechanism by whi ...
in skeletal muscle and by inhibiting
apoptosis of
skeletal muscle nuclei via unidentified mechanisms.
Based upon animal studies, HMB appears to be metabolized within skeletal muscle into
cholesterol, which may then be incorporated into the
muscle cell membrane, thereby enhancing membrane integrity and function.
The effects of HMB on muscle
protein metabolism may help stabilize muscle cell structure.
One review suggested that the observed HMB-induced reduction in the plasma concentration of muscle damage
biomarkers (i.e., muscle enzymes such as
creatine kinase and
lactate dehydrogenase) in humans following intense exercise may be due to a cholesterol-mediated improvement in muscle cell membrane function.
HMB has been shown to stimulate the
proliferation
Proliferation may refer to:
Weapons
*Nuclear proliferation, the spread of nuclear weapons, material, and technology
*Chemical weapon proliferation, the spread of chemical weapons, material, and technology
* Small arms proliferation, the spread of ...
,
differentiation, and
fusion of human
myosatellite cells
Myosatellite cells, also known as satellite cells, muscle stem cells or MuSCs, are small multipotent cells with very little cytoplasm found in mature muscle. Satellite cells are precursors to skeletal muscle cells, able to give rise to satellite ...
''
in vitro'', which potentially increases the regenerative capacity of skeletal muscle, by increasing the protein expression of certain
myogenic regulatory factors (e.g.,
myoD and
myogenin) and gene
transcription factors (e.g.,
MEF2).
HMB-induced human myosatellite cell proliferation ''in vitro'' is mediated through the phosphorylation of the
mitogen-activated protein kinase
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses to ...
s
ERK1 and
ERK2.
HMB-induced human myosatellite differentiation and accelerated fusion of myosatellite cells into muscle tissue ''in vitro'' is mediated through the phosphorylation of
Akt, a
serine/threonine-specific protein kinase.
Pharmacokinetics

The free acid () and monohydrated calcium salt () forms of HMB have different
pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
.
HMB-FA is more readily absorbed into the bloodstream and has a longer
elimination half-life (3 hours) relative to HMB-Ca (2.5 hours).
Tissue uptake and utilization of HMB-FA is higher than for HMB-Ca.
The fraction of an ingested dose that is excreted in urine does not differ between the two forms.
After ingestion, is converted to following
dissociation of the calcium
moiety
Moiety may refer to:
Chemistry
* Moiety (chemistry), a part or functional group of a molecule
** Moiety conservation, conservation of a subgroup in a chemical species
Anthropology
* Moiety (kinship), either of two groups into which a society is ...
in the gut.
When the HMB-Ca
dosage form is ingested, the magnitude and time at which the peak plasma concentration of HMB occurs depends on the dose and concurrent food intake.
Higher HMB-Ca doses increase the rate of
absorption, resulting in a peak plasma HMB level (
Cmax) that is disproportionately greater than expected of a linear
dose-response relationship and which occurs sooner relative to lower doses.
Consumption of HMB-Ca with sugary substances slows the rate of HMB absorption, resulting in a lower peak plasma HMB level that occurs later.
HMB is eliminated via the
kidneys, with roughly of an ingested dose being excreted unchanged in urine.
The remaining of the dose is retained in tissues or excreted as HMB metabolites.
The fraction of a given dose of HMB that is excreted unchanged in urine increases with the dose.
Metabolism
The metabolism of HMB is catalyzed by an uncharacterized enzyme which converts it to
().
HMB-CoA is metabolized by either
enoyl-CoA hydratase or another uncharacterized enzyme, producing
β-methylcrotonyl-CoA
3-Methylcrotonyl-CoA or β-Methylcrotonyl-CoA is an intermediate in the metabolism of leucine.
It is found in mitochondria, where it is formed from isovaleryl-coenzyme A by isovaleryl coenzyme A dehydrogenase. It then reacts with CO2 to yield 3- ...
() or
hydroxymethylglutaryl-CoA
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase. The research of M ...
() respectively.
is then converted by the enzyme
methylcrotonyl-CoA carboxylase to
methylglutaconyl-CoA
3-Methylglutaconyl-CoA (MG-CoA), also known as β-methylglutaconyl-CoA, is an intermediate in the metabolism of leucine. It is metabolized into HMG-CoA.
Leucine metabolism
See also
* Methylcrotonyl-CoA carboxylase
* Methylglutaconyl-CoA hydrat ...
(), which is subsequently converted to by methylglutaconyl-CoA hydratase.
is then cleaved into and acetoacetate by HMG-CoA lyase, lyase or used in the production of cholesterol via the mevalonate pathway.
Biosynthesis
HMB is synthesized in the human body through the metabolism of leucine, , a branched-chain amino acid. In healthy individuals, approximately 60% of dietary is metabolized after several hours, with roughly 5% ( range) of dietary being converted to .
Around 40% of dietary is converted to , which is subsequently used in the synthesis of other compounds.
The vast majority of metabolism is initially catalyzed by the branched-chain amino acid aminotransferase enzyme, producing (α-KIC).
Figure 8.57: Metabolism of -leucine
α-KIC is mostly metabolized by the mitochondrial enzyme branched-chain alpha-keto acid dehydrogenase, branched-chain dehydrogenase, which converts it to isovaleryl-CoA.
Isovaleryl-CoA is subsequently metabolized by isovaleryl-CoA dehydrogenase and converted to , which is used in the synthesis of acetyl-CoA and other compounds.
During biotin deficiency, HMB can be synthesized from via
enoyl-CoA hydratase and an unknown thioesterase enzyme,
which convert into and into HMB respectively.
A relatively small amount of α-KIC is metabolized in the liver by the cytosolic enzyme 4-hydroxyphenylpyruvate dioxygenase (KIC dioxygenase), which converts α-KIC to HMB.
In healthy individuals, this minor pathway – which involves the conversion of to α-KIC and then HMB – is the predominant route of HMB synthesis.
Chemistry
acid is a carboxylic acid, monocarboxylic β-hydroxy acid and natural product with the molecular formula .
At room temperature, pure acid occurs as a transparent, colorless to light yellow liquid which is soluble in water.
acid is a weak acid with a pKa, p''K''
a of 4.4.
Its refractive index (
) is 1.42.
Chemical structure
acid is a member of the carboxylic acid family of organic compounds.
It is a structural analog of butyric acid with a hydroxy group, hydroxyl functional group and a methyl group, methyl substituent located on its Alpha and beta carbon, beta carbon.
By extension, other structural analogs include β-hydroxybutyric acid, acid and β-methylbutyric acid, acid.
Synthesis
A variety of synthetic routes to acid have been developed. The first reported chemical syntheses approached HMB by oxidation of alkene, vicinal (chemistry), vicinal diol, and Alcohol (chemistry), alcohol precursors:
* in 1877, Russian chemists Michael and Alexander Mikhaylovich Zaytsev, Alexander Zaytsev reported the preparation of HMB by oxidation of 2-methylpent-4-en-2-ol with chromic acid (H
2CrO
4);
[The earliest citation for the synthesis of β-hydroxy β-methylbutyric acid in the Reaxys chemical database as of September 2016 is:]
* in 1880 and 1889, Schirokoff and Reformatsky (respectively) reported that the oxidative cleavage of the vicinal diol 4-methylpentane-1,2,4-triol with acidified potassium permanganate (KMnO
4) yields HMB – this result is closest related to the first synthesis as cold dilute KMnO
4 oxidises alkenes to vicinal ''cis''-diols which hot acid KMnO
4 further oxidises to carbonyl-containing compounds, and the diol intermediate is not obtained when hot acidic conditions are used for alkene oxidation. In other words, racemic 4-methylpentane-1,2,4-triol is a derivative (chemistry), derivative of 2-methylpent-4-en-2-ol and β-hydroxy β-methylbutyric acid is a derivative of both; and,
* in 1892, Kondakow reported the preparation of HMB by permanganate oxidation of 3-methylbutane-1,3-diol.

Depending on the experimental conditions, cycloaddition of acetone and ketene produces either or 4,4-dimethyloxetan-2-one, both of which Hydrolysis, hydrolyze under basic conditions to yield the conjugate base of HMB. The haloform reaction provides another pathway to HMB involving the exhaustive halogenation of the methyl-ketone region of diacetone alcohol with sodium hypobromite or sodium hypochlorite;
Diacetone alcohol is readily available from the aldol condensation of acetone.
An organometallic chemistry, organometallic approach to HMB involves the carboxylation of tert-butyl alcohol, ''tert''-butyl alcohol with carbon monoxide and Fenton's reagent (hydrogen peroxide and ferrous iron).
Alternatively, HMB can be prepared through fermentation, microbial oxidation of acid by the fungus ''Galactomyces reessii''.
Detection in body fluids
The concentration of naturally produced HMB has been measured in several human body fluids using nuclear magnetic resonance spectroscopy, liquid chromatography–mass spectrometry, and gas chromatography–mass spectrometry methods.
In the blood plasma and cerebrospinal fluid (CSF) of healthy adults, the average molar concentration of HMB has been measured at 4.0 micromolar (μM).
The average concentration of HMB in the sarcoplasma, intramuscular fluid of healthy men of ages has been measured at 7.0 μM.
In the urine of healthy individuals of any age, the excreted urinary concentration of HMB has been measured in a range of micromoles per millimole (μmol/mmol) of creatinine.
In the breast milk of healthy lactating women, HMB and have been measured in ranges of μg/L and mg/L.
In comparison, HMB has been detected and measured in the milk of healthy cows at a concentration of μg/L.
This concentration is far too low to be an adequate dietary source of HMB for obtaining pharmacologically active concentrations of the compound in blood plasma.
In a study where participants consumed 2.42 grams of pure while fasting, the average plasma HMB concentration increased from a basal level of 5.1 to 408 μM after 30 minutes.
At 150 minutes post-ingestion, the average plasma HMB concentration among participants was 275 μM.
Abnormal HMB concentrations in urine and blood plasma have been noted in several disease states where it may serve as a diagnostic biomarker, particularly in the case of metabolic disorders.
The following table lists some of these disorders along with the associated HMB concentrations detected in urine or blood plasma.
History
The first reported chemical synthesis of HMB was published in 1877 by the Russian chemists Michael and Alexander Mikhaylovich Zaytsev, Alexander Zaytsev.
HMB was isolated from the bark of ''Erythrophleum, Erythrophleum couminga'' (a Madagascan tree) in 1941 by Leopold Ružička. The earliest reported isolation of HMB as a human metabolite was by Tanaka and coworkers in 1968 from a patient with isovaleric acidemia.
The effects of HMB on human skeletal muscle were first discovered by Steven L. Nissen at
Iowa State University in the .
Nissen founded a company called
Metabolic Technologies, Inc.
Metabolic Technologies, Inc is an American life sciences company that sells dietary supplements and analytical services. Metabolic Technologies is headquartered in Ames, Iowa.
The company has sponsored a number of clinical trial
Clinical tria ...
(MTI) around the time of his discovery, which later acquired six HMB-related patents that the company has used to license the right to manufacture and incorporate HMB into dietary supplements.
granted patents include: , , , , and . When it first became available commercially in the late 1990s, HMB was marketed solely as an exercise supplement to help athletes and bodybuilders build muscle.
MTI subsequently developed two HMB-containing products, Juven and Revigor, to which Abbott Nutrition obtained the market rights in 2003 and 2008 respectively.
Since then, Abbott has marketed Juven as a medical food and the Revigor brand of HMB as an active ingredient in food products for athletes (e.g., certain formulations of Myoplex) and other medical foods (e.g., certain formulations of Ensure).
See also
* 3-Aminoisobutyric acid
Notes
Reference notes
References
External links
*
{{DEFAULTSORT:Hydroxy beta-methylbutyric acid, beta-
Amino acid derivatives
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