Β-Hydroxy β-methylbutyric acid

Metabolite of leucine involved in muscle metabolism

Beta-Hydroxy beta-methylbutyric acid 2

Beta-Hydroxy beta-methylbutyrate 2

Calcium β-hydroxy β-methylbutyrate monohydrate

Muscle protein synthesis signaling cascades

β-Hydroxy β-methylbutyric acid (HMB) is a naturally occurring metabolite of the essential amino acid leucine. It plays a crucial role in protein metabolism, muscle recovery, and anabolic processes. HMB is often used as a dietary supplement to support muscle growth, reduce muscle breakdown, and enhance exercise performance.

Biosynthesis and Metabolism

HMB is produced in the human body through the metabolism of leucine:

1. Leucine is first converted into α-ketoisocaproate (KIC) via branched-chain aminotransferase (BCAT).
2. KIC is then metabolized by ketoisocaproate dioxygenase (KICD) in the liver to form HMB.
3. Approximately 5% of dietary leucine is converted into HMB.

HMB undergoes further metabolism:

• It is converted into β-hydroxy β-methylbutyryl-CoA (HMB-CoA).
• HMB-CoA enters the cholesterol synthesis pathway, supporting cell membrane repair.
• A portion of HMB is also metabolized into β-hydroxy β-methylglutaryl-CoA (HMG-CoA), a precursor to cholesterol.

Physiological Functions

HMB is believed to have several physiological roles, including:

• Reducing muscle protein breakdown (anti-catabolic effect).
• Enhancing muscle protein synthesis via the mTOR signaling pathway.
• Improving recovery from resistance training and high-intensity exercise.
• Supporting immune function and reducing muscle loss in individuals with cachexia or sarcopenia.

Dietary Sources

HMB is naturally found in small amounts in:

• Animal-based foods such as milk, cheese, and eggs.
• Plant-based sources such as alfalfa.
• Muscle tissue metabolism following dietary leucine intake.

Use as a Dietary Supplement

HMB is available as a nutritional supplement in two main forms:

• HMB-Free Acid (HMB-FA) – Rapidly absorbed and bioavailable.
• HMB-Calcium Salt (HMB-Ca) – More stable, commonly used in commercial products.

It is often used for:

• Sports performance enhancement – Reducing exercise-induced muscle damage.
• Elderly health – Preventing muscle wasting and promoting functional mobility.
• Clinical applications – Used in conditions like cachexia, cancer-related muscle loss, and HIV/AIDS-associated wasting.

Clinical Research

Studies on HMB have shown:

• Muscle Mass and Strength – HMB supplementation combined with resistance training improves muscle strength and lean body mass.
• Endurance Performance – May reduce exercise-induced muscle damage and enhance recovery.
• Aging and Sarcopenia – Beneficial in preventing age-related muscle loss.
• Medical Conditions – Used in patients with chronic diseases to preserve muscle mass.

Safety and Side Effects

HMB is generally considered safe when used at recommended doses (3g/day). Potential side effects include:

• Gastrointestinal discomfort in some individuals.
• No reported toxicity at commonly used doses.

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  ISSN HMB statement Fig 2

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  Butyric acid carbons 2

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  Beta-Hydroxy beta-methylbutyric acid 2

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  HMB synthesis historical

See Also

• Leucine
• Muscle protein synthesis
• Amino acid metabolism
• Sarcopenia
• Dietary supplements