Meta Information
ID:hmb
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/intervention/resistance-training
Target name:
Resistance Training
Severity:
major
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
null
Description:
HMB reduces muscle protein breakdown and enhances recovery. Peak blood levels occur 1-2 hours post-ingestion, making pre-workout timing ideal to counteract exercise-induced muscle damage and improve adaptation.
Actionable advice:
An HMB dose should be taken 30-60 minutes before starting a resistance training session for maximal benefit.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The primary mode of action of HMB appears to be through its dual mechanism to enhance muscle protein synthesis and suppress muscle protein breakdown. HMB's activation of mTORC1 is independent of the leucine-sensing pathway (Sestrin2-GATOR2 complex). 5. HMB may help reduce muscle damage and promote muscle recovery, which can promote muscle growth/repair.
Label source:
PubMed: International society of sports nutrition position stand: β-hydroxy-β-methylbutyrate (HMB). (PMID 39699070)
Action type:
separate
Target id:
/intervention/creatine
Target name:
Creatine
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
HMB and creatine work via different pathways to improve muscle health; HMB reduces breakdown while creatine enhances cellular energy (ATP), leading to additive benefits in strength, power, and lean mass.
Actionable advice:
Consider taking HMB and creatine together, as they work synergistically to support muscle growth and strength.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In summary, CR and HMB can increase LBM and strength, and the effects are additive. Although not definitive, these results suggest that CR and HMB act by different mechanisms.
Label source:
PubMed: Nutrition (Burbank, Los Angeles County, Calif.) (2001)
Source url:
Exact phrase from label:
The primary mode of action of HMB appears to be through its dual mechanism to enhance muscle protein synthesis and suppress muscle protein breakdown. HMB's activation of mTORC1 is independent of the leucine-sensing pathway (Sestrin2-GATOR2 complex).
Label source:
PubMed: Journal of the International Society of Sports Nutrition (2025)
Source url:
Exact phrase from label:
Creatine monohydrate (3-5 g·day-1, with or without loading) produced measurable increases in muscle thickness or cross-sectional area in interventions lasting ≥8-12 weeks, mediated by enhanced training volume and quality. β-hydroxy-β-methylbutyrate (HMB, 3 g·day-1) demonstrated conditional utility during high training stress or caloric deficit, but was largely neutral in well-fed, resistance-trained cohorts.
Label source:
PubMed: Nutrients (2025)
Action type:
informational_none
Target id:
/intervention/protein
Target name:
Dietary Protein / Essential Amino Acids
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
HMB signals for muscle protein synthesis and prevents breakdown, but it does not provide the amino acid building blocks itself. Adequate protein intake is necessary to realize HMB's muscle-building benefits.
Actionable advice:
Adequate daily protein from food or supplements is a good idea for HMB to be effective at building muscle.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In conclusion, supplementation with either 1.5 or 3 g HMB/day can partly prevent exercise-induced proteolysis and/or muscle damage and result in larger gains in muscle function associated with resistance training.
Label source:
PubMed: Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. (PMID 8941534)
Action type:
informational_none
Target id:
/intervention/vitamin-d
Target name:
Vitamin D
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both HMB and Vitamin D support muscle function and strength, particularly in older adults. Combining them has shown greater benefits for combating age-related muscle loss (sarcopenia) than either alone.
Actionable advice:
HMB and Vitamin D are best taken concurrently, especially for older adults concerned with muscle health.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Moreover, combination therapies, such as nutritional supplementation with HMB and vitamin D, showed promise in improving muscle function.
Label source:
PubMed: Therapeutics for Sarcopenia and Functional Disabilities in Older Adults: A Review of Phase 4 Clinical Trials. (PMID 40165996)
Action type:
informational_none
Target id:
/intervention/calorie-restriction-diet
Target name:
Calorie Restriction / Dieting
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
HMB's primary anti-catabolic effect helps preserve lean muscle mass during periods of caloric deficit, which is crucial for maintaining metabolic rate and strength while losing fat.
Actionable advice:
Daily HMB supplementation is a good idea when following a calorie-restricted diet, to help prevent muscle loss.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
HMB improves body composition and sensorimotor function during normal training and attenuates muscle mass and strength loss during catabolic conditions. HMB intake attenuates the loss of gastrocnemius mass and myofiber CSA during catabolic conditions imposed by calorie restriction and prolonged endurance exercise.
Label source:
Primary literature: https://nationalmaglab.org/library/publications/NHMFL_Publication-7197.pdf
Action type:
informational_none
Target id:
/intervention/high-intensity-interval-training
Target name:
High-Intensity Interval Training (HIIT)
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
null
Description:
Taking HMB before intense training like HIIT can help mitigate muscle damage and soreness, improving recovery between sessions.
Actionable advice:
HMB is best taken 30-60 minutes before a HIIT session to reduce muscle damage and support recovery.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
HMB supplementation can be considered as an effective nutritional strategy to minimize EIMD. HMB-FA supplementation seemed to mitigate resistance exercise–induced muscle damage and speed recovery in trained men. With respect to acute effects, HMB supplementation can be taken 30 to 60 min prior to commencing high-intensity exercise.
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC9925108/
Action type:
separate
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The safety of HMB supplementation during pregnancy has not been established. It should be avoided due to unknown effects on fetal development.
Actionable advice:
HMB should not be taken during pregnancy.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
There isn't enough reliable information to know if HMB is safe to use when pregnant or breast-feeding.
Label source:
Anecdotal: WebMD
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is unknown if HMB is excreted into breast milk or what its effects might be on a nursing infant. Therefore, its use should be avoided during lactation.
Actionable advice:
HMB should not be taken while breastfeeding.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
There isn't enough reliable information to know if HMB is safe to use when pregnant or breast-feeding.
Label source:
Anecdotal: WebMD
Action type:
avoid
Target id:
/condition/renal-impairment
Target name:
Renal Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While HMB is generally safe, its clearance may be altered in individuals with significantly impaired kidney function. Caution is advised due to a lack of specific safety data in this population.
Actionable advice:
It is important to talk to a physician before using HMB with known kidney disease.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
These data indicate that 8 wk of HMB supplementation (< or = 76 mg x kg(-1) x d(-1)) during resistance training had no adverse affects on hepatic enzyme function, lipid profile, renal function, or the immune system.
Label source:
PubMed: Medicine and science in sports and exercise (2000)
Source url:
Exact phrase from label:
A half quantity of the defined dose of the supplement combination, with an enteral nutrition product, was administered to the patients twice a day. This combination improved the PUs, with no effect on renal function.
Label source:
PubMed: Journal of wound care (2015)
Source url:
Exact phrase from label:
Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the amino acid leucine that has been shown to improve lean mass and physical function in elderly and clinical populations, but had not been studied in MHD patients.
Label source:
PubMed: Hemodialysis international. International Symposium on Home Hemodialysis (2017)
Action type:
informational_none
Target id:
/condition/hepatic-impairment
Target name:
Hepatic Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The metabolism of HMB in individuals with severe liver disease has not been well-studied. Prudence dictates caution until more safety data is available.
Actionable advice:
It is important to talk to a physician before using HMB with known liver disease.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Although most of the endogenous HMB is produced in the liver, there are no reports regarding the levels and the effects of HMB supplementation in subjects with liver disease.
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC5566641/
Action type:
informational_none
Target id:
/dietary/high-protein-meal
Target name:
Large Protein-Rich Meal
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
0.5
Hours after target:
1
Description:
Taking HMB with a large amount of other amino acids (from a protein meal) may create competition for absorption, potentially slowing its uptake and blunting the peak concentration needed for pre-workout effects.
Actionable advice:
For optimal pre-workout timing, HMB is best taken on an empty stomach or with carbohydrates, not with a large protein shake or meal.
Validation status:
validated_via_clinical_guidance
Evidence tier:
tier_b
Evidence basis:
clinical_guidance_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA
Label source:
Clinical guidance: ISSN Position Stand on HMB (Wilson et al. J Int Soc Sports Nutr 2013;10:6 PMID 23374455)
Action type:
separate
Target id:
/intervention/calcium-citrate
Target name:
Calcium Supplements
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
HMB is commonly sold as a calcium salt (Calcium-HMB), meaning each dose contributes to your total calcium intake. This should be factored into your overall daily calcium supplementation.
Actionable advice:
Account for the calcium in your HMB supplement when calculating your total daily calcium intake to avoid excess.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Two forms of HMB have been studied: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA).
Label source:
PubMed: Journal of the International Society of Sports Nutrition (2025)
Source url:
Exact phrase from label:
The calcium salt of HMB is the most used chemical form in dietary supplements, being the most common dose 3 g of HMB/day.
Label source:
PubMed: Nutricion hospitalaria (2014)
Source url:
Exact phrase from label:
The leucine metabolite, 3-hydroxy-3-methylbutyrate (HMB), primarily utilized as the calcium salt (CaHMB) has become one of the most widely used supplements and food ingredients to promote muscle health.
Label source:
PubMed: Regulatory toxicology and pharmacology : RTP (2022)
Action type:
avoid