HMB Supplementation for Muscle Atrophy After Surgery

(FAKS-HMB Trial)

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Kansas Medical Center

Must not be taking: Nutritional supplements

Disqualifiers: Sleep disorder, Depression, Orthopedic history, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial will test if a muscle-building supplement called caHMB can help female athletes recover better after ACL knee surgery. The study will compare the effects of caHMB in women over 18 who have injured their ACL. caHMB works by helping muscles grow and preventing them from shrinking when not used. HMB in its free acid formulation is suggestive of having a greater potential for efficacy in both trained and untrained populations than its calcium-salt form.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who are currently consuming nutritional supplements other than multivitamins and minerals. It's best to discuss your specific medications with the trial coordinators.

What data supports the effectiveness of the treatment CaHMB for muscle atrophy after surgery?

Research shows that HMB, a component of CaHMB, can help improve muscle mass and strength in various groups, including athletes, older adults, and patients with cancer. Additionally, studies indicate that HMB can reduce muscle wasting and promote muscle recovery in aged animals and improve muscle function in older adults, suggesting potential benefits for muscle atrophy after surgery. ^{1 2 3 4 5}

Is HMB supplementation safe for humans?

Research shows that HMB, including its calcium salt form CaHMB, is generally safe for humans. Studies in animals and humans have not found any harmful effects, and it has been well-tolerated in various doses. ^{1 2 6 7 8}

How does HMB supplementation differ from other treatments for muscle atrophy after surgery?

HMB supplementation is unique because it enhances muscle protein synthesis and reduces muscle breakdown, which helps prevent muscle loss and promotes recovery. Unlike other treatments, HMB is available in two forms, calcium salt and free acid, with the calcium salt form having greater bioavailability, meaning the body can use it more effectively. ^{3 9 10 11 12}

Research Team

Eligibility Criteria

This trial is for female athletes aged 18-35 who are undergoing ACL knee surgery and will do their rehab at an affiliated clinic. They must not be taking supplements (other than basic vitamins), have no recent injuries or surgeries on the other leg, no metal implants affecting body composition measurements, not pregnant, and free from certain psychiatric conditions.

Inclusion Criteria

Participant has provided written and dated informed consent to participate in the study

I plan to attend physical therapy at a specific clinic after surgery.

I am a woman aged between 18 and 35.

Exclusion Criteria

Participant is currently consuming nutritional supplements or has recently (regularly) consumed nutritional supplements, other than multivitamins and minerals in <9 weeks prior to participation

I have a sleep disorder or mental health condition that could affect my recovery.

Participant has a known allergy or sensitivity to any ingredient in the test product/s

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgery Supplementation

Participants begin supplementation of HMB or placebo 2 weeks prior to surgery

2 weeks

1 visit (in-person)

Post-operative Monitoring

Participants are monitored and measured at 2-weeks post-operative and every 6 weeks until cleared to return to sport

9 months

Every 6 weeks (in-person)

Rehabilitation and Supplementation

Participants continue rehabilitation and supplementation with HMB or placebo, with assessments of muscle mass and function

9 months

Regular physical therapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CaHMB (Other)

Trial Overview The study tests if a dietary supplement called CaHMB can help maintain muscle mass and function after ACL knee surgery compared to a placebo. Participants will be randomly assigned to either the supplement group or placebo group in a double-blind manner and monitored over several weeks during rehabilitation.

Participant Groups

Group I: CaHMB+Vitamin D3-Active Experimental Experimental Treatment 1 Intervention

Participants will consume 3 g HMB with 2000 IU Vitamin D3 per day, split into two doses daily for the duration of the study, beginning 2 weeks prior to their surgical date. The first dose will be consumed 60 minutes prior to any at- home or outpatient physical therapy session and a second will be consumed immediately following the session. If a treatment day does not include any rehabilitation session, the participant will consume one dose in the morning prior to food consumption and the second dose approximately 90 minutes later.

Group II: Calcium Lactate-Control Placebo Placebo Group 1 Intervention

Participants will consume inactive 510 mg Ca Lactate capsules per day, split into two doses daily for the duration of the study, beginning 2 weeks prior to their surgical date. The first dose will be consumed 60 minutes prior to any at- home or outpatient physical therapy session and a second will be consumed immediately following the session. If a treatment day does not include any rehabilitation session, the participant will consume one dose in the morning prior to food consumption and the second dose approximately 90 minutes later.

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Dr. Steve Stites

University of Kansas Medical Center

Chief Executive Officer

MD from University of Kansas School of Medicine

Dr. Matthias Salathe

University of Kansas Medical Center

Chief Medical Officer

MD from University of Kansas School of Medicine

National Strength and Conditioning Association

Collaborator

Trials

3

Recruited

110+

Metabolic Technologies Inc.

Industry Sponsor

Trials

21

Recruited

800+

Founded

1990

Headquarters

Ames, USA

Known For

Muscle Health Supplements

Top Products

myHMB, myHMB Clear, myHMB + Vitamin D, BetaTOR

Findings from Research

In a post-hoc analysis of the HMB-ICU trial involving ICU patients on mechanical ventilation, the administration of HMB (3 g/day) for 30 days did not significantly affect plasma levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), C-peptide, or 25-OH vitamin-D compared to placebo.

Both groups showed a significant increase in IGF-1 levels from day 4 to day 15, indicating that while HMB did not have a distinct effect, there may be other factors influencing IGF-1 levels in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of ß-hydroxy-ß-methylbutyrate (HMB) in critically ill patients on the endocrine axis - A post-hoc cohort study of the HMB-ICU trial. Pantet, O., Viana, MV., Engelen, MPKJ., et al.[2023]

A study involving 72 obese Chinese adults will evaluate the effectiveness of HMB-enriched nutritional supplements over 12 weeks, focusing on improving muscle mass and function during calorie restriction.

The primary outcome will measure changes in whole-body skeletal muscle mass, with additional assessments on body fat, metabolic rate, and muscle function, ensuring a comprehensive understanding of HMB's impact on body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-hydroxy-β-methylbutyrate-enriched nutritional supplements for obese adults during weight loss: study protocol of a randomised, double-blind, placebo-controlled clinical trial. Jing, X., Liang, Y., Wang, R., et al.[2022]

In a study involving aged rats, β-Hydroxy-β-methylbutyrate (HMB) effectively prevented the decline in muscle force and promoted muscle fiber growth after a period of disuse, indicating its potential to aid muscle recovery.

HMB treatment reduced markers of muscle cell death, such as cleaved caspases, suggesting that its protective effects against muscle loss may be linked to inhibiting apoptosis in muscle cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats. Hao, Y., Jackson, JR., Wang, Y., et al.[2023]

This study is a feasibility trial involving 50 participants over 18 months, aiming to assess the practicality of administering β-Hydroxy-β-methylbutyrate (HMB) to critically ill patients after major trauma in the ICU.

The trial will evaluate the impact of HMB on muscle mass and nutrition-related outcomes, with the goal of informing a larger study on its potential to reduce muscle wasting in ICU patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-Hydroxy-β-methylbutyrate (HMB) supplementation and functional outcomes in multi-trauma patients: a study protocol for a pilot randomised clinical trial (BOOST trial). Wittholz, K., Fetterplace, K., Ali Abdelhamid, Y., et al.[2022]

Supplementation with calcium β-hydroxy-β-methylbutyrate (HMB) and vitamin D3 significantly improved lean body mass and muscle strength in older adults (over 60 years) who were not exercising, with notable benefits observed at 6 months and 3 months respectively.

The study, which involved 117 participants over 12 months, found that HMB+D supplementation enhanced physical functionality, as measured by a composite functional index, even in non-exercisers, indicating its potential as a beneficial intervention for maintaining muscle health in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Effects of Calcium β-Hydroxy-β-Methylbutyrate and Vitamin D3 Supplementation on Muscular Function in Older Adults With and Without Resistance Training: A Randomized, Double-blind, Controlled Study. Rathmacher, JA., Pitchford, LM., Khoo, P., et al.[2021]

Three genotoxicity studies conducted on calcium HMB (CaHMB) showed no harmful effects on genetic material, indicating it is safe for use in humans.

In tests involving bacteria and mammalian cells, CaHMB did not cause any significant changes in mutation rates or chromosomal abnormalities, supporting its safety as a sports nutrition supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotoxicity assessment of calcium β-hydroxy-β-methylbutyrate. Pitchford, LM., Fuller, JC., Rathmacher, JA.[2019]

In a study of 47 patients on the liver transplantation waiting list, both β-hydroxy β-methylbutyrate (HMB) and a control supplement improved muscle mass (measured by arm circumference) and strength (measured by dynamometry) over 12 weeks, indicating potential benefits of HMB supplementation.

Both groups showed a decrease in the frailty index, suggesting improved functionality and quality of life, although the specific advantages of HMB over the control were not clearly established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of β-hydroxy β-methylbutyrate (HMB) with nutritional counselling on anthropometric muscle mass markers, strength, functionality, and quality of life in patients on the waiting list for liver transplantation: A double-blind study. Ferreira, SC., Souza, NP., Amado, LRN., et al.[2023]

A 90-day study on rats showed that calcium 3-hydroxy-3-methyl butyrate (CaHMB) was well-tolerated at dietary levels up to 5%, with no adverse effects on health or behavior observed.

The study established a no-observed-adverse-effect level (NOAEL) of 5% CaHMB in the diet, indicating it is safe for consumption at this level without negative health impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary toxicity of calcium beta-hydroxy-beta-methyl butyrate (CaHMB). Baxter, JH., Carlos, JL., Thurmond, J., et al.[2012]

The study found that the calcium salt form of HMB (CaHMB) has significantly higher relative bioavailability compared to the free acid form (FAHMB) when administered orally, with increases of 49%, 54%, and 27% for different doses.

After intravenous administration, CaHMB also showed an 80% greater bioavailability than FAHMB, suggesting that CaHMB may be more effective in enhancing muscle protein synthesis and preventing muscle loss due to its better absorption and lower systemic clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relative bioavailability of the calcium salt of β-hydroxy-β-methylbutyrate is greater than that of the free fatty acid form in rats. Shreeram, S., Johns, PW., Subramaniam, S., et al.[2023]

A single dose of approximately 3 grams of calcium β-hydroxy-β-methylbutyrate (Ca-HMB) significantly increased muscle protein synthesis (MPS) and reduced muscle protein breakdown (MPB) in healthy young males, indicating its effectiveness in promoting muscle health.

The study demonstrated that Ca-HMB activates the mTORc1 signaling pathway, similar to the free acid form of HMB, suggesting that both forms are effective in enhancing muscle mass preservation despite differences in bioavailability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism. Wilkinson, DJ., Hossain, T., Limb, MC., et al.[2023]

The study demonstrated that administering a daily enteral supplement of 3g of HMB in the ICU is feasible, with 84.3% adherence to the prescribed regimen among 50 participants over 28 days.

While there was a trend suggesting that HMB may help reduce muscle loss compared to placebo, the results were inconclusive, indicating that further research is needed to confirm its efficacy in preventing muscle wasting after traumatic injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-hydroxy-beta-methylbutyrate supplementation and functional outcomes in multitrauma patients: A pilot randomized controlled trial. Wittholz, K., Fetterplace, K., Karahalios, A., et al.[2023]

A systematic review of 15 randomized controlled trials involving 2137 patients found that β-Hydroxy-β-methylbutyrate (HMB) and HMB-containing supplements can lead to small increases in skeletal muscle mass and strength, with effect sizes of 0.25 and 0.31 respectively.

Despite the positive findings, the studies had a high risk of bias, indicating a need for further high-quality research to confirm these results and their applicability in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-Hydroxy-β-methylbutyrate and its impact on skeletal muscle mass and physical function in clinical practice: a systematic review and meta-analysis. Bear, DE., Langan, A., Dimidi, E., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Impact of ß-hydroxy-ß-methylbutyrate (HMB) in critically ill patients on the endocrine axis - A post-hoc cohort study of the HMB-ICU trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

β-hydroxy-β-methylbutyrate-enriched nutritional supplements for obese adults during weight loss: study protocol of a randomised, double-blind, placebo-controlled clinical trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats. [2023]

4. England pubmed.ncbi.nlm.nih.gov

β-Hydroxy-β-methylbutyrate (HMB) supplementation and functional outcomes in multi-trauma patients: a study protocol for a pilot randomised clinical trial (BOOST trial). [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Long-term Effects of Calcium β-Hydroxy-β-Methylbutyrate and Vitamin D3 Supplementation on Muscular Function in Older Adults With and Without Resistance Training: A Randomized, Double-blind, Controlled Study. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Genotoxicity assessment of calcium β-hydroxy-β-methylbutyrate. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

The effect of β-hydroxy β-methylbutyrate (HMB) with nutritional counselling on anthropometric muscle mass markers, strength, functionality, and quality of life in patients on the waiting list for liver transplantation: A double-blind study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Dietary toxicity of calcium beta-hydroxy-beta-methyl butyrate (CaHMB). [2012]

9. United States pubmed.ncbi.nlm.nih.gov

The relative bioavailability of the calcium salt of β-hydroxy-β-methylbutyrate is greater than that of the free fatty acid form in rats. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Beta-hydroxy-beta-methylbutyrate supplementation and functional outcomes in multitrauma patients: A pilot randomized controlled trial. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

β-Hydroxy-β-methylbutyrate and its impact on skeletal muscle mass and physical function in clinical practice: a systematic review and meta-analysis. [2023]