HMB Supplementation for Muscle Atrophy After Surgery

(FAKS-HMB Trial)

Overseen By Sharon Bradshaw

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must not be taking: Nutritional supplements

Disqualifiers: Sleep disorder, Depression, Orthopedic history, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a supplement called CaHMB (also known as HMB or β-hydroxy-β-methylbutyrate) to determine if it reduces muscle loss after knee surgery. The researchers aim to discover if CaHMB can improve muscle size and strength in the legs of female athletes undergoing ACL surgery. Participants will receive either CaHMB or a placebo (an inactive substance) to compare effects. This trial suits women with an ACL injury who plan to have surgery and are not currently taking other nutritional supplements. As a Phase 2 trial, this research measures how well CaHMB works in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CaHMB, a supplement, is generally safe for people. Studies indicate it can be used for up to a year without major safety issues. This supplement helps prevent muscle loss and can improve muscle function, proving beneficial for individuals with muscle-wasting conditions like AIDS and cancer.

In this trial, CaHMB is combined with Vitamin D3, both known to support muscle health. While Vitamin D3 is a common supplement, CaHMB has also been used safely in other studies. Overall, the combination of CaHMB and Vitamin D3 is well-tolerated, and previous research has not reported any significant safety concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for muscle atrophy?

Unlike traditional treatments for muscle atrophy, which often focus on exercise and nutrition alone, CaHMB supplementation is unique because it combines the muscle-preserving benefits of HMB (beta-hydroxy beta-methylbutyrate) with Vitamin D3. This combination aims to reduce muscle loss more effectively by both supporting muscle protein synthesis and enhancing muscle strength and recovery. Researchers are particularly excited about CaHMB because it is taken in conjunction with physical therapy, potentially accelerating recovery and improving outcomes for patients post-surgery, providing a promising new approach to managing muscle atrophy.

What evidence suggests that CaHMB supplementation could be effective for muscle atrophy after ACL surgery?

Research shows that CaHMB, a dietary supplement, can help build muscle and reduce muscle breakdown. This trial will evaluate the effects of CaHMB combined with Vitamin D3 on muscle recovery after surgery. Studies have found that CaHMB improves muscle function, prevents muscle wasting, and aids recovery post-surgery. It also supports wound healing and helps regain muscle strength and movement. Although one study did not find a significant reduction in muscle wasting over a short period, others have observed better muscle recovery, such as shorter hospital stays. Overall, evidence suggests CaHMB aids muscle recovery, especially after surgery. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

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

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

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

Participant has implants, hardware, devices, or other non-removable metal material in the body that would limit the accuracy of body composition assessments within the measurement area

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• CaHMB

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.

How Is the Trial Designed?

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+

National Strength and Conditioning Association

Collaborator

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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HMB Supplementation for Muscle Atrophy After Surgery

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