THE OVRL QUALITY STANDARD

Recovery Is Not Only About Building New Muscle — It Is Also About Limiting What Exercise Breaks Down

At OVRL, we believe recovery should be viewed as a balance between two simultaneous biological processes: muscle protein synthesis and muscle protein breakdown.

Training provides the stimulus for adaptation, but intense exercise also creates muscular stress. For a positive change in muscle protein over time, synthesis must exceed breakdown.

This is why HMB — β-hydroxy-β-methylbutyrate, a naturally occurring metabolite of leucine — is scientifically interesting. Research reviewed by the International Society of Sports Nutrition describes HMB as acting on both sides of this balance: stimulating pathways associated with muscle protein synthesis while also influencing mechanisms involved in muscle protein breakdown.

For OVRL, this makes HMB fundamentally different from simply adding another amino acid to a formulation. Its relevance lies in the biological mechanisms being investigated around muscle protein turnover, exercise-induced muscle damage and functional recovery.

But dose transparency is essential.

The OVRL Whey Isolate formula provides 1 g of HMB per serving. Most of the clinical research highlighted in the 2024 ISSN position stand used approximately 3 g of HMB per day, including the human studies cited for muscle protein synthesis, protein breakdown and several recovery outcomes.

Therefore, OVRL does not present a single 1 g serving as equivalent to the 3 g/day protocols most commonly studied in the literature.

That distinction is part of the OVRL Quality Standard: the science behind an ingredient should be presented together with the dose actually present in the product.

WHAT THE RESEARCH SHOWS

“Changes in muscle mass are regulated by the balance of muscle protein synthesis and muscle protein breakdown [38]. When the rate of muscle protein synthesis exceeds the rate of muscle protein breakdown, there is a net increase in muscle protein. Conversely, when the rate of muscle protein breakdown exceeds the rate of muscle protein synthesis, there is a net decrease in muscle protein. The primary and most investigated mode of action of HMB has been through its dual mechanism to enhance muscle protein synthesis and suppress muscle protein breakdown. Like its parent amino acid, leucine, HMB upregulates muscle protein synthesis via the mammalian target of rapamycin (mTOR) and its downstream targets ribosomal protein S6 kinase (p70S6K1) and eukaryotic initiation factor-4 binding protein-1 (4EBP1) in vitro [39]. It is thought that leucine metabolites, such as HMB, may contribute to or directly drive the anabolic responses to leucine because leucine is metabolized within the muscle. In vitro evidence suggests that the conversion of leucine into HMB is necessary for the maximal stimulation of protein synthesis [40]. Furthermore, Suryawan et al. [41] demonstrated that both leucine and HMB stimulate the mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation in muscle. Leucine’s action involves the dissociation of the Sestrin2-GATOR2 complex and increased binding of Rag A/C to mTOR, whereas, HMB’s activation of mTORC1 is independent of this leucine-sensing pathway. Clinical study results show that a 3 g dose of HMB induces a robust (near-maximal) stimulation of muscle protein synthesis in human muscle via activation of mTORC1 and downstream phosphorylation of p70S6K1, in agreement with in vitro evidence [28,42]. This stimulation is independent of the HMB form, with similar results observed for HMB-Ca and HMB-FA in separate studies [28,42]. As HMB supplementation can increase growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels [29], it may also stimulate protein synthesis via GH/IGF-1 axis signaling, though HMB-induced increases in these hormones have not been directly linked to protein synthesis. Preclinical evidence shows that HMB also decreases muscle protein breakdown through multiple pathways, including the suppression of the ubiquitin-proteasome pathway [49–51], inhibition of myonuclear apoptosis via mitochondrial-associated caspase signaling [52], and suppression of lysosomal autophagy pathways [53]. Clinical studies show that 3 g of HMB significantly decreases muscle protein breakdown independent of HMB form (i.e. calcium vs free acid) [28,42].”

“Data suggests that HMB may help reduce muscle damage and promote muscle recovery. Indeed, two studies support the hypothesis that HMB supplementation helps prevent exercise-induced muscle damage and improves recovery following exercise [56,57]. Supplementation with 3 g of HMB-Ca resulted in a decreased creatine phosphokinase (CK) and LDH response after a prolonged run [57], and HMB-Ca protected against the exercise-induced rise in CK in men [56] in response to progressive resistance-exercise training. Panton et al. [58] reported that men and women who supplemented for four weeks with 3 g HMB-Ca in conjunction with progressive resistance training saw a significantly decreased CK response following the intervention. Furthermore, compared to a placebo group, 14 days of HMB-Ca supplementation (3 g/d) prior to an eccentric bicep curl exercise reduced the subsequent CK elevation, which corresponded with better maintenance of 1-repetition maximum (1-RM) curl strength and reduced soreness compared to placebo during a 72-hours of recovery [59]. Additionally, a muscle-damaging bout of isokinetic, eccentric knee extensor and flexor exercise was performed by 16 untrained participants who were given 3 g of HMB-Ca 60 minutes before or immediately after exercise. In contrast to the post-exercise feeding group, those who supplemented with HMB pre-exercise showed lower elevations in LDH in recovery [60]. Recently, Tsuchiya et al. [61] supplemented untrained males with 3 g/d of HMB-Ca for 2 or 4 weeks before an eccentric upper-body muscle damaging protocol. The results indicated that both 2 and 4 weeks of HMB supplementation improved the recovery of MVC torque and range of motion compared to a placebo while reducing muscle stiffness and swelling. Moreover, while most investigations to date utilized a 3 g/d dose of HMB, a subsequent study from these researchers investigated the efficacy of a 1.5 g/d HMB dose taken for two weeks before eccentric damage to the elbow flexors. Interestingly, the low dose of HMB was also efficacious for improving functional recovery, including improvements in maximal voluntary contraction and range of motion of the elbow flexors in these untrained males [62].”

THE BIOLOGICAL MECHANISM

HMB Is a Metabolite of Leucine — But Its Signaling Is Not Identical to Leucine

One particularly interesting aspect of the paper is the relationship between leucine and HMB.

HMB is a metabolite derived from leucine, but the authors do not describe HMB merely as another way of delivering leucine.

The position stand discusses evidence suggesting that both compounds can stimulate signaling associated with mTORC1, an important regulator of muscle protein synthesis.

However, their pathways may not be identical.

The authors describe leucine signaling as involving the Sestrin2-GATOR2 complex and Rag proteins.

By contrast, the paper states that HMB's activation of mTORC1 appears to occur independently of that leucine-sensing pathway.

This distinction is scientifically important because it suggests that HMB's biological effects cannot simply be reduced to the statement:

“HMB is leucine.”

It is derived from leucine, but research is investigating HMB as a metabolite with its own signaling characteristics.

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MUSCLE PROTEIN SYNTHESIS

3 g of HMB Produced a Robust Response in the Human Studies Reviewed

The position stand reports clinical evidence in which:

3 g HMB

produced what the authors describe as a:

“robust (near-maximal) stimulation of muscle protein synthesis”

in human muscle.

The pathway described involved:

mTORC1 activation

and downstream phosphorylation of:

p70S6K1

The authors also state that similar stimulation was observed with both major forms evaluated:

HMB-Ca — calcium HMB

and:

HMB-FA — free acid HMB

This suggests that, within the studies cited by the position stand, stimulation of muscle protein synthesis was not restricted to only one of these HMB forms.

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MUSCLE PROTEIN BREAKDOWN

HMB Is Also Investigated for Its Anti-Catabolic Mechanisms

The paper places substantial emphasis on the other side of muscle protein balance: protein breakdown.

Preclinical evidence discussed by the authors points toward several pathways.

Ubiquitin–proteasome pathway

The paper reports suppression of pathways involved in the breakdown of cellular proteins.

Myonuclear apoptosis

The authors discuss inhibition of myonuclear apoptosis through mitochondrial-associated caspase signaling.

Lysosomal autophagy

The position stand also identifies suppression of lysosomal autophagy pathways as another potential mechanism.

Most importantly, the authors then connect these mechanistic findings with human evidence.

They report that clinical studies using:

3 g HMB

significantly decreased muscle protein breakdown.

Again, this effect was described as occurring independently of whether HMB was provided in calcium or free-acid form.

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EXERCISE-INDUCED MUSCLE DAMAGE

Several Studies Reported Lower CK or LDH Responses After Exercise

One of the primary recovery outcomes discussed in the position stand is the response of blood markers commonly associated with exercise-induced muscle damage.

Two markers appear repeatedly:

Creatine kinase / creatine phosphokinase — CK

and:

Lactate dehydrogenase — LDH

The position stand reports several studies in which HMB supplementation was associated with smaller increases in these markers following demanding exercise.

For example:

3 g HMB-Ca + prolonged running

The authors report a decreased CK and LDH response following prolonged running.

Progressive resistance exercise

HMB-Ca was reported to protect against the exercise-induced increase in CK in men completing progressive resistance training.

Four weeks of resistance training

Men and women receiving:

3 g HMB-Ca

for four weeks alongside progressive resistance training showed a significantly lower CK response following the intervention.

These findings form part of the basis for the authors' statement that HMB may help reduce muscle damage and promote muscle recovery.

The wording “may help” matters: the position stand does not describe every study or every population as producing identical results.

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FUNCTIONAL RECOVERY

The Evidence Extends Beyond Blood Markers

Reduced CK or LDH would be less meaningful to an athlete if those differences were never accompanied by changes in actual function.

The paper therefore also discusses functional recovery outcomes.

In one study described by the authors, participants received:

3 g HMB-Ca per day for 14 days

before an eccentric biceps exercise protocol.

Compared with placebo, supplementation was associated with:

• lower subsequent CK elevation;
• better maintenance of 1-repetition maximum curl strength;
• reduced muscle soreness;
• differences observed during the 72-hour recovery period.

This is particularly relevant because it links a biochemical marker with outcomes the athlete can actually perceive or measure: strength maintenance and soreness.

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TIMING

Pre-Exercise Intake Produced a Different LDH Response in One Study

The review also describes an experiment involving:

16 untrained participants

who completed damaging eccentric exercise involving the knee extensors and flexors.

Participants received:

3 g HMB-Ca

either:

60 minutes before exercise

or:

immediately after exercise.

According to the authors, participants receiving HMB before exercise experienced lower elevations in LDH during recovery than the post-exercise group.

This is an interesting finding, although it comes from a specific study and population and should not be interpreted as establishing one universally optimal HMB timing strategy.

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TWO TO FOUR WEEKS OF SUPPLEMENTATION

Recovery of Strength, Mobility, Stiffness and Swelling Were Examined Together

The paper discusses work by Tsuchiya and colleagues in untrained men who consumed:

3 g HMB-Ca per day

for either:

2 weeks

or:

4 weeks

before an eccentric upper-body muscle-damaging protocol.

Compared with placebo, the position stand reports improvements in:

maximal voluntary contraction torque

and:

range of motion

alongside reductions in:

muscle stiffness

and:

muscle swelling.

This is important because recovery is multidimensional.

The studies were not evaluating only whether a participant “felt better.”

They examined strength-related, mobility-related and physical muscle-damage outcomes.

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LOWER-DOSE RESEARCH

Not Every Positive Study Used 3 g Per Day

The authors explicitly note:

“most investigations to date utilized a 3 g/d dose of HMB”

However, the paper also describes later research using:

1.5 g HMB/day

for:

two weeks

before eccentric damage to the elbow flexors.

In these untrained male participants, the authors report that the lower dose was also effective for aspects of functional recovery, including:

maximal voluntary contraction

and:

range of motion.

This finding is relevant because it demonstrates that the scientific literature is not limited exclusively to 3 g/day.

At the same time, 1.5 g/day is still higher than the 1 g contained in one serving of OVRL Whey Isolate, and the evidence from a 1.5 g protocol should not automatically be extrapolated downward to 1 g.

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WHY THIS MATTERS

Recovery Is a Balance Between Anabolic and Catabolic Processes

Sports nutrition conversations often reduce recovery to one question:

“How much protein did you consume?”

The HMB literature adds another dimension.

Muscle tissue is continuously undergoing both:

protein synthesis

and:

protein breakdown.

The net result depends on the balance between the two.

The ISSN position stand describes HMB as being investigated precisely because it may affect both sides of this balance.

On one side, the research discusses:

mTORC1 signaling and muscle protein synthesis.

On the other, it describes:

protein breakdown pathways and exercise-induced muscle damage.

The recovery research then extends the discussion into practical outcomes including:

• preservation of strength;
• soreness;
• range of motion;
• stiffness;
• swelling;
• CK;
• LDH.

For OVRL, this makes HMB scientifically relevant to a formulation designed around recovery rather than protein quantity alone.

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HOW OVRL APPLIES THIS STANDARD

1 g of HMB Per Serving — Clearly Distinguished From the 3 g Protocol Used in Most Research

OVRL Whey Isolate provides:

1 g HMB per serving

The ISSN position stand makes the dosage context particularly important.

Most of the research highlighted in the paper used:

3 g HMB/day

including studies evaluating:

• muscle protein synthesis;
• muscle protein breakdown;
• CK and LDH responses;
• muscle soreness;
• strength maintenance;
• functional recovery.

The paper also describes positive findings with:

1.5 g/day

in a specific study of untrained men undergoing eccentric muscle damage.

However:

1 g per serving remains below both of these research doses.

OVRL therefore should not claim that one serving reproduces the effects observed with 3 g/day, nor should results from 1.5 g/day automatically be assumed to apply to a 1 g intake.

The appropriate connection with the research is more precise:

the OVRL formula contains an ingredient with a scientifically investigated role in muscle protein turnover and recovery, but the amount delivered in one serving is lower than the dose used in most of the clinical protocols highlighted by the ISSN.

This distinction protects the scientific integrity of the formulation.

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WHAT THE FORMULA DOES — AND DOES NOT — ALLOW US TO SAY

What we can say

OVRL Whey Isolate contains:

1 g HMB per serving.

HMB is a metabolite of leucine investigated for its effects on:

• muscle protein synthesis;
• muscle protein breakdown;
• exercise-induced muscle damage;
• functional recovery.

The 2024 ISSN position stand reviews multiple human studies reporting recovery-related outcomes with HMB supplementation.

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What we should not say

A single serving of OVRL Whey Isolate should not be described as having been demonstrated to:

• maximize muscle protein synthesis through HMB;
• reproduce the near-maximal MPS response reported with 3 g HMB;
• significantly decrease muscle protein breakdown based on the 3 g studies;
• reproduce the CK, LDH, soreness or strength outcomes of the 3 g/day protocols;
• reproduce the results observed with 1.5 g/day.

Those conclusions would go beyond the dosage actually supplied by one serving.

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THE OVRL INTERPRETATION

An Advanced Formula Should Be Transparent About Both Ingredient Selection and Dose

Including a research-supported ingredient is only the beginning.

The amount matters.

The studied population matters.

The protocol matters.

The outcome measured matters.

For this reason, OVRL does not believe it is scientifically responsible to take a result obtained with 3 g/day and present it as if it were automatically reproduced by 1 g.

Instead, the presence of HMB in the formula should be understood as one component within a broader recovery formulation.

This distinction reinforces a fundamental principle of the OVRL Quality Standard:

ingredients create a scientific rationale; dosage determines how closely the finished formula corresponds to the research protocol.

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RESEARCH AT A GLANCE

Lead author: John A. Rathmacher

Affiliations: MTI Biotech Inc., Ames, Iowa, USA; Iowa State University, Department of Animal Science, Ames, Iowa, USA

Scientific body: International Society of Sports Nutrition

Publication: Journal of the International Society of Sports Nutrition

Year: 2024

Article type: ISSN Position Stand

Ingredient: β-hydroxy-β-methylbutyrate — HMB

Biological origin: Metabolite of leucine

Primary mechanisms discussed:
Muscle protein synthesis and muscle protein breakdown

Key signaling pathway:
mTORC1 and downstream p70S6K1 signaling

Other pathways discussed:
Ubiquitin-proteasome pathway, myonuclear apoptosis and lysosomal autophagy

Most commonly discussed clinical dose:
3 g HMB/day

Lower dose highlighted in recovery research:
1.5 g/day

Forms discussed:
HMB-Ca and HMB-FA

Recovery outcomes reviewed:
CK, LDH, soreness, maximal voluntary contraction, 1-RM strength, range of motion, stiffness and swelling

Primary populations in several recovery studies cited:
Untrained individuals and participants undergoing damaging or progressive exercise protocols

Important qualification:
Results vary according to dose, study design, training status and outcome measured.

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READ THE ORIGINAL RESEARCH

International Society of Sports Nutrition Position Stand: β-Hydroxy-β-Methylbutyrate (HMB)

Rathmacher, J. A., Pitchford, L. M., Stout, J. R., Townsend, J. R., Jäger, R., Kreider, R. B., Campbell, B. I., Kerksick, C. M., Harty, P. S., Candow, D. G., Roberts, B. M., Arent, S. M., Kalman, D. S., & Antonio, J.

Journal of the International Society of Sports Nutrition

2024

DOI: 10.1080/15502783.2024.2434734

Licence: CC BY 4.0 — Open Access