RCTJadad 5/5RandomizedDouble-BlindPlacebo-Controlled

Creatine + HMB for Active Older Adults: What This 21-Week Crossover Trial Found About Mobility and Metabolism

Aging Clinical and Experimental ResearchJanuary 9, 2026Vol. 38 (1)

Summary

If you're over 60 and already exercising regularly, you might assume you've "done enough" to stay mobile and independent. A new randomized, double-blind, placebo-controlled crossover trial (published January 2026 in Aging Clinical and Experimental Research) suggests that pairing two inexpensive, widely available supplements — creatine monohydrate and β-hydroxy-β-methylbutyrate (HMB) — with structured exercise can push functional performance even further.

Researchers in Tenerife, Spain, recruited 30 physically active adults aged 60–82 (20 men, 10 women) who were already meeting activity guidelines (≥150 min/week of moderate exercise). Using a crossover design — where every participant cycled through both conditions — each person did two 6-week blocks of a supervised, 4-day-a-week multicomponent exercise program (strength, power, circuits, HIIT, and steady-state cardio). During one block they took 3 g/day creatine monohydrate plus 3 g/day HMB (dissolved in yogurt or juice before bed); during the other, an identical-looking inulin placebo. A 3-week washout separated the two phases, and neither participants nor assessors knew which supplement was which.

The headline results: compared with placebo, the creatine+HMB phase produced significantly larger improvements in four core "mobility vital signs" — 4-meter gait speed, the 5-times sit-to-stand test, Timed Up and Go, and the 400-meter walk (all p<0.05, with large effect sizes, partial η² up to 0.42). These are the same measures geriatricians use to flag frailty risk and predict falls, hospitalization, and loss of independence — so the size of the effect here is clinically, not just statistically, notable. The placebo-plus-exercise phase, by contrast, showed no significant within-phase improvement on these tests, suggesting the supplement combo added something beyond the training program alone.

Beyond mobility, basal metabolic rate (BMR) and a "metabolic rate index" rose more with creatine+HMB, and visceral fat trended lower (though not statistically significant). Effects diverged somewhat by sex: women saw a modest (<5 mmHg) reduction in diastolic blood pressure and greater gains in expiratory muscle strength, while men showed a small, transient rise in a vascular marker called EPCR — interpreted by the authors as adaptive rather than harmful, since it wasn't paired with blood pressure or inflammation increases. Notably, a composite score (SPPB) didn't budge, likely because these already-active participants scored near the test's maximum at baseline — a ceiling effect rather than a true lack of benefit. This builds on the same team's earlier 2025 trial in the same population, which found creatine+HMB improved strength endurance independent of muscle mass — together painting a consistent picture that this combo may sharpen "muscle quality" and functional efficiency even without visible size gains.

What This Means For You

For supplement shoppers, the protocol here is simple and matches mainstream sports-nutrition guidance: 3 g/day creatine monohydrate (no loading phase needed) plus 3 g/day HMB (as calcium HMB), taken together once daily — the study used bedtime dosing dissolved in yogurt or juice, which may help gastrointestinal tolerance. Creatine monohydrate is the cheapest, most-studied form; look for third-party-tested products (e.g., Informed Sport/NSF Certified for Sport) since supplements aren't FDA-verified for purity. HMB is sold as HMB-Ca or the more bioavailable HMB-FA; the 3 g/day dose used here matches the amount most consistently linked to reduced muscle protein breakdown in prior research.

The key caveat: supplements alone weren't tested. Every participant, in both phases, did 4 supervised 60-minute sessions/week combining strength, power, balance, and cardio work. The exercise is almost certainly doing the heavy lifting — the supplements appear to amplify it, not replace it. So the practical takeaway isn't "take creatine and skip the gym," it's "if you're already training consistently, this stack may extract more functional gain from that same effort."

Who benefits most? Physically active, independent older adults looking to preserve gait speed, chair-rising ability, and walking endurance — all strong predictors of fall risk and independence. The ISSN reaffirmed in 2025 that creatine is safe across the lifespan at doses well above 3 g/day, and no renal symptoms or serious adverse events emerged here (though formal kidney function testing wasn't done). People with kidney disease, uncontrolled chronic conditions, or those on blood thinners (given the EPCR/coagulation signal in men) should check with a doctor before starting. Cost is modest — both ingredients are inexpensive, widely available commodities — making this a low-risk, low-cost adjunct to consider alongside, not instead of, consistent multicomponent training.

Important Considerations

This was a small trial (30 completers, only 10 women) over just six weeks per phase — far shorter than the years-long timelines over which real-world sarcopenia and mobility decline unfold. We don't know whether benefits persist after stopping supplementation, or whether starting sooner versus later in aging matters. Participants were already physically active and had high baseline functional scores (hence the ceiling effect on the SPPB test) — results may not generalize to frail, sedentary, or institutionalized older adults, which the authors explicitly flag as a direction for future research (a related "MULTI-FRAIL" trial is reportedly already underway in that population).

Body composition and BMR were measured with bioelectrical impedance (a home-scale-type technology), not gold-standard DEXA scans or indirect calorimetry, so absolute numbers should be taken as estimates, not precise values. The dose (3 g/day each) wasn't adjusted for body weight, which may explain some of the sex differences seen. Critically, this trial tested creatine and HMB together — there's no arm testing either supplement alone, so it can't tell you whether one ingredient is doing most of the work or whether they're truly synergistic. Adherence was tracked by sachet counts and logs, not blood tests, so actual compliance is somewhat assumed rather than verified.

Red flag for marketing: don't expect visible muscle bulk from this stack — the companion trial from this group found strength gains occurred independent of muscle mass changes, so "get bigger muscles" claims aren't supported here. As with any supplement study, consult a physician before starting, especially if you have kidney, liver, or cardiovascular conditions, or take medications affecting blood clotting.

Terms Explained

Creatine monohydrateA naturally occurring compound stored in muscle that helps rapidly regenerate ATP (cellular energy) during short, intense efforts like sit-to-stands or fast walking.
HMB (β-hydroxy-β-methylbutyrate)A metabolite of the amino acid leucine that may reduce muscle protein breakdown and support recovery, often marketed as HMB-Ca or HMB-FA.
Crossover trialA study design where every participant experiences both the treatment and placebo (in random order, separated by a washout period), letting each person serve as their own control.
Washout periodA supplement-free interval between treatment phases in a crossover trial, meant to let the first treatment's effects fade before starting the next.
Timed Up and Go (TUG)A test of mobility and fall risk measuring how long it takes to stand from a chair, walk 3 meters, turn, and sit back down.
Short Physical Performance Battery (SPPB)A 0–12 composite score of balance, gait speed, and chair-stand ability used to assess physical function in older adults; scores can 'ceiling out' in very fit people.
Basal metabolic rate (BMR)The number of calories your body burns at rest just to maintain basic functions; it tends to decline with age as muscle mass drops.
Ceiling effectWhen a test can't detect further improvement because participants are already scoring near the maximum possible value at baseline.
Partial eta squared (η²p)A statistic describing how much of the variation in an outcome is explained by the treatment; values above 0.14 are considered a 'large' effect.
Endothelial Protein C Receptor (EPCR)A marker on blood vessel lining cells involved in inflammation and blood clotting regulation; used here as an exploratory vascular health indicator.
Technical Study Details

Study Design

Duration21 weeks
RegistrationClinicalTrials.gov: NCT05951439

Total Score

JADAD Quality Assessment
5
/ 5

評価詳細

Randomization

2 / 2
Is the study described as randomized?
Yes+1
Rationale: The article explicitly and repeatedly describes the study as "randomized" (e.g., "randomized, double-blind, placebo-controlled crossover trial") and details the random allocation process ("randomly allocated (1:1) to one of two treatment sequences...using a computer-generated sequence").
Is the method of randomization described and appropriate?
Yes+1
Rationale: The article explicitly describes the randomization method as stratification by sex followed by 1:1 random allocation to treatment sequences using a computer-generated sequence, executed by an independent researcher. Computer-generated randomization is an appropriate and standard method for RCTs, and the description includes who generated it (an independent researcher, reducing selection bias), satisfying the Jadad criterion for an appropriate randomization method.

Blinding

2 / 2
Is the study described as double-blind?
Yes+1
Rationale: The article explicitly and repeatedly describes the trial as "double-blind" in the abstract, methods (Study design and participants), introduction, and conclusion sections.
Is the method of blinding described and appropriate?
Yes+1
Rationale: The article explicitly describes the double-blind method: identical, opaque sachets containing the same amount of powder for both CRE+HMB and placebo (inulin), with the placebo specifically chosen for near-identical visual and textural properties to maintain blinding. All participants, researchers, and outcome assessors were blinded. This constitutes an appropriate, well-described blinding method (identical appearance/packaging of active and placebo), satisfying the "yes" criteria.</rationale> </invoke>

Dropouts/Withdrawals

1 / 1
Is there a description of dropouts and withdrawals?
Yes+1
Rationale: The Methods section (Participants subsection) explicitly states the number of volunteers screened, the number excluded, the number who withdrew, and the reason for withdrawal (personal reasons unrelated to the intervention), as well as clarifying no withdrawals were due to adverse effects. This provides both the number and reasons for dropouts, satisfying the Jadad Q5 criterion, even though all 30 participants who began the crossover completed both phases (i.e., there was no differential per-arm attrition to report beyond this pre-randomization/overall accounting).</rationale> </invoke>

Study Population

Sample Size30
Age Range60-82 years
ConditionAge-related decline in functional capacity in physically active older adults
Inclusion Criteria
  • Age ≥ 60 years
  • Physical independence
  • Engagement in ≥ 150 min/week of moderate-intensity physical activity

Interventions

Creatine monohydrate (CRE)

Treatment
Dose3 g/day
Frequencyonce daily (dissolved in yogurt or fruit juice, ~30 min before bedtime)
Duration6 weeks per phase
Routeoral

β-Hydroxy-β-methylbutyrate (HMB, as calcium HMB/HMB-Ca)

Treatment
Dose3 g/day
Frequencyonce daily (dissolved in yogurt or fruit juice, ~30 min before bedtime)
Duration6 weeks per phase
Routeoral

Placebo (Inulin)

Control
Dose6 g/day
Frequencyonce daily
Duration6 weeks per phase
Routeoral

Integral Physical Conditioning (IPC) multicomponent exercise program

Treatment
Frequency4 supervised sessions/week, 60 minutes each
DurationTwo 6-week training blocks (separated by 3-week washout)

Outcomes

OutcomeTypeEffectp-value
4-m Gait SpeedPrimary-p < 0.001 (interaction); p < 0.05 (POST between-group)Significant
5-Repetition Sit-to-Stand (5R-STS)Primary-p < 0.001 (interaction); p < 0.05 (POST between-group)Significant
Timed Up and Go (TUG)Primary-p < 0.001 (interaction); p < 0.05 (POST between-group)Significant
400-Meter Walk TestPrimary-p < 0.001 (interaction); p < 0.05 (POST between-group)Significant
Short Physical Performance Battery (SPPB) total scoreSecondary--
Static Balance (SPPB subtest)Secondary--
Basal Metabolic Rate (BMR)Secondary-p < 0.001Significant
Visceral Fat IndexSecondary--
Metabolic Rate IndexSecondary-p = 0.026Significant
Metabolic AgeSecondary--
Systolic Blood Pressure (SBP)Secondary--
Diastolic Blood Pressure (DBP)Secondary-p = 0.020 (interaction, women); p = 0.015 (DBP reduction, women)Significant
Resting Heart RateSecondary--
Peripheral Oxygen Saturation (SpO2)Secondary--
Maximal Expiratory Pressure (MEP)Secondary--Significant
Endothelial Protein C Receptor (EPCR)Secondary-p = 0.021 (men); p = 0.920 (total sample, not significant)Significant

Safety

Serious AEs0
Dropout Rate10.0%
No serious adverse events occurred during either supplementation phase or the exercise program. The only adverse effect reported was mild, transient muscle soreness during initial training sessions, which resolved spontaneously without intervention. No withdrawals were due to adverse effects from supplementation or exercise. Overall adherence exceeded 90% for supplementation and exercise components (sachet return >95%). No participants reported renal-related symptoms (e.g., edema, changes in urinary patterns) despite creatine supplementation; formal renal function testing was not performed.

Conclusion

Six weeks of combined creatine monohydrate and HMB supplementation, integrated with a supervised multicomponent exercise program (IPC), produced meaningful improvements in functional performance (4-m gait speed, 5R-STS, TUG, 400-m walk), metabolic efficiency (BMR, metabolic rate index), and selected physiological outcomes (MEP, and sex-specific DBP and EPCR changes) in physically active older adults, with large effect sizes and no significant period, sequence, or carryover effects. CRE + HMB supplementation combined with exercise appears to be a safe, feasible, and practical strategy to sustain mobility, metabolic health, and functional independence with aging, though findings should be confirmed in longer trials and in frail or sedentary populations.

Limitations

  • Short intervention period (six weeks) limits assessment of persistence of benefits or long-term adaptations after cessation.
  • Body composition and BMR were estimated using multifrequency bioelectrical impedance analysis rather than gold-standard methods (DXA or indirect calorimetry), reducing precision of absolute values.
  • Fixed dosing strategy (3 g/day CRE and 3 g/day HMB) was not normalized to body mass, potentially contributing to interindividual and sex-specific variability.
  • No biochemical verification of supplement adherence was performed (relied on sachet counts, logs, and supervision).
  • No single-supplement comparison arms (CRE-only or HMB-only) were included, precluding evaluation of additive versus synergistic effects.
  • No statistical adjustment for sex-related differences in fat-free mass was applied, to avoid model overfitting given the modest sample size.
  • Sex-specific analyses were exploratory; the study was not powered a priori to formally test sex-by-intervention interactions.
  • Confidence intervals were not systematically reported for all effect size estimates, limiting precision of interpretation.
  • High baseline functional status of participants likely produced a ceiling effect limiting the sensitivity of the SPPB to detect further improvement.
  • Training-induced baseline improvement across phases may have attenuated some between-condition contrasts.
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Creatine + HMB for Active Older Adults: What This 21-Week Crossover Trial Found About Mobility and Metabolism | Re:Vital Nexus