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Study 18 of 22PT-141 (Bremelanotide) literatureJournal of the International Society of Sports Nutrition · RCT2026

HMB supplementation combined with high-intensity functional exercise supports aerobic capacity but not strength in trained and untrained males: a randomized controlled trial.

HMB supplementation at 90 mg/kg FFM/day improves aerobic capacity in trained individuals but not strength, with limited effects in untrained individuals.

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Where it sits

this study against the rest of the pt-141 (bremelanotide) corpus
7
Preclinical
6
Observational
0
Open-label
2
Randomised · this one
7
Reviews

Summary and findings

The study evaluated the effects of liquid HMB free acid supplementation on aerobic fitness and isometric strength in trained and untrained males. Participants received 90 mg/kg FFM/day of HMB or placebo, combined with high-intensity functional training. HMB improved aerobic capacity metrics but not strength indices.

How much of this paper we could read: full text read (0.90). We had a clear abstract, so the summary below closely tracks the paper. What this means →
VO2MAX increased with HMB in TR, p=0.024.n=902026

Abstract

The authors’ words, as Journal of the International Society of Sports Nutrition supplied them

<h4>Background</h4><i>β</i>-hydroxy-<i>β</i>-methylbutyrate (HMB) supplementation may support aerobic capacity and isometric strength. Its utility has been studied mainly for 3 g <sub>HMB</sub>·day<sup>-1</sup>. Therefore, new and personalized HMB supplementation protocols should be verified. This parallel randomized placebo(PLA)-controlled triple-blind study was designed to evaluate the effects of liquid HMB free acid supplementation during customary training/lifestyle or combined with high-intensity functional training (HIFT) on aerobic fitness, physical capacity, and isometric strength indices following an incremental cycling test (ICT) in trained (TR) and untrained (UTR) males.<h4>Methods</h4>Fifty-three TR (29.1 ± 7.7 years; body mass (BM): 84.8 ± 10.0 kg; FFM: 71.2 ± 8.9 kg) and 37 UTR participants (32.3 ± 7.6 years; BM: 90.1 ± 16.5 kg; FFM: 68.4 ± 10.3 kg) completed two 3-weeks periods, including: <i>1)</i> supplementation period (<i>SUP</i>)-ingesting 90 mg·kg<sub>FFM</sub> <sup>-1</sup>·day<sup>-1</sup> of either HMB or PLA and performing usual training (TR) or lifestyle (UTR), and <i>2)</i> HMB/PLA ingestion combined with the additional HIFT stimuli (2 units per week; <i>SUP + EX</i>). <i>TR_HMB</i>, <i>TR_PLA</i>, <i>UTR_HMB</i>, <i>UTR_PLA</i> groups were analyzed. Testing visits were performed at baseline (<i>T</i> <sub><i>BAS</i></sub> ), and after the <i>SUP</i> (<i>T</i> <sub><i>SUP</i></sub> ) and the <i>SUP + EX</i> (<i>T</i> <sub><i>SUP+EX</i></sub> ). The following evaluations were performed: BM and body composition, ICT, and maximal voluntary isometric contraction (MVIC) of the lower limb. A general linear model was conducted to examine the main effects and interaction of <i>treatment</i> (supplementation) (HMB/PLA), <i>training status</i> (TS; TR/UTR), and <i>baseline values</i> (<i>BAS</i>) over repeated measurements (<i>T</i> <sub><i>BAS</i></sub> <i>, T</i> <sub><i>SUP</i></sub> , <i>T</i> <sub><i>SUP+EX</i></sub> ). The following interactions were tested: <i>visit × treatment</i>; <i>visit × TS</i>; <i>visit × treatment × TS; and visit × treatment × TS × BAS</i>. One-way ANOVA or Kruskal-Wallis ANOVA (non-normal distribution) were conducted to examine differences in the degree of absolute changes (<i>ΔT</i> <sub><i>SUP</i></sub> <i>-T</i> <sub><i>BAS</i></sub> , <i>ΔT</i> <sub><i>SUP+EX</i></sub> <i>-T</i> <sub><i>SUP</i></sub> , <i>ΔT</i> <sub><i>SUP+EX</i></sub> <i>-T</i> <sub><i>BAS</i></sub> ) in the measured indices between studied subgroups.<h4>Results</h4>Increases (<i>T</i> <sub><i>SUP+EX</i></sub> <i>-T</i> <sub><i>BAS</i></sub> ) in VO<sub>2MAX</sub> (<i>p</i> = 0.024), time to the anaerobic threshold (AT; <i>p</i> < 0.001), VO<sub>2AT</sub> (<i>p</i> = 0.001), power output at the AT (<i>p</i> < 0.001), heart rate at the AT (<i>p</i> < 0.001), time to the respiratory compensation point (RCP; <i>p</i> < 0.001), VO<sub>2RCP</sub> (<i>p</i> < 0.001), power output at the RCP (<i>p</i> < 0.001) were higher in <i>TR_HMB vs. TR_PLA</i>. Simultaneously, in UTR, greater increases in Time<sub>RCP</sub> (<i>p</i> = 0.001) and Power<sub>RCP</sub> (<i>p</i> = 0.002) occurred with HMB supplementation compared to PLA. MVIC indices did not change due to the treatment.<h4>Conclusions</h4>Supplementation of high HMB dose combined with HIFT increases aerobic fitness and capacity, especially RCP and AT indices. HMB supplementation combined with HIFT evoked significant favorable changes in a greater number of the evaluated aerobic fitness and capacity indices in trained compared to untrained individuals. Thus, untrained individuals probably need greater exercise stimuli (>2 HIFT units per week) and a longer intervention period to obtained greater benefits. These findings suggest that incorporating liquid HMB supplementation at a dose of 90 mg·kg<sub>FFM</sub> <sup>-1</sup>·day<sup>-1</sup> alongside HIFT is an effective strategy to enhance aerobic fitness and capacity in trained individuals, while further research including longer intervention periods and greater training stimuli is needed to determine the optimal supplementation protocol for untrained individuals.

Background

The study investigates the potential of HMB supplementation to enhance aerobic capacity and isometric strength, particularly in the context of high-intensity functional training. Previous research has focused on a standard dose of 3 g/day, but personalized dosing protocols are less explored. This study aims to fill this gap by assessing the effects of a tailored HMB dose in both trained and untrained males.

Methods

This was a parallel, randomized, placebo-controlled, triple-blind study involving 53 trained and 37 untrained male participants. They received 90 mg/kg FFM/day of HMB or placebo over two 3-week periods. The first period involved usual training or lifestyle, while the second included additional high-intensity functional training. Primary outcomes were changes in aerobic fitness and isometric strength measured through incremental cycling tests and maximal voluntary isometric contraction.

Results

The primary endpoint showed significant improvements in VO2MAX, time to anaerobic threshold, and power output at the anaerobic threshold in the trained HMB group compared to placebo. The p-values for these improvements were 0.024, <0.001, and <0.001, respectively. In untrained participants, HMB led to significant increases in time and power at the respiratory compensation point. However, no significant changes were observed in maximal voluntary isometric contraction indices.

Interpretation

The study suggests that HMB supplementation can enhance aerobic capacity metrics in trained individuals when combined with high-intensity functional training. The effect sizes were statistically significant, but the clinical significance, particularly in untrained individuals, remains uncertain due to the short duration and limited exercise stimulus. The findings align with previous literature on HMB's role in aerobic performance but highlight the need for longer and more intensive interventions for untrained populations.

Key findings

  • VO2MAX increased with HMB in TR, p=0.024.
  • Time to anaerobic threshold improved with HMB, p<0.001.
  • VO2AT increased with HMB, p=0.001.
  • Power output at AT increased with HMB, p<0.001.
  • MVIC indices did not change with HMB.

Limitations

  • 3-week study duration
  • Limited to 2 HIFT units per week
  • No strength improvement observed
  • Untrained individuals may need longer interventions
  • Single-site study

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