# Association of skeletal muscle and serum metabolites with maximum power output gains in response to continuous endurance or high-intensity interval training programs: The TIMES study - A randomized controlled trial

PMID: 30742692
Journal: PLoS ONE
Published: 2019 Feb 11
Authors: Castro A, Duft RG, Ferreira MLV, Andrade ALL, Gáspari AF, Silva LM, Oliveira-Nunes SG, Cavaglieri CR, Ghosh S, Bouchard C, Chacon-Mikahil MPT

## Question

Which baseline serum and skeletal muscle metabolites are associated with gains in maximum power output after continuous endurance training or HIIT?

## Summary

The TIMES study randomized sedentary young men to 8 weeks of supervised cycling HIIT, continuous endurance training, or control. HIIT and endurance training produced similar improvements in maximal power output, while control declined slightly. The main focus was metabolomics: baseline serum and muscle metabolites were associated with who improved more, but these associations are exploratory and not ready for workout prescription.

## Population

- Seventy healthy sedentary young Caucasian men included in the metabolomics/completer analysis.
- Sample size: 70
- Age: Eligible age 18-31 years.
- Sex: Men only.
- Fitness level: Sedentary; no regular exercise by study definition.
- Health status: Healthy after medical screening; smokers and major cardiometabolic or musculoskeletal conditions excluded.

## Methodology

- Randomized controlled trial with supervised cycling endurance training, HIIT, and control groups, plus baseline metabolomic association analyses.
- 8-week training intervention.
- Exercise laboratory setting in Campinas, Brazil.
- Randomized and controlled study design.

## Protocol

- TIMES cycling HIIT.
- Modality: Cycle ergometer.
- Work intervals: 5 x 4 min at 90% HRR.
- Recovery: 3 min active recovery at 50% HRR in weeks 1-4 and 60% HRR in weeks 5-8.
- Sets or repetitions: 5 intervals.
- Intensity: 90% HRR work intervals, cadence 70-80 rpm.
- Session duration: 40 min.
- Frequency: 3 days/week for weeks 1-4, then 4 days/week for weeks 5-8.
- Program length: 8 weeks.
- Progression: Frequency and recovery intensity increased after week 4.
- Continuous endurance training and control.
- Modality: Cycle ergometer continuous training; no-training control.
- Work intervals: Continuous 40 min cycling.
- Sets or repetitions: Single continuous bout.
- Intensity: 70% HRR weeks 1-4, 75% HRR weeks 5-8.
- Session duration: 40 min.
- Frequency: 3 days/week then 4 days/week.
- Program length: 8 weeks.
- Progression: Frequency and intensity increased after week 4.

## Outcomes

### Maximum power output
Status: improved
HIIT and endurance training similarly improved maximum power output compared with control.

ET +49.0 +/- 15.3 W (+21.4 +/- 8.0%); HIIT +56.6 +/- 17.2 W (+24.3 +/- 8.5%); control -10.0 +/- 9.3 W; p<0.01 vs pre and control.

### Metabolite associations
Status: mixed
Different baseline serum and muscle metabolites were associated with response to ET and HIIT, with shared pathway themes involving amino acid and carbohydrate metabolism.

HIIT-associated examples included serum lysine, phenylalanine, creatine, and muscle glycolate; ET-associated examples included serum glycerol and several muscle amino acid-related metabolites.

### Heart-rate maximum
Status: no clear change
HRmax did not change after training.

### Adherence
Status: improved
Completers attended more than 90% of prescribed sessions.

>90% session attendance among completers.

## Practical Insights

- A supervised 5 x 4 min cycling HIIT protocol can improve maximal power output in sedentary young men.
- Continuous cycling produced similar performance gains, so this paper should not be used for HIIT superiority claims.
- Metabolomics findings are useful background for response variability, not current app personalization.

## Limitations

- Young Caucasian men only.
- Short 8-week duration.
- Metabolite associations were exploratory.
- Targeted metabolomics limited coverage.
- No clinical or long-term adherence outcomes.

## Safety And Adherence

- Participants were medically screened with ECG.
- No adverse event signal was reported in the extracted NXML.
- High-intensity protocol was supervised.

## Original Sources

- [PubMed](https://pubmed.ncbi.nlm.nih.gov/30742692/) (pubmed)
- [DOI](https://doi.org/10.1371/journal.pone.0212115) (doi)
- [PMC full text](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370248/) (full text)

## Agent Guidance

Preserve the paper-level scope of this note. Do not generalize beyond the population, protocol, measured outcomes, and limitations above.