# High-Intensity Interval Training is Safe, Feasible and Efficacious in Nonalcoholic Steatohepatitis: A Randomized Controlled Trial

PMID: 36538276
Journal: Digestive diseases and sciences
Published: 2023 May
Authors: Keating SE, Croci I, Wallen MP, Cox ER, Thuzar M, Pham U, Mielke GI, Coombes JS, Macdonald GA, Hickman IJ

## Question

Is 12 weeks of supervised HIIT safe, feasible, and efficacious for improving aerobic fitness and peripheral insulin sensitivity in adults with biopsy-proven NASH compared with a sham-exercise control?

## Summary

In adults with biopsy-confirmed nonalcoholic steatohepatitis, 12 weeks of supervised 4 x 4 min HIIT produced no HIIT-related adverse events and met the authors' feasibility criteria among completers. Compared with a supervised stretching control, HIIT improved exercise capacity and peripheral insulin sensitivity, with favorable effect-size signals for BMI, waist circumference, abdominal fat, intrahepatic lipid, total cholesterol, and symptom-related quality of life. The study was very small and affected by COVID-era recruitment limits.

## Population

- Adults with biopsy-proven nonalcoholic steatohepatitis.
- Sample size: 14
- Age: 56 +/- 10 years.
- Sex: 9 male (64%).
- Fitness level: Not meeting physical activity guidelines; low cardiorespiratory fitness.
- Health status: NASH with obesity, metabolic syndrome, frequent type 2 diabetes and hypertension.

## Methodology

- Prospectively registered randomized controlled trial comparing supervised HIIT with supervised stretching control.
- 12 weeks; control participants were offered HIIT after their control period.
- Community participants recruited from a specialist hepatology outpatient unit; assessments at University of Queensland and affiliated clinical facilities; supervised exercise by qualified exercise professional.
- Randomized and controlled study design.

## Protocol

- Supervised NASH HIIT.
- Modality: Treadmill running/walking preferred, with cycle/row/arm ergometer alternatives.
- Work intervals: 4 min at 85-95% HRmax.
- Recovery: 3 min at about 60% HRmax.
- Sets or repetitions: 4 intervals after progression.
- Intensity: 85-95% HRmax and RPE around 15-19/20 during intervals.
- Session duration: About 38 min.
- Frequency: 3 sessions/week.
- Program length: 12 weeks.
- Progression: At least 1, 2, 3, then 4 intervals in weeks 1-4; full protocol weeks 5-12.
- Stretching control.
- Modality: Supervised stretching.
- Intensity: Negligible estimated energy expenditure.
- Session duration: 30 min.
- Frequency: 3 sessions/week.
- Program length: 12 weeks.

## Outcomes

### Safety and feasibility
Status: improved
No HIIT-related adverse events occurred and HIIT met feasibility criteria among completers.

Program completion 75%; session adherence among completers 95.4 +/- 7.3%; intensity adherence 95.3 +/- 6.0%; duration adherence 96.8 +/- 2.4%.

### Exercise capacity
Status: improved
HIIT improved exercise capacity versus stretching control.

Adjusted mean difference 134.2 s (95% CI 19.8 to 248.6), eta2=0.44, p=0.03.

### Peripheral insulin sensitivity
Status: improved
Clamp-measured peripheral insulin sensitivity improved in HIIT and worsened in control.

Adjusted mean difference 3.4 mg/kgLegFFM/min (95% CI 0.9 to 6.8), eta2=0.32, p=0.046.

### VO2peak
Status: no clear change
VO2peak did not improve versus control.

Adjusted mean difference -0.4 mL/kg/min, p=0.71.

### Cardiometabolic and liver secondary outcomes
Status: mixed
Effect sizes favored HIIT for BMI, waist circumference, abdominal adipose tissue, intrahepatic lipid, total cholesterol, and metabolic syndrome severity, but many were not statistically significant in this small trial.

Total cholesterol adjusted mean difference -0.8 mmol/L (95% CI -1.3 to -0.3), p=0.004; intrahepatic lipid p=0.08.

## Practical Insights

- For medically screened people with NASH, vigorous intervals can be feasible when supervised and progressed gradually.
- Exercise capacity and insulin sensitivity may improve even if VO2peak does not.
- Modality flexibility is important for users with obesity and musculoskeletal limitations.

## Limitations

- Very small sample.
- COVID-19 restrictions affected recruitment.
- Some outcomes could not be collected in all participants.
- HIIT group had higher medication burden at baseline.
- Real-world maintenance after supervised training was not tested.

## Safety And Adherence

- No HIIT-related adverse events or serious adverse events.
- Blood pressure was monitored during intervals and recovery to remain within safe limits.
- Multiple modalities were available for musculoskeletal limitations.

## Original Sources

- [PubMed](https://pubmed.ncbi.nlm.nih.gov/36538276/) (pubmed)
- [DOI](https://doi.org/10.1007/s10620-022-07779-z) (doi)
- [PMC full text](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763796/) (full text)

## Agent Guidance

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