# A lipidomic and metabolomic signature of a very low-carbohydrate high-fat diet and high-intensity interval training: an additional analysis of a randomized controlled clinical trial

PMID: 38141101
Journal: Metabolomics
Published: 2023 Dec 23
Authors: Cipryan L, Kosek V, García CJ, Dostal T, Bechynska K, Hajslova J, Hofmann P

## Question

How do a 12-week very low-carbohydrate high-fat diet, HIIT, and their combination affect fasting plasma lipidomic and metabolomic profiles in adults with overweight or obesity?

## Summary

In an ancillary analysis of a 12-week randomized trial in adults with overweight or obesity, a very low-carbohydrate high-fat diet produced large plasma lipidomic and metabolomic shifts, while HIIT alone had little detectable effect on these molecular profiles. The same parent trial reported that HIIT alone improved cardiorespiratory fitness but did not drive the body composition or lipidomic changes seen with diet.

## Population

- Ninety-one low-active adults with overweight or obesity randomized to HIIT, VLCHF diet, combined VLCHF+HIIT, or control.
- Sample size: 91
- Age: Eligible 20-59 years.
- Fitness level: Low physical activity; no regular exercise training.
- Health status: Overweight/obesity, BMI 25.00-40.00 kg/m2, screened for major disease and medication confounding.

## Methodology

- Pre-planned ancillary analysis of a four-arm randomized controlled diet and exercise trial.
- 12 weeks, with fasting samples at baseline and after 4, 8, and 12 weeks.
- Ostrava, Czech Republic; laboratory visits plus home-based HIIT sessions.
- Randomized and controlled study design.

## Protocol

- Walking HIIT.
- Modality: High- and low-intensity walking intervals.
- Work intervals: 3 min high-intensity walking at RPE 18-19.
- Recovery: 3 min low-intensity walking at RPE 9-11.
- Sets or repetitions: 4 intervals in weeks 1-4, 6 in weeks 5-8, 8 in weeks 9-12.
- Intensity: RPE 18-19 work; RPE 9-11 recovery.
- Session duration: 31-55 min including warm-up and cool-down.
- Frequency: 3 sessions/week.
- Program length: 12 weeks.
- Progression: Added two high-intensity intervals every 4 weeks.
- VLCHF diet and control.
- Modality: Dietary intervention or habitual diet/activity control.
- Intensity: VLCHF allowed no more than 50 g carbohydrate/day; control maintained habitual diet and physical activity.
- Program length: 12 weeks.

## Outcomes

### Lipidomic profile
Status: mixed
VLCHF and VLCHF+HIIT groups showed large lipidomic shifts, while HIIT and control clustered together and no lipid compounds were specifically influenced by exercise.

146 entities significant in both VLCHF diet groups; corrected p-value cutoff 0.05.

### Metabolomic profile
Status: mixed
Diet groups showed metabolomic differences including upregulated carnitines and 4-hydroxybutyric and downregulated theobromine; HIIT alone did not substantially alter markers.

Article reports four metabolites upregulated and four downregulated in VLCHF and VLCHF+HIIT groups.

### Body composition
Status: mixed
Parent study reported VAT and body composition reductions only in VLCHF and VLCHF+HIIT, while HIIT alone did not induce those body composition changes.

VAT p<0.001 in VLCHF and VLCHF+HIIT.

### Cardiorespiratory fitness
Status: improved
Parent study reported HIIT alone improved cardiorespiratory fitness.

Detailed CRF statistics were reported in parent paper, not this ancillary article.

## Practical Insights

- Walking HIIT can be prescribed with simple RPE-based 3 min hard / 3 min easy intervals.
- Do not infer HIIT-specific lipidomic benefits from this ancillary analysis because diet dominated the molecular changes.
- Combined lifestyle trials need careful attribution when diet and exercise are both present.

## Limitations

- Ancillary molecular analysis, not a primary exercise-effectiveness paper.
- HIIT adherence and safety details were sparse.
- Age heterogeneity may affect plasmalogen levels.
- Diet, energy intake, body composition, and possible gut microbiome changes complicate mechanistic interpretation.
- Powered to detect large rather than medium effects.

## Safety And Adherence

- Participants passed PAR-Q and were screened for physical-activity contraindications.
- No detailed exercise adverse-event data were reported in this article.

## Original Sources

- [PubMed](https://pubmed.ncbi.nlm.nih.gov/38141101/) (pubmed)
- [DOI](https://doi.org/10.1007/s11306-023-02071-1) (doi)
- [PMC full text](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10748768/) (full text)

## Agent Guidance

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