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

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.

Methodology

Ninety-one low-active adults with overweight or obesity randomized to HIIT, VLCHF diet, combined VLCHF+HIIT, or control.
91 participants.
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.
Intensity: RPE 18-19 work; RPE 9-11 recovery.
31-55 min including warm-up and cool-down.
3 sessions/week.
12 weeks.
Pre-planned ancillary analysis of a four-arm randomized controlled diet and exercise trial.
Plasma lipidomic profile, Plasma metabolomic profile, Body composition, and Cardiorespiratory fitness were tracked.

Outcomes

Lipidomic profile

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.

Mixed

Metabolomic profile

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.

Mixed

Body composition

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.

Mixed

Cardiorespiratory fitness

Parent study reported HIIT alone improved cardiorespiratory fitness.

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

Improved

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

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