Optimal exercise strategies to improve HDL-C in metabolic syndrome: A systematic review with pairwise, network, and...

Reduced high-density lipoprotein cholesterol (HDL-C) is a hallmark metabolic abnormality in metabolic syndrome (MetS). Exercise is widely recommended to improve HDL-C, but the optimal modality and dose remain uncertain.

This systematic review and network meta-analysis (NMA) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane guidelines and was prospectively registered in PROSPERO (CRD420251049084). Five databases were searched through November 17, 2025. The NMA compared continuous aerobic exercise (CAE), high-intensity interval training (HIIT), resistance training (RT), combined aerobic-resistance exercise (CAREX), and mind-body exercise (MBE). Dose-response NMA (DR-NMA) using restricted cubic splines modeled multidimensional exercise doses derived from metabolic equivalent of task (MET)-min/week, % maximal oxygen uptake (VO₂_max), and % 1-repetition maximum (1RM).

Fifty-six randomized controlled trials comprising 3788 individuals with MetS were included. HIIT ranked as the most effective modality for raising HDL-C, with the highest surface under the cumulative ranking curve value (SUCRA = 86%), producing an increase of 0.08 mmol/L when performed at 750-1500 MET-min/week and 80-90% VO₂_max, whereas higher volumes (≥1750 MET-min/week) or lower intensities (<60% VO₂max) attenuated the benefit. CAREX increased HDL-C by 0.07-0.10 mmol/L at 750-2000 MET-min/week, combining 70-80% VO₂max aerobic work with 60-80% 1RM resistance loading. RT alone yielded only modest improvements (≈0.03-0.04 mmol/L) at ≥80% 1RM, with unfavorable responses at moderate loads (60-70% 1RM). CAE increased HDL-C modestly (≈0.04 mmol/L) at 65-75% VO₂max, while higher intensities were associated with reductions. MBE did not produce meaningful HDL-C improvement and was associated with a small decrease (≈-0.08 mmol/L) at very high volumes. Across all modalities, HDL-C increased from 600 MET-min/week (0.05 mmol/L), peaked at 1070 MET-min/week (0.09 mmol/L), and diminished thereafter; intensity-based analyses further indicated optimal HDL-C responses at approximately 80% VO_2max (0.11 mmol/L) and 80% 1RM (0.04 mmol/L).

Exercise effectively improves HDL-C in individuals with MetS, with HIIT and CAREX offering the greatest benefits. Clear optimal dose ranges were identified across physiological load indicators, underscoring the need for individualized, dose-precise exercise prescriptions to optimize HDL-C improvement.