Optimal exercise modalities and doses for improving pro-atherogenic lipid profiles in patients with metabolic syndrome: a systematic review with pairwise, network, and dose-response meta-analyses

Metabolic syndrome (MetS) confers a high risk of cardiovascular disease, type 2 diabetes, and premature mortality. Dyslipidemia, particularly abnormalities in pro-atherogenic lipid profiles, is a key pathophysiological feature. Although exercise is a cornerstone intervention for MetS, the optimal modalities and doses for improving pro-atherogenic lipid profiles remain unclear. This study compared the effects of different exercise interventions on pro-atherogenic lipid profiles in adults with MetS.

We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library through September 2025 for randomized controlled trials (RCTs) in adults with MetS. Pairwise meta-analyses, Bayesian network meta-analyses (NMAs), and dose-response models were performed. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated with the GRADE approach.

Forty-nine RCTs involving 4144 participants were included, comprising 88 intervention arms: 28 high-intensity interval training (HIIT), 25 conventional aerobic exercise (CAE), 15 resistance training (RT), 14 combined aerobic and resistance exercise (CAREX), and 6 mind-body exercise (MBE). NMA showed that MBE ranked highest across most lipid outcomes, although its results were sensitive to a single trial. CAREX produced consistent and clinically meaningful reductions in non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides (TG), and total cholesterol (TC), particularly at 500-1000 METs-min/week, while HIIT was most effective at 600-1000 METs-min/week. CAE and RT yielded overall favorable effects, but their dose-response thresholds were uncertain due to clustering of available trials around 600-900 METs-min/week. Low-density lipoprotein cholesterol (LDL-C) improved at≈244 METs-min/week (- 0.02 to - 0.28 mmol/L) and TG at≈510 METs-min/week(- 0.05 to - 0.10 mmol/L), with benefits plateauing above≈900 METs-min/week. Most outcomes were rated as moderate certainty using GRADE, with some downgraded for risk of bias and imprecision.

Structured exercise may improve pro-atherogenic lipid profiles in MetS. CAREX and HIIT appear promising at moderate doses, while MBE could serve as a feasible low-impact alternative for individuals with reduced exercise tolerance. These findings suggest preliminary dose-based targets that may help guide personalized exercise prescriptions in clinical practice.

PROSPERO CRD420251082352.