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Cited by 31Cardiovascular and exercise physiologyLipoproteins and Cardiovascular HealthPhysical Activity and Health

Estimating the Effect of Aerobic Exercise Training on Novel Lipid Biomarkers: A Systematic Review and Multivariate Meta-Analysis of Randomized Controlled Trials

Open access
Wood, Gina, Taylor, Emily, Ng, Vanessa, Murrell, Anna, Patil, Aditya, van der Touw, Tom, Wolden, Mitch, Andronicos, Nick +1 more·2023·Sports Medicine
DOI 10.1007/s40279-023-01817-0PMC PMC10036419
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Abstract

Background: Aerobic exercise training (AET) prescribed as lipid management treatment positively affects the standard lipid profile and reduces cardiovascular disease (CVD) risk. Apolipoproteins, lipid and apolipoprotein ratios, and lipoprotein sub-fractions may more effectively predict CVD risk than the standard lipid profile but an AET response in these biomarkers has not been established. Objectives: We conducted a quantitative systematic review of randomised controlled trials (RCTs) to (1) determine the effects of AET on lipoprotein sub-fractions, apolipoproteins and relevant ratios; and (2) identify study or intervention covariates associated with change in these biomarkers. Methods: We searched PubMed, EMBASE, all Web of Science and EBSCO health and medical online databases from inception to 31 December 2021. We included published RCTs of adult humans with ≥ 10 per group of participants; an AET intervention duration ≥ 12 weeks of at least moderate intensity (> 40% maximum oxygen consumption); and reporting pre/post measurements. Non-sedentary subjects, or those with chronic disease other than Metabolic Syndrome factors, or pregnant/lactating, as well as trials testing diet/medications, or resistance/isometric/unconventional training interventions, were excluded. Results: Fifty-seven RCTs totalling 3194 participants were analysed. Multivariate meta-analysis showed AET significantly raised antiatherogenic apolipoproteins and lipoprotein sub-fractions (mmol/L mean difference (MD) 0.047 (95% confidence interval (CI) 0.011, 0.082), P = .01); lowered atherogenic apoliproteins and lipoprotein sub-fractions (mmol/L MD − 0.08 (95% CI − 0.161, 0.0003), P = .05); and improved atherogenic lipid ratios (MD − 0.201 (95% CI − 0.291, − 0.111), P < .0001). Multivariate meta-regression showed intervention variables contributed to change in lipid, sub-fraction, and apoliprotein ratios. Conclusion: Aerobic exercise training positively impacts atherogenic lipid and apolipoprotein ratios, alipoproteins, and lipoprotein sub-fractions; and antiatherogenic apolipoproteins and lipoprotein sub-fractions. Cardiovascular disease risk predicted by these biomarkers may be lowered when AET is prescribed as treatment or prevention. PROSPERO ID: CRD42020151925.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and multivariate meta-analysis of 57 RCTs (3194 sedentary adults) found that aerobic exercise training (AET) of ≥12 weeks at >40% VO2MAX improved several novel lipid biomarkers, including raising antiatherogenic apolipoproteins/lipoprotein sub-fractions and reducing atherogenic lipid/apolipoprotein ratios. Exploratory meta-regression suggested AET volume was associated with improvement in these biomarkers.

Key findings

  • AET significantly raised antiatherogenic Apo A1 + A2 + HDL2 + HDL3 mmol/L (MD 0.047, 95% CI 0.011–0.082, P=0.01) and Apo A1 + A2 mg/dL (MD 2.297, 95% CI 0.441–4.153, P<0.02).
  • AET significantly improved the joined atherogenic ratio TC/HDL-C + LDL-C/HDL-C + Apo B100/Apo A1 (MD −0.201, 95% CI −0.291 to −0.111, P<0.001).
  • Joined atherogenic Apo B100 + VLDL mmol/L was not significant in the main model (MD −0.053, 95% CI −0.114 to 0.008, P=0.087), but became significant in the TESTEX ≥10 subanalysis (MD −0.08, 95% CI −0.161 to 0.000, P=0.05); Apo B100 mg/dL alone was not significant (MD −0.953, 95% CI −2.616 to 0.710, P=0.261).
  • Exploratory meta-regression associated AET volume (intensity, minutes/session, sessions/week, intervention duration) with improvement in the joined TC/HDL-C + LDL-C/HDL-C + Apo B100/Apo A1 ratio (τ²=0.0023, R²=0.84); publication year was minimally associated (τ²=0.0134, R²=0.07). The authors estimated that a 2.073 mg/dL decrease in ApoB100 could anticipate a 4.34% decrease in coronary heart disease.

Methods

  • Systematic review with multivariate meta-analysis and meta-regression (PROSPERO CRD42020151925; PRISMA), searching PubMed, EMBASE, all Web of Science, and EBSCO health/medical databases from inception to 31 December 2021, plus hand searches.
  • Included published RCTs of sedentary adults without chronic disease other than MetS factors, with ≥10 per group, AET ≥12 weeks at >40% VO2MAX versus non-exercising control, and pre/post apolipoprotein, lipoprotein sub-fraction, or ratio outcomes; excluded non-sedentary participants, chronic disease other than MetS, pregnancy/lactation, and diet/medication or resistance/isometric/unconventional training trials.
  • Fifty-seven RCTs totalling 3194 participants (exercise 1721; control 1473) were analysed. Continuous random-effects multivariate meta-analysis in CMA joined correlated/non-independent outcomes by atherogenic potential, direction, and unit; unjoinable outcomes used univariate models. Analyses included cumulative chronological pooling, TESTEX quality and risk-of-bias subanalyses, leave-one-out sensitivity, small-study tests, heterogeneity, and exploratory meta-regression with a priori intervention and study covariates.

Limitations

  • Stated: aggregate RCT data rather than individual participant data (except one study); English-language search; exclusion of groups with N<10; few longer-duration RCTs; inclusion of lower-end moderate intensity (>40% VO2MAX) may understate effects; adherence/intensity reporting varied and some measures were subjective; a few control groups increased physical activity; meta-regression covariates were not randomised at study level, so findings are exploratory; imputed SDs/CIs/P values were conservative.
  • Evident from the text: the main joined atherogenic Apo B100 + VLDL mmol/L result was not statistically significant (P=0.087) and reached significance only in the TESTEX ≥10 subanalysis; the abstract’s P=.05 for lowered atherogenic apolipoproteins/sub-fractions corresponds to that subanalysis rather than the main model. Meta-regression for the antiatherogenic Apo A1 + A2 + HDL2 + HDL3 mmol/L outcome alluded to overfitting.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/s40279-023-01817-0

Cites

112 of 112 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

28 of 60 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    A priori aerobic exercise training intervention covariates (intensity, frequency, session duration and intervention duration) have been shown to influence lipid outcomes.

    “A priori AET intervention covariates (intensity, frequency, session duration and intervention duration) that have been shown to influence lipid outcomes were analysed [19, 45, 46].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [19] Fikenzer K, Fikenzer S, Laufs U, Werner C. Effects of endurance training on serum lipids. Vasc Pharmacol. 2018;101:9–20. https://doi.org/10.1016/j.vph.2017.11.005. source
    • cites [45] Hespanhol Junior LC, Pillay JD, van Mechelen W, Verhagen E. Meta-analyses of the effects of habitual running on indices of health in physically inactive adults. Sports Med. 2015;45(10):1455–68. https://doi.org/10.1007/s40279-015-0359-y. source

      The Results section (Blood Serum Concentration Outcomes; page not provided) reports changes in triglycerides and HDL cholesterol after one year of running, supporting a connection between intervention duration and lipid outcomes. But the Dose-Response Analysis (page not provided) does not report that intensity, frequency, or session duration influenced lipid outcomes; its reported significant associations concern body mass and VO2max. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [46] Kodama S, Tanaka S, Saito K, Shu M, Sone Y, Onitake F, et al. Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis. JAMA Intern Med. 2007;167(10):999–1008. https://doi.org/10.1001/archinte.167.10.999. source
  • Premisecitation

    Apolipoproteins and the Apo B100/Apo A1 ratio have been investigated as biomarkers more sensitive to identifying cardiovascular disease risk than total cholesterol, triglycerides and LDL-C.

    “Apolipoproteins and the Apo B100/Apo A1 ratio have been investigated as biomarkers more senstive to identifying CVD risk than TC, TRG and LDL-C [9–11].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [9] Pischon T, Girman CJ, Sacks FM, Rifai N, Stampfer MJ, Rimm EB. Non-high-density lipoprotein cholesterol and apolipoprotein b in the prediction of coronary heart disease in men. Circulation. 2005;112(22):3375–83. https://doi.org/10.1161/CIRCULATIONAHA.104.532499. source

      The Results and Discussion report that apoB was more strongly associated with coronary heart disease risk than LDL-C and triglycerides in the men studied. The paper measured apoB100 but did not evaluate the Apo B100/Apo A1 ratio; it says only that lipid ratios may improve prediction. The ratio-specific part of the claim is therefore not supported by this source. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [10] Chan DC, Watts GF. Apolipoproteins as markers and managers of coronary risk. QJM Int J Med. 2006;99(5):277–87. https://doi.org/10.1093/qjmed/hcl027. source
    • cites [11] Wang F, Wang X, Ye P, Cao R, Zhang Y, Qi Y, et al. High-density lipoprotein 3 cholesterol is a predictive factor for arterial stiffness: a community-based 4.8-year prospective study. Lipids Health Dis. 2018;17(1):5. https://doi.org/10.1186/s12944-017-0650-z. source

      The Background and Discussion discuss HDL subfractions and mention apoA1, but neither addresses the Apo B100/Apo A1 ratio or compares apolipoproteins with total cholesterol, triglycerides, and LDL-C for identifying CVD risk. Searches for that ratio and the claimed comparison found no supporting passage in our copy; page numbers were not provided. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
  • Premisecitation

    Trials reporting the effects of exercise on apolipoproteins and lipid ratios suggest that exercise training exerts a positive effect on these biomarkers.

    “Trials reporting the effects of exercise on apolipoproteins and lipid ratios suggest that exercise training exerts a positive effect on these biomarkers [23–25]”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [23] Yazdani R, Marefati H, Shahesmaeili A, Nakhaei S, Bagheri A, Dastoorpoor M. Effect of aerobic exercises on serum levels of apolipoprotein A1 and apolipoprotein B, and their ratio in patients with chronic obstructive pulmonary disease. Tanaffos. 2018;17(2):82–9.
    • cites [24] Edwards M, Loprinzi P. The dose–response association between reported moderate to vigorous intensity physical activity and atherogenic index of plasma: NHANES, 1999–2006. J Phys Act Health. 2019;16(5):368–70. https://doi.org/10.1123/jpah.2016-0389. source

      The paper’s Abstract reports that some aerobic exercise interventions reduced the atherogenic index of plasma, a lipid ratio, but also says intervention results were mixed: interval and resistance training showed no significant change. It does not report effects on apolipoproteins, and its own NHANES analysis was observational rather than a trial. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [25] Jeon YK, Kim SS, Kim JH, Kim HJ, Kim HJ, Park JJ, et al. Combined aerobic and resistance exercise training reduces circulating apolipoprotein J levels and improves insulin resistance in postmenopausal diabetic women. Diabetes Metab. 2020;44(1):103–12. https://doi.org/10.4093/dmj.2018.0160. source

      The Results report that exercise significantly reduced circulating ApoJ, supporting a positive effect on an apolipoprotein biomarker in the postmenopausal women with type 2 diabetes studied. The paper does not report an exercise-related improvement in lipid ratios; its Discussion instead says there was no discernible close relationship between changes in ApoJ and lipid profiles. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Premisecitation

    A recent comparison of high-intensity versus moderate-intensity aerobic exercise on lipids suggested that antiatherogenic HDL-C is positively affected by high intensity more than moderate intensity exercise.

    “Our recent comparison of the effects of high-intensity versus moderate-intensity aerobic exercise on lipids suggested that antiatherogenic HDL-C is positively affected by high intensity more than moderate intensity exercise [101].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [101] Wood G, Murrell A, van der Touw T, Smart N. HIIT is not superior to MICT in altering blood lipids: a systematic review and meta-analysis. BMJ Open Sport Exerc Med. 2019;5:e000647. https://doi.org/10.1136/bmjsem-2019-000647. source
  • Study design and conductcitation

    A potential limitation of the study is the use of aggregated randomized controlled trial data and not individual subject data, with the exception of one study.

    “A potential limitation of our work is the use of aggregated RCT data and not individual subject data [113, 114], with the exception of one study [86].”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [113] Greenland S, Morgenstern H. Ecological bias, confounding, and effect modification. Int J Epidemiol. 1989;18(1):269–74. https://doi.org/10.1093/ije/18.1.269. source
    • cites [114] Lyman GH, Kuderer NM. The strengths and limitations of meta-analyses based on aggregate data. BMC Med Res Methodol. 2005;5:14. https://doi.org/10.1186/1471-2288-5-14. source
    • cites [86] Sigal RJ, Kenny GP, Boulé NG, Wells GA, Prud’homme D, Fortier M, et al. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes. Ann Intern Med. 2007;147(6):357-W71. https://doi.org/10.7326/0003-4819-147-6-200709180-00005. source
  • Classified as probably not a substantial claim. 23
  • May combine two claims. 24

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Studies with intervention and control group sample sizes less than 10 were excluded to reduce the likelihood of small study effects, such as over-estimation of effect size.

    “Studies of intervention and control group population sample sizes (N) < 10 were excluded to reduce the likelihood of small study effects, for example over-estimation of effect size [33].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [33] Hackshaw A. Small studies: strengths and limitations. Eur Respir J. 2008;32:1141–3. https://doi.org/10.1183/09031936.00136408. source

      The LIMITATIONS section says small studies can overestimate the magnitude of an association, supporting the stated reason for exclusion. The HOW SMALL IS 'SMALL'? section says appropriate sample size depends on the expected effect; it does not establish fewer than 10 participants per group as a cutoff. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Sub-fractions of HDL-C may be more relevant in identifying cardiovascular disease risk than HDL-C.

    “Sub-fractions of HDL-C may be more relevant in identifying CVD risk than HDL-C [11].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [11] Wang F, Wang X, Ye P, Cao R, Zhang Y, Qi Y, et al. High-density lipoprotein 3 cholesterol is a predictive factor for arterial stiffness: a community-based 4.8-year prospective study. Lipids Health Dis. 2018;17(1):5. https://doi.org/10.1186/s12944-017-0650-z. source

  • May combine two claims.

    Premisecitation

    Systematic reviews found that Apo B100 and the Apo B100/Apo A1 ratio improved prediction of cardiovascular risk.

    “Systematic reviews have examined the risk prediction power of Apo A1, A2 and B100 for cardiovascular risk and found Apo B100 and the Apo B100/Apo A1 ratio improved prediction [12–14].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [12] Sandhu PK, Musaad SMA, Remaley AT, Buehler SS, Strider S, Derzon JH, et al. Lipoprotein biomarkers and risk of cardiovascular disease: a laboratory medicine best practices (LMBP) systematic review. J Appl Lab Med. 2016;1(2):214–29. https://doi.org/10.1373/jalm.2016.021006. source
    • cites [13] Sniderman AD, Williams K, Contois JH, Monroe HM, McQueen M, de Graaf J, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein b as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4(3):337–45. https://doi.org/10.1161/CIRCOUTCOMES.110.959247. source

      The Summary (page not provided) concludes that apoB is a better predictor of cardiovascular risk than non-HDL-C or LDL-C. The paper does not report a finding that the apoB/apoA-I ratio improves prediction, and its analysis does not examine apoA-I or apoA-II as predictors. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [14] Schmidt C, Bergström G. Apolipoprotein B/apolipoprotein A-I ratio and apolipoprotein B: long-term predictors of myocardial infarction in initially healthy middle-aged men—a 13-year follow-up. Angiology. 2013;65(10):901–5. https://doi.org/10.1177/0003319713511849. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent 17-year follow-up study of females concluded that the TC/HDL-C ratio was a potent predictor of cardiovascular disease events.

    “A recent 17-year follow-up study of females concluded the TC/HDL-C ratio was a potent predictor of CVD events [4].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Calling S, Johansson S-E, Wolff M, Sundquist J, Sundquist K. The ratio of total cholesterol to high density lipoprotein cholesterol and myocardial infarction in Women’s health in the Lund area (WHILA): a 17-year follow-up cohort study. BMC Cardiovasc Disord. 2019;19(1):239. https://doi.org/10.1186/s12872-019-1228-7. source

      The Abstract Conclusions call TC/HDL-C a powerful predictor of acute myocardial infarction (AMI) in middle-aged women, and the Discussion reports a strong association over a mean 17-year follow-up. The cited study examined AMI, not cardiovascular disease events broadly, so the claim extends its conclusion beyond the studied outcome. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    At least moderate intensity effort (>40% VO2MAX) is the minimum recommended for sedentary individuals.

    “Studies of either prescribed steady-state or interval AET that employed at least a moderate intensity effort (> 40% VO2MAX) were included, since this intensity is the minimum recommended for sedentary individuals [36, 37].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [36] Pollock ML, Gaesser GA, Butcher JD, Després J-P, Dishman RK, Franklin BA, et al. ACSM position stand: the recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults. Med Sci Sports Exerc. 1998;30(6):975–91. https://doi.org/10.1097/00005768-199806000-00032. source
    • cites [37] Swain DP. Moderate or vigorous intensity exercise: which is better for improving aerobic fitness? Prev Cardiol. 2005;8(1):55–8. https://doi.org/10.1111/j.1520-037X.2005.02791.x. source

      In “Increasing Aerobic Fitness” (p. 55), the paper identifies 40% VO₂ reserve as the lower recommended threshold for very-low-fit clients, versus 50% for most clients. This supports a lower threshold for some low-fitness individuals, but it does not state that >40% VO₂max is the minimum recommended for sedentary individuals generally; VO₂ reserve and VO₂max are different measures. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Aerobic exercise training positively affects dyslipidaemia and Metabolic Syndrome and lowers cardiovascular disease risk.

    “Aerobic exercise training (AET) positively affects dyslipidaemia and MetS [17–20] and lowers CVD risk [21, 22].”
    Quote in the paperSubstantial claim2 of 6 sources checked
    • cites [17] Greene NP, Martin SE, Crouse SF. Acute exercise and training alter blood lipid and lipoprotein profiles differently in overweight and obese men and women. Obesity. 2012;20(8):1618–27. https://doi.org/10.1038/oby.2012.65. source
    • cites [18] O’Donovan G, Owen A, Bird SR, Kearney EM, Nevill AM, Jones DW, et al. Changes in cardiorespiratory fitness and coronary heart disease risk factors following 24 wk of moderate- or high-intensity exercise of equal energy cost. J Appl Physiol (1985). 2005;98(5):1619–25. https://doi.org/10.1152/japplphysiol.01310.2004. source
    • cites [19] Fikenzer K, Fikenzer S, Laufs U, Werner C. Effects of endurance training on serum lipids. Vasc Pharmacol. 2018;101:9–20. https://doi.org/10.1016/j.vph.2017.11.005. source
    • cites [20] Mann S, Beedie C, Jimenez A. Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations. Sports Med. 2014;44(2):211–21. https://doi.org/10.1007/s40279-013-0110-5. source

      The Findings > Aerobic Exercise section reports improved lipid profiles with aerobic training, supporting the dyslipidaemia part. The Conclusion links physical activity and improved cholesterol to reduced risks of heart attacks, strokes and coronary artery disease, but the copy does not address Metabolic Syndrome or establish a direct reduction in CVD events from aerobic training. Page numbers were not available in the supplied copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [21] Wood G, Taylor E, Ng V, Murrell A, Patil A, van der Touw T, et al. Determining the effect size of aerobic exercise training on the standard lipid profile in sedentary adults with three or more metabolic syndrome factors: a systematic review and meta-analysis of randomised controlled trials. Br J Sports Med. 2022;56(18):1032–41. https://doi.org/10.1136/bjsports-2021-103999. source
    • cites [22] Pattyn N, Cornelissen VA, Eshghi SRT, Vanhees L. The effect of exercise on the cardiovascular risk factors constituting the metabolic syndrome: a meta-analysis of controlled trials. Sports Med. 2013;43(2):121–33. https://doi.org/10.1007/s40279-012-0003-z. source

      The Results report improvements in HDL-C, blood pressure and waist circumference after dynamic endurance training in patients with metabolic syndrome; triglycerides were statistically unaltered. The Discussion reports improvements in other lipid measures and says the changes are compatible with lower cardiovascular risk, but it estimates that risk reduction rather than demonstrating it directly. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    Reporting of apolipoprotein, lipid and sub-fraction ratios is less common than standard lipid outcomes.

    “Reporting of apolipoprotein, lipid and sub-fraction ratios is less common than standard lipid outcomes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Fifty-seven randomized controlled trials totalling 3194 participants were analysed.

    “Fifty-seven RCTs totalling 3194 participants were analysed.”
    • Also stated in: § Results · plain
      “Screening resulted in the inclusion of 57 RCTs for data extraction, pooling and analysis, published between 1979 and 2020.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Aerobic exercise training programs of moderate intensity with a minimum 12-week duration significantly reduced the joint TC/HDL-C, LDL-C/HDL-C and Apo B100/Apo A1 ratios in sedentary adults free of chronic disease other than possible metabolic syndrome factors.

    “This multivariate meta-analysis with meta-regression of pooled data indicated that AET programs of moderate intensity with a minimum 12-week duration significantly reduced the joint TC/HDL-C, LDL-C/HDL-C and Apo B100/Apo A1 ratios, as well as Apo B100 and VLDL values, while significantly raising Apo A1 and A2 and the sub-fractions HDL2 and HDL3, in sedentary adults free of chronic disease other th”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Variations of the model (restricted maximum likelihood, method of moments) suggested no fit or overfitting, respectively.

    “Variations of the model (restricted maximum likelihood, method of moments) suggested no fit or overfitting, respectively (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Better quality studies increased the effect size for Apo B100 reported in mg/dL but did not attain statistical significance.

    “Better quality studies increased the effect size for Apo B100 reported in mg/dL but did not attain statistical significance (Table S7, OSM).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    Some included randomized controlled trials used objective measures such as electronic devices, while other studies used subjective measures, for example, the Borg scale, self-reported heart rate, and log books, denoted by different indices of intensity.

    “Some RCTs used objective measures such as electronic devices. Other studies used subjective measures, for example, the Borg scale, self-reported heart rate, log books, denoted by different indices of intensity (energy expenditure, VO2MAX, maximum heart rate, METs, Borg scale).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For randomized controlled trials (RCTs) reporting apolipoprotein B100 (Apo B100) with a study quality score ≥ 10, aerobic exercise training beneficially decreased Apo B100 by 2.073 mg/dL, although this was not statistically significant.

    “While not statistically significant, for RCTs reporting Apo B100 with a study quality score ≥ 10, we showed that AET beneficially decreased Apo B100 by 2.073 mg/dL.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Few studies reported the Apo B100/Apo A1 ratio.

    “Few studies reported the Apo B100/Apo A1 ratio, considered an equivalent if not more accurate lipid CVD risk biomarker in comparison to standard lipid CVD risk biomarkers.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    A TESTEX score of at least 10 is considered good study quality and reporting.

    “A score ≥ 10 is considered good study quality and reporting [40].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Gilson N, Papinczak Z, Mielke G, Haslam C, McKenna J, Brown W. Intervention strategies to promote self-managed physical activity in service veterans and their dependants—a rapid evidence assessment. Brisbane: Centre for Research on Exercise, Physical Activity and Health, The University of Queensland, Australia, Department of Veterans Affairs AG;2019.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Lowered levels of lipoprotein sub-fractions HDL2 and HDL3 are considered to increase cardiovascular disease risk, although HDL3 may be less protective in the presence of Metabolic Syndrome.

    “Lowered levels of lipoprotein sub-fractions HDL2 and HDL3 are considered to increase CVD risk, although HDL3 may be less protective in the presence of MetS [15].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Rye K-A, Bursill CA, Lambert G, Tabet F, Barter PJ. The metabolism and anti-atherogenic properties of HDL. J Lipid Res. 2009;50(Suppl):S195–200. https://doi.org/10.1194/jlr.R800034-JLR200. source

  • Classified as probably not a substantial claim.

    Premisecitation

    An aerobic exercise training intervention of at least 12 weeks was considered the minimum time to affect lipid profiles.

    “An AET intervention ≥ 12 weeks was considered the minimum time to affect lipid profiles [34, 35].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [34] Leon AS, Sanchez OA. Response of blood lipids to exercise training alone or combined with dietary intervention. Med Sci Sports Exerc. 2001;33(6):S502–15. https://doi.org/10.1097/00005768-200106001-00021. source
    • cites [35] Tambalis K, Panagiotakos DB, Kavouras SA, Sidossis LS. Responses of blood lipids to aerobic, resistance, and combined aerobic with resistance exercise training: a systematic review of current evidence. Angiology. 2008;60(5):614–32. https://doi.org/10.1177/0003319708324927. source

  • May combine two claims.

    Interpretationown data

    In sedentary adults, aerobic exercise training lowers atherogenic apolipoprotein and lipoprotein sub-fractions and lipid ratios, and raises antiatherogenic apolipoproteins and lipoprotein sub-fractions.

    “Aerobic exercise training (AET) lowers atherogenic apolipoprotein and lipoprotein sub-fractions and lipid ratios, and raises antiatherogenic apolipoproteins and lipoprotein sub-fractions, in sedentary adults.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    A study quality sub-analysis of randomized controlled trials grouped according to a TESTEX score of at least 10 and a within-study risk evaluation of low-to-medium was conducted.

    “A study quality sub-analysis of RCTs grouped according to a TESTEX score ≥ 10 and a within-study risk evaluation of low-to-medium was conducted.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    GW and NS independently entered data in Comprehensive Meta-Analysis and reviewed each other's files for accuracy.

    “GW and NS independently entered data in CMA, and reviewed each other’s files for accuracy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    A leave-one-out sensitivity analysis was performed to evaluate the influence of each randomized controlled trial on the effect size of pooled data.

    “A leave-one-out (K − 1, where K = total number of pooled RCTs, and each RCT is excluded once) sensitivity analysis was also performed to evaluate the influence of each RCT on the effect size of pooled data [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Higgins J, Green S. Cochrane handbook for systematic reviews of interventions. Chichester: Wiley; 2008. source

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Study quality was determined using the validated Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX), a 15-point scale specific to exercise training studies.

    “Study quality was determined using the validated Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX) [39], a 15-point scale specific to exercise training studies”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] Smart NA, Waldron M, Ismail H, Giallauria F, Vigorito C, Cornelissen V, et al. Validation of a new tool for the assessment of study quality and reporting in exercise training studies: TESTEX. Int J Evid Based Healthc. 2015;13(1):9–18. source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    TC/HDL-C and LDL-C/HDL-C ratios better predicted cardiovascular disease risk than the standard lipid profile biomarkers.

    “A systematic review collating data from several large observational studies found TC/HDL-C and LDL-C/HDL-C ratios better predicted CVD risk than the SLP biomarkers [5].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Millán J, Pintó X, Muñoz A, Zúñiga M, Rubiés-Prat J, Pallardo LF, et al. Lipoprotein ratios: physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manag. 2009;5:757–65.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Within-study risk of bias was evaluated against seven criteria and scored as low, medium or high.

    “Within-study risk-of-bias was evaluated against seven criteria (see Table S4 (OSM)) and a score of low, medium or high was awarded.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Aerobic exercise training positively impacts atherogenic lipid and apolipoprotein ratios, apolipoproteins, and lipoprotein sub-fractions, and antiatherogenic apolipoproteins and lipoprotein sub-fractions.

    “Aerobic exercise training positively impacts atherogenic lipid and apolipoprotein ratios, alipoproteins, and lipoprotein sub-fractions; and antiatherogenic apolipoproteins and lipoprotein sub-fractions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Heterogeneity was quantified using the Q statistic, its corresponding P value, τ2, τ, and I2.

    “Heterogeneity was quantified using the Q statistic, and the corresponding P value, τ2, τ, and I2 [41].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1(2):97–111. https://doi.org/10.1002/jrsm.12. source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Raised levels of Apo A1 and A2 are considered antiatherogenic, while increased levels of Apo B100 and VLDL are atherogenic.

    “Raised levels of Apo A1 and A2 are considered to be antiatherogenic, while increased levels of Apo B100 and VLDL are atherogenic [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Brewer HB. High-density lipoprotein metabolism. In: Ballantyne CM, editor. Clinical lipidology. Philadelphia: W.B. Saunders; 2009. p. 45–55. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Small-study effects were examined using Rosenthal's failsafe N, Orwin's failsafe N, Duval and Tweedie's trim-and-fill, Egger's regression test, Begg and Mazumdar's rank correlation test, and precision and standard error funnel plots.

    “Each of Rosenthal’s failsafe N, Orwin’s failsafe N, Duval and Tweedie’s trim-and-fill, Egger’s regression test, Begg and Mazumdar’s rank correlation test, and precision and standard error funnel plots, were used to test for possible small-study effects.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    Some randomized controlled trials reported scant data on aerobic exercise training protocol or energy expenditure, and the study therefore estimated intensity as a percent of VO2MAX.

    “Some RCTs reported scant data on AET protocol or energy expenditure, and we therefore estimated intensity as a percent of VO2MAX.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    The study included aerobic exercise training protocols with an intensity (> 40% VO2MAX) at the lower end of the moderate-intensity range; this low-intensity may elicit very small changes in lipids, and the inclusion of these protocols may have resulted in understated effect sizes.

    “We included AET protocols with an intensity (> 40% VO2MAX) at the lower end of the moderate-intensity range; this low-intensity may elicit very small changes in lipids [19], and the inclusion of these protocols may have resulted in understated effect sizes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Fikenzer K, Fikenzer S, Laufs U, Werner C. Effects of endurance training on serum lipids. Vasc Pharmacol. 2018;101:9–20. https://doi.org/10.1016/j.vph.2017.11.005. source

  • May combine two claims.

    Study design and conductreasoning

    The imputation of these statistics was conservative and this approach may have weakened results.

    “Our imputation of these statistics was conservative and this approach may have weakened results.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Neither absolute between-study heterogeneity (τ2) nor relative heterogeneity (I2) for each analysed outcome indicated that trials should not be pooled or that significance testing should not be undertaken.

    “Neither the degree of absolute between-study heterogeneity (τ2) nor the relative heterogeneity (I2) for each analysed outcome indicated that trials should not be pooled, or that significance testing should not be undertaken; see Table S12 (OSM).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    The study searched using English language terms, potentially reducing the pool of available studies for selection and possibly introducing bias.

    “We searched using English language terms, potentially reducing the pool of available studies for selection and possibly introducing bias.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    A very small number of randomized controlled trials noted that control groups increased physical activity levels during the duration of the study; this may have reduced the study's estimated effect size.

    “A very small number of RCTs noted that control groups increased physical activity levels during the duration of the study; this may have reduced our estimated effect size.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    A minimum effective aerobic exercise training protocol requires an AET volume of > 45 min per session for 3-4 sessions per week for a duration of > 26 weeks at > 65% VO2MAX to positively affect lipids.

    “A previous systematic review pooling data from AET interventions compared thresholds of intensity and volume, and determined that a minimum effective AET protocol required an AET volume of > 45 min per session for 3–4 sessions per week for a duration of > 26 weeks at > 65% VO2MAX [19] to positively affect lipids.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Fikenzer K, Fikenzer S, Laufs U, Werner C. Effects of endurance training on serum lipids. Vasc Pharmacol. 2018;101:9–20. https://doi.org/10.1016/j.vph.2017.11.005. source

  • May combine two claims.

    Study design and conductnone given

    The study excluded studies with intervention and comparison group N < 10, and the number of randomized controlled trials included with longer durations were few, which may have reduced estimated effect sizes.

    “We excluded studies with intervention and comparison group N < 10, and the number of RCTs included with longer durations were few, which may have reduced estimated effect sizes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Aerobic exercise training at >40% VO2MAX for at least 12 weeks achieved better outcomes than no exercise for lipoprotein sub-fractions, lipid and apolipoprotein ratios, as well as Apo A1, A2 and B100.

    “we have shown that AET at > 40% VO2MAX for ≥ 12 weeks achieved better outcomes than no exercise for lipoprotein sub-fractions, lipid and Apo ratios, as well as Apo A1, A2 and B100”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Included randomized controlled trials extracted blood from individuals in fasted states and in seated or supine positions, and no trial was excluded for phlebotomy reasons.

    “The included RCTs extracted blood from individuals in fasted states and in seated or supine positions and thus no RCT was excluded for phlebotomy reasons (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The study quality sensitivity results allude to improvements in study design over time and/or the employment of more sensitive lipid assays, irrespective of study publication year.

    “These results allude to improvements in study design over time, and/or the employment of more sensitive lipid assays, irrespective of study publication year.”
    Quote in the paperNot a substantial claim
39 of 39

  • The paper relies on this without support.

    A comprehensive quantitative review investigating the effects of aerobic exercise training on apolipoproteins, lipoprotein sub-fractions, associated ratios and lipid ratios in adults free of chronic disease other than Metabolic Syndrome factors had not been conducted before this study.

    “however, to the best of our knowledge, a comprehensive quantitative review investigating the effects of AET on apolipoproteins, lipoprotein sub-fractions, associated ratios and lipid ratios in adults free of chronic disease other than MetS factors has yet to be conducted.”

  • The authors state this as an assumption.

    The raw data in the multivariate random effects model are normally distributed.

    “This model assumes normal distribution of raw data.”

  • The paper relies on this without support.

    This quantitative review is the first to compare the effects of a minimum prescribed aerobic exercise training dose against no exercise on lipid sub-fractions, ratios and apolipoproteins in a cohort free of chronic disease except possible metabolic syndrome factors, using a multivariate meta-analytic approach.

    “To the best of our knowledge, this quantitative review is the first to have compared the effects of a minimum prescribed AET dose against no exercise on lipid sub-fractions, ratios and apolipoproteins in a cohort characterised as free of chronic disease except for the possible presence of the CVD risk factors comprising MetS, using a multivariate meta-analytic approach.”

  • The paper relies on this without support.

    Previous systematic reviews did not use TESTEX to measure the quality of included studies.

    “Previous systematic reviews did not use TESTEX [39] to measure the quality of included studies.”

  • The paper relies on this without support.

    The Apo B100/Apo A1 ratio is considered an equivalent if not more accurate lipid cardiovascular disease risk biomarker in comparison to standard lipid cardiovascular disease risk biomarkers.

    “Few studies reported the Apo B100/Apo A1 ratio, considered an equivalent if not more accurate lipid CVD risk biomarker in comparison to standard lipid CVD risk biomarkers.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract presents a subgroup result as the overall result

    Major

    The abstract reports a significant −0.08 mmol/L result for atherogenic apolipoproteins and sub-fractions. The overall Apo B100 + VLDL analysis in Table 2 instead reports −0.053 mmol/L with P = 0.087; the −0.08 result is identified later as a study-quality sub-analysis.

  • Included trial is listed at the excluded intensity threshold

    Minor

    The eligibility rule requires intensity above 40% VO2MAX, but Table 1 lists the included Gordon et al. trial at exactly 40%.

  • Reported session-frequency range excludes listed trials

    Minor

    The stated range of 1.8 to 5.2 sessions per week excludes the listed Ring-Dimitriou trial at 1 session per week. Table 1 also lists Stensel et al. at 7 sessions per week, above the stated maximum.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Fu R, Vandermeer B, Shamliyan T, O’Neil M, Yazdi F, Fox S et al. Handling Continuous Outcomes in Quantitative Synthesis. In: Methods guide for effectiveness and comparative effectiveness reviews [Internet]. Agency for Healthcare Research and Quality (US); 2008, Rockville (MD). 2013. https://www.ncbi.nlm.nih.gov/books/NBK154408/. Accessed 22 May 2019.

Cited by

Sorted by citations

Related

Authors
Wood, G., Taylor, E., Ng, V., Murrell, A., Patil, A., van der Touw, T., Wolden, M., Andronicos, N., & Smart, N. A.
Affiliations
  • Curtin University (AU)
  • University of New England (AU)
  • University of Jamestown (US)
Corresponding author
Wood, Gina
ORCID
Venue
Sports Medicine
Publisher
Springer Science and Business Media LLC
Published
2023-03-02
Volume
53
Issue
4
Pages
871-886
ISSN
  • 0112-1642 (ISSN-L)
  • 1179-2035
DOI
10.1007/s40279-023-01817-0
PMC
PMC10036419
OpenAlex
W4322758115
Semantic Scholar
740a79130fe0891341ca5400cc41f8f1ca386ea1
Cited by
31
References
111
Citations by year
2026: 11 · 2025: 12 · 2024: 8
FWCI
3.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Sports Medicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Physiology › Physical Activity and Health
Keywords
aerobic exercise training, lipid biomarkers, apolipoproteins, cardiovascular risk, exercise dose-response, metabolic syndrome, cardiovascular risk prediction, lipid control, sedentary lifestyle
MeSH terms
Adult, Cardiovascular Diseases, Humans, Lipids, Lipoproteins, Randomized Controlled Trials as Topic, Resistance Training

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-19.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-19.

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Statistics and arithmetic are recomputed, not judged.

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