Skip to main content
Log in

Aerobic Capacity in Persons with Multiple Sclerosis: A Systematic Review and Meta-Analysis

  • Systematic Review
  • Published:
Sports Medicine Aims and scope Submit manuscript

Abstract

Background

Aerobic capacity (VO2max) is a strong health and performance predictor and is regarded as a key physiological measure in the healthy population and in persons with multiple sclerosis (PwMS). However, no studies have tried to synthesize the existing knowledge regarding VO2max in PwMS.

Objectives

The objectives of this study were to (1) systematically review the psychometric properties of the VO2max test; (2) systematically review the literature on VO2max compared with healthy populations; (3) summarize correlates of VO2max; and (4) to review and conduct a meta-analysis of longitudinal exercise studies evaluating training-induced effects on VO2max in PwMS.

Data Sources and Study Selection

A systematic literature search of six databases (PubMed, EMBASE, Cochrane Library, PEDro, CINAHL and SPORTDiscus) was performed. To be included, the study had to (1) enrol participants with definite MS according to defined criteria; (2) assess aerobic capacity (VO2max) by means of a graded exercise test to voluntary exhaustion; (3) had undergone peer review; and (4) be available in English, Danish or Dutch.

Study Appraisal and Synthesis Methods

The psychometric properties of the VO2max test in PwMS were reviewed with respect to reliability, validity and responsiveness. Simple Pearson correlation analysis was used to assess the relation between key study characteristics and the reported mean VO2max. The methodological quality of the intervention studies was evaluated using the original 11-item Physiotherapy Evidence Database (PEDro) scale. A random coefficient model was used to summarize individual, weighted, standardized effects of studies that assessed the effects of exercise on aerobic capacity in PwMS.

Results

A total of 40 studies, covering 165 healthy controls and 1,137 PwMS, fulfilled the inclusion criteria. VO2max testing in PwMS can be considered a valid measure of aerobic capacity, at least in PwMS having low-to-mild disability, and an ∼10 % change between two tests performed on separate days can be considered the smallest reliable change (with 95 % certainty) in VO2max in PwMS. The average body-weight-adjusted VO2max was significantly lower in PwMS (25.5 ± 5.2 mL·kg−1·min−1) compared with healthy controls (30.9 ± 5.4 mL·kg−1·min−1). The analysis of VO2max correlates revealed associations with a variety of outcomes covering all levels of the International Classification of Functioning, Disability and Health (ICF) model. The meta-analysis showed that aerobic training in PwMS may improve VO2max by as much as 3.5 mL·kg−1·min−1.

Conclusions

A valid and reliable test can be performed, in at least ambulant PwMS, by the gold standard whole-body maximal exercise test. Aerobic capacity in PwMS is impaired compared with healthy people, and is significantly associated with factors on all levels of the ICF model, including disease severity. Aerobic training can improve aerobic capacity in PwMS to a degree that is associated with secondary health benefits.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Koch-Henriksen N, Sorensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol. 2010;9(5):520–32.

    Article  PubMed  Google Scholar 

  2. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–17.

    Article  CAS  PubMed  Google Scholar 

  3. Motl RW, Pilutti LA. The benefits of exercise training in multiple sclerosis. Nat Rev Neurol. 2012;8(9):487–97.

    Article  PubMed  Google Scholar 

  4. Confavreux C, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain. 2006;129(Pt 3):606–16.

    Article  PubMed  Google Scholar 

  5. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology. 1983;33(11):1444–52.

    Article  CAS  PubMed  Google Scholar 

  6. Marrie RA, Horwitz RI. Emerging effects of comorbidities on multiple sclerosis. Lancet Neurol. 2010;9(8):820–8.

    Article  PubMed  Google Scholar 

  7. Ehde DM, Bombardier CH. Depression in persons with multiple sclerosis. Phys Med Rehabil Clin N Am. 2005;16(2):437–48 (ix).

    Article  PubMed  Google Scholar 

  8. Fisk JD, Pontefract A, Ritvo PG, et al. The impact of fatigue on patients with multiple sclerosis. Can J Neurol Sci. 1994;21(1):9–14.

    CAS  PubMed  Google Scholar 

  9. Dalgas U, Ingemann-Hansen T, Stenager E. Physical exercise and MS: recommendations. Int MS J. 2009;16(1):5–11.

    CAS  PubMed  Google Scholar 

  10. Wens I, Dalgas U, Stenager E, et al. Risk factors related to cardiovascular diseases and the metabolic syndrome in multiple sclerosis: a systematic review. Mult Scler. 2013;19(12):1556–64.

    Article  PubMed  Google Scholar 

  11. Carnethon MR, Gulati M, Greenland P. Prevalence and cardiovascular disease correlates of low cardiorespiratory fitness in adolescents and adults. JAMA. 2005;294(23):2981–8.

    Article  CAS  PubMed  Google Scholar 

  12. Eriksen L, Curtis T, Gronbaek M, et al. The association between physical activity, cardiorespiratory fitness and self-rated health. Prev Med. 2013;57(6):900–2.

    Article  PubMed  Google Scholar 

  13. Bassett DR Jr, Howley ET. Limiting factors for maximum oxygen uptake and determinants of endurance performance. Med Sci Sports Exerc. 2000;32(1):70–84.

    Article  PubMed  Google Scholar 

  14. Marrie RA, Hanwell H. General health issues in multiple sclerosis: comorbidities, secondary conditions, and health behaviors. Continuum (Minneap Minn). 2013;19(4 Multiple Sclerosis):1046–57.

    Google Scholar 

  15. Sandroff BM, Sosnoff JJ, Motl RW. Physical fitness, walking performance, and gait in multiple sclerosis. J Neurol Sci. 2013;328(1–2):70–6.

    Article  PubMed  Google Scholar 

  16. Sandroff BM, Motl RW. Fitness and cognitive processing speed in persons with multiple sclerosis: a cross-sectional investigation. J Clin Exp Neuropsychol. 2012;34(10):1041–52.

    Article  PubMed  Google Scholar 

  17. Prakash RS, Snook EM, Erickson KI, et al. Cardiorespiratory fitness: a predictor of cortical plasticity in multiple sclerosis. Neuroimage. 2007;34(3):1238–44.

    Article  PubMed  Google Scholar 

  18. Prakash RS, Snook EM, Motl RW, et al. Aerobic fitness is associated with gray matter volume and white matter integrity in multiple sclerosis. Brain Res. 2010;1341:41–51.

    Article  CAS  PubMed  Google Scholar 

  19. Cress ME, Meyer M. Maximal voluntary and functional performance levels needed for independence in adults aged 65 to 97 years. Phys Ther. 2003;83(1):37–48.

    PubMed  Google Scholar 

  20. Stickland MK, Butcher SJ, Marciniuk DD, et al. Assessing exercise limitation using cardiopulmonary exercise testing. Pulm Med. 2012;2012:824091.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Whipp B. The peak versus maximum oxygen uptake issue. CPX International Inc.; 2010. p. 1–9.

  22. Langeskov-Christensen M, Langeskov-Christensen D, Overgaard K, et al. Validity and reliability of VO-max measurements in persons with multiple sclerosis. J Neurol Sci. 2014;342(1–2):79–87.

    Article  PubMed  Google Scholar 

  23. Mokkink LB, Terwee CB, Patrick DL, et al. The COSMIN study reached international consensus on taxonomy, terminology, and definitions of measurement properties for health-related patient-reported outcomes. J Clin Epidemiol. 2010;63(7):737–45.

    Article  PubMed  Google Scholar 

  24. Waschbisch A, Wenny I, Tallner A, et al. Physical activity in multiple sclerosis: a comparative study of vitamin D, brain-derived neurotrophic factor and regulatory T cell populations. Eur Neurol. 2012;68(2):122–8.

    Article  CAS  PubMed  Google Scholar 

  25. Motl RW, Goldman M. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis. Acta Neurol Scand. 2011;123(2):98–104.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Bouchard C, An P, Rice T, et al. Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE family study. J Appl Physiol (1985). 1999;87(3):1003–8.

    CAS  Google Scholar 

  27. Dalgas U, Stenager E, Ingemann-Hansen T. Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training. Mult Scler. 2008;14(1):35–53.

    Article  CAS  PubMed  Google Scholar 

  28. Petajan JH, White AT. Recommendations for physical activity in patients with multiple sclerosis. Sports Med. 1999;27(3):179–91.

    Article  CAS  PubMed  Google Scholar 

  29. Latimer-Cheung AE, Pilutti LA, Hicks AL, et al. Effects of exercise training on fitness, mobility, fatigue, and health-related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development. Arch Phys Med Rehabil. 2013;94(9):1800–28.

    Article  PubMed  Google Scholar 

  30. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Howley ET, Bassett DR Jr, Welch HG. Criteria for maximal oxygen uptake: review and commentary. Med Sci Sports Exerc. 1995;27(9):1292–301.

    Article  CAS  PubMed  Google Scholar 

  33. Duncan GE, Howley ET, Johnson BN. Applicability of VO2max criteria: discontinuous versus continuous protocols. Med Sci Sports Exerc. 1997;29(2):273–8.

    Article  CAS  PubMed  Google Scholar 

  34. Midgley AW, McNaughton LR, Polman R, et al. Criteria for determination of maximal oxygen uptake: a brief critique and recommendations for future research. Sports Med. 2007;37(12):1019–28.

    Article  PubMed  Google Scholar 

  35. Maher CG, Sherrington C, Herbert RD, et al. Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther. 2003;83(8):713–21.

    PubMed  Google Scholar 

  36. Herbert R, Moseley A, Sherrington C. PEDro: a database of randomised controlled trials in physiotherapy. Health Inf Manag. 1998;28(4):186–8.

    CAS  PubMed  Google Scholar 

  37. Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep. 1985;100(2):126–31.

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12.

    Article  CAS  PubMed  Google Scholar 

  39. Higgins J, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available at: www.cochrane-handbook.org. Accessed 24 Nov 2014

  40. Bjarnadottir OH, Konradsdottir AD, Reynisdottir K, et al. Multiple sclerosis and brief moderate exercise. A randomised study. Mult Scler. 2007;13(6):776–82.

    Article  CAS  PubMed  Google Scholar 

  41. Rasova K, Havrdova E, Brandejsky P, et al. Comparison of the influence of different rehabilitation programmes on clinical, spirometric and spiroergometric parameters in patients with multiple sclerosis. Mult Scler. 2006;12(2):227–34.

    Article  CAS  PubMed  Google Scholar 

  42. Cohen J. Statistical power analysis for the behavioral sciences. New York: Academic Press; 1988.

    Google Scholar 

  43. Romberg A, Virtanen A, Ruutiainen J, et al. Effects of a 6-month exercise program on patients with multiple sclerosis: a randomized study. Neurology. 2004;63(11):2034–8.

    Article  CAS  PubMed  Google Scholar 

  44. Heine M, Hoogervorst EL, Hacking HG, et al. Validity of maximal exercise testing in patients with low to moderate multiple sclerosis. Phys Ther. 2014;94(8):1168–75.

    Article  PubMed  Google Scholar 

  45. Briken S, Gold SM, Patra S, et al. Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial. Mult Scler. 2014;20(3):382–90.

    Article  CAS  PubMed  Google Scholar 

  46. Schulz KH, Gold SM, Witte J, et al. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci. 2004;225(1–2):11–8.

    Article  CAS  PubMed  Google Scholar 

  47. Koseoglu BF, Gokkaya NK, Ergun U, et al. Cardiopulmonary and metabolic functions, aerobic capacity, fatigue and quality of life in patients with multiple sclerosis. Acta Neurol Scand. 2006;114(4):261–7.

    Article  CAS  PubMed  Google Scholar 

  48. Motl RW, Fernhall B. Accurate prediction of cardiorespiratory fitness using cycle ergometry in minimally disabled persons with relapsing-remitting multiple sclerosis. Arch Phys Med Rehabil. 2012;93(3):490–5.

    Article  PubMed  Google Scholar 

  49. Jette AM. Toward a common language for function, disability, and health. Phys Ther. 2006;86(5):726–34.

    PubMed  Google Scholar 

  50. Golzari Z, Shabkhiz F, Soudi S, et al. Combined exercise training reduces IFN-(gamma) and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis. Int Immunopharmacol. 2010;10(11):1415–9.

    Article  CAS  PubMed  Google Scholar 

  51. Petajan JH, Gappmaier E, White AT, et al. Impact of aerobic training on fitness and quality of life in multiple sclerosis. Ann Neurol. 1996;39(4):432–41.

    Article  CAS  PubMed  Google Scholar 

  52. Skjerbaek AG, Naesby M, Lutzen K, et al. Endurance training is feasible in severely disabled patients with progressive multiple sclerosis. Mult Scler. 2014;20(5):627–30.

    Article  CAS  PubMed  Google Scholar 

  53. Bansi J, Bloch W, Gamper U, et al. Endurance training in MS: short-term immune responses and their relation to cardiorespiratory fitness, health-related quality of life, and fatigue. J Neurol. 2013;260(12):2993–3001.

    Article  CAS  PubMed  Google Scholar 

  54. Bansi J, Bloch W, Gamper U, et al. Training in MS: influence of two different endurance training protocols (aquatic versus overland) on cytokine and neurotrophin concentrations during three week randomized controlled trial. Mult Scler. 2013;19(5):613–21.

    Article  CAS  PubMed  Google Scholar 

  55. Feltham MG, Collett J, Izadi H, et al. Cardiovascular adaptation in people with multiple sclerosis following a twelve week exercise programme suggest deconditioning rather than autonomic dysfunction caused by the disease. Results from a randomized controlled trial. Eur J Phys Rehabil Med. 2013;49(6):765–74.

    CAS  PubMed  Google Scholar 

  56. Collett J, Dawes H, Meaney A, et al. Exercise for multiple sclerosis: a single-blind randomized trial comparing three exercise intensities. Mult Scler. 2011;17(5):594–603.

    Article  PubMed  Google Scholar 

  57. Rampello A, Franceschini M, Piepoli M, et al. Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: a randomized crossover controlled study. Phys Ther. 2007;87(5):545–55.

    Article  PubMed  Google Scholar 

  58. Mostert S, Kesselring J. Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis. Mult Scler. 2002;8(2):161–8.

    Article  CAS  PubMed  Google Scholar 

  59. Ponichtera-Mulcare JA, Mathews T, Barrett PJ, et al. Change in aerobic fitness of patients with multiple sclerosis during a 6-month training program. Sports Med Train Rehabil. 1997;7(3–4):265–72.

    Article  Google Scholar 

  60. Rodgers MM, Mulcare JA, King DL, et al. Gait characteristics of individuals with multiple sclerosis before and after a 6-month aerobic training program. J Rehabil Res Dev. 1999;36(3):183–8.

    CAS  PubMed  Google Scholar 

  61. Buchfuhrer MJ, Hansen JE, Robinson TE, et al. Optimizing the exercise protocol for cardiopulmonary assessment. J Appl Physiol Respir Environ Exerc Physiol. 1983;55(5):1558–64.

    CAS  PubMed  Google Scholar 

  62. Mahler A, Steiniger J, Bock M, et al. Is metabolic flexibility altered in multiple sclerosis patients? PLoS One. 2012;7(8):e43675.

    Article  PubMed Central  PubMed  Google Scholar 

  63. Hale LA, Nukada H, Du Plessis LJ, et al. Clinical screening of autonomic dysfunction in multiple sclerosis. Physiother Res Int. 2009;14(1):42–55.

    Article  PubMed  Google Scholar 

  64. Gallien P, Nicolas B, Robineau S, et al. Physical training and multiple sclerosis. Ann Readapt Med Phys. 2007;50(6):373–6 (369–72).

    Article  CAS  PubMed  Google Scholar 

  65. Ponichtera-Mulcare JA, Mathews T, Glaser RM, et al. Maximal aerobic exercise of individuals with multiple sclerosis using three modes of ergometry. Clin Kinesiol. 1995;49(1):4–13.

    Google Scholar 

  66. Morrison EH, Cooper DM, White LJ, et al. Ratings of perceived exertion during aerobic exercise in multiple sclerosis. Arch Phys Med Rehabil. 2008;89(8):1570–4.

    Article  PubMed  Google Scholar 

  67. Ng AV, Kent-Braun JA. Quantitation of lower physical activity in persons with multiple sclerosis. Med Sci Sports Exerc. 1997;29(4):517–23.

    Article  CAS  PubMed  Google Scholar 

  68. Christou DD, Seals DR. Decreased maximal heart rate with aging is related to reduced {beta}-adrenergic responsiveness but is largely explained by a reduction in intrinsic heart rate. J Appl Physiol (1985). 2008;105(1):24–9.

    Article  Google Scholar 

  69. Foglio K, Clini E, Facchetti D, et al. Respiratory muscle function and exercise capacity in multiple sclerosis. Eur Respir J. 1994;7(1):23–8.

    Article  CAS  PubMed  Google Scholar 

  70. Taylor HL, Buskirk E, Henschel A. Maximal oxygen intake as an objective measure of cardio-respiratory performance. J Appl Physiol. 1955;8(1):73–80.

    CAS  PubMed  Google Scholar 

  71. Kodama S, Saito K, Tanaka S, et al. Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA. 2009;301(19):2024–35.

    Article  CAS  PubMed  Google Scholar 

  72. Romberg A, Virtanen A, Aunola S, et al. Exercise capacity, disability and leisure physical activity of subjects with multiple sclerosis. Mult Scler. 2004;10(2):212–8.

    Article  CAS  PubMed  Google Scholar 

  73. Motl RW, Goldman MD. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis. Mult Scler. 2010;16(8):1019.

    Google Scholar 

  74. Konecny L, Pospisil P, Dufek M, et al. Functional impairment in multiple sclerosis. Scr Med Fac Med Univ Brun Masarykianae. 2007;80(5):225–32.

    Google Scholar 

  75. Vigorito C, Giallauria F. Effects of exercise on cardiovascular performance in the elderly. Front Physiol. 2014;5:51.

    Article  PubMed Central  PubMed  Google Scholar 

  76. Hobart J, Freeman J, Thompson A. Kurtzke scales revisited: the application of psychometric methods to clinical intuition. Brain. 2000;123(Pt 5):1027–40.

    Article  PubMed  Google Scholar 

  77. Sharrack B, Hughes RA, Soudain S, et al. The psychometric properties of clinical rating scales used in multiple sclerosis. Brain. 1999;122(Pt 1):141–59.

    Article  PubMed  Google Scholar 

  78. Geidl W, Semrau J, Pfeifer K. Health behaviour change theories: contributions to an ICF-based behavioural exercise therapy for individuals with chronic diseases. Disabil Rehabil. 2014;36(24):2091–100.

    Article  PubMed  Google Scholar 

  79. Heine M, Verschuren O, Kwakkel G. Validity of oxygen uptake efficiency slope in patients with multiple sclerosis. J Rehabil Med. 2014;46(7):656–61.

    Article  PubMed  Google Scholar 

  80. Petruzzello SJ, Motl RW. Acute moderate-intensity cycling exercise is associated with reduced fatigue in persons with multiple sclerosis. Ment Health Phys Act. 2011;4(1):1–4.

    Article  Google Scholar 

  81. Petruzzello SJ, Snook EM, Gliottoni RC, et al. Anxiety and mood changes associated with acute cycling in persons with multiple sclerosis. Anxiety Stress Coping. 2009;22(3):297–307.

    Article  PubMed  Google Scholar 

  82. Kuspinar A, Andersen RE, Teng SY, et al. Predicting exercise capacity through submaximal fitness tests in persons with multiple sclerosis. Arch Phys Med Rehabil. 2010;91(9):1410–7.

    Article  PubMed  Google Scholar 

  83. Skjerbaek AG, Møller AB, Jensen E, et al. Heat sensitive persons with multiple sclerosis are more tolerant to resistance exercise than to endurance exercise. Mult Scler. 2013;19(7):932–40.

    Article  PubMed  Google Scholar 

  84. Møller AB, Bibby BM, Skjerbaek AG, et al. Validity and variability of the 5-repetition sit-to-stand test in patients with multiple sclerosis. Disabil Rehabil. 2012;34(26):2251–8.

    Article  PubMed  Google Scholar 

  85. Gold SM, Schulz KH, Hartmann S, et al. Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. J Neuroimmunol. 2003;138(1–2):99–105.

    Article  CAS  PubMed  Google Scholar 

  86. White AT, Wilson TE, Davis SL, et al. Effect of precooling on physical performance in multiple sclerosis. Mult Scler. 2000;6(3):176–80.

    Article  CAS  PubMed  Google Scholar 

  87. Heesen C, Gold SM, Hartmann S, et al. Endocrine and cytokine responses to standardized physical stress in multiple sclerosis. Brain Behav Immun. 2003;17(6):473–81.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Martin Langeskov-Christensen, Martin Heine, Gert Kwakkel and Ulrik Dalgas have no potential conflicts of interest that are directly relevant to the content of this review. The study was not funded by any external source.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin Langeskov-Christensen.

Additional information

M. Langeskov-Christensen and M. Heine share first authorship on this article. Both authors contributed equally to the paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Langeskov-Christensen, M., Heine, M., Kwakkel, G. et al. Aerobic Capacity in Persons with Multiple Sclerosis: A Systematic Review and Meta-Analysis. Sports Med 45, 905–923 (2015). https://doi.org/10.1007/s40279-015-0307-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40279-015-0307-x

Keywords

Navigation