Additional Files

Mansoubi, M., Coe, S., Cossington, J., Collet, J., Clegg, M., Palace, J., Cavey, A., DeLuca, G. C., Ovington, M., & Dawes, H. (2021). Physical Activity and Fatigue in Multiple Sclerosis: Secondary Outcomes from a Double-blinded Randomized Controlled Trial of Cocoa Flavonoid Drinks. Translational Medicine and Exercise Prescription, 1(1), 53–61. https://doi.org/10.53941/tmep.v1i1.36

Physical Activity and Fatigue in Multiple Sclerosis: Secondary Outcomes from a Double-blinded Randomized Controlled Trial of Cocoa Flavonoid Drinks

Maedeh Mansoubi()1,2, Shelly Coe1,2,3, Jo Cossington1, Johnny Collet1,2, Miriam Clegg4, Jacqueline Palace5, Ana Cavey5, Gabriele C DeLuca5, Martin Ovington1 and Helen Dawes1,2,6 

1Center for Movement, Occupational and Rehabilitation Sciences, Oxford Institute of Nursing, Midwifery and Allied Health Research, Oxford Brookes University, Oxford, United Kingdom

2Oxford Clinical Allied Technology and Trial Services Unit (OxCATTS), Oxford, United Kingdom

3Oxford Brookes Center for Nutrition and Health, Oxford Brookes University, Oxford, United Kingdom

4Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom

5Department of Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

6Oxford Health NHS Foundation Trust, United Kingdom

© The Authors


 

Abstract

Fatigue is a common and pervasive symptom reducing physical activity in people with multiple sclerosis (pwMS). Exercise may reduce fatigue, although evidence to guide optimal prescription is limited. Specifically, supportive evidence for the timing of exercise for fatigue management or the impact of dietary supplements is unavailable. We performed intensive phenotyping of the interrelation of time of day, physical activity levels, and fatigue to evidence exercise prescription in 40 pwMS participating in a six week randomized controlled trial of morning flavonoid intake (n=19) or a control (n=21). Physical activity was measured over seven days by using an accelerometer at baseline, week three and week six. Participants self-reported their fatigue on a 1–10 rating scale at 10 am, 3 pm, and 8 pm daily. Physical activity levels were calculated for 2.5 h before and after fatigue was reported. Generalized estimating equations were used to explore the time of day fatigue profiles, the relationship of physical activity to fatigue, and the effect of morning flavonoids on this relationship. Participants experienced higher fatigue at 8 pm (4.64±2.29) than at 3 pm (4.39±2.28) and 10 am (3.90±2.10) (P<0.001). Higher fatigue was shown to predict subsequent lower physical activity behavior (P=0.015), but physical activity did not predict higher subsequent fatigue (P>0.05). Morning flavonoid cocoa consumption reduced the relationship of fatigue to physical activity (P=0.049) and fatigue to time of the day (P<0.001). Fatigue levels increased during the day and higher fatigue reduced physical activity in pwMS, but physical activity did not increase fatigue. In addition, morning cocoa reduced daytime fatigue and the relationship of fatigue to subsequent physical activity levels. Therefore morning exercise prescription is indicated; in combination with dietary flavonoids, it may optimize exercise and physical activity potential in pwMS.

Trial registration: ISRCTN69897291, https://doi.org/10.1186/ISRCTN69897291

Registration name: A study to determine whether the daily consumption of flavonoid-rich pure cocoa has the potential to reduce fatigue in people with relapsing-remitting multiple sclerosis (RRMS).

Consort Statement: In this study, we adhered to CONSORT guidelines. As this paper is a secondary analysis, we therefore did not repeat some parts in the methods, results, diagrams, or tables that have been published in the first paper authored by Coe et al. 2019.

multiple sclerosis physical activity fatigue flavonoid

References

  1. Browne P, Chandraratna D, Angood C, Tremlett H, Baker C, Taylor BV, et al. Atlas of multiple sclerosis 2013: a growing global problem with widespread inequity. Neurology 2014, 83(11): 1022-24. https://doi.org/10.1212/wnl.0000000000000768
  2. Motl RW, Gosney JL. Effect of exercise training on quality of life in multiple sclerosis: a meta-analysis. Mult Scler 2008, 14: 129-35. https://doi.org/10.1177/1352458507080464
  3. Motl RW, McAuley E, Sandroff BM, Hubbard EA. Descriptive epidemiology of physical activity rates in multiple sclerosis. Acta Neurol Scand 2015, 131(6): 422-25. https://doi.org/10.1111/ane.12352
  4. Newland PK, Lunsford V, Flach A. The interaction of fatigue, physical activity, and health-related quality of life in adults with multiple sclerosis (MS) and cardiovascular disease (CVD). Appl Nurs Res 2017, 33: 49-53. https://doi.org/10.1016/j.apnr.2016.09.001
  5. Dalgas U, Langeskov-Christensen M, Stenager E, Riemenschneider M, Hvid LG. Exercise as medicine in multiple sclerosis-time for a paradigm shift: preventive, symptomatic, and disease-modifying aspects and perspectives. Curr Neurol Neurosci Rep 2019, 19 (11): 88. https://doi.org/10.1007/s11910-019-1002-3
  6. Hategeka C, Traboulsee AL, McMullen K, Lynd LD. Association of unemployment and informal care with stigma in multiple sclerosis. Int Journal MS Care 2019, 21(5): 214-25. https://doi.org/10.7224/1537-2073.2017-108
  7. Kesselring J, Beer S. Symptomatic therapy and neuro rehabilitation in multiple sclerosis. Lancet Neurol 2005, 4 (10): 643-52. https://doi.org/10.1016/S1474-4422(05)70193-9
  8. Stroud NM, Minahan CL. The impact of regular physical activity on fatigue, depression and quality of life in persons with multiple sclerosis. Health Qual Life Outcomes 2009, 7: 68. https://doi.org/10.1186/1477-7525-7-68
  9. Kalron A, Menascu S, Frid L, Aloni R, Achiron A. Physical activity in mild multiple sclerosis: contribution of perceived fatigue, energy cost, and speed of walking. Disabil Rehabil 2019, 8: 1-7. https://doi.org/10.1080/09638288.2018.1519603
  10. Multiple Sclerosis UW Rehabilitation Research. MS Research. http://msrrtc.washington.edu/info/factsheets/fatigue. Accessed Nov 1, 2019
  11. Greeke EE, Chua AS, Healy BC, Rintell DJ, Chitnis T, Glanz BI. Depression and fatigue in patients with multiple sclerosis. J Neurol Sci 2017, 380: 236-41. https://doi.org/10.1016/j.jns.2017.07.047
  12. Moss-Morris R, Harrison AM, Safari R, Norton S, van der Linden ML, Picariello F, et al. Which behavioral and exercise interventions targeting fatigue show the most promise in multiple sclerosis? A systematic review with narrative synthesis and meta-analysis. Behav Res Ther 2019, 137: 103464. https://doi.org/10.1016/j.brat.2019.103464
  13. Coe S, Cossington J, Collett J, Soundy A, Izadi H, Ovington M, et al. A randomized double-blind placebo-controlled feasibility trial of flavonoid-rich cocoa for fatigue in people with relapsing and remitting multiple sclerosis. J Neurol Neurosurg Psychiat 2019, 90(5): 507-13. https://doi.org/10.1136/jnnp-2018-319496
  14. Sathyapalan T, Beckett S, Rigby AS, Mellor D, Atkin S. High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in chronic fatigue syndrome. Nutr J 2010, 9: 55. https://doi.org/10.1186/1475-2891-9-55
  15. González-Garrido JA, García-Sánchez JR, Garrido-Llanos S, Olivares-Corichi IM. An association of cocoa consumption with improved physical fitness and decreased muscle damage and oxidative stress in athletes. J Sports Med Phys Fitness 2017, 57(4): 441-47. https://doi.org/10.23736/S0022-4707.16.06032-1
  16. Decroix L, Soares DD, Meeusen R, Heyman E, Tonoli C. Cocoa flavanol supplementation and exercise: a systematic review. Sports Med 2018, 48(4): 867-92. https://doi.org/10.1007/s40279-017-0849-1
  17. Gladman D, Nash P, Goto H, Birt JA, Lin CY, Orbai AM, Kvien TK. Fatigue numeric rating scale validity, discrimination and responder definition in patients with psoriatic arthritis. RMD Open 2020, 6(1):e000928. https://doi.org/10.1136/rmdopen-2019-000928
  18. Rich C, Geraci M, Griffiths L, Sera F, Dezateux C, Cortina-Borja M. Quality control methods in accelerometer data processing: defining minimum wear time. PLoS One 2013, 8(6): 1-8. https://doi.org/10.1371/journal.pone.0067206
  19. Meredith-Jones K, Williams S, Galland B, Kennedy G, Taylor R. 24 h Accelerometry: impact of sleep-screening methods on estimates of sedentary behaviour and physical activity while awake. J Sport Sci 2015.https://doi.org/10.1080/02640414.2015.1068438. https://doi.org/10.1080/02640414.2015.1068438
  20. Mansoubi M, Pearson N, Biddle SJ, Clemes SA. Using sit-to-stand workstations in offices: is there a compensation effect? Med Sci Sports Exerc 2016, 48(4): 720-25. https://doi.org/10.1249/MSS.0000000000000802
  21. Cohen J. Statistical power analysis for the behavioural sciences. Hillsdale, New Jersey: Lawrence Erlbaum Associates. 1988. https://doi.org/10.1016/0198-9715(90)90050-4
  22. Kratz AL, Fritz NE, Braley TJ, Scott EL, Foxen-Craft E, Murphy SL. Daily temporal associations between physical activity and symptoms in multiple sclerosis. Ann Behav Med 2019, 53(1): 98-108. https://doi.org/10.1093/abm/kay018
  23. Brown DMY, Bray SR. Effects of mental fatigue on exercise intentions and behavior. Ann Behav Med 2019, 53(5): 405-14. https://doi.org/https://doi.org/10.1093/abm/kay052
  24. Khan F, Amatya B, Galea M. Management of fatigue in persons with multiple sclerosis. Front Neurol 2014, 5:177. https://doi.org/10.3389/fneur.2014.00177
  25. Powell DJH, Liossi C, Schlotz W, Moss-Morris R. Tracking daily fatigue fluctuations in multiple sclerosis: ecological momentary assessment provides unique insights. J Behav Med 2017, 40(5): 772-83. https://doi.org/10.1007/s10865-017-9840-4
  26. Chtourou H, Hammouda O, Aloui A, Souissi N. Effect of time-of-day on muscle fatigue: A Review. J Nov Physiother 2013, 3: 160. https://doi.org/10.4172/2165-7025.1000160
  27. Coe S, Axelsson E, Murphy V, Santos M, Collett J, Clegg M, Izadi H, Harrison JM, Buckingham E, Dawes H. Flavonoid rich dark cocoa may improve fatigue in people with multiple sclerosis, yet has no effect on glycaemic response: An exploratory trial. Clin Nutr ESPEN 2017, 21: 20-25. https://doi.org/10.1016/j.clnesp.2017.07.002
  28. Goya L, Martín MÁ, Sarriá B, Ramos S, Mateos R, Bravo L. Effect of cocoa and its flavonoids on biomarkers of inflammation: studies of cell culture, animals and humans. Nutrients 2016, 8: 212. https://doi.org/10.3390/nu8040212
  29. Sorond FA, Lipsitz LA, Hollenberg NK, Fisher ND. Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans. Neuropsychiatr Dis Treat 2008, 4(2): 433-40. https://doi.org/10.2147/NDT.S2310
  30. Scholey AB, French SJ, Morris PJ, Kennedy DO, Milne AL, Haskell CF. Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort. J Psychopharmacol 2010, 24(10): 1505-14. https://doi.org/10.1177/0269881109106923