The effect of physical activity on total homocysteine concentrations and cardiovascular risk in older Brazilian adults with type 2 diabetes


A low level of physical activity has a potential association with high levels of homocysteine, which implies an increased chance of older adults with type 2 diabetes mellitus developing cardiovascular disease (CVD). However, the effects of physical activity on homocysteine levels have been poorly explored in the literature. Therefore, this study compared homocysteine levels and cardiovascular risk among physically active and inactive older women with type 2 diabetes mellitus. Fifty-nine women with type 2 diabetes mellitus, between 60 and 91 years old, were evaluated. The level of physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) long version to identify active and inactive older women. Blood samples were collected and anthropometric, body composition, and blood pressure measurements were performed to determine homocysteine levels and cardiovascular risk. The results demonstrated that active older women with type 2 diabetes mellitus have lower homocysteine values (F = 17.79, p < 0.001, ηp2 = 0.238), cardiovascular risk scores (F = 15.84, p = p < 0.001, ηp2 = 0.217), and waist circumferences (F = 2.95, p = 0.013, ηp2 = 0.049) when compared with inactive older women. It was concluded that there was a difference in the levels of homocysteine, cardiovascular risk, and waist circumference between active and inactive older women with type 2 diabetes. Active older women are less likely to have cardiovascular risk than inactive older women.

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Fig. 1
Fig. 2



Cardiovascular disease


Non-communicable diseases


International physical activity questionnaire


Informed consent form


High-density lipoprotein


Low-density lipoprotein


Very-low-density lipoprotein


Ethylenediaminetetraacetic acid


Glycated hemoglobin


High-performance liquid chromatography


Statistical Package for the Social Sciences


Body mass index


Physical activity of moderate to vigorous intensity


  1. 1.

    Chadt A, Al-Hasani H. Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease. Pflugers Arch. 2020;472(9):1273–98.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018;17(1):83.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Collaborators GBDCoD. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2017;390(10100):1151–210.

    Article  Google Scholar 

  4. 4.

    Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr Physiol. 2012;2(2):1143–211.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Booth FW, Roberts CK, Thyfault JP, Ruegsegger GN, Toedebusch RG. Role of inactivity in chronic diseases: evolutionary insight and pathophysiological mechanisms. Physiol Rev. 2017;97(4):1351–402.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020;54(24):1451–62.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Jefferis BJ, Sartini C, Lee IM, Choi M, Amuzu A, Gutierrez C, et al. Adherence to physical activity guidelines in older adults, using objectively measured physical activity in a population-based study. BMC Public Health. 2014;14:382.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Ortlieb S, Gorzelniak L, Nowak D, Strobl R, Grill E, Thorand B, et al. Associations between multiple accelerometry-assessed physical activity parameters and selected health outcomes in elderly people--results from the KORA-age study. PLoS One. 2014;9(11):e111206.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Dos Santos CES, Manta SW, Maximiano GP, Confortin SC, Benedetti TRB, d'Orsi E, et al. Accelerometer-measured physical activity and sedentary behavior: a cross-sectional study of Brazilian older adults. J Phys Act Health. 2018;15(11):811–8.

  10. 10.

    Ribeiro A, Verlengia R, de Oliveira MRM, Oliveira MVA, Pellegrinotti IL, Crisp AH. Compliance of the physical activity guidelines accumulated in bouts >/=10 min and Nonbouts and its association with body composition and physical function: a cross-sectional study in Brazilian older adults. J Aging Phys Act. 2020; 22:1-8.

  11. 11.

    Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT. Lancet Physical Activity Series Working Group. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012;380(9838):219–29.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    United Nations. Department of Economic and Social Affairs, population division. World population prospects: the 2015 revision. New York: United Nations; 2015.

    Google Scholar 

  13. 13.

    de Rezende LF, Rabacow FM, Viscondi JY, Luiz Odo C, Matsudo VK, Lee IM. Effect of physical inactivity on major noncommunicable diseases and life expectancy in Brazil. J Phys Act Health. 2015;12(3):299–306.

    Article  PubMed  Google Scholar 

  14. 14.

    Okura T, Rankinen T, Gagnon J, Lussier-Cacan S, Davignon J, Leon AS, et al. Effect of regular exercise on homocysteine concentrations: the HERITAGE family study. Eur J Appl Physiol. 2006;98(4):394–401.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Silva ASMM. Effects of physical activity and training programs on plasma homocysteine levels: a systematic review. Amino Acids. 2014;46(8):1795–804.

    CAS  Article  Google Scholar 

  16. 16.

    Han L, Liu Y, Wang C, Tang L, Feng X, Astell-Burt T, et al. Determinants of hyperhomocysteinemia in healthy and hypertensive subjects: a population-based study and systematic review. Clin Nutr. 2017;36(5):1215–30.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Neves LBMD, Lopes AC. Homocisteína. J Bras Patol Med Lab. 2004;40:311–20.

    CAS  Article  Google Scholar 

  18. 18.

    Rehman T, Shabbir MA, Inam-Ur-Raheem M, Manzoor MF, Ahmad N, Liu ZW, et al. Cysteine and homocysteine as biomarker of various diseases. Food Sci Nutr. 2020;8(9):4696–707.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Muniz MT, Siqueira ER, Fonseca RA, D'Almeida V, Hotta JK, dos Santos JE, et al. Evaluation of MTHFR C677T gene polymorphism and homocysteine level in coronary atherosclerotic disease. Arq Bras Endocrinol Metabol. 2006;50(6):1059–65.

    Article  PubMed  Google Scholar 

  20. 20.

    Wolfgang HOR, Jouma M. Hyperhomocysteinemia and vitamin B-12 deficiency are more striking in Syrians than in Germans - causes and implications. Atherosclerosis. 2003;166(1):143–50.

    Article  Google Scholar 

  21. 21.

    Anderson JL, Muhlestein JB, Horne BD, Carlquist JF, Bair TL, Madsen TE, et al. Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease. Circulation. 2000;102(11):1227–32.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Fan R, Zhang A, Zhong F. Association between Homocysteine levels and all-cause mortality: a dose-response meta-analysis of prospective studies. Sci Rep. 2017;7(1):4769.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Alomari MA, Khabour OF, Gharaibeh MY, Qhatan RA. Effect of physical activity on levels of homocysteine, folate, and vitamin B12 in the elderly. Phys Sportsmed. 2016;44(1):68–73.

    Article  PubMed  Google Scholar 

  24. 24.

    Benedetti TM, GZ, de Barros MVG. Aplicação do questionário internacional de atividades físicas para avaliação do nível de atividades física de mulheres idosas: Validade concorrente e reprodutibilidade teste-reteste. Rev Bras Ciênc Mov. 2008;12(1):25–34.

    Google Scholar 

  25. 25.

    Ichinose S, Nakamura M, Maeda M, Ikeda R, Wada M, Nakazato M, et al. A validated HPLC-fluorescence method with a semi-micro column for routine determination of homocysteine, cysteine and cysteamine, and the relation between the thiol derivatives in normal human plasma. Biomed Chromatogr. 2009;23(9):935–9.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Ferin R, Pavao ML, Baptista J. Methodology for a rapid and simultaneous determination of total cysteine, homocysteine, cysteinylglycine and glutathione in plasma by isocratic RP-HPLC. J Chromatogr B Analyt Technol Biomed Life Sci. 2012;911:15–20.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Sawula W, Banecka-Majkutewicz Z, Kadzinski L, Jakobkiewicz-Banecka J, Wegrzyn G, Nyka W, et al. Improved HPLC method for total plasma homocysteine detection and quantification. Acta Biochim Pol. 2008;55(1):119–25.

    CAS  Article  Google Scholar 

  28. 28.

    Vincent KR, Braith RW, Bottiglieri T, Vincent HK, Lowenthal DT. Homocysteine and lipoprotein levels following resistance training in older adults. Prev Cardiol. 2003;6(4):197–203.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Chen SM, Shen FC, Chen JF, Chang WD, Chang NJ. Effects of Resistance Exercise on Glycated Hemoglobin and Functional Performance in Older Patients with Comorbid Diabetes Mellitus and Knee Osteoarthritis: A Randomized Trial. Int J Environ Res Public Health. 2019;17(1):224.

    CAS  Article  PubMed Central  Google Scholar 

  30. 30.

    Assmann G, Jabs HU, Kohnert U, Nolte W, Schriewer H. LDL-cholesterol determination in blood serum following precipitation of LDL with polyvinylsulfate. Clin Chim Acta. 1984;140(1):77–83.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Martins RA, Verissimo MT, Coelho e Silva MJ, Cumming SP, Teixeira AM. Effects of aerobic and strength-based training on metabolic health indicators in older adults. Lipids Health Dis. 2010;9:76.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Gabriel R, Saiz C, Susi R, Alonso M, Vega S, Lopez I, et al. Epidemiology of lipid profile of the Spanish elderly population: the EPICARDIAN study. Med Clin (Barc). 2004;122(16):605–9.

    Article  Google Scholar 

  33. 33.

    D'Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham heart study. Circulation. 2008;117(6):743–53.

    Article  PubMed  Google Scholar 

  34. 34.

    Stewart A, Marfell-Jones M, Olds T, Ridder H. International standards for anthropometric assessment. International Society for the Advancement of Kinanthropometry: Lower Hutt; 2011.

    Google Scholar 

  35. 35.

    Orsatti FL, Nahas EA, Nahas-Neto J, Maesta N, Orsatti CL, Fernandes CE. Effects of resistance training and soy isoflavone on body composition in postmenopausal women. Obstet Gynecol Int. 2010;2010:156037.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Christos Z, Tokmakidis SP, Volaklis KA, Kotsa K, Touvra AM, et al. Lipoprotein proWle, glycemic control and physical Wtness after strength and aerobic training in post-menopausal women with type 2 diabetes. Eur J Appl Physiol. 2009;106:901–7.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Durnin JV, Womersley J. Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years. Br J Nutr. 1974;32(1):77–97.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Rech C, Lima LRA, Cordeiro BA, Petroski EL, Vasconcelos FAG. Validity of anthropometric equations for estimating body fat in the elderly in southern Brazil. Braz J Cineanthropometry Hum Perform. 2010;12(1):1–7.

    Article  Google Scholar 

  39. 39.

    Sink C, Mvududu NH. Statistical power, sampling, and effect sizes. Couns Outcome Res Eval. 2010;1(2):1–18.

    Article  Google Scholar 

  40. 40.

    Buckner SL, Loenneke JP, Loprinzi PD. Single and combined associations of accelerometer-assessed physical activity and muscle-strengthening activities on plasma homocysteine in a national sample. Clin Physiol Funct Imaging. 2017;37(6):669–74.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Hellgren M, Melander A, Ostgren CJ, Rastam L, Lindblad U. Inverse association between plasma homocysteine, sulphonylurea exposure and physical activity: a community-based sample of type 2 diabetes patients in the Skaraborg hypertension and diabetes project. Diabetes Obes Metab. 2005;7(4):421–9.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Unt E, Zilmer K, Magi A, Kullisaar T, Kairane C, Zilmer M. Homocysteine status in former top-level male athletes: possible effect of physical activity and physical fitness. Scand J Med Sci Sports. 2008;18(3):360–6.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Loprinzi PD, Cardinal BJ. Interrelationships among physical activity, depression, homocysteine, and metabolic syndrome with special considerations by sex. Prev Med. 2012;54(6):388–92.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Venâncio L, Burini RC, Yoshida WB. Dietary treatment of hyperhomocysteinemia in peripheral arterial disease. J Vasc Bras. 2010;9(1):28–41.

    Article  Google Scholar 

  45. 45.

    Norlund L, Grubb A, Fex G, Leksell H, Nilsson JE, Schenck H, et al. The increase of plasma homocysteine concentrations with age is partly due to the deterioration of renal function as determined by plasma cystatin C. Clin Chem Lab Med. 1998;36(3):175–8.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Brosnan JT, Jacobs RL, Stead LM, Brosnan ME. Methylation demand: a key determinant of homocysteine metabolism. Acta Biochim Pol. 2004;51(2):405–13.

    CAS  Article  Google Scholar 

  47. 47.

    Malinow MR, Duell PB, Williams MA, Kruger WD, Evans AA, Anderson PH, et al. Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations. Lipids. 2001;36 Suppl:S27–32.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Chen KJ, Pan WH, Yang FL, Wei IL, Shaw NS, Lin BF. Association of B vitamins status and homocysteine levels in elderly Taiwanese. Asia Pac J Clin Nutr. 2005;14(3):250–5.

    CAS  PubMed  Google Scholar 

  49. 49.

    Dankner RGG, Farber N, Novikov I, Segev S, Sela BA. Cardiorespiratory fitness and plasma homocysteine levels in adult males and females. Isr Med Assoc J. 2009;11(2):78–82.

    PubMed  Google Scholar 

  50. 50.

    Biswas A, Oh PI, Faulkner GE, Bajaj RR, Silver MA, Mitchell MS, et al. Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis. Ann Intern Med. 2015;162(2):123–32.

    Article  PubMed  Google Scholar 

  51. 51.

    Baker PR, Costello JT, Dobbins M, Waters EB. The benefits and challenges of conducting an overview of systematic reviews in public health: a focus on physical activity. J Public Health (Oxf). 2014;36(3):517–21.

    Article  Google Scholar 

  52. 52.

    Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke Statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–360.

    Article  PubMed  Google Scholar 

  53. 53.

    Sattelmair J, Pertman J, Ding EL, Kohl HW 3rd, Haskell W, Lee IM. Dose response between physical activity and risk of coronary heart disease: a meta-analysis. Circulation. 2011;124(7):789–95.

    Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Woodcock J, Franco OH, Orsini N, Roberts I. Non-vigorous physical activity and all-cause mortality: systematic review and meta-analysis of cohort studies. Int J Epidemiol. 2011;40(1):121–38.

    Article  PubMed  Google Scholar 

  55. 55.

    Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Eur Heart J. 2007;28(7):850–6.

    Article  PubMed  Google Scholar 

  56. 56.

    Han TS, Tajar A, Lean ME. Obesity and weight management in the elderly. Br Med Bull. 2011;97:169–96.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Figueiro TH, Arins GCB, Santos C, Cembranel F, Medeiros PA, d'Orsi E, et al. Association of objectively measured sedentary behavior and physical activity with cardiometabolic risk markers in older adults. PLoS One. 2019;14(1):e0210861.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Loureiro NSL, Amaral TLM, Amaral CA, Monteiro GTR, Vasconcellos MTL, Bortolini MJS. Relationship between anthropometric indicators and risk factors for cardiovascular disease in adults and older adults of Rio Branco, Acre. Rev Saude Publica. 2020;54:24.

    Article  PubMed  Google Scholar 

  59. 59.

    Del Pozo-Cruz J, Garcia-Hermoso A, Alfonso-Rosa RM, Alvarez-Barbosa F, Owen N, Chastin S, et al. Replacing sedentary time: meta-analysis of objective-assessment studies. Am J Prev Med. 2018;55(3):395–402.

    Article  PubMed  Google Scholar 

  60. 60.

    Carbone S, Del Buono MG, Ozemek C, Lavie CJ. Obesity, risk of diabetes and role of physical activity, exercise training and cardiorespiratory fitness. Prog Cardiovasc Dis. 2019;62(4):327–33.

    Article  PubMed  Google Scholar 

  61. 61.

    Silva ASE, Lacerda FV, da Mota MPG. Effect of strength training on plasma levels of Homocysteine in patients with type 2 diabetes. Int J Prev Med. 2019;10:80.

    Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Silva ASLF, Mota MPG. Effect of aerobic training on homocysteine levels in type 2 diabetic individuals. Rev Bras Med Esporte. 2015;21(4):275–8.

    Article  Google Scholar 

  63. 63.

    Silva A, Lacerda FV, da Mota MPG. The effect of aerobic vs. resistance training on plasma homocysteine in individuals with type 2 diabetes. J Diabetes Metab Disord. 2020;19(2):1003–9.

    CAS  Article  Google Scholar 

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The authors would like to thank the volunteers, collaborators of the research, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES) for the financial support through scholarships—Finance Code 001.

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de Oliveira, J.J., e Silva, A.d.S., Ribeiro, A.G.S.V. et al. The effect of physical activity on total homocysteine concentrations and cardiovascular risk in older Brazilian adults with type 2 diabetes. J Diabetes Metab Disord (2021).

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  • Atherosclerosis
  • Cardiac risk
  • Cardiovascular diseases
  • Diabetes
  • Homocysteine
  • Physical inactivity