Aspartame and Platelets in Type II Diabetic Patients



Abstract Views
634

Downloads
701

Citations

Share

##plugins.themes.bootstrap3.article.sidebar##

Submitted Apr 2, 2022
Published May 17, 2022
10.24018/ejmed.2022.4.3.1306

Abstract viewed = 634 times

Table of Contents

##plugins.themes.bootstrap3.article.main##

Background: For type II diabetes (T2D) subjects to better regulate carbohydrate consumption and manage blood glucose levels, a non-nutritive sweetener (aspartame) is prescribed as an alternative to natural sugar. Previous studies show that there was a 68% rise in the probability of aspartame consumers developing T2D compared with non-consumers. In diabetes and inflammation, deformed red blood cells (RBCs) and atypical fibrin fibre formation or an altered fibrin structure are especially prevalent.

Objective: The aim of this study was to investigate, in subjects with T2D taking aspartame, clot viscoelasticity and platelet structure.

Methodology: Blood was drawn from 12 T2D subjects from the diabetic clinic at the Steve Biko Academic Hospital, South Africa. Blood was used to perform a full blood count, thromboelastography (TEG) and scanning electron microscopy (SEM).

Results: SEM showed increased platelet activation and abnormal TEG parameters in T2D consuming aspartame.

Conclusion: A hypercoagulable state can increase the risk of thromboembolic complications and an increased incidence of vascular disease. This knowledge may be used to build awareness among consumers of aspartame.

Keywords: Aspartame, blood, coagulation, diabetes, platelets

Downloads

Download data is not yet available.

References

  1. Roberts HJ. Reactions attributed to aspartame-containing products: 551 cases. J Appl Nutr. 1988; 40: 85-94.
     Google Scholar
  2. Stegink LD, Filer LJ Jr, Bell EF, Ziegler EE, Tephly TR. Effect of repeated ingestion of aspartame-sweetened beverage on plasma amino acid, blood methanol, and blood formate concentrations in normal adults. Metabolism. 1989; 38:357-63.
    DOI  |   Google Scholar
  3. Butchko HH, Stargel WW. Aspartame: scientific evaluation in the postmarketing period. Regul Toxicol Pharmacol. 2001; 34:221-33.
    DOI  |   Google Scholar
  4. American Diabetes Association. Standards of medical care in diabetes-2006. Diabetes Care. 2006; 29 Suppl 1:S4-42.
    DOI  |   Google Scholar
  5. Gougeon R, Spidel M, Lee K, Field CJ: Canadian Diabetes Association National Nutrition Committee Technical Review: Non-nutritive intense sweeteners in diabetes management. Can J Diabetes, 2004; 28: 385-399.
     Google Scholar
  6. Lau DCW, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E, et al. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. CMAJ. 2007; 176(8):S1-13.
    DOI  |   Google Scholar
  7. Sandrou DK, Arvanitoyannis IS. Low-fat/calorie foods: current state and perspectives. Crit Rev Food Sci Nutr. 2000; 40(5):427-47.
    DOI  |   Google Scholar
  8. Mortensen A. Sweeteners permitted in the European Union, Safety aspects. Scandinavian Journal of Food and Nutrition. 2006; 50:104-16.
    DOI  |   Google Scholar
  9. Fagherazzi G, Vilier A, Saes Sartorelli D, Lajous M, Balkau B, Clavel-Chapelon F. Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l’Education Nationale-European Prospective Investigation into Cancer and Nutrition cohort. Am J Clin Nutr. 2013; 97(3):517-23.
    DOI  |   Google Scholar
  10. Pretorius E, Bester J, Vermeulen N, Alummoottil S, Soma P, Buys AV, et al. Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics. Cardiovasc Diabetol. 2015; 14(1):30.
    DOI  |   Google Scholar
  11. Bochenek M, Zalewski J, Sadowski J, Undas A. Type 2 diabetes as a modifier of fibrin clot properties in patients with coronary artery disease. J Thromb Thrombolysis. 2013; 35(2):264-70.
    DOI  |   Google Scholar
  12. Buys AV, Van Rooy M-J, Soma P, Van Papendorp D, Lipinski B, Pretorius E. Changes in red blood cell membrane structure in type 2 diabetes: a scanning electron and atomic force microscopy study. Cardiovasc Diabetol. 2013; 12(1):25.
    DOI  |   Google Scholar
  13. Dunn EJ, Philippou H, Ariëns RAS, Grant PJ. Molecular mechanisms involved in the resistance of fibrin to clot lysis by plasmin in subjects with type 2 diabetes mellitus. Diabetologia. 2006; 49(5):1071-80.
    DOI  |   Google Scholar
  14. Pretorius E, Oberholzer HM, van der Spuy WJ, Swanepoel AC, Soma P. Qualitative scanning electron microscopy analysis of fibrin networks and platelet abnormalities in diabetes. Blood Coagul Fibrinolysis. 2011; 22(6):463-7.
    DOI  |   Google Scholar
  15. Swanepoel AC, Nielsen VG, Pretorius E. Viscoelasticity and ultrastructure in coagulation and inflammation: Two diverse techniques, one conclusion. Inflammation. 2015; 38(4):1707-26.
    DOI  |   Google Scholar
  16. Bester J, Pretorius E. Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Sci Rep. 2016; 6(1).
    DOI  |   Google Scholar
  17. Borsey DQ, Prowse CV, Gray RS, Dawes J, James K, Elton RA, et al. Platelet and coagulation factors in proliferative diabetic retinopathy. J Clin Pathol. 1984; 37(6):659-64.
    DOI  |   Google Scholar
  18. Carr ME. Diabetes mellitus: a hypercoagulable state. J Diabetes Complications. 2001; 15(1):44-54.
    DOI  |   Google Scholar
  19. Roberts HJ. Aspartame-induced thrombocytopenia. South Med J. 2007; 100(5):543.
    DOI  |   Google Scholar
  20. Frade LG, De La Calle H, Alava I, Navarro J, Creighton L, Gaffney P. Diabetes mellitus as a hypercoagulable state: its relationship with fibrin fragments and vascular damage. Thrombosis research. 1987; 47:533-40.
    DOI  |   Google Scholar
  21. Hughes A, Mcverry B, Wilkinson L, Goldstone A, Lewis D, Bloom A. Diabetes, a hypercoagulable state? Haemostatic variables in newly diagnosed type 2 diabetic patients. Acta haematologica. 1983; 254-9.
    DOI  |   Google Scholar
  22. Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL. Platelet dysfunction in type 2 diabetes. Diabetes Care. 2001;24(8):1476-85.
    DOI  |   Google Scholar
  23. Pretorius E, Humphries P. Ultrastructural changes to rabbit fibrin and platelets due to aspartame. Ultrastruct Pathol. 2007; 31(2):77-83.
    DOI  |   Google Scholar
  24. Page MJ, Bester J, Pretorius E. Interleukin-12 and its procoagulant effect on erythrocytes, platelets and fibrin (ogen): the lesser known side of inflammation. British journal of haematology. 2018; 180:110-7.
    DOI  |   Google Scholar
  25. Marsh HC Jr, Meinwald YC, Lee S, Scheraga HA. Mechanism of action of thrombin on fibrinogen. Direct evidence for the involvement of phenylalanine at position P9. Biochemistry. 1982; 21(24):6167-71.
    DOI  |   Google Scholar
  26. Marsh HC Jr, Meinwald YC, Thannhauser TW, Scheraga HA. Mechanism of action of thrombin on fibrinogen. Kinetic evidence for involvement of aspartic acid at position P10. Biochemistry. 1983; 22(18):4170-4.
    DOI  |   Google Scholar
  27. Meinwald Y, Martinelli R, Van Nispen J, Scheraga H. Mechanism of action of thrombin on fibrinogen. Size of the A. alpha. fibrinogen-like peptide that contacts the active site of thrombin. Biochemistry. 1980; 19:3820-5.
    DOI  |   Google Scholar
  28. Scheffler JE, Berliner LJ. Aspartame and aspartame derivatives effect human thrombin catalytic activity. Biophys Chem. 2004; 112(2-3):285-91.
    DOI  |   Google Scholar
  29. Barradas MA, Gill DS, Fonseca VA, Mikhailidis DP, Dandona P. Intraplatelet serotonin in patients with diabetes mellitus and peripheral vascular disease. Eur J Clin Invest. 1988; 18(4):399-404.
    DOI  |   Google Scholar
  30. Mohammad-Zadeh LF, Moses L, Gwaltney-Brant SM. Serotonin: a review. J Vet Pharmacol Ther. 2008; 31(3):187-99.
    DOI  |   Google Scholar
  31. Stahl SM. The human platelet: a diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders. Archives of General Psychiatry. 1977; 34:509-16.
    DOI  |   Google Scholar
  32. Stahl SM, Meltzer HY. A kinetic and pharmacologic analysis of 5-hydroxytryptamine transport by human platelets and platelet storage granules: comparison with central serotonergic neurons. J Pharmacol Exp Ther. 1978; 205(1):118-32.
     Google Scholar
  33. Humphries P, Pretorius E, Naudé H. Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr. 2008; 62(4):451-62.
    DOI  |   Google Scholar
  34. Erem C, Nuhoglu I, Yilmaz M, Kocak M, Demirel A, Ucuncu O, et al. Blood coagulation and fibrinolysis in patients with Cushing’s syndrome: Increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels. J Endocrinol Invest. 2009; 32(2):169-74.
    DOI  |   Google Scholar
  35. Känel R, Mills PJ, Fainman C, Dimsdale JE. Effects of psychological stress and psychiatric disorders on blood coagulation and fibrinolysis: a biobehavioral pathway to coronary artery disease? Psychosomatic Medicine. 2001; 63:531-44.
    DOI  |   Google Scholar
  36. Van Zaane B, Nur E, Squizzato A, Dekkers OM, Twickler MTB, Fliers E, et al. Hypercoagulable state in Cushing’s syndrome: a systematic review. J Clin Endocrinol Metab. 2009; 94(8):2743-50.
    DOI  |   Google Scholar
  37. Choudhary AK, Devi RS. Imbalance of the oxidant-antioxidant status by aspartame in the organs of immune system of Wistar albino rats. African Journal of Pharmacy and Pharmacology. 2014; 8:220-30.
    DOI  |   Google Scholar
  38. Iyyaswamy A, Rathinasamy S. Effect of chronic exposure to aspartame on oxidative stress in brain discrete regions of albino rats. J Biosci. 2012; 37(4):679-88.
    DOI  |   Google Scholar
  39. Chaouloff F. Physiopharmacological interactions between stress hormones and central serotonergic systems. Brain Res Rev. 1993; 18(1):1-32.
    DOI  |   Google Scholar
  40. Pardridge WM, Mietus LJ. Transport of steroid hormones through the rat blood-brain barrier: primary role of albumin-bound hormone. Journal of Clinical Investigation. 1979; 64.
    DOI  |   Google Scholar
  41. Keaney JF Jr, Loscalzo J. Diabetes, oxidative stress, and platelet activation. Circulation. 1999; 99(2):189-91.
    DOI  |   Google Scholar
  42. Agamy N. Effects of the natural sweetener (stevia) and the artificial sweetener (aspartame) on some biochemical parameters in normal and alloxan-induced diabetic rats. N Biotechnol. 2009; 25:S12.
    DOI  |   Google Scholar
  43. Arbind K, Devi R, Sundareswaran L. Role of antioxidant enzymes in oxidative stress and immune response evaluation of aspartame in blood cells of wistar albino rats. International Food Research Journal. 2014; 21:2263-72.
     Google Scholar
  44. Choudhary AK, Devi RS. Serum biochemical responses under oxidative stress of aspartame in wistar albino rats. Asian Pac J Trop Dis. 2014; 4:S403-10.
    DOI  |   Google Scholar
  45. Tsakiris S, Giannoulia-Karantana A, Simintzi I, Schulpis KH. The effect of aspartame metabolites on human erythrocyte membrane acetylcholinesterase activity. Pharmacol Res. 2006; 53(1):1-5.
    DOI  |   Google Scholar
  46. Choudhary AK, Pretorius E. Revisiting the safety of aspartame. Nutr Rev. 2017; 75(9):718-30.
    DOI  |   Google Scholar
  47. Dunn EJ, Ariëns RAS, Grant PJ. The influence of type 2 diabetes on fibrin structure and function. Diabetologia. 2005; 48(6):1198-206.
    DOI  |   Google Scholar