Improvement of Heart Rate Variability with Benfothiamine and Alpha-Lipoic Acid in Type 2 Diabetic Patients - Pilot Study
DOI:
https://doi.org/10.12970/2311-052X.2014.02.01.9Keywords:
Cardiac autonomic neuropathy, heart rate variability, type 2 diabetes, benfothiamine, alpha-lipoic acidAbstract
According to hypothesis that the lower level of bioactive thiamine, vitamin B1, is partially responsible for microvascular complications in type 2 diabetes patients (T2DM), we investigated whether the supplementation with benfothiamine and alpha-lipoic acid (ALA) could improve cardiac autonomic neuropathy (CAN) in those patients. Heart rate variability (HRV) was used as a tool for the assessment of equilibrium in the activity of the autonomic nervous system (ANS) in the control of heart rate in T2DM patients, without serious co-morbidity. Blood samples for glucose, HbA1c, triglycerides, cholesterol, and HDL-C were obtained before and at the end of treatment. High-frequency ln (HFln), was significantly lower (p< 0.01) and low- frequency/ high frequency ln (LF/HFln) was significantly higher (p<0.01) in T2DM. After 12 weeks of supplementation, very low-frequency ln (VLFln), HFln and LF/HFln indices were changed significantly (p=0.03; p=0.01; p=0.04, respectively), and we concluded that benfothiamine associated with ALA could participate in repairing cardiac autonomic dysfunction in T2DM.
References
Vinik AI, Maser ER, Mitchell DB, Freeman R. Diabetic autonomic neuropathy. Diabetes Care 2003; 26: 1553-79. http://dx.doi.org/10.2337/diacare.26.5.1553
Kahn JK, Zola B, Juni JE, Vinik AI. Decreased exercise heart rate and blood pressure response in diabetic subjects with cardiac autonomic neuropathy. Diabetes Care 1986; 9: 389-94. http://dx.doi.org/10.2337/diacare.9.4.389
Airaksinen KEJ. Silent coronary artery disease in diabetes: a feature of autonomic neuropathy or accelerated atherosclerosis? Diabetologia 2001; 44: 259-66. http://dx.doi.org/10.1007/s001250051609
Veglio M, Chinaglia A, Cavallo-Perin P. QT interval, cardiovascular risk factors and risk of death in diabetes. J Endocrinol Invest 2004; 27: 175-81.
Task Force of the European Society of Cardiology and the North American Society of Pacing Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Circulation 1996; 93: 1043-65. http://dx.doi.org/10.1161/01.CIR.93.5.1043
Gerritsen J, Dekker JM, TenVoorde BJ, et al. Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: the Hoorn Study. Diabetes Care 2001; 24: 1793-8. http://dx.doi.org/10.2337/diacare.24.10.1793
Liao D, Carnethon M, Evans GW, Cascio WE, Heiss G. Lower heart rate variability is associated with the development of coronary heart disease in individuals with diabetes—the atherosclerosis risk in communities (ARIC) study. Diabetes 2002; 51: 3524-31. http://dx.doi.org/10.2337/diabetes.51.12.3524
Rasic-Milutinovic Z, Milicevic D, Milovanovic B, Perunicic-Pekovic G, Pencic B. Do components of metabolic syndrome contribute to cardiac autonomic neuropathy in non-diabetic patients? Saudi Med J 2010; 31: 650-9.
Bender DA. Optimum nutrition: thiamin, biotin and pantothenate. Proc Nutr Soc 1999; 58: 427-33. http://dx.doi.org/10.1017/S0029665199000567
Berrone E. Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose. J Biol Chem 2006; 281: 9307-13. http://dx.doi.org/10.1074/jbc.M600418200
Thornalley PJ. The potential role of thiamine (vitamin B(1)) in diabetic complications. Curr Diabetes Rev 2005; 11: 287-98. http://dx.doi.org/10.2174/157339905774574383
Stracke H, Gaus W, Achenbach U, Federlin K, Bretzel RG. Benfotiamine in Diabetic Polyneuropathy (BENDIP): Results of a Randomised, Double Blind, Placebo-controlled Clinical Study. Exp Clin Endocrinol Diabetes 2008; 116; 600-605. http://dx.doi.org/10.1055/s-2008-1065351
Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 1995; 19: 227-50. http://dx.doi.org/10.1016/0891-5849(95)00017-R
Kunt T, Forst T, Wilhelm A, et al. Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulatin with advanced glycation end products. Clin Sci 1999; 96: 75-82. http://dx.doi.org/10.1042/CS19980224
Zhang WJ, Frei B. Alpha-lipoic acid inhibits TNF-alpha-induced NFkappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 2001; 15: 2423-32. http://dx.doi.org/10.1096/fj.01-0260com
Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care 2003; 26: 770-6. http://dx.doi.org/10.2337/diacare.26.3.770
Ametov AS, Barinov A, Dyck PJ, et al. SYDNEY Trial Study Group. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care 2003; 26: 770-6. http://dx.doi.org/10.2337/diacare.26.3.770
Ziegler D, Ametov A, Barinov A, Dyck PJ, et al. Oral treatment with alphalipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care 2006; 29: 2365-70. http://dx.doi.org/10.2337/dc06-1216
Cameron N, Eaton SE, Cotter MA, Tesfaye S. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia 2001; 44: 1973-88. http://dx.doi.org/10.1007/s001250100001
Nagamatsu M, Nickander KK, Schmelzer JD, et al. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care 1995; 18: 1160-7. http://dx.doi.org/10.2337/diacare.18.8.1160
Saito N, Kimura M, Kuchiba A, Itokawa Y. Blood thiamine levels in outpatients with diabetes mellitus. J Nutr Sci Vitaminol (Tokyo) 1987; 33: 421-30. http://dx.doi.org/10.3177/jnsv.33.421
Obrenovich ME, Monnier VM. Vitamin B1 blocks damage caused by hyperglycemia. Sci Aging Knowledge Environ 2003; 2003: PE6
Stepuro II, Piletskaya TP, Stepuro VI, Maskevich SA. Thiamine oxidative transformations catalyzed by copper ions and ascorbic acid. Biochemistry 1997; 62: 1409-14.
Thornalley PJ, Babaei-Jadidi R, Al Ali H, et al. High prevalence of low plasma thiamine concentration in diabetes linked to marker of vascular disease. Diabetologia 2007; 50: 2164-70. http://dx.doi.org/10.1007/s00125-007-0771-4
Wu S, Ren J. Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha. Neurosci Lett 2006; 394: 158-62. http://dx.doi.org/10.1016/j.neulet.2005.10.022
Yenilmez A, Ozcifci M, Aydin Y, Turgut M, Uzuner K, Erkul A. Protective effect of high-dose thiamine (B1) on rat detrusor contractility in streptozotocin-induced diabetes mellitus. Acta Diabetol 2006; 43: 103-8. http://dx.doi.org/10.1007/s00592-006-0223-5
Stepuro AI, Adamchuk RI, Oparin AYu, and Stepuro II. Thiamine inhibits formation of dityrosine, a specific marker of oxidative injury, in reactions catalyzed by oxoferryl forms of hemoglobin. Biochemistry (Moscow) 2008; 73: 1031-41. http://dx.doi.org/10.1134/S0006297908090113
Maser RE, Mitchell BD, Vinik AI, Freeman R. The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care 2003; 26: 1895-901. http://dx.doi.org/10.2337/diacare.26.6.1895
DCCT Research Group: The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT). Diabetologia 1998; 41: 416-23. http://dx.doi.org/10.1007/s001250050924
Gaede P, Vedel P, Larsen N, Jensen GVH, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003; 348: 383-93. http://dx.doi.org/10.1056/NEJMoa021778
