Exp Clin Endocrinol Diabetes 2010; 118(9): 625-629
DOI: 10.1055/s-0029-1237702
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Alpha-lipoic Acid Improves Endothelial Dysfunction in Patients with Subclinical Hypothyroidism

Xiang GD1 , Pu JH1 , Sun HL1 , Zhao LS1
  • 1Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Hubei Province, P. R. China
Further Information

Publication History

received 22.04.2009 first decision 25.06.2009

accepted 30.07.2009

Publication Date:
16 February 2010 (online)

Abstract

Objective: Many studies showed that impairment of flow-mediated endothelium-dependent arterial dilation (FMD) exists in patients with subclinical hypothyroidism (sHT). The crucial mechanism of this endothelial dysfunction remain unclear. We hypothesized that oxidative stress may be partially responsible for the impairment in FMD in patients with sHT. Thus, the present study was designed to assess whether the antioxidant alpha-lipoic acid can improve endothelial dysfunction in patients with sHT.

Patients and methods: Forty women with newly diagnosed sHT and 18 healthy women with euthyroid status were enrolled. Patients were randomized into 2 groups to receive no treatment (n=20), alpha-lipoic acid (n=20) for 3 weeks. We measured the FMD at baseline and after 3 weeks.

Results: FMD in alpha-lipoic acid and no-treatment group were 3.92% and 4.02%, respectively, which were significantly lower than that in controls (5.64%) (p<0.001). After 3 weeks treatment, compared with before treatment in sHT patients, plasma thiobarbituric acid reactive substances (TBARS) levels decreased significantly in alpha-lipoic acid group (p<0.001), and remain unchanged in no-treatment group (p>0.05). FMD improved markedly (4.82%) in alpha-lipoic acid group (p<0.01), and remain unchanged in no-treatment group (p>0.05). The absolute changes in FMD showed significant negative correlation with the changes in TBARS (r=−0.773, p<0.001).

Conclusion: Our data showed that sHT patients exists impaired endothelial function, and antioxidant alpha-lipoic acid can improve endothelial function, through decrease of oxygen- derived free radicals.

References

  • 1 Kvetny J, Heldgaard PE, Bladbjerg RM. et al . Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years.  Clin Endocrinol (Oxf). 2004;  61 232-238
  • 2 Imaizumi M, Akahoshi M, Ichimaru S. et al . Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism.  J Clin Endocrinol Metab. 2004;  89 3365-3370
  • 3 Xiang GD, Sun HL, Cheng ZS. et al . Changes in plasma concentration of osteoprotegerin before and after levothyroxine replacement therapy in hypothyroid patients.  J Clin Endocrinol Metab. 2005;  90 5765-5768
  • 4 Taddei S, Caraccio N, Virdis A. et al . Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy.  J Clin Endocrinol Metab. 2003;  88 3731-3737
  • 5 Förstermann U. Oxidative stress in vascular disease: Causes, defense mechanisms and potential therapies.  Nat Clin Pract Cardiovasc Med. 2008;  5 338-349
  • 6 Nedelikovic ZS, Gokce N, Loscalzo J. Mechanisms of oxidative stress and vascular dysfunction.  Postgrad Med J. 2003;  79 195-199
  • 7 Taddei S, Caraccio N, Virdis A. et al . Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto’s thyroiditis.  J Clin Endocrinol Metab. 2006;  91 5076-5082
  • 8 Kawano H, Motoyama T, Hirashima O. et al . Hyperglycemia rapidly suppresses flow- mediated endothelium-dependent vasodilation of brachial artery.  JACC. 1999;  34 146-154
  • 9 Motoyama T, Kawano H, Kugiyama K. et al . Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina.  J Am Coll Cardiol. 1998;  32 1672-1679
  • 10 Buege JA, Aust SD. Microsomal lipid peroxidation.  Methods Enzymol. 1987;  52 302-310
  • 11 Xiang GD, Wu YH. Apolipoprotein e4 allele and endothelium-dependent arterial dilation in type 2 diabetes mellitus without angiopathy.  Diabetologia. 2003;  46 514-519
  • 12 Xiang GD, Wang YL. Regular aerobic exercise training improves endothelium-dependent artery dilation in patients with impaired fasting glucose.  Diabetes Care. 2004;  27 801-802
  • 13 Xiang GD, Xu L, Zhao LS. et al . The relationship between plasma osteoprotegerin and endothelium-dependent arterial dilation in type 2 diabetes.  Diabetes. 2006;  55 2126-2131
  • 14 Hak AE, Pols HA, Visser TJ. et al . Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women : the Rotterdam Study.  Ann Intern Med. 2003;  139 866-867
  • 15 Duman D, Sahin S, Esertas K. et al . Simvastatin improves endothelial function in patients with subclinical hypothyroidism.  Heart Vessels. 2007;  22 88-93
  • 16 Ferri C, Croce G, Cofini. et al . C-reactive protein: interaction with the vascular endothelium and possible role in human atherosclerosis.  Curr Pharm Des. 2007;  13 1631-1645
  • 17 Xiang GD, He YS, Zhao LS. et al . Impairment of endothelium-dependent arterial dilation in Hashimoto’s thyroiditis patients with euthyroidism.  Clin Endocrinol (Oxf). 2006;  64 698-702
  • 18 Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology.  Pharmacol Rev. 1991;  43 109-142
  • 19 Gryglewski RJ, Palmer RMJ, Moncada S. Superoxide anion is involved in the breakdown of endothelium-dependent vascular relaxing factor.  Nature (Lond). 1986;  320 454-456
  • 20 Rubanyi GM, Vanhoutte PM. Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle.  Am J Physiol. 1986;  250 H815-H821
  • 21 Xiang GD, Sun HL, Zhao LS. et al . The antioxidant alpha-lipoic acid improves endothelial dysfunction induced by acute hyperglycemia during OGTT in impaired glucose tolerance.  Clin Endocrinol (Oxf). 2008;  68 716-723
  • 22 Paolisso G, Tagliamonte MR, Barbieri M. et al . Chronic vitamin E administration improves brachial reactivity and increases intracellular magnesium concentration in type lldiabetic patients.  J Clin Endocrinol Metab. 2000;  85 109-115
  • 23 Title LM, Cummings PM, Giddens K. et al . Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamin C and E.  J Am Coll Cardiol. 2000;  36 2185-2191
  • 24 Overvad K, Diamant B, Holm L. et al . Coenzyme Q10 in health and disease.  Eur J Clin Nutr. 1999;  53 764-770
  • 25 Thomas SR, Witting PK, Stocker R. A role for reduced coenzyme Q in atherosclerosis?.  Biofactors. 1999;  9 207-224
  • 26 Watts GF, Playford DA, Croft KD. et al . Coenzyme Q10 improves endothelial dysfunction of the brachial artery in type II diabetes mellitus.  Diabetologia. 2002;  45 420-426
  • 27 Reed LJ. From lipoic acid to multi-enzyme complexes.  Protein Sci. 1998;  7 220-224
  • 28 Ziegler D, Nowak H, Kempler P. et al . Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis.  Diabet Med. 2004;  21 114-121
  • 29 Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly.  Am J Physiol. 1996;  271 C1424-C1437

Correspondence

XiangGD MD, PhD 

Department of Endocrinology

Wuhan General Hospital of Guangzhou Command

Wuluo Road 627

Wuhan 430070

Hubei Province

P. R. China

Phone: +8602768878410

Fax: +8602768878410

Email: Guangda64@hotmail.com

    >