The effect of vitamin E on endothelial function of micro- and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients.

We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients. Subjects (n = 89) were randomized to vitamin E (1,800 IU daily) or placebo and were followed for 12 months. High-resolution ultrasound images were used to measure the flow-mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (NID; endothelium independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin. Left ventricular function was evaluated using transthoracic echocardiogram. At the end of the 6-month period, a worsening in endothelium-dependent skin vasodilation (P = 0.02) and rise in endothelin levels (P = 0.01) were found in the vitamin E compared with the placebo group. At the end of the 12-month period, a worsening was observed in NID (P = 0.02) and a marginal worsening was seen in systolic blood pressure (P = 0.04) and FMD (P = 0.04) in the vitamin E compared with the placebo group. In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group (P = 0.05). No changes were observed in left ventricular function. We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients. Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects, the use of high dosages of vitamin E cannot be recommended.

[1]  J. Morrow,et al.  Long-term effect of combined vitamins E and C on coronary and peripheral endothelial function. , 2004, Journal of the American College of Cardiology.

[2]  A. Goldfine,et al.  Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus. , 2003, American journal of physiology. Heart and circulatory physiology.

[3]  P. Ridker,et al.  Antioxidant Vitamins C and E Improve Endothelial Function in Children With Hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial , 2003, Circulation.

[4]  D. Schade,et al.  Timing of Antioxidant Vitamin Ingestion Alters Postprandial Proatherogenic Serum Markers , 2003, Circulation.

[5]  J. Hsia,et al.  Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: A randomized control trial , 2003 .

[6]  J. Hsia,et al.  Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women. A randomized controlled trial , 2003 .

[7]  S. Devaraj,et al.  Antioxidants and atherosclerosis: don't throw out the baby with the bath water. , 2003, Circulation.

[8]  S. Devaraj,et al.  C-Reactive Protein Increases Plasminogen Activator Inhibitor-1 Expression and Activity in Human Aortic Endothelial Cells: Implications for the Metabolic Syndrome and Atherothrombosis , 2003, Circulation.

[9]  S. Yusuf,et al.  Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. , 2002, Diabetes care.

[10]  Tw.  MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial , 2002, The Lancet.

[11]  AndrewJ. S. Coats.  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial , 2002, The Lancet.

[12]  G. Paolisso,et al.  Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals. , 2002, Journal of the American College of Cardiology.

[13]  David M. Herrington,et al.  Erratum: Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. A report of the international brachial artery reactivity task force (Journal of American College of Cardiology (2002) 39 (257-265)) , 2002 .

[14]  S. Devaraj,et al.  α-tocopherol supplementation decreases plasminogen activator inhibitor-1 and P-selectin levels in type 2 diabetic patients , 2002 .

[15]  E. Benjamin,et al.  Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. , 2002, Journal of the American College of Cardiology.

[16]  O. Pedersen,et al.  Double‐blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients , 2001, Diabetic medicine : a journal of the British Diabetic Association.

[17]  L. Title,et al.  Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E. , 2000, Journal of the American College of Cardiology.

[18]  I. Meredith,et al.  Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study. , 2000, Journal of the American College of Cardiology.

[19]  J. Mann,et al.  Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes. , 2000, Diabetes care.

[20]  R. Cannon,et al.  Vascular effects of estrogen and vitamin E therapies in postmenopausal women. , 1999, Circulation.

[21]  F. Logerfo,et al.  Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. , 1999, Diabetes.

[22]  GISSI-Prevenzione Investigators,et al.  Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial , 1999, The Lancet.

[23]  Roberto Marchioli,et al.  Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. , 1999 .

[24]  L. Aiello,et al.  High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. , 1999, Diabetes care.

[25]  J. Cockcroft,et al.  Effect of oral vitamin E (α‐tocopherol) supplementation on vascular endothelial function in Type 2 diabetes mellitus , 1999, Diabetic medicine : a journal of the British Diabetic Association.

[26]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[27]  N. B. Tütüncü,et al.  Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study. , 1998, Diabetes care.

[28]  G. King,et al.  Protein kinase C activation and the development of diabetic complications. , 1998, Diabetes.

[29]  R. Freeman,et al.  Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration. , 1998, Diabetes.

[30]  G. Plotnick,et al.  Effect of antioxidant vitamins on the transient impairment of endothelium-dependent brachial artery vasoactivity following a single high-fat meal. , 1997, JAMA.

[31]  G. King,et al.  Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Fantone,et al.  Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus , 1997, Diabetes Care.

[33]  J. Keaney,et al.  Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation. , 1996, The Journal of clinical investigation.

[34]  G. King,et al.  Vitamin E Normalizes Diacylglycerol—Protein Kinase C Activation Induced by Hyperglycemia in Rat Vascular Tissues , 1996, Diabetes.

[35]  M. Brown,et al.  A Randomised Controlled Trial of Vitamin E in Patients with Coronary Disease: The Cambridge Heart Antioxidant Study (CHAOS) , 1996 .

[36]  E. Block.  Hydrogen peroxide alters the physical state and function of the plasma membrane of pulmonary artery endothelial cells , 1991, Journal of cellular physiology.

[37]  A. DeMaria,et al.  Recommendations Regarding Quantitation in M-Mode Echocardiography: Results of a Survey of Echocardiographic Measurements , 1978, Circulation.

[38]  W. Kannel,et al.  Role of diabetes in congestive heart failure: the Framingham study. , 1974, The American journal of cardiology.

[39]  A. Grishman,et al.  New type of cardiomyopathy associated with diabetic glomerulosclerosis. , 1972, The American journal of cardiology.

[40]  S. Yusuf.  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Commentary , 2002 .

[41]  A. Coats.  MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial , 2002 .

[42]  Loyd,et al.  SIMVASTATIN AND NIACIN , ANTIOXIDANT VITAMINS , OR THE COMBINATION FOR THE PREVENTION OF CORONARY DISEASE , 2001 .

[43]  A. Tajik,et al.  Quantitative hemodynamics by Doppler echocardiography: a noninvasive alternative to cardiac catheterization. , 1994, Progress in cardiovascular diseases.

[44]  S. Zarich,et al.  Diabetic cardiomyopathy. , 1989, American heart journal.