Effect of alpha-tocopherol and beta-carotene supplementation on macrovascular complications and total mortality from diabetes: Results of the ATBC Study

Kataja-Tuomola, Merja; Kontto, Jukka; Männistö, Satu; Albanês, Demetrius; Virtamo, Jarmo

doi:10.3109/07853890903508887

Cited by 40 publications

(33 citation statements)

References 21 publications

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“…Our findings may partially explain the inconsistent and mostly disappointing results with antioxidant use in diabetic patients (Darko et al 2002;Heart Protection Study Collaborative Group 2002;Ble-Castillo et al 2005;Lonn et al 2005;Lu et al 2005;Belch et al 2008;Song et al 2009;Kataja-Tuomola et al 2010) since inflammation rather than oxidative stress is the major contributor to diabetes vascular dysfunction. Consistent with this notion, endothelial function improved in type 2 diabetic patients treated with rosiglitazone, an agent that reduces inflammation but not oxidative stress (Kelly et al 2007).…”

Section: Discussionmentioning

confidence: 56%

Weight and inflammation are the major determinants of vascular dysfunction in the aortae of db/db mice

Sallam

Fisher

Golbidi

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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The key roles that obesity, hyperglycemia, hyperlipidemia, inflammation, and oxidative stress play in the progression of diabetes vascular complications are well recognized; however, the relative contribution and importance of these individual factors remain uncertain. At 6, 10, or 14 weeks old, blood samples and thoracic aortae were collected from db/db mice and their non-diabetic controls. Plasma samples were analyzed for glucose, 8-isoprostane, CRP, triglycerides, LDL, and HDL as markers of glycemic status, oxidative stress, inflammation, and dyslipidemia, respectively. The responses of the aortic rings to high KCl, phenylephrine (PE), acetylcholine (ACh), and sodium nitroprusside were examined. Statistical methods were used to estimate the strength of the association between plasma variables and vascular functions. Systemic inflammation occurred in db/db mice at an earlier age than did hyperglycemia or oxidative stress. Aortae of db/db showed augmented contractions to PE which were positively correlated with weight, plasma glucose, 8-isoprostane, and CRP. Also, db/db mice showed impaired endothelium-dependent ACh vasorelaxation which was negatively correlated with weight, plasma glucose, and 8-isoprostane. Multivariate analysis and stepwise modeling show that CRP is the major determinant of the contractile responses, while weight and HDL are the major determinants of ACh-induced relaxation. Among the traditional risk factors of obesity, hyperglycemia, oxidative stress, inflammation, and dyslipidemia, our study reveals that weight and inflammation are the major determinants of vascular dysfunction in the aortae of db/db mice. Our findings partially resolve the complexity of diabetes vasculopathies and suggest targeting weight loss and inflammation for effective therapeutic approaches.

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Section: Discussionmentioning

confidence: 56%

Weight and inflammation are the major determinants of vascular dysfunction in the aortae of db/db mice

Sallam

Fisher

Golbidi

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Tocopherol has also been shown to improve endothelial function and reduce blood pressure (13,14). Despite its observed benefits in cardiovascular diseases, there have been several unsuccessful clinical trials with tocopherol treatment (56,75,144,157). One limitation with tocopherol as an antioxidant-based therapeutic strategy is that low doses are ineffective but high doses are harmful (123).…”

Section: Dietary Sources Of Antioxidantsmentioning

confidence: 98%

Antioxidant-based therapies for angiotensin II-associated cardiovascular diseases

Rosenbaugh

Savalia

Manickam

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Cardiovascular diseases, including hypertension and heart failure, are associated with activation of the renin-angiotensin system (RAS) and increased circulating and tissue levels of ANG II, a primary effector peptide of the RAS. Through its actions on various cell types and organ systems, ANG II contributes to the pathogenesis of cardiovascular diseases by inducing cardiac and vascular hypertrophy, vasoconstriction, sodium and water reabsorption in kidneys, sympathoexcitation, and activation of the immune system. Cardiovascular research over the past 15-20 years has clearly implicated an important role for elevated levels of reactive oxygen species (ROS) in mediating these pathophysiological actions of ANG II. As such, the use of antioxidants, to reduce the elevated levels of ROS, as potential therapies for various ANG II-associated cardiovascular diseases has been intensely investigated. Although some antioxidant-based therapies have shown therapeutic impact in animal models of cardiovascular disease and in human patients, others have failed. In this review, we discuss the benefits and limitations of recent strategies, including gene therapy, dietary sources, low-molecular-weight free radical scavengers, polyethylene glycol conjugation, and nanomedicine-based technologies, which are designed to deliver antioxidants for the improved treatment of cardiovascular diseases. Although much work has been completed, additional research focusing on developing specific antioxidant molecules or proteins and identifying the ideal in vivo delivery system for such antioxidants is necessary before the use of antioxidant-based therapies for cardiovascular diseases become a clinical reality.

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“…While there has been significant interest in antioxidant supplementation as a treatment for diabetes, current evidence not only demonstrates a lack of benefit with respect to glycemic control and progression of complications, but also provides evidence of potential harm of vitamin E, carotene, and other antioxidant supplements (197)(198)(199)(200)(201)(202)(203).…”

Section: Micronutrients and Herbal Supplementsmentioning

confidence: 99%

Nutrition Therapy Recommendations for the Management of Adults With Diabetes

et al. 2013

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A healthful eating pattern, regular physical activity, and often pharmacotherapy are key components of diabetes management. For many individuals with diabetes, the most challenging part of the treatment plan is determining what to eat. It is the position of the American Diabetes Association (ADA) that there is not a "one-size-fits-all" eating pattern for individuals with diabetes. The ADA also recognizes the integral role of nutrition therapy in overall diabetes management and has historically recommended that each person with diabetes be actively engaged in self-management, education, and treatment planning with his or her health care provider, which includes the collaborative development of an individualized eating plan (1,2). Therefore, it is important that all members of the health care team be knowledgeable about diabetes nutrition therapy and support its implementation.This position statement on nutrition therapy for individuals living with diabetes replaces previous position statements, the last of which was published in 2008 (3). Unless otherwise noted, research reviewed was limited to those studies conducted in adults diagnosed with type 1 or type 2 diabetes. Nutrition therapy for the prevention of type 2 diabetes and for the management of diabetes complications and gestational diabetes mellitus is not addressed in this review.A grading system, developed by the ADA and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations (1) ( Table 1). The level of evidence that supports each recommendation is listed after the recommendation using the letters A, B, C, or E. A table linking recommendations to evidence can be reviewed at http:// professional.diabetes.org/nutrition. Members of the Nutrition Recommendations Writing Group Committee disclosed all potential financial conflicts of interest with industry. These disclosures were discussed at the onset of the position statement development process. Members of this committee, their employers, and their disclosed conflicts of interest are listed in the ACKNOWLEDGMENTS. The ADA uses general revenues to fund development of its position statements and does not rely on industry support for these purposes. GOALS OF NUTRITION THERAPY THAT APPLY TO ADULTS WITH DIABETES▪ To promote and support healthful eating patterns, emphasizing a variety of nutrient dense foods in appropriate portion sizes, in order to improve overall health and specifically to:c Attain individualized glycemic, blood pressure, and lipid goals. General recommended goals from the ADA for these markers are as follows:* c A1C ,7%. c Blood pressure ,140/80 mmHg. c LDL cholesterol ,100 mg/dL; triglycerides ,150 mg/dL; HDL cholesterol .40 mg/dL for men; HDL cholesterol .50 mg/dL for women.

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Effect of alpha-tocopherol and beta-carotene supplementation on macrovascular complications and total mortality from diabetes: Results of the ATBC Study

Abstract: Alpha-tocopherol or beta-carotene supplementation has no protective effect on macrovascular outcomes or total mortality of diabetic male smokers.

Cited by 40 publications

References 21 publications

Weight and inflammation are the major determinants of vascular dysfunction in the aortae of db/db mice

Weight and inflammation are the major determinants of vascular dysfunction in the aortae of db/db mice

Antioxidant-based therapies for angiotensin II-associated cardiovascular diseases

Nutrition Therapy Recommendations for the Management of Adults With Diabetes

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