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Effect of Dietary Antioxidants on Oxidative Stress, Inflammation and Metabolic Factors: Studies in Subjects with Overweight and with Type 2 Diabetes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Observational studies have indicated that fruit and vegetables, and dietary antioxidants may play an important role in reducing the risk of chronic diseases, potentially by affecting pathogenic mechanisms such as oxidative stress and inflammation. Clinical trials investigating the effects of supplementation with single or a few antioxidants in high doses have, however, shown inconsistent results and thus have not been able to support the observational findings.

It was therefore hypothesised that a supplement, containing a combination of antioxidants mainly extracted from fruit and vegetables, and supplied at moderate doses, might act more beneficially than single antioxidants given at pharmacological doses. The effects of such a supplement were investigated in two interventional studies described in this thesis. The effects on antioxidant status, metabolic control, oxidative stress and inflammation were investigated in overweight men and in patients with type 2 diabetes, subjects that could be expected to have elevated levels of oxidative stress and inflammatory activity.

The results of the studies did not support the hypothesis that supplementation with antioxidants from fruit and vegetables may have beneficial effects by counteracting oxidative stress and inflammation, despite markedly increased plasma antioxidant concentrations. However, interesting associations were observed in diabetes patients at baseline between intake of antioxidant rich food as well as levels of antioxidants in plasma, and markers of oxidative stress and inflammation. These associations are compatible with the hypothesis that a high intake of fruit and vegetables and dietary antioxidants decrease oxidative stress levels, have anti-inflammatory effects and a beneficial influence on glycaemic control. The results also indicated that glycaemic control may affect the level of oxidative stress.

The absence of beneficial effects from antioxidants might to some extent be explained by the initial levels of oxidative stress and inflammation and by the antioxidative status in the subjects included in the studies. Since the levels generally were comparable with those observed in healthy subjects, this might have decreased the ability to observe any beneficial effects of supplementation with additional antioxidants.

Continued investigations are needed to characterise the individuals who potentially might benefit from antioxidant supplementation. In view of apparent positive effects from a high intake of fruit and vegetables found in observational studies and until more knowledge is available from interventional trials about possible benefits and potential risks of antioxidant supplementation it still seems reasonable to recommend a diet rich in fruit and vegetables.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , p. 76
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 634
Keywords [en]
Antioxidants, supplementation, fruit and vegetables, oxidative stress, isoprostanes, lipid peroxidation, oxidative damage to DNA, glycaemic control, inflammation, overweight, type 2 diabetes
National Category
Medical and Health Sciences
Research subject
Nutrition
Identifiers
URN: urn:nbn:se:uu:diva-134938ISBN: 978-91-554-7977-0 (print)OAI: oai:DiVA.org:uu-134938DiVA, id: diva2:376804
Public defence
2011-02-04, Mariasalen, Stiftets Hus, Dragarbrunnsgatan 71, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2011-01-14 Created: 2010-12-02 Last updated: 2011-03-11Bibliographically approved
List of papers
1. Biomarkers of oxidative stress in overweight men are not influenced by a combination of antioxidants
Open this publication in new window or tab >>Biomarkers of oxidative stress in overweight men are not influenced by a combination of antioxidants
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2010 (English)In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 44, no 5, p. 522-528Article in journal (Refereed) Published
Abstract [en]

The effect of antioxidant supplementation on biomarkers of oxidative stress was investigated in a 6-week intervention study in 60 overweight men. The supplement contained a combination of antioxidants aiming to correspond to the antioxidant content found in a diet rich in fruit and vegetables. Placebo, single or double dose of antioxidants was provided to the subjects. Metabolic variables, plasma antioxidants and biomarkers of oxidative stress (lipid peroxidation and DNA damage) were measured. No effect of supplementation on biomarkers of oxidative stress was observed. Both intervention groups showed substantial increases of plasma antioxidants. This study demonstrated that supplementation with a combination of antioxidants did not affect lipid peroxidation and DNA damage in overweight men, despite increased concentrations of plasma antioxidants. The absence of antioxidant supplement effect might possibly be explained by the chosen study group having a normal level of oxidative stress, duration of the intervention and/or doses of antioxidants.

 

Keywords
Antioxidants, oxidative stress, isoprostanes, lipid peroxidation, DNA damage, overweight
National Category
Medical and Health Sciences
Research subject
Nutrition
Identifiers
urn:nbn:se:uu:diva-135865 (URN)10.3109/10715761003647101 (DOI)000276815300005 ()
Available from: 2010-12-08 Created: 2010-12-08 Last updated: 2017-12-11Bibliographically approved
2. High intake of fruit and vegetables is related to low oxidative stress and inflammation in a group of patients with type 2 diabetes
Open this publication in new window or tab >>High intake of fruit and vegetables is related to low oxidative stress and inflammation in a group of patients with type 2 diabetes
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2007 (English)In: Scandinavian Journal of Food and Nutrition, ISSN 1748-2976, E-ISSN 1748-2984, Vol. 51, no 4, p. 149-158Article in journal (Refereed) Published
Abstract [en]

Background : Patients with type 2 diabetes have increased levels of oxidative stress and inflammation. A high fruit and vegetable intake may be beneficial. Objective : To study whether fruit and vegetable intake and levels of plasma antioxidants relate to markers of oxidative stress and inflammation in a group of patients with type 2 diabetes. Further, to investigate whether plasma antioxidants are good biomarkers for intake of fruit and vegetables. Design : Patients with type 2 diabetes were studied. Their dietary intake and levels of plasma antioxidants, and markers of oxidative stress and inflammation were analysed. Results : Fruit and vegetable intake was inversely related to oxidative stress. Plasma carotenoids were negatively correlated with inflammation. The plasma levels of -carotene and β-carotene showed strongly positive associations with fruit and vegetable intake. Conclusions : The results suggest that fruit and vegetable intake may decrease oxidative stress and inflammation in this group of patients. An increased intake of fruit and vegetables can therefore be beneficial for patients with type 2 diabetes, since these patients are documented to have raised oxidative stress and inflammation. The study support the usefulness of plasma -carotene and β-carotene as biomarkers for fruit and vegetable intake.

Keywords
antioxidants, fruit, inflammatory cytokine, oxidative stress, type 2 diabetes, vegetables
National Category
Medical and Health Sciences
Research subject
Nutrition
Identifiers
urn:nbn:se:uu:diva-16051 (URN)10.1080/17482970701737285 (DOI)
Available from: 2008-04-11 Created: 2008-04-11 Last updated: 2017-12-08Bibliographically approved
3. Glycaemic status in relation to oxidative stress and inflammation in well-controlled type 2 diabetes subjects
Open this publication in new window or tab >>Glycaemic status in relation to oxidative stress and inflammation in well-controlled type 2 diabetes subjects
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2009 (English)In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 101, no 10, p. 1423-1426Article in journal (Refereed) Published
Abstract [en]

The aim of the present observational study was to investigate the relationships between glycaemic status and levels of oxidative stress and inflammation in well-controlled type 2 diabetes subjects. Metabolic variables (weight, BMI, waist circumference (waist), blood glucose, glycated Hb (HbA1c), insulin, blood lipids), biomarkers of oxidative stress (8-iso-PGF, malondialdehyde, 8-oxo-7,8-dihydro-2'-deoxyguanosine, formamido pyrimidine glycosylase-sites, frequency of micronucleated erythrocytes, nitrotyrosine) and inflammatory markers (high sensitivity C-reactive protein (hsCRP), IL-6, cyclo-oxygenase-catalyzed PGF-metabolite) were measured. Fifty-six patients (thirty women and twenty-six men, age 62.3 (SD 7.0) years, HbA1c 6.1 (SD 0.9) %, BMI 28.3 (SD 3.8) kg/m2, waist 99.6 (SD 11.1) cm) were included in the study. HbA1c (r 0.29, P=0.03) and blood glucose (r 0.33, P=0.01) correlated positively with 8-iso-PGF. Positive correlations were also observed between HbA1c and nitrotyrosine (r 0.42, P=0.01), waist and hsCRP (r 0.37, P=0.005), hsCRP and IL-6 (r 0.61, P<0.0001) and between PGF-metabolite and 8-iso-PGF (r 0.27, P=0.048). The present study indicates that glycaemic status is associated with oxidative stress even in subjects with well-controlled type 2 diabetes. Furthermore, inflammation was more related to abdominal obesity than to glycaemic control. A large number of biomarkers of oxidative stress and inflammation were investigated, but only a few associations were found between the markers. This could be due to the fact that none of these biomarkers biosynthesises via similar pathways or simultaneously owing to their diverse nature and origin.

Keywords
Glycaemic control, Oxidative stress, Inflammation, Diabetes mellitus type 2
National Category
Medical and Health Sciences
Research subject
Nutrition
Identifiers
urn:nbn:se:uu:diva-122214 (URN)10.1017/S0007114508076204 (DOI)000267026900001 ()19459227 (PubMedID)
Available from: 2010-04-14 Created: 2010-04-07 Last updated: 2017-12-12Bibliographically approved
4. Supplementation with a combination of antioxidants does not affect glycaemic control, oxidative stress or inflammation in type 2 diabetes subjects
Open this publication in new window or tab >>Supplementation with a combination of antioxidants does not affect glycaemic control, oxidative stress or inflammation in type 2 diabetes subjects
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2010 (English)In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 44, no 12, p. 1445-1453Article in journal (Refereed) Published
Abstract [en]

The present clinical trial examined the influence of a supplement, containing a combination of antioxidants extracted from fruit, berries and vegetables, on levels of plasma antioxidants (tocopherols, carotenoids and ascorbate), glycaemic control (blood glucose, HbA1c, insulin), oxidative stress biomarkers (F2-isoprostane, malondialdehyd, nitrotyrosine, 8-oxo-7, 8-dihydro-2'-deoxyguanosine, formamidopyrimidine glycosylase sites, frequency of micronucleated erythrocytes) and inflammatory markers (interleukin-6, C-reactive protein, prostaglandin F-metabolite) in type 2 diabetes. Forty subjects were randomly assigned to control, single or double dose group and completed the study. In summary, 12 weeks of antioxidant supplementation did neither affect glycaemic control nor the levels of biomarkers of oxidative stress or inflammation, despite substantially increased plasma concentrations of antioxidants. The absence of an effect may be explained by the selected study subjects with relatively well-controlled diabetes, a high intake of fruit and vegetable and levels of plasma antioxidants, biomarkers of oxidative stress and inflammatory markers comparable to those found in healthy subjects.

Keywords
Antioxidants, supplementation, glycaemic control, oxidative stress, inflammation, diabetes mellitus type 2
National Category
Medical and Health Sciences
Research subject
Nutrition
Identifiers
urn:nbn:se:uu:diva-134116 (URN)10.3109/10715762.2010.515219 (DOI)000283796300007 ()
Available from: 2010-12-02 Created: 2010-11-22 Last updated: 2017-12-12Bibliographically approved

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