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Supplementation with a combination of antioxidants does not affect glycaemic control, oxidative stress or inflammation in type 2 diabetes subjects
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University.
Department of Biosciences and Nutrition, Karolinska Institute.
Department of Biosciences and Nutrition, Karolinska Institute.
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2010 (English)In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 44, no 12, 1445-1453 p.Article 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.

Place, publisher, year, edition, pages
2010. Vol. 44, no 12, 1445-1453 p.
Keyword [en]
Antioxidants, supplementation, glycaemic control, oxidative stress, inflammation, diabetes mellitus type 2
National Category
Medical and Health Sciences
Research subject
Nutrition
Identifiers
URN: urn:nbn:se:uu:diva-134116DOI: 10.3109/10715762.2010.515219ISI: 000283796300007OAI: oai:DiVA.org:uu-134116DiVA: diva2:374127
Available from: 2010-12-02 Created: 2010-11-22 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Effect of Dietary Antioxidants on Oxidative Stress, Inflammation and Metabolic Factors: Studies in Subjects with Overweight and with Type 2 Diabetes
Open this publication in new window or tab >>Effect of Dietary Antioxidants on Oxidative Stress, Inflammation and Metabolic Factors: Studies in Subjects with Overweight and with Type 2 Diabetes
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. 76 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 634
Keyword
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:nbn:se:uu:diva-134938 (URN)978-91-554-7977-0 (ISBN)
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
2. Effects of Antioxidants and Pro-oxidants on Oxidative Stress and DNA Damage using the Comet Assay: Studies on Blood Cells from Type 2 Diabetes Subjects and Mouse Lymphoma Cells
Open this publication in new window or tab >>Effects of Antioxidants and Pro-oxidants on Oxidative Stress and DNA Damage using the Comet Assay: Studies on Blood Cells from Type 2 Diabetes Subjects and Mouse Lymphoma Cells
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diet and oral supplements comprise two distinct sources of antioxidants known to prevent oxidative stress. Beneficial effects from antioxidants have been seen for patients at risk for type 2 diabetes.

The aim of this thesis was to evaluate the positive effects of antioxidants against oxidative stress and DNA damage in type 2 diabetes subjects. We also used antioxidants as tools to determine the mechanisms behind genotoxicity induced by mutagenic pro-oxidative agents in mouse lymphoma cells. Several techniques were used to measure oxidative stress and DNA damage, but the main technique used was alkaline comet assay.

The results showed that the fruit and vegetable intake was inversely related to oxidative stress in type 2 diabetes subjects. However, oral supplementary intake of 20 antioxidants did not decrease oxidative stress biomarkers.

In studies on mouse lymphoma cells, using the alkaline comet assay, DNA damage was induced by catechol and o-phenylenediamine (OPD), while 4-nitro-o-phenylenediamine (4-NOPD) induced only oxidative damage, showing different mechanisms of action behind the mutagenicity of the compounds. Also, oxidative stress was induced by catechol and 4-NOPD, whereas imbalances in the nucleotide pool were seen after exposure to OPD or 4-NOPD. Addition of antioxidants together with these pro-oxidants showed that β-carotene was able to reduce DNA damage at low concentrations of catechol, but increased DNA damage at high concentration. In comparison, addition of α-tocopherol slightly decreased catechol-induced DNA damage at all concentrations of catechol. However, no effect of α-tocopherol was seen on OPD-or 4-NOPD-induced DNA damage.

In conclusion, antioxidants from fruits and vegetables, but not from oral supplements, reduced oxidative stress in type 2 diabetes patients, suggesting fruits and vegetables being a healthier source for antioxidant-intake, as compared to oral supplements. Different mechanisms of action for mutagenic pro-oxidants were shown in mouse lymphoma cells, introducing the nucleotide pool as an interesting target for oxidative stress. Reduction of catechol-induced DNA damage by β-carotene or α-tocopherol was shown, with a pro-oxidative action of β-carotene at high concentration of catechol, Interestingly, α-tocopherol was not able to decrease OPD- or 4-NOPD-induced DNA damage, supporting different mechanisms of action behind the genotoxicity from the three pro-oxidants.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 78 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 185
Keyword
metabolic syndrome, fruit and vegetable intake, plasma antioxidants, beta-carotene, alpha-tocopherol, inflammation, oxidative DNA damage, lipid peroxidation, mouse lymphoma assay, ROS, nucleotide pool, viability, DNA dye
National Category
Pharmacology and Toxicology
Research subject
Toxicology
Identifiers
urn:nbn:se:uu:diva-217886 (URN)978-91-554-8877-2 (ISBN)
Public defence
2014-03-28, A1:107a, Biomedical center, Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2014-03-06 Created: 2014-02-05 Last updated: 2014-04-29

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