Blueberries improve biomarkers of cardiometabolic function in participants with metabolic syndrome-results from a 6-month, double-blind, randomized controlled trial.


Journal

The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027

Informations de publication

Date de publication:
01 06 2019
Historique:
received: 01 11 2018
accepted: 10 12 2018
entrez: 29 5 2019
pubmed: 29 5 2019
medline: 6 2 2020
Statut: ppublish

Résumé

Anthocyanin-rich blueberry intake is associated with reduced type 2 diabetes and cardiovascular disease (CVD) risk in prospective studies, although long-term randomized controlled trials (RCTs) have not been conducted in at-risk populations. In the longest-duration RCT to date, we examined the effect of 6-mo blueberry intake on insulin resistance and cardiometabolic function in metabolic syndrome. A double-blind, parallel RCT (n = 115; age 63 ± 7 y; 68% male; body mass index 31.2 ± 3.0 kg/m2) was conducted, which fed 2 dietarily achievable blueberry intakes [equivalent to 1/2 and 1 cup/d (75/150 g)] compared with matched placebo. Insulin resistance was assessed via the homeostasis model assessment of insulin resistance (primary endpoint) and confirmed by [6-6-2H2]-glucose-labeled, 2-step hyperinsulinemic clamp (n = 20). Clinically relevant cardiometabolic endpoints [including flow-mediated dilatation, augmentation index, lipoprotein status (by nuclear magnetic resonance spectroscopy), and nitric oxide (NO)-related metabolite assay] and anthocyanin metabolism were assessed. A daily intake of 1 cup of blueberries improved endothelial function (flow-mediated dilatation: +1.45%; 95% CI: 0.83%, 2.1%; P = 0.003), systemic arterial stiffness (augmentation index: -2.24%; 95% CI: -3.97%, -0.61%; P = 0.04) and attenuated cyclic guanosine monophosphate concentrations. In statin nonusers (n = 71), elevated high-density lipoprotein cholesterol (+0.08 mmol/L; P = 0.03), high-density lipoprotein particle density (+0.48n, ×10-6; P = 0.002) and apolipoprotein A-I (+0.05 g/L; P = 0.01) concentrations were observed following the 1-cup/d intervention. Treatment compliance was 94.1% (wrapper returns) and total concentrations of anthocyanin-derived phenolic acid metabolites significantly increased, dose-dependently, in serum and 24-h urine (P < 0.01 and P < 0.001, respectively). Insulin resistance, pulse wave velocity, blood pressure, NO, and overall plasma thiol status were unaffected. Likewise, a half cup per day had no effect on any biomarkers. Despite insulin resistance remaining unchanged we show, to our knowledge, the first sustained improvements in vascular function, lipid status, and underlying NO bioactivity following 1 cup blueberries/d. With effect sizes predictive of 12-15% reductions in CVD risk, blueberries should be included in dietary strategies to reduce individual and population CVD risk. This study was registered at clinicaltrials.gov as NCT02035592.

Sections du résumé

BACKGROUND
Anthocyanin-rich blueberry intake is associated with reduced type 2 diabetes and cardiovascular disease (CVD) risk in prospective studies, although long-term randomized controlled trials (RCTs) have not been conducted in at-risk populations.
OBJECTIVE
In the longest-duration RCT to date, we examined the effect of 6-mo blueberry intake on insulin resistance and cardiometabolic function in metabolic syndrome.
METHODS
A double-blind, parallel RCT (n = 115; age 63 ± 7 y; 68% male; body mass index 31.2 ± 3.0 kg/m2) was conducted, which fed 2 dietarily achievable blueberry intakes [equivalent to 1/2 and 1 cup/d (75/150 g)] compared with matched placebo. Insulin resistance was assessed via the homeostasis model assessment of insulin resistance (primary endpoint) and confirmed by [6-6-2H2]-glucose-labeled, 2-step hyperinsulinemic clamp (n = 20). Clinically relevant cardiometabolic endpoints [including flow-mediated dilatation, augmentation index, lipoprotein status (by nuclear magnetic resonance spectroscopy), and nitric oxide (NO)-related metabolite assay] and anthocyanin metabolism were assessed.
RESULTS
A daily intake of 1 cup of blueberries improved endothelial function (flow-mediated dilatation: +1.45%; 95% CI: 0.83%, 2.1%; P = 0.003), systemic arterial stiffness (augmentation index: -2.24%; 95% CI: -3.97%, -0.61%; P = 0.04) and attenuated cyclic guanosine monophosphate concentrations. In statin nonusers (n = 71), elevated high-density lipoprotein cholesterol (+0.08 mmol/L; P = 0.03), high-density lipoprotein particle density (+0.48n, ×10-6; P = 0.002) and apolipoprotein A-I (+0.05 g/L; P = 0.01) concentrations were observed following the 1-cup/d intervention. Treatment compliance was 94.1% (wrapper returns) and total concentrations of anthocyanin-derived phenolic acid metabolites significantly increased, dose-dependently, in serum and 24-h urine (P < 0.01 and P < 0.001, respectively). Insulin resistance, pulse wave velocity, blood pressure, NO, and overall plasma thiol status were unaffected. Likewise, a half cup per day had no effect on any biomarkers.
CONCLUSIONS
Despite insulin resistance remaining unchanged we show, to our knowledge, the first sustained improvements in vascular function, lipid status, and underlying NO bioactivity following 1 cup blueberries/d. With effect sizes predictive of 12-15% reductions in CVD risk, blueberries should be included in dietary strategies to reduce individual and population CVD risk. This study was registered at clinicaltrials.gov as NCT02035592.

Identifiants

pubmed: 31136659
pii: S0002-9165(22)03206-3
doi: 10.1093/ajcn/nqy380
pmc: PMC6537945
doi:

Substances chimiques

Apolipoproteins 0
Biomarkers 0
Cholesterol, HDL 0
Cholesterol, LDL 0

Banques de données

ClinicalTrials.gov
['NCT02035592']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1535-1545

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © American Society for Nutrition 2019.

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Auteurs

Peter J Curtis (PJ)

Department of Nutrition & Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Vera van der Velpen (V)

Department of Nutrition & Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Lindsey Berends (L)

Department of Nutrition & Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Amy Jennings (A)

Department of Nutrition & Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Martin Feelisch (M)

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.

A Margot Umpleby (AM)

Department of Nutritional Sciences, University of Surrey, Guildford, United Kingdom.

Mark Evans (M)

Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.

Bernadette O Fernandez (BO)

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.

Mia S Meiss (MS)

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.

Magdalena Minnion (M)

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.

John Potter (J)

Department of Nutrition & Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Anne-Marie Minihane (AM)

Department of Nutrition & Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Colin D Kay (CD)

Department of Nutrition & Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Eric B Rimm (EB)

Departments of Epidemiology & Nutrition, Harvard TH Chan School of Public Health, and Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Aedín Cassidy (A)

Department of Nutrition & Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

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Classifications MeSH