Blueberries improve biomarkers of cardiometabolic function in participants with metabolic syndrome-results from a 6-month, double-blind, randomized controlled trial.
Aged
Apolipoproteins
/ blood
Biomarkers
/ blood
Blood Pressure
Blueberry Plants
/ metabolism
Cholesterol, HDL
/ blood
Cholesterol, LDL
/ blood
Double-Blind Method
Female
Fruit
/ metabolism
Heart
/ physiopathology
Humans
Insulin Resistance
Male
Metabolic Syndrome
/ blood
Middle Aged
Prospective Studies
Pulse Wave Analysis
metabolic syndrome, blueberry anthocyanins, flavonoids, cardiovascular disease risk, anthocyanin-derived phenolic acid metabolites
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
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
1535-1545Subventions
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © American Society for Nutrition 2019.
Références
Circulation. 2017 Jun 20;135(25):2494-2504
pubmed: 28450350
Am J Clin Nutr. 2016 Sep;104(3):587-94
pubmed: 27488237
Clin Chem. 1972 Jun;18(6):499-502
pubmed: 4337382
J Am Coll Cardiol. 2002 Mar 20;39(6):1005-11
pubmed: 11897443
BMJ. 2015 Jul 14;351:h3764
pubmed: 26173600
Diabetes Care. 2013 Dec;36(12):3961-70
pubmed: 24130345
Circulation. 1989 Jan;79(1):8-15
pubmed: 2642759
Hypertension. 2010 Oct;56(4):591-7
pubmed: 20696989
J Am Coll Cardiol. 1997 Aug;30(2):325-33
pubmed: 9247501
J Nutr. 2010 Oct;140(10):1764-8
pubmed: 20724487
Nutr Res. 2014 Jul;34(7):577-84
pubmed: 25150116
Am J Clin Nutr. 2018 Jul 1;108(1):49-61
pubmed: 29931039
Int J Epidemiol. 1997;26 Suppl 1:S137-51
pubmed: 9126542
Am J Clin Nutr. 2017 Jan;105(1):10-22
pubmed: 27881391
BMJ. 2013 Aug 28;347:f5001
pubmed: 23990623
Circulation. 2009 Oct 20;120(16):1640-5
pubmed: 19805654
Nutr J. 2013 May 02;12:56
pubmed: 23638799
Free Radic Biol Med. 2002 Dec 1;33(11):1590-6
pubmed: 12446216
Gut. 2015 Jun;64(6):872-83
pubmed: 25080446
Pol Arch Med Wewn. 2013;123(9):443-52
pubmed: 24025637
Clin Chem. 2011 Nov;57(11):1524-33
pubmed: 21926181
Eur J Pharmacol. 2014 Nov 15;743:117-25
pubmed: 25239071
J Am Coll Cardiol. 2018 Feb 13;71(6):620-632
pubmed: 29420958
J Hypertens. 2013 Aug;31(8):1570-4
pubmed: 23625114
Br J Nutr. 2017 May;117(10):1470-1477
pubmed: 28606222
Mol Nutr Food Res. 2014 Oct;58(10):1952-61
pubmed: 25044909
J Hum Hypertens. 2017 Mar;31(3):165-171
pubmed: 27654329
Am J Clin Nutr. 2016 Nov;104(5):1301-1309
pubmed: 27655438
Maturitas. 2011 Oct;70(2):169-75
pubmed: 21839593
J Nutr. 2010 Sep;140(9):1582-7
pubmed: 20660279
Nutr Res. 2013 Mar;33(3):220-7
pubmed: 23507228
Diabetes. 2015 Aug;64(8):2847-58
pubmed: 25845659
Eur J Nutr. 2013 Apr;52(3):949-61
pubmed: 22733001
PLoS One. 2016 Sep 02;11(9):e0162089
pubmed: 27589062
J Med Food. 2010 Aug;13(4):808-14
pubmed: 20553191
Br J Nutr. 2014 Sep 28;112(6):925-36
pubmed: 25089359
Pharmacol Res. 2016 Sep;111:452-458
pubmed: 27378569
Am J Clin Nutr. 2013 May;97(5):936-42
pubmed: 23553151
J Diabetes Investig. 2016 Jan;7(1):56-69
pubmed: 26816602
Anal Chem. 2014 Oct 21;86(20):10052-8
pubmed: 24828315
J Acad Nutr Diet. 2015 Mar;115(3):369-77
pubmed: 25578927
Food Chem Toxicol. 2018 May;115:88-97
pubmed: 29530637
J Clin Endocrinol Metab. 2000 Jul;85(7):2402-10
pubmed: 10902785
Clin Sci (Lond). 2016 Jan;130(2):93-104
pubmed: 26424731
Diabetologia. 1985 Jul;28(7):412-9
pubmed: 3899825
Int J Cardiovasc Imaging. 2010 Aug;26(6):631-40
pubmed: 20339920
Food Funct. 2017 Jan 25;8(1):372-380
pubmed: 28059417
J Nutr. 2014 Feb;144(2):202-8
pubmed: 24336456
Atherosclerosis. 2015 Nov;243(1):278-85
pubmed: 26409627
Am J Clin Nutr. 2013 Nov;98(5):1179-91
pubmed: 24004888
Nutrients. 2015 May 27;7(6):4107-23
pubmed: 26024297
J Athl Train. 2008 Apr-Jun;43(2):215-21
pubmed: 18345348
Circulation. 2013 Jan 15;127(2):188-96
pubmed: 23319811
BMJ. 2016 Jan 28;352:i17
pubmed: 26823518
Am J Clin Nutr. 2016 Apr;103(4):1091-8
pubmed: 26936332