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

Abstract

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.

An 8-Week Freeze-Dried Blueberry Supplement Impacts Immune-Related Pathways: A Randomized, Double-Blind Placebo-Controlled Trial

“…Circulating concentrations of hypoxanthine, a purine molecule which is a by-product of adenosine triphosphate catabolism; are elevated following an ischemic event (62). On the other hand, the increase in plasma hippuric acid we observed has been previously reported following anthocyanin supplementation (20,(63)(64)(65). The signi cant increases in several TG metabolites following BBP supplementation was, to our knowledge, a novel nding.…”

“…MetS-related health outcomes may occur beyond an 8-week intake period or from an intervention with whole blueberries rather than BBP or a higher dosage. For example, a long-term BBP supplementation study in individuals with MetS investigated the bene ts of taking 13 g or 22 g BBP on a daily basis (representing respectively a quarter and a half of the dose given in the present study), for a period of 6 months found signi cant improvements of endothelial function and arterial stiffness in subjects consuming the highest dose of BBP (20).…”

“…Blueberry consumption has also been demonstrated to be protective against the risk of myocardial infarction (15) and diabetes (16). However, these results are inconsistent in the literature, with some clinical trials showing no improvement on lipid pro le (11,(17)(18)(19), insulin resistance (11,18,20) or blood pressure (17)(18)(19)(20). Differences in study designs and populations tested (21) could explain these equivocal results, highlighting the need for further research on blueberry health properties.…”

Food intake biomarkers for berries and grapes

“…After careful application of the inclusion and exclusion criteria to the citations collected with the databases search, the numbers of human studies selected for this review were 22 studies out of 206 for blueberry intake [ 2 , 3 , 12 , 13 , 32 , 34 , 37 , 50 , 81 – 83 , 91 , 103 , 105 , 106 , 112 , 137 , 153 , 160 , 178 , 185 ]; 20 out of 137 for strawberries [ 4 , 5 , 9 , 14 , 20 , 22 , 26 , 31 , 41 , 48 , 74 , 75 , 113 , 126 , 129 , 141 , 147 , 148 , 165 , 179 ], 7 out of 87 for raspberry [ 70 , 78 , 86 , 95 , 98 , 156 , 184 ], 5 out of 66 for blackberries [ 47 , 64 , 89 , 100 , 161 ], 13 out of 236 for cranberries [ 7 , 27 , 49 , 51 , 94 , 108 , 119 , 127 , 135 , 174 – 176 , 183 ], and 8 out of 61 for blackcurrant […”

Anthocyanins as Antidiabetic Agents—In Vitro and In Silico Approaches of Preventive and Therapeutic Effects

“…In the longest-duration randomized controlled trials, the effect of 6-month blueberry intake on insulin resistance and cardiometabolic function in metabolic syndrome was evaluated in 115 volunteers [ 47 ]. A daily intake of 1 cup of blueberries improved endothelial function, systemic arterial stiffness and attenuated cyclic guanosine monophosphate concentrations.…”