A Single Supplement of a Standardised Bilberry Extract Modifies Glycaemic Response

Not Applicable

Completed

Conditions: Type 2 Diabetes

Interventions: Dietary Supplement: Control capsule first then bilberry cap
Dietary Supplement: Bilberry capsule first, then control cap

Registration Number: NCT01245270

Lead Sponsor: University of Aberdeen

Brief Summary: Dietary strategies for alleviating health complications associated with type 2 diabetes (T2D) are being pursued as alternatives to pharmaceutical interventions. Berries such as bilberries that are rich in polyphenols may influence carbohydrate digestion and absorption and thus postprandial glycaemia. In addition berries have been reported to alter incretins as well as to have anti-oxidant and anti-inflammatory properties that may also affect postprandial glycaemia. This study investigated the acute affect of a standardised bilberry extract on glucose metabolism in T2D.

Eight male volunteers with T2D controlling their diabetes by diet and lifestyle alone were given a single oral capsule of either 0.47g standardized bilberry extract (36% (w/w) anthocyanins) which equates to ∼50 g of fresh bilberries or placebo followed by a polysaccharide drink (equivalent to 75 g glucose) in a double blinded cross over intervention with a two week washout period.

This study demonstrates that the ingestion of a concentrated bilberry extract reduces postprandial glycaemia and insulin in volunteers with T2D. The most likely mechanism for the lower glycaemic response involves reduced rates of carbohydrate digestion and/or absorption.

Detailed Description: Dietary strategies for alleviating health complications, such as premature vascular disease, associated with type 2 diabetes (T2D) and obesity are actively being pursued as alternatives to pharmaceutical interventions. The genus Vaccinium (e.g. blueberry, bilberry, cranberry) has been used traditionally as a source of folk remedies for established diabetic symptoms.

Berries from this genus are enriched in anthocyanins, polyphenols recognized for their ability to provide and activate cellular antioxidant protection and inhibit inflammatory gene expression, activities that may contribute to the efficacy of the Vaccinium genus as ameliorators for type 2 diabetes. Consumption of a freeze-dried blueberry beverage for an 8 week period for example decreased plasma concentrations of the cardiovascular risk factors oxidized LDL, malondialdehyde and hydroxynonenal. In another trial, bioactives from blueberries improved insulin sensitivity in obese insulin-resistant men and women. In both these studies the investigators reported no change in inflammatory markers following supplementation although bilberry juice was shown to modulate plasma markers of inflammation C-reactive protein and IL-6 in subjects with increased risk of cardiovascular disease. These beneficial responses from human studies are supported by data that demonstrate long-term beneficial effects of anthocyanins from mouse models of obesity and diabetes.

There are also a number of studies in vitro and in vivo that suggest that polyphenols influence carbohydrate digestion and absorption, resulting in improved postprandial glycaemia in the short term. Polyphenols inhibit intestinal alpha glucosidase activity and glucose transport in vitro. In association with this, polyphenols administered to rodents suppress the elevation of blood glucose concentration after oral administration of mono- and di-saccharides. In humans, several studies have examined the effect of polyphenols on the post-prandial glycaemic response. In one study a test meal of mixed berry purée with sucrose showed a lower plasma glucose concentration after 15-30 min compared with a control matched for sugars.

Overall, evidence suggests that consuming edible berries, particularly from the genus Vaccinium, that have high concentrations of anthocyanins could provide a supplementary intervention to improve glycaemia in subjects with T2D or impaired glucose tolerance. The object of this study was to investigate whether a single supplementation with a standardised (36% w/w anthocyanins) concentrated bilberry extract could alter glucose metabolism in overweight/obese volunteers with impaired glucose intolerance or T2D compared with a control capsule matched for sugars and to explore the possible mechanisms of action.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 8

Inclusion Criteria

Male subjects
Aged >40 and <70
Clinical diagnosis of Type 2 diabetes controlling their diabetes by diet alone
All subjects must live in the Aberdeenshire area of Scotland

Exclusion Criteria

Medical exclusion criteria
Clinical diagnosis of thromboembolic or coagulation disease
Clinical diagnosis of unregulated thyroid disease
Clinical diagnosis of kidney disease
Clinical diagnosis of severe gastrointestinal disorders
History of Alcohol or any other substance abuse

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Control capsule first, then bilberry cap	Control capsule first then bilberry cap	Volunteers will be given a single control placebo capsule followed by a 14 day washout period the a single capsule of 0.47 grams of mirtoselect (a concentrated bilberry extract) First Intervention (1 day), Washout (14 days), Second Intervention (1 day)
Bilberry capsule first, then control cap	Bilberry capsule first, then control cap	Volunteers will be given a single capsule of 0.47 grams of mirtoselect (a concentrated bilberry extract) followed by a 14 day washout period then a single control placebo capsule. First Intervention (1 day), Washout (14 days), Second Intervention (1 day)

Primary Outcome Measures

Name	Time	Method
Plasma Glucose iAUC (Incremental Area Under the Curve; mM*Min)	Plasma was collected at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min post capsule	Volunteers were fasted (10-12 h) overnight before the OGTT. Venous blood samples were taken through an indwelling cannula inserted into a forearm vein at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min after consuming 75 g of Polycal liquid (carbohydrate, 61·9%; polysaccharide, 49·2 %; sugars, 12·2%; glucose, 0·6%; maltose, 11·6%; http://www. nutricia.co.uk). Polycal was selected as the main carbohydrate as it is in the form of polysaccharides and this is closer to normal dietary consumption than glucose only.The volunteers consumed the appropriate capsule (0 min), glucose load and a further sample of water (70 ml) within 3 min. For those volunteers taking the control capsule, additional sugar (fructose and dextrose/glucose) was added double-blinded to the water to match the free sugar content of the Mirtoselect® capsules. Movement during the 300 min OGTT was kept to a minimum.
Plasma Insulin iAUC (Incremental Area Under the Curve; ng/ml*Min)	Plasma was collected at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min after the capsule	Volunteers were fasted (10-12 h) overnight before the OGTT. Venous blood samples were taken through an indwelling cannula inserted into a forearm vein at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min after consuming 75 g of Polycal liquid (carbohydrate, 61•9%; polysaccharide, 49•2 %; sugars, 12•2%; glucose, 0•6%; maltose, 11•6%; http://www. nutricia.co.uk). Polycal was selected as the main carbohydrate as it is in the form of polysaccharides and this is closer to normal dietary consumption than glucose only.The volunteers consumed the appropriate capsule (0 min), glucose load and a further sample of water (70 ml) within 3 min. For those volunteers taking the control capsule, additional sugar (fructose and dextrose/glucose) was added double-blinded to the water to match the free sugar content of the Mirtoselect® capsules. Movement during the 300 min OGTT was kept to a minimum.

Secondary Outcome Measures

Name	Time	Method
Bioavailability in Urine	Urine will also be collected (if possible) 0, 1, 3 and 5 hours, with all urine collected within the 24 hour time period post intervention	To measure the amount of anthocyanins and phenolic-derived metabolites by liquid chromatography mass spectrometry (LC-MS) being absorbed from the gut and excreted following the single intervention.
Bioavailability in Plasma	Plasma will also be collected -15,-10, -5, 15, 30, 45, 60, 90, 120, 150, and 300 minutes and 24 hours post intervention	To measure the amount of anthocyanins and phenolic-derived metabolites by liquid chromatography mass spectrometry (LC-MS) being absorbed from the gut and excreted following the single intervention.