A Single Supplement of a Standardised Bilberry Extract Modifies Glycaemic Response

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Aberdeen
ClinicalTrials.gov Identifier:
NCT01245270
First received: November 16, 2010
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Type 2 Diabetes
Dietary Supplement: Bilberry capsule first, then control cap
Dietary Supplement: Control capsule first then bilberry cap

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Single Supplement of a Standardised Bilberry Extract (36% (w/w) Anthocyanins) Modifies Glycaemic Response in Persons With Type 2 Diabetes Controlled by Diet and Lifestyle.

Resource links provided by NLM:


Further study details as provided by University of Aberdeen:

Primary Outcome Measures:
  • Plasma Glucose iAUC (Incremental Area Under the Curve; mM*Min) [ Time Frame: Plasma was collected at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min post capsule ] [ Designated as safety issue: No ]

    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) [ Time Frame: Plasma was collected at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min after the capsule ] [ Designated as safety issue: No ]

    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:
  • Bioavailability in Plasma [ Time Frame: Plasma will also be collected -15,-10, -5, 15, 30, 45, 60, 90, 120, 150, and 300 minutes and 24 hours post intervention ] [ Designated as safety issue: No ]
    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 Urine [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 8
Study Start Date: September 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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)

Dietary Supplement: Bilberry capsule first, then control cap

Male subjects aged >40 and <70 years, with type 2 diabetes controlling their diabetes by diet alone closely matched for adiposity as determined by waist circumference (n=8).

Volunteers will be randomised double blinded into two groups (n=4 per group) and given a single capsule of either 0.47 grams of a bilberry extract (mirtoselect provided by Indena S.p.A (http://www.mirtoselect.info/) or a control capsule. Following a two week wash out period the volunteers will be asked to take a second single capsule of either of 0.47 grams of mirtoselect or a control capsule in a cross over study, the opposite of what they took the first time.

Experimental: 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)

Dietary Supplement: Control capsule first then bilberry cap

Male subjects aged >40 and <70 years, with type 2 diabetes controlling their diabetes by diet alone closely matched for adiposity as determined by waist circumference (n=8).

Volunteers will be randomised double blinded into two groups (n=4 per group) and given a single capsule of either 0.47 grams of a bilberry extract (mirtoselect provided by Indena S.p.A (http://www.mirtoselect.info/) or a control capsule. Following a two week wash out period the volunteers will be asked to take a second single capsule of either of 0.47 grams of mirtoselect or a control capsule in a cross over study, the opposite of what they took the first time.


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.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01245270

Locations
United Kingdom
University of Aberdeen Rowett Institute of Nutrition and Health
Aberdeen, United Kingdom, AB21 9SB
Sponsors and Collaborators
University of Aberdeen
Investigators
Principal Investigator: Nigel Hoggard, PhD University of Aberdeen Rowett Institute of Nutrition and Health
  More Information

Publications:
Responsible Party: University of Aberdeen
ClinicalTrials.gov Identifier: NCT01245270     History of Changes
Other Study ID Numbers: REC 10/S0801/54, 902
Study First Received: November 16, 2010
Results First Received: August 23, 2013
Last Updated: August 13, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Aberdeen:
anthocyanin
blaeberries
bilberries
blueberries
mirtoselect
glucose AUC

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 18, 2014