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NCT Number: NCT01245270

A Single Supplement of a Standardised Bilberry Extract Modifies Glycaemic Response

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.

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Key information

Conditions

Type 2 Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

40 year–70 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

University of Aberdeen Rowett Institute of Nutrition and Health

Aberdeen, AB21 9SB, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Bilberry capsule first, then control cap

Dietary Supplement

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.

Control capsule first then bilberry cap

Dietary Supplement

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.

Primary outcomes

  1. 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

    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.

  2. 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

    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 outcomes

  1. 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

    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.

  2. 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

    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.

Sponsors and collaborators

Lead sponsor

University of Aberdeen

Other

Registry information

Official study 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.

Important dates

Study start
2010
Primary completion
2013
Study completion
2013
First posted
Nov 22, 2010
Registry last updated
Mar 10, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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