Clinical trial NCT01245270: A Single Supplement of a Standardised Bilberry Extract Modifies Glycaemic Response
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Keywords: anthocyanin
blaeberries
bilberries
blueberries
mirtoselect
glucose AUC
Lead sponsor: University of Aberdeen
Sponsor class: OTHER
First posted: 2010-11-22
Enrollment: 8
Sex: MALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Plasma Glucose iAUC (Incremental Area Under the Curve; mM*Min)
timeFrame: Plasma was collected at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min post capsule
measure: Plasma Insulin iAUC (Incremental Area Under the Curve; ng/ml*Min)
timeFrame: Plasma was collected at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min after the capsule
Secondary outcomes:
measure: Bioavailability in Plasma
timeFrame: Plasma will also be collected -15,-10, -5, 15, 30, 45, 60, 90, 120, 150, and 300 minutes and 24 hours post intervention
measure: Bioavailability in Urine
timeFrame: 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
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: University of Aberdeen Rowett Institute of Nutrition and Health
Study officials:
affiliation: University of Aberdeen Rowett Institute of Nutrition and Health
name: Nigel Hoggard, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martineau LC, Couture A, Spoor D, Benhaddou-Andaloussi A, Harris C, Meddah B, Leduc C, Burt A, Vuong T, Mai Le P, Prentki M, Bennett SA, Arnason JT, Haddad PS. Anti-diabetic properties of the Canadian lowbush blueberry Vaccinium angustifolium Ait. Phytomedicine. 2006 Nov;13(9-10):612-23. doi: 10.1016/j.phymed.2006.08.005. Epub 2006 Sep 18.
citation: Zafra-Stone S, Yasmin T, Bagchi M, Chatterjee A, Vinson JA, Bagchi D. Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res. 2007 Jun;51(6):675-83. doi: 10.1002/mnfr.200700002.
citation: Lau FC, Bielinski DF, Joseph JA. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. J Neurosci Res. 2007 Apr;85(5):1010-7. doi: 10.1002/jnr.21205.
citation: DeFuria J, Bennett G, Strissel KJ, Perfield JW 2nd, Milbury PE, Greenberg AS, Obin MS. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. J Nutr. 2009 Aug;139(8):1510-6. doi: 10.3945/jn.109.105155. Epub 2009 Jun 10.
citation: Hoggard N, Cruickshank M, Moar KM, Bestwick C, Holst JJ, Russell W, Horgan G. A single supplement of a standardised bilberry (Vaccinium myrtillus L.) extract (36 % wet weight anthocyanins) modifies glycaemic response in individuals with type 2 diabetes controlled by diet and lifestyle. J Nutr Sci. 2013 Jul 24;2:e22. doi: 10.1017/jns.2013.16. eCollection 2013.