An interventional study of Bilberry capsule first, then control cap and Control capsule first then bilberry cap in Type 2 Diabetes, sponsored by University of Aberdeen. Completed at 1 site in United Kingdom. Open to male participants aged 40 Years to 70 Years. Per ClinicalTrials.gov, last updated 2021-03-10.
Sponsored by University of Aberdeen · Not applicable, Interventional, and Treatment
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.
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.
9,589 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.
This study's enrollment of 8 is below the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →University of Aberdeen is the lead sponsor of 175 studies on the registry; 23 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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
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.
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.
Plasma Glucose iAUC (Incremental Area Under the Curve; mM*Min)
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.
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
Plasma Insulin iAUC (Incremental Area Under the Curve; ng/ml*Min)
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.
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
Bioavailability in Plasma
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.
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
Bioavailability in Urine
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.
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
Eight male volunteer subjects with T2D controlled by diet and lifestyle alone or with impaired glucose tolerance were recruited from the Aberdeen area of the UK. Subjects were only included if they were not on any special religious or prescribed diet and had a stable weight.
| Milestone | Single Control Capsule First Then Bilberry Capsule | Single Bilberry Capsule First Then Control Capsule |
|---|---|---|
| Started | 4 | 4 |
| Completed | 4 | 4 |
| Not completed | 0 | 0 |
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.
| glucose iAUC (mM*min) | Single Placebo Capsule | Single Blaeberry Capsule |
|---|---|---|
| Plasma Glucose iAUC (Incremental Area Under the Curve; mM*Min) | 836 ± 97 | 693 ± 103 |
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.
| insulin iAUC (ng/ml*min) | Single Control Capsule | Single Bilberry Capsule |
|---|---|---|
| Plasma Insulin iAUC (Incremental Area Under the Curve; ng/ml*Min) | 358 ± 131 | 294 ± 113 |
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Single Bilberry Capsule | — | 0/8 (0%) | 0/8 (0%) |
| Single Placebo Capsule | — | 0/8 (0%) | 0/8 (0%) |
| Age, Categorical(Participants) | Bilberry Capsule First, Then Control Capsule | Control Capsule First, Then Bilberry Capsule | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 4 | 4 | 8 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Bilberry Capsule First, Then Control Capsule | Control Capsule First, Then Bilberry Capsule | Total |
|---|---|---|---|
| Mean | 62 ± 5 | 62 ± 5 | 62 ± 5 |
| Sex: Female, Male(Participants) | Bilberry Capsule First, Then Control Capsule | Control Capsule First, Then Bilberry Capsule | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 4 | 4 | 8 |
| Region of Enrollment(participants) | Bilberry Capsule First, Then Control Capsule | Control Capsule First, Then Bilberry Capsule | Total |
|---|---|---|---|
| United Kingdom | 4 | 4 | 8 |
| BMI(Kg/m2) | Bilberry Capsule First, Then Control Capsule | Control Capsule First, Then Bilberry Capsule | Total |
|---|---|---|---|
| Mean | 30 ± 4 | 30 ± 4 | 30 ± 4 |
Plan to share: Undecided
This study is completed, as verified in Feb 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.