Acute Effects of Blackcurrant and Citrus Polyphenol Extracts on Postprandial Glycaemia

Postprandial Period Clinical Trial

— Glu-FX  

Official title:

Acute Effects of Blackcurrant and Citrus Polyphenol Extracts on Postprandial Glycaemia: The Glu-FX Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03184064
• Other study ID #: HVS-007
• Status: Completed
• Phase: N/A
• Start date: May 30, 2017
• Est. completion date: June 1, 2018

Study information

• Verified date: August 2018
• Source: Lucozade Ribena Suntory
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Large postprandial glucose responses are associated with increased risk of chronic diseases, including diabetes and cardiovascular disease. Our group have previously shown that fruit polyphenol extracts, when consumed immediately before a mixed carbohydrate meal, reduce postprandial glycaemia. The aim of this study is to investigate the effects of a blackcurrant polyphenol extract and citrus polyphenol extract (and their combination), on postprandial glycaemia, insulinaemia and gastrointestinal hormone concentrations following a mixed carbohydrate test meal. It is hypothesised that blackcurrant and citrus extracts alone will inhibit glycaemia compared to placebo, and a combination of the two will have a greater effect.

Description:

Intake of carbohydrate-rich foods transiently increases blood glucose levels (known as postprandial glycaemia). Repeated high postprandial glucose responses are evidenced to dysregulate functional proteins, oxidative stress and pancreatic beta cell function; thus increasing the risk of diabetes and cardiovascular disease. Accordingly, meals that elicit a reduced, or more gradual, rise in blood glucose levels are desirable. Fruit polyphenols may help to limit the glucose excursion following a high carbohydrate meal. Previous research by our group has demonstrated that blackcurrant polyphenols significantly inhibited the average incremental area under the curve (T+0 to +30 min) of plasma glucose. Possible mechanisms include inhibition of intestinal enzymes and inhibition of intestinal glucose absorption by decreasing Sodium-glucose linked transporter 1 (SGLT-1) / Glucose transporter 2 (GLUT-2) glucose transporter activity. In vitro data suggests that citrus polyphenols may impact on carbohydrate metabolism by binding to starch molecules, however, effects on postprandial glycaemia are not yet known. Blackcurrants and citrus fruits have distinct polyphenol profiles and may therefore act on glucose homeostasis via different mechanisms. Blackcurrants are rich in anthocyanins and flavanols, whereas citrus fruits are rich in flavanones, hesperetin and naringenin. Theoretically, combining blackcurrant with citrus extracts may have synergistic effects.

The aim of this study is to investigate the effects of blackcurrant polyphenol extracts and citrus polyphenol extracts (and their combination), on postprandial glycaemia, insulinaemia and gastrointestinal hormone concentrations following a mixed carbohydrate test meal. It is hypothesised that blackcurrant and citrus extracts alone will inhibit glycaemia compared to placebo, a combination of the two will have a greater effect.

Study design: A randomised, controlled, double-blind, cross-over study will be conducted. Subjects will consume different drinks at 4 separate study visits. Drinks will contain either: blackcurrant extract (low dose), blackcurrant extract (high dose), citrus extract (low dose), blackcurrant and citrus extract (low dose + low dose), or placebo (no polyphenols). The study will utilise an incomplete block design. Subjects will consume the placebo drink and 3 out of 4 of the polyphenol-containing drinks during the study. At least a 7-day wash-out period will be required between study days. Baseline (fasted) blood samples will be taken in duplicate at T-10 min and T-5 min before consuming the test drink (T+0 min). Immediately following consumption of the drink, a mixed carbohydrate test meal will be consumed. Further blood samples will be collected at 10 min intervals for the first 30 min and then every 15 min until T+90 min and at T+120 min. Blood samples will be analysed for plasma glucose, insulin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), C-peptide and nonesterified fatty acids (NEFA).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 1, 2018
• Est. primary completion date: February 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age: 18-70 years

• Men and women

• Healthy (free of diagnosed diseases listed in the exclusion criteria)

• Body Mass Index 18-35 kg/m2

• Able to understand the information sheet and willing to comply with study protocol

• Able to give informed written consent

Exclusion Criteria:

• Those diagnosed with Phenylketonuria (PKU)

• Those with known or suspected food intolerances, allergies or hypersensitivity

• Women who are known to be pregnant or who are intending to become pregnant over the course of the study

• Women who are breast feeding

• Participation in another clinical trial

• Those who have donated blood within 3 months of the screening visit and participants for whom participation in this study would result in having donated more than 1500 millilitres of blood in the previous 12 months.

• Full Blood Counts and Liver Function test results outside of the normal range.

• Current smokers, or reported giving up smoking within the last 6 months

• History of substance abuse or alcoholism

• Reported history of Cardiovascular disease, diabetes (or fasting glucose = 7.1 mmol/L), cancer, kidney, liver or bowel disease, gastrointestinal disorder or use of drug likely to alter gastrointestinal function

• Unwilling to restrict consumption of specified high polyphenol foods for 48 h before the study

• Weight change >3kg in preceding 2 months

• Blood pressure =160/100 mmHg

• Total cholesterol = 7.5 mmol/L; fasting triacylglycerol concentrations = 5.0 mmol/L

• Medications that may interfere with the study: alpha-glucosidase inhibitors (acarbose:

Glucobay), insulin sensitizing drugs (metformin: Glucophage, Glucophage SR, Eucreas, Janumet; thiazolidinediones: Actos, Competact), sulfonylureas (Daonil, Diamicron, Diamicron MR, Glibenese, Minodiab, Amaryl Tolbutamide), and lipid lowering drugs (statins, nicotinic acid, colestyramine anhydrous, ezetimibe, fibrates). Other medications should be reviewed by medical representative from KCL on a case by case basis.

• Nutritional supplements that may interfere with the study: higher dose vitamins/minerals (>200% Recommend Nutrient Intake), B vitamins, Vitamin C, calcium, copper, chromium, iodine, iron, magnesium, manganese, phosphorus, potassium and zinc. Subjects already taking vitamin or minerals at a dose around 100% or less up to 200% of the RNI, or evening primrose/algal/fish oil supplements will be asked to maintain habitual intake patterns, ensuring that they take them every day and not sporadically. They will be advised not to stop taking supplements or start taking new supplements during the course of the study.

Related Conditions & MeSH terms

• Postprandial Period

Intervention

Dietary Supplement:
• Blackcurrant extract (low dose)
Participants will consume a small beverage that contains blackcurrant extract (low dose) immediately before a high-carbohydrate meal.
• Placebo
Participants will consume a small beverage that contains no fruit extracts immediately before a high-carbohydrate meal.
• Citrus extract (low dose)
Participants will consume a small beverage that contains citrus extract (low dose) immediately before a high-carbohydrate meal.
• Blackcurrant extract (high dose)
Participants will consume a small beverage that contains blackcurrant extract (high dose) immediately before a high-carbohydrate meal.
• Blackcurrant and citrus extracts (low dose / low dose)
Participants will consume a small beverage that contains blackcurrant and citrus extracts (low dose / low dose)immediately before a high-carbohydrate meal.

Locations

Country	Name	City	State
United Kingdom	Metabolic Research Unit	London	England

Sponsors (2)

Lead Sponsor	Collaborator
Lucozade Ribena Suntory	King's College London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Castro-Acosta ML, Smith L, Miller RJ, McCarthy DI, Farrimond JA, Hall WL. Drinks containing anthocyanin-rich blackcurrant extract decrease postprandial blood glucose, insulin and incretin concentrations. J Nutr Biochem. 2016 Dec;38:154-161. doi: 10.1016/j.jnutbio.2016.09.002. Epub 2016 Sep 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Food diary (estimated/unweighed)	Habitual dietary intake analysis	7-days, collected at screening
Other	VAS measures of the palatability of the study drink	Descriptive statistics	10 min following the test drink
Other	VAS measures of mood, satiety and digestive comfort	Descriptive statistics	120 min
Other	Buccal mouth swab	Future exploratory analysis of lactase activity via the derived allele at the European lactase persistence (LP) locus	One off sample, collected at screening
Primary	Postprandial glycaemia (iAUC 0-30 min)	The primary endpoint is iAUC 0-30 min for plasma glucose concentrations	30 min
Secondary	Postprandial glycaemia: iAUC 0-120 min	iAUC 0-120 min for plasma glucose concentrations	120 min
Secondary	Postprandial glycaemia: iCmax	iCmax for plasma glucose concentrations	120 min
Secondary	Postprandial glycaemia: Tmax	Tmax for plasma glucose concentrations	120 min
Secondary	Postprandial glycaemia: absolute concentrations at specific time points	Absolute concentrations at specific time points, for plasma glucose concentrations	120 min
Secondary	Postprandial insulinemia: iAUC 0-30 min	iAUC 0-30 min for serum insulin concentrations	30 min
Secondary	Postprandial insulinemia: iAUC 0-120 min	iAUC 0-120 min for serum insulin concentrations	120 min
Secondary	Postprandial insulinemia: iCmax	iCmax, for serum insulin concentrations	120 min
Secondary	Postprandial insulinemia: Tmax	Tmax for serum insulin concentrations	120 min
Secondary	Postprandial insulinemia: absolute concentrations at specific time points	Absolute concentrations at specific time points, for serum insulin concentrations	120 min
Secondary	Postprandial C-peptide: iAUC 0-30 min	iAUC 0-30 min for plasma C-peptide concentrations	30 min
Secondary	Postprandial C-peptide: iAUC 0-120 min	iAUC 0-120 min for plasma C-peptide concentrations	30 min
Secondary	Postprandial C-peptide: iCmax	iCmax for plasma C-peptide concentrations	120 min
Secondary	Postprandial C-peptide: Tmax	Tmax for plasma C-peptide concentrations	120 min
Secondary	Postprandial C-peptide: Absolute concentrations at specific time points	Absolute concentrations at specific time points, for plasma C-peptide concentrations	120 min
Secondary	Postprandial non-esterified fatty acids (NEFA): iAUC 0-30 min	iAUC 0-30 min for serum NEFA concentrations	30 min
Secondary	Postprandial non-esterified fatty acids (NEFA): iAUC 0-120 min	iAUC 0-120 min for serum NEFA concentrations	120 min
Secondary	Postprandial non-esterified fatty acids (NEFA): iCmax	iCmax for serum NEFA concentrations	120 min
Secondary	Postprandial non-esterified fatty acids (NEFA): Tmax	Tmax for serum NEFA concentrations	120 min
Secondary	Postprandial non-esterified fatty acids (NEFA): Absolute concentrations at specific time points	Absolute concentrations at specific time points, for serum NEFA concentrations	120 min
Secondary	Postprandial blood glucose-dependent insulinotropic peptide (GIP): iAUC 0-30 min	iAUC 0-30 min for plasma GIP concentrations	30 min
Secondary	Postprandial blood glucose-dependent insulinotropic peptide (GIP): iAUC 0-120 min	iAUC 0-120 min for plasma GIP concentrations	120 min
Secondary	Postprandial blood glucose-dependent insulinotropic peptide (GIP): iCmax	iCmax, for plasma GIP concentrations	120 min
Secondary	Postprandial blood glucose-dependent insulinotropic peptide (GIP): Tmax	Tmax for plasma GIP concentrations	120 min
Secondary	Postprandial blood glucose-dependent insulinotropic peptide (GIP): Absolute concentrations at specific time points	Absolute concentrations at specific time points, for plasma GIP concentrations	120 min
Secondary	Postprandial blood Glucagon-like peptide 1 (GLP-1): iAUC 0-30 min	iAUC 0-30 min for plasma GLP-1 concentrations	30 min
Secondary	Postprandial blood Glucagon-like peptide 1 (GLP-1): iAUC 0-120 min	iAUC 0-120 min, for plasma GLP-1 concentrations	120 min
Secondary	Postprandial blood Glucagon-like peptide 1 (GLP-1): iCmax	iCmax for plasma GLP-1 concentrations	120 min
Secondary	Postprandial blood Glucagon-like peptide 1 (GLP-1): Tmax	Tmax for plasma GLP-1 concentrations	30 min
Secondary	Postprandial blood Glucagon-like peptide 1 (GLP-1): Absolute concentrations at specific time points	Absolute concentrations at specific time points, for plasma GLP-1 concentrations	120 min
Secondary	Postprandial blood peptide YY (PYY): iAUC 0-30 min	iAUC 0-30 min for plasma PYY concentrations	30 min
Secondary	Postprandial blood peptide YY (PYY): iAUC 0-120 min	iAUC 0-120 minfor plasma PYY concentrations	120 min
Secondary	Postprandial blood peptide YY (PYY): iCmax	iCmax for plasma PYY concentrations	120 min
Secondary	Postprandial blood peptide YY (PYY): Tmax	Tmax for plasma PYY concentrations	120 min
Secondary	Postprandial blood peptide YY (PYY): Absolute concentrations at specific time points	Absolute concentrations at specific time points, for plasma PYY concentrations	120 min