Acute Effects of Blackcurrant and Citrus Polyphenol Extracts on Postprandial Glycaemia

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.

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).

Eligibility Criteria:
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.