Metabolism of Anthocyanins and Heart Health (AMP)

The Effects of Blueberry Anthocyanin Metabolism on Acute Cardiometabolic Health

This study aims to find out if consuming a single dose of blueberries, rich in anthocyanins, within an energy dense meal, improves blood vessel function and biomarkers of heart health. The study specifically aims to confirm if differences in how individuals process the bioactive compounds in blueberries, called anthocyanins, has an influence on heart health. The investigators will assess the effects of eating one portion of blueberries on vascular health over a 48hour period, and will track the breakdown compounds within blood and urine, to see if health effects are related to metabolism.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Other: Freeze dried blueberry powder; Other: Anthocyanin free, sugar-matched placebo

Detailed Description

The primary aim of this cross-over designed, placebo controlled, acute dietary intervention study, is to prospectively recruit participants on the basis of anthocyanin metabolism profiles (based on profiles confirmed in our previous studies) following a 'blueberry challenge'. Acute cardio and metabolic function responses will be assessed (by metaboliser profile), following an energy dense test meal with/without the addition of blueberries.

Participants will be healthy, but overweight and obese (BMI inclusion: ≥ 25kg/m2) men and women (aged 50 y to 80 y), who will initially undertake a 'blueberry challenge' by consuming a single dose of freeze dried blueberries. Anthocyanin metaboliser type will be profiled from the analysis of metabolites within urine, collected for 48h following the 'challenge'.

A total of 70 participants will complete the intervention (n=35 FAST and n=35 SLOW metabolisers) which consists of two, test meal periods (separated by at least 7d and allocated in random order); 1) energy dense test meal plus freeze dried blueberries, 2) energy dense test meal plus an isocaloric matched placebo material. Urine samples and ambulatory blood pressure measures will be collected for 24h prior to, and then over the 48h period which follows the test meal intake. Further assessment of vascular and metabolic function will be made at pre-defined times over the 48h postprandial period. Dietary restrictions to abstain from blueberries and reduce the anthocyanin intake level, will be applied for 5d before each test meal intake. In addition, all food and drink will be provided for a 4d period (2d before and during the 48h following the energy dense test meal) to further control the intake of flavonoids and to standardise the influence of background diet on metabolism profile.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UQ
      • Quadram Institute Clinical Research Facility; a partnership facility of the NHS, UEA and QIB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI >= 25 kg/m2
• Adults aged 50 - 80 years old
• Successful biochemical, haematological, and urinalysis assessment at screening

Exclusion Criteria:

• Current smokers, or ex-smokers ceasing < 6 months ago
• existing or significant past medical history of vascular disease or medical conditions likely to affect the study measures
• Fructose or lactose intolerant subjects or known allergies to intervention treatments
• Those unprepared to adhere to dietary instructions
• Parallel participation in another research project involving dietary intervention and/or sampling of biological fluids/material
• Those on therapeutic diets or having experienced substantial weight loss within 2 months of screening.
• Those taking flavonoid, nitrate / nitrite containing or fish oil containing supplements (and unwilling to cease intake during, and 1 month preceding the trial) or unwilling to maintain existing intake of other supplements.
• Prescribed hypoglycaemic, anti-hypertensive, vasodilator or hormone replacement therapy (HRT) medication.
• Unsatisfactory biochemical, haematological or urinary results or measurements considered to be counter indicative for the study
• Undiagnosed hypertension (elicited at screening; i.e. ≥ 180 / 110mmHg) at a level requiring immediate referral back to general practitioner for follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SLOW anthocyanin metabolisers; Participants will be prospectively recruited to the SLOW anthocyanin metaboliser group, following a pre-intervention screen (blueberry challenge). Participants in this arm will consume (in random order) blueberry and placebo interventions (both consumed with an energy dense meal) in a cross-over manner. At least 7 days washout will be observed between the two treatments.	Other: Freeze dried blueberry powder; 36 g of freeze-dried blueberry powder to be mixed with milk and served together with an energy-dense meal.; Other: Anthocyanin free, sugar-matched placebo; 36 g of isocaloric placebo, matched for sugars to be mixed with milk and served together with an energy-dense meal.
EXPERIMENTAL: FAST anthocyanin metabolisers; Participants will be prospectively recruited to the FAST anthocyanin metaboliser group, following a pre-intervention screen (blueberry challenge). Participants in this arm will consume (in random order) blueberry and placebo interventions (both consumed with an energy dense meal) in a cross-over manner. At least 7 days washout will be observed between the two treatments.	Other: Freeze dried blueberry powder; 36 g of freeze-dried blueberry powder to be mixed with milk and served together with an energy-dense meal.; Other: Anthocyanin free, sugar-matched placebo; 36 g of isocaloric placebo, matched for sugars to be mixed with milk and served together with an energy-dense meal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brachial artery endothelial function	percentage maximum dilatation assessed via flow mediated dilation (%FMD): (diametermax-diameterbaseline) / diameterbaseline×100.	assessed at 0, 1.5, 3, 6, 24, 48 hours after intervention intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Office blood pressure	Measurements of blood pressure	Assessed at 0, 3, 6, 24, 48 hours after intervention intake.
Bioavailability - serum	Assessment of flavonoid and metabolite levels in blood samples	Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake.
Postprandial Insulin response	Assessment of postprandial insulin control	Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake.
Total cholesterol	Assessment of blood cholesterol	Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome assessment of phyla and species	Assessment of the gut microbiome from faecal samples collected from FAST and SLOW anthocyanin metabolisers.	Sample collected up to 2 days prior to test meal 1 and assessed within 5 years of study completion
Ambulatory blood pressure	Measurement of pre-intervention and postprandial ambulatory blood pressure	1 day before, and the two days following the intake of each energy dense test meal
Aortic arterial stiffness (cf-PWV)	Measurement of carotid to femoral pulse wave velocity	assessed at 0, 3, 6, 24, 48 hours after intervention intake
Systemic arterial stiffness (AIx)	Measurement of brachial augmentation index (adjusted to 75 beats per minute heart rate)	assessed at 0, 3, 6, 24, 48 hours after intervention intake
Bioavailability - urine	Assessment of flavonoid and metabolite levels in 24 hour urine samples	3 days during the blueberry challenge (1 day before and the two days of the assessment) and 3 days during each test meal assessment (1 day before and the two days of the assessment)
Postprandial glucose response	Assessment of postprandial glucsoe control	Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake.
High density lipoprotein cholesterol	Assessment of blood high density lipoprotein cholesterol	Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake.
Triglycerides	Assessment of blood triglycerides	Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake.
Low density lipoprotein cholesterol	Assessment of blood low density lipoprotein cholesterol	Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake.

Collaborators and Investigators

• Sponsor: University of East Anglia

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 4, 2019
• Primary Completion (ACTUAL): January 6, 2021
• Study Completion (ACTUAL): January 6, 2021

Study Registration Dates

• First Submitted: March 4, 2019
• First Submitted That Met QC Criteria: March 7, 2019
• First Posted (ACTUAL): March 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Metabolism; Blueberry; Anthocyanins; Cardiometabolic health; Inter-individual variation
• Other Study ID Numbers: AMP001_22NOV2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No