Clinical trial NCT03869086: Metabolism of Anthocyanins and Heart Health
Official title: The Effects of Blueberry Anthocyanin Metabolism on Acute Cardiometabolic Health
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Healthy
Keywords: Blueberry
Metabolism
Anthocyanins
Inter-individual variation
Cardiometabolic health
Lead sponsor: University of East Anglia
Sponsor class: OTHER
First posted: 2019-03-11
Enrollment: 49
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Our research design involves screening individuals and then prospectively recruiting on the basis of two distinct blueberry metabolism profiles based on our previous research findings (in a population with metabolic syndrome). Our study will assess whether individuals with SLOW and FAST anthocyanin metabolism profiles respond differently and will test if the difference in processing may influence cardio metabolic responses. Our study involves feeding a single energy-dense meal which we anticipate will have a transient deleterious effect on acute markers of health. We will test whether adding blueberries to the energy dense meal improves acute responses compared against when adding the equivalent isocaloric amount of placebo. Participants will experience the blueberry and placebo treatments in random order
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Brachial artery endothelial function
timeFrame: assessed at 0, 1.5, 3, 6, 24, 48 hours after intervention intake
Secondary outcomes:
measure: Office blood pressure
timeFrame: Assessed at 0, 3, 6, 24, 48 hours after intervention intake.
measure: Bioavailability - serum
timeFrame: 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.
measure: Postprandial Insulin response
timeFrame: 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.
measure: Total cholesterol
timeFrame: 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 outcomes:
measure: Microbiome assessment of phyla and species
timeFrame: Sample collected up to 2 days prior to test meal 1 and assessed within 5 years of study completion
measure: Ambulatory blood pressure
timeFrame: 1 day before, and the two days following the intake of each energy dense test meal
measure: Aortic arterial stiffness (cf-PWV)
timeFrame: assessed at 0, 3, 6, 24, 48 hours after intervention intake
measure: Systemic arterial stiffness (AIx)
timeFrame: assessed at 0, 3, 6, 24, 48 hours after intervention intake
measure: Bioavailability - urine
timeFrame: 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)
measure: Postprandial glucose response
timeFrame: 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.
measure: High density lipoprotein cholesterol
timeFrame: 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.
measure: Triglycerides
timeFrame: 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.
measure: Low density lipoprotein cholesterol
timeFrame: 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.
Locations:
city: Norwich
country: United Kingdom
facility: Quadram Institute Clinical Research Facility; a partnership facility of the NHS, UEA and QIB
state: Norfolk
Study officials:
affiliation: University of East Anglia
name: Aedin Cassidy, PhD
role: PRINCIPAL_INVESTIGATOR
References: