Study title
Effect of Apples on cardioVascular risk And Gut health
Template
Intervention/Observation study
title
Effect of Apples on cardioVascular risk And Gut health
description
Work aimed to prove that a frequent apple intake will reduce the risk of cardiovascular disease risk factors in mildly hypercholesterolaemic subjects by improving blood lipid levels, vascular function, inflammatory markers and gut microbiota composition and metabolomic activity.
MEtabolights Code: MTBLS469
startDate
2010-06-16 00:00:00.0
Study type
Human Intervention
Principle Investigator
Julie Lovegrove
Primary endpoint
Work aimed to prove that a frequent apple intake will reduce the risk of cardiovascular disease risk factors in mildly hypercholesterolaemic subjects by improving blood lipid levels, vascular function, inflammatory markers and gut microbiota composition a
Objectives
The overall objective was to explore the effects of fresh whole apples on cardiovascular disease risk factors and gut microbiota composition and metabolomic activity using an in vitro batch culture and a chronic human randomized controlled trial. An Illumina based 16S rRNA gene amplicon sequencing was performed to capture in detail the faecal microbiota community, and metabolomics was used to identify microbial derived metabolites.
Central conclusion
The present study has shown that whole apples can modify the human faecal microbiota composition and activity in vitro. Effects were observed at both phylum and taxa level. Consumption of 2 fresh whole apples (Renetta Canada, 340g/d containing 1013 mg of polyphenols, 854 mg PAs, 8.5 g fibre of which 3.7 g soluble) significantly decreased serum TC and LDL-C with no detrimental effect on HDL-C compared with sugar-matched control in a RCT in 40 men and women with moderately raised serum cholesterol. A wide range of metabolites was found un 24h urine and plasma that were associated with microbiota activities.
Exclusion criteria
an abnormal blood biochemistry profile, based on standard clinical cut-offs, were excluded. Further exclusion criteria included medical history of heart disease (or family history) and diabetes mellitus; kidney, liver or pancreatic diseases; hematological and gastrointestinal disorders; medication for hyperlipidaemia, hypertension, hypercoagulation, inflammation and gastrointestinal motility. Other ineligibility criteria were pregnancy (current or planned) or lactating, smoker, history of alcohol misuse, antibiotic intake <3 months before the study, food supplement use, including fish oil, vitamins, phytochemicals, probiotics and prebiotics (unless willing to stop 2-month before study commencement), habitual intake of more than one apple/d, vegetarian and vegan diet and planned weight loss regime
Inclusion criteria
Mildly hypercholesterolemic: TC >5.2 and < 7.9 mmol/L; BMI: 20-35; Age: 23-69
Institute
Hugh Sinclair Unit of Human Nutrition and the Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional SciencesUniversity of ReadingReadingUK and Fondazione Edmund Mach
Country (for multicentre study overall PI)
UK
Funding body
The study is funded by the University of Reading (RETF) and the IASMA Research and Innovation Centre-Fondazione Edmund Mach, San Michele all’ Adige, North Italy.
Clinicaltrials.gov or similar number
NCT01988389
Was the study approved by an ethics committee?
Yes
Ethical approval number
University of Reading Research Ethics Committee (UREC Project No. 13/22 (AVAG study)),
Did the individuals providing data sign informed consent?
Yes
Study design
Case-control
Type of controls
placebo juice with aroma of apple
Blinding method
Envelopes without safeguards (e.g. unsealed or transparent or un-numbered);
Compliance assessment (for each treatment)
24 hour urinary phloretin
Number of factors (for factorial designs only)
3
Total number of arms (Give number of distinct treatments in study)
2
Explanatory text (Give a textual account of the overall design leading to the total number of groups) or provide the study protocol.
The present trial was a randomized, controlled, crossover, dietary intervention study. Forty-three volunteers were recruited onto the study, three volunteers dropped out due to personal reasons, and forty subjects completed the trial (n=40, 17 males, 23 females). For a 2-week run-in period prior to the dietary intervention, volunteers followed their habitual diet but were required not to consume probiotics (e.g. live yogurts, fermented milk drinks), prebiotics (such as inulin, oligofructose) and any apples, apple juice or apple containing foods. Probiotics, prebiotics and any other apple products (apart from the provided items) were also strictly avoided throughout the study period (20 weeks). Volunteers were randomly allocated into two groups, stratified by age, gender, BMI and serum cholesterol, to receive daily either 2 apples or a sugar-matched control beverage. One group (n=22) consumed 2 apples daily (340g without core) for 8 weeks, and then after a 4-week washout period, consumed 500 ml of a sugar-matched control apple beverage (100 ml concentrated + 400 ml water) daily for a further 8 weeks, whereas the other group (n=18) received the intervention foods in the reverse order. Volunteers were asked to incorporate the intervention products into their normal habitual diet, and understood that both products had potential benefit. Clear instructions were given to eat the apple skin and flesh and not to consume the apple core.
The study included 4 main visits before and after each intervention period (Day 1, 56, 84 and 140). Twenty-four hours before each study visit, volunteers were asked to refrain from intensive exercise, alcohol, oily fish and any caffeine intake (e.g. coffee, tea). The night before they consumed a standardized low-fat, low-flavonoid meal followed by an overnight fast consuming only water. The volunteers were asked to attend the Hugh Sinclair Unit of Human Nutrition in the morning on each of the 4 study visits and a fasted blood samples and a 24-hour urine sample were collected. During these visits anthropometrical (height, weight, waist-hip circumference), % body fat composition (body composition analyzer, Tanita, BC-418 digital scale), blood pressure (30-minute measurement), arterial stiffness (Pulse Wave Analysis, PWA) and microvascular reactivity (Laser Doppler imaging with iontophoresis, LDI) measurement were taken. Volunteers collected the intervention products every fortnight when they were also asked if there were any changes to their lifestyle, such as diet, exercise levels and medication. Finally, compliance and liking of the apples were assessed with the daily completion of a tick sheet and a nine-point visual analogue scale (1= dislike extremely and 9=like extremely), respectively.
Number of volunteers screened N(M:xx, F: xx)
43 (M:18, F:25)
Number of volunteers enrolled N(M:xx, F: xx)
40 (M:17, F:23)
Number of subjects (Male; Female)
40 (M:17, F:23)
Start of recruitment (Start year or date)
2013-01-01 00:00:00.0
End of recruitment (End year or date)
2013-12-30 00:00:00.0
