Replacement of Saturated Fat in Dairy on Total Cholesterol (RESET)

• ClinicalTrials.gov Identifier: NCT02089035
• Recruitment Status: Completed
• First Posted: March 17, 2014
• Last Update Posted: July 24, 2017
• Sponsor: University of Reading
• Collaborator: Medical Research Council
• Information provided by (Responsible Party): Julie Lovegrove, University of Reading

Study Description

Brief Summary:

The consumption of milk and dairy products is recognised as an essential part of a healthy diet as it represents an important source of key micro- and macronutrients. Nevertheless, there is still a widespread conviction that the overall high energy density and concentration of long-chain saturated fatty acids (SFA) present in dairy have detrimental health effects, contributing to the progression of cardiovascular disease, obesity and diabetes.

Supplementation of the bovine diet with a source of MUFA, such as rapesee oil, has become an achievable strategy in order to reduce the amount of SFA present in dairy products.

The aim of this project is to observe the effects of three types of dairy products (UHT milk, cheese and butter) produced from milk derived from cows fed withhigh-oleic sunflower oil, on CVD risk biomarkers and plasma total cholesterol levels in adults with an increased risk of developing CVD. The aim is to determine whether an isoenergetic exchange of dairy products will affect vascular function and CVD biomarkers.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Dietary Supplement: MUFA-rich dairy products (UHT milk, cheese and butter); Dietary Supplement: Conventional dairy products (UHT milk, cheese, butter)	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Replacement of Saturated Fat in Dairy on Total Cholesterol, Vascular Function, Ambulatory Blood Pressure and Cardiovascular Risk Biomarkers
• Study Start Date: May 2014
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: April 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: MUFA-rich dairy products; Subjects are asked to exchange habitual dairy products for modified MUFA-rich experimental dairy products for a 12 week period. Participants will provided with standardised quantities of pasteurised UHT milk, cheese and butter that they will be asked to consume on a daily basis.	Dietary Supplement: MUFA-rich dairy products (UHT milk, cheese and butter)
Experimental: Conventional dairy products; Subjects are asked to consume habitual non-modified dairy products for a period of 12 weeks. Participants will provided with standardised quantities of pasteurised UHT milk, cheese and butter that they will be asked to consume on a daily basis.	Dietary Supplement: Conventional dairy products (UHT milk, cheese, butter)

Outcome Measures

Primary Outcome Measures :

1. Chronic study: Changes in fasting plasma circulating levels of total cholesterol [ Time Frame: Chronic study: Baseline and week 12 for both intervention arms ]
2. Acute study: Changes in postprandial flow-mediated dilatation [ Time Frame: Acute study: 0, 180, 300 and 420 min at baseline and week 12 for both intervention arms ]

Secondary Outcome Measures :

1. Changes in vascular stiffness by Carotid Intima Media Thickness (CIMT) [ Time Frame: Chronic study: Baseline measurements (0min) for both intervention arms ]
2. Change in 24-hour ambulatory blood pressure [ Time Frame: Chronic study: baseline (-1week) and week 11, 19 and 31 for 24 hours. Measurements will be recorded every 30min (7am to 10pm) and every hour (10pm-7am) ]
3. Changes in plasma circulating markers of vascular health [ Time Frame: Chronic study: Baseline and week 12 for both intervention arms. Acute study: area under the curve from 0-8 h after consumption of breakfast (0 min) and lunch (330 min) for both intervention arms ]
4. Changes in plasma circulating markers of inflammatory status [ Time Frame: Chronic study: Baseline and week 12 for both intervention arms. Acute study: area under the curve from 0-8 h after consumption of breakfast (0 min) and lunch (330 min) for both intervention arms ]
5. Changes in plasma circulating markers related to lipid metabolism [ Time Frame: Chronic study: Baseline and week 12 for both intervention arms. Acute study: area under the curve from 0-8 h after consumption of breakfast (0 min) and lunch (330 min) for both intervention arms ]
6. Changes in plasma circulating markers related to insulin resistance [ Time Frame: Chronic study: Baseline and week 12 for both intervention arms. Acute study: area under the curve from 0-8 h after consumption of breakfast (0 min) and lunch (330 min) for both intervention arms ]
7. Changes in vascular stiffness by Pulse Wave Velocity (PWV) [ Time Frame: Chronic study: Baseline (0 min) and week 12 for both intervention arms ]
8. Changes in vascular stiffness by Pulse Wave Analysis (PWA) [ Time Frame: Chronic study: Baseline (0 min) and week 12 for both intervention arms ]
9. Changes in vascular stiffness by Digital Volume Pulse (DVP) [ Time Frame: Chronic study: Baseline (0 min) and week 12 for both intervention arms ]
10. Changes in monocytic cytokine production from whole blood culture [ Time Frame: Chronic and acute study: Baseline and week 12 for both intervention arms. Acute: area under the curve from 0-8 h following consumption of breakfast (0 min) and lunch (330 min) for both intervention arms ]
11. Changes in vascular reactivity by Flow Mediated Dilatation (FMD) [ Time Frame: Chronic study: Baseline and assessment at 12 weeks for each intervention arm. ]
12. Changes in anthropometric measurements [ Time Frame: Chronic study: Baseline and assessment at 12 weeks for each intervention arm. ]
13. Change in plasma phospholipid fatty acid composition [ Time Frame: Chronic and acute study: Baseline and week 12 for both intervention arms. Acute study: 0, 180, 300 and 420 min at baseline and week 12 for both intervention arms ]

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Mildly hypercholesterolemic: TC <5.2 and <8mmol/L
• Age: 25-70
• BMI: 19-32 kg/m2
• Haemoglobin: >125g/L for women and 135g/L for men
• Normal liver and kidney function

Exclusion Criteria:

• Milk, cheese, butter, lactose allergy
• Drug treatment for hyperlipidaemia, hypertension, inflammation and hypercoagulation
• Suffered myocardial infarction/stroke in the past 12months
• Diabetic (diagnosed or fasting glucose > 7 mmol/l) or suffer from other endocrine disorders
• Surgery in the previous 6 months
• Excessive alcohol consumption (>28 unit/wk man; >21 unit/wk women)
• Taking vitamin, mineral or fatty acid supplements (e.g. fish oil, calcium)
• Pregnant, lactating, planning a pregnancy or not using effective contraceptive precautions
• Smokers
• Vegans
• Anaemic
• Planning or on a weight reduction scheme
• Parallel participation in another intervention study
• Participating in intensive aerobic activity for > 20 minutes 3 times per week
• Use of anti-inflammatory medication

Contacts and Locations

Locations

United Kingdom

Department of Food and Nutritional Sciences, University of Reading

Reading, Berks, United Kingdom, RG6 6AP

Sponsors and Collaborators

University of Reading

Medical Research Council

Investigators

• Principal Investigator: Julie A. Lovegrove, BSc, PhD, RNutr; University of Reading

More Information

Publications:

Livingstone KM, Lovegrove JA, Givens DI. The impact of substituting SFA in dairy products with MUFA or PUFA on CVD risk: evidence from human intervention studies. Nutr Res Rev. 2012 Dec;25(2):193-206. doi: 10.1017/S095442241200011X. Epub 2012 Aug 6. Review.

Elwood PC, Pickering JE, Givens DI, Gallacher JE. The consumption of milk and dairy foods and the incidence of vascular disease and diabetes: an overview of the evidence. Lipids. 2010 Oct;45(10):925-39. doi: 10.1007/s11745-010-3412-5. Epub 2010 Apr 16. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vasilopoulou D, Markey O, Kliem KE, Fagan CC, Grandison AS, Humphries DJ, Todd S, Jackson KG, Givens DI, Lovegrove JA. Reformulation initiative for partial replacement of saturated with unsaturated fats in dairy foods attenuates the increase in LDL cholesterol and improves flow-mediated dilatation compared with conventional dairy: the randomized, controlled REplacement of SaturatEd fat in dairy on Total cholesterol (RESET) study. Am J Clin Nutr. 2020 Apr 1;111(4):739-748. doi: 10.1093/ajcn/nqz344.

Markey O, Vasilopoulou D, Kliem KE, Koulman A, Fagan CC, Summerhill K, Wang LY, Grandison AS, Humphries DJ, Todd S, Jackson KG, Givens DI, Lovegrove JA. Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial. Nutr J. 2017 May 23;16(1):33. doi: 10.1186/s12937-017-0249-2.

• Responsible Party: Julie Lovegrove, Professor, University of Reading
• ClinicalTrials.gov Identifier: NCT02089035
• Other Study ID Numbers: 13/43; University of Reading ( Other Identifier: University of Reading )
• First Posted: March 17, 2014
• Last Update Posted: July 24, 2017
• Last Verified: May 2016

Keywords provided by Julie Lovegrove, University of Reading:

Milk fatty acids; Total cholesterol; Vascular function; Blood pressure

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases