RISSCI-1 Blood Cholesterol Response Study

NCT03270527 | Completed DMC

• 1 other identifier: RN0307A
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 2

Brief Summary

Raised blood cholesterol (also referred to as blood LDL-cholesterol) is a major risk factor for developing heart disease. Dietary saturated fat is recognised as the main dietary component responsible for raising blood LDL-cholesterol, and reducing its intake has been the mainstay of dietary guidelines for the prevention of heart disease for over 30 years. However, there is very little evidence for a direct link between the intake of saturated fat and risk of dying from heart disease. One explanation for this, is that the link between saturated fat intake and heart disease is not a direct one, but relies heavily on the ability of saturated fat to raise blood LDL-cholesterol levels. This LDL cholesterol-raising effect of saturated fat is complex, and highly variable between individuals because of differences in the metabolism of dietary fat and cholesterol between people. The main aim of this study is to measure the amount of variation in blood LDL-cholesterol in healthy volunteers at the Universities of Surrey and Reading in response to lowering the amount of saturated fat in the diet to the level recommended by the government for the prevention of heart disease. This collaborative project between the Universities of Reading, Surrey and Imperial ('RISSCI-1' Blood Cholesterol Response Study') will permit identification of two subgroups of men who show either a high or low LDL-cholesterol response to a reduction in dietary saturated intake. These two groups of participants will be provided with an opportunity to participate in a similar follow-up study ('RISSCI-2') that will also take place at the University of Surrey and Reading. In this follow-up study, the participants will be asked to repeat a similar study protocol as for RISSCI-1, but undergo more detailed measurements to investigate the metabolic and genetic origins of how saturated fat is metabolised in the body and influences blood LDL-cholesterol (LDL-C).

Conditions

Lipids; Lipid Metabolism; Healthy

Keywords

Dietary fat modification; Lipids; LDL cholesterol; Dietary fatty acids; Saturated fat

Outcome Measures

Primary Outcomes (1)

• Changes in fasting total cholesterol (consisting of LDL-cholesterol and HDL) concentrations

  Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)

Secondary Outcomes (18)

• Fasting triacylglycerol

  Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)

• HDL immune functions

  Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)

• HDL anti-inflammatory and anti-oxidant (PON-1) properties

  Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)

• HDL capacity to promote cholesterol efflux (ex-vivo)

  Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)

• Fasting insulin, glucose

  Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)

Other Outcomes (1)

• Genotyping for apolipoprotein E to determine the impact of this genotype on changes in the primary and secondary outcome measurements in response to dietary fat intake

  Baseline

Study Arms (1)

High SFA diet to low SFA diet

EXPERIMENTAL

Participants will undergo, sequentially, a high SFA diet (Diet 1) followed by a low SFA diet (Diet 2) for 4 weeks each. Study visits will occur before and after each dietary intervention period. To comply with current UK dietary recommendations, Diets 1 and 2 will both contain \~35% energy from total fat. These diets will be consumed within the homes of free-living participants, by the substitution of \~40g of habitual fat, with either SFA-rich or mono/poly-unsaturated fatty acid-rich (MUFA/PUFA) cooking oils, spreads and snack foods, while maintaining their habitual diet (consistent intake of protein and carbohydrates, including dietary fibre). This will be achieved using a dietary exchange model developed and peer-reviewed for a previous dietary intervention study ('DIVAS') at the University of Reading, U.K.

Other: High SFA diet (Diet 1); Other: Low SFA diet (Diet 2)

Interventions

High SFA diet (Diet 1) OTHER

'Diet 1' will contain \~18% of its total energy as SFA .

High SFA diet to low SFA diet

Low SFA diet (Diet 2) OTHER

'Diet 2' will contain \~10% of its total energy as SFA. The SFA-replacement fats will be mixture of PUFA/MUFA.

High SFA diet to low SFA diet

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI of 19-32 kg/m2
• Fasting serum total cholesterol \< 7.5 mmol/l and triacylglycerol \< 2.3 mmol/l

You may not qualify if:

• Smokers
• Medical history of myocardial ischemia or stroke in the past 12 months;
• Diabetes (defined as fasting glucose \> 7.0 mmol/l) or other endocrine disorders; kidney, liver, pancreas or gastrointestinal disorders
• Hypertension (blood pressure \> 140/90 mmHg),
• Cancer
• Medication for hyperlipidaemia (e.g. statins), hypertension, inflammation or prescribed antibiotics within the last three months
• Drinking in excess of 14 units of alcohol per week,
• Anaemia (\<130 g/L haemoglobin), or planning on a weight-reducing regime
• Taking any dietary supplements known to influence lipids/gut microbiota (eg. plant stanols, fish oil, phytochemicals, natural laxatives, probiotics and prebiotics)
• Any other unusual medical history or diet and lifestyle habits or practices that would preclude volunteers from participating in a dietary intervention and metabolic study.

Sponsors & Collaborators

• University of Surrey: lead
• University of Reading: collaborator
• Imperial College London: collaborator

Study Sites (2)

Department of Food and Nutritional Sciences, University of Reading

Reading, Berkshire, RG6 6AP, United Kingdom

Location

Department of Nutritional Sciences, University of Surrey

Guildford, Surrey, GU2 7WG, United Kingdom

Location

Related Publications (3)

• Vafeiadou K, Weech M, Altowaijri H, Todd S, Yaqoob P, Jackson KG, Lovegrove JA. Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study. Am J Clin Nutr. 2015 Jul;102(1):40-8. doi: 10.3945/ajcn.114.097089. Epub 2015 May 27.

  PMID: 26016869 BACKGROUND

• Koutsos A, Griffin BA, Antoni R, Ozen E, Sellem L, Wong G, Ayyad H, Fielding BA, Robertson MD, Swann J, Jackson KG, Lovegrove JA. Variation of LDL cholesterol in response to the replacement of saturated with unsaturated fatty acids: a nonrandomized, sequential dietary intervention; the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention ("RISSCI"-1) study. Am J Clin Nutr. 2024 Oct;120(4):854-863. doi: 10.1016/j.ajcnut.2024.07.032. Epub 2024 Aug 5.

  PMID: 39111551 DERIVED

• Sellem L, Antoni R, Koutsos A, Ozen E, Wong G, Ayyad H, Weech M, Schulze MB, Wernitz A, Fielding BA, Robertson MD, Jackson KG, Griffin BA, Lovegrove JA. Impact of a food-based dietary fat exchange model for replacing dietary saturated with unsaturated fatty acids in healthy men on plasma phospholipids fatty acid profiles and dietary patterns. Eur J Nutr. 2022 Oct;61(7):3669-3684. doi: 10.1007/s00394-022-02910-2. Epub 2022 Jun 6.

  PMID: 35668120 DERIVED

Study Officials

• Bruce Griffin, PhD

  University of Surrey

  PRINCIPAL INVESTIGATOR

• Julie Lovegrove, PhD

  University of Reading

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 10, 2017
• First Posted: September 1, 2017
• Study Start: September 1, 2017
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: October 25, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)