Heart disease risk Circulatory System
Conditions
Interventions
Participants will undergo, sequentially, a high (18%) SFA diet (Diet 1) followed by a low (10%) SFA diet (Diet 2) for 4 weeks each. Metabolic assessments will be conducted at the end of Diets 1 and 2.
Sponsors
University of Surrey
University of Reading
Imperial College London
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Hyper- and hypo-responsive males, defined as the participants (derived from the first stage of the project, RISSCI-1: https://clinicaltrials.gov/ct2/show/NCT03270527) exhibiting changes in serum LDL-cholesterol in response to a lowering of SFA intake in the top and bottom 10% of a larger cohort (n=150) 2. Middle-aged men (30-65 years) 3. BMI 19-32 kg/m2 4. Fasting serum total cholesterol < 7.5 mmol/l and TAG < 2.3 mmol/l
Exclusion criteria
Exclusion criteria: 1. Smokers 2. Medical history of MI or stroke in the past 12 months 3. Diabetes (defined as fasting glucose > 7.0 mmol/l) or other endocrine disorders 4. Medication for hyperlipidaemia (e.g. statins) or prescribed antibiotics within the last three months 5. Drinking in excess of 14 units of alcohol per week, anaemia (<130 g/L haemoglobin) 6. Planning a weight-reducing regime or taking any dietary supplements known to influence lipids/gut microbiota (e.g. plant stanols, fish oil, phytochemicals, natural laxatives, probiotics and prebiotics) 7. Unwilling to regularly consume study intervention products (butter/spreads, oils, dairy, snacks) 8. Any other unusual medical history or diet and lifestyle habits or practices that would preclude participants from participating in a dietary intervention metabolic study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Lipid profile (Total Cholesterol (TC), LDL-C, HDL-C and triacylglycerol (TAG)) measured via direct quantification and/or auto-analyser at baseline, the end of diet 1 and at the end of diet 2 2. Dietary fat absorption, measured by feeding a manufactured fat that has been labelled with safe stable isotope tracer that can be traced in the body and can be used to measure how much is excreted in the stool, at the end of diet 1 and at the end of diet 2 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Gut permeability measured using the urinary recovery of ingested carbohydrates provided as part of a drink, at baseline, the end of diet 1 and at the end of diet 2 2. LDL-receptor expression measured in peripheral blood mononuclear cells (PBMC) via PCR at baseline, the end of diet 1 and at the end of diet 2 3. Gut microbiota composition measured in stool samples using NGS/FISH at baseline, the end of diet 1 and at the end of diet 2 4. Endogenous cholesterol synthesis measured by measuring serum phytosterols, a biomarker of this process, using GCMS at baseline, the end of diet 1 and at the end of diet 2 5. Serum deconjugated bile acids measured using targeted UPLC-MS at baseline, the end of diet 1 and at the end of diet 2 7. Metabolomic signatures in urine, plasma and stool measured using 1H-NMR & UPLC-MS metabonomics at baseline, the end of diet 1 and at the end of diet 2 8. Markers of inflammation and endothelial function measured using commercially available kits (e.g. ELISA) at baseline, the end of diet 1 and at the end of diet 2 9. HDL composition/function measured via cell-based cholesterol efflux capacity assay at baseline, the end of diet 1 and at the end of diet 2 | — |
Countries
England, United Kingdom
Outcome results
None listed