Cardiovascular disease Circulatory System
Conditions
Interventions
We will conduct a randomised control trial design to investigate how a fish diet modulates blood and urinary levels of TMAO, alongside blood plasma concentrations of cholesterol and triglycerides, and
Sponsors
University of Aberdeen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Overweight (body mass index [BMI] 25-29.9 kg/m2) 2. Aged 30-65 years 3. Mild, non-treated dyslipidaemia (fasted triglyceride [TG] between 1.7 and 8.5 mmol/l and/or cholesterol between 5.6 and 6.6 mmol/L 4. Fasting glucose between 5.6 and 6.9 mmol/L and/or systolic blood pressure (SBP) between 91 and 159mm Hg and/or diastolic blood pressure (DBP) between 61 and 89 mm Hg and glucose 5. Volunteers with low HDL cholesterol (130/85 mmHg) and/or central obesity (waist circumference >102 cm for men, >88 cm for women) and/or if they have moderate hypercholesterolemia (total cholesterol between 5.6 and 6.6 mmol/L) will also be included
Exclusion criteria
Exclusion criteria: 1. Stage 2+ hypertensive (SBP >159 mmHg and/or DBP >99 mmHg) 2. Existing or active/prior health conditions including diabetes (or fasting glucose >7.0 mmol/L) or CVD 3. Taking medication to control BP or lipid levels 4. Unwillingness to comply with study protocol including stopping vitamins/minerals that may affect the trial 5. BMI>29.9 or BMI <25 kg/m2 6. consuming more than 14 alcohol units per week 7. People with thyroid gland disorders or eating disorders 8. People taking regular medication or supplements known to affect any dependant variable measured 9. SBP <90 mmHg and /or DBP <60 mmHg 10. Pregnant women 11. Individuals with bowel disorders (Crohn’s, IBS, coeliac)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measured before the run-in period, at baseline, mid-point and at the end of the three diets (day 0, 7, 28, 49, 56, 77, 98): 1. Blood and urinary TMAO concentrations determined in samples using liquid chromatography-mass spectrometry (LC-MS) 2. Plasma total and HDL cholesterol and TAG concentrations measured by standardised automated procedures. LDL cholesterol will be calculated using the Friedewald equation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured before the run-in period, at baseline and at the end of the three diets (day 0, 7, 28, 49, 56, 77, 98) unless specified otherwise: 1. Blood pressure determined using an automated oscillometric sphygmomanometer and over 24 hours using 24-hour ambulatory blood pressure monitors 2. Markers of inflammation and endothelial function (hsCRP, slCAM1, IL-1ß) measured by immunoassays 3. Urine sodium, calcium and potassium concentrations assayed by elemental analysis 4. Plasma lipidomics analyses carried out using an Agilent Ultra High Performance Liquid Chromatography QToF 6560 Mass Spectrometer 5. Plasma metabolomic analyses performed using LC-MS/MS on a Thermo Quantiva to profile ~200 core metabolites representing amino acid metabolism, ß-oxidation, the citric acid cycle, glycolysis, gluconeogenesis, products of reactive oxygen species (oxidised amino acids and nucleotides) and anti-oxidants (glutathione and vitamin C). 6. Short-chain fatty acids and bile acids from blood samples, as well as the gut microbiota-derived metabolites hydroxyindole sulfate, phenylacetylglutamine, indoxyl-sulfate, p-cresol sulfate, 4-methylcatechol sulfate and methionine sulfone, and the meat biomarker 1-methylhistidine, determined using LC-MS. 7. Similar analysis for the gut microbiome metabolites mentioned above will be conducted in urine samples 8. Augmentation index and central blood pressures measured by applanation tonometry using Sphygmocor at day 7, 49, 56 and 98 9. Faecal DNA will be extracted and 16S rRNA amplicon sequencing carried out to assess microbiota compositional changes in response to diet. Quantitative PCR (qPCR) will also be employed to establish changes in total bacteria in absolute terms, as well as for selected microbes that show diet-specific changes and/or that have previously been identified as TMA producers, as qPCR allows for higher phylogenetic resolution than short amplicon sequencing. 10. Short-chain fatty acids extracted from stool samples will be measu | — |
Countries
Scotland, United Kingdom
Contacts
Public ContactFrank Thies
Outcome results
None listed