Long chain monounsaturated fatty acids from fish and their effect on metabolic health (MonoFish)

INTERVENTION: Adults aged 18–65 years with moderately elevated low‐density lipoprotein (LDL) cholesterol concentrations (115–159 mg/dL) will be recruited to participate in this 12‐week, randomised, double‐blind, placebo‐controlled, parallel‐group intervention study. Participants will be recruited through local general practitioners (GP’s) and community‐based recruitment strategies. Eligibility will be confirmed through screening questionnaires, assessment of medical history, and measurement of LDL cholesterol using a finger‐prick blood sample. Participants recruited from the community will additionally undergo cardiovascular risk assessment using the QRISK3 calculator, a validated algorithm that estimates an individual’s 10‐year risk of developing cardiovascular disease A total of 174 participants will be recruited. Sample size calculations were based on a fixed‐effects one‐way ANOVA assuming a 5–6% reduction in LDL cholesterol, a within‐cell standard deviation of 15, 80% statistical power, and a two‐sided significance level of 0.05. To account for an anticipated 10% attrition rate, 58 participants will be recruited into each intervention arm. Following completion of baseline assessments, participants will be randomly assigned in equal numbers to one of three intervention groups: Arm 1 – Omega‐3 supplement taken twice daily with 20mg LCMUFA per day) Arm 2 – Omega 3‐9‐11 supplement taken twice daily with 956mg LCMUFAs per day) Arm 3 – Placebo supplement taken twice daily (2g/day corn oil) Randomisation will be conducted by an independent researcher and stratified by se Xand body mass inde X(BMI; 18–24.9 kg/m² and 25–30 kg/m²). Participants will attend study visits at baseline and following completion of the 12‐week intervention. At each visit, anthropometric measurements will be obtained using standardised procedures, including body weight, body composition, waist circumference, and blood pressure. Height will be measured at baseline only for the calculation of BMI. Body composition measures will include fat mass, fat‐free mass, and lean body mass assessed using TANITA scales. Blood pressure will be measured following a period of seated rest using an automated blood pressure monitor, with duplicate measurements obtained and averaged. Fasting venous blood samples will be collected at baseline and post‐intervention Secondary outcomes will include changes in red blood cell fatty acid composition and omega‐3 index, lipid profiles, blood pressure, body composition, markers of inflammation, oxidative stress, endothelial function, and clinical chemistry. Inflammatory biomarkers will include adiponectin, leptin, C‐reactive protein (CRP), tumour necrosis factor‐alpha (TNF‐a), interferon‐gamma (IFN‐?), interleukins (IL‐1ß, IL‐2, IL‐4, IL‐6, and IL‐10), intracellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) Untargeted and targeted lipidomic analyses will be performed using mass spectrometry to investigate the effects of supplementation on plasma lipid mediators, including oxylipins and other specialised pro‐resolving mediators. Rout CONDITION: Elevated cholesterol ; Nutritional, Metabolic, Endocrine PRIMARY OUTCOME: Low density lipoprotein (LDL) cholesterol measured using RX Daytona+ Analyser at baseline and 12 weeks SECONDARY OUTCOME: Adipokine concentrations (adiponectin and leptin; ng/mL or µg/mL) measured using validated immunoassays at baseline and 12 weeks Apolipoprotein B concentrations (mg/dL) measured using R XDaytona+ Analyser at baseline and 12 weeks Blood lipids (Total cholesterol, High Density Lipoprotein, Triglycerides: mmol/L) measured using R XDaytona+ Analyser at baseline and 12 weeks Blood pressure (systolic and diastolic) measured using standard clinical sphygmomanometry at baseline and 12 weeks Body composition (weight (kg), fat mass (kg), fat free mass (kg), waist circumference (cm)) measured using TANITA scales at baseline and 12 weeks Cardiovascular inflammatory markers (intercellular adhesion molecule‐1 [ICAM‐1], vascular cell adhesion molecule‐1 [VCAM‐1]) measured using validated immunoassays at baseline and 12 weeks Clinical chemistry markers (full blood profile; liver enzymes [ALT, AST, GGT, ALP] and kidney function markers) measured using Sysme Xand R XDaytona+ clinical chemistry analyser. at baseline and 12 weeks Inflammatory cytokine concentrations (e.g., C‐reactive protein (CRP) interleukin‐5 [IL‐5], interferon‐gamma [IFN‐?], interleukin‐10 [IL‐10], interleukin‐1ß [IL‐1ß], interleukin‐4 [IL‐4], interleukin‐6 [IL‐6], tumour necrosis factor‐alpha [TNF‐a]; pg/mL) measured using validated immunoassays at baseline and 12 weeks Lipidomic profile (sphingolipids, phospholipids, oxylipins) measured using mass spectrometry at baseline and 12 weeks Red blood cell polyunsaturated fatty acid status (linoleic acid [LA], arachidonic acid [AA], alpha‐linolenic acid [ALA], eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], Omega‐3 inde X(% EPA and DHA in red blood cell membranes); % weight) measured using gas chromatography–mass spectrometry (GC/MS) at baseline and 12 weeks INCLUSION CRITERIA: 1. Aged 18‐65 years 2. BMI 18‐30 kg/m² 3. LDL cholesterol 115‐159 mg/dL 4. Able to fast from 22:00 the night before the appointment 5. Non‐smoker and non‐e‐cigarette user 6. Not currently using fish oil or omega‐3 supplements 7. No allergies to fish oil products 8. No known diagnosis of a chronic condition, for example type 2 diabetes or autoimmune disease 9. Not regularly taking food supplements that influence cholesterol levels, for example plant sterols or stanols