The Postprandial Impact of Dietary Fats on Measures of Endothelial Function

Abstract

Postprandial lipaemia (PPL) is the increase in circulating triglycerides (TAG) following consumption of a fat containing meal and is an independent risk factor for cardiovascular disease (CVD). Postprandial lipaemia elicits an increase in inflammation and oxidative stress which may have an unfavourable effect on vascular function via endothelial dependent mechanisms. The overall aim of this thesis was to explore the postprandial effect of fat-rich meal on endothelial function. Chapter 2 of the thesis is a systematic review and meta- analysis aimed to assess the postprandial effect of fat-rich meals on endothelial function and inflammation, undertaken using the procedures outlined in the PRISMA statement according to the PROSPERO protocol (CRD42021258803). The systematic review included 50 studies, and the meta- analysis concluded that there is no consistent effect of fat-rich meals (30 – 80 g) on postprandial endothelial function measured by flow- mediated dilation (FMD) in healthy adults compared to low fat meals (< 30g). Chapter 3 aimed to investigate the variability in postprandial endothelial function following a fat-rich meal and the meal and person specific factors associated with this variability. Data was collected from 5 previously conducted RCTs. The analysis revealed high inter-individual variability in postprandial endothelial function which was partially explained by age and the polyunsaturated fatty acid (PUFA) composition of the meal. An increase of 1 year in age predicted a decrease in FMD by 0.04 %, and an increase in 1 gram of PUFA in a fat-rich meal predicted a decrease in FMD by 0.38 %. Given the inconsistent evidence relating dietary fat to postprandial endothelial function, Chapter 4 aimed to explore the impact of commonly consumed fats spreads that have different fatty acid composition but similar physical properties on endothelial function in an RCT (RCT; ethical; HR-17/18 5499 and NCT03438084). It was a randomised, controlled, 4-armed crossover, double-blind design study (25 men and 25 women, 35-75 years), compared the postprandial (0-8 hours) effect of mixed meals containing 50g fat interesterified (IE) spread, non-IE spread and spreadable butter, with rapeseed oil as a reference oil on changes in PPL (plasma TAG) and endothelial function (FMD). Secondary outcomes included nitrite, glucose, insulin, interleukin-6 (IL-6), glycoprotein acetylation (GlycA), endotoxemia, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Findings revealed no postprandial change in FMD and no association between postprandial TAG concentrations and FMD change. However, there was a significant treatment effect on the males’ FMD, with a greater postprandial reduction in males’ FMD following consumption of non- IE fat in comparison to IE fat (-0.99%, 95% CI -1.95, -0.03, p= 0.041) whereas no difference was observed in females (p=0.279). This occurred in the absence of any differences in TAG concentrations, inflammation, oxidative stress, and endotoxemia between fats. This thesis highlights the lack of consistent evidence on the effect of fat rich meals on postprandial endothelial function. Furthermore, this thesis demonstrates the large inter-individual variability in the postprandial vascular response measured by FMD.