Stacey Lockyer

APOE genotype influences triglyceride and C-reactive protein responses to altered dietary fat intake in UK adults

BACKGROUND The response of plasma lipids to dietary fat manipulation is highly heterogeneous, with some indications that APOE genotype may be important. OBJECTIVE The objective was to use a prospective recruitment approach to determine the effect of dietary fat quantity and composition on both lipid and nonlipid cardiovascular disease biomarkers according to APOE genotype. DESIGN Participants had a mean (±SD) age of 51 ± 9 y and a BMI (in kg/m²) of 26.0 ± 3.8 (n = 44 E3/E3, n = 44 E3/E4) and followed a sequential dietary intervention (the SATgenε study) in which they were assigned to a low-fat diet, a high-fat high-SFA (HSF) diet, and the HSF diet with 3.45 g DHA/d (HSF-DHA), each for 8 wk. Fasting blood samples were collected at the end of each intervention arm. RESULTS An overall diet effect was evident for all cholesterol fractions (P < 0.01), with no significant genotype × diet interactions observed. A genotype × diet interaction (P = 0.033) was evident for plasma triglycerides, with 17% and 30% decreases in APOE3/E3 and APOE3/E4 individuals after the HSF-DHA diet relative to the low-fat diet. A significant genotype × diet interaction (P = 0.009) was also observed for C-reactive protein (CRP), with only significant increases in concentrations after the HSF and HSF-DHA diets relative to the low-fat diet in the APOE3/E4 group (P < 0.015). CONCLUSIONS Relative to the wild-type APOE3/E3 group, our results indicate a greater sensitivity of fasting triglycerides and CRP to dietary fat manipulation in those with an APOE3/E4 genotype (25% population), with no effect of this allelic profile on cholesterol concentrations.

Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial

The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P< 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

SATgenε dietary model to implement diets of differing fat composition in prospectively genotyped groups (apoE) using commercially available foods.

Response to dietary fat manipulation is highly heterogeneous, yet generic population-based recommendations aimed at reducing the burden of CVD are given. The APOE epsilon genotype has been proposed to be an important determinant of this response. The present study reports on the dietary strategy employed in the SATgenε (SATurated fat and gene APOE) study, to assess the impact of altered fat content and composition on the blood lipid profile according to the APOE genotype. A flexible dietary exchange model was developed to implement three isoenergetic diets: a low-fat (LF) diet (target composition: 24 % of energy (%E) as fat, 8 %E SFA and 59 %E carbohydrate), a high-saturated fat (HSF) diet (38 %E fat, 18 %E SFA and 45 %E carbohydrate) and a HSF-DHA diet (HSF diet with 3 g DHA/d). Free-living participants (n 88; n 44 E3/E3 and n 44 E3/E4) followed the diets in a sequential design for 8 weeks, each using commercially available spreads, oils and snacks with specific fatty acid profiles. Dietary compositional targets were broadly met with significantly higher total fat (42·8 %E and 41·0 %E v. 25·1 %E, P ≤ 0·0011) and SFA (19·3 %E and 18·6 %E v. 8·33 %E, P ≤ 0·0011) intakes during the HSF and HSF-DHA diets compared with the LF diet, in addition to significantly higher DHA intake during the HSF-DHA diet (P ≤ 0·0011). Plasma phospholipid fatty acid analysis revealed a 2-fold increase in the proportion of DHA after consumption of the HSF-DHA diet for 8 weeks, which was independent of the APOE genotype. In summary, the dietary strategy was successfully implemented in a free-living population resulting in well-tolerated diets which broadly met the dietary targets set.

Long chain n−3 PUFA-rich meal reduced postprandial measures of arterial stiffness

BACKGROUND & AIMS The consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) is known to be cardio-protective. Data on the influence of LC n-3 PUFA on arterial stiffness in the postprandial state is limited. The aim of this study was to investigate the acute effects of a LC n-3 PUFA-rich meal on measures of arterial stiffness. METHODS Twenty-five healthy subjects (12 men, 13 women) received a control and a LC n-3 PUFA-rich meal on two occasions in a random order. Arterial stiffness was measured at baseline, 30, 60, 90, 120, 180 and 240 min after meal consumption by pulse wave analysis and digital volume pulse to derive an augmentation index and a stiffness index respectively. Blood samples were taken for measurement of lipids, glucose and insulin. RESULTS Consumption of the LC n-3 PUFA-rich meal had an attenuating effect on augmentation index (P=0.02) and stiffness index (P=0.03) compared with the control meal. A significant treatment effect (P=0.036) was seen for plasma non-esterified fatty acids concentrations. CONCLUSIONS These data indicate that acute LC n-3 PUFA-rich meal consumption can improve postprandial arterial stiffness. This has important implications for the beneficial properties of LC n-3 PUFA and cardiovascular risk reduction.

Dietary fat manipulation has a greater impact on postprandial lipid metabolism than the apolipoprotein E (epsilon) genotype-insights from the SATgenε study.

SCOPE Our aim was to determine the effects of chronic dietary fat manipulation on postprandial lipaemia according to apolipoprotein (APO)E genotype. METHODS AND RESULTS Men (mean age 53 (SD 9) years), prospectively recruited for the APOE genotype (n = 12 E3/E3, n = 11 E3/E4), were assigned to a low fat (LF), high fat, high-saturated fat (HSF), and HSF diet with 3.45 g/day docosahexaenoic acid (HSF-DHA), each for an 8-week period in the same order. At the end of each dietary period, a postprandial assessment was performed using a test meal with a macronutrient profile representative of that dietary intervention. A variable postprandial plasma triacylglycerol (TAG) response according to APOE genotype was evident, with a greater sensitivity to the TAG-lowering effects of DHA in APOE4 carriers (p ≤ 0.005). There was a lack of an independent genotype effect on any of the lipid measures. In the groups combined, dietary fat manipulation had a significant impact on lipids in plasma and Svedberg flotation rate (S(f) ) 60-400 TAG-rich lipoprotein fraction, with lower responses following the HSF-DHA than HSF intervention (p < 0.05). CONCLUSION Although a modest impact of APOE genotype was observed on the plasma TAG profile, dietary fat manipulation emerged as a greater modulator of the postprandial lipid response in normolipidaemic men.

Olive leaf phenolics and cardiovascular risk reduction: Physiological effects and mechanisms of action

Olive oil, an important component of the Mediterranean diet, is rich in polyphenols and is known to possess positive health effects relative to other dietary fats. In addition, the leaves of the olive plant (Olea europaea) contain similar phenolics (oleuropein, luteolin-7-glucoside, apigenin-7-glucoside, verbascoside and hydroxytyrosol) to those of olives and olive oil, although at higher concentrations. For example, the most abundant is the secoiridoid, oleuropein, representing 1-14% of olive leaf weight vs. 0.005-0.12% in olive oil. Although currently considered a waste product of the olive oil industry, recent research has suggested beneficial effects of phenolic-rich olive leaf extracts (OLE) in modifying cardiovascular risk biomarkers such as blood pressure, hyperglycaemia, oxidative stress and inflammation, as well as improving vascular function and lipid profiles. Despite this, data regarding the biological actions of OLE has mostly derived from animal, in vitro and ex vivo studies, with limited evidence deriving from human trials. Although the absorption and metabolism of olive oil phenolics has been investigated, less is known about the bioavailability of phenolics from OLE, limiting the interpretation of existing in vitro and ex vivo data. The current review will begin by describing the phenolic composition of olive leaves in comparison with that of the better studied olive oil. It will then review the effects of OLE on cardiovascular risk factors, covering both animal and human studies and will end by considering potential mechanisms of action.

Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production – Insights from the SATgenε study

Highlights • The effect of diet and genotype on inflammatory response was explored in humans.• Cytokine production was not affected by apolipoprotein E (APOE) genotype.• TNF-α concentration significantly increased after a high saturated fat diet.• IL-10 concentration was significantly higher after a low fat diet.• The amount and type of dietary fat modulated cytokine production.

SATgenε dietary strategy to investigate the impact of the apo E genotype on LDL-cholesterol response to dietary fat manipulation

There is emerging evidence that polymorphisms in the gene encoding for apoE impact on the LDL-cholesterol (LDL-C) response to dietary fat intake. It has been reported that carriers of the apoE4 allele have higher plasma LDL-C concentrations after ingestion of saturated fat (SFA) and docosahexanaeoic acid (DHA) (>2g/d) compared with the apoE3 wild-type. The aim of the SATgene study was to investigate the impact of a combination of SFA and DHA intake on plasma lipids according to apoE genotype.

Postprandial effects of supplementing a moderate-fat meal with long-chain n -3 PUFA on measures of arterial stiffness

It is well established that the consumption of long-chain (LC) n-3 PUFA, EPA and DHA, found in fish oils are cardio-protective. Arterial stiffening is a manifestation of vascular dysfunction and is recognised as a biomarker for CVD. There are limited and inconsistent data on the influence of LC n-3 PUFA on arterial stiffness in the postprandial state. The aim of the present study was to investigate the effects of a moderate-fat meal enriched with LC n-3 PUFA on arterial stiffness determined by two different techniques, digital volume pulse analysis (DVP) and pulse wave analysis (PWA), both of which have been described previously. The DVP was obtained by photoplethysmography using the PulseTrace system (Micro Medical, Chatham Maritime, Kent, UK) to calculate stiffness index (SI). PWA was performed by applanation tonometry at the radial artery using the SphygmoCor (ScanMed Medical, Moreton-in-Marsh, Glos., UK) to calculate augmentation index (AIx). Twenty-five healthy subjects (twelve males, thirteen females; age 47 (SD 4) years, BMI 23.4 (SD 0.7) kg/m received either a control (CT) meal (30 g mixed fat; fatty acid profile representative of the UK diet) or an LC n-3 PUFA-rich meal (23 g mixed fat, 6.7 g fish oil, which provided 2.0 g EPA and 2.7 g DHA) on two occasions in a random order. DVP and PWA measurements were taken at baseline and 30, 60, 90, 120, 180 and 240 min after meal consumption to derive SI and AIx respectively. Blood samples were taken at baseline and 120 and 240 min after meal consumption and were analysed for glucose, TAG, insulin and NEFA.