Michelle Weech

A review of the evidence for the effects of total dietary fat, saturated, monounsaturated and n-6 polyunsaturated fatty acids on vascular function, endothelial progenitor cells and microparticles

Vascular dysfunction is recognised as an integrative marker of CVD. While dietary strategies aimed at reducing CVD risk include reductions in the intake of SFA, there are currently no clear guidelines on what should replace SFA. The purpose of this review was to assess the evidence for the effects of total dietary fat and individual fatty acids (SFA, MUFA and n-6 PUFA) on vascular function, cellular microparticles and endothelial progenitor cells. Medline was systematically searched from 1966 until November 2010. A total of fifty-nine peer-reviewed publications (covering fifty-six studies), which included five epidemiological, eighteen dietary intervention and thirty-three test meal studies, were identified. The findings from the epidemiological studies were inconclusive. The limited data available from dietary intervention studies suggested a beneficial effect of low-fat diets on vascular reactivity, which was strongest when the comparator diet was high in SFA, with a modest improvement in measures of vascular reactivity when high-fat, MUFA-rich diets were compared with SFA-rich diets. There was consistent evidence from the test meal studies that high-fat meals have a detrimental effect on postprandial vascular function. However, the evidence for the comparative effects of test meals rich in MUFA or n-6 PUFA with SFA on postprandial vascular function was limited and inconclusive. The lack of studies with comparable within-study dietary fatty acid targets, a variety of different study designs and different methods for determining vascular function all confound any clear conclusions on the impact of dietary fat and individual fatty acids on vascular function.

Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study

BACKGROUND Public health strategies to lower cardiovascular disease (CVD) risk involve reducing dietary saturated fatty acid (SFA) intake to ≤10% of total energy (%TE). However, the optimal type of replacement fat is unclear. OBJECTIVE We investigated the substitution of 9.5-9.6%TE dietary SFAs with either monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on vascular function and other CVD risk factors. DESIGN In a randomized, controlled, single-blind, parallel-group dietary intervention, 195 men and women aged 21-60 y from the United Kingdom with moderate CVD risk (≥50% above the population mean) followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA) that were rich in SFAs (36:17:11:4, n = 65), MUFAs (36:9:19:4, n = 64), or n-6 PUFAs (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation; secondary outcome measures included fasting serum lipids, microvascular reactivity, arterial stiffness, ambulatory blood pressure, and markers of insulin resistance, inflammation, and endothelial activation. RESULTS Replacing SFAs with MUFAs or n-6 PUFAs did not affect the percentage of flow-mediated dilatation (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFAs with MUFAs attenuated the increase in night systolic blood pressure (-4.9 mm Hg, P = 0.019) and reduced E-selectin (-7.8%, P = 0.012). Replacement with MUFAs or n-6 PUFAs lowered fasting serum total cholesterol (-8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%), and total cholesterol to high-density lipoprotein cholesterol ratio (-5.6% and -8.5%) (P ≤ 0.001). These changes in low-density lipoprotein cholesterol equate to an estimated 17-20% reduction in CVD mortality. CONCLUSIONS Substitution of 9.5-9.6%TE dietary SFAs with either MUFAs or n-6 PUFAs did not significantly affect the percentage of flow-mediated dilatation or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure, and E-selectin offer a potential public health strategy for CVD risk reduction. This trial was registered at www.clinicaltrials.gov as NCT01478958.

Development of a Food-Exchange Model to Replace Saturated Fat with MUFAs and n–6 PUFAs in Adults at Moderate Cardiovascular Risk

The recommendation to reduce saturated fatty acid (SFA) consumption to ≤10% of total energy (%TE) is a key public health target aimed at lowering cardiovascular disease (CVD) risk. Replacement of SFA with unsaturated fats may provide greater benefit than replacement with carbohydrates, yet the optimal type of fat is unclear. The aim of the DIVAS (Dietary Intervention and Vascular Function) study was to develop a flexible food-exchange model to investigate the effects of substituting SFAs with monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on CVD risk factors. In this parallel study, UK adults aged 21-60 y with moderate CVD risk (50% greater than the population mean) were identified using a risk assessment tool (n = 195; 56% females). Three 16-wk isoenergetic diets of specific fatty acid (FA) composition (%TE SFA:%TE MUFA:%TE n-6 PUFA) were designed using spreads, oils, dairy products, and snacks as follows: 1) SFA-rich diet (17:11:4; n = 65); 2) MUFA-rich diet (9:19:4; n = 64); and 3) n-6 PUFA-rich diet (9:13:10; n = 66). Each diet provided 36%TE total fat. Dietary targets were broadly met for all intervention groups, reaching 17.6 ± 0.4%TE SFA, 18.5 ± 0.3%TE MUFA, and 10.4 ± 0.3%TE n-6 PUFA in the respective diets, with significant overall diet effects for the changes in SFAs, MUFAs, and n-6 PUFAs between groups (P < 0.001). There were no differences in the changes of total fat, protein, carbohydrate, and alcohol intake or anthropometric measures between groups. Plasma phospholipid FA composition showed changes from baseline in the proportions of total SFAs, MUFAs, and n-6 PUFAs for each diet group, with the changes in SFAs and MUFAs differing between the groups (P < 0.001). In conclusion, successful implementation of the food-exchange model broadly achieved the dietary target intakes for the exchange of SFAs with MUFAs or n-6 PUFAs with minimal disruption to the overall diet in a free-living population. This trial was registered at clinicaltrials.gov as NCT01478958.

High prevalence of undernutrition and low dietary diversity in institutionalised elderly living in Sri Lanka

OBJECTIVE The present study aimed to assess nutritional status, dietary diversity and lifestyle risk factors associated with undernutrition in an institutionalised Sri Lankan elderly population. DESIGN The study was of cross-sectional design followed by a stratified sampling method. SETTING Twelve homes for the elderly recruited from six provinces in Sri Lanka. SUBJECTS A total of 311 institutionalised elderly aged ≥60 years. RESULTS The mean age of the study population was 75 (sd 8) years. Prevalence of undernutrition was 30 %. Mean food variety score, dietary diversity score and dietary serving score of the study population were 8·7 (sd 1·5), 7·3 (sd 1·2) and 10·9 (sd 2·0), respectively. Mean daily intakes of fruit, vegetables, meat, fish, eggs and pulses and dairy portions were below the national recommendations, whereas the mean consumption of sugar exceeded the national recommendation. Only the mean intake of starch was within the recommendation. Food allergies (OR=8·0; 95 % CI 3·9, 16·2), skipping meals (OR=3·8; 95 % CI 2·0, 7·5) and lack of leisure activities (OR=3·1; 95 % CI 1·5, 6·7) significantly increased the risk of undernutrition, whereas the use of dentures decreased the risk (OR=0·20; 95 % CI 0·06, 0·69). CONCLUSIONS High prevalence of undernutrition and low dietary diversity were observed in an institutionalised elderly Sri Lankan population. Therefore, there is an urgent need to implement nutrition interventions as part of geriatric care to reduce undernutrition and improve the diets of the institutionalised elderly population in Sri Lanka.

Meal Fatty Acids Have Differential Effects on Postprandial Blood Pressure and Biomarkers of Endothelial Function but Not Vascular Reactivity in Postmenopausal Women in the Randomized Controlled Dietary Intervention and VAScular function (DIVAS)-2 Study

Background Elevated postprandial triacylglycerol concentrations, impaired vascular function, and hypertension are important independent cardiovascular disease (CVD) risk factors in women. However, the effects of meal fat composition on postprandial lipemia and vascular function in postmenopausal women are unknown. Objective This study investigated the impact of sequential meals rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on postprandial flow-mediated dilatation (FMD; primary outcome measure), vascular function, and associated CVD risk biomarkers (secondary outcomes) in postmenopausal women. Methods A double-blind, randomized, crossover, postprandial study was conducted in 32 postmenopausal women [mean ± SEM ages: 58 ± 1 y; mean ± SEM body mass index (in kg/m2): 25.9 ± 0.7]. After fasting overnight, participants consumed high-fat meals at breakfast (0 min; 50 g fat, containing 33-36 g SFAs, MUFAs, or n-6 PUFAs) and lunch (330 min; 30 g fat, containing 19-20 g SFAs, MUFAs, or n-6 PUFAs), on separate occasions. Blood samples were collected before breakfast and regularly after the meals for 480 min, with specific time points selected for measuring vascular function and blood pressure. Results Postprandial FMD, laser Doppler imaging, and digital volume pulse responses were not different after consuming the test fats. The incremental area under the curve (iAUC) for diastolic blood pressure was lower after the MUFA-rich meals than after the SFA-rich meals (mean ± SEM: -2.3 ± 0.3 compared with -1.5 ± 0.3 mm Hg × 450 min × 103; P = 0.009), with a similar trend for systolic blood pressure (P = 0.012). This corresponded to a lower iAUC for the plasma nitrite response after the SFA-rich meals than after the MUFA-rich meals (-1.23 ± 0.7 compared with -0.17 ± 0.4 μmol/L × 420 min P = 0.010). The soluble intercellular adhesion molecule 1 (sICAM-1) time-course profile, AUC, and iAUC were lower after the n-6 PUFA-rich meals than after the SFA- and MUFA-rich meals (P ≤ 0.001). Lipids, glucose, and markers of insulin sensitivity did not differ between the test fats. Conclusion Our study showed a differential impact of meal fat composition on blood pressure, plasma nitrite, and sICAM-1, but no effect on postprandial FMD or lipemia in postmenopausal women. This trial was registered at www.clinicaltrials.gov as NCT02144454.

Meal fat composition has differential effects on biomarkers of postprandial endothelial function in postmenopausal women

Decline in oestrogen at menopause is associated with adverse effects on lipid metabolism, vascular function and blood pressure, markedly increasing cardiovascular disease (CVD) risk in postmenopausal women. As a key public health strategy to reduce the incidence of CVD in the UK, dietary saturated fatty acid (SFA) intake of ⩽10 % of total energy is recommended. The Dietary Intervention and Vascular Function-2 study aimed to investigate the effects of sequential meals of varying fat composition on postprandial vascular reactivity and associated biomarkers of endothelial function in postmenopausal women. In an acute, double-blind, randomised, cross-over study, 32 women (mean age of 57 ± 1 y and BMI of 26 ± 0·7 kg/m) consumed sequential mixed test meals (0 min, 50 g fat and 330 min, 30 g fat) rich in SFA, monounsaturated (MUFA) or n-6 polyunsaturated (PUFA) fatty acids on 3 separate occasions, each 4–6 weeks apart. Blood samples were collected and real-time measures of vascular reactivity (flow-mediated dilatation, laser Doppler imaging, digital volume pulse) were performed before and at regular intervals after the breakfast for 480 min. There were no differences in the real-time measures of vascular function after the SFA, n-6 PUFA and MUFA-rich meals. A significant effect of meal fat composition was evident for the incremental area under the curve (IAUC) for the postprandial plasma nitrite (a biomarker for nitric oxide, an important vasodilator) response (p= 0·010), with a lower IAUC after consumption of the SFA than MUFA-rich meals (p= 0·007). There was also a trend for the IAUC for the nitrate and NOx (both nitrite and nitrate combined) responses (p= 0·054) to be influenced by the meal fatty acids, with a lower IAUC after the SFA than n-6 PUFA-rich meals (p= 0·024). There were significant test fat* time interactions for the time course profiles for soluble intracellular cell adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1), with a lower sICAM-1 response after the n-6 PUFA than SFA and MUFA-rich (p< 0·001) meals whereas the sVCAM-1 response was different after the SFA than MUFA and PUFA-rich meals (Figure). E-selectin and P-selectin responses were not affected by meal fat composition.

The effects of substitution of dietary saturated fatty acids with either monounsaturated fatty acids or n-6 polyunsaturated fatty acids on measures of endothelial function, arterial stiffness and blood pressure: results from the DIVAS study

Endothelial dysfunction has been recognised as an early modifiable marker in the development of atherosclerosis and risk of cardiovascular disease (CVD). A central public health strategy for the reduction of CVD includes the reduction in dietary saturated fatty acid (SFA) intake. However, it remains unclear whether monounsaturated fatty acids (MUFA) or n-6 polyunsaturated fatty acids (n-6 PUFA) are the optimal fatty acids to replace dietary SFA. The aim of this study was to determine the effects of substitution of SFA with either MUFA or n-6 PUFA on measures of endothelial function, arterial stiffness and blood pressure in men and women at increased risk of developing CVD. A total of 195 men and women at increased CVD risk (mean age 44 (SD 10) years and BMI 26.9 (SD 4.0) kg/m) participated in a 16-week, parallel, randomised, controlled, single-blinded intervention study (DIVAS – (Dietary Intervention and VAscular function Study; ClinicalTrials.gov NCT01478958). Participants were randomly assigned (minimised for gender, age, BMI and CVD risk score) to one of the following isoenergetic diets: SFA-rich (target composition: 36% of total energy (%E) as total fat, 17%E SFA, 11%E MUFA, 4%E n-6 PUFA), MUFA-rich (36%E total fat, 9%E SFA, 19%E MUFA, 4%E n-6 PUFA), or n-6 PUFA-rich (36%E total fat, 9%E SFA, 13%E MUFA, 10%E n-6 PUFA). A flexible dietary model was developed to deliver the dietary interventions in which exchangeable fats in the habitual diet were replaced by study foods (spreads, oils, snacks) with a specific fatty acid composition. Flow-Mediated Dilatation (FMD) and Laser Doppler imaging (LDI) with iontophoresis were measured for assessing the endothelial function of the macroand microcirculation, respectively. Pulse Wave Velocity/Analysis (PWV/PWA), Digital Volume Pulse (DVP) (measures of arterial stiffness) and 24-h Ambulatory Blood Pressure (24-h ABP) were also measured at baseline and following 16 weeks of intervention. A significant deterioration in the FMD response, endothelium-dependent vasodilation of the microvascular circulation (LDI) and mean night SBP and DBP was observed following the SFA-rich diet relative to baseline (P<0.05), but not following either n-6 PUFA or MUFA-rich diet. A significant diet interaction was observed for mean night SBP where replacement of SFA with MUFA attenuated the increase observed with SFA (P<0.05). In conclusion, this study showed that dietary SFA had a detrimental effect on vascular reactivity and blood pressure in a group at risk from CVD, which was not observed following the diets rich in unsaturated fatty acids. These data support current public health recommendations to reduce dietary SFA intake as a strategy for CVD risk reduction.

Number of endothelial progenitor cells are associated with body composition, but not fat intake or blood lipids

The endothelium plays an essential role in vascular homoeostasis and regulation of vascular tone. Endothelial dysfunction occurs in the early stages of atherosclerosis, and contributes to the formation of atherosclerotic plaques. Circulating markers of endothelial function include endothelial progenitor cells (EPC), which play a role in repair and maintenance of damaged endothelium, and endothelial microparticles (EMP) and platelet microparticles (PMP) that are produced directly as a result of endothelial activation. There is little data on the effects of dietary fat or body composition on these novel markers of endothelial function. The aim of this study was to examine the influence of habitual dietary fat intake, body composition and blood lipids on circulating EPC, EMP and PMP numbers in a cohort of human subjects with moderate cardiovascular risk. Intakes of total fat, SFA, MUFA, n3 PUFA and n 6 PUFA in the habitual diet of fifty-five volunteers were correlated with absolute numbers of blood EPC, EMP and PMP which were analysed using flow cytometry. EPC were stained with a combination of anti-CD34 and anti-CD309 (VEGFR2), and EMP and PMP were stained with anti-CD31 and anti-CD42b.