Meal fatty acids and postprandial vascular reactivity

With increasing recognition of the pivotal role of vascular dysfunction in the progression of atherosclerosis, the vasculature has emerged as an important target for dietary therapies. Recent studies have indicated that chronic fatty acid manipulation alters vascular reactivity, when measured after an overnight fast. However, individuals spend a large proportion of the day in the postprandial (non-fasted) state. Several studies have shown that high fat meals can impair endothelial function within 3-4 h, a time period often associated with peak postprandial lipaemia. Although the impact of meal fatty acids on the magnitude and duration of the postprandial lipaemic response has been extensively studied, very little is known about their impact on vascular reactivity after a meal.

Fish oil fatty acids improve postprandial vascular reactivity in healthy men

Chronic fish oil intervention had been shown to have a positive impact on endothelial function. Although high-fat meals have often been associated with a loss of postprandial vascular reactivity, studies examining the effects of fish oil fatty acids on vascular function in the postprandial phase are limited. The aim of the present study was to examine the impact of the addition of fish oil fatty acids to a standard test meal on postprandial vascular reactivity. A total of 25 men received in a random order either a placebo oil meal (40 g of mixed fat; fatty acid profile representative of the U.K. diet) or a fish oil meal (31 g of mixed fat and 9 g of fish oil) on two occasions. Vascular reactivity was measured at baseline (0 h) and 4 h after the meal by laser Doppler iontophoresis, and blood samples were taken for the measurement of plasma lipids, total nitrite, glucose and insulin. eNOS (endothelial NO synthase) and NADPH oxidase gene expression were determined in endothelial cells after incubation with TRLs (triacylglycerol-rich lipoproteins) isolated from the plasma samples taken at 4 h. Compared with baseline, sodium nitroprusside (an endothelium-independent vasodilator)-induced reactivity (P = 0.024) and plasma nitrite levels (P = 0.001) were increased after the fish oil meal. In endothelial cells, postprandial TRLs isolated after the fish oil meal increased eNOS and decreased NADPH oxidase gene expression compared with TRLs isolated following the placebo oil meal (P <= 0.03). In conclusion, meal fatty acids appear to be an important determinant of vascular reactivity, with fish oils significantly improving postprandial endothelium-independent vasodilation.

A randomised trial to investigate the effects of acute consumption of a blackcurrant juice drink on markers of vascular reactivity and bioavailability of anthocyanins in human subjects

Objective: To study the bioavailability of anthocyanins and the effects of a 20% blackcurrant juice drink on vascular reactivity, plasma antioxidant status and other CVD risk markers. Subjects/Methods: The study was a randomised, cross over, double blind, placebo controlled acute meal study. Twenty healthy volunteers (11 females 9 males) were recruited, and all subjects completed the study. Fasted volunteers consumed a 20% blackcurrant juice drink (250 ml) or a control drink following a low-flavonoid diet for the previous 72 hours. Vascular reactivity was assessed at baseline and 120 mins after juice consumption by Laser Doppler Imaging (LDI). Plasma and urine samples were collected periodically over an 8 hour period for analysis, with a final urine sample collected at 24h. The cross over was performed after a 4-week washout. Results: There were no significant effects of the 20% blackcurrant juice drink on acute measures of vascular reactivity, biomarkers of endothelial function or lipid risk factors. Consumption of the test juice caused increases in plasma vitamin C (P=0.006), and urinary anthocyanins (P<0.001). Delphinidin-3-rutinoside and cyanidin-3-rutinoside were the main anthocyanins excreted in urine with delphinidin-3-glucoside also detected. The yield of anthocyanins in urine was 0.021 ± 0.003% of the dietary intake of delphinidin glycosides and 0.009 ± 0.002 % of the dietary intake of cyanidin glycosides. Conclusions: The juice consumption did not have a significant effect on vascular reactivity. Anthocyanins were present at low concentrations in the urine, and microbial metabolites of flavonoids were detected in plasma after juice consumption.

DHA-rich fish oil reverses the detrimental effects of saturated fatty acids on postprandial vascular reactivity

Background: Experimental elevation of nonesterified fatty acids (NEFAs) impairs endothelial function, but the effect of NEFA composition is unknown. Objective: The objective was to test the effect of acute elevation of NEFAs enriched with either saturated fatty acids (SFAs) or SFAs with long-chain (LC) n−3 (omega-3) PUFAs on vascular function measured via flow-mediated dilatation (FMD), laser Doppler iontophoresis (LDI), and digital volume pulse (DVP). Design: In 59 subjects (30 men and 29 women), repeated oral fat feeding of either palm stearin (SFA) or palm stearin with DHA-rich fish oil (SFA + LC n−3 PUFA) was performed on 2 separate occasions with continuous heparin infusion to elevate NEFAs for a duration of 60 to 240 min. Vascular function was measured at baseline and at the end of NEFA elevation; venous blood was collected for measurement of lipids and circulating markers of endothelial function. Results: NEFA elevation during consumption of the SFA-rich drinks was associated with a marked impairment of FMD, whereas consumption of SFAs + LC n−3 PUFAs improved FMD response, with a mean (±SEM) difference of 2.06 ± 0.29% (P < 0.001). Positive correlations were found with percentage weight of LC n−3 PUFAs in circulating NEFAs and change in FMD response [Spearman's rho (rs) = 0.460, P < 0.001]. LDI measures increased during both treatments (P ≤ 0.026), and there was no change in DVP indexes. Conclusions: The composition of NEFAs can acutely affect FMD. The beneficial effect of LC n−3 PUFAs on postprandial vascular function warrants further investigation but may be mediated by nitric oxide–independent mechanisms. This trial is registered at clinicaltrials.gov as NCT01351324.

The impact of catechol-O-methyltransferase genotype on the acute responsiveness of vascular reactivity to a green tea extract

The beneficial effects of green tea catechins, such as the proposed improvement in endothelial function, may be influenced by phase II metabolism during and after absorption. The methylation enzyme, catechol-O-methyltransferase (COMT), has a missense mutation rs4680 (G to A), proposed to result in a 40 % reduction in enzyme activity. In the present pilot study, twenty subjects (ten of each homozygous COMT genotype) were recruited. Green tea extract capsules (836 mg green tea catechins) were given in a fasted state, and a high-carbohydrate breakfast was given after 60 min. Blood samples and vascular function measurements were taken at regular intervals. The change in digital volume pulse stiffness index (SI) from baseline was shown to be different between genotype groups at 120 and 240 min, with a lower SI in the GG individuals (P ≤ 0·044). The change in blood pressure from baseline also differed between genotype groups, with a greater increase in systolic (P = 0·023) and diastolic (P = 0·034) blood pressure at 120 min in the GG group. The AA group was shown to have a greater increase in insulin concentrations at 120 min (P = 0·019) and 180 min (P = 0·008) compared with baseline, despite similar glucose profiles. No genotypic differences were found in vascular reactivity measured using laser Doppler iontophoresis, total nitrite, lipids, plasma total antioxidant capacity or inflammatory markers after ingestion of the green tea extract. In conclusion, SI and insulin response to the glucose load differed between the COMT genotype groups, and this may be suggestive of a green tea extract and genotype interaction.

Fish oil fatty acids and vascular reactivity

Endothelial dysfunction and an associated increase in vascular tone are risk factors for cardiovascular disease and highly predictive of future cardiovascular events. A part of the benefits associated with increased intake of the long chain (LC) n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid and docosahexaenoic acid, found in fish oils is a positive impact on cardiovascular health. Here, the recent evidence from human observational and intervention trials are reviewed, and an insight into potential mechanisms underlying the impact of LC n-3 PUFA on vascular reactivity is provided.

Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers

Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric acid, protocatechuic acid and isoferulic acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity.

The impact of age on the postprandial vascular response to a fish oil-enriched meal

Although chronic fish oil intervention had been shown to have a positive impact on vascular reactivity, very little is known about their acute effects during the postprandial phase. Our aim was to examine the impact of a fish oil-enriched test meal on postprandial vascular reactivity in healthy younger ( < 50 years) v. older ( ≥ 50 years) men. Vascular reactivity was measured at baseline (0 h), 2 and 4 h after the meal by laser Doppler iontophoresis and blood samples taken at 0 and 4 h for the measurement of plasma lipids, total nitrite, glucose and insulin. Acetylcholine- (ACh, endothelial-dependent vasodilator) and sodium nitroprusside (SNP, endothelial-independent vasodilator)-induced reactivities were greater at 4 h than at baseline or 2 h in the younger men (P < 0·04). These changes were not observed in the older men. Comparison of the male groups revealed significantly greater responses to ACh (P = 0·006) and SNP (P = 0·05) at 4 h in the younger compared with the older males. Postprandial NEFA concentrations were also greater at 4 h in the younger compared with the older men (P = 0·005), with no differences observed for any of the other analytes. Multiple regression analysis revealed age to be the most significant predictor of both ACh and SNP induced reactivity 4 h after the meal. In conclusion, the ingestion of a meal enriched in fish oil fatty acids was shown to improve postprandial vascular reactivity at 4 h in our younger men, with little benefit evident in our older men.

A review of the evidence for the effects of total dietary fat, SFA, MUFA and n-6 PUFA 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.

The Glu298Asp single nucleotide polymorphism in the endothelial nitric oxide synthase gene differentially effects the vascular response to acute consumption of fruit and vegetable puree-based drinks

Scope Diets low in fruits and vegetables (FV) are responsible for 2.7 million deaths from cardiovascular diseases (CVD) and certain cancers annually. Many FV and their juices contain flavonoids, some of which increase endothelial nitric oxide synthase (eNOS) activity. A single nucleotide polymorphism in the eNOS gene, where thymine (T) replaces guanine (G) at position 894 predicting substitution of glutamate for aspartate at codon 298 (Glu298Asp), has been associated with increased CVD risk due to effects on nitric oxide synthesis and subsequently vascular reactivity. Individuals can be homozygous for guanine (GG), thymine (TT) or heterozygous (GT). Methods and results We investigated the effects of acute ingestion of a FV-puree-based-drink (FVPD) on vasodilation and antioxidant status in subjects retrospectively genotyped for this polymorphism. Healthy volunteers (n = 24; 11 GG, 11 GT, 2 TT) aged 30–70 were recruited to a randomized, controlled, crossover, acute study. We showed that acute consumption of 400 mL FVPD differentially affected individuals depending on their genotype. There was a significant genotype interaction for endothelium-dependent vasodilation measured by laser Doppler imaging with iontophoresis (P < 0.05) and ex vivo low-density lipoproteins (LDL) oxidation (P = 0.002). GG subjects had increased endothelium-dependent vasodilation 180 min (P = 0.028) and reduced ex vivo LDL oxidation (P = 0.013) after 60 min after FVPD compared with control, no differences were observed in GT subjects. Conclusion eNOS Glu298Asp genotype differentially affects vasodilation and ex vivo LDL oxidation after consumption of FV in the form of a puree-based drink.

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 SFA with either monounsaturated (MUFA) or n-6 polyunsaturated fatty acids (PUFA) on vascular function and other CVD risk factors. Design: Using a randomized, controlled, single-blind, parallel group dietary intervention, 195 men and women aged 21-60 y with moderate CVD risk (≥50% above the population mean) from the United Kingdom followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA): SFA-rich (36:17:11:4, n = 65), MUFA-rich (36:9:19:4, n = 64) or n-6 PUFA-rich (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation (%FMD); 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 SFA with MUFA or n-6 PUFA did not significantly impact on %FMD (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFA with MUFA 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 MUFA or n-6 PUFA lowered fasting serum total cholesterol (TC; -8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%) and TC 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 SFA with either MUFA or n-6 PUFA did not impact significantly on %FMD 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.

Effects of chronic and acute fruit and vegetable juice consumption on cardiovascular disease risk factors

Diets low in fruit and vegetables are reportedly responsible for 2.7 million deaths annually from cardiovascular diseases (CVD) and certain cancers. A daily fruit and vegetable intake of five 80 g portions is recommended for chronic disease prevention. However, in the UK, average adult consumption is less than three portions. It is suggested that fruit juice should only count as one portion. However, fruit juices are a beneficial source of phytochemicals. The preliminary results of two randomized, controlled, crossover, dietary intervention studies investigating the effects of chronic and acute consumption of fruit and vegetable puree and juice based drinks (FVPJ) on bioavailability, antioxidant status, vascular reactivity, and risk factors for CVD are reported. In the first study, 39 volunteers consumed 200 ml FVPJ, or fruit-flavoured control, daily for six weeks. In the second study, 24 volunteers consumed 400 mL FVPJ, or sugar-matched control, on the morning of the study day. Blood and urine samples were collected throughout both studies and real-time measurements of vascular tone were performed using laser Doppler imaging with iontophoresis. Overall, the studies showed that the fruit and vegetable puree and juice based drink increased dietary phytochemicals. There was a trend towards increased vasodilation following both acute and chronic fruit juice consumption. Measurements of antioxidant status, oxidative stress and other cardiovascular disease risk factors are currently being determined.

Daily consumption of an aqueous green tea extract supplement does not impair liver function or alter cardiovascular disease risk biomarkers in healthy men

Regular consumption of green tea polyphenols (GTP) is thought to reduce the risk of cardiovascular disease (CVD) but has also been associated with liver toxicity. The present trial aimed to assess the safety and potential CVD health beneficial effects of daily GTP consumption. We conducted a placebo-controlled parallel study to evaluate the chronic effects of GTP on liver function and CVD risk biomarkers in healthy men. Volunteers (treatment: n = 17, BMI 26.7 +/- 3.3 kg/m(2), age 41 +/- 9 y; placebo, n = 16, BMI 25.4 +/- 3.3 kg/m(2), age 40 +/- 10 y) consumed for 3 wk 6 capsules per day (2 before each principal meal) containing green tea extracts (equivalent to 714 mg/d GTP) or placebo. At the beginning and end of the intervention period, we collected blood samples from fasting subjects and measured vascular tone using Laser Doppler lontophoresis. Biomarkers of liver function and CVD risk (including blood pressure, plasma lipids, and asymmetric dimethylarginine) were unaffected by GTP consumption. After treatment, the ratio of total:HDL cholesterol was significantly reduced in participants taking GTP capsules compared with baseline. Endothelial-dependent and -independent vascular reactivity did not significantly differ between treatments. In conclusion, the present data suggests that the daily consumption of high doses of GTP by healthy men for 3 wk is safe but without effects on CVD risk biomarkers other than the total:HDL cholesterol ratio. J. Nutr. 139: 58-62, 2009.

Molecular mechanisms by which dietary isoflavones potentially prevent atherosclerosis

Dietary isoflavones are currently receiving much attention because of their potential role in preventing coronary artery disease and other chronic diseases. Accumulating evidence from cell culture and laboratory animal experiments indicates that isoflavones have the potential to prevent or delay atherogenesis. Suggested mechanisms of action include: a reduction in low-density lipoprotein (LDL) cholesterol and a potential reduction in the susceptibility of the LDL particle to oxidation; (2) an improvement in vascular reactivity; (3) an inhibition of pro-inflammatory cytokines, cell adhesion proteins and nitric oxide (NO) production; and (4) an inhibition of platelet aggregation. These mechanisms are consistent with the epidemiological evidence that a high consumption of isoflavone-rich soy products is associated with a reduced incidence of coronary artery disease. Biological effects of isoflavones are dependent on many factors, including dose consumed, duration of use, protein-binding affinity, and an individual's metabolism or intrinsic oestrogenic state. Further clinical studies are necessary to determine the potential health effects of isoflavones in specific population groups as we currently know little about age-related differences in exposure to these compounds and there are few guidelines on optimal dose for cardiovascular health benefits.

Combined oral contraceptive pills containing desogestrel or drospirenone enhance large vessel and microvasculature vasodilation in healthy premenopausal women

OBJECTIVE: To determine the effects of different COCs on endothelial function. BACKGROUND: COCs all contain ethinylestradiol, but different progestins; three of the more common progestins are DSG, LN, and DR. Ethinylestradiol enhances some measures of vascular reactivity, but certain progestins may increase risk of vascular diseases and impair endothelial vasodilation. METHODS: Twenty-nine healthy women taking COCs containing 30 μg ethinylestradiol and 150 μg DSG (Marvelon, n = 10), 150 μg LN (Microgynon, n = 10), or 3 mg DR (Yasmin, n = 9) had their vascular reactivity measured using various techniques during their pill-free week (days 5-7) and the third week of active pills (days 26-28). A reference group (n = 10) underwent the same measurements on two consecutive cycles. RESULTS: FMD and LDI were significantly higher during active-pill visits than pill-free visits in women taking DSG and DR (p < 0.02), but not in women taking LN. There were no differences between the duplicate measures in the reference group. CONCLUSIONS: COCs containing 150 μg DSG or 3 mg DR significantly increase endothelium-dependent vasodilation in both large vessels and peripheral microvasculature. These effects may be due to the progestins exhibiting differential effects on eNOS expression.