Hypercholesterolemic Men Research Articles

Effects of Chokeberries (Aronia spp.) on Cytoprotective and Cardiometabolic Markers and Semen Quality in 109 Mildly Hypercholesterolemic Danish Men: A Prospective, Double-Blinded, Randomized, Crossover Trial.

Background: Chokeberries (Aronia spp.) are known to exhibit both direct and indirect antioxidant properties and have been associated with beneficial effects on human health, including cardiovascular risk factors (inflammation, serum lipids, sugars, blood pressure), oxidative stress, and semen quality. This prospective, double-blinded, randomized, crossover clinical trial was conducted to elucidate the effects of Aronia supplementation on these health targets in mildly hypercholesterolemic men. Methods: The standardized Aronia supplementation comprised three wild Aronia spp. (A. arbutifolia, A prunifolia and A. melanocarpa) and the Aronia hybrid × Sorbaronia mitschurinii (standardized to 150 mg anthocyanins daily). Participants (n = 109) were healthy men with respect to all outcome targets except for the total cholesterol level (5.0−7.0 mM). Participants were randomized to supplementation with either Aronia or placebo for 90 days, followed by a wash-out period and lastly the complementary supplementation. Effects on the health parameters were compared among both the whole group of men and in subgroups according to age, body mass index (BMI), lifestyle, dietary habits, and serum glutathione levels at baseline. The study is registered in ClinicalTrials.gov.: NCT03405753. Results: Glutathione levels were significantly improved after 90 days intake of Aronia supplementation compared to placebo in the subgroup of men with a low level of glutathione at baseline (p = 0.038) and a high coffee intake (p = 0.045). A significant decrease in levels of sperm DNA fragmentation and an increase in the percentage of motile sperm were observed in men aged >40 and in men with BMI > 25. Further, these parameters were significantly improved in the dietary subgroup defined by a high level of coffee intake. Total cholesterol and low-density lipoprotein-cholesterol levels decreased significantly in men <40 years after Aronia supplementation. No statistically significant effects were observed regarding blood pressure, markers of blood sugar regulation, hemoglobin A1c, superoxide dismutase, catalase, isoprostane levels, high sensitivity C reactive protein, or other semen parameters. Conclusions: This study demonstrated a significant increase in glutathione levels and improvement of cytoprotective targets following Aronia supplementation in specific subgroups of men >40 years of age and BMI > 25 but did not demonstrate a significant effect in the overall analysis. The observed concurrent increase in glutathione levels and improvement of cytoprotective targets following Aronia supplementation in subgroups of men, suggests that the endogenous phase II antioxidant glutathione is involved in the modulation of the observed cytoprotective effects. This study is a good foundation for further investigation of these cytoprotective effects in groups with oxidative stress in a dose−response study.

Oatmeal induced gut microbiota alteration and its relationship with improved lipid profiles: a secondary analysis of a randomized clinical trial

BackgroundIn vitro and animal experiments reported a microbiota-regulating ability of oatmeal, however, related in vivo evidences remained limited. Thus, we conducted this study aiming to investigate the oatmeal-induced alteration of gut microbiota and its potential relationship with the improvements of lipid profiles.Methods and study designData of anthropometric measurements and biochemical parameters were extracted from a randomized, controlled clinical trial, in which 62 hypercholesterolemic men and women (18–65 years old) were provided with either treatment of 80 g/day oatmeal or 80 g/day refined white rice for 45 days. Fasting blood samples and fecal samples were collected both at baseline and endpoint of the study for lipid profiling and microbiota 16S rRNA amplicon sequencing, respectively.ResultsTotally 28 participants (56 fecal samples) qualified with the new criteria and were thus included in this secondary analysis. The results of microbiota analysis showed that no significant difference was observed in the alteration of its overall α or β diversity between two groups throughout the study. Nor did any notable between-group difference was found in the relative abundance changes of microorganism at different taxonomies. However, results from linear discriminant analysis effect size in the oatmeal group indicated a significant positive response of Firmicutes phylum following oatmeal consumption. Further Procrustes analysis suggested a concordance trend between microorganism alteration and alleviation of hypercholesterolemia phenotypes throughout the study (P = 0.05). The results of within-group comparison from Spearman’s correlation in the oatmeal group demonstrated a significant association between the enrichment of Blautia genus and the reduction of serum total cholesterol (P < 0.05), low-density lipoprotein cholesterol (P < 0.01), and apolipoprotein B (P < 0.05).ConclusionsPositive response of Firmicutes phylum might be a critical characteristic of oatmeal-induced alteration of microbiota, whereas, one of the underlying cholesterol-lowering mechanism of oatmeal consumption might be its microbiota-manipulating ability, in which the enrichment of Blautia genus played a potentially significant role. Current results should be taken cautiously and more studies were needed for further verification.Trial registration: ChiCTR, ChiCTR180001864. Registered 30 September 2018, http://www.chictr.org.cn/showproj.aspx?proj=31469.

Effect of rosuvastatin on the concentration of each fatty acid in the fraction of free fatty acids and total lipids in human plasma: The role of cholesterol homeostasis

Each fatty acid (FA) or class of FAs has a different behavior in the pathologies of atherosclerosis. The aim of this study was to investigate changes in the concentration of each fatty acid in the fraction of free fatty acids (FFAs) and total lipids in human plasma after short-term therapy with rosuvastatin as a cholesterol-lowering statin drug. Six hypercholesterolemic men on a habitual diet were studied in a randomized, double-blind, and crossover process. They received 20 mg rosuvastatin or placebo in random order, each for 4 weeks and after 2 weeks of washout period, they received another medication (placebo or rosuvastatin) for another period of 4 weeks. Rosuvastatin treatment significantly decreased the absolute concentrations of saturated and monounsaturated FAs in the total FAs as well as in FFAs. Long chain polyunsaturated fatty acids with 20 and 22 carbon atoms in the molecule had no significant change in the fraction of FFAs. Rosuvastatin is directly involved in cholesterol biosynthesis and indirectly through cholesterol homeostasis in the biosynthesis of other plasma lipids.In conclusion, our findings show that rosuvastatin treatment leads to significant changes in the concentration of each fatty acid, except for long-chain polyunsaturated fatty acids in FFAs. Our observations indicate that cholesterol homeostasis through its regulatory mechanisms appears to be the main cause of changes in the concentration of each plasma fatty acid during rosuvastatin treatment. These changes can be a source of beneficial consequences, in addition to lowering low-density lipoprotein cholesterol in cardiovascular diseases.

Cereal-Based Snack Bar with Added Plant Stanol Ester (Benecol®) Consumed between Meals Lowers Serum Total and LDL Cholesterol Effectively in Mildly to Moderately Hypercholesterolemic Subjects.

The cholesterol-lowering effect of foods with added plant sterols or stanols consumed as snacks might be compromised. The purpose of this study was to confirm the cholesterol-lowering efficacy of a specially formulated cereal-based snack bar with added plant stanol ester (1.6 g plant stanols/day) when consumed between meals twice a day. In a double-blind, placebo-controlled, 4-week parallel-design study, 71 mildly to moderately hypercholesterolemic subjects were randomized into one of two groups, stanol or placebo group. Subjects were advised to replace their ordinary snacks with test products in an isocaloric manner and otherwise keep their habitual diet unchanged. The study showed that a snack bar product with added plant stanol ester lowered LDL and non-HDL cholesterol by 8.6% and 9.2% (mean%-change), respectively, as compared to the placebo product. The change in LDL cholesterol was statistically significantly different (P = 0.001) between the groups while the change in HDL cholesterol or triglycerides did not differ between the groups. In conclusion, the cereal-based snack bar with added plant stanol ester ingested without a meal reduced LDL cholesterol significantly without affecting HDL cholesterol or triglyceride concentrations in mildly hypercholesterolemic men and women. The study is registered as NCT03284918.

Simvastatin reduces circulating oxysterol levels in men with hypercholesterolaemia

Oxysterols (OHC) are biologically active cholesterol metabolites circulating in plasma that may be formed enzymatically (e.g. 24S-OHC, 25-OHC and 27-OHC) or by autoxidative mechanisms (e.g. 7-ketocholesterol, 7β-OHC and 25-OHC). Oxysterols are more soluble than cholesterol and are reported to exert inflammatory, cytoprotective and apoptotic effects according to concentration and species. Esterified oxysterols have been analysed in people with dementia and cardiovascular diseases although there is no consistent relationship between oxysterol esters and disease. However, oxysterol esters are held in lipoprotein core and may not relate to the concentration and activity of plasma free oxysterols. Methodological limitations have challenged the analysis of free oxysterols to date.We have developed a fast, sensitive and specific quantitative LC-MS/MS, multiple reaction monitoring (MRM) method to target five oxysterols in human plasma with analyte recoveries between 72% and 82% and sensitivities between 5 and 135 pg/ml. A novel method was used to investigate the hypothesis that simvastatin may reduce the concentrations of specific plasma free oxysterols in hypercholesterolaemia.Twenty healthy male volunteers were recruited (aged 41–63 years); ten were asymptomatic with high plasma cholesterol > 6.5 mM and ten were healthy with normal plasma cholesterol (< 6.5 mM). Simvastatin (40 mg/day) was prescribed to those with hypercholesterolaemia. Plasma samples were taken from both groups at baseline and after three months. Simvastatin reduced plasma cholesterol by ~35% (p < 0.05) at the end of three months.Oxysterols generated by autoxidation (but not enzymatically) were elevated up to 45 fold in hypercholesterolaemic midlife men. Plasma oxysterols were restored to those of healthy controls after simvastatin intervention suggesting that autoxidation is either prevented by simvastatin directly or that autoxidation is less prevalent when plasma cholesterol concentrations are within the normal range.

Lactic-fermented egg white reduced serum cholesterol concentrations in mildly hypercholesterolemic Japanese men: a double-blind, parallel-arm design

BackgroundLactic-fermented egg white (LE), produced by lactic acid fermentation of egg white, is an easy-to-consume form of egg white. Here we assessed the effect of daily consumption of LE for 8 weeks on serum total cholesterol (TC) levels.MethodsThe study followed a double-blind, parallel-arm design and included 88 adult men with mild hypercholesterolemia (mean ± standard error) serum TC levels, 229 ± 1.6 mg/dL; range, 204–259 mg/dL). The subjects were randomly divided into three groups, which consumed LE containing 4, 6, or 8 g of protein daily for 8 weeks. Blood samples were collected before starting LE consumption (baseline) and at 4 and 8 weeks to measure serum TC and low-density lipoprotein cholesterol (LDL-C) levels.ResultsAfter 8 weeks of consumption, serum TC levels in the 8 g group decreased by 11.0 ± 3.7 mg/dL, a significant decrease compared to baseline (p < 0.05) and a significantly greater decrease than for the 4 g group (3.1 ± 3.4 mg/dL; p < 0.05). Serum LDL-C levels in the 8 g group decreased by 13.7 ± 3.1 mg/dL, again a significant decrease compared with baseline (p < 0.05) and a significantly greater decrease than that for the 4 g group (2.1 ± 2.9 mg/dL; p < 0.05).ConclusionConsumption of LE for 8 weeks at a daily dose of 8 g of proteins reduced serum TC and LDL-C levels in men with mild hypercholesterolemia, suggesting this may be effective in helping to prevent arteriosclerotic diseases.Trial registrationThis clinical trial was retrospectively registered with the Japan Medical Association Center for Clinical Trials, (JMA-IIA00279; registered on 13/03/2017; https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRE02_04/JMACTRE02_04.aspx?kbn=3&seqno=6530).

Effects of Ready-to-Eat-Cereals on Key Nutritional and Health Outcomes: A Systematic Review.

BackgroundIn many countries breakfast cereals are an important component of breakfast. This systematic review assesses the contribution of consumption of ready-to eat cereal (RTEC) to the recommended nutrient intake. Furthermore, the effects of RTEC consumption on key health parameters are investigated as well as health promoting properties of RTEC.MethodThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL have been searched up till 16th of June 2015. Randomized controlled trials were excluded if RTEC were used during hypocaloric diets, if RTEC were eaten at other times than breakfast and if breakfasts included other products than RTEC, milk and fruit. Observational studies were excluded when “breakfast cereals” were not defined or their definition included cooked cereals. From cross-sectional studies only data concerning energy and nutrient intake as well as micronutrient status were used.ResultsFrom 4727 identified citations 64 publications met the inclusion criteria of which 32 were cross-sectional studies, eight prospective studies and 24 randomized controlled trials. Consumption of RTEC is associated with a healthier dietary pattern, concerning intake of carbohydrates, dietary fiber, fat and micronutrients, however total sugar intake is higher. Persons consuming RTEC frequently (≥ 5 times/week) have a lower risk of inadequate micronutrient intake especially for vitamin A, calcium, folate, vitamin B 6, magnesium and zinc. Evidence from prospective studies suggests that whole grain RTEC may have beneficial effects on hypertension and type 2 diabetes. Consumption of RTEC with soluble fiber helps to reduce LDL cholesterol in hypercholesterolemic men and RTEC fortified with folate can reduce plasma homocysteine.DiscussionOne of the review’s strengths is its thorough ex/inclusion of studies. Limitations are that results of observational studies were based on self-reported data and that many studies were funded by food-industry.ConclusionConsumption of RTEC, especially of fiber-rich or whole grain RTEC, is implicated with several beneficial nutritional and health outcomes. The effect on body weight, intestinal health and cognitive function needs further evaluation. Of concern is the higher total sugar intake associated with frequent RTEC consumption.

Regularly consuming a green/roasted coffee blend reduces the risk of metabolic syndrome.

Preventive health effects of coffee could have a widespread impact on public health. Green coffee has more phenols than roasted, and thus is healthier, although withless acceptable organoleptic properties. Therefore, the effects of regularly consuming a green/roasted coffee blend (35/65) on the main components of MetS in humans were evaluated. A crossover, randomized, controlled study was performed in 25 normocholesterolaemic and 27 hypercholesterolaemic men and women aged 18-45years with BMI 18-25kg/m2. Three servings/day of the blend, providing 510.6mg hydroxycinnamic acids and 121.2mg caffeine/day, were consumed versus a control drink, during 8weeks each. Polyphenol and methylxanthine-rich foods were restricted along the study. At the beginning (baseline) and end of the control and coffee interventions, blood samples were collected and glucose, HDL-cholesterol, triglycerides, insulin, leptin, plasminogen activator inhibitor-1 (PAI-1), resistin and visfatin were analysed; waist circumference, %body fat, and blood pressure were measured and dietary records and physical activity questionnaires completed. Systolic and diastolic blood pressure decreased (p=0.001 and p<0.001, respectively) in both groups as well as %body fat (p=0.001) which may be related to the lower leptin (p=0.001), PAI-1 (p<0.001) and resistin (p=0.034) levels in the two groups after coffee consumption. Glucose concentration (p=0.030) and insulin resistance (p=0.011; HOMA-IR) also decreased, as well as triglyceride levels (p=0.017), so that the reduction was much greater in the hypercholesterolaemics (group effect, p=0.027). Regular consumption of the green/roasted coffee blend may be recommended to healthy and hypercholesterolaemic subjects to prevent MetS, as it produces positive effects on blood pressure, glucose and triglyceride levels.

Probiotic Soy Product Supplemented with Isoflavones Improves the Lipid Profile of Moderately Hypercholesterolemic Men: A Randomized Controlled Trial.

Background: Cardiovascular disease is the leading cause of worldwide morbidity and mortality. Several studies have demonstrated that specific probiotics affect the host’s metabolism and may influence the cardiovascular disease risk. Objectives: The aim of this study was to investigate the influence of an isoflavone-supplemented soy product fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416 on cardiovascular risk markers in moderately hypercholesterolemic subjects. Design: Randomized placebo-controlled double-blind trial Setting: São Paulo State University in Araraquara, SP, Brazil. Participants: 49 male healthy men with total cholesterol (TC) >5.17 mmol/L and <6.21 mmol/L Intervention: The volunteers have consumed 200 mL of the probiotic soy product (group SP-1010 CFU/day), isoflavone-supplemented probiotic soy product (group ISP–probiotic plus 50 mg of total isoflavones/100 g) or unfermented soy product (group USP-placebo) for 42 days in a randomized, double-blind study. Main outcome measures: Lipid profile and additional cardiovascular biomarkers were analyzed on days 0, 30 and 42. Urine samples (24 h) were collected at baseline and at the end of the experiment so as to determine the isoflavones profile. Results: After 42 days, the ISP consumption led to improved total cholesterol, non-HDL-C (LDL + IDL + VLDL cholesterol fractions) and electronegative LDL concentrations (reduction of 13.8%, 14.7% and 24.2%, respectively, p < 0.05). The ISP and SP have prevented the reduction of HDL-C level after 42 days. The C-reactive protein and fibrinogen levels were not improved. The equol production by the ISP group subjects was inversely correlated with electronegative LDL concentration. Conclusions: The results suggest that a regular consumption of this probiotic soy product, supplemented with isoflavones, could contribute to reducing the risk of cardiovascular diseases in moderately hypercholesterolemic men, through the an improvement in lipid profile and antioxidant properties.

Effect of a plant sterol-enriched spread on biomarkers of endothelial dysfunction and low-grade inflammation in hypercholesterolaemic subjects.

Plant sterols (PS) lower LDL-cholesterol, an established risk factor for CHD. Endothelial dysfunction and low-grade inflammation are two important features in the development of atherosclerosis. Whether PS affect biomarkers of endothelial function and low-grade inflammation is not well studied. The aim of the present study was to investigate the effect of regular intake of PS on biomarkers of endothelial dysfunction and low-grade inflammation. In a double-blind, randomised, placebo-controlled, parallel-group study, which was primarily designed to investigate the effect of PS intake on vascular function (clinicaltrials.gov: NCT01803178), 240 hypercholesterolaemic but otherwise healthy men and women consumed a low-fat spread with added PS (3 g/d) or a placebo spread for 12 weeks. Endothelial dysfunction biomarkers (both vascular and intracellular adhesion molecules 1 and soluble endothelial-selectin) and low-grade inflammation biomarkers (C-reactive protein, serum amyloid A, IL-6, IL-8, TNF-α and soluble intercellular adhesion molecule-1) were measured using a multi-array detection system based on electrochemiluminescence technology. Biomarkers were combined using z-scores. Differences in changes from baseline between the PS and the placebo groups were assessed. The intake of PS did not significantly change the individual biomarkers of endothelial dysfunction and low-grade inflammation. The z-scores for endothelial dysfunction (-0·02; 95 % CI -0·15, 0·11) and low-grade inflammation (-0·04; 95 % CI -0·16, 0·07) were also not significantly changed after PS intake compared with placebo. In conclusion, biomarkers of endothelial dysfunction and low-grade inflammation were not affected by regular intake of 3 g/d PS for 12 weeks in hypercholesterolaemic men and women.

The effect of a low-fat spread with added plant sterols on vascular function markers: Results of the investigating vascular function effects of plant sterols (invest) study

Background: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage. Objectives: This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD. Design: This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed. Results: In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: −0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: −0.40, −0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 μmol/L and 13.9 μmol/L (expressed as geometric means), respectively. Conclusions: The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as {type:clinical-trial,attrs:{text:NCT01803178,term_id:NCT01803178}}NCT01803178.

The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study

Background: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage.Objectives: This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD.Design: This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed.Results: In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: −0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: −0.40, −0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 μmol/L and 13.9 μmol/L (expressed as geometric means), respectively.Conclusions: The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as NCT01803178.

A study in familial hypercholesterolemia suggests reduced methylomic plasticity in men with coronary artery disease.

To assess whether DNA methylation is associated with coronary artery disease (CAD). An epigenome-wide analysis has been performed on leucocytes from familial hypercholesterolemic (FH) men with (n = 6) or without CAD (n = 6). The results were replicated in an extended sample of FH men (n = 61) and in non-FH men (n = 100) for two of the top differentially methylated loci. FH men with CAD had significantly more hypomethylated and hypermethylated loci and showed less DNA methylation level variability compared with men without CAD (p < 0.001). Moreover, COL14A1 and MMP9 DNA methylation levels were associated with CAD, age of onset of CAD or CAD risk factors. These results suggest that epigenome-wide changes are associated with CAD occurrence in men.

Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men

Blond orange juice is the most consumed fruit juice in the world. It is a source of hesperidin, a bioavailable flavonoid reported to exhibit potential vascular protective actions. However, the specific impact on vascular function of Citrus phytomicronutrients, is unknown. For the first time, we investigated the effects of blond orange juice compared with a control beverage mimicking the composition of orange juice (including Vitamin C but no phytomicronutrients), on antioxidant markers, cardiovascular risk factors and endothelial function. Twenty five male volunteers with two cardiovascular risk factors (age over 50 years and LDL-cholesterol between 130 and 190mg/L) were enrolled in a randomized cross-over study. They received 3 times daily 200mL of either blond orange juice or control beverage for 4 weeks, spaced by a 5-week wash-out. Endothelial function (flow mediated dilatation and plasma markers), oxidative status, lipid profile and inflammatory markers were assessed. Daily intakes of orange juice significantly led to a marked antioxidant effect which was correlated to hesperetin plasma levels and related with a decrease in reactive oxygen species. A tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I concentration were also observed. This allows further experiments demonstrating the specific effect of phytomicronutrients from orange juice. These findings suggest that daily intake of nutritionally relevant dose of blond orange juice may contribute for a significant antioxidant effect through the phytochemicals contained in. Orange juice may be associated to other healthy foods to achieve a significant effect on the vascular function. This study is recorded in ClinicalTrials.com as NCT00539916.

Correction: Statin Treatment in Hypercholesterolemic Men Does Not Attenuate Angiotensin II-Induced Venoconstriction

Correction: Statin Treatment in Hypercholesterolemic Men Does Not Attenuate Angiotensin II-Induced Venoconstriction

Low Doses of Eicosapentaenoic Acid and Docosahexaenoic Acid From Fish Oil Dose-Dependently Decrease Serum Triglyceride Concentrations in the Presence of Plant Sterols in Hypercholesterolemic Men and Women

Plant sterols (PSs) lower LDL cholesterol (LDL-C) concentrations, whereas the n–3 (ω-3) fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglyceride (TG) concentrations. Incorporating both PSs and EPA+DHA from fish oil (FO) in a single food format was expected to beneficially affect 2 blood lipid risk factors. The aim of this study was to investigate the dose-response relation between low doses (<2 g/d) of EPA+DHA from FO, incorporated in a low-fat PS-enriched spread, and TG concentrations. In addition, effects on LDL-C were investigated. The study was designed as a randomized, double-blind, placebo-controlled parallel study. After a 4-wk run-in period, subjects were randomly assigned to consume either a control (C) spread (no PSs, no FO) or 1 of 4 intervention spreads containing a fixed amount of PSs (2.5 g/d) and varying amounts of FO (0.0, 0.9, 1.3, and 1.8 g/d of EPA+DHA) for 4 wk. Before and after the intervention, fasting blood samples were drawn for measuring serum lipids and EPA and DHA in erythrocyte membranes. In total, 85 hypercholesterolemic men and 247 women with a mean age of 57.9 y (range: 25–74 y) were included. Eighteen subjects dropped out during the study. At baseline, mean TG and LDL-C concentrations were 1.09 and 4.00 mmol/L, respectively. After the intervention, a significant dose-response relation for the TG-lowering effect of EPA+DHA [βln(TG) = −0.07 mmol/L per gram of EPA+DHA; P < 0.01] was found. Compared with the C group, TG concentrations were 9.3–16.2% lower in the different FO groups (P < 0.05 for all groups). LDL-C concentrations were 11.5–14.7% lower in the different PS groups than in the C group (P < 0.01 for all groups). EPA and DHA in erythrocyte membranes were dose-dependently higher after FO intake than after the C spread, indicating good compliance. Consumption of a low-fat spread enriched with PSs and different low doses of n–3 fatty acids from FO decreased TG concentrations in a dose-dependent manner and decreased LDL-C concentrations. This trial was registered at >clinicaltrials.gov as NCT01313988.

Statin treatment in hypercholesterolemic men does not attenuate angiotensin II-induced venoconstriction.

Experimental studies suggested that statins attenuate vascular AT1 receptor responsiveness. Moreover, the augmented excessive pressor response to systemic angiotensin II infusions in hypercholesterolemic patients was normalized with statin treatment. In 12 hypercholesterolemic patients, we tested the hypothesis that statin treatment attenuates angiotensin II-mediated vasoconstriction in hand veins assessed by a linear variable differential transducer. Subjects ingested daily doses of either atorvastatin (40 mg) or positive control irbesartan (150 mg) for 30 days in a randomized and cross-over fashion. Ang II–induced venoconstriction at minute 4 averaged 59%±10% before and 28%±9% after irbesartan (mean ± SEM; P<0.05) compared to 65%±11% before and 73%±11% after 30 days of atorvastatin treatment. Plasma angiotensin levels increased significantly after irbesartan treatment (Ang II: 17±22 before vs 52±40 pg/mL after [p = 0.048]; Ang-(1–7): 18±10 before vs 37±14 pg/mL after [p = 0.002]) compared to atorvastatin treatment (Ang II: 9±4 vs 11±10 pg/mL [p = 0.40]; Ang-(1–7): 24±9 vs 32±8 pg/mL [p = 0.023]). Our study suggests that statin treatment does not elicit major changes in angiotensin II-mediated venoconstriction or in circulating angiotensin II levels whereas angiotensin-(1–7) levels increased modestly. The discrepancy between local vascular and systemic angiotensin II responses might suggest that statin treatment interferes with blood pressure buffering reflexes.Trial RegistrationClinicalTrials.gov NCT00154024

Bovine Peptic Casein Hydrolysate Ameliorates Cardiovascular Risk Factors in a Model of ApoE-deficient Mice but not Overweight, Mildly Hypercholesterolaemic Men

Associations have been shown between consumption of bovine dairy and decreased prevalence of metabolic related disorders. Milk peptides may promote both angiotensin-I- converting enzyme (ACE) inhibition for blood pressure (BP) lowering and insulin action for better glycaemic control. Less is known of other metabolic parameters. The aim of this study was to investigate effects of dairy peptic casein hydrolysate (CH) on markers of cardiovascular disease (CVD) risk in (1) an apolipoproteinE (ApoE) - deficient mouse model of high-fat fed hypercholesterolaem- ia, and, (2) a clinical study of moderate overweight and hypercholesterolaemia. In Trial 1, ApoE-deficient mice were supplemented with high dose CH (~1g/kg body weight) in a randomised, 9-wk, parallel design intervention, and blood and tissue samples harvested. In Trial 2, 24 mildly hypercholesterolaemic men were supplemented with lower dose CH (~0.1g/kg body weight, 10g/day, 3-wks) and matched whey protein control (WP, 10g/day, 3-wks) in a randomised, 9-wk, cross-over design intervention. Diets were separated by a 3-wk washout. Fasting blood and urine samples were collected, and blood pressure (BP) measured weekly. Clinical trial registration number, ACTRN 12611001013954. In ApoE-deficient mice, administration of CH significantly inhibited circulating total cholesterol concentrations by 37% (TC, P&lt;0.01) and decreased aorta atherosclerotic lesion score by 25% (P&lt;0.01). In the clinical study there were no significant differential effects of CH supplementation on CV markers, including serum lipids (TC, LDL-C, HDL-C, triglyceride), glucose and BP. Whilst high dose bovine peptic CH attenuated CVD risk in a murine ApoE deficient model of aggressive hypercholesterolaemia, no evidence of amelioration of risk by supplementation with a lower dose of CH in an overweight population of mildly hypercholesterolaemic men was found.

Daily kiwifruit consumption did not improve blood pressure and markers of cardiovascular function in men with hypercholesterolemia

Increasing fruit and vegetable consumption is a key lifestyle modification in the prevention and treatment of hypertension. Kiwifruit has previously been shown to have favorable effects on blood pressure (BP), likely through inhibiting angiotensin I–converting enzyme activity. We hypothesized that the replacement of 2 fruit servings in a healthy diet with 2 green kiwifruit a day would significantly improve BP and other markers of cardiovascular function, including heart rate, stroke volume, cardiac output, and total peripheral resistance, in a group of hypercholesterolemic men. Using a controlled cross-over study design, 85 subjects completed a 4-week healthy diet run-in period before randomization to one of two 4-week intervention sequences in which they either consumed 2 green kiwifruit a day plus a healthy diet (intervention) or consumed a healthy diet alone (control). Blood pressure and other measures of cardiovascular function (using a Finometer MIDI [Finapres Medical Systems B.V, Amsterdam, The Netherlands] and standard oscillometric device) and anthropometric measurements were taken before and at the end of the treatment periods. A physical activity questionnaire was completed during the last visit. Subjects were found to be predominantly normotensive (43.5%) or prehypertensive (50.6%) and quite physically active (>30 minutes of moderate to vigorous physical activity/day in >80% subjects). No significant differences were seen for BP or any of the other markers, including heart rate, stroke volume, cardiac output, and total peripheral resistance. In conclusion, in this hypercholesterolemic, nonhypertensive group, no beneficial effects on BP or other markers of cardiovascular function were seen when consuming 2 kiwifruit a day against the background of a healthy diet.

TaqIB polymorphism in the cholesteryl ester transfer protein (CETP) gene influences lipid responses to the consumption of kiwifruit in hypercholesterolaemic men

Fruit and vegetables are key elements of a cardioprotective diet, but benefits on plasma lipids, especially HDL-cholesterol (HDL-C), are inconsistent both within and between studies. In the present study, we investigated whether four selected HDL-C-related polymorphisms (cholesteryl ester transfer protein (CETP) Taq1B, APOA1 -75G/A, hepatic lipase (LIPC) -514C→T, and endothelial lipase (LIPG) I24582) modulate the plasma lipid response to a kiwifruit intervention. This is a retrospective analysis of data collected during a 12-week randomised controlled cross-over trial. A total of eighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in period before being randomised to one of two 4-week intervention sequences of two green kiwifruit/d plus healthy diet (kiwifruit intervention) or healthy diet alone (control intervention). The measurement of anthropometric parameters and collection of fasting blood samples were carried out at baseline 1 and after the run-in (baseline 2) and intervention periods. At baseline 2, B1/B1 homozygotes of the CETP Taq1B gene had significantly higher total cholesterol:HDL-C, TAG:HDL-C, and apoB:apoA1 ratios and small-dense LDL concentrations than B2 carriers. A significant CETP Taq1B genotype×intervention interaction was observed for the TAG:HDL-C ratio (P=0·03). B1/B1 homozygotes had a significantly lower TAG:HDL-C (-0·23 (sd 0·58)mmol/l; P=0·03) ratio after the kiwifruit intervention than after the control intervention, whereas the ratio of B2 carriers was not affected. The lipid response was not affected by other gene polymorphisms. In conclusion, the significant decrease in the TAG:HDL-C ratio in B1/B1 homozygotes suggests that regular inclusion of green kiwifruit as part of a healthy diet may improve the lipid profiles of hypercholesterolaemic men with this genotype.