Dietary monounsaturated fatty acids and haemostasis

Diets high in monounsaturated fatty acids (MUFA) are increasingly being recommended as a highly-effective cholesterol-lowering strategy in populations at risk of CHD. However, the need for a re-appraisal of the benefits of diets rich in MUFA became apparent as a result of recent studies showing that meals high in olive oil cause greater postprandial activation of blood coagulation factor VII than meals rich in saturated fatty acids. The present review evaluates the evidence for the effects of MUFA-rich diets on fasting and postprandial measurements of haemostasis, and describes data from a recently-completed long-term controlled dietary intervention study. The data show that a background diet high in MUFA has no adverse effect on fasting haemostatic variables and decreases the postprandial activation of factor VII in response to a standard fat-containing meal. Since the same study also showed a significant reduction in the ex vivo activation of platelets in subjects on the high-MUFA diet, the overall findings suggest that there is no reason for concern regarding adverse haemostatic consequences of high-MUFA diets.

Genetic predisposition influences plasma lipids of participants on habitual diet, but not the response to reductions in dietary intake of saturated fatty acids

Objective: SNPs identified from genome wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the ‘RISCK’ study cohort. Methods: Participants (n = 490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. Results: The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total(P = 0.02) and LDL (P = 0.002) cholesterol, triglycerides (P = 0.001) and apolipoprotein B (P = 0.004), and with lower baseline concentrations of HDL cholesterol (P < 0.001) and apolipoprotein A-I (P < 0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. Conclusion: Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.

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.

PPARγ2 gene Pro12Ala and PPARα gene Leu162Val single nucleotide polymorphisms interact with dietary intake of fat in determination of plasma lipid concentrations

Background/Aims: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of lipid metabolism, activated by unsaturated fatty acids. We investigated independent and interactive effects of PPARγ2 gene PPARG Pro12Ala (rs1801282) andPPARαgene PPARA Leu162Val (rs1800206) genotypes with dietary intake of fatty acids on concentrations of plasma lipids in subjects of whom 47.5% had metabolic syndrome. Methods: The RISCK study is a parallel design, randomised controlled trial. Plasma lipids were quantified at baseline after a 4-week high saturated fatty acids diet and after three parallel 24-week interventions with reference (high saturated fatty acids), high monounsaturated fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in 466 subjects. Results: At baseline, the PPARG Ala12allele was associated with increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p = 0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At baseline, PPARA Leu162Val × PPARG Pro12Ala genotype interaction did not significantly influence plasma lipid concentrations. After dietary intervention, gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and small dense LDL as a proportion of LDL (p = 0.005) after adjustments. Conclusions: Interaction between PPARG Pro12Ala and PPARA Leu162Valgenotypes may influence plasma LDL cholesterol concentration and the proportion as small dense LDL after a high monounsaturated fatty acids diet.

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. The SATgenϵ study was registered at clinicaltrials.gov as NCT01384032.

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 (Sf) 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.

Assessment of the dietary intake of total flavan-3-ols, monomeric flavan-3-ols, proanthocyanidins and theaflavins in the European Union

Dietary interventions with flavan-3-ols have shown beneficial effects on vascular function. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations. Therefore, in the present study, we assessed the habitual intake of flavan-3-ol monomers, proanthocyanidins (PA) and theaflavins in the European Union (EU) and determined their main food sources using the EFSA (European Food Safety Authority) Comprehensive European Food Consumption Database. Data for adults aged 18–64 years were available from fourteen European countries, and intake was determined using the FLAVIOLA Flavanol Food Composition Database, developed for the present study and based on the latest US Department of Agriculture and Phenol-Explorer databases. The mean habitual intake of flavan-3-ol monomers, theaflavins and PA ranged from 181 mg/d (Czech Republic) to 793 mg/d (Ireland). The highest intakes of flavan-3-ol monomers and theaflavins were observed in Ireland (191/505 mg/d) and the lowest intakes in Spain (24/9 mg/d). In contrast, the daily intake of PA was highest in Spain (175 mg/d) and lowest in The Netherlands (96 mg/d). Main sources were tea (62 %), pome fruits (11 %), berries (3 %) and cocoa products (3 %). Tea was the major single contributor to monomer intake (75 %), followed by pome fruits (6 %). Pome fruits were also the main source of PA (28 %). The present study provides important data on the population-based intake of flavanols in the EU and demonstrates that dietary intake amounts for flavan-3-ol monomers, PA and theaflavins vary significantly across European countries. The average habitual intake of flavan-3-ols is considerably below the amounts used in most dietary intervention studies.

Impact of dietary polydextrose fiber on the human gut metabolome

The aim of the present study was to elucidate the impact of polydextrose PDX an soluble fiber, on the human fecal metabolome by high-resolution nuclear magnetic resonance (NMR) spectroscopy-based metabolomics in a dietary intervention study (n = 12). Principal component analysis (PCA) revealed a strong effect of PDX consumption on the fecal metabolome, which could be mainly ascribed to the presence of undigested fiber and oligosaccharides formed from partial degradation of PDX. Our results demonstrate that NMR-based metabolomics is a useful technique for metabolite profiling of feces and for testing compliance to dietary fiber intake in such trials. In addition, novel associations between PDX and the levels of the fecal metabolites acetate and propionate could be identified. The establishment of a correlation between the fecal metabolome and levels of Bifidobacterium (R2 = 0.66) and Bacteroides (R2 = 0.46) demonstrates the potential of NMR-based metabolomics to elucidate metabolic activity of bacteria in the gut.

Carotenoids but not flavonoids are associated with improvements in spatial working memory in younger adults in a flavonoid-rich v. -poor fruit and vegetable intervention study

Findings from animal studies suggest that components of fruit and vegetables (F&V) may protect against, and even reverse, age-related decline(1,2) in aspects of cognitive functioning such as spatial working memory (SWM). Human subjects in vivo and in vitro studies indicate that anti-inflammatory, anti-oxidant and cell-signalling properties of flavonoids and carotenoids, non-nutrient components of F&V, may underpin this protective effect(3–5). The Flavonoid University of Reading Study (FLAVURS), designed to explore the dose-response relationship between dietary F&V flavonoids and CVD, enabled the investigation of such an association with SWM. FLAVURS is an 18-week parallel three-arm randomised controlled dietary intervention trial with four time points, measured at 6-weekly intervals from baseline. Low F&V consumers at risk of CVD aged 26–70 years were randomly assigned to high flavonoid (HF), low flavonoid (LF) or control group. F&V intake increased by two daily 80 g portions every 6 weeks, with either HF or LF F&V, in addition to each participant's habitual diet, while controls maintained their habitual diet. At each visit, participants completed a cognitive test battery with SWM as the primary outcome. The HF group showed significantly higher levels of urinary flavonoids than LF or controls at 12 weeks (P<0.001) as expected, but surprisingly only higher levels than LF at 18 weeks (P<0.01). The LF group showed higher levels of plasma carotenoids than the other groups at 18 weeks (P<0.001). No group differences were found for SWM overall, however, age-group sub-analyses (26–50 and 51–70 years of age) showed differences from 0 to 18 weeks for younger adults, with LF improving significantly more than the other two groups on SWM (P<0.05). As nutritional absorption is known to decrease with age, separate stepwise regressions were performed on the two age groups irrespective of dietary group, with urinary flavonoids and plasma carotenoids as predictors. For younger adults, improved SWM performance from 0 to 18 weeks was associated with higher carotenoid levels, β=0.28, t(55)=2.10, P<0.05, accounting for 7.5% of the variance, R2=0.075, F(1,54)=4.41, P=0.040. For older adults, no between-group SWM differences were found. Findings suggest that F&V-based flavonoids and carotenoids may provide benefits for cognitive function, and that carotenoids in particular may improve cognitive performance in SWM. Given that these benefits were restricted to younger adults, future work is needed to test the reliability of this finding, as well as determine the mechanisms by which age-dependent differences in F&V responsiveness occur.

Interactions between cocoa flavanols and inorganic nitrate: additive effects on endothelial function at achievable dietary amounts

Dietary intervention studies have shown that flavanols and inorganic nitrate can improve vascular function, suggesting that these two bioactives may be responsible for beneficial health effects of diets rich in fruits and vegetables. We aimed to study interactions between cocoa flavanols (CF) and nitrate, focusing on absorption, bioavailability, excretion, and efficacy to increase endothelial function. In a double-blind randomized, dose-response crossover study, flow-mediated dilation (FMD) was measured in 15 healthy subjects before and at 1, 2, 3, and 4 h after consumption of CF (1.4-10.9 mg/kg bw) or nitrate (0.1-10 mg/kg bw). To study flavanol-nitrate interactions, an additional intervention trial was performed with nitrate and CF taken in sequence at low and high amounts. FMD was measured before (0 h) and at 1h after ingestion of nitrate (3 or 8.5 mg/kg bw) or water. Then subjects received a CF drink (2.7 or 10.9 mg/kg bw) or a micro- and macronutrient-matched CF-free drink. FMD was measured at 1, 2, and 4 h thereafter. Blood and urine samples were collected and assessed for CF and nitric oxide (NO) metabolites with HPLC and gas-phase reductive chemiluminescence. Finally, intragastric formation of NO after CF and nitrate consumption was investigated. Both CF and nitrate induced similar intake-dependent increases in FMD. Maximal values were achieved at 1 h postingestion and gradually decreased to reach baseline values at 4 h. These effects were additive at low intake levels, whereas CF did not further increase FMD after high nitrate intake. Nitrate did not affect flavanol absorption, bioavailability, or excretion, but CF enhanced nitrate-related gastric NO formation and attenuated the increase in plasma nitrite after nitrate intake. Both flavanols and inorganic nitrate can improve endothelial function in healthy subjects at intake amounts that are achievable with a normal diet. Even low dietary intake of these bioactives may exert relevant effects on endothelial function when ingested together.

Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study

Background: Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established. OBJECTIVE: Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors. DESIGN: In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined. RESULTS: Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05). CONCLUSIONS: Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features.

Preschool children and excess weight: the impact of a low complexity intervention in public day care centers

Introduction: childhood obesity is a major public health problem, affecting children even at early ages. Objective: to assess the impact of dietary intervention and relatively simple physical activity on the nutritional state of preschoolers. Method: this was an intervention study in public daycare centers targeting children from 2 to 4 years of age, in the State of São Paulo. The sample consisted of 9 daycare centers covering 578 children, with 264 children in the intervention group (IG) and 314 in the comparison group (CG). Intervention was focused on modifications in diet and physical activity, avoiding overloading the routine of daycare centers, for duration of one year. A zBMI score > 1 (zBMI) and < 2 was considered risk of being overweight, and > 2 zBMI was considered excess weight (overweight and obese). Analysis was done by frequency calculations, comparisons of proportions by χ2, mean comparisons by t-student and calculations according to Pearson’s correlation coefficient. Results: IG showed an inverse correlation between the initial zBMI of the children and the difference with the zBMI at the end of the intervention (rP = -0.39, p <0.0001). The mean difference of zBMI of the overweight children in IG between the beginning and the end of the study period was negative (-0.46 z score), indicating weight reduction, while the children in the CG was positive (+0. 17 z score) (p = 0.0037). Conclusion: intervention in diet and physical activity in overweight preschool children in daycare centers could have a favorable impact on the evolution of their nutritional state.

Two patterns of adipokine and other biomarker dynamics in a long-term weight loss intervention

Long-term dietary intervention frequently induces a rapid weight decline followed by weight stabilization/regain. Here, we sought to identify adipokine biomarkers that may reflect continued beneficial effects of dieting despite partial weight regain.

The food choice at work study: effectiveness of complex workplace dietary interventions on dietary behaviours and diet-related disease risk - study protocol for a clustered controlled trial

Background: Dietary behaviour interventions have the potential to reduce diet-related disease. Ample opportunity exists to implement these interventions in the workplace. The overall aim is to assess the effectiveness and cost-effectiveness of complex dietary interventions focused on environmental dietary modification alone or in combination with nutrition education in large manufacturing workplace settings. Methods/design: A clustered controlled trial involving four large multinational manufacturing workplaces in Cork will be conducted. The complex intervention design has been developed using the Medical Research Council's framework and the National Institute for Health and Clinical Excellence (NICE) guidelines and will be reported using the TREND statement for the transparent reporting of evaluations with non-randomized designs. It will draw on a soft paternalistic 'nudge' theoretical perspective. It will draw on a soft paternalistic "nudge" theoretical perspective. Nutrition education will include three elements: group presentations, individual nutrition consultations and detailed nutrition information. Environmental dietary modification will consist of five elements: (a) restriction of fat, saturated fat, sugar and salt, (b) increase in fibre, fruit and vegetables, (c) price discounts for whole fresh fruit, (d) strategic positioning of healthier alternatives and (e) portion size control. No intervention will be offered in workplace A (control). Workplace B will receive nutrition education. Workplace C will receive nutrition education and environmental dietary modification. Workplace D will receive environmental dietary modification alone. A total of 448 participants aged 18 to 64 years will be selected randomly. All permanent, full-time employees, purchasing at least one main meal in the workplace daily, will be eligible. Changes in dietary behaviours, nutrition knowledge, health status with measurements obtained at baseline and at intervals of 3 to 4 months, 7 to 9 months and 13 to 16 months will be recorded. A process evaluation and cost-effectiveness economic evaluation will be undertaken. Discussion: A 'Food Choice at Work' toolbox (concise teaching kit to replicate the intervention) will be developed to inform and guide future researchers, workplace stakeholders, policy makers and the food industry. Trial registration: Current Controlled Trials, ISRCTN35108237.

A genetic variant of the CAPN10 gene in Mexican subjects with dyslipidemia is associated with increased HDL-cholesterol concentrations after the consumption of a soy protein and soluble fiber dietary portfolio

Dyslipidemia is a major public health problem, and therefore, it is important to develop dietary strategies to diminish the prevalence of this disorder. It was recently reported that diet may play an important role in triggering insulin resistance by interacting with genetic variants at the CAPN10 gene locus in patients with metabolic syndrome. Nonetheless, it remains unknown whether genetic variants of genes involved in the development of type 2 diabetes are associated with variations in high-density lipoprotein cholesterol (HDL-C). The study used a single-center, prospective, cohort design. Here, we assessed the effect of four variants of the CAPN10 gene on HDL-C levels in response to a soy protein and soluble fiber dietary portfolio in subjects with dyslipidemia. In 31 Mexican dyslipidemic individuals, we analyzed four CAPN10 gene variants (rs5030952, rs2975762, rs3792267, and rs2975760) associated with type 2 diabetes. Subjects with the GG genotype of the rs2975762 variant of the CAPN10 gene were better responders to dietary intervention, showing increased HDL-C concentrations from the first month of treatment. HDL-C concentrations in participants with the wild type genotype increased by 17.0%, whereas the HDL-C concentration in subjects with the variant genotypes increased by only 3.22% (p = 0.03); the low-density lipoprotein cholesterol levels of GG carriers tended to decrease (-12.6%). These results indicate that Mexican dyslipidemic carriers of the rs2975762-GG genotype are better responders to this dietary intervention.