Epidemiological studies have reported a greater reduction in cardiovascular risk and metabolic disorders associated with diets rich in polyphenols. The antioxidant effects of polyphenols are attributed to the regulation of redox enzymes by reducing reactive oxygen species production from mitochondria, NADPH oxidases and uncoupled endothelial NO synthase in addition to also up-regulating multiple antioxidant enzymes. Although data supporting the effects of polyphenols in reducing oxidative stress are promising, several studies have suggested additional mechanisms in the health benefits of polyphenols. Polyphenols from red wine increase endothelial NO production leading to endothelium-dependent relaxation in conditions such as hypertension, stroke or the metabolic syndrome. Numerous molecules contained in fruits and vegetables can activate sirtuins to increase lifespan and silence metabolic and physiological disturbances associated with endothelial NO dysfunction. Although intracellular pathways involved in the endothelial effects of polyphenols are partially described, the molecular targets of these polyphenols are not completely elucidated. We review the novel aspects of polyphenols on several targets that could trigger the health benefits of polyphenols in conditions such as metabolic and cardiovascular disturbances.

Preclinical studies have suggested an anti-colorectal cancer effect of n-3 fatty acids, yet epidemiological studies have reported mixed results. The goal of the present meta-analysis was to examine the association between the dietary intake of n-3 fatty acids and colorectal cancer risk by conducting a meta-analysis of prospective cohort studies. We searched the PubMed database up to February 2012 to identify eligible studies. Either a fixed- or random-effects model was used to obtain a pooled relative risk (RR) comparing the highest intake of n-3 fatty acids with the lowest. We conducted subgroup analyses according to sex, geographic region, length of follow-up, cancer site and type of n-3 fatty acids. We included seven prospective studies in the meta-analysis, comprising 489 465 participants and 4656 incident cases. The pooled RR of colorectal cancer in relation to n-3 fatty acids was 0·98 (95 % CI 0·88, 1·09). The results from subgroup analysis indicated a significant reduced risk of colorectal cancer in relation to n-3 fatty acids among men (RR 0·87, 95 % CI 0·75, 1·00; n 4). No significant association was observed in other subgroups. There was no evidence of publication bias as suggested by Begg's test (P = 0·76) and Egger's test (P = 0·66). The present meta-analysis showed insufficient evidence of a protective effect of n-3 fatty acids on colorectal cancer risk. However, a reduced risk observed in men warrants further investigation.

Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin D2 and D3 (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (sd 10) years, 43 % male) and twenty-five Hadzabe hunter–gatherers (35 (sd 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. Their 25(OH)D concentrations were measured by liquid chromatography–MS/MS. The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58–167) and 109 (range 71–171) nmol/l, respectively. These concentrations were not related to age, sex or BMI. People with traditional lifestyles, living in the cradle of mankind, have a mean circulating 25(OH)D concentration of 115 nmol/l. Whether this concentration is optimal under the conditions of the current Western lifestyle is uncertain, and should as a possible target be investigated with concomitant appreciation of other important factors in Ca homeostasis that we have changed since the agricultural revolution.

Macrophages play an important role in immunogenic challenges by producing reactive oxygen species, NO and proinflammatory cytokines that can aggravate and propagate local inflammation. Multiple mechanisms regulate these inflammatory processes. NF-κB and activator protein 1 pathways are crucial in the expression of proinflammatory genes, such as TNF-α, IL-1 (α or β) and -6. Some polyphenols, which are present in beverages, vegetables and fruits, and PUFA, which are present in marine oils and fish food, possess anti-inflammatory effects in vivo and in vitro. Our aim in the present study was to assess whether polyphenols and PUFA have synergistic anti-inflammatory effects in murine macrophages in vitro. Inflammation in RAW 264.7 macrophages was induced by lipopolysaccharide at 100 ng/ml. The treatments with molecules were performed by co-incubation for 19 h. A NO production assay by Griess reaction, a phosphoprotein assay by Pathscan ELISA kit and gene expression analysis using the TaqMan® Low-density Array for ninety-one genes related to inflammation, oxidative stress and metabolism were performed to assess the synergistic anti-inflammatory effects of polyphenols, epigallocatechin gallate and resveratrol (Res; 2·5 μg/ml), and the PUFA, DHA and EPA (30 μm). Adding Res+EPA had an enhanced anti-inflammatory effect, in comparison with EPA and Res alone, leading to decreased NO levels; modulating the phospho-stress activated protein kinase/Jun N-terminal kinase (P-SAPK/JNK) level; down-regulating proinflammatory genes, such as IL, chemokines, transcription factors; and up-regulating several antioxidant genes. Therefore, this combination has a stronger anti-inflammatory effect than either of these molecules separately in RAW macrophages.

Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for the treatment of numerous forms of cancer, but it has pronounced adverse effects, namely nephrotoxicity, ototoxicity, neurotoxicity, hepatotoxicity, diarrhoea and nausea. CDDP-induced emesis and diarrhoea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants, possesses multiple biological activities, such as antioxidant and anti-inflammatory properties. In the present study, we investigated the protective effect of chrysin against CDDP-induced jejunal toxicity. The plausible mechanism of CDDP-induced jejunal toxicity includes oxidative stress, p53 and apoptosis via up-regulating the expression of caspase-6 and -3. Chrysin was administered to Wistar rats orally in maize oil. A single intraperitoneal injection of CDDP was given and the animals were killed after 24 h of CDDP injection. Chrysin ameliorated CDDP-induced lipid peroxidation, increase in xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6-phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin attenuated CDDP-induced goblet cell disintegration, enhanced expression of p53 and apoptotic tissue damage. Histological findings further substantiated the protective effects of chrysin against CDDP-induced damage in the jejunum. The results of the present study demonstrate that oxidative stress and apoptosis are closely associated with CDDP-induced toxicity and chrysin shows the protective efficacy against CDDP-induced jejunum toxicity possibly via attenuating the oxidative stress and apoptotic tissue damage.

The aim of the present study was to evaluate the anti-diabetic mechanism of Asparagus officinalis, a dietary agent used for the management of diabetes. Streptozotocin (90 mg/kg) was injected in 2-d-old Wistar rat pups to induce non-obese type 2 diabetes. After confirmation of diabetes on the 13th week, diabetic rats were treated with a methanolic extract of A. officinalis seeds (250 and 500 mg/kg per d) or glibenclamide for 28 d. After the treatment, fasting blood glucose, serum insulin and total antioxidant status were measured. The pancreas was examined by haematoxylin–eosin staining and immunostained β- and α-cells were observed using a fluorescence microscope. Treatment of the diabetic rats with the A. officinalis extract at doses of 250 and 500 mg/kg suppressed the elevated blood glucose in a dose- and time-dependent manner. The 500 mg/kg, but not 250 mg/kg, dose significantly improved serum insulin levels in the diabetic rats. The insulin:glucose ratio was significantly increased at both doses in the A. officinalis-treated rats. Both qualitative and quantitative improvements in β-cell function were found in the islets of the A. officinalis-treated rats. The extract showed potent antioxidant activity in an in vitro assay and also improved the total antioxidant status in vivo. In most cases, the efficacy of A. officinalis (500 mg/kg) was very similar to a standard anti-diabetic drug, glibenclamide. Thus, the present study suggests that A. officinalis extract exerts anti-diabetic effects by improving insulin secretion and β-cell function, as well as the antioxidant status.

The present study was conducted to show that dietary supplementation with a fungus, Aspergillus awamori, modifies muscle fatty acid profiles in broiler chickens. A total of thirty chicks, selected from a group of 100 chicks aged 15 d, were divided into a control group and two treatment groups (ten birds per treatment). The control group was fed a basal diet, and the treatment groups were fed basal diets supplemented with A. awamori at levels of 0·05 and 0·2 %. From the start of the study at 15 d, the birds were raised for an additional 12 d, and growth and the muscle fatty acid profile were evaluated. Although feed intake was decreased by the fungus, body-weight gain and breast muscle weight were increased, and thus, feed efficiency was improved. Abdominal fat and plasma cholesterol and TAG were decreased, while plasma HDL-cholesterol and breast muscle fat content were increased. Interestingly, muscle α-tocopherol content was increased and muscle thiobarbituric acid-reactive substances were decreased by A. awamori. Furthermore, there was an observed decrease in SFA and an increase in unsaturated fatty acids in the muscle fat due to the fungus feeding. The mRNA of fatty acid synthase, acetyl-CoA carboxylase and Δ-6 desaturase in the muscle were all increased, while the mRNA of 3-hydroxyl-3-methylglutaryl-CoA reductase and carnitine palmitoyl transferase 1A were decreased by the fungus. In conclusion, the present study clearly shows that the muscle lipid profile could be modified by the addition of A. awamori to the diet.

Soya is considered to be one of the eight most significant food allergens. Among the allergenic soya proteins determined to date, P34 has been identified as one of the immunodominant soya antigens. Sensitisation to a specific food antigen like P34 generally follows the transit of intact antigens across the intestinal barrier and usually occurs in infants, who are most susceptible to food allergies. In the present study, we used the intestinal epithelial cell line IPEC-J2, which was originally derived from the jejunum of a neonatal piglet, to recapitulate the infant intestinal epithelium and study the binding and uptake of P34 protein. P34 was partially resistant to degradation in an in vitro proteolysis assay. IPEC-J2 cells were able to endocytose intact P34, as shown by immunofluorescence and immunoelectronmicroscopy methods. P34 associated with lipid raft microdomains of IPEC-J2 cells, and disruption of caveolae/lipid raft microdomains using methyl-β-cyclodextrin abolished P34 endocytosis, indicating that the observed endocytosis was mediated by caveolae. Using IPEC-J2 cells grown on Transwell filters, we further demonstrated that P34 is transported through the epithelial monolayer by transcytosis. Piglets frequently show hypersensitivity to soya antigens, and in this study, we show that healthy adult pigs with dietary exposure to soya protein mount an antibody response to soyabean protein P34, suggesting that this protein has entered the body, probably through gastrointestinal uptake. In summary, our data suggest that soya P34 resists proteolysis in the gastrointestinal tract and is transported through the intestinal epithelial barrier, thereby allowing sensitisation of immune cells in the sub-epithelial compartment.

Increasing prevalence of inflammatory bowel disease may be due to imbalance in the intake of n-6 and n-3 PUFA in the diet. This study investigates the impact of varying ratios of dietary linoleic acid (LA, 18 : 2n-6) to α-linolenic acid (ALA, 18 : 3n-3) on the inflammatory response in dextran sulphate sodium (DSS)-induced colitis. Weanling male Sprague–Dawley rats were divided into five groups: a non-colitic group with a LA:ALA ratio of 215 (CON-215), and colitic groups with LA:ALA ratios of 215 (DSS-215), 50 (DSS-50), 10 (DSS-10) and 2 (DSS-2). Blends of groundnut, palmolein and linseed oils were used to provide varying LA:ALA ratios. All the rats were fed the respective experimental isoenergetic diets containing 10 % fat for 90 d and DSS was administered during the last 11 d. Colonic inflammation was evaluated by clinical, biochemical and histological parameters. The results showed attenuation of colitis in the DSS-2 group as evidenced by significant reductions in disease activity index, mucosal myeloperoxidase activity (P < 0·05), alkaline phosphatase activity (P < 0·01) and increase in colon length (P < 0·01) compared to the groups fed with higher ratios (DSS-215). This was accompanied by significant reductions in mucosal proinflammatory cytokines TNF-α (P < 0·01) and IL-1β (P < 0·01) and improvement in the histological score. Further, ALA supplementation increased long-chain (LC) n-3 PUFA and decreased LC n-6 PUFA in colon structural lipids. These data suggest that substitution of one-third of LA with ALA (LA:ALA ratio 2) mitigates experimental colitis by down-regulating proinflammatory mediators.

Resveratrol, a polyphenol abundantly found in grapes and red wine, exhibits beneficial health effects due to its anti-inflammatory properties. In the present study, we evaluated the effect of resveratrol on inflammatory responses induced by lipopolysaccharide (LPS) treatment of human intestinal Caco-2 and SW480 cell lines. In the LPS-treated intestinal cells, resveratrol dose-dependently inhibited the expression of inducible NO synthase (iNOS) mRNA as well as protein expression, resulting in a decreased production of NO. In addition, Toll-like receptor-4 expression was significantly diminished in LPS-stimulated cells after resveratrol pre-treatment. To investigate the mechanisms by which resveratrol reduces NO production and iNOS expression, we examined the activation of inhibitor of κB (IκB) in LPS-stimulated intestinal cells. Results demonstrated that resveratrol inhibited the phosphorylation, as well as the degradation, of the IκB complex. Overall, these results show that resveratrol is able to reduce LPS-induced inflammatory responses by intestinal cells, interfering with the activation of NF-κB-dependent molecular mechanisms.

Modulation of intestinal microbiota by non-digestible carbohydrates may reduce inflammation in inflammatory bowel disease (IBD). The aim of the present study was to assess the effects of inulin and fructo-oligosaccharides (FOS) on intestinal microbiota and colitis in HLA-B27 transgenic rats, a well-validated rodent model for IBD. In this study, 4-week-old rats were fed 8 g/kg body weight inulin or FOS for 12 weeks, or not. Faeces were collected at 4 and 16 weeks of age; and caecal samples were collected at necropsy. The effects of inulin and FOS on chronic intestinal inflammation were assessed using a gross gut score, histology score and levels of mucosal IL-1β. Intestinal microbiota were characterised by quantitative PCR and denaturing gradient gel electrophoresis. Colitis was significantly reduced in all FOS-fed rats compared to the control diet, whereas inulin decreased chronic intestinal inflammation in only half the number of animals. Quantitative analysis of caecal microbiota demonstrated that inulin increased the numbers of total bacteria and the Bacteroides-Prevotella-Porphyromonas group, FOS increased bifidobacteria, and both fructans decreased Clostridium cluster XI. In the faecal samples, both inulin and FOS decreased total bacteria, Bacteroides-Prevotella-Porphyromonas group, and Clostridium clusters XI and XIVa. FOS increased Bifidobacterium spp., and mediated a decrease of gene copies of Enterobacteriaceae and Clostridium difficile toxin B in faeces. SCFA concentrations in the faecal and caecal samples were unaffected by the diets. In conclusion, FOS increased the abundance of Bifidobacterium spp., whereas both fructans reduced Clostridium cluster XI and C. difficile toxin gene expression, correlating with a reduction of chronic intestinal inflammation.

Observational data show an inverse association between the consumption of wholegrain foods, and inflammation and related diseases. Although the underlying mechanisms are unclear, wholegrains, and in particular the aleurone layer, contain a wide range of components with putative antioxidant and anti-inflammatory effects. We evaluated the effects of a diet high in wheat aleurone on plasma antioxidants status, markers of inflammation and endothelial function. In this parallel, participant-blinded intervention, seventy-nine healthy, older, overweight participants (45–65 years, BMI>25 kg/m2) incorporated either aleurone-rich cereal products (27 g aleurone/d), or control products balanced for fibre and macronutrients, into their habitual diets for 4 weeks. Fasting blood samples were taken at baseline and on day 29. Results showed that, compared to control, consumption of aleurone-rich products provided substantial amounts of micronutrients and phytochemicals which may function as antioxidants. Additionally, incorporating these products into a habitual diet resulted in significantly lower plasma concentrations of the inflammatory marker, C-reactive protein (P = 0·035), which is an independent risk factor for CVD. However, no changes were observed in other markers of inflammation, antioxidant status or endothelial function. These results provide a possible mechanism underlying the beneficial effects of longer-term wholegrain intake. However, it is unclear whether this effect is owing to a specific component, or a combination of components in wheat aleurone.

Vitamin K is required for the carboxylation of Gla-proteins in the liver (coagulation factors) and extra-hepatic tissues, such as bone (osteocalcin, OC), and arterial wall (matrix Gla-protein, MGP). Although the coagulation factors are essentially fully carboxylated under normal conditions, 10–40 % of OC and MGP remains undercarboxylated. We were therefore interested to study the dose–response effects of extra intake of menaquinones on the carboxylation of the extra-hepatic Gla-proteins. A total of forty-two healthy Dutch men and women aged between 18 and 45 years were randomised into seven groups to receive: placebo capsules or menaquinone-7 (MK-7) capsules at a daily dose of 10, 20, 45, 90, 180 or 360 μg. Circulating uncarboxylated OC (ucOC), carboxylated OC (cOC) and desphospho-uncarboxylated MGP were measured by ELISA. The ucOC:cOC ratio was calculated from circulating ucOC and cOC values. Endogenous thrombin potential and peak height were determined by calibrated automated thrombography. To increase the statistical power, we collapsed the treatment groups into three dosage groups: placebo, low-dose supplementation (doses below RDA, Commission Directive 2008/100/EC), and high-dose supplementation (doses around RDA, Commission Directive 2008/100/EC). MK-7 supplementation at doses in the order of the RDA (Commission Directive 2008/100/EC) increased the carboxylation of circulating OC and MGP. No adverse effects on thrombin generation were observed. Extra MK-7 intake at nutritional doses around the RDA (Commission Directive 2008/100/EC) improved the carboxylation of the extra-hepatic vitamin K-dependent proteins. Whether this improvement contributes to public health, i.e. increasing the protection against age-related diseases needs further investigation in specifically designed intervention trials.

Overweight and obesity are growing problems both in Canada and around the world. Obesity is associated with a number of chronic diseases including type 2 diabetes and CVD, which puts a tremendous burden on the health care systems in place. The present study sought to investigate whether there were differences in the effectiveness of three low-fat, hypo- and isoenergetic diets differing in protein:carbohydrate ratio, low protein (LP, 1 g protein:4 g carbohydrate), normal protein (NP, 1 g protein:2 g carbohydrate) or high protein (HP, 1 g protein:1 g carbohydrate), on weight loss and markers of the metabolic syndrome (MetS) in overweight women. Subjects were randomly assigned to receive one of three intervention diets, all of which included a 60 min exercise programme three times/week for 12 weeks. Of the total subjects, fifty-four overweight and obese local women with MetS risk factors completed the study. All groups had similar improvements in body weight, insulin sensitivity, lipid profile, blood pressure and fitness. Subjects reported that the NP diet was easier to comply with and achieved better improvements in body fat, waist circumference and waist:hip ratio, and preservation of lean mass compared with the other two diets. In conclusion, energy restriction and exercise both facilitate weight loss in overweight and obese subjects and reduce symptoms of the MetS. A diet with a 1:2 protein:carbohydrate ratio promoted better improvements than either the LP or HP diets, and may be superior in reducing long-term chronic disease risk in this population.

Children in China are experiencing a rapid increase in the prevalence of obesity, which is associated with hypertension. To compare the effect of body fat on blood pressure (BP) with that of the normal physical growth, we compared BP levels in Chinese children with different body fat levels. In the present population-based study, 13 972 children in the highest-skinfold-thickness-quartile group were individually matched to 13 972 children in the lowest-skinfold-thickness-quartile group by height and weight. Similarly, 5103 children in the highest-waist-circumference-quartile group were matched to the same number of children in the lowest-waist-circumference-quartile group. The high- and low-fat groups had similar height and weight but the high-fat group had significantly higher skinfold and waist circumference measurements. The differences in systolic BP (SBP) between the high- and low-skinfold-thickness groups were small: 0·01 (95 % CI − 0·41, 0·44) mmHg in boys and 0·20 (95 % CI − 0·15, 0·54) mmHg in girls. The differences in diastolic BP (DBP) were also small (0·39 and 0·38 mmHg for boys and girls, respectively) but were statistically significant. The differences in both SBP and DBP between the high- and low-waist-circumference groups were small but not statistically significant. For a given body size as measured by height and weight, relative body fat had little impact on BP levels in these children. Fat mass and lean mass may have a similar quantitative impact on BP in healthy-weight children.

Dietary determinants of adolescent blood pressure (BP) are poorly understood. The goal of the present study was to assess the effects of an eating pattern similar to that from the Dietary Approaches to Stop Hypertension (DASH) study on adolescent BP. Data from 2185 girls followed-up over 10 years (until the girls were 18–20 years of age) in the National Heart Lung and Blood Institute's Growth and Health Study were used in this analysis. Diet was assessed during eight examination cycles using 3 d dietary records; girls were classified according to their consumption of foods associated with a DASH-style eating pattern. Analysis of covariance modelling, multiple logistic regression and longitudinal mixed models were used to control for potential confounding by age, race, socio-economic status, height, physical activity, television viewing time and other dietary factors. Girls who consumed ≥ 2 daily servings of dairy and ≥ 3 servings of fruits and vegetables (FV) had a 36 % lower risk (95 % CI: 0·43, 0·97) of elevated BP (EBP) in late adolescence. In longitudinal modelling, two dietary factors were associated with a lower systolic BP throughout adolescence: higher ( ≥ 2 daily servings) dairy intakes (P < 0·0001) and a DASH-style pattern (P = 0·0002). Only the DASH-style pattern led to consistently lower diastolic BP levels (P = 0·0484). Adjustment for BMI did not appreciably modify the results. In this study, adolescent girls whose diets were rich in dairy products and FV during the early- and mid-adolescent years were less likely to have EBP levels in later adolescence.

Tea consumption may be associated with reduced risk of morbidity and mortality; however, this association is not conclusive and has rarely been investigated among very old adults. The present study examines how self-reported frequency of tea consumption in daily life is associated with health and mortality among very old adults in China. The data are from a national longitudinal data set that included 32 606 individuals (13 429 men and 19 177 women) aged 65 years and older: 11 807 respondents aged 65 to 84 years and 20 799 respondents aged 85 years and older. A total of four measurements between 1998 and 2005 resulted in 51 668 observations. Hazard regressions showed that men who drink tea almost every day have a 10–20 % lower risk of death compared to their counterparts who seldom drink tea, after adjusting for numerous confounders including baseline health. This relationship was stronger in younger male elders aged 65 to 84 years than in the oldest-old men aged 85 years and older. However, frequency of tea consumption was not significantly associated with mortality in women. Our analyses further show that high frequency of tea consumption is significantly associated with reduced OR of disability in activities of daily living, cognitive impairment, self-rated poor health, cumulative health deficits and CVD in both young elders and the oldest-old, and in both men and women. These results suggest that the health benefit of drinking tea is universal. We conclude that frequent tea consumption probably helps one achieve healthy longevity and that men benefit more from such lifestyles.

Previous studies have suggested that the daidzein metabolite equol rather than daidzein itself contributes to the beneficial effect of soya foods in the prevention of CVD. The aim of the present study is to examine the proportion of equol excretion in Chinese adults and compare plasma lipids and carotid artery intima–media thickness (IMT) between equol excretors and non-excretors, and to evaluate the effect of soya isoflavone intakes on serum lipids and IMT in either equol excretors or non-excretors. Subjects (n 572; women n 362, men n 210) were recruited for the present study. An overnight urine sample was provided by each subject on their usual diet to quantify urinary concentrations of daidzein and equol. Far-wall IMT was determined by B-mode ultrasound in the right carotid at two sites, carotid bulb (CB-IMT) and common carotid artery (CCA-IMT), and fasting serum lipids were measured. Habitual dietary intakes were estimated with a FFQ, and soya isoflavone intake derived from the FFQ was assessed. Of the 572 subjects, the proportion of equol excretors on their usual diet was 25·0 % (n 143). Compared with non-excretors, equol excretors showed significantly lower serum TAG ( − 38·2 (95 % CI − 70·4, − 5·9) %, P = 0·012) and CCA-IMT ( − 4·9 (95 % CI − 9·7, − 0·3) %, P = 0·033). Equol excretors with higher daily isoflavone intakes ( − 5·4 mg/d) had significantly lower IMT ( − 16·2 %, P = 0·035) and tended to have higher HDL-cholesterol (P = 0·055) than did those with lower daily isoflavone intakes (1·5 mg/d), while no association was observed between soya isoflavone intakes and serum lipids or IMT in non-excretors. In conclusion, the benefits of soya isoflavones in preventing CVD may be apparent among equol excretors only.

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