Effect of changing the amount and type of fat and carbohydrate on insulin sensitivity and cardiovascular risk: the RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) trial

Background: Insulin sensitivity (Si) is improved by weight loss and exercise, but the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI) are uncertain. Objective: We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome. Design: We conducted a 5-center, parallel design, randomized controlled trial [RISCK (Reading, Imperial, Surrey, Cambridge, and Kings)]. The primary and secondary outcomes were changes in Si (measured by using an intravenous glucose tolerance test) and cardiovascular risk factors. Measurements were made after 4 wk of a high-SFA and HGI (HS/HGI) diet and after a 24-wk intervention with HS/HGI (reference), high-MUFA and HGI (HM/HGI), HM and LGI (HM/LGI), low-fat and HGI (LF/HGI), and LF and LGI (LF/LGI) diets. Results: We analyzed data for 548 of 720 participants who were randomly assigned to treatment. The median Si was 2.7 × 10−4 mL · μU−1 · min−1 (interquartile range: 2.0, 4.2 × 10−4 mL · μU−1 · min−1), and unadjusted mean percentage changes (95% CIs) after 24 wk treatment (P = 0.13) were as follows: for the HS/HGI group, −4% (−12.7%, 5.3%); for the HM/HGI group, 2.1% (−5.8%, 10.7%); for the HM/LGI group, −3.5% (−10.6%, 4.3%); for the LF/HGI group, −8.6% (−15.4%, −1.1%); and for the LF/LGI group, 9.9% (2.4%, 18.0%). Total cholesterol (TC), LDL cholesterol, and apolipoprotein B concentrations decreased with SFA reduction. Decreases in TC and LDL-cholesterol concentrations were greater with LGI. Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations. Conclusions: This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si. Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects, with tentative evidence of improvements in Si in the LF-treatment group. This trial was registered at clinicaltrials.gov as ISRCTN29111298.

Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults.

The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk. The objective was to investigate the relationship among LEPR polymorphisms, insulin resistance, and MetS risk and whether plasma fatty acids, a biomarker of dietary fatty acids, modulate this. LEPR polymorphisms (rs10493380, rs1137100, rs1137101, rs12067936, rs1805096, rs2025805, rs3790419, rs3790433, rs6673324, and rs8179183), biochemical measurements, and plasma fatty acid profiles were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). LEPR rs3790433 GG homozygotes had increased MetS risk compared with the minor A allele carriers [odds ratio (OR) = 1.65; 95% CI: 1.05–2.57; P = 0.028], which may be accounted for by their increased risk of elevated insulin concentrations (OR 2.40; 95% CI: 1.28–4.50; P = 0.006) and insulin resistance (OR = 2.15; 95% CI: 1.18–3.90; P = 0.012). Low (less than median) plasma (n-3) and high (n-6) PUFA status exacerbated the genetic risk conferred by GG homozygosity to hyperinsulinemia (OR 2.92–2.94) and insulin resistance (OR 3.40–3.47). Interestingly, these associations were abolished against a high (n-3) or low (n-6) PUFA background. Importantly, we replicated some of these findings in an independent cohort. Homozygosity for the LEPR rs3790433 G allele was associated with insulin resistance, which may predispose to increased MetS risk. Novel gene-nutrient interactions between LEPR rs3790433 and PUFA suggest that these genetic influences were more evident in individuals with low plasma (n-3) or high plasma (n-6) PUFA.

Fruit polyphenols and CVD risk: a review of human intervention studies.

Epidemiological evidence suggests that polyphenols may, in part, explain the cardioprotective properties of fruits. This review aims to summarise the evidence for the effects of fruit polyphenols on four risk factors of CVD: platelet function, blood pressure, vascular function and blood lipids. This review includes human dietary intervention studies investigating fruits and their polyphenols. There was some evidence to suggest that fruits containing relatively high concentrations of flavonols, anthocyanins and procyanindins, such as pomegranate, purple grapes and berries, were effective at reducing CVD risk factors, particularly with respect to anti-hypertensive effects, inhibition of platelet aggregation and increasing endothelial-dependent vasodilation than other fruits investigated. Flavanone-rich fruits, such as oranges and grapefruits, were reported to have hypocholesterolaemic effects, with little impact on other risk factors being examined. However, the evidence was limited, inconsistent and often inconclusive. This is in part due to the heterogeneity in the design of studies, the lack of controls, the relatively short intervention periods and low power in several studies. Details of the polyphenol content of the fruits investigated were also omitted in some studies, negating comparison of data. It is recommended that large, well-powered, long-term human dietary intervention studies investigating a wider range of fruits are required to confirm these observations. Investigations into the potential synergistic effects of polyphenols on a combination of CVD risk markers, dose–response relationships and standardisation in methodology would facilitate the comparison of studies and also provide valuable information on the types of fruits which could confer protection against CVD.

Chronic disease risk associated with different dietary saturated fatty acids

This chapter compares the risks of chronic disease, and cardiovascular disease in particular, associated with consumption of different saturated fatty acids. Emphasis is placed on the effects of stearic acid as this has potential to replace trans fatty acids in certain manufactured food products. The chapter first reviews the effects of individual saturated fatty acids on blood lipids, including cholesterol, as these are commonly used as markers of disease risk. It then looks directly at evidence in relation to health outcomes. Finally, recent evidence specifically on the effect of stearic acid relative to other fatty acids, including trans fatty acids, is summarised.

Single nucleotide polymorphisms at the ADIPOQ gene locus interact with age and dietary intake of fat to determine serum adiponectin in subjects at risk of the metabolic syndrome

Background: Adiponectin gene expression is modulated by peroxisome proliferator–activated receptor γ, which is a transcription factor activated by unsaturated fatty acids. Objective: We investigated the effect of the interaction between variants at the ADIPOQ gene locus, age, sex, body mass index (BMI), ethnicity, and the replacement of dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates on serum adiponectin concentrations. Design: The RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) study is a parallel-design, randomized controlled trial. Serum adiponectin concentrations were measured after a 4-wk high-SFA (HS) diet and a 24-wk intervention with reference (HS), high-MUFA (HM), and low-fat (LF) diets. Single nucleotide polymorphisms at the ADIPOQ locus −11391 G/A (rs17300539), −10066 G/A (rs182052), −7734 A/C (rs16861209), and +276 G/T (rs1501299) were genotyped in 448 participants. Results: In white Europeans, +276 T was associated with higher serum adiponectin concentrations (n = 340; P = 0.006) and −10066 A was associated with lower serum adiponectin concentrations (n = 360; P = 0.03), after adjustment for age, BMI, and sex. After the HM diet, −10066 G/G subjects showed a 3.8% increase (95% CI: −0.1%, 7.7%) and G/A+A/A subjects a 2.6% decrease (95% CI: −5.6%, 0.4%) in serum adiponectin (P = 0.006 for difference after adjustment for the change in BMI, age, and sex). In −10066 G/G homozygotes, serum adiponectin increased with age after the HM diet and decreased after the LF diet. Conclusion: In white −10066 G/G homozygotes, an HM diet may help to increase adiponectin concentrations with advancing age. This trial was registered at clinicaltrials.gov as ISRCTN29111298.

Inequalities in diet and nutrition

The inequality of nutrition and obesity re-focuses concern on who in society is consuming the worst diet. Identification of individuals with the worst of dietary habits permits for targeting interventions to assuage obesity among the population segment where it is most prevalent. We argue that the use of fiscal interventions does not appropriately take into account the economic, social and health circumstances of the intended beneficiaries of the policy. This paper reviews the influence of socio-demographic factors on nutrition and health status and considers the impacts of nutrition policy across the population drawing on methodologies from both public health and welfare economics. The effects of a fat tax on diet are found to be small and while other studies show that fat taxes saves lives, we show that average levels of disease risk do not change much: those consuming particularly bad diets continue to do so. Our results also suggest that the regressivity of the policy increases as the tax becomes focused on products with high saturated fat contents. A fiscally neutral policy that combines the fat tax with a subsidy on fruit and vegetables is actually more regressive because consumption of these foods tends to be concentrated in socially undeserving households. We argue that when inequality is of concern, population-based measures must reflect this and approaches that target vulnerable populations which have a shared propensity to adopt unhealthy behaviours are appropriate.

NANA: Novel assessment of nutrition and ageing

Purpose NANA is a 3-year project using sensitively-designed technology to improve data collection and integrate information on nutrition, physical and cognitive function and mental health to identify individuals at risk of under-nourishment and improve targeting of interventions. This research will also improve our understanding of the interactions between these factors, in order to better medical treatment and social provision. The toolkit has potential for commercial development for additional segments of the population. Method This is a multi-disciplinary program involving psychology, nutrition, engineering and software engineering. The first phase is a user needs analysis and will involve consulting with a broad cross-section of older people, caregivers, and health professionals, to establish what technical approaches would be useful and acceptable. The second phase focuses on the development of an integrated measurement toolkit. There are three inter-related subsections: (i) an iterative program to develop the assessment technology, (ii) techniques for dietary assessment in older people, and (iii) a parallel investigation of measures of cognition and mental health in older people. It includes a full validation of the assessment toolkit and will comprise a comparison of the new, integrated assessment with traditional 'pen and paper' methods with volunteers having the equipment installed in their homes.

Impact of the quantity and flavonoid content of fruits and vegetables on markers of intake in adults with an increased risk of cardiovascular disease: the FLAVURS Trial

Purpose Limited robust randomised controlled trials investigating fruit and vegetable (F&V) intake in people at risk of cardiovascular disease (CVD) exist. We aimed to design and validate a dietary strategy of increasing flavonoid-rich versus flavonoid-poor F&V consumption on nutrient biomarker profile. Methods A parallel, randomised, controlled, dose–response dietary intervention study. Participants with a CVD relative risk of 1.5 assessed by risk scores were randomly assigned to one of the 3 groups: habitual (control, CT), high-flavonoid (HF) or low-flavonoid (LF) diets. While the CT group (n = 57) consumed their habitual diet throughout, the HF (n = 58) and LF (n = 59) groups sequentially increased their daily F&V intake by an additional 2, 4 and 6 portions for 6-week periods during the 18-week study. Results Compliance to target numbers and types of F&V was broadly met and verified by dietary records, and plasma and urinary biomarkers. Mean (±SEM) number of F&V portions/day consumed by the HF and LF groups at baseline (3.8 ± 0.3 and 3.4 ± 0.3), 6 weeks (6.3 ± 0.4 and 5.8 ± 0.3), 12 weeks (7.0 ± 0.3 and 6.8 ± 0.3) and 18 weeks (7.6 ± 0.4 and 8.1 ± 0.4), respectively, was similar at baseline yet higher than the CT group (3.9 ± 0.3, 4.3 ± 0.3, 4.6 ± 0.4, 4.5 ± 0.3) (P = 0.015). There was a dose-dependent increase in dietary and urinary flavonoids in the HF group, with no change in other groups (P = 0.0001). Significantly higher dietary intakes of folate (P = 0.035), non-starch polysaccharides (P = 0.001), vitamin C (P = 0.0001) and carotenoids (P = 0.0001) were observed in both intervention groups compared with CT, which were broadly supported by nutrient biomarker analysis. Conclusions The success of improving nutrient profile by active encouragement of F&V intake in an intervention study implies the need for a more hands-on public health approach.

The impact of substituting SFA in dairy products with MUFA or PUFA on CVD risk: evidence from human intervention studies

With the substantial economic and social burden of CVD, the need to modify diet and lifestyle factors to reduce risk has become increasingly important. Milk and dairy products, being one of the main contributors to SFA intake in the UK, are a potential target for dietary SFA reduction. Supplementation of the dairy cow's diet with a source of MUFA or PUFA may have beneficial effects on consumers' CVD risk by partially replacing milk SFA, thus reducing entry of SFA into the food chain. A total of nine chronic human intervention studies have used dairy products, modified through bovine feeding, to establish their effect on CVD risk markers. Of these studies, the majority utilised modified butter as their primary test product and used changes in blood cholesterol concentrations as their main risk marker. Of the eight studies that measured blood cholesterol, four reported a significant reduction in total and LDL-cholesterol (LDL-C) following chronic consumption of modified milk and dairy products. Data from one study suggested that a significant reduction in LDL-C could be achieved in both the healthy and hypercholesterolaemic population. Thus, evidence from these studies suggests that consumption of milk and dairy products with modified fatty acid composition, compared with milk and dairy products of typical milk fat composition, may be beneficial to CVD risk in healthy and hypercholesterolaemic individuals. However, current evidence is insufficient and further work is needed to investigate the complex role of milk and cheese in CVD risk and explore the use of novel markers of CVD risk.

Breast, colorectal, and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition–Norfolk in relation to phytoestrogen intake derived from an improved database

Background: The characterization of phytoestrogen intake and cancer risk has been hindered by the absence of accurate dietary phytoestrogen values. Objective: We examined the risk of breast, colorectal, and prostate cancers relative to phytoestrogen intake on the basis of a comprehensive database. Design: Demographic and anthropometric characteristics, a medical history, and 7-d records of diet were collected prospectively from participants (aged 40–79 y) in the European Prospective Investigation into Cancer and Nutrition–Norfolk (EPIC-Norfolk). Five hundred nine food items were analyzed by liquid chromatography–mass spectrometry/mass spectrometry, and 13C3-labeled internal standards were analyzed for isoflavones (genistein, daidzein, glycitein, biochanin A, and formononetin), lignans (secoisolariciresinol and matairesinol), and enterolignans from gut microbial metabolism in animal food sources (equol and enterolactone). From the direct analysis, values for 10,708 foods were calculated. Odds ratios (ORs) for breast (244 cases, 941 controls), colorectal (221 cases, 886 controls), and prostate (204 cases, 812 controls) cancers were calculated relative to phytoestrogen intake. Results: Phytoestrogen intake was not associated with breast cancer among women or colorectal cancer among men. Among women, colorectal cancer risk was inversely associated with enterolactone (OR: 0.33; 95% CI: 0.14, 0.74) and total enterolignans (OR: 0.32; 95% CI: 0.13, 0.79), with a positive trend detected for secoisolariciresinol (OR: 1.60; 95% CI: 0.96, 2.69). A positive trend between enterolignan intake and prostate cancer risk (OR: 1.27; 95% CI: 0.97, 1.66) was attenuated after adjustment for dairy intake (OR: 1.19; 95% CI: 0.77, 1.82). Conclusion: Dietary phytoestrogens may contribute to the risk of colorectal cancer among women and prostate cancer among men.

Olive leaf phenolics and cardiovascular risk reduction: Physiological effects and mechanisms of action

Olive oil, an important component of the Mediterranean diet, is rich in polyphenols and is known to possess positive health effects relative to other dietary fats. In addition, the leaves of the olive plant (Olea europaea) contain similar phenolics (oleuropein, luteolin-7-glucoside, apigenin-7-glucoside, verbascoside and hydroxytyrosol) to those of olives and olive oil, although at higher concentrations. For example, the most abundant is the secoiridoid, oleuropein, representing 1–14% of olive leaf weight vs. 0.005–0.12% in olive oil. Although currently considered a waste product of the olive oil industry, recent research has suggested beneficial effects of phenolic-rich olive leaf extracts (OLE) in modifying cardiovascular risk biomarkers such as blood pressure, hyperglycaemia, oxidative stress and inflammation, as well as improving vascular function and lipid profiles. Despite this, data regarding the biological actions of OLE has mostly derived from animal, in vitro and ex vivo studies, with limited evidence deriving from human trials. Although the absorption and metabolism of olive oil phenolics has been investigated, less is known about the bioavailability of phenolics from OLE, limiting the interpretation of existing in vitro and ex vivo data. The current review will begin by describing the phenolic composition of olive leaves in comparison with that of the better studied olive oil. It will then review the effects of OLE on cardiovascular risk factors, covering both animal and human studies and will end by considering potential mechanisms of action

Flavonoid-rich fruits and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease – FLAVURS: a randomized controlled trial

BACKGROUND: Observed associations between increased fruit and vegetable (F&V) consumption, particularly those F&Vs that are rich in flavonoids, and vascular health improvements require confirmation in adequately powered randomized controlled trials. OBJECTIVE: This study was designed to measure the dose-response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual F&V intakes and vascular function and other cardiovascular disease (CVD) risk indicators. DESIGN: A single-blind, dose-dependent, parallel randomized controlled dietary intervention study was conducted. Male and female low-F&V consumers who had a ≥1.5-fold increased risk of CVD (n = 174) were randomly assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every 6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO), vascular function, and inflammation were determined at baseline and at 6, 12, and 18 wk. RESULTS: In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with +2 portions/d (at 6 wk) and reduced C-reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion molecule (P = 0.0468) with +4 portions/d (at 12 wk). HF F&Vs increased plasma NO (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO (P = 0.0299) in the control group. CONCLUSION: These data support recommendations to increase F&V intake to ≥6 portions daily, with additional benefit from F&Vs that are rich in flavonoids, particularly in men with an increased risk of CVD. This trial was registered at www.controlled-trials.com as ISRCTN47748735.