In order to establish firm evidence for the health effects of dietary polyphenol consumption, it is essential to have quantitative information regarding their dietary intake. The usefulness of the current methods, which rely mainly on the assessment of polyphenol intake using food records and food composition tables, is limited as they fail to assess total intake accurately. This review highlights the problems associated with such methods with regard to polyphenol-intake predictions. We suggest that the development of biological biomarkers, measured in both blood and urine, are essential for making accurate estimates of polyphenol intake. However, the relationship between dietary intakes and nutritional biomarkers are often highly complex. This review identifies the criteria that must be considered in the development of such biomarkers. In addition, we provide an assessment of the limited number of potential biomarkers of polyphenol intake currently available. In the last decade, there has been intense interest in the potential health benefits of dietary-derived plant polyphenols. An everincreasing number of studies have described their antioxidant properties and linked this to their proposed role in the prevention of human disease. Plant polyphenols are abundant in the human diet, particularly in fruit, vegetables and pulses which have been consistently associated with a decreased risk of cancer 1 -3 , CVD 4 -6 and a range of other chronic disorders. The likely active components of fruits, vegetables and pulses are a group of phytochemicals, known as polyphenols. However, it has proved extremely difficult to quantitatively establish the benefit afforded by polyphenols for a number of reasons: (1) there is a great diversity of polyphenol content between foods; (2) there is limited data regarding the polyphenol content of specific foods within the commonly-used food composition databases; (3) there are challenges in characterising and quantifying habitual food intake; and (4) there is a limited understanding regarding the extent of absorption and metabolic fate of individual polyphenols from particular foods.Biological markers of nutrient exposure, as an alternative to the more traditional dietary assessment tools, have been used for many years. In this approach one or more biochemical moieties are measured in an accessible fluid or tissue to provide a semi-quantitative index of the exposure to individual food constituents. For polyphenols, this may appear to be an attractive approach. However, the relationship between dietary intake and resulting concentrations of biomarkers in body fluids is highly complex. Before a particular dietary component, or its metabolite, can be used as a sensitive and accurate biomarker of exposure to a specific polyphenol, a number of factors must be realised. Firstly, a full understanding of the metabolism of polyphenols in human subjects is required in order to select credible biomarkers. Secondly, it is important to understand the time -response relationship between polyphenol int...

Although in developing countries an apolipoprotein E4 (apoE4) genotype may offer an evolutionary advantage, as it has been shown to offer protection against certain infectious disease, in Westernised societies it is associated with increased morbidity and mortality, and represents a significant risk factor for cardiovascular disease, late-onset Alzheimer's disease and other chronic disorders. ApoE is an important modulator of many stages of lipoprotein metabolism and traditionally the increased risk was attributed to higher lipid levels in E4 carriers. However, more recent evidence demonstrates the multifunctional nature of the apoE protein and the fact that the impact of genotype on disease risk may be in large part due to an impact on oxidative status or the immunomodulatory/anti-inflammatory properties of apoE. An increasing number of studies in cell lines, targeted replacement rodents and human volunteers indicate higher oxidative stress and a more pro-inflammatory state associated with the epsilon4 allele. The impact of genotype on the antioxidant and immunomodulatory/anti-inflammatory properties of apoE is the focus of the current review. Furthermore, current information on the impact of environment (diet, exercise, smoking status, alcohol) on apoE genotype-phenotype associations are discussed with a view to identifying particular lifestyle strategies that could be adapted to counteract the 'at-risk' E4 genotype.

Abstract-The study assessed the efficacy of fish oil supplementation in counteracting the classic dyslipidemia of the atherogenic lipoprotein phenotype (ALP). In addition, the impact of the common apolipoprotein E (apoE) polymorphism on the fasting and postprandial lipid profile and on responsiveness to the dietary intervention was established. Fifty-five ALP males (aged 34 to 69 years, body mass index 22 to 35 kg/m 2 , triglyceride [TG] levels 1.5 to 4.0 mmol/L, high density lipoprotein cholesterol [HDL-C] Ͻ1.1 mmol/l, and percent low density lipoprotein [LDL]-3 Ͼ40% total LDL) completed a randomized placebo-controlled crossover trial of fish oil (3.0 g eicosapentaenoic acid/docosahexaenoic acid per day) and placebo (olive oil) capsules with the 6-week treatment arms separated by a 12-week washout period. In addition to fasting blood samples, at the end of each intervention arm, a postprandial assessment of lipid metabolism was carried out. Fish oil supplementation resulted in a reduction in fasting TG level of 35% (PϽ0.001), in postprandial TG response of 26% (TG area under the curve, PϽ0.001), and in percent LDL-3 of 26% (PϽ0.05). However, no change in HDL-C levels was evident (Pϭ0.752). ANCOVA showed that baseline HDL-C levels were significantly lower in apoE4 carriers (Pϭ0.035). The apoE genotype also had a striking impact on lipid responses to fish oil intervention. Individuals with an apoE2 allele displayed a marked reduction in postprandial incremental TG response (TG incremental area under the curve, Pϭ0.023) and a trend toward an increase in lipoprotein lipase activity relative to non-E2 carriers. In apoE4 individuals, a significant increase in total cholesterol and a trend toward a reduction in HDL-C relative to the common homozygous E3/E3 profile was evident. Our data demonstrate the efficacy of fish oil fatty acids in counteracting the proatherogenic lipid profile of the ALP but also that the apoE genotype influences responsiveness to this dietary treatment.

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