Daily consumption of an aqueous green tea extract supplement does not impair liver function or alter cardiovascular disease risk biomarkers in healthy men

Regular consumption of green tea polyphenols (GTP) is thought to reduce the risk of cardiovascular disease (CVD) but has also been associated with liver toxicity. The present trial aimed to assess the safety and potential CVD health beneficial effects of daily GTP consumption. We conducted a placebo-controlled parallel study to evaluate the chronic effects of GTP on liver function and CVD risk biomarkers in healthy men. Volunteers (treatment: n = 17, BMI 26.7 +/- 3.3 kg/m(2), age 41 +/- 9 y; placebo, n = 16, BMI 25.4 +/- 3.3 kg/m(2), age 40 +/- 10 y) consumed for 3 wk 6 capsules per day (2 before each principal meal) containing green tea extracts (equivalent to 714 mg/d GTP) or placebo. At the beginning and end of the intervention period, we collected blood samples from fasting subjects and measured vascular tone using Laser Doppler lontophoresis. Biomarkers of liver function and CVD risk (including blood pressure, plasma lipids, and asymmetric dimethylarginine) were unaffected by GTP consumption. After treatment, the ratio of total:HDL cholesterol was significantly reduced in participants taking GTP capsules compared with baseline. Endothelial-dependent and -independent vascular reactivity did not significantly differ between treatments. In conclusion, the present data suggests that the daily consumption of high doses of GTP by healthy men for 3 wk is safe but without effects on CVD risk biomarkers other than the total:HDL cholesterol ratio. J. Nutr. 139: 58-62, 2009.

Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study

BACKGROUND AND OBJECTIVE: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242). DESIGN AND METHODS: The study populations included the Northern Finland Birth Cohort 1966 (n=4996), Netherlands Study of Depression and Anxiety (n=1883) and LifeLines Cohort Study (n=13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test. RESULTS: In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (Pinteraction=0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations). CONCLUSION: In conclusion, our findings in 20 242 individuals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake.

Sulfation of genistein alters its antioxidant properties and its effect on platelet aggregation and monocyte and endothelial function

Soy isoflavones have been extensively studied because of their possible benefits to human health. Genistein, the major isoflavone aglycone, has received most attention; however, it undergoes extensive metabolism (e.g. conjugation with sulfuric acid) in the gut and liver, which may affect its biological proper-ties. This study investigated the antioxidant activity and free radical-scavenging properties of genistein, genistein-4'-sulfate and genistein-4'-7-disulfate as well as their effect on platelet aggregation and monocyte and endothelial function. Electron spin resonance spectroscopy (ESR) and spin trapping data and other standard antioxidant assays indicated that genistein is a relatively weak antioxidant compared to quercetin and that its sulfated metabolites are even less effective. Furthermore, genistein-4'-sulfate was less potent than genistem, and genistein-4'-7-disulfate even less potent, at inhibiting collagen-induced platelet aggregation, nitric oxide (NO) production by macrophages, and secretion by primary human endothelial cells of monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). The current data suggest that sulfation of genistein, with the associated loss of hydroxyl groups, decreases its antioxidant activity and its effect on platelet aggregation, inflammation, cell adhesion and chemotaxis. (C) 2004 Elsevier B.V All rights reserved.

The effect of impaired thyroid function during development on the mechanical properties of avian bone

Thyroid hormones show fluctuating levels during the post-hatching development of birds. In this paper we report the results of the first mechanical tests to quantify the effect of hypothyroidism, during post-natal development, on the skeletal properties of a precocial bird, the barnacle goose, as determined by microhardness testing. The effect of hypothyroidism is tissue-specific; bone from the femora of birds is not significantly affected by induced hypothyroidism, however, there is a strong positive relationship between the levels of circulating thyroid hormones and the mechanical properties of bone from humeri. In the barnacle goose the development of the wing skeleton and musculature depends on an increase in circulating thyroid hormones and our analysis shows that, in its absence, the mechanical competence of the bone mineral itself is reduced in addition to the decreased bone length and muscle development previously reported in the literature. (C) 2004 Wiley-Liss, Inc.

Sulfation of genistein alters its antioxidant properties and its effect on platelet aggregation and monocyte and endothelial function

Soy isoflavones have been extensively studied because of their possible benefits to human health. Genistein, the major isoflavone aglycone, has received most attention; however, it undergoes extensive metabolism (e.g. conjugation with sulfuric acid) in the gut and liver, which may affect its biological proper-ties. This study investigated the antioxidant activity and free radical-scavenging properties of genistein, genistein-4'-sulfate and genistein-4'-7-disulfate as well as their effect on platelet aggregation and monocyte and endothelial function. Electron spin resonance spectroscopy (ESR) and spin trapping data and other standard antioxidant assays indicated that genistein is a relatively weak antioxidant compared to quercetin and that its sulfated metabolites are even less effective. Furthermore, genistein-4'-sulfate was less potent than genistem, and genistein-4'-7-disulfate even less potent, at inhibiting collagen-induced platelet aggregation, nitric oxide (NO) production by macrophages, and secretion by primary human endothelial cells of monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). The current data suggest that sulfation of genistein, with the associated loss of hydroxyl groups, decreases its antioxidant activity and its effect on platelet aggregation, inflammation, cell adhesion and chemotaxis. (C) 2004 Elsevier B.V All rights reserved.

Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies

Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.

The physics of baking: rheological and polymer molecular structure-function relationships in breadmaking

Molecular size and structure of the gluten polymers that make up the major structural components of wheat are related to their rheological properties via modem polymer rheology concepts. Interactions between polymer chain entanglements and branching are seen to be the key mechanisms determining the rheology of HMW polymers. Recent work confirms the observation that dynamic shear plateau modulus is essentially independent of variations in MW amongst wheat varieties of varying baking performance and is not related to variations in baking performance, and that it is not the size of the soluble glutenin polymers, but the structural and rheological properties of the insoluble polymer fraction that are mainly responsible for variations in baking performance. The rheological properties of gas cell walls in bread doughs are considered to be important in relation to their stability and gas retention during proof and baking, in particular their extensional strain hardening properties. Large deformation rheological properties of gas cell walls were measured using biaxial extension for a number of doughs of varying breadmaking quality at constant strain rate and elevated temperatures in the range 25-60 degrees C. Strain hardening and failure strain of cell walls were both seen to decrease with temperature, with cell walls in good breadmaking doughs remaining stable and retaining their strain hardening properties to higher temperatures (60 degrees C), whilst the cell walls of poor breadmaking doughs became unstable at lower temperatures (45-50 degrees C) and had lower strain hardening. Strain hardening measured at 50 degrees C gave good correlations with baking volume, with the best correlations achieved between those rheological measurements and baking tests which used similar mixing conditions. As predicted by the Considere failure criterion, a strain hardening value of I defines a region below which gas cell walls become unstable, and discriminates well between the baking quality of a range of commercial flour blends of varying quality. This indicates that the stability of gas cell walls during baking is strongly related to their strain hardening properties, and that extensional rheological measurements can be used as predictors of baking quality. (C) 2004 Elsevier B.V. All rights reserved.

The physics of baking: rheological and polymer molecular structure-function relationships in breadmaking

Molecular size and structure of the gluten polymers that make up the major structural components of wheat are related to their rheological properties via modern polymer rheology concepts. Interactions between polymer chain entanglements and branching are seen to be the key mechanisms determining the rheology of HMW polymers. Recent work confirms the observation that dynamic shear plateau modulus is essentially independent of variations in MW amongst wheat varieties of varying baking performance and is not related to variations in baking performance, and that it is not the size of the soluble glutenin polymers, but the structural and rheological properties of the insoluble polymer fraction that are mainly responsible for variations in baking performance. The rheological properties of gas cell walls in bread doughs are considered to be important in relation to their stability and gas retention during proof and baking, in particular their extensional strain hardening properties. Large deformation rheological properties of gas cell walls were measured using biaxial extension for a number of doughs of varying breadmaking quality at constant strain rate and elevated temperatures in the range 25oC to 60oC. Strain hardening and failure strain of cell walls were both seen to decrease with temperature, with cell walls in good breadmaking doughs remaining stable and retaining their strain hardening properties to higher temperatures (60oC), whilst the cell walls of poor breadmaking doughs became unstable at lower temperatures (45oC to 50oC) and had lower strain hardening. Strain hardening measured at 50oC gave good correlations with baking volume, with the best correlations achieved between those rheological measurements and baking tests which used similar mixing conditions. As predicted by the Considere failure criterion, a strain hardening value of 1 defines a region below which gas cell walls become unstable, and discriminates well between the baking quality of a range of commercial flour blends of varying quality. This indicates that the stability of gas cell walls during baking is strongly related to their strain hardening properties, and that extensional rheological measurements can be used as predictors of baking quality.

PASSCLAIM - gut health and immunity

Background The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. Aim To define normal function of the gut and immune system and describe available methods of measuring it. Results We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be "improved". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo, measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens, determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.

Cognitive tests used in chronic adult human randomised controlled trial micronutrient and phytochemical intervention studies

In recent years there has been a rapid growth of interest in exploring the relationship between nutritional therapies and the maintenance of cognitive function in adulthood. Emerging evidence reveals an increasingly complex picture with respect to the benefits of various food constituents on learning, memory and psychomotor function in adults. However, to date, there has been little consensus in human studies on the range of cognitive domains to be tested or the particular tests to be employed. To illustrate the potential difficulties that this poses, we conducted a systematic review of existing human adult randomised controlled trial (RCT) studies that have investigated the effects of 24 d to 36 months of supplementation with flavonoids and micronutrients on cognitive performance. There were thirty-nine studies employing a total of 121 different cognitive tasks that met the criteria for inclusion. Results showed that less than half of these studies reported positive effects of treatment, with some important cognitive domains either under-represented or not explored at all. Although there was some evidence of sensitivity to nutritional supplementation in a number of domains (for example, executive function, spatial working memory), interpretation is currently difficult given the prevailing 'scattergun approach' for selecting cognitive tests. Specifically, the practice means that it is often difficult to distinguish between a boundary condition for a particular nutrient and a lack of task sensitivity. We argue that for significant future progress to be made, researchers need to pay much closer attention to existing human RCT and animal data, as well as to more basic issues surrounding task sensitivity, statistical power and type I error.

Criteria for validation and selection of cognitive tests for investigating the effects of foods and nutrients.

This review is an output of the International Life Sciences Institute (ILSI) Europe Marker Initiative, which aims to identify evidence-based criteria for selecting adequate measures of nutrient effects on health through comprehensive literature review. Experts in cognitive and nutrition sciences examined the applicability of these proposed criteria to the field of cognition with respect to the various cognitive domains usually assessed to reflect brain or neurological function. This review covers cognitive domains important in the assessment of neuronal integrity and function, commonly used tests and their state of validation, and the application of the measures to studies of nutrition and nutritional intervention trials. The aim is to identify domain-specific cognitive tests that are sensitive to nutrient interventions and from which guidance can be provided to aid the application of selection criteria for choosing the most suitable tests for proposed nutritional intervention studies using cognitive outcomes. The material in this review serves as a background and guidance document for nutritionists, neuropsychologists, psychiatrists, and neurologists interested in assessing mental health in terms of cognitive test performance and for scientists intending to test the effects of food or food components on cognitive function.

Impairments in glucose tolerance can have a negative impact on cognitive function: a systematic research review

There is an increasing body of research investigating whether abnormal glucose tolerance is associated with cognitive impairments, the evidence from which is equivocal. A systematic search of the literature identified twenty-three studies which assessed either clinically defined impaired glucose tolerance (IGT) or variance in glucose tolerance within the clinically defined normal range (NGT). The findings suggest that poor glucose tolerance is associated with cognitive impairments, with decrements in verbal memory being most prevalent. However, the evidence for decrements in other domains was weak. The NGT studies report a stronger glucose tolerance-cognition association than the IGT studies, which is likely to be due to the greater number of glucose tolerance parameters and the more sensitive cognitive tests in the NGT studies compared to the IGT studies. It is also speculated that the negative cognitive impact of abnormalities in glucose tolerance increases with age, and that glucose consumption is most beneficial to individuals with poor glucose tolerance compared to individuals with normal glucose tolerance. The role of potential mechanisms are discussed.

Flavonoid-rich orange juice is associated with acute improvements in cognitive function in healthy middle-aged males

Purpose: Epidemiological evidence suggests that chronic consumption of fruit based flavonoids is associated with cognitive benefits, however, the acute effects of flavonoid rich drinks on cognitive function in the immediate postprandial period requires examination. The objective was to investigate whether consumption of flavonoid rich orange juice is associated with acute cognitive benefits over six hours in healthy middle-aged adults. Methods: Males aged 30-65 consumed a 240ml flavonoid rich (FR) orange juice (272mg) and a calorie matched placebo in a randomized, double-blind, counterbalanced order on two days separated by a two week washout. Cognitive function and subjective mood were assessed at baseline (prior to drink consumption) and 2hrs and 6hrs post consumption. The cognitive battery included eight individual cognitive tests. A standardized breakfast was consumed prior to the baseline measures, and a standardized lunch was consumed 3hrs post drink consumption. Results: Change from baseline analysis revealed that performance on tests of executive function and psychomotor speed was significantly better following the FR drink compared to the placebo. The effects for objective cognitive function were supported by significant benefits for subjective alertness following the FR drink relative to the placebo. Conclusions: These data demonstrate that consumption of flavonoid rich orange juice can acutely enhance objective and subjective cognition over the course of six hours in healthy middle-aged adults.