Protein synthesis is affected when an insufficient level of sulfur amino acids is available. This defect may originate from dietary amino acid deficiency and/or excessive amino acid utilisation for other purposes such as the synthesis of glutathione and acute-phase proteins during catabolic stress. Sulfur amino acids are recognised to exert other significant functions since they are precursors of essential molecules, are involved in the methylation process, participate in the control of oxidative status, and may act as mediators affecting metabolism and cell functions. Despite this increased understanding of the role of sulfur amino acids, many questions still remain unanswered due to the complexity of the mechanisms involved. Moreover, surprising effects of dietary sulfur amino acids have been reported, with the development of disorders in cases of both deficiency and excess. These findings indicate the importance of defining adequate levels of intake and providing a rationale for nutritional advice. The aim of the present review is to provide an overview on the roles of sulfur amino acids as regulators of nutrient metabolism and cell functions, with emphasis placed on the implications for nutrition.

The shifting focus from infectious to non-communicable diseases has changed what and how nutritional epidemiology evaluates in the relationships between foods, nutrients and the occurrence of disease. The classically applied vision based on individual nutrients, ‘research from the bottom up’, has now been complemented with new approaches, such as applying the analysis of food combinations (dietary patterns) to study exposure and outcome. Methods of estimating nutrient adequacy have also changed over time, starting from calculating the nutrient adequacy ratio to the use of the probabilistic approach. In the present work constituting Research Activity 1.1, conducted within the EURopean micronutrient RECommendations Aligned Network of Excellence, we have set out to rationalise and harmonise the science of estimating micronutrient intake and nutritional adequacy in Europe. A review of food and nutrition initiatives previously conducted in Europe is presented to set the background and context for the present efforts towards developing a harmonised framework on the dietary assessment of micronutrient intakes.

Certain dietary components which could affect oestrogen may have implications in the aetiology of uterine fibroids. We previously found that soya intake was inversely associated with a subsequent risk of hysterectomy, suggesting a potentially protective effect of soya against uterine fibroids, the major clinical indication for hysterectomy. We cross-sectionally assessed the associations of intakes of fat, soya foods, dietary fibre and alcohol with uterine fibroids. Study subjects were 285 premenopausal Japanese women participating in a health-check up programme, including gynaecological examinations, provided by a general hospital between October 2003 and March 2006. The presence of fibroids was confirmed by transvaginal sonogram. If women had undergone hysterectomy, self-report of fibroids was accepted. Each subject's usual diet, including alcohol, was determined with the use of a validated FFQ. Fifty-four women were identified as prevalent cases of fibroids or having had hysterectomy due to fibroids. The mean alcohol intake was statistically significantly higher among women with fibroids than among those without fibroids after controlling for known or suspected risk factors. For the highest compared with the lowest tertile of alcohol intake, the OR of uterine fibroids was 2·78 (95 % CI 1·25, 6·20). There was no significant association of intake of fats, soya isoflavones or dietary fibre with uterine fibroids. The data suggest that higher alcohol intake is associated with a higher prevalence of uterine fibroids. Further studies on diet, especially phyto-oestrogens, and uterine fibroids are needed given the limited data currently available.

There is a growing awareness that the gut microbiota and an appropriately functioning immune system play an important role in maintaining human health. Recent population statistics have highlighted some worrying trends, specifically that there is a growing burden of immunological disease in Western populations, that Western populations are ageing, and that obesity, with its strong inflammatory component, is reaching epidemic proportions.

Body fat mass (FM) adds to the variance in resting energy expenditure (REE). However, the nature and extent of this relationship remains unclear. Using a database of 1306 women and a linear regression model, we systematically analysed the contribution of FM to the total variance in REE at different grades of adiposity (ranges of body %FM). After adjusting for age, the relative contribution of FM on REE variance increased from low ( ≤ 10 %FM) to normal (>10– ≤ 30 %FM) and moderately elevated (>30– ≤ 40 %FM) grades of adiposity but decreased sharply at high (>40– ≤ 50 %FM) and very high (>50 %FM) grades of adiposity according to the ratio between regression coefficients. These data suggest that the specific metabolic rate of fat tissue is reduced at high adiposity. This should be considered when REE is normalized for FM in obesity.

European Union Regulation 258/97 defines novel foods as food products and food ingredients that have not been consumed to a significant degree in the European Union before May 1997. However, there are new foods that for some reason are not considered as novel foods, though we think that safety of these products is not always a priori established. We defined a ‘grey area’ which consists of such foods, and the present paper intends to raise awareness of this ‘grey area’ of unidentified novel foods. The grey area of novel foods is divided into two categories: (1) food products or ingredients for which the current Regulation leaves too much space for different interpretations and (2) food products or ingredients that are not novel according to the current Regulation, because the current Regulation contains gaps. These categories are illustrated by means of products already on the market in The Netherlands. We found about two dozen examples of products that had not been identified as novel foods according the current Regulation, yet could be considered to be classified as novel foods and hence for which a safety evaluation (toxicological and/or nutritional) would be indicated.

Like all scientific innovations, nutrigenomics develops through a constant interplay with society. Normative assumptions, embedded in the way researchers formulate strands of nutrigenomics research, affect this interplay. These assumptions may influence norms and values on food and health in our society. To discuss the possible pros and cons of a society with nutrigenomics, we need to reflect ethically on assumptions rooted in nutrigenomics research. To begin with, we analysed a set of scientific journal articles and explicated three normative assumptions embedded in the present nutrigenomics research. First, values regarding food are exclusively explained in terms of disease prevention. Health is therefore a state preceding a sum of possible diseases. Second, it is assumed that health should be explained as an interaction between food and genes. Health is minimised to quantifiable health risks and disease prevention through food–gene interactions. The third assumption is that disease prevention by minimisation of risks is in the hands of the individual and that personal risks, revealed either through tests or belonging to a risk group, will play a large role in disease prevention. Together, these assumptions suggest that the good life (a life worth living, with the means to flourish and thrive) is equated with a healthy life. Our thesis is that these three normative assumptions of nutrigenomics may strengthen the concerns related to healthism, health anxiety, time frames and individual responsibilities for health. We reflect on these ethical issues by confronting them in a thought experiment with alternative, philosophical, views of the good life.

It is not known whether trace amounts of proteins that may remain in cereal-starch-derived food ingredients even after food processing can trigger allergic symptoms in cereal-allergic individuals. The aim of this study was to find out if barley starch syrup causes allergic reactions in patients with allergy to wheat, barley, rye or oats. Fifteen children with allergy to these cereals, confirmed by double-blind placebo-controlled food challenge (DBPCFC), were selected for the study. When exposed to cereals, seven of the children (47 %) showed immediate type reactions, such as urticaria, rash or anaphylaxis. Eight of the children (53 %) showed delayed type reactions, such as deterioration of atopic dermatitis or diarrhoea. The fifteen children with allergy to cereals were exposed to barley starch syrup in DBPCFC and none of them showed any objective signs of allergy. On skin-prick tests (SPT), five of the children (33·3 %) showed a positive ( ≥ 3 mm) reaction to at least one of the cereals but none of them to barley starch syrup. This study confirmed with 98 % confidence that at least 90 % of the patients with verified allergy to cereals will not react with allergic symptoms to barley starch syrup.

Vitamin D is a fat-soluble, seco-steroid hormone. In man, the vitamin D receptor is expressed in almost all tissues, enabling effects in multiple systems of the human body. These effects can be endocrine, paracrine and autocrine. The present review summarises the effects of ageing on the vitamin D endocrine system and on Ca homeostasis. Furthermore, consequences for vitamin D supplementation are discussed.

The way in which the quality of life related to health (HRQoL) is affected by the nutritional status of the patient is a subject of constant interest and permanent debate. The purpose of the present paper is to review those studies that relate HRQoL to nutritional status and examine the tools (questionnaires) that they use to investigate this relationship. A critical review of published studies was carried out via an investigation of the following databases: MEDLINE (via PubMed); EMBASE; The Cochrane Library; Cumulative Index to Nursing and Allied Health Literature (CINAHL); Institute for Scientific Information (ISI) Web of Science; Latin American and Caribbean Health Sciences Literature (LILACS); Spanish Health Sciences Bibliographic Index (IBECS). The search was carried out from the earliest date possible until July 2007.The medical subject heading terms used were ‘quality of life’, ‘nutritional status’ and ‘questionnaires’. The articles had to contain at least one questionnaire that evaluated quality of life. Twenty-eight documents fulfilling the inclusion criteria were accepted, although none of them used a specific questionnaire to evaluate HRQoL related to nutritional status. However, some of them used a combination of generic questionnaires with the intention of evaluating the same. Only three studies selectively addressed the relationship between nutritional status and quality of life, this evaluation being performed not by means of specific questionnaires but by statistical analysis of data obtained via validated questionnaires.

Due to the incorporation of niacin into the coenzymes NAD and NADP, niacin is of great importance for the metabolism of man and animals. Apart from niacin in feed and endogenous formation, microbial niacin synthesis in the rumen is an important source for dairy cows. But the amount synthesised seems to differ greatly, which might be influenced by the ration fed. Many studies revealed a positive impact of a niacin supplementation on rumen protozoa, but microbial protein synthesis or volatile fatty acid production in the rumen showed inconsistent reactions to supplemental niacin. The amount of niacin reaching the duodenum is usually higher when niacin is fed. However, not the whole quantity supplemented reaches the duodenum, indicating degradation or absorption before the duodenal cannula. Furthermore, supplementation of niacin did not always lead to a higher niacin concentration in blood. Effects on other blood parameters have been inconsistent, but might be more obvious when cows are in a tense metabolic situation, for example, ketosis or if high amounts are infused post-ruminally, since ruminal degradation appears to be substantial. The same is valid for milk parameters. In the few studies where blood niacin and milk parameters have been investigated, enhanced niacin concentrations in blood did not necessarily affect milk production or composition. These results are discussed in the present review, gaps of knowledge of niacin's mode of action on the metabolism of dairy cows are identified and directions for future research are suggested.

β2-1 Fructans are carbohydrate molecules with prebiotic properties. Through resistance to digestion in the upper gastrointestinal tract, they reach the colon intact, where they selectively stimulate the growth and/or activity of beneficial members of the gut microbiota. Through this modification of the intestinal microbiota, and by additional mechanisms, β2-1 fructans may have beneficial effects upon immune function, ability to combat infection, and inflammatory processes and conditions. In this paper, we have collated, summarised and evaluated studies investigating these areas. Twenty-one studies in laboratory animals suggest that some aspects of innate and adaptive immunity of the gut and the systemic immune systems are modified by β2-1 fructans. In man, two studies in children and nine studies in adults indicate that the adaptive immune system may be modified by β2-1 fructans. Thirteen studies in animal models of intestinal infections conclude a beneficial effect of β2-1 fructans. Ten trials involving infants and children have mostly reported benefits on infectious outcomes; in fifteen adult trials, little effect was generally seen, although in specific situations, certain β2-1 fructans may be beneficial. Ten studies in animal models show benefit of β2-1 fructans with regard to intestinal inflammation. Human studies report some benefits regarding inflammatory bowel disease (four positive studies) and atopic dermatitis (one positive study), but findings in irritable bowel syndrome are inconsistent. Therefore, overall the results indicate that β2-1 fructans are able to modulate some aspects of immune function, to improve the host's ability to respond successfully to certain intestinal infections, and to modify some inflammatory conditions.

Hypoxia/reoxygenation is one of the causes of the increased expression of inducible NO synthase in cardiomyocytes. In a recent study we demonstrated that a single, high dose of green tea extract (GT) supplemented to the medium of cultured cardiomyocytes just before hypoxia/reoxygenation is able to prevent the increased expression of inducible NO synthase, therefore reducing NO overproduction. In the present study we investigated the mechanism by which GT reduces NO production. Since a molecular mechanism for polyphenol activity has been postulated, and PPAR activation is related to the transcription of the inducible NO synthase gene, we evaluated the activation of PPAR by GT. A moderate GT concentration, supplemented to the cardiomyocyte medium since the initial seeding, selectively activated the PPAR-β/δ isoform. Furthermore, we observed a reduction in NO production and an increase in total antioxidant activity, indicating that GT components may act on both reactive oxygen species, via an antioxidant mechanism, and NO overproduction. PPAR-β/δ activation could represent the key event in the reduction of NO production by GT. Although PPAR activation by GT was lower than activation by fenofibrate, it is very interesting to note that it was selective for the β/δ isoform, at least in neonatal cardiomyocytes.

We evaluated the influence of the main cereal of the diet and the degree of heat processing of rice on apparent ileal and total tract digestibility of nutrients and ileum morphology of pigs at 37 d of age. Control pigs were fed a complex diet that contained 500 g/kg cooked and flaked maize with a degree of starch gelatinisation (SG) of 840 g/kg. Experimental groups received the same complex diet in which maize was substituted (w/w) by rice with three different degrees of SG; 110, 520 and 760 g/kg that corresponded to raw rice and cooked rice processed under two different set of conditions. The digestibility of dietary components, except for nitrogen, was greater for the cooked rice – than for the raw rice – and the maize diet (P < 0·001). Pigs fed cooked rice had higher villus height to crypt depth ratio (P < 0·001) and greater percentage of zigzag-oriented villi and lesser percentage of tongue-oriented villi (P < 0·01) than pigs fed other diets. Compared with feeding maize, feeding rice improved dietary component digestibility and ileal morphology in piglets. Mild cooking of rice (SG = 520 g/kg) enhanced diet digestibility and ileum morphology. However, processing the rice to increase SG to 760 g/kg did not increase nutrient digestibility further and in fact impaired ileal morphology.

The objective of the present paper is to review the methods of measuring micronutrient intake adequacy for individuals and for populations in order to ascertain best practice. A systematic review was conducted to locate studies on the methodological aspects of measuring nutrient adequacy. The results showed that for individuals, qualitative methods (to find probability of adequacy) and quantitative methods (to find confidence of adequacy) have been proposed for micronutrients where there is enough data to set an average nutrient requirement (ANR). If micronutrients do not have ANR, an adequate intake (AI) is often defined and can be used to assess adequacy, provided the distribution of daily intake over a number of days is known. The probability of an individual's intake being excessive can also be compared with the upper level of safe intake and the confidence of this estimate determined in a similar way. At the population level, adequacy can be judged from the ANR using the probability approach or its short cut – the estimated average requirement cut-point method. If the micronutrient does not have an ANR, adequacy cannot be determined from the average intake and must be expressed differently. The upper level of safe intake can be used for populations in a similar way to that of individuals. All of the methodological studies reviewed were from the American continent and all used the methodology described in the Institute of Medicine publications. The present methodology should now be adapted for use in Europe.

Artificial nutrition is an inherent part of management in acute pancreatitis. However, there is no consensus regarding the optimal time of the commencement of feeding in these patients. Our aim was to compare the effect of enteral v. parenteral nutrition with regard to the time points when they were administered in the randomised controlled trials. The search was undertaken in the Cochrane Central Register of Controlled Trials, MEDLINE and Science Citation Index as well as in the proceedings of major gastroenterology meetings. The summary estimate of the effect associated with artificial nutrition was calculated using a random-effects model and presented as a risk ratio (RR) and 95 % CI. A total of eleven randomised controlled trials were included. When started within 48 h of admission, enteral nutrition, in comparison with parenteral nutrition, resulted in a statistically significant reduction in the risks of multiple organ failure (RR 0·44; 95 % CI 0·23, 0·84), pancreatic infectious complications (RR 0·46; 95 % CI 0·27, 0·77) and mortality (RR 0·46; 95 % CI 0·20, 0·99). After 48 h of admission, enteral nutrition, in comparison with parenteral nutrition, did not result in a statistically significant reduction in the risks of multiple organ failure (RR 0·73; 95 % CI 0·33, 1·63), pancreatic infectious complications (RR 0·31; 95 % CI 0·07, 1·34) and mortality (RR 0·67; 95 % CI 0·22, 2·10). Enteral nutrition is more effective than parenteral nutrition in reducing the risk of multiple organ failure, pancreatic infectious complications and mortality in patients with acute pancreatitis. The magnitude of these benefits may depend on the timing of the commencement of nutrition.

Whole grains are known to influence postprandial glucose response and insulin demand and are inversely associated with diabetes risk. Genetic variation of the transcription factor-7-like 2 encoding gene (TCF7L2) is assumed to promote an early insulin secretory defect and has been consistently attributed to the risk of developing type 2 diabetes. The present study examined the hypothesis that the protective effect of whole grains might be attenuated in the presence of the rs7903146 risk-conferring T-allele. We employed a case–cohort study of 2318 randomised individuals and 724 incident type 2 diabetes cases from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Multivariate Cox regression was used to estimate relative risks of diabetes including product terms testing for the genotype-specific effect modification of dietary whole grain. Dietary intake of whole grains was assessed by a validated FFQ. The TCF7L2 rs7903146 T-allele was associated with type 2 diabetes (hazard ratio = 1·51; 95 % CI 1·21, 1·87) and modified the inverse association between whole-grain intake and diabetes risk (P = 0·016 for interaction). While whole-grain intake was inversely associated with diabetes risk among rs7903146 CC homozygote carriers (hazard ratio for 50 g portion per d = 0·86; 95 % CI 0·75, 0·99), the T-allele negated the protective effect of whole-grain intake (hazard ratio among T-allele carriers for 50 g portion per d = 1·08; 95 % CI 0·96, 1·23). These data provide evidence that the beneficial effect of whole-grain intake on diabetes risk is modified by TCF7L2 rs7903146.

Ascorbate can act as both a reducing and oxidising agent in vitro depending on its environment. It can modulate the intracellular redox environment of cells and therefore is predicted to modulate thiol-dependent cell signalling and gene expression pathways. Using proteomic analysis of vitamin C-treated T cells in vitro, we have previously reported changes in expression of five functional protein groups associated with signalling, carbohydrate metabolism, apoptosis, transcription and immune function. The increased expression of the signalling molecule phosphatidylinositol transfer protein (PITP) was also confirmed using Western blotting. Herein, we have compared protein changes elicited by ascorbate in vitro, with the effect of ascorbate on plasma potassium levels, on peripheral blood mononuclear cell (PBMC) apoptosis and PITP expression, in patients supplemented with vitamin C (0–2 g/d) for up to 10 weeks to investigate whether in vitro model systems are predictive of in vivo effects. PITP varied in expression widely between subjects at all time-points analysed but was increased by supplementation with 2 g ascorbate/d after 5 and 10 weeks. No effects on plasma potassium levels were observed in supplemented subjects despite a reduction of K+ channel proteins in ascorbate-treated T cells in vitro. Similarly, no effect of vitamin C supplementation on PBMC apoptosis was observed, whilst ascorbate decreased expression of caspase 3 recruitment domain protein in vitro. These data provide one of the first demonstrations that proteomics may be valuable in developing predictive markers of nutrient effects in vivo and may identify novel pathways for studying mechanisms of action in vivo.