The post-genomic technologies are generating vast quantities of data but many nutritional scientists are not trained or equipped to analyse it. In high-resolution NMR spectra of urine, for example, the number and complexity of spectral features mean that computational techniques are required to interrogate and display the data in a manner intelligible to the researcher. In addition, there are often multiple underlying biological factors influencing the data and it is difficult to pinpoint which are having the most significant effect. This is especially true in nutritional studies, where small variations in diet can trigger multiple changes in gene expression and metabolite concentration. One class of computational tools that are useful for analysing this highly multivariate data include the well-known ‘whole spectrum’ methods of principal component analysis and partial least squares. In this work, we present a nutritional case study in which NMR data generated from a human dietary Cu intervention study is analysed using multivariate methods and the advantages and disadvantages of each technique are discussed. It is concluded that an alternative approach, called feature subset selection, will be important in this type of work; here we have used a genetic algorithm to identify the small peaks (arising from metabolites of low concentration) that have been altered significantly following a dietary intervention.

To be able to perform a comprehensive and rigorous benefit-risk analysis of individual food components, and of foods, a number of fundamental questions need to be addressed first. These include whether it is feasible to detect all relevant biological effects of foods and individual food components, how such effects can confidently be categorised into benefits and risks in relation to health and, for that matter, how health can be quantified. This article examines the last of these issues, focusing upon concepts for the development of new biomarkers of health. Clearly, there is scope for refinement of classical biomarkers so that they may be used to detect even earlier signs of disease, but this approach defines health solely as the absence of detectable disease or disease risk. We suggest that the health of a biological system may better be reflected by its ability to withstand and manage relevant physiological challenges so that homeostasis is maintained. We discuss the potential for expanding the range of current challenge tests for use in conjunction with functional genomic technologies to develop new types of biomarkers of health.

A deficiency of dietary protein or amino acids has long been known to impair immune function and increase the susceptibility of animals and humans to infectious disease. However, only in the past 15 years have the underlying cellular and molecular mechanisms begun to unfold. Protein malnutrition reduces concentrations of most amino acids in plasma. Findings from recent studies indicate an important role for amino acids in immune responses by regulating: (1) the activation of T lymphocytes, B lymphocytes, natural killer cells and macrophages; (2) cellular redox state, gene expression and lymphocyte proliferation; and (3) the production of antibodies, cytokines and other cytotoxic substances. Increasing evidence shows that dietary supplementation of specific amino acids to animals and humans with malnutrition and infectious disease enhances the immune status, thereby reducing morbidity and mortality. Arginine, glutamine and cysteine precursors are the best prototypes. Because of a negative impact of imbalance and antagonism among amino acids on nutrient intake and utilisation, care should be exercised in developing effective strategies of enteral or parenteral provision for maximum health benefits. Such measures should be based on knowledge about the biochemistry and physiology of amino acids, their roles in immune responses, nutritional and pathological states of individuals and expected treatment outcomes. New knowledge about the metabolism of amino acids in leucocytes is critical for the development of effective means to prevent and treat immunodeficient diseases. These nutrients hold great promise in improving health and preventing infectious diseases in animals and humans.

Consensus recommendations on behalf of the European Commission research projects Perinatal Lipid Metabolism (PeriLip; www.perilip.org) and Early Nutrition Programming (EARNEST; www.metabolic-programming.org), developed jointly with representatives of the Child Health Foundation (Stiftung Kindergesundheit; www.kindergesundheit.de), the Diabetic Pregnancy Study Group (DPSG; www.medfak.uu.se/dpsg), the European Association of Perinatal Medicine (EAPM; www.europerinatal.com), the European Society for Clinical Nutrition and Metabolism (ESPEN; www.espen.org), the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, Committee on Nutrition (ESPGHAN; www.espghan.org), the International Federation of Placenta Associations (IFPA; http://aculeate.hopto.org/IFPA) and the International Society for the Study of Fatty Acids and Lipids (ISSFAL; email www.issfal.org.uk).

Members of the Perinatal Lipid Intake Working Group

Gioia Alvino, Juliana von Berlepsch, Hans Konrad Biesalski, Tom Clandinin, Hildegard Debertina, Tamás Decsi, Hans Demmelmaira, Gernot Desoyebc, Veronika Dietz, Peter Dodds, Pauline Emmett, Fabio Facchinettid, Matthew W. Gillman, Joachim Heinrich, Emilio Herrerab, Irene Hoesli, William C. Heird, Matthew Hyde, Kirsi Laitinen, John Laws, Elvira Larqué Daza, Iliana Lopez-Soldado, Maria Makrides, Kim Fleischer Michaelsene, Sjurdur Olsen, Henar Ortega, Guy Putet, Imogen Rogers, Paola Roggero, Lubos Sobotkaf, Hania Szajewskag, Hope Weiler.

(Representing: aChild Health Foundation, bDPSG, cIFPA, dEAPM, eISSFAL, fESPEN, gESPGHAN.)

Dietary fat intake in pregnancy and lactation affects pregnancy outcomes and child growth, development and health. The European Commission charged the research project PERILIP, jointly with the Early Nutrition Programming Project, to develop recommendations on dietary fat intake in pregnancy and lactation. Literature reviews were performed and a consensus conference held with international experts in the field, including representatives of international scientific associations. The adopted conclusions include: dietary fat intake in pregnancy and lactation (energy%) should be as recommended for the general population; pregnant and lactating women should aim to achieve an average dietary intake of at least 200 mg DHA/d; intakes of up to 1 g/d DHA or 2·7 g/d n-3 long-chain PUFA have been used in randomized clinical trials without significant adverse effects; women of childbearing age should aim to consume one to two portions of sea fish per week, including oily fish; intake of the DHA precursor, α-linolenic acid, is far less effective with regard to DHA deposition in fetal brain than preformed DHA; intake of fish or other sources of long-chain n-3 fatty acids results in a slightly longer pregnancy duration; dietary inadequacies should be screened for during pregnancy and individual counselling be offered if needed.

It is hypothesized that the intake of long-chain PUFA (LC-PUFA) throughout pregnancy could protect against pre-eclampsia, pregnancy-induced hypertension or intra-uterine growth retardation, and is essential for optimal neural development. The objective of the present study was to systematically evaluate the effect of LC-PUFA supplementation of high-risk pregnant women's diets on pregnancy outcomes and growth measures at birth. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library through March 2006 and references in reviewed articles for randomized controlled trials (RCT) comparing LC-PUFA supplementation with placebo or no supplementation in women with high-risk pregnancies. We found no evidence that supplementation influenced the duration of pregnancy or the percentage of preterm deliveries < 37 weeks of gestation. However, compared with controls, supplementation was associated with a significantly lower rate of early preterm delivery ( < 34 weeks of gestation) (two RCT; n 291; relative risk 0·39 (95 % CI 0·18, 0·84)). There was no significant difference in the infant birth weight, the rate of low birth weight ( < 2500 g or < 10th percentile) and the recurrence of intra-uterine growth retardation. Other pregnancy outcomes (for example, the rate of pregnancy-induced hypertension, the rate of pre-eclampsia and the rate of Caesarean section) were also similar in both groups. In conclusion, the present data suggest that supplementation with n-3 LC-PUFA in women with high-risk pregnancies reduced the risk of early preterm delivery in the fatty acid-supplemented group compared with the placebo group, while no other effects on pregnancy outcomes were detected.

The prevalence of non-communicable diseases (for example, cardiovascular disorders, type 2 diabetes and cancer) is rampant in Western societies, accounting for approximately 60 % of all causes of death. A large proportion of non-communicable diseases can be prevented through appropriate diets and lifestyles. Accordingly, several health authorities and regulatory bodies are assessing the nutritional profiles of food items and whole diets, to implement guidelines aimed at improving the diet of the general population. While a global approach is desirable, the need of individuals to maintain their distinct dietary habits must also be taken into account. The portion sizes of food as well as pattern of food consumption, for example during or between the main meals, are very important in determining the nutritional profile of a diet. A novel method to assess the nutritional profile of foods is being proposed and made available on-line. Its main innovative aspects are (1) the comprehensive manner with which the system analyses and computes a great range of features of individual food items and (2) the distinction among eating occasions, namely during or in-between the main meals. Moreover, this approach allows for rapid modification and great flexibility to suit individual needs and gastronomic habits.

This study investigated the associations among vitamin D receptor (VDR) BsmI polymorphism, calcium intake and bone strength as indicated by the broadband ultrasound attenuation (BUA) measured by calcaneal quantitative ultrasound at the left calcaneus in community-dwelling subjects with a low calcium intake. The VDR BsmI polymorphism was analysed in 335 women older than 65 years residing in rural Asan, Korea. Calcium intake was assessed with a 2 d, 24 h recall method. The distribution of genotypes was similar to that reported in other Asian populations (92 % bb, 7 % Bb and 1 % BB). The calcaneal BUA was significantly higher (P = 0·013) in the bb genotype than in the Bb or BB genotype (Bb and BB genotypes were combined due to the small number of BB subjects) in a multiple regression model after adjusting for age, body weight, height, physical activity and nutritional factors. BUA was not significantly affected by the calcium intake regardless of the genotype, cross-sectionally. The energy-adjusted average calcium intake of this population was 439·6 mg/d (432·5 mg/d for bb and 522·3 mg/d for Bb or BB), and 96 % of the subjects had dietary intakes that were less than the recommended Dietary Reference Intake for Koreans (which for calcium is 800 mg/d for women older than 65 years). In summary, the BUA in older Korean women with a low calcium intake was significantly influenced by the VDR genotype but not by the calcium intake, cross-sectionally.

It has been shown that treatment of rats with clofibrate, a synthetic agonist of PPARα, increases mRNA concentration of organic cation transporters (OCTN)-1 and -2 and concentration of carnitine in the liver. Since oxidised fats have been demonstrated in rats to activate hepatic PPARα, we tested the hypothesis that they also up regulate OCTN. Eighteen rats were orally administered either sunflower-seed oil (control group) or an oxidised fat prepared by heating sunflower-seed oil, for 6 d. Rats administered the oxidised fat had higher mRNA concentrations of typical PPARα target genes such as acyl-CoA oxidase, cytochrome P450 4A1 and carnitine palmitoyltransferases-1A and -2 in liver and small intestine than control rats (P < 0·05). Furthermore, rats treated with oxidised fat had higher hepatic mRNA concentrations of OCTN1 (1·5-fold) and OCTN2 (3·1-fold), a higher carnitine concentration in the liver and lower carnitine concentrations in plasma, gastrocnemius and heart muscle than control rats (P < 0·05). Moreover, rats administered oxidised fat had a higher mRNA concentration of OCTN2 in small intestine (2·4-fold; P < 0·05) than control rats. In conclusion, the present study shows that an oxidised fat causes an up regulation of OCTN in the liver and small intestine. An increased hepatic carnitine concentration in rats treated with the oxidised fat is probably at least in part due to an increased uptake of carnitine into the liver which in turn leads to reduced plasma and muscle carnitine concentrations. The present study supports the hypothesis that nutrients acting as PPARα agonists influence whole-body carnitine homeostasis.

High postprandial levels of TAG may further induce endothelial dysfunction and inflammation in subjects with high fasting levels of TAG, an effect that seems to be related to oxidative stress. The present study investigated whether minor compounds of olive oil with antioxidant activity decrease postprandial levels of soluble isoforms of intercellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), as surrogate markers of vascular inflammation, after a high-fat meal. A randomized crossover and blind trial on fourteen healthy and fourteen hypertriacylglycerolaemic subjects was performed. The study involved a 1-week adaptation lead-in period on a National Cholesterol Education Program Step I diet supplemented with extra-virgin olive oil (EVOO) containing 1125 mg polyphenols/kg and 350 mg tocopherols/kg, or refined olive oil (ROO) with no polyphenols or tocopherols. After a 12 h fast, the participants ate a high-fat meal enriched in EVOO or ROO (50 g/m2 body surface area), which on average provided 3700 kJ energy with a macronutrient profile of 72 % fat, 22 % carbohydrate and 6 % protein. Blood samples drawn hourly over the following 8 h demonstrated a similar postprandial TAG response for both EVOO and ROO meals. However, in both healthy and hypertriacylglycerolaemic subjects the net incremental area under the curve for sICAM-1 and sVCAM-1 were significantly lower after the EVOO meal. In conclusion, the consumption of EVOO with a high content of minor antioxidant compounds may have postprandial anti-inflammatory protective effects.

Zn-deficient (ZD) rats have a lower proportion of splenic CD90+T-cells which could be due to fewer new T-cells exiting the thymus, defective post-thymic maturation or increased cell death. Post-thymic maturation of splenic lymphocytes and their viability were determined by flow cytometry in weanling rats assigned to ZD ( < 1 mg Zn/kg; ad libitum), diet-restricted (DR; 30 mg Zn/kg; limited to the amount of feed as consumed by ZD rats), marginally Zn-deficient (MZD; 10 mg Zn/kg; ad libitum) or control (30 mg Zn/kg; ad libitum) groups for 3 weeks. ZD rats had a 29 % lower percentage of splenic CD90+T-cells and both ZD and DR rats had a 30 % lower proportion of splenic CD90+B-cells compared with control rats. When the splenic CD90+T-cells were characterised further, there was no difference among the groups in the first two stages of post-thymic development; however, ZD, DR and MZD rats had a 42 % lower proportion of late thymic emigrants (TCRαβ+CD90+CD45RC+RT6.1+) compared with control rats. There was no difference among groups in the proportion of splenic CD90+T-cells in the non-viable region; however, ZD rats had a higher proportion of CD90+B-cells in the non-viable region compared with MZD and control animals, suggesting that this phenotype was more susceptible to cell death during deficiency. The lower proportion of splenic CD90+T-cells in ZD rats does not appear to be due to a defect in thymic production or increased cell death in the spleen. Future studies should determine if late thymic emigrants have homed to other peripheral organs.

Following an introduction of the importance of folates and the rationale for seeking to estimate fractional folate absorption from foods (especially for countries not having a mandatory folic acid fortification policy), scientific papers covering the mechanisms of folate absorption and initial biotransformation are discussed. There appears (post-1983) to be a consensus that physiological doses of folic acid undergo biotransformation in the absorptive cells of the upper small intestine to 5-methyltetrahydrofolic acid (as happens for all naturally-occurring reduced 1-carbon-substituted folates). This ‘validates’ short-term experimental protocols assessing ‘relative’ folate absorption in human subjects that use folic acid as the ‘reference’ dose. The underlying scientific premise on which this consensus is based is challenged on three grounds: (i) the apparent absence of a 5-methyltetrahydrofolic acid response in the human hepatic portal vein following absorption of folic acid, (ii) the low dihydrofolate reductase activity peculiar to man and (iii) the implications derived from recent stable-isotope studies of folate absorption. It is concluded that the historically accepted case for folic acid being a suitable ‘reference folate’ for studies of the ‘relative absorption’ of reduced folates in human subjects is invalid. It is hypothesised that the liver, and not the absorptive cells of the upper small intestine, is the initial site of folic acid metabolism in man and that this may have important implications for its use as a supplement or fortificant since human liver's low capacity for reduction may eventually give rise to saturation, resulting in significant (and potentially deleterious) unmetabolised folic acid entering the systemic circulation.

It is unclear whether postprandial blood glucose or insulin exerts a regulatory function in short-term appetite regulation in humans. The aim of this study was to investigate, by use of meta-analysis, the role of blood glucose and insulin in short-term appetite sensation and energy intake (EI) in normal weight and overweight participants. Data from seven test meal studies were used, including 136 healthy participants (ALL) (92 normal weight (NW) and 44 overweight or obese (OW)). All meals were served as breakfasts after an overnight fast, and appetite sensations and blood samples were obtained frequently in the postprandial period. Finally, an ad libitum lunch was served. Data were analysed by fixed effects study level (SL) meta-regression analysis and individual participant data (IPD) regression analysis, using STATA software. In SL analysis, postprandial insulin response was associated with decreased hunger in ALL, NW and OW (P < 0·019), and with increased satiety in NW (P = 0·004) and lower subsequent EI in OW (P = 0·022). Multivariate IPD analysis showed similar associations, but only in NW for hunger, satiety and EI (P < 0·028), and in ALL for EI (P = 0·016). The only association involving blood glucose was the multivariate IPD analysis showing an inverse association between blood glucose and EI in ALL (P = 0·032). Our results suggest that insulin, but not glucose, is associated with short-term appetite regulation in healthy participants, but the relationship is disrupted in the overweight and obese. We conclude that the postprandial insulin response may be an important satiety signal, and that central nervous system insulin resistance in overweight might explain the blunted effect on appetite.

The original Scrimshaw, Taylor and Gordon conceptual framework for the interaction of nutrition and infection has well served the scientific community for almost half a century. At its core is the notion of synergistic (mutually reinforcing) and antagonistic (mutually nullifying) influences of the malnourished state on infectious conditions and vice versa. Research on a series of advancing fronts, however, has allowed the incorporation of both relevant public health issues (parasitosis, emerging infectious diseases, obesity and overweight, etc.) and advancing science (molecular immunology, oxidation biology, multiple micronutrient deficiencies, etc.). The present review is an interpretative update on close to 50 years of demographic and epidemiological evolution in the field of human nutrition and the implications for the interaction in the context of microbiological and immunological developments on the infectious side of the dialectic.