Nutrition Research Reviews

Published by Cambridge University Press (CUP)
Online ISSN: 1475-2700
Print ISSN: 0954-4224
Flow of the systematic review procedure. WC, waist circumference; WHtR, waist-to-height ratio. 
Summary of the results of all cross-sectional studies in adults, analysing data with OR, by outcome* 
This systematic review collated seventy-eight studies exploring waist-to-height ratio (WHtR) and waist circumference (WC) or BMI as predictors of diabetes and CVD, published in English between 1950 and 2008. Twenty-two prospective analyses showed that WHtR and WC were significant predictors of these cardiometabolic outcomes more often than BMI, with similar OR, sometimes being significant predictors after adjustment for BMI. Observations from cross-sectional analyses, forty-four in adults, thirteen in children, supported these predictions. Receiver operator characteristic (ROC) analysis revealed mean area under ROC (AUROC) values of 0·704, 0·693 and 0·671 for WHtR, WC and BMI, respectively. Mean boundary values for WHtR, covering all cardiometabolic outcomes, from studies in fourteen different countries and including Caucasian, Asian and Central American subjects, were 0·50 for men and 0·50 for women. WHtR and WC are therefore similar predictors of diabetes and CVD, both being stronger than, and independent of, BMI. To make firmer statistical comparison, a meta-analysis is required. The AUROC analyses indicate that WHtR may be a more useful global clinical screening tool than WC, with a weighted mean boundary value of 0·5, supporting the simple public health message 'keep your waist circumference to less than half your height'.
The nutrient intakes of mammalian herbivores depend on the amount and the nutrient content of the plant species and plant parts which they eat. We review the merits of oesophageal-fistulated (OF) animals, microhistological procedures, stable C-isotope discrimination and plant cuticular-wax markers as methods for estimating diet composition and intake in both ruminant and non-ruminant herbivores. We also briefly discuss methods based on grazing behaviour measurements or on H2O or Na turnover, and methods for estimating supplement or soil intake. Estimates of intake in ruminants are often based on separate measurements of faecal output and herbage digestibility. We review this approach and emphasize that, under some circumstances, the applicability of in vitro digestibility estimates based on OF extrusa is questionable. We discuss how plant-wax marker patterns can be used to check whether OF and test animals are consuming similar diets, but also emphasize that a major advantage of the use of plant-wax markers is that this approach may obviate altogether the need for OF animals. Estimates of total herbage intake can be partitioned into the intakes coming from different plant species and/or parts, provided diet composition can be measured. Diet composition estimates based on C-isotope discrimination have the major disadvantage that they cannot be taken to species level. By contrast, microhistological methods can identify many plant species in extrusa, digesta or faeces, but often a large proportion of plant fragments remains unidentifiable. Plant-wax hydrocarbons show great promise as markers for estimating diet composition and intake. However, we suggest that to be applicable in complex plant communities there is a need with this method either to recruit a wider range of wax markers (e.g. alcohols, sterols, fatty acids) or to use it in combination with other methods. We suggest that, in turn, this generates an urgent need for research on statistical aspects of the combined use of markers or methods, in relation to the error structures of the data or methods being combined and the standard errors of the resultant estimates of diet composition and intake. We conclude by discussing the extension of intake and/or diet composition measurements to the measurement of nutrient transactions within the gut, particularly in relation to the supply of absorbable nutrients.
Prebiotics are non-digestible (by the host) food ingredients that have a beneficial effect through their selective metabolism in the intestinal tract. Key to this is the specificity of microbial changes. The present paper reviews the concept in terms of three criteria: (a) resistance to gastric acidity, hydrolysis by mammalian enzymes and gastrointestinal absorption; (b) fermentation by intestinal microflora; (c) selective stimulation of the growth and/or activity of intestinal bacteria associated with health and wellbeing. The conclusion is that prebiotics that currently fulfil these three criteria are fructo-oligosaccharides, galacto-oligosaccharides and lactulose, although promise does exist with several other dietary carbohydrates. Given the range of food vehicles that may be fortified by prebiotics, their ability to confer positive microflora changes and the health aspects that may accrue, it is important that robust technologies to assay functionality are used. This would include a molecular-based approach to determine flora changes. The future use of prebiotics may allow species-level changes in the microbiota, an extrapolation into genera other than the bifidobacteria and lactobacilli, and allow preferential use in disease-prone areas of the body.
Weight losses induced by several hypoenergetic diets, following two energy-restricted approaches with different fat or carbohydrate content and similar energy coming from proteins. (a) From McManus et al. (2001); (b) from Petersen et al. (2006).  
Weight losses induced by diets with very different fat content (high v. low) when prescribed ad libitum or under an energy-restriction pattern. (a) From Volek et al. (2004); (b) from Brehm et al. (2003).  
Weight losses induced by low-to moderate-fat-containing diets with different MUFA or long-chain triacylglycerol (LCT) or medium-chain triacylglycerol (MCT) content, and prescribed following energy-restricted or ad libitum approaches. (a) From Pelkman et al. (2004); (b) from Kasai et al. (2003).
Weight losses induced by ad libitum diets with different type of carbohydrate or fibre content and low-to-moderate fat amounts. (a) From Saris et al. (2000); (b) from Hays et al. (2004).  
Weight losses induced by high-protein diets (.20 % energy) as compared with other dietary interventions based on energy-restricted or ad libitum strategies. (a) From Skov et al. (1999); (b) from Samaha et al. (2003).  
Obesity is a chronic disorder caused by an imbalance of the energy metabolism with high associated burdens. Therefore, huge efforts are being currently devoted in studying new types of hypoenergetic diets and their composition, in order to characterise more specific, long-lasting and safe slimming protocols. A number of investigations are trying to determine the specific influence of the macronutrient distribution in energy-restricted diets on the management of excessive body weight. In this context, very-low-energy diets supplying between 1670 and 3350 kJ (400 and 800 kcal)/d have been beneficial in short-term treatments causing a weight loss of 300-500 g/d. Such strategies place more emphasis on energy restriction than on the macronutrient composition of the diet prescription. Weight loss produced by either low-carbohydrate or low-fat moderately energy-restricted diets ranges from 0.5 to 1.0 kg/week, while diets with high or moderately high protein content have also been applied in weight-reducing programmes by inducing losses of 0.2-0.4 kg/week. Other factors that determine weight loss by dieting are sex, age, initial body weight, race, genetics, regional fat deposition, etc, which must be taken into account to explain the variability in the outcomes of different low-energy diets. Therefore, more research is needed about the impact of diets with different fuel substrates and foods on the characteristics of the weight-loss process.
Food insecurity is one of the most important social issues faced today, with 840 million individuals enduring chronic hunger and three billion individuals suffering from nutrient deficiencies. Most of these individuals are poverty stricken and live in developing countries. Strategies to address food insecurity must aim to increase agricultural productivity in the developing world in order to tackle poverty, and must provide long-term improvements in crop yields to keep up with demand as the world's population grows. Genetically enhanced plants provide one route to sustainable higher yields, either by increasing the intrinsic yield capability of crop plants or by protecting them from biotic and abiotic constraints. The present paper discusses a range of transgenic approaches that could increase agricultural productivity if applied on a large scale, including the introduction of genes that confer resistance to pests and diseases, or tolerance of harsh environments, and genes that help to lift the intrinsic yield capacity by increasing metabolic flux towards storage carbohydrates, proteins and oils. The paper also explores how the nutritional value of plants can be improved by genetic engineering. Transgenic plants, as a component of integrated strategies to relieve poverty and deliver sustainable agriculture to subsistence farmers in developing countries, could have a significant impact on food security now and in the future.
Diet, nutritional status and lifestyle practices are significant determinants of the risk of certain cancers. In 1997 The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) developed a series of evidence-based recommendations to help reduce the population and individual risk of cancer. However, guidance for evaluating concordance or compliance with these recommendations is limited. To illustrate the challenges in evaluation, four publications were reviewed that explored the task of creating operative criteria from which to assess concordance with the tenets of the WCRF/AICR recommendations. Three documents dealt with secondary analysis, whereas one was a prospective inquiry, with procedures and instruments designed to obtain responses to WCRF/AICR cancer-prevention specification. One considered only population-goal criteria, and two dealt implicitly or explicitly with criteria at both population and individual levels. The assessment approaches used by the authors were compared with alternative semantic and conceptual interpretations of the WCRF/AICR population goals and individual guidelines. Attempts to develop operative criteria for assessment of concordance (reflecting either a more superficial or more in-depth parsing of recommendations) have been inconsistent. The results indicate that the language of the WCRF/AICR leaves a certain degree of semantic ambiguity for evaluation purposes. Future design of prospective studies for analyses of behaviours and relevant exposures (including those reported in the 2007 WCRF/AICR report) should carefully consider evaluation criteria and fully document detailed methodology.
The present review provides an investigation into the food choice decisions made by individuals in relation to fruit and vegetable consumption. A comprehensive body of evidence now exists concerning the protective effect of fruit and vegetables against a number of diseases, particularly cardiovascular disease and certain forms of cancer. Current UK recommendations are to increase intakes of fruit and vegetables to 400 g/person per d. In the main body of the review the factors that affect food choice decisions of adults in relation to fruit and vegetable consumption are studied, following a suggested framework of food choice. Factors covered include sensory appeal, familiarity and habit, social interactions, cost, availability, time constraints, personal ideology, media and advertising and health. The content of the review shows just how complex the food choice process can be. Health promotion techniques can be better targeted towards certain groups of individuals, all holding similar sets of values, when making food choice decisions. Food choice, in relation to fruit and vegetable intake, needs to be studied in more depth, in order to provide effective nutrition education programmes, in particular the sets of priorities that different sub-groups of the population consider when making food choice decisions.
For at least 40-50,000 years, plants played an important but supplementary role in the animal-dominated diet of Australian Aboriginal (AA) hunter-gatherers. New knowledge of the nutrient composition and the special physiological effects of their foods provides another perspective in the current debate on the composition of the 'prudent' diet and the diet on which humans evolved. In the present paper we have calculated the average nutrient composition of over 800 Aboriginal plant foods (in total and by food group) and highlighted the differences between these and modern cultivated foods. The data enable us to calculate the absolute contribution of plant foods to total food and nutrient intake of traditional living AA. If plants provided 20-40% of the energy in the diet (the most likely range), then plants would have contributed 22-44 g protein, 18-36 g fat, 101-202 g carbohydrate, 40-80 g fibre and 90-180 mg vitamin C in a 12500 kJ (3000 kcal) diet. Since all the carbohydrate came from plant foods, the traditional AA diet would have been relatively low in carbohydrate (especially starch) but high in dietary fibre in comparison with current recommendations. Over half the carbohydrate could have been in the form of sugars derived from fruit and honey. The low glycaemic index of their carbohydrate foods, however, would generate a relatively low demand for insulin secretion and this characteristic may have protected AA from a genetic predisposition to insulin resistance and its consequences (non-insulin-dependent diabetes mellitus, coronary heart disease, obesity). The dietary pattern and active lifestyle of recent hunter-gatherers such as AA may be a reference standard for modem human nutrition and a model for defence against diseases of affluence.
Examples of bioactive peptides derived from bovine milk proteins 
Digestion and absorption of protein by the mammalian small-intestinal enterocyte (from Brandsch & Brandsch (16) ; reproduced with the permission of Wageningen Academic Publishers). At the apical membrane: 1, peptidases; 2, amino acid transport systems, such as the B 0 system; 3, peptide transporter; 4, cytosolic peptidases. At the basolateral membrane: 5, amino acid transport systems; 6, unknown peptide transport system. 
Exorphins: peptides derived from milk having opioid properties 
For over 100 years it was believed that dietary protein must be completely hydrolysed before its constituent amino acids could be absorbed via specific amino acid transport systems. It is now known that the uptake of di- and tripeptides into the enterocyte is considerable, being transported across the intestinal endothelium by the PepT1 H+/peptide co-transporter. There is also evidence that some di- and tripeptides may survive cytosolic hydrolysis and be transported intact across the basolateral membrane. However, other than antigen sampling, the transport of larger intact macromolecules across the intestinal endothelium of the healthy adult human remains a controversial issue as there is little unequivocal in vivo evidence to support this postulation. The aim of the present review was to critically evaluate the scientific evidence that peptides/proteins are absorbed by healthy intestinal epithelia and pass intact into the hepatic portal system. The question of the absorption of oliogopeptides is paramount to the emerging science of food-derived bioactive peptides, their mode of action and physiological effects. Overall, we conclude that there is little unequivocal evidence that dietary bioactive peptides, other than di- and tripeptides, can cross the gut wall intact and enter the hepatic portal system in physiologically relevant concentrations.
Although stearic acid is a saturated fatty acid, its influence on plasma cholesterol acid other health variables is neutral; possibly owing in part to poor absorption. Reduced absorption of stearic acid from particular triacylglycerols, cocoa butter and novel fats formulated with short- and long-chain acid triacylglycerol molecules (Salatrims) has been attributed to high intakes. However, the circumstances and causes of poor stearic acid digestion from triacylglycerols are unclear; published data were therefore collected and analysed, with emphasis on human studies. Of twenty-eight studies conducted in adults, most are in men (>90%). The assertion that reduced absorption is due to a high intake of stearoyl groups is not supported: dietary intakes of stearoyl of 0.05-0.65 g stearic acid equivalent/kg body weight (cf typical intake of 0.2 g stearic acid equivalent/kg body weight in the Western diet) indicate that the 'true' digestibility of stearoyl is 0.98 (SE 0.01) g/g, with apparent digestibility less than this value at low intakes owing to endogenous stearic acid excretion and to inter-publication variation of unidentified cause. The neutral health impact of stearic acid must be due to factors other than availability. Exceptions include cocoa butter, Salatrims and tristearin, for which digestibility is an additional factor. The efficiency with which human subjects digest stearoyl from cocoa butter still remains uncertain, while the digestion of total long-chain fat from this source is 0.89-0.95 g/g, high in comparison with 0.33 g/g for Salatrim 23CA and 0.15 g/g for tristearin in their prepared states. Salatrims contain the highest proportion of long-chain fatty acids that are stearic acid-rich other than tristearin, which is the main component of fully-hydrogenated soyabean and rapeseed oil. Analysis shows that apparent digestibility of stearic acid is associated with stearoyl density within the triacylglycerol molecule and that, in Salatrims, the occurrence of short-chain fatty acids in place of long-chain fatty acids increases this density. Soap formation appears not to be a major factor in the reduced digestion of stearic acid from tristearin under regular dietary circumstances, but both microcrystallinity and reduced digestibility of tri-, di- and monostearoylglycerols appears to be important. Solubilisation of high-melting-point tristearin in low-melting-point oils improves the digestibility of its stearic acid, particularly when emulsified or liquidized at above melting point. However, without such artificial aids, the digestive tracts of the rat, dog and man have a low capacity for emulsifying and digesting stearic acid from tristearin. Reduced digestibility of stearic acid from Salatrim 23CA also appears to be attributable to reduced digestibility of di- and monostearoylglycerols and is particularly due to remnants with the 1- or 3-stearoylglycerol intact after initial hydrolytic cleavage. Short-chain organic acid in Salatrim 23CA, which is readily hydrolysed, leaves such remnants. Unlike tristearin, Salatrim 23CA melts at body temperature and mixing it with low-melting-point oils is not expected to cause further disruption of microcrystalline structures to aid digestibility of its stearoyl groups. The low digestibility of stearoyl in Salatrim 23CA, together with the occurrence of short-chain organic acids in this product, account for its relatively low nutritional energy value (about 20 kJ (5 kcal)/g) compared with traditional fats (37 kJ (9 kcal)/g) and low fat value (<20:37 kJ/kJ; <5:9 kcal/kcal) relative to traditional fats. In part these differences are because of minor effects of Salatrim 23CA on the excretion of other fat and protein, due to the bulking properties of this poorly-digestible fat.
Common anthocyanidin structures.
Structures of cyanidin (a), quercetin (b) and catechin (c). 
Potential mechanisms of anthocyanin (Anth) absorption. SGLT, sodium-glucose co-transporter; Anth-3-gly, anthocyanin 3-glycoside; CBG, cytosolic b-glucosidase; LPH, lactate phlorizin hydrolase; UDP-GT, UDP-glucuronosyltransferase; Anth-gluc, anthocyanin glucuronide; COMT, catechol-O-methyltransferase; SULT, sulfotransferase. (Adapted from Gee et al. (2000) and Day et al. (2000).)
Potential route for anthocyanin absorption, metabolism and elimination. 
Interest in the health-promoting properties of berry anthocyanins is intensifying; however, findings are primarily based on in vitro characteristics, leaving mechanisms associated with absorption, metabolism and pharmacokinetics largely unexplored. The present review integrates the available anthocyanin literature with that of similar flavonoids or polyphenols in order to form hypotheses regarding absorption, metabolism and clearance in humans. Of the limited available literature regarding the absorption and clearance kinetics of anthocyanins, maximum plasma concentrations are reported anywhere between 1.4 and 592 nmol/l and occur at 0.5-4 h post-consumption (doses; 68-1300 mg). Average urinary excretion is reported between 0.03 and 4 % of the ingested dose, having elimination half-lives of 1.5-3 h. In addition, much is unknown regarding the metabolism of anthocyanins. The most commonly cited conjugation reactions involved in the metabolism of other flavonoids include glucuronidation, methylation and sulfation. It is reasonable to suspect that anthocyanins are metabolised in much the same manner; however, until recently, there was little evidence to suggest that anthocyanins were metabolised to any significant extent. New evidence now suggests that anthocyanins are absorbed and transported in human serum and urine primarily as metabolites, with recent studies documenting as much as 68-80 % of anthocyanins as metabolised derivatives in human urine. Further research is required to resolve mechanisms associated with the absorption, metabolism and clearance of anthocyanins in order to establish their true biological activities and health effects. The presented evidence will hopefully focus future research, refining study design and propagating a more complete understanding of anthocyanins' biological significance in humans.
Effect of calcium on the absorption of non-haem-iron in single-meal studies 
Effect of calcium on the absorption of supplementary iron (data from Cook et al. 1991b) 
Effect of calcium on dietary iron absorption: multiple-meal studies 
The experimental and epidemiological evidence demonstrating that Ca inhibits Fe absorption was reviewed, with the objectives of estimating the potential impact of variations in Ca intake on dietary Fe bioavailability and of providing some guidelines for predicting the effects on Fe status of recent recommendations for higher dietary Ca intake. In animal models Ca salts reduced both haem- and non-haem-Fe absorption, the effect being dependent on the amount of Ca administered rather than the Ca:Fe molar ratio; dairy products had a variable effect; factors other than Ca may have been important. In single-meal human absorption studies, both haem- and non-haem-Fe absorption was inhibited by Ca supplements and by dairy products, the effect depending on the simultaneous presence of Ca and Fe in the lumen of the upper small intestine and also occurring when Ca and Fe were given in the fasting state. The quantitative effect, although dose dependent, was modified by the form in which Ca was administered and by other dietary constituents (such as phosphate, phytate and ascorbic acid) known to affect Fe bioavailability. The mechanism by which Ca influences Fe absorption has not been elucidated. The effects of factors that modulate Fe bioavailability are known to be exaggerated in single-meal studies, and measurements based on several meals are more likely to reflect the true nutritional impact. The results of most multiple-meal human studies suggest that Ca supplementation will have only a small effect on Fe absorption unless habitual Ca consumption is very low. Outcome analyses showed that Ca supplements had no effect on Fe status in infants fed Fe-fortified formula, lactating women, adolescent girls and adult men and women. However it should be noted that the subjects studied had adequate intakes of bioavailable Fe and, except in one study, had relatively high habitual Ca intakes. Although cross-sectional analyses in Europe have shown a significant inverse correlation between Ca intake (derived primarily from dairy foods) and Fe stores, the quantitative effect was relatively small. The general conclusion is that dietary Ca supplements are unlikely to have a biologically significant impact on Fe balance in Western societies unless Ca consumption is habitually very low; however, increased consumption of dairy products may have a small negative effect that could be functionally important in pregnancy if Fe supplements are not taken. It is uncertain whether the inverse relationship between consumption of dairy products and Fe status is due entirely to increased Ca intake; substitution of milk proteins for meat may also have negative effects on Fe balance.
Ruminal mechanism for the interaction of Cu, Mo, S and Fe and routes of absorption for the interaction products. MoS n is used diagrammatically to represent the thiomolybdate series (MoS n O 22 ð42nÞ , where n is 1 to 4). 
The rumen is the site of significant interactions between Cu, S and Mo. It also shows reactions between Cu, S and Fe. The interaction between Mo and S results in the formation of thiomolybdates, which in the absence of adequate quantities of rumen Cu are absorbed into the animal and bind to Cu in biological compounds. This is the cause of thiomolybdate toxicity, often misleadingly called Cu deficiency. The effects of thiomolybdates being absorbed into the animal are considered, especially how thiomolybdates bind to Cu-containing compounds such as enzymes, decreasing their activity without removing the active Cu component. The sources of Cu, Mo, Fe and S are examined, including the impacts of water and soil on the animal's intake. Within the present review we have been able to provide evidence that: all classes of thiomolybdates are formed in the rumen; in the absence of available Cu all thiomolybdates can be absorbed into the animal rapidly though the rumen wall or via the small intestine; thiomolybdates bind to Cu in biological compounds and are able to cause problems; effects of thiomolybdate are reversible in vivo and in vitro on cessation of thiomolybdate challenge; the tetra-thiomolybdate form is the most potent Cu binder with decreased potency with decreasing S in the compound. Fe will exacerbate a thiomolybdate problem but will not directly cause it.
Baseline gene expression in rodent strains 
Functional enrichment clustering of genes associated with alcohol abuse in the human prefrontal cortex (PFC)* 
Functional enrichment clustering of genes associated with alcohol abuse in the human nucleus accumbens (NAC)* 
Alcohol intake at levels posing an acute heath risk is common amongst teenagers. Alcohol abuse is the second most common mental disorder worldwide. The incidence of smoking is decreasing in the Western world but increasing in developing countries and is the leading cause of preventable death worldwide. Considering the longstanding history of alcohol and tobacco consumption in human societies, it might be surprising that the molecular mechanisms underlying alcohol and smoking dependence are still incompletely understood. Effective treatments against the risk of relapse are lacking. Drugs of abuse exert their effect manipulating the dopaminergic mesocorticolimbic system. In this brain region, alcohol has many potential targets including membranes and several ion channels, while other drugs, for example nicotine, act via specific receptors or binding proteins. Repeated consumption of drugs of abuse mediates adaptive changes within this region, resulting in addiction. The high incidence of alcohol and nicotine co-abuse complicates analysis of the molecular basis of the disease. Gene expression profiling is a useful approach to explore novel drug targets in the brain. Several groups have utilised this technology to reveal drug-sensitive pathways in the mesocorticolimbic system of animal models and in human subjects. These studies are the focus of the present review.
Accelerator mass spectrometry (AMS) is an ultrasensitive analytical technique for measuring rare nuclides such as 14C, 26Al and 41Ca. The low detection limit and wide dynamic range of AMS allow long-term and highly sensitive tracer studies in nutrition that cannot be performed with other methods. The present paper is intended to provide a description of AMS to the interested nutritionist and present proven applications. AMS is compared to liquid scintillation counting and stable isotope MS. A description of common AMS methodology is presented that consists of determining the dose, preparing the sample, diluting the sample (if necessary), and measuring the sample. Applications include Ca metabolism, Al uptake from the environment, dietary intake of carcinogens, fat meta-bolism and folate metabolism. Throughout this discussion the experimental advantages (small doses that pose no health risk, extremely long experimental lifetime, small sample sizes and high sensitivity) made possible by the unique analytical capabilities of AMS are emphasized. The future of AMS is discussed. As the number of AMS centres, instruments, and studies increases, the number of nutritional applications that employ AMS will continue to grow. The coupling of AMS with other analytical techniques (e.g. high performance liquid chromatography) will be developed as access to AMS improves.
It is predicted that non-communicable diseases will account for over 73 % of global mortality in 2020. Given that the majority of these deaths occur in developed countries such as the UK, and that up to 80 % of chronic disease could be prevented through improvements in diet and lifestyle, it is imperative that dietary guidelines and disease prevention strategies are reviewed in order to improve their efficacy. Since the completion of the human genome project our understanding of complex interactions between environmental factors such as diet and genes has progressed considerably, as has the potential to individualise diets using dietary, phenotypic and genotypic data. Thus, there is an ambition for dietary interventions to move away from population-based guidance towards 'personalised nutrition'. The present paper reviews current evidence for the public acceptance of genetic testing and personalised nutrition in disease prevention. Health and clear consumer benefits have been identified as key motivators in the uptake of genetic testing, with individuals reporting personal experience of disease, such as those with specific symptoms, being more willing to undergo genetic testing for the purpose of personalised nutrition. This greater perceived susceptibility to disease may also improve motivation to change behaviour which is a key barrier in the success of any nutrition intervention. Several consumer concerns have been identified in the literature which should be addressed before the introduction of a nutrigenomic-based personalised nutrition service. Future research should focus on the efficacy and implementation of nutrigenomic-based personalised nutrition.
The biofortification of staple crops with vitamins is an attractive strategy to increase the nutritional quality of human food, particularly in areas where the population subsists on a cereal-based diet. Unlike other approaches, biofortification is sustainable and does not require anything more than a standard food-distribution infrastructure. The health-promoting effects of vitamins depend on overall intake and bioavailability, the latter influenced by food processing, absorption efficiency and the utilisation or retention of the vitamin in the body. The bioavailability of vitamins in nutritionally enriched foods should ideally be adjusted to achieve the dietary reference intake in a reasonable portion. Current vitamin biofortification programmes focus on the fat-soluble vitamins A and E, and the water-soluble vitamins C and B9 (folate), but the control of dosage and bioavailability has been largely overlooked. In the present review, we discuss the vitamin content of nutritionally enhanced foods developed by conventional breeding and genetic engineering, focusing on dosage and bioavailability. Although the biofortification of staple crops could potentially address micronutrient deficiency on a global scale, further research is required to develop effective strategies that match the bioavailability of vitamins to the requirements of the human diet.
Sulfur amino acid metabolism. AMT, aminotransferase; BHMT, betaine-homocysteine methyltransferase; CBS, cystathionine b -synthase; CDO, cysteine dioxygenase; CGL, cystathionine g -lyase; CSD, cysteine sulfinate decarboxylase; DHFR, dihydrofolate reductase; DMG, dimethyl- glycine; dTMP, thymidylate; dUMP, deoxyuridylate; MAT, methionine adenosyltransferase; MS, methionine synthase; MT, methyl transferases; MTHFR, methylenetetrahydrofolate reductase, SAH, S -adenosylhomocysteine; SAHH, S -adenosylhomocysteine hydrolase; SAM, S -adenosylmethionine; SHMT, serine hydroxymethyltransferase; TS, thymidylate synthetase. 
Stable isotopic tracer model used by Storch et al. (14) . This model is based on the intravenous infusion of a methionine isotopomer [1- 13 C; methyl- 2 H 3 ]methionine [M þ 4]. The [ 2 H 3 ]methyl group is lost during transmethylation from S -adenosylmethionine (SAM) to S adenosylhomocysteine (SAH), whereas the [ 13 C]carbon group is transferred to [1- 13 C]homocysteine [M þ 1], [1- 13 C]cystathionine [M þ 1] and finally, oxidised to 13 CO 2 via a -ketobutyrate in the tricarboxylic acid cycle. 
Methionine salvage pathway from 5 0 -methylthioadenosine 
The gastrointestinal tract (GIT) is a metabolically significant site of sulfur amino acid (SAA) metabolism in the body and metabolises about 20 % of the dietary methionine intake which is mainly transmethylated to homocysteine and trans-sulfurated to cysteine. The GIT accounts for about 25 % of the whole-body transmethylation and trans-sulfuration. In addition, in vivo studies in young pigs indicate that the GIT is a site of net homocysteine release and thus may contribute to the homocysteinaemia. The gut also utilises 25 % of the dietary cysteine intake and the cysteine uptake by the gut represents about 65 % of the splanchnic first-pass uptake. Moreover, we recently showed that SAA deficiency significantly suppresses intestinal mucosal growth and reduces intestinal epithelial cell proliferation, and increases intestinal oxidant stress in piglets. These recent findings indicate that intestinal metabolism of dietary methionine and cysteine is nutritionally important for intestinal mucosal growth. Besides their role in protein synthesis, methionine and cysteine are precursors of important molecules. S-adenosylmethionine, a metabolite of methionine, is the principal biological methyl donor in mammalian cells and a precursor for polyamine synthesis. Cysteine is the rate-limiting amino acid for glutathione synthesis, the major cellular antioxidant in mammals. Further studies are warranted to establish how SAA metabolism regulates gut growth and intestinal function, and contributes to the development of gastrointestinal diseases. The present review discusses the evidence of SAA metabolism in the GIT and its functional and nutritional importance in gut function and diseases.
The present review summarises current knowledge and recent findings on the modulation of appetite by dietary protein, via both peripheral and central mechanisms. Of the three macronutrients, proteins are recognised as the strongest inhibitor of food intake. The well-recognised poor palatability of proteins is not the principal mechanism explaining the decrease in high-protein (HP) diet intake. Consumption of a HP diet does not induce conditioned food aversion, but rather experience-enhanced satiety. Amino acid consumption is detected by multiple and redundant mechanisms originating from visceral (during digestion) and metabolic (inter-prandial period) sources, recorded both directly and indirectly (mainly vagus-mediated) by the central nervous system (CNS). Peripherally, the satiating effect of dietary proteins appears to be mediated by anorexigenic gut peptides, principally cholecystokinin, glucagon-like peptide-1 and peptide YY. In the CNS, HP diets trigger the activation of noradrenergic and adrenergic neurons in the nucleus of the solitary tract and melanocortin neurons in the arcuate nucleus. Additionally, there is evidence that circulating leucine levels may modulate food intake. Leucine is associated with neural mechanisms involving mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), energy sensors active in the control of energy intake, at least in the arcuate nucleus of the hypothalamus. In addition, HP diets inhibit the activation of opioid and GABAergic neurons in the nucleus accumbens, and thus inhibit food intake by reducing the hedonic response to food, presumably because of their low palatability. Future studies should concentrate on studying the adaptation of different neural circuits following the ingestion of protein diets.
The way in which the composition of the diet may affect appetite, food intake and body weight is now receiving considerable attention in a bid to halt the global year-on-year rise in obesity prevalence. Epidemiological evidence suggests that populations who follow a fibre-rich, traditional diet are likely to have a lower body weight and improved metabolic parameters than their Western-diet counterparts. The colonic effects of fibre, and more specifically the SCFA that the fermentation process produces, may play a role in maintaining energy homeostasis via their action on the G-coupled protein receptor free fatty acid receptor 2 (FFA2; formerly GPR43). In the present review, we summarise the evidence for and against the role of FFA2 in energy homeostasis circuits and the possible ways that these could be exploited therapeutically. We also propose that the decline in fibre content of the diet since the Industrial Revolution, particularly fermentable fractions, may have resulted in the FFA2-mediated circuits being under-utilised and hence play a role in the current obesity epidemic.
Desaturation and elongation of n-3 long-chain PUFA.
Forest plot for the meta-analysis of all randomised controlled trials investigating the effects of n-3 long-chain PUFA on depressed mood up to September 2007 (taken from Appleton et al. (141) ).  
Selected biochemical evidence suggests a potential role for n-3 long-chain PUFA (n-3PUFA) in the regulation of mood and behaviour. The present paper reviews the relevant evidence, to date, from epidemiological studies, clinical studies and intervention trials. Most evidence is available investigating a role for n-3PUFA in depression, depressive illness and suicidal behaviour, but work is also available on anxiety and anxiety-related disorders, fatigue and fatigue-related disorders, aggression, hostility and anti-social behaviour, inattention, impulsivity and attention deficit hyperactivity disorder and schizophrenic disorders. For all these aspects of mood and behaviour, the evidence available is currently limited and highly inconsistent, both in terms of study methodology and study findings. There is a clear need for further work in this area.
The present review comes from the authors of the recent Scientific Advisory Committee on Nutrition (SACN) review Update on Trans Fatty Acids and Health, and focuses on assessing the strength of the evidence for a link between trans-fatty acid (trans-FA) intake and cancer. It evaluates a range of human ecological, case-control and prospective studies with trans-FA exposure assessed using either dietary assessment methods or trans-FA levels in tissues. Relevant animal studies are also presented in order to elucidate potential mechanisms. It concludes that there is weak and inconsistent evidence for a relationship between trans-FA and breast or colorectal cancer. Evidence for an association between trans-FA and prostate cancer is limited, but a recent large case-control study has shown a strong interaction between risk and trans-FA intake for the RNASEL QQ/RQ genotype that is present in about 35 % of the population. This potential association requires further investigation. The single study on non-Hodgkin's lymphoma reported a strong positive association, but only used a single assessment of dietary trans-FA made at the start of the study in 1980, and the significant changes in trans-FA intakes between then and the end of follow-up in 1994 limit the reliability of this observation. There is insufficient evidence to allow any differentiation between the effects of trans-FA from animal or vegetable origin on cancer risk.
Organic acids and their salts appear to be potential alternatives to prophylactic in-feed antibiotics and growth promoters in order to improve the performance of weaned piglets, fattening pigs and reproductive sows, although their growth-promoting effects are generally less than that of antibiotics. Based on an analysis of published data, the growth-promoting effect of formates, fumarates and citrates did not differ in weaned piglets. In fattening pigs, formates were the most effective followed by fumarates, whereas propionates did not improve growth performance. These acids improved the feedgain ratio of both weaned piglets and fattening pigs. In weaned piglets, the growth-promoting effects of dietary organic acids appear to depend greatly on their influence on feed intake. In sows, organic acids may have anti-agalactia properties. Successful application of organic acids in the diets for pigs requires an understanding of their modes of action. It is generally considered that dietary organic acids or their salts lower gastric pH, resulting in increased activity of proteolytic enzymes and gastric retention time, and thus improved protein digestion. Reduced gastric pH and increased retention time have been difficult to demonstrate, whereas improved apparent ileal digestibilities of protein and amino acids have been observed with growing pigs, but not in weaned piglets. Organic acids may influence mucosal morphology, as well as stimulate pancreatic secretions, and they also serve as substrates in intermediary metabolism. These may further contribute to improved digestion, absorption and retention of many dietary nutrients. Organic acid supplementation reduces dietary buffering capacity, which is expected to slow down the proliferation and|or colonization of undesirable microbes, e.g. Escherichia coli, in the gastro-ileal region. However, reduced scouring has been observed in only a few studies. As performance responses to dietary organic acids in pigs often varies, more specific studies are necessary to elucidate an explanation.
In the search for alternatives to banned in-feed antibiotics, a concept was developed based on studies with medium-chain fatty acid-containing triacylglycerols (MCTAG) and selected lipases for in situ generation of diacylglycerols, monoacylglycerols and medium-chain fatty acids (MCFA) in the stomach and proximal gut of piglets. MCFA are known to have strong antibacterial properties but can hardly be used as such because of their repellent odour and taste. Those problems could be overcome by the generation of MCFA in situ. The concept was tested in vitro and validated in vivo with gastric-cannulated piglets and under field conditions, including effects on zootechnical performance, with classical antibacterial growth promoters or organic acids acting as positive controls. Furthermore, the metabolic and dietary constraints on the nutritional and nutritive use of MCTAG and/or MCFA (for example, the effects on digestive physiology, gut flora, feed intake, performance, carcass composition) are reviewed. The role of natural preduodenal lipase activity, the presence of endogenous plant lipase activity in raw materials and the feasibility for exogenous lipase addition to the feed are discussed, in order to optimize the concept. The present review illustrates the similarity of the action of MCFA and commonly used antimicrobials on the flora (total flora, Gram-positive flora, Gram-negative flora, potential pathogens) and epithelial morphology and histology in the foregut. These observations are believed to be the basis for obtaining optimal growth performances. In addition, these naturally occurring antimicrobial agents have little or no human or animal toxicity and induce no problems of residues and cross-resistance induction. They are proposed as a valuable alternative to in-feed antibiotics, used for growth promotion, and even for the preventive and curative treatment of gastrointestinal diseases.
Chemical composition of various fatty acids.  
Estimated daily intakes
Desaturation and elongation of n-3 and n-6 fatty acids.  
A considerable literature has been published on the health benefits of fish, oil-rich fish and fish oils and their constituent long-chain (LC) n-3 PUFA. Evidence from epidemiological studies highlights the cardioprotective attributes of diets rich in fish, especially oil-rich fish. Data from intervention trials are consistent in suggesting that LC n-3 PUFA lower the risk of CVD, probably by the multiple mechanisms of lowering serum triacylglycerols, improving the LDL:HDL ratio, anti-arrhythmic effects on heart muscle, improved plaque stability, anti-thrombotic effects and reduced endothelial activation. Research indicates LC n-3 PUFA provision has an impact during development, and there is preliminary evidence that docosahexaenoic acid supplementation during pregnancy could optimise brain and retina development in the infant. LC n-3 PUFA are also postulated to ameliorate behavioural and mental health disturbances such as depression, schizophrenia, dementia and attention deficit hyperactivity disorder. However, despite some positive evidence in each of these areas, use of LC n-3 PUFA in these conditions remains at the experimental stage. In the case of immune function, there is little doubt that LC n-3 PUFA have a positive effect. Although intervention trials in rheumatoid arthritis show strong evidence of benefit, evidence for efficacy in other inflammatory conditions, including Crohn's disease, ulcerative colitis, psoriasis, lupus, multiple sclerosis, cystic fibrosis and asthma, is inconsistent or inadequate. More promising evidence in some conditions may come from studies which attempt to modify the fetal environment using LC n-3 PUFA supplementation during pregnancy.
Experimental studies of enhanced cytotoxicity of chemotherapy drugs by n-3 fatty acids 
Experimental studies of the protective effects of n-3 fatty acids to the host during chemotherapy 
n-3 Fatty acid effects on anorexia cachexia syndrome: animal and human studies 
Evidence from epidemiological studies suggests that diets rich in n-3 PUFA may be associated with reduced cancer risk. These observations have formed the rationale for exploring the mechanisms by which n-3 PUFA may be chemoprotective and have resulted in significant advances in our mechanistic understanding of n-3 PUFA action on tumour growth. Various interrelated and integrated mechanisms may be at work by which n-3 PUFA influence cancer at all stages of initiation, promotion, progression, and neoplastic transformation. More recently, experimental studies have reported enhanced tumour cell death with chemotherapy when fish oil is provided while toxic side effects to the host are reduced. Furthermore, cancer-associated wasting has been shown to be attenuated by fish oil supplementation. Clinical evidence suggests that the n-3 PUFA status of newly diagnosed cancer patients and individuals undergoing chemotherapy is low. Therefore, both the disease itself and therapeutic treatments may be contributing factors in the decline of n-3 PUFA status. Dietary supplementation to maintain and replenish n-3 PUFA status at key points in the cancer disease trajectory may provide additional health benefits and an enhanced quality of life. The present review will focus on and critically examine current research efforts related to the putative anti-cancer effects of n-3 PUFA and their suggested ability to palliate cancer-associated and treatment-associated symptoms.
Biotransformation mechanism of acrylamide. CYP2E1, cytochrome 2E1; GST, glutathione S -transferase. 
The daily intake of acrylamide of children in several European countries
Studies on acrylamide contamination in baby foods and infant formulas and estimated daily exposures of acrylamide
Contaminants are a vast subject area of food safety and quality and can be present in our food chain from raw materials to finished products. Acrylamide, an α,β-unsaturated (conjugated) reactive molecule, can be detected as a contaminant in several foodstuffs including baby foods and infant formulas. It is anticipated that children will generally have intakes that are two to three times those of adults when expressed on a body-weight basis. Though exposure to acrylamide is inevitable, it is necessary to protect infant and children from high exposure. The present review focuses on the several adverse health effects of acrylamide including mutagenicity, genotoxicity, carcinogenicity, neurotoxicity and reproductive toxicity, and the possible outcomes of childhood exposure from baby foods and infant formulas.
Chemical structures of sapogenins: triterpenoid, for example, oleanane (a); steroids, for example, spirostanol (b) and furostanol (c). 
A schematic presentation of the proposed effects of saponins on rumen microbes and fermentation. Primary effects modify the composition of rumen microbes and secondary effects modify the rumen fermentation. þ , Increase; 2, decrease; OM, organic matter; VFA, volatile fatty acids; P, propionate.
A schematic presentation of factors affecting the effects of saponins on rumen microbes. 
The growing public concerns over chemical residues in animal-derived foods and threats of antibiotic-resistant bacteria have renewed interest in exploring safer alternatives to chemical feed additives in ruminant livestock. Various bioactive phytochemicals including saponins appear to be potential 'natural' alternatives to 'chemical' additives in modulating rumen fermentation favourably and animal performance. Saponins are a diverse group of glycosides present in many families of plants. The primary effect of saponins in the rumen appears to be to inhibit the protozoa (defaunation), which might increase the efficiency of microbial protein synthesis and protein flow to the duodenum. Furthermore, saponins may decrease methane production via defaunation and/or directly by decreasing the activities (i.e. rate of methanogenesis or expression of methane-producing genes) and numbers of methanogens. Saponins may also selectively affect specific rumen bacteria and fungi, which may alter the rumen metabolism beneficially or adversely. The ammonia-adsorption and modulation of digesta passage in the rumen by saponins have also been implicated in altering rumen metabolism, but their physiological responses are likely to be negligible compared with microbiological effects. The effects of saponins on rumen fermentation have not been found to be consistent. These discrepancies appear to be related to the chemical structure and dosage of saponins, diet composition, microbial community and adaptation of microbiota to saponins. There is need for systematic research based on chemical structures of saponins, nutrient composition of diets and their effects on rumen microbial ecosystem to obtain consistent results. The present paper reviews and discusses the effects and mode of action of saponins on microbial community and fermentation in the rumen, and ruminant performance.
An overview is given of the current position of medicinal herbs in general in relation to usage, market and production, types of pharmacological activity and how they differ from conventional drugs. The increasing importance of quality and manufactured products is also discussed. A more detailed consideration of these issues is given in relation to echinacea, valerian and St John's wort as these herbs are well studied, are market leaders and have widespread community usage.
Effect of colipase presence and bile salt concentration on porcine pancreatic lipase activity. (a) Lipase activity over a pH range in the presence (B; 23·8mg/ml) and absence (A) of colipase. (b) Lipase activity over a range of bile salt (sodium taurodeoxycholate; NaTDC) concentrations at pH 7. Values are means, with standard errors represented by vertical bars. Olive oil micelles were used as a substrate using procedures modified from Vogel & Zieve (97) . 
The most widely used pharmacological therapies for obesity and weight management are based on inhibition of gastrointestinal lipases, resulting in a reduced energy yield of ingested foods by reducing dietary lipid absorption. Colipase-dependent pancreatic lipase is believed to be the major gastrointestinal enzyme involved in catalysis of lipid ester bonds. There is scant literature on the action of pancreatic lipase under the range of physiological conditions that occur within the human small intestine, and the literature that does exist is often contradictory. Due to the importance of pancreatic lipase activity to nutrition and weight management, the present review aims to assess the current body of knowledge with regards to the physiology behind the action of this unique gastrointestinal enzyme system. Existing data would suggest that pancreatic lipase activity is affected by intestinal pH, the presence of colipase and bile salts, but not by the physiological range of Ca ion concentration (as is commonly assumed). The control of secretion of pancreatic lipase and its associated factors appears to be driven by gastrointestinal luminal content, particularly the presence of acid or digested proteins and fats in the duodenal lumen. Secretion of colipase, bile acids and pancreatic lipase is driven by cholecystokinin and secretin release.
Pathway of synthesis of citrulline in intestinal mucosal mitochondria of species capable of supplying their arginine requirements de novo. The activities of the enzymes pyrroline-5-carboxylate (P-5-C) synthase and ornithine aminotransferase in the intestinal mucosa of cats are low, which precludes effective synthesis of citrulline. OAA, oxaloacetate;-KG,-ketoglutarate; CPS1, carbamoyl phosphate synthetase 1; C~P, carbamoyl phosphate. (Adapted from Wu et al. 1997.) 
General pathway of taurine synthesis in the liver from sulphur amino acids ( ). The activities of the enzymes cysteine dioxygenase and cysteinesulphinic acid decarboxylase are low in cats, which severely restricts synthesis of taurine. Cysteine is largely metabolised to pyruvate, which provides an energy substrate whereas taurine cannot be oxidised by cats.-KG,-ketoglutarate; GLU, glutamate. 
Cats have obligatory requirements for dietary nutrients that are not essential for other mammals. The present review relates these idiosyncratic nutritional requirements to activities of enzymes involved in the metabolic pathways of these nutrients. The high protein requirement of cats is a consequence of the lack of regulation of the aminotransferases of dispensable N metabolism and of the urea cycle enzymes. The dietary requirements for taurine and arginine are consequences of low activities of two enzymes in the pathways of synthesis that have a negative multiplicative effect on the rate of synthesis. Cats have obligatory dietary requirements for vitamin D and niacin which are the result of high activities of enzymes that catabolise precursors of these vitamins to other compounds. The dietary requirement for pre-formed vitamin A appears to result from deletion of enzymes required for cleavage and oxidation of carotenoids. The n-3 polyunsaturated fatty acids (PUFA) requirements have not been defined but low activities of desaturase enzymes indicate that cats may have a dietary need for pre-formed PUFA in addition to those needed by other animals to maintain normal plasma concentrations. The nutrient requirements of domestic cats support the thesis that their idiosyncratic requirements arose from evolutionary pressures arising from a rigorous diet of animal tissue. These pressures may have favoured energy conservation through deletion of redundant enzymes and modification of enzyme activities to result in metabolites more suited to the cat's metabolism. However, this retrospective viewpoint allows only recognition of association rather than cause and effect.
The value of added feed enzymes (FE) in promoting growth and efficiency of nutrient utilisation is well recognised in single-stomached animal production. However, the effects of FE on the microbiome of the gastrointestinal tract (GIT) are largely unrecognised. A critical role in host nutrition, health, performance and quality of the products produced is played by the intestinal microbiota. FE can make an impact on GIT microbial ecology by reducing undigested substrates and anti-nutritive factors and producing oligosaccharides in situ from dietary NSP with potential prebiotic effects. Investigations with molecular microbiology techniques have demonstrated FE-mediated responses on energy utilisation in broiler chickens that were associated with certain clusters of GIT bacteria. Furthermore, investigations using specific enteric pathogen challenge models have demonstrated the efficacy of FE in modulating gut health. Because FE probably change the substrate characteristics along the GIT, subsequent microbiota responses will vary according to the populations present at the time of administration and their reaction to such changes. Therefore, the microbiota responses to FE administration, rather than being absolute, are a continuum or a population of responses. However, recognition that FE can make an impact on the gut microbiota and thus gut health will probably stimulate development of FE capable of modulating gut microbiota to the benefit of host health under specific production conditions. The present review brings to light opportunities and challenges for the role of major FE (carbohydrases and phytase) on the gut health of poultry and swine species with a specific focus on the impact on GIT microbiota.
In this rewiev we describe the development of theories concerning links between diet and behavior, discuss the methods employed by allergists and psychologists to examine these theories, and describe and analyse recent literature on the subject. We conclude that there is indeed scientifically sound evidence to support an association between foods and abnormal behavior in children, however with a frequency less than claimed by some theories
Incidence rates for oesophageal adenocarcinoma have increased by over 500% during the past few decades without clear reasons. Gastro-oesophageal reflux disease, obesity and smoking have been identified as risk factors, although the demographic distribution of these risk factors is not consistent with the demographic distribution of oesophageal adenocarcinoma, which is substantially more common among whites and males than any other demographic groups. Numerous epidemiological studies have suggested associations between dietary factors and the risks of oesophageal adenocarcinoma and its precursor, Barrett's oesophagus, though a comprehensive review is lacking. The main aim of the present review is to consider the evidence linking dietary factors with the risks of oesophageal adenocarcinoma, Barrett's oesophagus, and the progression from Barrett's oesophagus to oesophageal adenocarcinoma. The existing epidemiological evidence is strongest for an inverse relationship between intake of vitamin C, β-carotene, fruits and vegetables, particularly raw fruits and vegetables and dark green, leafy and cruciferous vegetables, carbohydrates, fibre and Fe and the risk of oesophageal adenocarcinoma and Barrett's oesophagus. Patients at higher risk for Barrett's oesophagus and oesophageal adenocarcinoma may benefit from increasing their consumption of fruits and vegetables and reducing their intake of red meat and other processed food items. Further research is needed to evaluate the relationship between diet and the progression of Barrett's oesophagus to oesophageal adenocarcinoma. Evidence from cohort studies will help determine whether randomised chemoprevention trials are warranted for the primary prevention of Barrett's oesophagus or its progression to cancer.
Chemical structures of niacin compounds: (a) nicotinamide; (b) nicotinic acid; (c) nicotinamide adenine dinucleotide (NAD þ ); (d) nicotinamide adenine dinucleotide phosphate (NADP þ ).
Structure and origin of cyclic adenosine diphosphate ribose. 
(a) Cumulative error of niacin-deficient ( – X – ) and pair-fed (– W –) rats in the water maze. Rats were tested in three daily trials across 6 d with an inter-trial interval of 2 h. The results of the three daily trials were averaged to give a mean value for each day of testing. Values are means ( n 8), with their standard errors represented by vertical bars. * Mean value was significantly different from that of the pair-fed rats ( P # 0·05). (b) Cumulative error of niacin-deficient ( – X –; n 9) and partially feed-restricted ( – W – ; n 8) rats in the water maze. Rats were tested in three daily trials across 6 d with an inter-trial interval of 2 h. The results of the three daily trials were averaged to give a mean value for each day of testing. Values are means, with their standard errors represented by vertical bars. * Mean value was significantly different from that of the partially feed- restricted rats ( P # 0·05). (c) Cumulative error of niacin-deficient ( – X –) and niacin-recovered ( – W – ) rats during reversal training in the water maze. Rats were tested in three daily trials across 4 d with an inter-trial interval of 2 h. The reversal training followed an initial acquisition phase in the water maze and 4 d of niacin refeeding. The results of the three daily trials were averaged to give a mean value for each day of testing. Values are means ( n 9), with their standard errors represented by vertical bars. * Mean value was significantly different from that of the niacin-recovered rats ( P # 0·05). (d) Cumulative error of niacin-supplemented ( – X –; n 18) and control ( – W –; n 15) rats in the water maze. Rats were tested in three daily trials across 6 d with an inter-trial interval of 2 h. The results of the three daily trials were averaged to give a mean value for each day of testing. Values are means, with their standard errors represented by vertical bars. * Mean value was significantly different from that of the control rats ( P # 0·05). (e) Proximity averages to the platform during hidden platform testing by Cd38 2 / 2 ( – X – ) and wild-type ( – W – ) mice across 7 d of testing. Mice were tested in three daily trials across 6 d with an inter-trial interval of 2 h. The results of the three daily trials were averaged to give a 
Composition of experimental diets (g/kg diet)
Brain NAD þ and cyclic adenosine diphosphate ribose (cADPR) in rats with differing niacin intakes and in Cd38 2/2 mice (nmol/g tissue) (Mean values with their standard errors)
The pyridine nucleotide NAD+ is derived from dietary niacin and serves as the substrate for the synthesis of cyclic ADP-ribose (cADPR), an intracellular Ca signalling molecule that plays an important role in synaptic plasticity in the hippocampus, a region of the brain involved in spatial learning. cADPR is formed in part via the activity of the ADP-ribosyl cyclase enzyme CD38, which is widespread throughout the brain. In the present review, current evidence of the relationship between dietary niacin and behaviour is presented following investigations of the effect of niacin deficiency, pharmacological nicotinamide supplementation and CD38 gene deletion on brain nucleotides and spatial learning ability in mice and rats. In young male rats, both niacin deficiency and nicotinamide supplementation significantly altered brain NAD+ and cADPR, both of which were inversely correlated with spatial learning ability. These results were consistent across three different models of niacin deficiency (pair feeding, partially restricted feeding and niacin recovery). Similar changes in spatial learning ability were observed in Cd38- / - mice, which also showed decreases in brain cADPR. These findings suggest an inverse relationship between spatial learning ability, dietary niacin intake and cADPR, although a direct link between cADPR and spatial learning ability is still missing. Dietary niacin may therefore play a role in the molecular events regulating learning performance, and further investigations of niacin intake, CD38 and cADPR may help identify potential molecular targets for clinical intervention to enhance learning and prevent or reverse cognitive decline.
Observational studies of added sugars 
Observational studies of other definitions of sugars 
Observational studies of food and drinks containing sugars 
Guidelines for sugars intake range from a population mean of less than 10 % energy from free sugars, to a maximum for individuals of 25 % energy from added sugars. The aim of the present review was to examine the evidence for micronutrient dilution by sugars and evaluate its nutritional significance. From a web-based search of MEDLINE and hand search of linked papers, forty-eight relevant publications were identified on sugars (total sugars, non-milk extrinsic sugars, or added sugars) or sugar-containing drinks. These included five reports from expert committees, six reviews, thirty-three observational studies and four small-scale interventions. There was inconsistency between studies as to the relationship between sugars intake (however expressed) and micronutrients. The statistical patterns varied between nutrients and population groups. Curvilinear associations were found in some analyses, with lower nutrient intakes at both extremes of sugar intake; however, factors such as dieting and under-reporting may confound the associations observed. Some studies found statistically significant inverse associations but these were weak, with sugars explaining less than 5 % of the variance. Mean intakes of most micronutrients were above the RDA or reference nutrient intake except among very high consumers of sugars. The available evidence does not allow for firm conclusions on an optimal level of added sugars intake for micronutrient adequacy and the trends that exist may have little biological significance except for a few nutrients (for example, Fe). It is established that energy intake is the prime predictor of micronutrient adequacy. A better understanding of valid approaches to energy adjustment, misreporting and the assessment of micronutrient adequacy is crucial to further progress in this area.
Research conducted among adults has mainly shown that visceral adipose tissue (VAT) is strongly linked to insulin resistance, type 2 diabetes, hypertension and dyslipidaemia, leading to increased risk of CVD or the metabolic syndrome. However, little is known about the aetiology, determinants and consequences of VAT in children. The present article reviews the current literature relating to the factors influencing visceral fat accumulation in children and adolescents. The literature used in the present study was collected by searching a PubMed database, in which studies up to 2008 exploring the factors influencing accumulation of visceral fat among children and youth were found on the basis of appropriate keywords. Further studies concerning different factors influencing deposition of VAT among children and youth should first of all concentrate on: carrying out long-term analyses among children of different ethnical groups, which should begin in the period of prepuberty and which should cover the whole period of puberty till adulthood; drawing up norms specifying the amount of VAT among healthy children; identification of anthropometric indicators which will help to determine the VAT:subcutaneous adipose tissue ratio in the most precise way; broader studies of the influence of eating habits on developing VAT deposit among children and youth.
Top-cited authors
Jan Van Loo
Fred Brouns
  • Maastricht University
Anthony Fardet
  • French National Institute for Agriculture, Food, and Environment (INRAE)
Lucy M Browning
  • University of Cambridge
Margaret Ashwell