Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

Home parenteral nutrition is an established method of supporting patients with intestinal failure, but this treatment may be life long and imposes severe restrictions on daily life. Impact on quality of life is an important outcome when considering the management of home parenteral nutrition patients. This paper reviews studies in which the quality of life of patients receiving home parenteral nutrition has been assessed. A systematic search of electronic databases and relevant publications was undertaken to identify generic or treatment-specific questionnaires used with home parenteral nutrition patients. Many of the thirty-four reports discovered were small studies. Nineteen used non-specific generic instruments, eight used non-validated questionnaires, four used a combination of both, and three did not use any formal tool. Few systematic patterns emerged. There are few available data on the quality of life of home parenteral nutrition patients, and there is a need for standardised, scientifically validated, treatment-specific instruments to measure quality of life in this population.

Previous studies indicate that regular consumption of a diet rich in fruits and vegetables is associated with a lower risk for age-related diseases. The aim of the present study was to evaluate whether the often-reported age-related decrease of plasma antioxidants in man depends on differences in dietary intake or on other age- and gender-related factors. In this observational case-control study, thirty-nine community-dwelling healthy subjects aged 65 years and older consuming high intakes of fruits and vegetables daily (HI) and forty-eight healthy subjects aged 65 and older consuming low intakes of fruit and vegetables daily (LI) were enrolled. Plasma levels of retinol, tocopherols, carotenoids and malondialdehyde (MDA) as well as content of protein carbonyls in Ig G were measured. Plasma levels of retinol, tocopherols and carotenoids were significantly higher in group HI than in group LI subjects independent of age and gender. MDA levels were inversely correlated with vitamin A and α-carotene. Protein carbonyls were inversely correlated with γ-tocopherol. In the elderly, a higher daily intake of fruits and vegetables is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables. Modification of nutritional habits among other lifestyle changes should be encouraged to lower prevalence of disease risk factors in later life.

Erythritol, a naturally occurring polyol, is gaining attention as a bulk sweetener for human nutrition. Industrially, it is produced from glucose by fermentation. From various studies it is known to be non-cariogenic. Moreover, it is rapidly absorbed in the small intestine and quantitatively excreted in the urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that erythritol remained unfermented for a fermentation period of 12 h. In order to investigate whether fresh human intestinal microbiota is able to adapt its enzyme activities to erythritol, a 24 h lasting fermentation was carried out under well-standardised in vitro conditions. For comparison maltitol, lactulose and blank (faecal inoculum only) were incubated as well. Fermentation patterns were established by following total gas production, hydrogen accumulation, changes in pH value, SCFA production and substrate degradation. Taking all fermentation parameters into account, erythritol turned out to be completely resistant to bacterial attack within 24 h, thus excluding an adaptation within that period. Since under in vivo conditions more easily fermentable substrates enter the colon continuously, it seems very unlikely that erythritol will be fermented in vivo.

The sympathetic nervous system is involved in the control of energy metabolism and expenditure. Diet-induced thermogenesis is mediated partly by the ß-adrenergic component of this system. The aim of the present study was to investigate the role of genetic variation in the ß2-adrenoceptor in diet-induced thermogenesis. Data from twenty-four subjects (fourteen men and ten women; BMI 26·7(sem 0·8) kg/m2; age 45·2(sem1·4) years) with different polymorphisms of the ß2-adrenoceptor at codon 16 (Gly16Gly, Gly16Arg or Arg16Arg) were recruited for this study. Subjects were given a high-carbohydrate liquid meal, and the energy expenditure, respiratory exchange ratio, and plasma concentrations of NEFA, glycerol, glucose, insulin and catecholamines were measured before and over 4 h after the meal. The AUC of energy expenditure (diet-induced thermogenesis) was not significantly different between polymorphism groups, nor was the response of any of the other measured variables to the meal. In a multiple regression model, the only variable that explained a significant proportion (32 %) of the variation in diet-induced thermogenesis was the increase in plasma adrenaline in response to the meal (P<0·05). The ß2-adrenoceptor codon16 polymorphisms did not contribute significantly. In conclusion, an independent contribution of the codon 16 polymorphism of the ß2-adrenoceptor gene to the variation in thermogenic response to a high-carbohydrate meal could not be demonstrated. The interindividual variation in thermogenic response to the meal was correlated with variations in the plasma adrenaline response to the meal.

Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein, and such an understanding of the structure of the whole protein is often vital to understanding its digestive behaviour and nutritive value in animals. The main protein secondary structures are the α-helix and β-sheet. The percentage of these two structures in protein secondary structures influences protein nutritive value, quality and digestive behaviour. A high percentage of β-sheet structure may partly cause a low access to gastrointestinal digestive enzymes, which results in a low protein value. The objectives of the present study were to use advanced synchrotron-based Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the molecular chemistry of the protein secondary structures of feed tissues affected by heat-processing within intact tissue at a cellular level, and to quantify protein secondary structures using multicomponent peak modelling Gaussian and Lorentzian methods, in relation to protein digestive behaviours and nutritive value in the rumen, which was determined using the Cornell Net Carbohydrate Protein System. The synchrotron-based molecular chemistry research experiment was performed at the National Synchrotron Light Source at Brookhaven National Laboratory, US Department of Energy. The results showed that, with S-FTIR microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and nutritive characteristics could be revealed at a high ultraspatial resolution (∼10 μm). S-FTIR microspectroscopy revealed that the secondary structure of protein differed between raw and roasted golden flaxseeds in terms of the percentages and ratio of α-helixes and β-sheets in the mid-IR range at the cellular level. By using multicomponent peak modelling, the results show that the roasting reduced (P<0·05) the percentage of α-helixes (from 47·1 % to 36·1 %: S-FTIR absorption intensity), increased the percentage of β-sheets (from 37·2 % to 49·8 %: S-FTIR absorption intensity) and reduced the α-helix to β-sheet ratio (from 0·3 to 0·7) in the golden flaxseeds, which indicated a negative effect of the roasting on protein values, utilisation and bioavailability. These results were proved by the Cornell Net Carbohydrate Protein System in situ animal trial, which also revealed that roasting increased the amount of protein bound to lignin, and well as of the Maillard reaction protein (both of which are poorly used by ruminants), and increased the level of indigestible and undegradable protein in ruminants. The present results demonstrate the potential of highly spatially resolved synchrotron-based infrared microspectroscopy to locate ‘pure’ protein in feed tissues, and reveal protein secondary structures and digestive behaviour, making a significant step forward in and an important contribution to protein nutritional research. Further study is needed to determine the sensitivities of protein secondary structures to various heat-processing conditions, and to quantify the relationship between protein secondary structures and the nutrient availability and digestive behaviour of various protein sources. Information from the present study arising from the synchrotron-based IR probing of the protein secondary structures of protein sources at the cellular level will be valuable as a guide to maintaining protein quality and predicting digestive behaviours.

The purpose of the present study was to clarify the manner by which the supplementation of high-P diet induces bone loss. Eighteen 4-week-old male Wistar-strain rats were assigned randomly to three groups and fed diets containing three P levels (0·3, 0·9, and 1·5%) for 21d. A lower serum Ca concentration was observed in the rats fed on the 1·5% P diet than in the other two groups. Serum P and parathyroid hormone concentrations and urinary excretion of C-terminal telopeptide of type I collagen were elevated with increasing dietary P levels. Serum osteocalcin concentration was increased in the rats fed on the 1·5% P diet than in the other two groups. Bone formation rate of the lumbar vertebra was significantly increased in the two high-P groups than in the 0·3% P group. Osteoclast number was significantly increased with increasing dietary P levels. Bone mineral content and bone mineral density of the femur and lumbar vertebra and ultimate compression load of the lumbar vertebra were decreased with increasing dietary P levels. Additionally, ultimate bending load of the femur was decreased in the rats fed on the 1·5% P diet than in the other two groups. Receptor activator of NF-κB ligand (RANKL) mRNA expression in the femur was significantly higher with increasing dietary P levels. These results suggest that secondary hyperparathyroidism due to a high-P diet leads to bone loss via an increase in bone turnover. Furthermore, an increase in osteoclast number was caused by increased RANKL mRNA expression.

Amiodarone, an antiarrhythmic drug, and trimeprazine, an antipsychotic drug, are both in vitro inhibitors of retinyl ester hydrolase. To determine whether these agents have deleterious effects on aspects of vitamin A metabolism, Brown Norway rats (n 18) were treated at clinically equivalent doses once daily for 26d with either oral drug. On day 27, a tolerance test was used to determine whether these agents interfered with vitamin absorption. During the first 8d, the plasma retinol level declined in all animals. Between days 12 and 27, it rose to near pre-treatment concentrations in the control and trimeprazine groups and remained relatively constant at low levels (P<0·001) in the amiodarone group. The intestinal absorption of vitamin A was reduced (P<0·05) in the amiodarone group compared with the placebo and trimeprazine groups, which did not differ significantly from each other. At the end of the 4-week treatment period, hepatic retinyl ester hydrolase activity was lower in the drug-dosed rats (P=0·06 for amiodarone) than in the controls. With regard to effects on liver reserves, drug treatment resulted in vitamin A depletion (P<0·019), and distinctive patterns of retinol and its esters were seen in response to dosing. In conclusion, amiodarone and trimeprazine have been shown to influence different aspects of retinoid metabolism, namely absorption, storage and transport. In clinical practice, the routine unmonitored use of these drugs and the suggestion that these agents be taken with meals are not recommended.

The effects of high dietary levels of phosphatidylethanolamine (PE) on plasma concentrations of homocysteine (tHcy) have not previously been studied. Eighteen mink (Mustela vison) studied were fed one of three diets during a 25d period in a parallel-group design. The compared diets had 0, 17 and 67% extracted lipids from natural gas-utilising bacteria (LNGB), which were rich in PE. The group with 0% LNGB was fed a diet of 100% soyabean oil (SB diet). Phospholipids are the main lipid components in LNGB and Methylococcus capsulatus is the main bacteria (90%). The fasting plasma concentration of tHcy was significantly higher when the mink consumed the diet with 67% LNGB than when they consumed the SB diet (P=0·039). A significantly lower glutathione peroxidase activity was observed in mink consuming the 17% LNGB diet or the 67% LNGB diet than was observed in mink fed the SB diet. The lack of significant differences in the level of plasma PE due to the diets indicates that most of the PE from the 67% LNGB diet was converted to phosphatidylcholine (PC) in the liver. It has previously been hypothesised that phosphatidylethanolamine N-methyltransferase is an important source of tHcy. The present results indicate that plasma tHcy is at least partly regulated by phospholipid methylation from PE to PC. This methylation reaction is a regulator of physiological importance.

The effects of two kinds of Escherichia coli (E. coli) strain, wild-type E. coli W3110 and E. coli nir-Ptac, which has enhanced NO2 reduction activity, on oral CH4 emission and NO3 toxicity in NO3-treated sheep were assessed in a respiratory hood system in a 4×6 Youden square design. NO3 (1·3g NaNO3/kg0·75 body weight) and/or E. coli strains were delivered into the rumen through a fistula as a single dose 30min after the morning meal. Escherichia coli cells were inoculated for sheep to provide an initial E. coli cell density of optical density at 660nm of 2, which corresponded to 2×1010 cells/ml. The six treatments consisted of saline, E. coli W3110, E. coli nir-Ptac, NO3, NO3 plus E. coli W3110, and NO3 plus E. coli nir-Ptac. CH4 emission from sheep was reduced by the inoculation of E. coli W3110 or E. coli nir-Ptac by 6% and 12%, respectively. NO3 markedly inhibited CH4 emission from sheep. Compared with sheep given NO3 alone, the inoculation of E. coli W3110 to NO3-infused sheep lessened ruminal and plasma toxic NO2 accumulation and blood methaemoglobin production, while keeping ruminal methanogenesis low. Ruminal and plasma toxic NO2 accumulation and blood methaemoglobin production in sheep were unaffected by the inoculation of E. coli nir-Ptac. These results suggest that ruminal methanogenesis may be reduced by the inoculation of E. coli W3110 or E. coli nir-Ptac. The inoculation of E. coli W3110 may abate NO3 toxicity when NO3 is used to inhibit CH4 emission from ruminants.

Exercise prior to eating has repeatedly been shown to reduce postprandial lipaemia. The aim of the present study was to investigate whether this effect was manifest in the presence of two factors that independently mitigate postprandial lipaemia: eumenorrhoea and moderate fat intake. Eight healthy eumenorrhoeic rowers consumed a meal of moderate fat content (35% total energy, 0·66g/kg body mass) 14h after having either rowed at 55% of maximal aerobic power (81% of maximal heart rate) for 80min or rested. Both trials were performed during the luteal phase. Blood samples were drawn before the meal and for 8h postprandially for the measurement of individual fatty acids in the triacylglycerol and NEFA fractions, as well as of glucose, insulin and oestradiol. Plasma oestradiol concentrations were not significantly different in the two trials. The postprandial lipaemic response, expressed as either plasma triacylglycerol concentration or area under the triacylglycerol–time curve, was 35% lower (P<0·05) after exercise. The postprandial glycaemic and insulinaemic responses were also lower, indicating increased insulin sensitivity, whereas the NEFA response was higher, suggesting a lower entrapment of dietary fatty acids in adipose tissue after exercise. Finally, exercise increased the proportion of unsaturated:saturated NEFA during the postprandial period. In conclusion, aerobic exercise performed 14h before a moderate-fat meal reduced postprandial lipaemia in women in the luteal phase. This effect shows the potential of exercise to mitigate even moderate lipaemic responses in eumenorrhoeic women.

The contents of short-chain fatty acids were investigated in rats fed lactitol, lactulose and four fructo-oligosaccharides of different degree of polymerisation and solubility. Fructo-oligosaccharides with a low degree of polymerisation (2–8) generated the highest levels of butyric acid all along the hindgut, whereas fructo-oligosaccharides with a high degree of polymerisation (10–60) generated the highest levels of propionic acid. These specific differences were also generally reflected in the caecal pools and molar proportions of short-chain fatty acids. The lower solubility of the fructo-oligosaccharides was related to a lower degree of caecal fermentation. Lactulose and lactitol yielded high proportions of acetic acid and low proportions of butyric acid. It is concluded that both the degree of polymerisation and the solubility may affect short-chain fatty acid formation, whereas the fructose content per se seem to be of less importance. This may be of interest when designing foods with specific health effects.

The aim of the present study is to investigate the effect of acetic acid feeding on the circadian changes in glycogen concentration in liver and skeletal muscle. Rats were provided meal once daily (09.00–13.00 hours) for 10d. On the 11th day, they were either killed immediately or given 9g diet containing either 0 (control) or 0·7g/kg-diet acetic acid beginning at 09.00 hours for 4h, as in the previous regimen. Rats in the fed group were killed at 4, 8 or 24h after the start of feeding. At 4h after the start of feeding, the acetic acid group had significantly greater liver and gastrocnemius muscle glycogen concentrations (P<0·05). Also, at this same point, liver xylulose-5-phosphate, a key stimulator of glycolysis, the ratio of fructose-1,6-bisphosphate to fructose-6-phosphate in skeletal muscle, which reflects phosphofructokinase-1 activity, and liver malonyl-CoA, an allosteric inhibitor of carnitine palmitoyl-transferase, were significantly lower in the acetic acid group than in the control group (P<0·05). In addition, the acetic acid group had a significantly lower serum lactate concentration and lower ratio of insulin to glucagon than the control group at the same point (P<0·05). We conclude that a diet containing acetic acid may enhance glycogen repletion but not induce supercompensation, a large increase in the glycogen level that is beneficial in improving performance, in liver and skeletal muscle by transitory inhibition of glycolysis. Further, we indicate the possibility of a transient enhancement of fatty acid oxidation in liver by acetic acid feeding.

Fe absorption is affected by many dietary factors. The objective of the present study was to measure the effects of high v. low content of vitamin C, meat and phytic acid in whole diets with Fe-fortified bread on the efficacy of Fe absorption. Thirty-two healthy women with low Fe stores were randomised to three groups, each of which was given two of six test diets containing either low/high amounts of vitamin C, meat or phytic acid, respectively, in a cross-over design. Each diet was served throughout a 5 d period. Fe-fortified rye bread, extrinsically labelled with 59Fe, was given with all main meals. Fe absorption was determined from whole-body counter measurements of 59Fe retention. The fractional non-haem Fe absorption (corrected to a 40% standard absorption by measurements from the reference dose) was 1·9% v. 3·4% (P=0·04) for the low/high vitamin C diets, 3·0% v. 3·5% (P=0·58) on the low/high meat diets and 4·9% v. 3·8% (P=0·24) on the low/high phytic acid diet, respectively. The total Fe absorbed (geometric mean with standard error) varied from 0·43 (se 0·11) mg from the diet with lowest bioavailability to 1·09 (se 0·18) mg from the diet with highest bioavailability (P<0·001). The present whole-diet study indicates that diet composition is a strong predictor of Fe absorption. In the diet with a low content of enhancers and a high content of inhibitors, vitamin C improved non-haem Fe absorption. The total Fe absorption varied 2·5-fold after small alterations of the content of enhancers and inhibitors in the diet.

Oral folic acid above certain threshold doses results in unmetabolised folic acid in serum. This raises a number of public health safety issues, principally the potential to mask pernicious anaemia; more recently the theoretical potential for high-dose folic acid to promote cancer has been highlighted. In this paper we set out to examine the appearance of unmetabolised folic acid both in cord blood from newborn full-term and premature infants and serum from 4-d-old infants post-formula feeding. Blood was collected from the umbilical cord of eleven infants in the delivery room immediately after birth. A follow-up serum sample (n 9) was collected 4d later from infants post-formula feeding. We detected unmetabolised folic acid in cord blood from all infants at birth. In addition, unmetabolised folic acid was present in serum of seven infants post-formula feeding, six of which had increased from birth. Our results imply that infants in Ireland, which does not yet have mandatory fortification, could potentially have circulatory unmetabolised folic acid at the time of birth. We do not know if the presence of folic acid in cord blood will have any adverse consequences. However, if theoretical safety concerns are borne out by future research, the likelihood is that the longer the exposure the more likely the potential for harm. This would also be the case in infants exposed to unmetabolised folic acid as a result of formula feeding.

In the present study we evaluate the blood pressure-lowering effect of the following products: the hydrolysate obtained from egg white (EW) by enzymatic treatment with pepsin (HEW), the peptide fraction of HEW with molecular mass lower than 3000 Da (HEW<3000 Da), and three peptide sequences isolated from HEW<3000 Da (Tyr-Ala-Glu-Glu-Arg-Tyr-Pro-Ile-Leu: YAEERYPIL); (Arg-Ala-Asp-His-Pro-Phe-Leu: RADHPFL); and (Ile-Val-Phe (IVF)). These peptides, and also HEW and HEW<3000 Da, had been characterized previously in vitro as potent inhibitors of angiotensin-converting enzyme (ACE). EW and the products mentioned earlier were orally administered by gastric intubation, to 17–20-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto (WKY) rats. We measured the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats by the tail cuff method before administration and also 2, 4, 6, 8 and 24h post-administration. Distilled water served as negative control, and we used captopril (50mg/kg) as positive control to carry out similar experiments with a known ACE inhibitor. HEW, HEW<3000 Da and the three peptide sequences decreased SBP and DBP in SHR but they did not modify these variables in WKY rats. The peptide sequences YAEERYPIL, RADHPFL and IVF showed a potency to decrease blood pressure greater than HEW or HEW<3000 Da. The results obtained suggest that the studied products could be used as a functional food with potential therapeutic benefit in the prevention and treatment of hypertension.

To determine whether or not the weight (and fat) loss induced by oleoyl-oestrone treatment results only as a consequence of decreased food intake, we compared treated animals with a pair-fed model. To this end, Wistar female rats received daily oral gavages of 10μmol/kg per d oleoyl-oestrone in sunflower oil, or vehicle alone for 10 or 20d. A second group of rats received the gavage of sunflower oil and the same amount of food ingested as the oleoyl-oestrone-treated animals (pair-fed group). Rats treated with oleoyl-oestrone maintained glucidic metabolism homeostasis despite a marked decrease in adipose tissue weight (P<0·001). Pair-fed rats exhibited a different pattern, comparable to short-term starvation, with greatly decreased glycogen stores (P<0·0001). The most significant effects were detected in the 10d period groups. Oleoyl-oestrone affected the activity of the ponderostat system not only by decreasing appetite but also by modifying energy partition: treated animals maintained their glucose and energy homeostasis despite decreased food intake and the massive depletion of lipid stores.

This study was undertaken to investigate the growth performance and immune responses of broiler chicks fed diets supplemented with conjugated linoleic acid (CLA). Two hundred and forty day-old Arbor Acre male broiler chicks were randomly allotted into four dietary treatments with different inclusion levels of CLA (0, 2·5, 5·0 or 10·0g pure CLA/kg) for 6 weeks. Growth performance, lysozyme activity, peripheral blood mononuclear cell (PBMC) proliferation, prostaglandin E2 (PGE2) synthesis and antibody production were investigated. There were no significant differences in growth performance among treatments (P>0·05). Chicks fed 10·0g CLA/kg diet produced 40% and 49% more lysozyme activity in serum and spleen than the control group at 21d of age (P<0·05). Dietary CLA enhanced the PBMC proliferation in response to concanavalin A at the age of 21 and 42d (P<0·05). Systemic and peripheral blood lymphocytic synthesis of PGE2 in chicks fed 10·0g CLA/kg diet was significantly decreased by 57% and 42% compared to chicks fed control diet (P<0·05). Antibody production to sheep red blood cell and bovine serum albumin were elevated in either 2·5 or 10·0g CLA/kg dietary treatments (P<0·05). The results indicated dietary CLA could enhance the immune response in broiler chicks, but did not alter the growth performance.

Shark-liver oil (SLO) contains two bioactive lipids: alkylglycerols and n-3 PUFA. Alkylglycerols have immunostimulating and haematopoietic properties, while n-3 PUFA are essential for optimal neonatal development. We investigated the beneficial effects of dietary supplementation with 32g SLO/d to twelve pregnant and then lactating sows (from day 80 of pregnancy to weaning) on the growth and immune status of their offspring, compared with a control group. Sows were vaccinated against Aujeszky's disease 21d before term. Blood samples were collected from sows before treatment, on delivery and 14d later, and from five piglets per litter on days 2, 21 and 36 after birth; colostrum and milk samples were collected 12h, 14 and 28d postpartum. Compared with controls, supplemented sows had higher levels of both erythrocytes and Hb in their blood, and higher concentrations of IgG, alkylglycerols and n-3 PUFA in their mammary secretions. In piglets from supplemented sows, leucocytes and IgG were higher. Supplementation with SLO resulted in an increase in Aujeszky antibodies in both blood and colostrum of sows after vaccination, together with an increase in Aujeszky antibodies in piglet blood. Our findings demonstrate that improvement of both passive and active immune status in piglets is related to the consumption of alkylglycerols associated with n-3 PUFA in the sow diet. The overall improvement in offspring health status by SLO supplementation to the mother could be of interest for optimisation of the lipid diet during and after pregnancy.