There is substantial evidence which shows that constraints in the early life environment are an important determinant of risk of metabolic disease and CVD. There is emerging evidence that higher birth weight, which reflects a more abundant prenatal environment, is associated with increased risk of cancer, in particular breast cancer and childhood leukaemia. Using specific examples from epidemiology and experimental studies, this review discusses the hypothesis that increased susceptibility to CVD, metabolic disease and cancer have a common origin in developmental changes induced in the developing fetus by aspects of the intra-uterine environment including nutrition which involve stable changes to the epigenetic regulation of specific genes. However, the induction of specific disease risk is dependent upon the nature of the environmental challenge and interactions between the susceptibility set by the altered epigenome and the environment throughout the life course.

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

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

This randomized, double-blind, placebo-controlled study was conducted to compare the effect of a 15-week weight-reducing programme ( − 2900 kJ/d) coupled with a calcium plus vitamin D (calcium+D) supplementation (600 mg elemental calcium and 5 μg vitamin D, consumed twice a day) or with a placebo, on body fat and on spontaneous energy/macronutrient intake. Sixty-three overweight or obese women (mean age 43 years, mean BMI 32 kg/m2) reporting a daily calcium intake < 800 mg participated in present study. Anthropometric variables, resting energy expenditure and spontaneous energy intake were measured before and after the 15-week programme. The calcium+D supplementation induced no statistically significant increase in fat mass loss in response to the programme. However, when analyses were limited to very low-calcium consumers only (initial calcium intake ≤ 600 mg/d, n 7 for calcium+D, n 6 for placebo), a significant decrease in body weight and fat mass (P < 0·01) and in spontaneous dietary lipid intake (P < 0·05) was observed in the calcium+D but not in the placebo group. In very low-calcium consumers, change in fat mass was positively correlated with change in lipid intake. During the weight-reducing programme, a calcium+D supplementation was necessary in female overweight/obese very low-calcium consumers to reach significant fat mass loss that seemed to be partly explained by a decrease in lipid intake. We propose that this change in lipid intake could be influenced by a calcium-specific appetite control.

Oranges are rich sources of flavonoids that are bioactive and may protect against age-related diseases. The absorption of orange flavanones may be affected by factors such as processing and subject anthropometric variables, and the bioactivity of the absorbed phytochemicals depends on how they are metabolised during absorption. In a randomised cross-over study, twenty subjects consumed a single portion of orange fruit (150 g) or juice (300 g) that contained the flavanones narirutin and hesperidin, and an additional 109 subjects across a broad age range (18–80 years) consumed the juice. Flavanone metabolites were measured in regularly collected samples of plasma and urine. After consumption of fruit or juice, flavanone conjugates, but not the aglycones, were detected in plasma and urine. The flavanone conjugates were shown to include the 7- and 4′-O-monoglucuronides of naringenin, the 7- and 3′-O-monoglucuronides of hesperetin, two hesperetin diglucuronides and a hesperetin sulfo-glucuronide, but no aglycones or rutinosides. Analysis of the plasma pharmacokinetic and urinary excretion data on a dose-adjusted basis indicated no difference in absorption or excretion of either flavanone between the fruit and juice matrices. In the extended urinary excretion dataset the individual variation was very large (range 0–59 % urinary yield). There was a small but significant (P < 0·05) decrease in the excretion of hesperetin (but not naringenin) with increasing age (P < 0·05), but the effects of sex, BMI and contraceptive pill use were shown not to be associated with the variation in flavanone excretion.

Inflammatory bowel disease (IBD) is often associated with malnutrition. The aim of this study was to compare the body composition of outpatients with IBD during remission and active phase. In order to evaluate disease activity we used Crohn's Disease Activity Index for Crohn's disease (CD) patients and Lichtiger's Index for ulcerative colitis (UC) patients. All patients underwent the analysis of BMI, arm muscle area (AMA) and triceps plus subscapula skinfold thickness (TST+SST) to identify total, muscle and fat mass, respectively. In total 102 patients were evaluated (CD, n 50; UC, n 52) and the majority was young women. Malnutrition according to BMI was found in 14·0 % of patients with CD and 5·7 % of UC patients. Muscle mass depletion was detected in more than half of the CD and UC patients. The BMI, TST+SST and AMA values were lower in the active phase only in CD patients (P < 0·05). Fat mass depletion was associated with active phase in both CD and UC patients. Body composition parameters obtained using BMI, TST+SST and AMA were not correlated with the presence of fistula in CD patients (P>0·05). In conclusion, patients without signs of malnutrition had fat mass depletion especially in the active phase and muscle mass depletion occurred both in CD and UC patients.

Plasma concentrations of vitamin E and carotenoids are governed by several factors, including genetic factors. Single nucleotide polymorphisms (SNP) in some genes involved in lipid metabolism have recently been associated with fasting plasma concentrations of these fat-soluble micronutrients. To further investigate the role of genetic factors that modulate the plasma concentrations of these micronutrients, we assessed whether SNP in five candidate genes (apo C-III, CETP, hepatic lipase, I-FABP and MTP) were associated with the plasma concentrations of these micronutrients. Fasting plasma vitamin E and carotenoid concentrations were measured in 129 French Caucasian subjects (forty-eight males and eighty-one females). Candidate SNP were genotyped by PCR amplification followed by restriction fragment length polymorphisms. Plasma γ-tocopherol, α-carotene and β-carotene concentrations were significantly different (P < 0·05) in subjects who carried different SNP variants in hepatic lipase. Plasma α-tocopherol concentrations were significantly different in subjects who had different SNP variants in apo C-III and cholesteryl ester transfer protein (CETP). Plasma lycopene concentrations were significantly different (P < 0·05) in women who had different SNP variants in intestinal fatty acid binding protein (I-FABP). Finally, there was no effect of SNP variants in microsomal TAG transfer protein upon the plasma concentrations of these micronutrients. Most of the observed differences remained significant after the plasma micronutrients were adjusted for plasma TAG and cholesterol. These results suggest that apo C-III, CETP and hepatic lipase play a role in determining the plasma concentrations of tocopherols while hepatic lipase and I-FABP may modulate plasma concentrations of carotenoids.

Both epidemiological and experimental studies indicate that dietary n-3 PUFA inhibit carcinogenesis and tumour growth. Metastatic diffusion has also been found to be affected in animals fed diets containing purified n-3 PUFA or fish oil. In the present study, we investigated whether the metastatic diffusion of a highly metastatic variant (F10-SR cells) isolated from the B16 melanoma F10 line was affected by feeding host animals a diet containing 5 % fish oil. In these animals, compared with those fed a diet containing 5 % maize oil, there was a reduced number of metastatic pulmonary colonies. The immunohistochemical analysis of appropriate markers revealed that the antimetastatic effect of dietary n-3 PUFA was not related to a reduction of proliferation, but rather to an enhanced apoptotic activity. The reduction of von Willebrand factor immunoreactivity found in pulmonary colonies of F10-SR cells grown in fish oil-fed animals indicates that a decrease of angiogenesis contributes to the antimetastatic effect of dietary n-3 PUFA. This conclusion stands in spite of the higher expression of vascular endothelial growth factor observed in pulmonary colonies grown in fish oil-fed animals.

Gangliosides are glycosphingolipids found in cell membranes and human milk with important roles in cell proliferation, differentiation, growth, adhesion, migration, signalling and apoptosis. Similar changes in ganglioside composition occur during embryonic development, lactation and cancer cell differentiation. It is not known, however, whether ganglioside compositional changes that occur in differentiating colon cancer cells reflect changes that occur during intestinal development. The Caco-2 cell line is commonly used to study physiological and pathophysiological processes in the small intestine and colon. Therefore, to examine this question, undifferentiated and differentiated Caco-2 cells were grown and total lipid was extracted from cell supernatant fractions using the Folch method. The upper aqueous phase containing gangliosides was collected and purified. Total gangliosides were measured as ganglioside-bound N-acetyl neuraminic acid, while individual ganglioside content was quantified via a colorimetric assay for sialic acid and scanning densitometry. The total ganglioside content of differentiated Caco-2 cells was 2·5 times higher compared with undifferentiated cells. Differentiated Caco-2 cells had significantly more (N-acetylneuraminyl) 2-galactosylglucosyl ceramide (GD3) and polar gangliosides, and a lower N-acetylneuraminylgalactosylglucosylceramide (GM3):GD3 ratio than undifferentiated cells. The present study demonstrates that the total ganglioside content and individual ganglioside composition of differentiated Caco-2 cells are similar to those of human colostrum and neonatal rat intestine. Differentiated Caco-2 cells may therefore be an alternative model for studying physiological and pathological processes in the small intestine and colon, and may help to elucidate possible functions for specific gangliosides in development and differentiation. Further research using more sensitive techniques of ganglioside analysis is needed to confirm these findings.

Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found in 35 and 30 % of US adults, respectively. Trans-10, cis-12-conjugated linoleic acid (CLA) has been found to cause both these disorders in several animal models. We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed either a control diet or diets containing trans-10, cis-12-CLA (0·5 %) or CLA+flaxseed oil (FSO) (0·5 %+0·5 %) for 8 weeks. Weights of livers, concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for IR and HOMA1 for β cell function were higher by 160, 636, 985 and 968 % in the CLA group compared with those in the control group. FSO decreased fasting glucose by 20 % and liver weights by 37 % compared with those in the CLA group; it maintained circulating insulin, HOMA1-IR and HOMA1 for β cell function at levels found in the control group. CLA supplementation decreased n-6 and n-3 wt% concentrations of liver lipids by 57 and 73 % and increased the n-6:n-3 ratio by 58 % compared with corresponding values in the control group. FSO increased n-6 and n-3 PUFA in liver lipids by 33 and 342 % and decreased the n-6:n-3 ratio by 70 % compared with corresponding values in the CLA group. The present results suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and that these can be corrected by a concomitant increase in the intake of α-linolenic acid, 18 : 3n-3.

α-Linolenic acid (ALA; 18 : 3n-3) and stearidonic acid (SDA; 18 : 4n-3) are on the biosynthetic pathway of EPA (20 : 5n-3) and DHA (22 : 6n-3). The n-3 fatty acid in rapeseed oil is ALA while Echium oil contains both ALA and SDA. To determine the comparative efficacy of ALA- and SDA-rich oils in enriching broiler meat with n-3 PUFA, we offered diets supplemented with rapeseed oil (rapeseed group) or Echium oil (Echium group) for 35 d to two groups of chicks (age 21 d). There were no differences in carcass weight (2·20 (sem 0·06) v. 2·23 (sem 0·05) kg), boned, skinless thigh muscle (494 (sem 20·5) v. 507 (sem 16·7) g), boned, skinless breast muscle (553 (sem 13·4) v. 546 (sem 11·6) g) or organ weights (heart, liver and gizzard) between the two groups. The total intramuscular fat (IMF) percentage of thigh (8·0 (sem 0·64) v. 8·1 (sem 0·62) %) and breast muscles (2·3 (sem 0·24) v. 2·0 (sem 0·19) %) were also similar between the groups. In contrast, the concentrations of most of the individual n-3 fatty acids (ALA, SDA, EPA and docosapentaenoic acid) were all higher in the Echium than the rapeseed group (P < 0·05). However, differences in DHA concentrations were significant in breast but not thigh muscle IMF. The total n-3 yields/100 g serve thigh muscle were 265 and 676 mg for the rapeseed and Echium groups, respectively (P < 0·0001). The corresponding values for equivalent breast muscles were 70 and 137 mg, respectively (P < 0·01). We conclude that Echium oil is a better lipid supplement than rapeseed oil in changing the concentration and yield of n-3 fatty acids, except DHA, in broiler meat.

We have demonstrated previously that a diet containing skimmed milk (SM) fermented by Lactobacillus gasseri SBT2055 (LGSP) reduces adipocyte size in Sprague–Dawley rats. Two experiments were conducted to extend these observations in order to elucidate the mechanism involved. In experiment 1, lean and obese Zucker rats were fed a diet containing SM or LGSP for 4 weeks. The LGSP diet, compared with the SM diet, resulted in lowering of the mesenteric adipose tissue weight (23 %; P < 0·05), adipocyte sizes (28 %; P < 0·001) and serum leptin concentration (36 %; P < 0·05) in lean rats. Obese Zucker rats did not display such dietary effects. Only the number of smaller adipocytes was increased (P < 0·05) by the LGSP diet in the subcutaneous adipose tissue of obese rats. The LGSP diet significantly reduced the serum and hepatic cholesterol in rats. In addition, the LGSP diet led to an increased excretion of faecal fatty acids and total neutral faecal sterols in both rat strains. In experiment 2, Sprague–Dawley rats with permanent cannulation of the thoracic duct were fed either the SM or LGSP diets and their lymph was collected. The LGSP diet lowered the maximum transport rate of TAG and phospholipids. These results indicate that fermented milk regulates adipose tissue growth through inhibition at the stage of dietary fat absorption in lean Zucker rats.

Hypertension is a major risk factor for the development of CVD. Epidemiological studies have shown that low birth weight increases the risk of developing hypertension in adulthood. Hypertension increases the risk of suffering IHD and early findings provide evidence that hearts from prenatally protein-restricted, hypertensive, male offspring are more susceptible to cardiac dysfunction following ischaemic events. Hypertension and abnormalities in cardiac function following ischaemia–reperfusion in the human population are treated therapeutically with β-adrenergic antagonists. We hypothesised that increased susceptibility to myocardial ischaemia–reperfusion injury in prenatally programmed offspring may be due to sympathetic hyperactivity. Pregnant Wistar rats were fed control or low-protein (maternal low protein; MLP) diets throughout gestation. At age 6 months, hearts were rapidly excised and retro-perfused using the Langendorff apparatus, to assess isolated cardiac function following stimulation with increasing doses of the non-specific β-agonist isoproterenol. Baseline heart rates were similar in control and MLP-fed offspring. With significant diet × sex interactions (P < 0·01) maximum heart rate response following isoproterenol infusion was significantly longer in MLP than control. Prenatal diet had no effect on maximal left ventricular developed pressure (LVDP) response, but the LVDP isoproterenol response was significantly longer in duration in MLP-exposed male offspring (diet × sex P < 0·001). Myocardial mRNA expression of β2-adrenergic receptors was increased in 2-week-old female MLP offspring only (P < 0·049). In conclusion, maternal protein restriction programmes cardiac sympathetic activity in a sex-specific manner, and may explain increased susceptibility to ischaemia–reperfusion injury in males subject to fetal undernutrition.

The dietary lectin phytohaemagglutinin (PHA) induces gut growth and precocious maturation in suckling rats after mucosal binding. The present study investigated the dose range in which PHA provokes gut maturation and if it coincided with immune activation. Suckling rats, aged 14 d, were orogastrically fed a single increasing dose of PHA: 0 (control), 2, 10, 50 or 250 μg/g body weight (BW) in saline. The effect on gut, lymphoid organs and appearance of CD3+ (T-lymphocyte) and CD19+ (B-lymphocyte) cells in the small-intestinal mucosa was studied at 12 h (acute) and 3 d (late phase) after treatment. The low PHA doses (2 and 10 μg/g BW) induced intestinal hyperplasia without mucosal disarrangement but did not provoke gut maturation. Only the high PHA doses (50 and 250 μg/g BW) temporarily disturbed the intestinal mucosa with villi shortening and decrease in disaccharidase activities, and later after 3 d provoked precocious maturation, resulting in an increase in maltase and sucrase activities and decrease in lactase activity and disappearance of the fetal vacuolated enterocytes in the distal small intestine. Exposure to the high, but not to the low, PHA doses increased the number of mucosal CD19+ and CD3+ cells in the small intestine after 12 h, a finding also observed in untreated weaned rats aged 21–28 d. In conclusion, there was a dose-related effect of PHA on gastrointestinal growth and precocious maturation that coincided with a rapid expansion of mucosal B- and T-lymphocytes, indicating a possible involvement of the immune system in this process.

The impact of nutrition on the epigenetic machinery has increasingly attracted interest. The aim of the present study was to demonstrate the effects of various diets on methylation and gene expression. The antioxidative enzyme mitochondrial superoxide dismutase (MnSOD) was chosen as the model system because epigenetic regulation has been previously shown in cell lines for this gene. Promoter methylation and gene expression of MnSOD in buccal swabs from three sample groups were analysed. The three groups included: (1) forty vegetarians (aged 20–30 years); (2) age-matched omnivores; (3) elderly omnivores (aged>85 years). A 3-fold increase in the expression of the MnSOD gene was associated with decreased CpG methylation of the analysed promoter region in the vegetarian group compared with the age-matched omnivores group. Expression and promoter methylation of the MnSOD gene in elderly omnivores showed no significant differences compared with younger omnivores. In accordance with previous findings in various tissues, DNA global methylation was found to be significantly higher (30 %) in buccal swabs of younger subjects (independent of the diet), than in those of elderly omnivores. In the control experiment which was designed to verify the findings of the human buccal swab studies, the Caco-2 cell line was treated with zebularine. Results of the control study showed a 6-fold increase of MnSOD expression, an approximately 40 % decreased methylation of specified CpG in the MnSOD promoter and a 50 % reduction of global DNA methylation. These results indicate that diet affects the epigenetic regulation of human MnSOD.

Controlled human intervention trials are required to confirm the hypothesis that dietary fat quality may influence insulin action. The aim was to develop a food-exchange model, suitable for use in free-living volunteers, to investigate the effects of four experimental diets distinct in fat quantity and quality: high SFA (HSFA); high MUFA (HMUFA) and two low-fat (LF) diets, one supplemented with 1·24 g EPA and DHA/d (LFn-3). A theoretical food-exchange model was developed. The average quantity of exchangeable fat was calculated as the sum of fat provided by added fats (spreads and oils), milk, cheese, biscuits, cakes, buns and pastries using data from the National Diet and Nutrition Survey of UK adults. Most of the exchangeable fat was replaced by specifically designed study foods. Also critical to the model was the use of carbohydrate exchanges to ensure the diets were isoenergetic. Volunteers from eight centres across Europe completed the dietary intervention. Results indicated that compositional targets were largely achieved with significant differences in fat quantity between the high-fat diets (39·9 (sem 0·6) and 38·9 (sem 0·51) percentage energy (%E) from fat for the HSFA and HMUFA diets respectively) and the low-fat diets (29·6 (sem 0·6) and 29·1 (sem 0·5) %E from fat for the LF and LFn-3 diets respectively) and fat quality (17·5 (sem 0·3) and 10·4 (sem 0·2) %E from SFA and 12·7 (sem 0·3) and 18·7 (sem 0·4) %E MUFA for the HSFA and HMUFA diets respectively). In conclusion, a robust, flexible food-exchange model was developed and implemented successfully in the LIPGENE dietary intervention trial.

Several recent reports have found a high prevalence of vitamin D deficiency in the adult British population. The present paper investigates the associations of low income/material deprivation and other predictors of serum 25-hydroxyvitamin D (25(OH)D) status in two surveys: The National Diet and Nutrition Survey (NDNS) of the population aged 19–64 years in mainland Britain and the Low Income Diet and Nutrition Survey (LIDNS) of adults aged ≥ 19 years in all regions of the UK who were screened to identify low-income/materially deprived households. A valid serum 25(OH)D sample was obtained in 1297 and 792 participants from the NDNS and LDNS respectively. The NDNS participants who were not receiving benefits (n 1054) had a mean 25(OH)D of 50·1 nmol/l, which was higher than among NDNS participants receiving benefits (n 243) with a mean 25(OH)D of 43·0 nmol/l (P < 0·001) and the LIDNS sample (46·5 nmol/l; P < 0·05). For all three samples, the season of drawing blood, skin colour, dietary intake of vitamin D, and intake of dietary supplements were significant predictors (P < 0·05) of serum 25(OH)D status in mutually adjusted regression models. National prevention and treatments strategies of poor vitamin D status need to be targeted to include the adult population, particularly deprived populations, in addition to the elderly and ethnic minorities.

The aim of the present study was to investigate the relationships of physical activity types and sedentary behaviour with BMI and waist circumference (WC). The sample comprised 6215 adults (2775 men, 3440 women) aged 16 years and over living in Scotland. Self-reported physical activity of moderate to vigorous intensity (MVIA) included domestic activity, walking, and sports and exercises. MVIA levels were classified as being inactive, being insufficiently active, being sufficiently active for general health benefits and being sufficiently active for obesity prevention. Sedentary time was defined as television and other screen-based entertainment time (TVSE). Dependent variables were BMI-defined obesity (BMI-OB) and WC-defined obesity (WC-OB). TVSE was positively related to both WC-OB (adjusted OR 1·69 (95 % CI 1·39, 2·05) for ≥ 4 h of TVSE per d compared with < 2 h/d) and BMI-OB (OR 1·88; 95 % CI 1·51, 2·35) independently of MVIA. Those classified as most active who reported ≥ 4 h/d of TVSE had higher prevalence of BMI-OB (18·9 v. 8·3 %; P < 0·05) and WC-OB (28·0 v. 10·0 %; P < 0·01) than those equally active with < 2 h/d of TVSE. Sports and walking were related inversely to WC-OB (OR for no time compared with ≥ 30 min/d: 1·55 (95 % CI 1·24, 1·94); 2·06 (95 % CI 1·64, 2·58)), but only walking was related to BMI-OB (OR 1·94; 95 % CI 1·58, 2·37). Domestic physical activity was not related to BMI-OB or WC-OB. In conclusion, physical activity and sedentary behaviour are independently related to obesity. Public health recommendations should both promote physical activity and discourage engagement in sedentary pursuits.