We examined the effects of two levels of gestational undernutrition (50% and 40% of ad libitum) on postnatal growth rate, skeletal muscle cellularity and the expression of genes that control muscle growth, in the offspring at weaning. The results showed that the rat pups born to mothers fed the 50% diet during gestation and a control diet during lactation had an increased postnatal growth rate compared with the pups fed the more restricted diet (40% of ad libitum). Surprisingly, the growth rate of the control group (ad libitum) was intermediate between the 50% and 40% groups. The restricted diets did not alter the number of muscle fibres in the semitendinosus muscle of the offspring but the number of muscle nuclei was reduced by 16% in the 40% group compared with the control group. In the 50% group, the lightest pups at birth (L) had elevated muscle insulin-like growth factor (IGF)-1, IGF binding protein (BP)-5 and proliferating cell nuclear antigen (PCNA) mRNA compared with the L pups from both the control and 40% groups. The heaviest pups at birth (H) in the 50% group had increased levels of IGFBP-4, PCNA and M-cadherin mRNA compared with both the control and 40% groups. Levels of IGF-1 receptor, myostatin and MyoD mRNA did not correlate with postnatal growth. Both H and L pups from the 40% group had reduced muscle IGF-1 mRNA but all other transcripts examined were similar to control levels. The results suggest that the increased postnatal growth rate, which accompanied milder fetal undernutrition (50%), may be due to a more active local muscle IGF system and increased muscle-cell proliferation.

We investigated the dietary influence of low and high levels of fish oil, supplemented with or without dietary cholesterol, on the plasma lipoprotein profile in Bio F1B hamsters, a model susceptible to diet-induced hyperlipidaemia. The MIX diet, a diet supplemented with a mixture of lard and safflower-seed oil, was used as the control diet to maintain the saturated MUFA and PUFA levels similar to the fish-oil diet. The animals were fed the specific diets for 2 weeks and fasted for 14h before killing. The plasma from the animals fed high levels of fish oil was milky and rich in chylomicron-like particles. The plasma total cholesterol, VLDL- and LDL-cholesterol and -triacylglycerol concentrations were significantly higher, whereas HDL-cholesterol was lower in hamsters fed fish oil compared with the MIX-diet-fed hamsters. Increasing the amount of fat in the diet increased plasma lipids in both the fish-oil- and the MIX-diet-fed hamsters; however, this hyperlipidaemic effect of dietary fat level was greater in the hamsters fed the fish-oil diet. The hepatic lipid concentrations were not dramatically different between the fish-oil-fed and the MIX-diet-fed hamsters. However, the hepatic LDL-receptor mRNA levels were significantly low in the fish-oil-fed hamsters compared with the MIX-diet-fed hamsters. Increasing the amount of fish oil in the diet further decreased the hepatic LDL-receptor mRNA expression. It is concluded that F1B hamsters are susceptible to fish-oil-induced hyperlipidaemia, especially at high fat levels, and this increase is partially explained by the inhibition of hepatic LDL-receptor mRNA expression.

Serotonin (5-HT) is an important neurotransmitter involved in the brain–gut axis. It is possible to lower the 5-HT level in the body by means of a nutritional intervention using an amino acid mixture; the acute tryptophan depletion (ATD) method. We studied the effect of ATD on gastric emptying in healthy females, who received both ATD and placebo in a random order. Gastric emptying was measured using the [13C]octanoic acid breath test. The present data demonstrate significant differences in both gastric emptying and lag phase (Tlag) between the ATD and placebo experiment. Eight out of ten subjects showed a delayed gastric emptying in the ATD experiment. Both the gastric half-emptying time (T1/2) and the Tlag were significantly higher in the ATD experiment. T1/2 in the ATD experiment was 137·2 (range 76·2–634·8) min; T1/2 for the placebo experiment was 98·5 (range 63·7–168·8) min (P=0·028). Tlag in the ATD experiment was 83·7 (range 45·1–356·2) min; Tlag for the placebo experiment was 56·9 (range 23·2–101·2) min (P=0·007). We conclude that lowering the 5-HT level in the body using the ATD method leads to a significantly delayed gastric emptying of a solid meal. Nutritional manipulation of the serotonergic system in healthy volunteers may lead to alterations in gastrointestinal motility.

Acarbose (Glucobay®; Bayer) is an α-glucosidase inhibitor used to treat diabetes and which may have a role in the prevention of type 2 diabetes. The present study investigated the effects of acarbose treatment on the site and extent of starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation. Eighteen young male Wistar rats were fed ‘Westernised’ diets containing 0, 250 and 500mg acarbose/kg (six rats/diet) for 21d. For most variables measured, both acarbose doses had similar effects. Acarbose treatment suppressed starch digestion in the small bowel but there was compensatory salvage by bacterial fermentation in the large bowel. This was accompanied by a substantial hypertrophy of small- and large-bowel tissue and a consistent increase in crypt width along the intestine. Caecal total SCFA pool size was increased more than 4-fold, with even bigger increases for butyrate. These changes in butyrate were reflected in increased molar proportions of butyrate in blood from both the portal vein and heart. There was little effect of acarbose administration on crypt-cell proliferation (significant increase for mid-small intestine only). This is strong evidence against the hypothesis that increased fermentation and increased supply of butyrate enhances intestinal mucosal cell proliferation. In conclusion, apart from the increased faecal loss of starch, there was no evidence of adverse effects of acarbose on the aspects of large-bowel function investigated.

New Zealand White rabbits were used to investigate the influence of increasing dietary P concentrations on growth performance, mineral balance, kidney calcification and bone development. The minimum dietary P requirement of 0·22% (National Research Council) is usually exceeded in commercial natural-ingredient chows, leading to undesirable kidney calcifications. In order to study the optimal dietary P level, rabbits were fed semi-purified diets with four different P levels (0·1, 0·2, 0·4, and 0·8%; w/w) at a constant dietary Ca concentration (0·5%) during an 8-week period. Body weight and growth were not influenced by the dietary P level. During two periods (days 20–23 and 48–51), faeces and urine were collected quantitatively for the analysis of Ca, Mg and P and balances were calculated. Increased dietary P intake caused increased urinary and faecal P excretion and P apparent absorption and retention. Faecal Ca excretion increased with higher dietary P levels, whereas urinary Ca excretion reacted inversely. The apparent absorption of Ca became reduced at higher dietary P concentrations, but Ca retention was unchanged. The response of Mg was in a similar direction to that of the Ca balance. Kidney mineral content increased with higher dietary P levels, indicating the presence of calcified deposits. Nephrocalcinosis became more severe in kidney cortex and medulla at increasing dietary P levels, as was confirmed by histological analysis. Femur bone length was not differentially influenced by dietary P. Bone density (g/cm3) of the femur diaphysis became significantly lower at the 0·8% dietary P level as compared with the 0·2% P group only. The bone Mg content was significantly increased on the 0·8% P diet, both in the diaphysis and epiphysis. Plasma P concentration increased and plasma Ca decreased with higher dietary P levels, whereas plasma Mg levels were unaffected. The present study shows that the current recommended minimum dietary P level of 0·2% for rabbits, as advised by the National Research Council in 1977, leads to a normal growth and bone development, but also causes some degree of kidney calcifications at a dietary Ca level of 0·5%. As the dietary P level of 0·1% virtually prevented kidney calcification and at the same time did not give evidence for any deleterious effects on growth and bone development, this indicates that the current recommended dietary P level for rabbits should be regarded as a maximum advisable concentration, and that a lower P level may be more optimal.

The effect of sesame (Sesamum orientale) lignan preparation containing equivalent amounts of sesamin and episesamin on hepatic fatty acid metabolism was compared in rats, mice and hamsters. Animals were fed on either a diet free of lignan or a diet containing 2glignan/kg for 15d. The lignan preparation greatly increased hepatic activity and the mRNA levels of enzymes involved in fatty acid oxidation, while it strongly down-regulated those of enzymes involved in lipogenesis in rats. In contrast, lignan did not modify these variables in mice and hamsters. Changes observed, if any, were more attenuated in these mice and hamsters than in rats. Sesamin and episesamin concentrations in serum and liver of animals fed on lignan-containing diets were significantly greater (P<0·05) in rats than in mice and hamsters. Moreover, sesamin:episesamin values in tissues were far from that expected from the value in the lignan preparation given to the animals and were dependent on the animal species. Liver microsomes from each animal species degraded sesamin and episesamin in the presence of NADPH. The combined value of sesamin and episesamin degradation rates was lower in rats than in mice and hamsters. In addition, there was considerable diversity in the specificity of the enzyme reaction toward sesamin and episesamin among animal species. The differences in the amounts of lignan remaining in the tissues may account for the species dependence of the physiological activity of sesame lignan in affecting hepatic fatty acid oxidation and synthesis.

The present study was designed to elucidate the mechanisms accounting for disruption of the normal function of the testis exposed to various levels of Pb. Three different doses of Pb (10, 50, 200mg Pb/kg body weight per d) were given orally to male Portan rats (groups 2, 3, 4). Zn (1mg Zn/kg body weight per d) was also given with Pb (50mg Pb/kg body weight per d) in group 5. Treatments continued for 3 months. Plasma luteinizing hormone and follicle-stimulating hormone concentrations were found to be decreased in Pb-exposed rats. This was in turn reflected in the appreciable decline in fertility status. In cell kinetic studies, significant declines in various cell populations (preleptotene, pachytene, young (step 7) spermatids and mature (step 19) spermatids) were seen. However, in group 5 after Zn supplementation, hormone levels, cell numbers and fertility status were found to be close to normal. It is concluded that Pb might act at maturation level to cause conspicuous degenerative changes in the testis; Zn supplementation protected against these effects.

The objective was to study whether a yoghurt containing isolated soya protein with standardised levels of isoflavones, cotyledon soya fibres and soya phospholipids is more effective in lowering total and LDL-cholesterol than a placebo. One hundred and forty-three subjects were randomised to the soya group (n 69) or to the placebo (n 74). The mean baseline levels were 7·6 and 5·1mmol/l for total and LDL-cholesterol, respectively. Fasting serum lipoproteins were assessed five times during the 8-week intervention period, and 4 weeks thereafter. The results were analysed by a mixed model for unbalanced repeated measurements. During the intervention, there were highly significant differences in lipid-lowering effect in favour of the active soya intervention group compared with the control group. The significant differences were for total cholesterol (estimated mean difference 0·40mmol/l; P<0·001), LDL-cholesterol (0·39mmol/l; P<0·001), non-HDL-cholesterol (0·40mmol/l; P<0·001) and for the total:HDL-cholesterol ratio (0·23; P=0·005). There was no difference in the effects on HDL-cholesterol, triacylglycerols or homocysteine. The lipid-lowering effect occurred within 1–2 weeks of intervention, and was not due to weight loss. The safety profile for active soya was similar to the placebo group, except for gastrointestinal symptoms, which caused a significantly higher dropout rate (fourteen v. three subjects) among the subjects taking active soya.

Dietary Si, as soluble orthosilicic acid (OSA), may be important for the growth and development of bone and connective tissue. Beer appears to be a major contributor to Si intake, although the Si content of beer and its bioavailability in human subjects have not been well established. Here we investigated the Si content of different beers and then estimated Si absorption from beer in healthy volunteers. The Si content of seventy-six different beers was estimated using inductively coupled plasma optical emission spectrometry and one of the beers, used in the ingestion study, was ultrafiltered to determine OSA content. Next, following the ingestion of 0·6 litres beer (22·5mg Si; 4·6% (v/v) ethanol), serum and urinary Si levels were measured in nine healthy volunteers over a 6h period. A solution of OSA was similarly investigated as a positive control and water and 4·6% ethanol as negative controls. The mean Si level of beer was 19·2 (SD 6·6) mg/l; the median Si level was 18·0mg/l. There was no significant difference in the Si levels of the different beers by geographical origin or type of beer. Serum and urinary Si levels increased considerably following the ingestion of beer or a solution of OSA but not with the ingestion of either 4·6% ethanol or water. The ultrafilterability of Si from beer (about 80%) and its absorption in volunteers (about 55%) was comparable with that of a solution of OSA suggesting that Si in beer is present chiefly in a monomeric form and is readily bioavailable.

The role for leptin in food intake regulation in the mink, a polytocous seasonal breeder with altricial young, was investigated in pregnant and lactating dams and data were related to quantitative energy metabolism measurements and plasma concentrations of other important metabolic hormones. A total of nine mink dams were measured in consecutive 1-week balance periods, each including a 22h measurement of heat production by means of indirect calorimetry, and blood was sampled at weekly intervals throughout gestation and during lactation weeks 1–4. Intake of metabolisable energy (ME) was high and energy balance was positive until the first third of true gestation. During mid- and late gestation ME intake decreased (P<0·001) while heat production remained almost constant, resulting in negative energy balance and the loss of body weight. From late gestation until lactation week 4, ME intake increased by 3·5 times, but weight loss continued. Plasma concentrations of leptin were approximately doubled during the last two-thirds of true gestation (P<0·01), demonstrating a clear gestational hyperleptinaemia. Concentrations declined rapidly after parturition and then remained stable. Insulin was independent of leptin, with low concentrations coincident with hyperleptinaemia. Also, concentrations of thyroid hormones declined during gestation, probably reflecting the low food intake. Hyperleptinaemia concomitant with low ME intake, negative energy balance and mobilisation of body reserves suggested an anorexigenic effect of leptin in pregnant mink. This suppression of food intake in late gestation might be permissive for the rapid increase in food intake occurring after parturition.

The present study examined the effect of glutamine (Gln)-enriched diets before sepsis or Gln-containing total parenteral nutrition (TPN) after sepsis, or both, on the phagocytic activity and blood lymphocyte subpopulation in rats with gut-derived sepsis. Rats were assigned to a control group or one of four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet; groups 3 and 4 had part of casein replaced by Gln. After feeding the diets for 10d, sepsis was induced by caecal ligation and puncture (CLP); TPN was maintained for 3d after CLP. The control group and groups 1 and 3 were infused with conventional TPN and groups 2 and 4 were supplemented with Gln in the TPN solution. All rats were killed 3d after CLP or sham operation to examine their immune responses. The results showed that compared with the control group, the phagocytic activities of peritoneal macrophages were enhanced in groups 3 and 4, but not in groups 1 and 2. The proportion of CD3+ cells in group 1 was significantly lower (P<0·05) than that of the control group, whereas no differences were observed among the control and Gln-supplemented groups. The CD4+ cell proportion was significantly lower (P<0·05) in group 1 compared with the control group and groups 3 and 4. These findings suggest that Gln-enriched diets before CLP significantly enhanced peritoneal macrophage phagocytic activity, preserved CD4+ cells and maintained blood total T lymphocytes in gut-derived sepsis. However, parenteral Gln administration after caecal ligation and puncture had no favourable effects on modulating immune response in septic rats.

The present study was conducted to investigate whether green tea may improve weight maintenance by preventing or limiting weight regain after weight loss of 5 to 10% in overweight and moderately obese subjects. The study had a randomised, parallel, placebo-controlled design. A total of 104 overweight and moderately obese male and female subjects (age 18–60 years; BMI 25–35kg/m2) participated. The study consisted of a very-low-energy diet intervention (VLED; 2·1MJ/d) of 4 weeks followed by a weight-maintenance period of 13 weeks in which the subjects received green tea or placebo. The green tea contained caffeine (104mg/d) and catechins (573mg/d, of which 323mg was epigallocatechin gallate). Subjects lost 6·4 (sd 1·9) kg or 7·5 (sd 2·2) % of their original body weight during the VLED (P<0·001). Body-weight regain was not significantly different between the green tea and the placebo group (30·5 (sd 61·8) % and 19·7 (sd 56·9)%, respectively). In the green tea treatment, habitual high caffeine consumption was associated with a higher weight regain compared with habitual low caffeine consumption (39 (sd 17) and 16 (sd 11)%, respectively; P<0·05). We conclude that weight maintenance after 7·5% body-weight loss was not affected by green tea treatment and that habitual caffeine consumption affected weight maintenance in the green tea treatment.

Recombinant glucagon-like peptide-1 (7–36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1 was given for 5d by prandial subcutaneous injections (PSI) (76nmol 30min before meals, four times daily; a total of 302·4nmol/24h) or by continuous subcutaneous infusion (CSI) (12·7nmol/h; a total of 304·8nmol/24h). This was performed in nineteen healthy obese subjects (mean age 44·2 (sem 2·5) years; BMI 39·0 (sem 1·2)kg/m2) in a prospective randomised, double-blind, placebo-controlled, cross-over study. Compared with the placebo, rGLP-1 administered as PSI and by CSI generated a 15% reduction in mean food intake per meal (P=0·02) after 5d treatment. A weight loss of 0·55 (sem 0·2) kg (P<0·05) was registered after 5d with PSI of rGLP-1. Gastric emptying rate was reduced during both PSI (P<0·001) and CSI (P<0·05) treatment, but more rapidly and to a greater extent with PSI of rGLP-1. To conclude, a 5d treatment of rGLP-1 at high doses by PSI, but not CSI, promptly slowed gastric emptying as a probable mechanism of action of increased satiety, decreased hunger and, hence, reduced food intake with an ensuing weight loss.

Estimating intake of phyto-oestrogens (PO) is difficult because there is inadequate information on the PO content of foods. Development of a biomarker of intake is therefore necessary for carrying out epidemiological studies. We aimed to validate a newly constructed PO database, containing more than 600 values assigned to foods by using duplicate diet analysis, and to investigate the relationships between measured PO intake, urinary excretion and plasma concentrations of PO. Fourteen subjects with estimated dietary intakes of PO ranging from 0 to 44mg/d, measured by 7d weighed intake, completed a duplicate diet collection over 24h. Concurrently, a 24h urine collection, validated using p-aminobenzoic acid, was obtained and one timed spot plasma sample taken. Duplicate diets, complete urine collections and plasma samples were analysed for total genistein and daidzein using liquid chromatography–MS to determine PO intake. The potential for 24h urinary excretion and plasma PO concentrations to reflect dietary intake was investigated. Mean estimated and measured dietary PO intakes were 12·3 and 11·0mg/d respectively. The correlation between estimated intake and measured intake of PO was highly significant (r 0·98, P<0·001). Urinary excretion (24h) and plasma concentrations of PO were significantly related to measured dietary PO intake (r 0·97, P<0·001 and r 0·92, P<0·001 respectively). The relationship between 24h urinary PO excretion and timed plasma concentrations was also significant (r 0·99, P<0·001). These findings validate the PO database and indicate that 24h urinary excretion and timed plasma concentrations can be used as biomarkers of PO intake.

The fetal-origins hypothesis suggests that maternal and fetal nutrition can have a profound and sustained impact on the health of the offspring in adult life. Although there is abundant literature reporting on the associations between birth weight and disease risk factors, only a handful of studies have been able to examine the relationship between maternal nutrition in pregnancy with the health of offspring in adult life directly. Between 1942 and 1944, nearly 400 pregnant women were recruited into a dietary study to determine whether the wartime dietary rations were sufficient to prevent nutritional deficiencies. Detailed biochemical and clinical assessments were conducted for each of the women, who were followed-up until after delivery. More than 50 years later, approximately one-quarter of the adult offspring were recruited into a study to explore the possible impact of maternal nutrition in pregnancy on CHD risk factors, including glucose tolerance, blood pressure and components of the lipid profile. Results from the present study provide no evidence to support the hypothesis that birth weight or maternal nutrition in pregnancy are associated with CHD risk factors in adult life.

This is the first study to investigate how food and nutrient intakes vary with the levels of acculturation of Korean Americans using a dietary assessment tool tested for validity and reliability. The respondents were Korean Americans (n 486) resident in the Greater New York metropolitan area, USA. They were divided into two groups according to the total score of acculturation: low- and high-acculturated groups. Using a food-frequency questionnaire and a modified Suinn-Lew Asian self-identity acculturation scale, differences in the frequencies of food items, food groups and nutrient intakes consumed were analysed by level of acculturation. The low-acculturated group tended to consume significantly more rice, mixed rice, soyabean paste chigae (pot stew), saengsun (fish) chigae, kimchi chigae, other fish broiled or baked, eggs, kimchi, spinach, persimmons, and white or brown sugar in coffee or tea. The high-acculturated group demonstrated a statistically greater tendency to consume bread, cereal, spaghetti, ham, green salad, sweetcorn, chocolate, candies and diet soft drinks. The more acculturated an individual, the more significant was the tendency to consume sweets. The more acculturated group had significantly (P<0·05) higher intakes of % energy from total fat, thiamin, vitamin E and folate, while the low-acculturated group consumed greater amounts of Na, niacin and dietary fibre. The information from the present study can be used to describe dietary habits according to various aspects of acculturation, and allows a better understanding of the dynamics of acculturation and dietary habits.

The existence of a set-point for homeostatic control of human body weight is uncertain. To investigate its existence, technically difficult determinations of energy expenditure must be performed: this has resulted in contradictory reports. The present study was performed with new methods in two stages (77 and 133d respectively). Two healthy male subjects with rigorously controlled physical activity ingested three standardized diets of processed foods from the same manufacturer. Hypo-, iso- and hyperenergetic diets containing 6255kJ (1494kcal), 10073kJ (2406kcal) and 13791kJ (3294kcal) respectively were ingested during alternate periods; changes in body weight were measured. A new index of energy expenditure was calculated as the amount of weight lost in an 8h overnight period (WL8H). A digital scale was used in stage 1 and a mechanical scale in stage 2. The change in body weight in response to the isoenergetic diet differed according to the circumstances. In basal conditions, it was associated with weight stability. After weight loss from energy restriction, the isoenergetic diet led to weight gain. After weight gain from overeating, it led to weight loss. Diets of higher energy content were associated with greater WL8H (F>20; P<0·0001 for both subjects). Measurement variability was lower using a mechanical scale. The present study demonstrates the existence of a homeostatic control of human weight and describes a new index of energy expenditure measured in weight units. It also demonstrates that strict dietary supervision for months is possible. Investigation of the human body weight set-point is vital in understanding obesity.

In the factorial estimation of total energy expenditure it is assumed that the intra-individual variation in RMR is small. Little is known about the intra-individual variation in RMR in older subjects. The present study investigated the intra-individual variation in RMR in older people. Measurements of RMR were made in twenty-seven older subjects, mean age 71·6 (sd 6·1) years, on two separate occasions (T1 and T2) and on a third occasion (T3) in nineteen of the subjects. Measurements of height and weight were taken in all subjects. RMR measurements were made in the laboratory using a Deltatrac™ (ventilated-hood indirect calorimeter; Datex, Helsinki, Finland). All subjects had fasted overnight for 12h and refrained from strenuous exercise before measurements. The intra-individual CV in RMR (kJ/d) after T1 and T2 was 2·5% in women and 3·6% in men and was 2·6% in women and 3·4% in men after all three sets of measurements. Although mean RMR did not vary across T1, T2 and T3, there was significant ‘crossing tracks’ across the three measurement occasions in some individuals, reflecting a high degree of within-subject variability. The methods used had a significant measurement error associated with them (high R value; significant F ratio in three-way ANOVA). In conclusion, the results from the present study indicate that intra-individual variation in RMR was low in older people. The intra-individual variation in the elderly is similar to that seen in younger age groups.