Postprandial plasma insulin concentrations after a single high-fat meal may be modified by the presence of specific fatty acids although the effects of sequential meal ingestion are unknown. The aim of the present study was to examine the effects of altering the fatty acid composition in a single mixed fat–carbohydrate meal on glucose metabolism and insulin sensitivity of a second meal eaten 5 h later. Insulin sensitivity was assessed using a minimal model approach. Ten healthy post-menopausal women underwent four two-meal studies in random order. A high-fat breakfast (40 g fat) where the fatty acid composition was predominantly saturated fatty acids (SFA), n-6 polyunsaturated fatty acids (PUFA), long-chain n-3 PUFA or monounsaturated fatty acids (MUFA) was followed 5 h later by a low-fat, high-carbohydrate lunch (5·7 g fat), which was identical in all four studies. The plasma insulin response was significantly higher following the SFA meal than the other meals after both breakfast and lunch (P<0·006) although there was no effect of breakfast fatty acid composition on plasma glucose concentrations. Postprandial insulin sensitivity (SI(Oral)) was assessed for 180 min after each meal. SI(Oral) was significantly lower after lunch than after breakfast for all four test meals (P=0·019) following the same rank order (SFA < n-6 PUFA < n-3 PUFA < MUFA) for each meal. The present study demonstrates that a single meal rich in SFA reduces postprandial insulin sensitivity with ‘carry-over’ effects for the next meal.

The present study investigated metabolic responses to fat and carbohydrate ingestion in lean male individuals consuming an habitual diet high or low in fat. Twelve high-fat phenotypes (HF) and twelve low-fat phenotypes (LF) participated in the study. Energy intake and macronutrient intake variables were assessed using a food frequency questionnaire. Resting (RMR) and postprandial metabolic rate and substrate oxidation (respiratory quotient; RQ) were measured by indirect calorimetry. HF had a significantly higher RMR and higher resting heart rate than LF. These variables remained higher in HF following the macronutrient challenge. In all subjects the carbohydrate load increased metabolic rate and heart rate significantly more than the fat load. Fat oxidation (indicated by a low RQ) was significantly higher in HF than in LF following the fat load; the ability to oxidise a high carbohydrate load did not differ between the groups. Lean male subjects consuming a diet high in fat were associated with increased energy expenditure at rest and a relatively higher fat oxidation in response to a high fat load; these observations may be partly responsible for maintaining energy balance on a high-fat (high-energy) diet. In contrast, a low consumer of fat is associated with relatively lower energy expenditure at rest and lower fat oxidation, which has implications for weight gain if high-fat foods or meals are periodically introduced to the diet.

In a randomized, double-blind, placebo-controlled trial we evaluated the effect of dietary chocolates enriched with a wood-based phytosterol–phytostanol mixture, containing 18% (w/w) sitostanol, compared with placebo dietary chocolates in seventy subjects with primary hypercholesterolaemia (total cholesterol levels below 8 mmol/l). For 4 weeks, participants consumed three servings of the phytosterol-enriched chocolate/d that provided 1·8 g unesterified phytosterols/d or a placebo chocolate in conjunction with a low-fat, low-cholesterol diet. Plasma total and LDL-cholesterol levels were statistically significantly reduced by 6·4% (−0·44 mmol/l) and 10·3% (−0·49 mmol/l), respectively, after 4 weeks of phytosterol-enriched-chocolate treatment. Plasma HDL-cholesterol and triacylglycerol levels were not affected. Consumption of phytosterol-enriched chocolates significantly increased plasma lathosterol concentration (+20·7%), reflecting an increased endogenous cholesterol synthesis in response to phytosterol-induced decreased intestinal cholesterol absorption. Furthermore, the chocolates enriched with phytosterols significantly increased both plasma sitosterol (+95·8%) and campesterol (+64·1%) levels, compared with the placebo chocolate group. However, the absolute values of plasma sitosterol and campesterol remained within the normal range, that is, below 10 mg/l. The chocolates with phytosterols were palatable and induced no clinical or biochemical side effects. These findings indicate that dietary chocolate enriched with tall oil-derived phytosterols (1·8 g/d) is effective in lowering blood total and LDL-cholesterol levels in subjects with mild hypercholesterolaemia and thus may be helpful in reducing the risk of CHD in these individuals.

We investigated the effects of dietary oligofructose and Ca on bone structure in ovariectomized rats, using microradiography and histomorphometry. Ninety-six animals were allocated to seven experimental groups: G1, sham-operated; G2–G7, ovariectomized. Semi-purified diets containing 5 g Ca/kg (recommended content) without oligofructose (G1, G2) or with 25, 50 or 100 g oligofructose/kg (G3, G4, G5) or 10 g Ca/kg (high content) without oligofructose (G6) or with 50 g oligofructose/kg (G7) were fed for 16 weeks. At the recommended level of Ca, high oligofructose (G5) increased femur mineral levels in ovariectomized rats, while medium oligofructose did so at high Ca. Increasing Ca in the absence of oligofructose did not increase femur mineral content. Trabecular bone area (%) analysed in the tibia was 10·3 (SEM 1·2) (G1), 7·7 (SEM 0·6) (G2), 9·3 (SEM 0·7) (G3), 9·4 (SEM 1·0) (G4), 9·5 (SEM 0·7) (G5), 10·2 (SEM 0·8) (G6), and 12·6 (SEM 0·8) (G7). At the recommended level of Ca, 25 g oligofructose/kg prevented loss of trabecular area due to increased trabecular thickness, while 50 or 100 g oligofructose/kg increased trabecular perimeter. At high Ca, oligofructose prevented loss of bone area due to increased trabecular number but similar thickness (G7 v. G6). When Ca was raised in the presence of oligofructose (G7), trabecular area and cortical thickness were highest, while loss of trabecular connectivity was lowest of all groups. At the same time, lumbar vertebra Ca was higher; 44·0 (SEM 0·8) (G7) compared with 41·6 (SEM 0·8) (G2), 41·4 (SEM 0·7) (G4), and 40·5 (SEM 1·0) mg (G6). We conclude that ovariectomy-induced loss of bone structure in the tibia was prevented but with different trabecular architecture, depending on whether dietary Ca was increased, oligofructose was incorporated, or both. Oligofructose was most effective when dietary Ca was high.

Fat in human milk is extremely variable and can represent up to 50 % of infant energy intake. To accurately determine milk composition and infant intake at 1 (n 17), 2 (n 17), 4 (n 17), 6 (n 15), 9 (n 6) and 12 (n 5) months of lactation, samples of fore- and hind-milk were collected from each breast at each feed over 24 h periods from an initial group of seventeen women. The content of fat in milk varied over 24 h, with a mean CV of 47·6 (SE 2·1) % (N 76) AND 46·7 (se 1·7) % (n 76) for left and right breasts respectively. The 24 h amounts of fat, lactose and protein in milk differed between women (P=0·0001), but were consistent between left and right breasts. Daily milk production differed between breasts (P=0·0001) and women (P=0·0001). Accordingly, amounts of fat (P=0·0008), lactose (P=0·0385) and protein (P=0·0173) delivered to the infant over 24 h also differed between breasts and women (P=0·0001). The energy content of milk and the amount of energy delivered to the infant over 24 h were the same between breasts, but differed between women (P=0·0001). The growth rate of a group of only six infants in the present study was not related to either the concentrations or amounts of fat, lactose, protein and energy in milk over the first 6 months of life. These results show the individuality of milk composition and suggest that only a rigorous sampling routine that takes into account all levels of variation will allow the accurate determination of infant intake of fat, lactose, protein and energy.

The present experiment aimed to determine the effects of supplements of folic acid (FA) alone or in combination with vitamin B12 on folate and homocysteine metabolism in gestating nulliparous Yorkshire–Landrace (YL) and multiparous Landrace (LD) occidental sows and multiparous Chinese Meishan–Landrace (ML) sows. LD sows were randomly assigned to two treatments: 0 or 15 mg FA/kg diet while YL and ML sows were assigned to three treatments: 0 mg FA/kg diet, 15 mg FA/kg or 15 mg FA+160 μg vitamin B12/kg diet. Supplements were given from the oestrus preceding insemination up to slaughter on day 15 of gestation. At slaughter, a uterine flush was collected to determine uterine contents of homocysteine, methionine, tetrahydrofolate (THF), 5-methyl-THF, pyridoxal 5-phosphate (P5P) and vitamin B12. Blood samples were taken at first oestrus, at insemination and on days 5, 10 and 15 of gestation to determine plasma concentrations of homocysteine, methionine, THF, 5-methyl-THF, P5P, vitamin B12 and relative total folate-binding capacity. In occidental sows (YL and LD), the FA supplement tended to decrease uterine flush content of homocysteine (P=0·06) and concentrations of plasma homocysteine (P=0·09). Nulliparous YL sows had lower concentrations of plasma homocysteine, methionine, THF and 5-methyl-THF (P<0·05) than multiparous LD sows. Multiparous ML and LD sows had similar concentrations of plasma THF, 5-methyl-THF, methionine and vitamin B12, but ML sows had lower concentrations of plasma homocysteine (P<0·05). The vitamin B12 supplement increased concentrations of plasma vitamin B12 (P<0·05) both in multiparous ML and nulliparous YL sows, but had no effect on the composition of either uterine flush or plasma. The present results showed also that sows had a low vitamin B12 status (<200 pg/ml) and high circulating homocysteine levels (>15 μM) during the first 15 d of gestation. Furthermore, the vitamin B12 content in uterine secretions represented between 180 and 300 % of the total content in plasma. The low plasma concentrations of homocysteine in multiparous ML sows suggest a more efficient remethylation pathway which may not be dependent upon dietary supply of FA or vitamin B12. In nulliparous YL sows, low concentrations of both homocysteine and methionine suggest that the methionine requirement for protein deposition might have reduced the amount of methionine available for the methylation pathway. The results of the present experiment suggest that the reduction of uterine homocysteine may be an important aspect of the role of FA supplement on the uterine environment in occidental sows. The presence of high levels of vitamin B12 in uterine secretions merits further investigation in relation to embryonic development.

During pregnancy, the accumulation of long-chain polyunsaturated fatty acids (LCPUFA) in fetal tissues places a substantial demand upon maternal lipid metabolism. As lipid metabolism is intimately linked to aspects of protein metabolism, a reduced protein intake in pregnancy may impair activities of enzymes and transport proteins responsible for supplying LCPUFA to the fetus, thereby compromising fetal development. We have investigated the effect of reduced protein intake on LCPUFA status in the non-pregnant rat and in the pregnant rat, and in fetus at day 20 of gestation. Female rats (n 5 per group) were either mated and fed the control diet (180 g protein/kg) or low-protein diet (90 g protein/kg, LPD) diet throughout pregnancy, or fed the control diet or LPD for 20 d (non-pregnant animals). The fatty acid compositions of maternal liver and plasma, and fetal liver and brain were determined by GC. Feeding the LPD did not lead to any gross changes either in adult or fetal growth, or in total lipid concentrations in adult rat liver. However, the LPD was associated specifically with lower liver (42·6 %) and plasma (19·4 %) phosphatidylcholine (PC), and plasma triacylglycerol (28·6 %) docosahexaenoic acid (DHA) concentrations in pregnant rats and reduced fetal brain PC- (26·1 %) and phosphatidylethanolamine- (25·6 %) DHA concentrations. Together, these results show that variations in maternal dietary protein consumption alter DHA status in pregnancy and modify DHA accumulation into the fetal brain. The present results suggest that lower maternal protein intakes reduce delivery of DHA from the mother to the fetus, which may impair development and function of the fetal brain.

Twenty-four finishing pigs (twelve Iberian and twelve Landrace) were used in a growing and slaughtering experiment. Animals were fed two diets differing in their ingredients, maize (diet C) or sorghum–acorn (diet A). At an average weight of 107·0 kg pigs were slaughtered and hindgut digesta sampled to study the effect of breed and diet on large bowel fermentation. Flows of digesta to the hindgut compartment were estimated based on an indigestible flow marker (Cr2O3) and were higher in Iberian than in Landrace pigs (P<0·001), and higher in animals fed diet A than diet C (P=0·07). The higher flows in Iberian pigs were mainly associated with a higher voluntary feed intake (3·50 v. 2·70 kg/d, P<0·01) and lower ileal digestibility of NSP (−12·8 v. 47·8, P<0·01). Differences between diets were mainly associated with a lower ileal digestibility of starch from diet A (89·2 v. 96·9%, P=0·06), although no differences in the resistant starch content were observed in vitro. Fermentation of different carbohydrates through the large bowel showed that NSP-glucose had lower digestibility in Iberian than in Landrace pigs (62·5 v. 94·2%, P<0·001), but no differences were observed in starch, or other NSP-fibre fractions (arabinose, xylose and galactose). The type and amount of carbohydrates reaching the large bowel were related to the diet but also to breed, and promoted differences in the fermentative activity associated with different volatile fatty acid patterns and changes in microbial enzymic activity.

The perspectives of Latin America as a potential producer and consumer of functional foods will depend largely on the level of information and income of the population, credibility of the products, research investments and regulatory practices. The characteristics of Latin America are diverse at the regional and sub-regional levels. However, as part of the demographic and epidemiological transition currently underway, common trends can be identified such as increasing urbanization and life expectancy, the occurrence of obesity and malnutrition, increasing incidences of chronic diseases and causes of mortality rates, all of which suggests the importance of diet and functional foods in public health policies. The Latin American population in general has no knowledge of functional foods, but in the more urbanized areas there is an increasingly health-conscious consumer, aware of the importance of food for health, due to the media and local traditions. More investment in research is important to explore the existing plant biodiversity that is a rich source of new foods and bioactive compounds, some of which are already used for health improvement and wellbeing. Clinical validation of functional foods should consider functional food science concepts and also the diverse cultural and genetic background of the local population. In Latin American scientific and regulatory communities, the functional foods concept has been associated with foods having health benefits beyond those of basic nutrition but is not defined officially in the emerging regulatory codes. Regulation existing in some countries is focused on safety and efficacy; both functional and health claims are allowed (risk reduction) provided they have scientific validation. This allowed introduction on the market of several products with health claims, some of them submitted to post-marketing surveillance.

The effects of dietary protein content and feeding level on the utilization of metabolizable energy (ME) and on the rates of gain, protein and fat deposition have been studied in seventy-two Iberian pigs growing from 15 to 50 kg body weight (BW) by means of comparative slaughter experiments. The animals were fed on six diets providing 223, 192, 175, 156, 129 and 101 g crude ideal protein (N×6·25; CP)/kg DM and 14·64, 14·14, 14·37, 14·80, 15·36 and 15·53 MJ ME/kg DM respectively. Each diet was offered at three levels of feeding: 0·60, 0·80 and 0·95×ad libitum intake. Protein deposition (PD) increased significantly (P<0·01) with each decrease in dietary CP content and reached a maximum value (74·0 g) when the diet providing 129 g CP/kg DM (6·86 g digestible ideal protein/MJ ME) was offered at the highest feeding level. This feeding regimen resulted in average values for live-weight gain and retained energy (RE) of 559 g/d and 10·9 MJ/d respectively. RE increased significantly (P<0·001) from 480 to 626 kJ/kg BW0·75 with each decrease in dietary CP content from 192 to 129 g/kg DM. Raising the level of feed intake led to significant linear increases in PD and RE irrespective of the diet fed (P<0·001). When diets approaching an adequate supply of CP were given, the net efficiency of use of ME for growth (kw) and the maintenance energy requirements were 58·2 % and 422 kJ/kg BW0·75 per d respectively.

Probiotics are viable non-pathogenic micro-organisms which, when ingested, exert a positive influence on host health or physiology. We have critically analysed the evidence for the efficacy of specific probiotic strains in human gastrointestinal diseases. The best evidence can be obtained with randomised controlled trials which avoid bias. Good evidence has been obtained with several strains in the prevention or treatment of antibiotic-associated disorders, in the treatment (and to a lesser extent prevention) of gastroenteritis and acute diarrhoea and in the alleviation of lactose intolerance. We also analysed the recent randomised controlled trials performed in patients with Clostridium difficile or Helicobacter pylori, inflammatory bowel disease, irritable bowel syndrome, non-ulcer dyspepsia and colon cancer.

The present study aimed to study the effects of food deprivation and subsequent postprandial changes in plasma somatotrophic and thyrotrophic hormone levels and focused on the inter-relationships between these hormonal axes and representative metabolites of the intermediary metabolism of meal-fed broiler chickens. Male broiler chickens (2 weeks old) were fed a meal of 40–45 g/bird per d for two consecutive weeks (food-restricted (FR) treatment). The daily allowance was consumed in about 30 min. At 4 weeks of age, FR chickens were killed at several time intervals (ten per sampling time) in relation to the daily food allowance: before feeding (about 23·5 h of food deprivation), and at 10, 20, 30 (end of feeding), 40, 50, 60, 90, 120 and 200 min after initiation of feeding. Birds fed ad libitum served as controls (ad-libitum (AL) treatment). Liver tissue was collected for deiodinase type I and type III activity measurements and blood samples for analysis of growth hormone (GH), insulin-like growth factor (IGF)-I, thyroxine (T4), 3,3′,5-triiodothyronine (T3), glucose, non-esterified fatty acids (NEFA), uric acid, triacylglycerol (TG) and lactate levels. Food deprivation caused a shift from lipogenesis to lipolysis and increased fatty acid turnover, a reduction in protein anabolism and reduced metabolic rate. Food intake was followed immediately by a pronounced increase in metabolic rate, initially mainly based on anaerobic mechanisms. Refeeding gradually reversed the fasting-induced alterations in plasma hormone and metabolite levels, but the time course of changes differed between metabolites, which clearly preceded those of the hormones investigated. The order of responsiveness after food provision were glucose>uric acid≥NEFA>lactate>TG for the plasma metabolites and GH>T3>T4>IGF–I for hormones. Based on these different postprandial time courses, several functional relationships are proposed. Glucose is believed to be the primary trigger for the normalisation of the effects of fasting on these plasma variables by restoring hepatic GH receptor capacity, as well as decreasing deiodinase type III activity.

The work presented here examines the possible effects of nutritional deficiencies on the characteristics of the plasma transport protein for vitamin D and its metabolites (vitamin D binding protein, DBP) in the growing rat. Deficiencies in both dietary protein intake and dietary energy intake may decrease the concentration of DBP in the circulation, although plasma DBP was not affected by dietary Ca deficiency. None of the dietary factors examined appears to influence the affinity of DBP for its major ligand, 25-hydroxycholecalciferol (25(OH)D3). Protein-deficient rats seemed to have difficulty in maintaining adequate concentrations of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in the circulation. The sensitivity of DBP to dietary protein and energy intake may constitute a novel mechanism that may help to explain the observed associations between malnutrition and the development of metabolic bone disease, through alterations to the cellular availability of vitamin D ligands to DBP.

Cardiovascular disease (CVD) is the leading cause of death in most developed countries. Most CVD deaths are preventable through life-style measures such as diet, exercise and avoidance of cigarette smoking. Decreased intake of saturated fat and cholesterol and increased intake of cholesterol-reducing foods, such as pulses, deserve a high priority for activities designed to prevent CVD. Epidemiological and observational studies indicate that habitual intakes of large amounts of dietary fibre or of vegetables are associated with significantly lower rates of CVD. Studies over four decades document the hypocholesterolaemic effect of pulses and soyabeans. We performed a meta-analysis of eleven clinical trials that examined the effects of pulses (not including soyabeans) on serum lipoproteins. Intake of non-soya pulses was associated with these changes: fasting serum cholesterol, –7·2%, 95% CI –5·8, –8·6%; LDL–cholesterol, –6·2%, 95% CI –2·8, –9·5%; HDL–cholesterol, +2·6%, 95% CI +6·3, –1·0%; triacylglycerols, –16·6 %, 95% CI –11·8 %, –21·5 %; and body weight, –20·9%, 95% CI +2·2%, –4·1%. The hypocholesterolaemic effects of pulses appear related, in estimated order of importance, to these factors: soluble dietary fibre, vegetable protein, oligosaccharides, isoflavones, phospholipids and fatty acids, saponins and other factors. Intake of pulses may also reduce risk for CVD by favourable effects on blood pressure, glycaemia and risk for diabetes, and risk for obesity. Overall, the available evidence indicates that regular consumption of pulses may have important protective effects on risk for CVD.

Consumption of pulses as components of healthy diets is encouraged because it is believed that this is likely to help in reducing the risk of common non-communicable diseases, including cancers. However, the evidence base for the role of pulses in prevention of cancers is unconvincing because of the difficulties, using conventional epidemiological tools, in ascertaining the quantitative contribution made by pulses to cancer risk. Advances in understanding of the biological basis of cancer and of the mechanisms of action of cancer-preventing compounds offer new insights into the role of food-derived substances and of diet—gene interactions in modulating cancer risk. Pulses contain a rich variety of compounds which, if consumed in sufficient quantities, may help to reduce tumour risk.

Duodenal Fe2+ uptake is essential to body Fe2+ homeostasis, but the interaction of metals with the uptake process remains unclear. The present study compared the effects of four essential trace metals (Mn2+, Zn2+, Co2+ and Ni2+) with two toxic metals (Pb2+ and Cd2+) on Fe2+ uptake across the brush border membrane of villus-attached duodenal enterocytes. Everted rat duodenum was exposed to buffer containing 0·2 mM-59FE2+–ASCORBATE WITH OR WITHOUT THE COMPETING METAL (2 Mm) and the tissue was then processed for autoradiography allowing Fe2+ uptake to be determined at specific crypt–villus regions. The quantification method ensured that uptake by cells, rather than Fe2+ binding to the tissue surface, was measured. Fe2+ uptake was significantly inhibited by Cd2+ in upper villus enterocytes only and Pb2+ was without effect on Fe2+ uptake. The inhibition by Cd2+ was not due to general cell damage as judged by the release of lactate dehydrogenase from tissue into incubation fluid. Essential divalent trace metals reduced uptake significantly along the whole length of the crypt–villus axis. Cd2+ uptake, measured separately, took place at all regions of the villus–crypt axis, highest uptake being into crypt enterocytes. The very different uptake profiles for Cd2+ and Fe2+ suggests that the divalent metal transporter 1 is not the principal transporter of Cd2+. The addition of Fe2+ to incubation buffer inhibited Cd2+ uptake by both crypt and villus enterocytes. The possibility that the inhibitory actions of Fe2+ and Cd2+ on the uptakes of Cd2+ and Fe2+ respectively can be explained by a non-competitive action or the involvement of an additional metal transporter is discussed.

Linkages between diet habits and the quality of life continue to surface on numerous fronts. Collectively these epidemiological, pre-clinical and clinical studies provide rather compelling evidence that numerous essential and non-essential dietary components are capable of influencing growth, development and performance and disease prevention. Scientific discoveries and widespread interest in the potential medicinal benefits of foods and food components have fostered a variety of content, health and structure–function claims. Unfortunately, defining the ideal diet is complicated by the numerous and diverse components that may influence biological processes. Inconsistencies in the literature may reflect the multi-factorial nature of these processes and the specificity that individual dietary constituents have in modifying genetic and epigenetic events. New and emerging genomic and proteonomic approaches and technologies offer exciting opportunities for identifying molecular targets for dietary components and thus determining mechanisms by which they influence the quality of life. All cells have unique ‘signatures’ that are characterized by active and inactive genes and cellular products. It is plausible that bridging knowledge about unique cellular characteristics with molecular targets for nutrients can be used to develop strategies to optimize nutrition and minimize disease risk.

Small bowel enteropathy (assessed by the lactulose (L): mannitol (M) permeability test) is a major factor in infant growth faltering and malnutrition in The Gambia. However, little is known about its persistence and nutritional effect beyond 2 years of age. This was addressed by two cross-sectional studies of intestinal permeability and nutritional status in 162 residents, aged 2–60 years, living in three villages in rural Gambia. L:M ratio was found to be highest in the youngest children and although there was a significant improvement with age (P<0·0001), values were always greater than the range found in UK counterparts. M recovery (mean value 5·68 (SE 0·12)%) was at all times between one-third and one-half of expected UK values and showed no improvement with age. Gut barrier function, assessed by L uptake, improved with age (P<0·001) and fell within the UK normal range beyond age 10 years. Both the L:M permeability ratio and L recovery were significantly associated with height-for-age z-scores (r−0·31 and −0·22 respectively, P<0·001), a relationship that persisted throughout childhood and into adulthood. Change in height-for-age z-score beween the two visits was also related to the L:M ratio (r−0·24, P=0·018). The close within-subject correlation of permeability variabilities between the two visits suggests a long-term persistence of enteropathy within individuals. It appears that the small bowel enteropathy previously described in Gambian infants persists through to adulthood. Although the lesion improves with age, the relationship between attained height and L:M permeability raises the possibility that enteropathy may continue to limit growth throughout childhood and puberty.

Free radicals and reactive species produced in vivo can trigger cell damage and DNA modifications resulting in carcinogenesis. Dietary antioxidants trap these species limiting their damage. The present study evaluated the role of vitamins C and E in the prevention of potentially premalignant modifications to DNA in the human stomach by supplementing patients who, because of hypochlorhydria and possible depletion of gastric antioxidants, could be at increased risk of gastric cancer. Patients undergoing surveillance for Barrett's oesophagus (n 100), on long-term proton pump inhibitors were randomized into two groups: vitamin C (500 mg twice/d) and vitamin E (100 mg twice/d) for 12 weeks (the supplemented group) or placebo. Those attending for subsequent endoscopy had gastric juice, plasma and mucosal measurements of vitamin levels and markers of DNA damage. Seventy-two patients completed the study. Plasma ascorbic acid, total vitamin C and vitamin E were elevated in the supplemented group consistent with compliance. Gastric juice ascorbic acid and total vitamin C levels were raised significantly in the supplemented group (P=0·01) but supplementation had no effect on the mucosal level of this vitamin. However, gastric juice ascorbic acid and total vitamin C were within normal ranges in the unsupplemented group. Mucosal malondialdehyde, chemiluminescence and DNA damage levels in the comet assay were unaffected by vitamin supplementation. In conclusion, supplementation does not affect DNA damage in this group of patients. This is probably because long-term inhibition of the gastric proton pump alone does not affect gastric juice ascorbate and therefore does not increase the theoretical risk of gastric cancer because of antioxidant depletion.

Since excess dietary lysine (Lys) can increase the chick's arginine (Arg) requirement and excess Arg can increase the chick's methionine (Met) requirement, experiments were conducted to test the hypothesis that responses to dietary Lys and Met are also interrelated. Day-old Ross × Ross chicks were fed a maize–soyabean meal-based diet supplemented with four levels of L-Arg (0, 5, 10 or 20 g/kg), factorially arranged with four levels of supplemental DL-Met (0, 1, 2 or 3 g/kg). Three replicate pens of ten chicks each were randomly assigned to each treatment and fed for 14 d. An increase in Arg in the diet caused growth and feed-intake depression (P=0·0001), but increasing Met in the diet enhanced growth and feed intake (P=0·0001). Arg toxicity was dependent on the Met level of the diet (Arg × Met interaction; P=0·0153). Experiment 2 was conducted to study interrelationships among Arg, Met, and Lys. Eight treatments were factorially combined: two levels of supplemental L-Arg (0 or 10 g/kg), two levels of supplemental DL-Met (0 or 2 g/kg), and two levels of supplemental L-Lys (0 or 6 g/kg). Six replicate pens of eight chicks per treatment were used. A three-way interaction among Arg, Met, and Lys was observed for body-weight gain and feed intake (P<0·023). As expected, kidney arginase activity increased as dietary Lys increased (P=0·0004). No interactions were found for kidney arginase activity. Muscle creatine increased when chicks were fed the higher Arg (25·2 g/kg) diet (P=0·0047). A three-way interaction among Arg, Met, and Lys was found for muscle creatine (P=0·0075). Excess dietary Lys depressed muscle creatinine concentration, but only in the presence of the lower concentrations of Arg and Met. To conclude, an interrelationship among Arg, Met, and Lys was demonstrated, and it was probably related to creatine biosynthesis.