In an intensive livestock production, a shorter suckling period allows more piglets to be born. However, this practice leads to a number of disorders including nutrient malabsorption, resulting in diarrhoea, malnutrition and dehydration. A number of strategies have been proposed to overcome weaning problems. Artificial sweeteners, routinely included in piglets' diet, were thought to enhance feed palatability. However, it is shown in rodent models that when included in the diet, they enhance the expression of Na+/glucose co-transporter (SGLT1) and the capacity of the gut to absorb glucose. Here, we show that supplementation of piglets' feed with a combination of artificial sweeteners saccharin and neohesperidin dihydrochalcone enhances the expression of SGLT1 and intestinal glucose transport function. Artificial sweeteners are known to act on the intestinal sweet taste receptor T1R2/T1R3 and its partner G-protein, gustducin, to activate pathways leading to SGLT1 up-regulation. Here, we demonstrate that T1R2, T1R3 and gustducin are expressed together in the enteroendocrine cells of piglet intestine. Furthermore, gut hormones secreted by the endocrine cells in response to dietary carbohydrates, glucagon-like peptides (GLP)-1, GLP-2 and glucose-dependent insulinotrophic peptide (GIP), are co-expressed with type 1 G-protein-coupled receptors (T1R) and gustducin, indicating that L- and K-enteroendocrine cells express these taste elements. In a fewer endocrine cells, T1R are also co-expressed with serotonin. Lactisole, an inhibitor of human T1R3, had no inhibitory effect on sweetener-induced SGLT1 up-regulation in piglet intestine. A better understanding of the mechanism(s) involved in sweetener up-regulation of SGLT1 will allow the identification of nutritional targets with implications for the prevention of weaning-related malabsorption.

The present study reports the Na intake of a representative sample of Spanish young and middle-aged adults aged 18–60 years (n 418, 53·1 % women, selected from the capitals of fifteen provinces and the surrounding semi-urban/rural area), measured with a 24 h urinary Na excretion method. To validate the paper collection of 24 h urine, the correlation between fat-free mass determined by electrical bioimpedance (50·8 (sd 11·3) kg) and that determined via urinary creatinine excretion (51·5 (sd 18·8) kg) was calculated (r 0·633, P < 0·001). Urinary Na excretion correlated with systolic and dyastolic blood pressure data (r 0·243 and 0·153, respectively). Assuming that all urinary Na (168·0 (sd 78·6) mmol/d) comes from the diet, Na excretion would correspond with a dietary salt intake of 9·8 (sd 4·6) g/d, and it would mean that 88·2 % of the subjects had salt intakes above the recommended 5 g/d. Logistic regression analysis, adjusted for sex, age and BMI, showed male sex (OR 3·678, 95 % CI 2·336, 5·791) and increasing BMI (OR 1·069, 95 % CI 1·009, 1·132) (P < 0·001) to be associated with excreting >200 mmol/d urinary Na – a consequence of the higher salt intake in men and in participants with higher BMI. The present results help us to know the baseline salt intake in the Spanish young and middle-aged adult population, and can be used as the baseline to design policies to reduce salt consumption.

The risk of Alzheimer's disease is increased for carriers of apoE4 (E4) or the PPAR-α L162V polymorphism (L162V), but it is decreased in fish and seafood consumers. The link between high fish intake and reduced risk of cognitive decline in the elderly appears not to hold in carriers of E4, possibly because better cognition is linked to EPA+DHA in the blood, but only in non-carriers of E4. As yet, no such studies exist in carriers of L162V. Our objective was to determine whether the plasma fatty acid response to a dietary supplement of EPA+DHA was altered in carriers of L162V and/or E4. This was an add-on project; in the original study, men were selected based on whether or not they were carriers of L162V (n 14 per group). E4 status was determined afterwards. All subjects received an EPA+DHA supplement for 6 weeks. L162V polymorphism did not interact with the supplement in a way to alter EPA and DHA incorporation into plasma lipids. However, when the groups were separated based on the presence of E4, baseline EPA and DHA in plasma TAG were 67 and 60 % higher, respectively, in E4 carriers. After the supplementation, there were significant gene × diet interactions in which only non-carriers had increased EPA and DHA in plasma NEFA and TAG, respectively.

1. The cellular proteins of Butyrivibrio jibrisolvens, Lactobacillus casei, Megasphaera elsdenii, Selenomonas ruminantium and Streptococcus bovis were labelled by growth in the presence of L-[14C]leucine, and the breakdown of labelled protein was measured in incubations of these bacteria with rumen fluid to which unlabelled 5 mM-L-leucine was added. The rate of protein breakdown was estimated from the rate of release of radioactivity into acid-soluble material.

2. Protein breakdown occurred at different rates in different species. The mean rates for B. fibrisolvens, L. casei, M. elsdenii, Sel. ruminantium and Str. bovis were 28.6, 18.1, 17.7, 10.5 and 5.3% /h respectively in samples of strained rumen fluid (SRF) with different protozoal populations. Rates of 3% /h or less were found in SRF from ciliate-free sheep or in faunated SRF from which protozoa had been removed by centrifugation. Further removal of mixed rumen bacteria had little effect. Suspensions of washed protozoa degraded bacterial protein at rates which were of the same order as those found in SRF.

3. The rate of breakdown of bacterial protein in different samples of SRF tended to increase as the numbers of small entodiniomorphid protozoa increased. The numbers of larger entodiniomorphs and holotrichs had no obvious influence on this rate.

4. Autoclaved and u.v.-treated bacteria were generally no different from live bacteria in their susceptibility to breakdown in SRF from faunated sheep, indicating that endogenous protein turnover was not a significant cause of bacterial protein catabolism.

5. The rate of bacterial protein breakdown was unrelated to the proteolytic activity of SRF.

6. It was concluded that predation by small protozoa is by far the most important cause of bacterial protein turnover in the rumen, with autolysis, other lytic factors and endogenous proteolysis being of minor importance.

The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (>70 %) energy restriction (ER) interspersed with normal eating. Studies to date comparing IER to continuous energy restriction (CER) have predominantly measured fasting indices of cardiometabolic risk. This study aimed to compare the effects of IER and CER on postprandial glucose and lipid metabolism following matched weight loss. In all, twenty-seven (thirteen male) overweight/obese participants (46 (sem 3) years, 30·1 (sem 1·0) kg/m2) who were randomised to either an IER intervention (2638 kJ for 2 d/week with an overall ER of 22 (sem 0·3) %, n 15) or a CER intervention (2510 kJ below requirements with overall ER of 23 (sem 0·8) %) completed the study. Postprandial responses to a test meal (over 360 min) and changes in anthropometry (fat mass, fat-free mass, circumferences) were assessed at baseline and upon attainment of 5 % weight loss, following a 7-d period of weight stabilisation. The study found no statistically significant difference in the time to attain a 5 % weight loss between groups (median 59 d (interquartile range (IQR) 41–80) and 73 d (IQR 48–128), respectively, P=0·246), or in body composition (P≥0·437). For postprandial measures, neither diet significantly altered glycaemia (P=0·266), whereas insulinaemia was reduced comparatively (P=0·903). The reduction in C-peptide tended (P=0·057) to be greater following IER (309 128 (sem23 268) to 247781 (sem20 709) pmol×360 min/l) v. CER (297 204 (sem25 112) to 301 655 (sem32 714) pmol×360 min/l). The relative reduction in TAG responses was greater (P=0·045) following IER (106 (sem30) to 68 (sem 15) mmol×360 min/l) compared with CER (117 (sem 43) to 130 (sem 31) mmol×360 min/l). In conclusion, these preliminary findings highlight underlying differences between IER and CER, including a superiority of IER in reducing postprandial lipaemia, which now warrant targeted mechanistic evaluation within larger study cohorts.

The prenatal diet can program an individual's cardiovascular system towards later higher resting blood pressure and kidney dysfunction, but the extent to which these programmed responses are directly determined by the timing of maternal nutritional manipulation is unknown. In the present study we examined whether maternal nutrient restriction targeted over the period of maximal placental growth, i.e. days 28–80 of gestation, resulted in altered blood pressure or kidney development in the juvenile offspring. This was undertaken in 6-month-old sheep born to mothers fed control (100–150 % of the recommended metabolisable energy (ME) intake for that stage of gestation) or nutrient-restricted (NR; 50 % ME; n 6) diets between days 28 and 80 of gestation. Controls were additionally grouped according to normal (>3, n 7) or low body condition score (LBCS; <2, n 6), thereby enabling us to examine the effect of maternal body composition on later cardiovascular function. From day 80 to term (approximately 147 d) all sheep were fed to 100 % ME. Offspring were weaned at 12 weeks and pasture-reared until 6 months of age when cardiovascular function was determined. Both LBCS and NR sheep tended to have lower resting systolic (control, 85 (SE 2); LBCS, 77 (SE 3); NR, 77 (SE 3) mmHg) and diastolic blood pressure relative to controls. Total nephron count was markedly lower in both LBCS and NR relative to controls (LBCS, 59 (SE 6); NR, 56 (SE 12) %). Our data suggest that maternal body composition around conception is as important as the level of nutrient intake during early pregnancy in programming later cardiovascular health.

Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases. The present study aimed to estimate dietary flavan-3-ol, proanthocyanidin (PA) and theaflavin intakes, their food sources and potential determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration cohort. Dietary data were collected using a standardised 24 h dietary recall software administered to 36 037 subjects aged 35–74 years. Dietary data were linked with a flavanoid food composition database compiled from the latest US Department of Agriculture and Phenol-Explorer databases and expanded to include recipes, estimations and retention factors. Total flavan-3-ol intake was the highest in UK Health-conscious men (453·6 mg/d) and women of UK General population (377·6 mg/d), while the intake was the lowest in Greece (men: 160·5 mg/d; women: 124·8 mg/d). Monomer intake was the highest in UK General population (men: 213·5 mg/d; women: 178·6 mg/d) and the lowest in Greece (men: 26·6 mg/d in men; women: 20·7 mg/d). Theaflavin intake was the highest in UK General population (men: 29·3 mg/d; women: 25·3 mg/d) and close to zero in Greece and Spain. PA intake was the highest in Asturias (men: 455·2 mg/d) and San Sebastian (women: 253 mg/d), while being the lowest in Greece (men: 134·6 mg/d; women: 101·0 mg/d). Except for the UK, non-citrus fruits (apples/pears) were the highest contributors to the total flavan-3-ol intake. Tea was the main contributor of total flavan-3-ols in the UK. Flavan-3-ol, PA and theaflavin intakes were significantly different among all assessed groups. This study showed heterogeneity in flavan-3-ol, PA and theaflavin intake throughout the EPIC countries.

Certain dietary patterns may be related to the risk of CVD. We hypothesised that a plant-centred dietary pattern would be associated with a reduced risk of first myocardial infarction (MI). A case–control study of Norwegian men and postmenopausal women (age 45–75 years) was performed. A FFQ was administered, generally within 3 d after incident MI (n 106 cases). Controls (n 105) were frequency matched on sex, age and geographic location. On the FFQ, 190 items were categorised into thirty-five food groups and an a priori healthy diet pattern score was created. We estimated OR using logistic regression with adjustment for energy intake, family history of heart disease, marital status, current smoking, education and age. Among food groups, the risk of MI was significantly higher per sd of butter and margarine (OR 1·66 (95 % CI 1·12, 2·46)), and lower per sd of tomatoes (OR 0·53 (95 % CI 0·35, 0·79)), high-fat fish (OR 0·57 (95 % CI 0·38, 0·86)), wine (OR 0·58 (95 % CI 0·41, 0·83)), salad (OR 0·59 (95 % CI 0·40, 0·87)), wholegrain breakfast cereals (OR 0·64 (95 % CI 0·45, 0·90)), cruciferous vegetables (OR 0·66 (95 % CI 0·47, 0·93)) and non-hydrogenated vegetable oil (OR 0·68 (95 % CI 0·49, 0·95)). An abundance of cases were found to have a low a priori healthy diet pattern score. A dietary pattern emphasising nutrient-rich plant foods and high-fat fish and low in trans fatty acids was associated with decreased risk of MI among Norwegians.

The UK Food Standards Agency (FSA) convened an international group of scientific experts to review three Agency-funded projects commissioned to provide evidence for the relative contributions of two sources, dietary vitamin D intake and skin exposure to UVB rays from sunlight, to vitamin D status. This review and other emerging evidence are intended to inform any future risk assessment undertaken by the Scientific Advisory Committee on Nutrition. Evidence was presented from randomised controlled trials to quantify the amount of vitamin D required to maintain a serum 25-hydroxy vitamin D (25OHD) concentration >25 nmol/l, a threshold that is regarded internationally as defining the risk of rickets and osteomalacia. Longitudinal evidence was also provided on summer sunlight exposure required to maintain 25OHD levels above this threshold in people living in the British Isles (latitude 51°–57°N). Data obtained from multi-level modelling of these longitudinal datasets showed that UVB exposure (i.e. season) was the major contributor to changes in 25OHD levels; this was a consistent finding in two Caucasian groups in the north and south of the UK, but was less apparent in the one group of British women of South Asian origin living in the south of the UK. The FSA-funded research suggested that the typical daily intake of vitamin D from food contributed less than UVB exposure to average year-round 25OHD levels in both Caucasian and Asian women. The low vitamin D status of Asian women has been acknowledged for some time, but the limited seasonal variation in Asian women is a novel finding. The Workshop also considered the dilemma of balancing the risks of vitamin D deficiency (from lack of skin exposure to sunlight in summer) and skin cancer (from excessive exposure to sunlight with concomitant sunburn and erythema). Cancer Research UK advises that individuals should stay below their personal sunburn threshold to minimise their skin cancer risk. The evidence suggests that vitamin D can be produced in summer at the latitude of the UK, with minimal risk of erythema and cell damage, by exposing the skin to sunlight for a short period at midday, when the intensity of UVB is at its daily peak. The implications of the new data were discussed in the context of dietary reference values for vitamin D for the general population aged 4–64 years. Future research suggestions included further analysis of the three FSA-funded studies as well as new research.

The inhibitory effect on human and rat intestinal disaccharidase by the extractive from the leaves ofMorus alba (ELM) containing 0·24% 1-deoxynojirimycin equivalent and its inhibitory activities were investigated by the modified Dahlqvist method. In the presence of 1000-fold diluted ELM solution, the sucrase activity of four human samples was inhibited by 96% and that of maltase and isomaltase by 95 and 99 %, respectively. The activities of trehalase and lactase were inhibited by 44 and 38 %, respectively. The human disaccharidase activities varied from sample to sample because the samples were obtained from different resected regions after surgery. However, the ratio of the inhibitory effect for sucrase, maltase, isomaltase, trehalase and lactase was very similar among the four samples, and also that of resembled rat intestinal disaccharides. The inhibitory constant of the 1-deoxynojirimycin equivalent for sucrase, maltase and isomaltase was 2·1× 10−4, 2·5 × 10−4 and 4·5 10−4μM, respectively, and these inhibitory activities were shown, using rat brush border membrane vesicles, to be competitive. These results demonstrate that digestion is inhibited when an appropriate amount of ELM is orally ingested with sucrose or polysaccharide in man. When ELM was orally administered in a sucrose solution to fasted rats, the elevation in blood glucose was significantly suppressed, depending on the concentration of ELM given. These results suggest that ELM could be used as an ingredient in health foods and in foods that help to prevent diabetes.

1. Twenty-two British Friesian bull calves were used in a comparative slaughter experiment to determine the effects of a β-agonist (clenbuterol) on body composition and energy retention. Four calves were slaughtered at 18 d of age and constituted the initial slaughter group. Of the remaining calves, eight (group A, controls) were given milk replacer only, and ten calves (groups B and C, five calves per group) were given milk replacer plus clenbuterol(O.1 and 1.0 mg clenbuterol/kg milk replacer equivalent to approximately 2 and 20 μg/kg body-weight respectively over the 105±3 d of the experimental period). Calves were slaughtered over the weight range 146–177 kg.

2. Clenbuterol had no significant effect on dry matter (DM) intake, daily live-weight gain or feed conversion ratio. DM digestibility of the milk replacer was not affected by treatment. Nitrogen balance was measured on three separate occasions starting when the calves weighed approximately 60, 110 and 130 kg. N retention was increased over the experimental period in clenbuterol-treated calves, although the effect only achieved significance in calves weighing approximately 110 kg live weight (P < 0.05).

3. Clenbuterol (20 μg/kg body-weight) increased estimated mean daily N retention in the carcass of the calves from 22 to 25 g whilst N retention in the non-carcass components decreased from 10 to 8 g/d. Effects of clenbuterol on N retention occurred mainly in skeletal muscle. Fat in both carcass and non-carcass components was reduced by treatment with clenbuterol. The total energy content of live-weight gain was reduced from 1077 to 897 MJ in clenbuterol-treated calves and mean daily heat production was estimated to increase from 23.1 in controls to 25.9 MJ/d in calves in group C.

4. In calves of mean live weight during balance of 120 and 136 kg, clenbuterol significantly increased daily urinary creatinine excretion and in 120 kg calves NT-methylhistidine was significantly decreased (P < 0.05). Based on estimates of muscle mass from urinary creatinine and protein degradation fromN7-methylhistidine NT-methylhistidine excretion, the fractional breakdown rate of muscle protein in clenbuterol-treated calves was only 0.66 of that in the controls when the calves weighed 120 kg.

1. Forty-eight intact male lambs (30 kg) were fed to gain 16 (H), 5 (M) or –6 (L) kg during a 42 d interval (period 1). Lambs from each of the H and M groups were fed to gain either 16 (HH, MH), 5 (HM, MM) or –6 (HL, ML) kg and lambs from the L group were fed to gain 27 (LS), 16 (LH) or 5 (LM) kg during the ensuing 42 d (period 2).

2. Fasting heat production (FHP) of four lambs from each treatment was determined at the end of period 2.

3. Weights and compositions of the carcass, offal and digesta-free body as well as weights of major internal organs were determined for four lambs of each treatment at the end of periods 1 and 2.

4. Within groups of lambs of similar weight at the end of period 2, body composition was, in general, similar, but FHP was greater in lambs that had been on higher planes of nutrition during period 2.

5. Within groups of lambs of similar weight, lambs that were fed at higher planes of nutrition during period 2 had greater weights or proportions of liver, small intestine, large intestine and stomach.

6. Neither weight of the liver, kidney, stomach, small intestine, large intestine nor daily fasting heat production were constant functions of body-weight. Relations of these traits to body-weight changed with rate of gain.

7. Regression analysis indicated that the feeding of lambs at higher planes of nutrition during period 1 resulted in higher maintenance requirements of those lambs during period 2.

Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts. RS diets were assigned at random within the context of higher (51–53 %E) v. lower CHO (39–40 %E) intake. Measurements were obtained in the fasting state and, for glucose and insulin, during a meal test matching the composition of the assigned diet. With lower CHO intake, plasma TMAO, carnitine, betaine and γ-butyrobetaine concentrations were higher after the high- v. low-RS diet (P<0·01 each). These metabolites were not differentially affected by high v. low RS when CHO intake was high. Although the high-RS meal reduced postprandial insulin and glucose responses when CHO intake was low (P<0·01 each), RS did not affect fasting lipids, lipoproteins, glucose or insulin irrespective of dietary CHO content. In conclusion, a lower-CHO diet high in RS was associated with higher plasma TMAO levels. These findings, together with the absence of change in fasting lipids, suggest that short-term high-RS diets do not improve markers of cardiometabolic health.

1. A technique is described for the measurement of the extent of 65Zn absorption by different regions of the intestine in the intact rat. Using this technique it was shown that the duodenum contributed 60%, the ileum 30% and the jejunum 10% to the over-all absorption of 65Zn. Negligible absorption of 65Zn occurred from the caecum and colon.

2. Using ligated loops of rat duodenum in situ, 65Zn absorption was shown to be rapid, with 1% of a 5 μg dose being transferred to the carcase within 1 min of intraluminal dosing.

3. When 65Zn was injected into ligated loops in a dose range of 1–200 μg Zn/ml the rate of absorpion was linear with respect to time over the first 15 min. The rates of 65Zn absorption v. dose of 65Zn exhibited saturation kinetics indicating absorpion by a ‘carrier’ or enzyme-mediated process.

4. The binding of 65Zn to loop tissue showed biphasic kinetics which suggested that at low intraluminal concentrations of Zn (1–50 μg Zn/ml) binding was to specific sites whereas, at higher concentrations (50–200 μg Zn/ml), non-specific binding occurred.

5. A study of the fate of mucosally bound 65Zn showed that over the first 30 min a proportion of the 65Zn was rapidly transferred to the carcase and this was probably associated with the rapid phase of 65Zn absorption described previously. From 30 min up to 6 h after the initial binding, 65Zn was also transferred to the carcase albeit at a much slower rate indicating a slow phase of Zn absorption. A study of the kinetics of this slow phase indicated that the loss of bound 65Zn to the body was a saturable process indicating an enzyme or ‘carrier’-mediated process. A comparison of the kinetics of the slow and rapid phases of 65Zn absorption suggests that these processes are distinct.

6. Histological examination of mucosal tissue of loops exposed to 200 μg Zn/ml revealed no discernable damage. Similarly, no effect was observed on either arginine or glucose uptake by isolated duodenal loops in situ, although this concentration of Zn completely abolished fluid uptake. A study of the effect of different doses of Zn showed that 50 μg Zn/ml inhibited mucosal fluid uptake by more than 50% and 100 μg Zn/ml by more than 90%. It was concluded that these effects were due to a specific action on the fluid-transfer process and not due to a general poisoning of the mucosa.

1. Studies were made on the lysine content of casein reacted with caffeic acid oxidized aerobically under alkaline conditions or enzymically with tyrosinase (EC 1.14.18.1).

2. Loss of fluorodinitrobenzene (FDNB)-reactive lysine was rapid at pH 10 and increased with time and the temperature of the reaction, with concentration of caffeic acid and with the oxygenation of the mixture. In presence of the enzyme mushroom tyrosinase, maximum reduction of reactive lysine occurred at pH 7 and was dependent on the reaction time and on the concentration of caffeic acid.

3. Reaction of α-formyl-L-[U- 14C]lysine with caffeic acid at pH 10 showed the rapid formation of five reaction products which appeared to polymerize gradually as the reaction progressed.

4. The nutritionally available lysine content of the casein-caffeic acid mixtures, as assayed with rats, was reduced after both alkaline and enzymic reactions, as were faecal digestibility, net protein ratio and net protein utilization. Biological value however was not reduced.

5. In metabolic studies using goat milk casein labelled with L-[3H]lysine and reacted with caffeic acid in the same way, the lysine–caffeoquinone reaction products were not absorbed by the rat but were excreted directly in the faeces.

6. The importance of the reaction of proteins with caffeoquinone and chlorogenoquinone (formed by the oxidation of caffeic and chlorogenic acids respectively) is discussed in relation to the production of sunflower protein, leaf protein and other vegetable-protein concentrates.

Cu is an essential nutrient for man, but can be toxic if intakes are too high. In sensitive populations, marginal over- or under-exposure can have detrimental effects. Malnourished children, the elderly, and pregnant or lactating females may be susceptible for Cu deficiency. Cu status and exposure in the population can currently not be easily measured, as neither plasma Cu nor plasma cuproenzymes reflect Cu status precisely. Some blood markers (such as ceruloplasmin) indicate severe Cu depletion, but do not inversely respond to Cu excess, and are not suitable to indicate marginal states. A biomarker of Cu is needed that is sensitive to small changes in Cu status, and that responds to Cu excess as well as deficiency. Such a marker will aid in monitoring Cu status in large populations, and will help to avoid chronic health effects (for example, liver damage in chronic toxicity, osteoporosis, loss of collagen stability, or increased susceptibility to infections in deficiency). The advent of high-throughput technologies has enabled us to screen for potential biomarkers in the whole proteome of a cell, not excluding markers that have no direct link to Cu. Further, this screening allows us to search for a whole group of proteins that, in combination, reflect Cu status. The present review emphasises the need to find sensitive biomarkers for Cu, examines potential markers of Cu status already available, and discusses methods to identify a novel suite of biomarkers.

Long-chain n-3 fatty acids (FA) consistently inhibit the growth of human breast cancer (BC) cells both in culture and in grafts in immunosuppressed mice. Large cohort studies have, however, failed to confirm a protective effect for fish oils rich in n-3 FA against BC risk. The present review examines new evidence on biological mechanisms which may be involved in the inhibition of mammary carcinogenesis by long-chain n-3 FA, focusing on an apoptotic effect by its lipid peroxidation products. Dietary intake of n-3 FA leads to their incorporation into cell membrane lipids. Increased apoptosis in human BC cells following exposure to long-chain n-3 FA such as eicosapentaenoic and docosahexaenoic acids is generally ascribed to their inhibition of cyclooxygenase 2 which promotes mammary carcinogenesis. In addition however, long-chain n-3 FA are particularly likely to activate peroxisome proliferator-activated receptor (PPAR)-γ, a key regulator of lipid metabolism but also capable of modulating proliferative activity in a variety of cells including mammary cells. Expression of PPAR-γ in the nucleus is activated by second messengers such as J series prostaglandins and the latter have been shown to cause apoptosis in vivo in explants of human BC cells in immunosuppressed mice. In mammary tumours, it is observed that long-chain FA not only increase apoptosis, but also increase lipid peroxidation, and the apoptotic effect can be reversed by antioxidants. The rationale for use of n-3 FA dietary supplements in counteracting BC progression needs to be tested clinically in a phase 2 pilot study, while at the same time, the effect on whole-body lipid peroxidation needs to be monitored. Dietary supplements of fish oil rich in n-3 FA are proposed for premenopausal women over the age of 40 years who are shown to be at increased BC risk. Biological markers in breast tissue of BC progression will be monitored, and observed changes related to serial plasma levels of isoprostanes as a measure of whole-body lipid peroxidation.

Studies on the association between plant foods and cerebrovascular diseases have given contradictory results suggesting the existence of some effect-modifying factors. The present study determines whether the consumption of plant foods (i.e. fruits and berries, vegetables, and cereals) predicts a decreased cerebrovascular disease incidence in a population with low fruit and vegetable and high wholegrain intake. This cohort study on 3932 men and women was based on data from the Finnish Mobile Clinic Health Examination Survey, conducted in 1968–72. The participants were 40–74 years of age and free of cardiovascular diseases at baseline. Data on the plant food consumption were derived from a 1-year dietary history interview. During a 24-year follow-up 625 cases of cerebrovascular diseases occurred, leading to either hospitalisation or death. An inverse association was found between fruit consumption and the incidence of cerebrovascular diseases, ischaemic stroke and intracerebral haemorrhage. The adjusted relative risks (RR) between the highest and lowest quartiles of intake of any cerebrovascular disease, ischaemic stroke and intracerebral haemorrhage were 0·75 (95 % CI 0·59, 0·94), 0·73 (95 % CI 0·54, 1·00) and 0·47 (95 % CI 0·24, 0·92), respectively. These associations were primarily due to the consumption of citrus fruits and occurred only in men. Total consumption of vegetables or cereals was not associated with the cerebrovascular disease incidence. The consumption of cruciferous vegetables, however, predicted a reduced risk of cerebrovascular diseases (RR 0·79; 95 % CI 0·63, 0·99), ischaemic stroke (RR 0·67; 95 % CI 0·49, 0·92) and intracerebral haemorrhage (RR 0·49; 95 % CI 0·25, 0·98). In conclusion, the consumption of fruits, especially citrus, and cruciferous vegetables may protect against cerebrovascular diseases.

Subjects with obesity and elevated fasting blood glucose are at high risk of developing type 2 diabetes which may be reduced by a dietary intervention leading to an improvement of insulin resistance. We investigated the potential of a whole-grain based dietary product (WG) with reduced starch content derived from double-fermented wheat during a hypo-energetic diet to positively influence body weight, fasting blood glucose, insulin resistance and lipids in comparison to a nutrient-dense meal replacement product (MR) in a randomized two-way cross-over study with two 4-week treatment periods separated by a 2-week wash-out. Subjects replaced at least two daily meals with WG and MR, respectively, targeting for a consumption of 200 g of either product per day. Total daily energy intake was limited to 7120 kJ. Thirty-one subjects (BMI 33·9 (sd 2·7) kg/m2, fasting blood glucose 6·3 (sd 0·8) mmol/l) completed the study. In both treatment groups body weight ( − 2·5 (sd 2·0) v. − 3·2 (sd 1·6) kg for WG v. MR), fasting blood glucose ( − 0·4 (sd 0·3) v. − 0·5 (sd 0·5) mmol/l), total cholesterol ( − 0·5 (sd 0·5) v. − 0·6 (sd 0·5) mmol/l), TAG ( − 0·3 (sd 0·9) v. − 0·3 (sd 1·2) mmol/l) and homeostasis model assessment (HOMA) insulin resistance score ( − 0·7 (sd 0·8) v. − 1·1 (sd 1·7) μU/ml ×  mmol/l) improved (P < 0·05) with no significant differences between the treatments. After statistical adjustment for the amount of body weight lost, however, the comparison between both groups revealed that fasting serum insulin (P = 0·031) and HOMA insulin resistance score (P = 0·049) improved better with WG than with MR. We conclude that WG favourably influences metabolic risk factors for type 2 diabetes independent from the amount of body weight lost during a hypo-energetic diet.