Vitamins A and E are essential, naturally occurring, fat-soluble nutrients that are involved in several important biological processes such as immunity, protection against tissue damage, reproduction, growth and development. They are extremely important during the early stages of life and must be transferred adequately to the young during gestation and lactation. The present article presents an overview of their biological functions, metabolism and dynamics of transfer to offspring in mammals. Among other topics, the review focuses on the biochemical aspects of their intestinal absorption, blood transport, tissue uptake, storage and catabolism. It also describes their different roles as well as their use as preventive and therapeutic agents. Finally, the mechanisms involved in their transfer during gestation and lactation are discussed.

The HDL-bound enzyme paraoxonase (PON) protects LDL from oxidation and may therefore attenuate the development of atherosclerosis. We examined the effect of tomato and carrot juice consumption on PON1 activity and lipid peroxidation in healthy young volunteers with different PON1-192 genotypes (Q/R substitution at position 192). In this randomized cross-over study twenty-two healthy, non-smoking men on a low-carotenoid diet received 330 ml/d tomato juice (37·0 mg lycopene, 1·6 mg β-carotene) or carrot juice (27·1 mg β-carotene, 13·1 mg α-carotene) for 2 weeks. Intervention periods were preceded by 2-week low-carotenoid intake. We determined the PON1-192 genotype by restriction fragment length polymorphism–polymerase chain reaction (RFLP-PCR) and measured ex vivo LDL oxidation (lag time), plasma malondialdehyde and PON1 activity at the beginning and end of each intervention period. At baseline, lag time was higher (P<0·05) in QQ (111 (sd 9) min) than in QR/RR subjects (101 (sd 8) min). Neither tomato nor carrot juice consumption had significant effects on PON1 activity. However, tomato juice consumption reduced (P<0·05) plasma malondialdehyde in QR/RR (Δ: −0·073 (sd 0·11) μmol/l) as compared to QQ subjects (Δ:+0·047 (sd 0·13) μmol/l). Carrot juice had no significant effect on malondialdehyde irrespective of the PON1-192 genotype. Male volunteers with the QR/RR genotype showed an increased lipid peroxidation at baseline. Although tomato and carrot juice fail to affect PON1 activity, tomato juice intake reduced lipid peroxidation in healthy volunteers carrying the R-allele of the PON1-192 genotype and could thus contribute to CVD risk reduction in these individuals.

The aim of this paper is to discuss issues that fall within the general concept of well-being, with special emphasis on approaches that have been used in studies of nutrition and behaviour. Following this, two specific studies are described in detail, the first examining high-fibre breakfast cereals and the second investigating effects of inulin. Studies of nutrition and well-being can be categorised in a number of ways. One method involves examining acute effects of nutrition on mood and cognitive functioning. Another method has been to examine cross-sectional associations between dietary habits and questionnaire measures of reported health. Examples are given showing that regular consumption of a high-fibre diet is associated with better-reported physical and mental health. The problem with such correlational studies is that it is impossible to infer causality. Intervention studies are necessary to achieve this and some examples of this approach are given. In the first study reported here, we examined whether consumption of high-fibre breakfast cereal led to an increase in energy. Such an effect was observed and plausible biological mechanisms underlying such results are described. A similar methodology has recently been used to examine the effects of inulin. In this case the results showed no negative side-effects of taking inulin but there were no beneficial effects of inulin on measures of well-being (both subjective reports and objective measures). Possible reasons for these effects are discussed.

Physiological stimuli in the gut induce regulatory reflexes to accomplish the digestive process, but are normally not perceived. However, under some circumstances, gut stimuli may activate perception pathways and induce conscious sensations. Experimental evidence gathered during the past decade suggests that patients with functional gut disorders and unexplained abdominal symptoms may have a sensory dysfunction of the gut, so that physiological stimuli would induce symptoms. Assessment of visceral sensitivity is still poorly developed, but in analogy to somatosensory testing, differential stimulation of visceral afferents may be achieved by a combination of stimulation techniques, which may help to characterize sensory dysfunctions. Visceral afferent input is modulated by a series of mechanisms at different levels of the brain–gut axis, and conceivably, a dysfunction of these regulatory mechanisms could cause hyperalgesia. The sensory dysfunction in functional patients seems to be associated with altered reflex activity, and both mechanisms may interact to produce the symptoms. Evidence of a gut sensory–reflex dysfunction as a common pathophysiological mechanism in different functional gastrointestinal disorders would suggest that they are different forms of the same process, and that the clinical manifestations depend on the specific pathways affected.

The responses of renal vitamin D metabolism to its major stimuli alter with age. Previous studies showed that the increase in circulating 1,25-dihydroxyvitamin D (1,25(OH)2D3) as well as renal 25-hydroxyvitamin D3 1-α hydroxylase (1-OHase) activity in response to dietary Ca or P restriction reduced with age in rats. We hypothesized that the mechanism involved in increasing circulating 1,25(OH)2D3 in response to mineral deficiency alters with age. In the present study, we tested the hypothesis by studying the expression of genes involved in renal vitamin D metabolism (renal 1-OHase, 25-hydroxyvitamin D 24-hydroxylase (24-OHase) and vitamin D receptor (VDR)) in young (1-month-old) and adult (6-month-old) rats in response to low-phosphate diet (LPD). As expected, serum 1,25(OH)2D3 increased in both young and adult rats upon LPD treatment and the increase was much higher in younger rats. In young rats, LPD treatment decreased renal 24-OHase (days 1–7, P<0·01) and increased renal 1-OHase mRNA expression (days 1–5, P<0·01). LPD treatment failed to increase renal 1-OHase but did suppress 24-OHase mRNA expression (P<0·01) within 7 d of LPD treatment in adult rats. Renal expression of VDR mRNA decreased with age (P<0·001) and was suppressed by LPD treatment in both age groups (P<0·05) Feeding of adult rats with 10 d of LPD increased 1-OHase (P<0·05) and suppressed 24-OHase (P<0·001) as well as VDR (P<0·05) mRNA expression. These results indicate that the increase in serum 1,25(OH)2D3 level in adult rats during short-term LPD treatment is likely to be mediated by a decrease in metabolic clearance via the down-regulation of both renal 24-OHase and VDR expression. The induction of renal 1-OHase mRNA expression in adult rats requires longer duration of LPD treatment than in younger rats.

In most carbohydrate-containing foods, the blood insulin response is predictable and is closely linked to the food's glycaemic index (GI). A single study, examining whole milk and fermented milk products made from whole milk, recently reported a large dissociation between the GI and insulinaemic index (II) in healthy normal adults. Because the fat component of a food may influence the GI and II, it is unclear if a similar dissociation may exist for skimmed milk in normal adults. We determined the GI and II of both skimmed and whole milk in nine healthy, male (n 6) and female (n 3) subjects (23·6 (sd 1·4) years). No significant (P>0·05) differences existed between GI and II for skimmed and whole milks. Significant (P<0·05) differences were observed between the actual and predicted areas under the insulin curves for both skimmed milk (predicted 1405 (sd 289) pmol×min/l; actual 6152 (sd 1177) pmol×min/l) and whole milk (predicted 1564 (sd 339) pmol×min/l; actual 5939 (sd 1095) pmol×min/l). Consequently, a large and similar dissociation of the GI and II existed for both whole milk (42 (sd 5) and 148 (sd 14)) and skimmed milk (37 (sd 9) and 140 (sd 13)). It is concluded that the dissociation of the GI and II in milk is not related to its fat content.

Chronic inflammation of the vascular endothelium produces endothelial dysfunction and ultimately atherogenesis. Postprandial hyperlipidaemia is an independent risk factor for cardiovascular disease. Recent studies show that the magnitude of postprandial lipaemia following a single fatty meal is negatively related to vascular function. This is associated with a transient increase in the concentrations of pro-inflammatory cytokines and soluble adhesion molecules and in pro-oxidant activity. One possible interpretation is that repeated exposure of the blood vessel wall to the activities of pro-inflammatory cytokines and pro-oxidants may damage the vascular endothelium and promote atherogenesis. Based on these results, we propose a model of a causal mechanism to explain how consumption of a fatty meal may impair vascular dysfunction.

The objective of the research was to determine the blood pressure (BP) lowering effects in older people of 50 g carbohydrate drinks with varying carbohydrate content using a randomised, cross-over study with ten (six females) healthy older subjects (mean age 72·20 (sem 1·50) years). BP, heart rate and glucometer-derived blood glucose levels were determined at baseline and following the ingestion of equal volumes (300 ml) of water and carbohydrate drinks with varying nutrient content (glucose, sucrose and fructose). A significant decline in BP over the first 60 min was seen following glucose (systolic BP (SBP) P<0·01, diastolic BP (DBP) P<0·01, mean arterial BP (MAP) P=0·03) and sucrose (SBP P<0·01, DBP P<0·01, MAP P<0·01) ingestion, although the decrease occurred earlier after glucose than sucrose ingestion (SBP 7·33 (sem 2·19) v. 21·00 (sem 4·30) min (P=0·03) and MAP 11·22 (sem 3·10) v. 17·00 (sem 3·78) min (P=0·03)). BP increased after water ingestion (SBP P=0·04, DBP P=0·18, MAP P=0·02) but did not change after fructose ingestion (SBP P=0·36, DBP P=0·81, MAP P=0·34). Post hoc analyses revealed that the BP (SBP, DBP and MAP) decrease following glucose and sucrose ingestion were similar but significantly greater than following fructose or water ingestion. Sucrose, which is used widely (table sugar), reduces BP as much as glucose. In contrast to this, fructose ingestion causes no change in BP. Further studies are required to determine if the substitution of glucose or sucrose with fructose may be beneficial in the medical management of older people with severe symptomatic postprandial hypotension.

Alkylresorcinols (AR), a group of phenolic lipids, exist in the human diet in whole-grain rye and wheat. They are absorbed by humans and have been quantified in plasma. In this 2-week study we assessed AR incorporation into human erythrocyte membranes. Nine subjects attended the study; four avoided whole-grain products for 1 week and then included whole-grain rye and wheat bread in the diet for the second week, four included whole-grain rye and wheat products in the diet during the whole follow-up and one followed a gluten-free diet. Plasma and erythrocyte membrane AR were analysed after weeks 1 and 2. Erythrocyte membrane AR concentrations increased an average of 231 nmol/l of packed erythrocytes (P=0·036) after consumption of whole-grain rye and wheat products. Plasma AR levels increased an average of 175 nmol/l (P=0·058) When intake of whole-grain products was constant, erythrocyte membrane and plasma AR levels remained stable. Long-chain AR were incorporated into erythrocyte membranes in a higher proportion compared to shorter-chain AR. This preliminary study shows that AR are incorporated into human erythrocyte membranes in vivo.

Microarrays represent a powerful tool for studies of diet–gene interactions. Their use is, however, associated with a number of technical challenges and potential pitfalls. The cost of microarrays continues to drop but is still comparatively high. This, coupled with the complex logistical issues associated with performing nutritional microarray studies, often means that compromises have to be made in the number and type of samples analysed. Additionally, technical variations between array platforms and analytical procedures will almost inevitably lead to differences in the transcriptional responses observed. Consequently, conflicting data may be produced, important effects may be missed and/or false leads generated (e.g. apparent patterns of differential gene regulation that ultimately prove to be incorrect or not significant). This is likely to be particularly true in the field of nutrition, in which we expect that many dietary bioactive agents at nutritionally relevant concentrations will elicit subtle changes in gene transcription that may be critically important in biological terms but will be difficult to detect reliably. Thus, great care should always be taken in designing and executing microarray studies. This article seeks to provide an overview of both the main practical and theoretical considerations in microarray use that represent potential sources of technical variation and error. Wherever possible, recommendations are made on what we propose to be the best approach. The overall aims are to provide a basic framework of advice for researchers who are new to the use of microarrays and to promote a discussion of standardisation and best practice in the field.

Elevated postprandial glycaemia has been linked to CVD in a number of different epidemiological studies involving predominantly non-diabetic volunteers. The MiniMed continuous glucose monitor, which measures blood glucose every 5 min, over a 24 h period, was used to investigate changes in blood glucose readings before and after instigating a diet with low glycaemic index (GI) for 1 week in free-living healthy individuals. Nine healthy people (age 27 (sem 1·3) years, BMI 23·7 (sem 0·7) kg/m2, one male, eight females) completed the study. A reduction in GI (59·7 (sem 2) v. 52·1 (sem 2), P<0·01) occurred in all nine subjects while energy and other macronutrients remained constant. A significant reduction was also observed in fasting glucose at 06·00 hours (5·4 (sem 0·2) v. 4·4 (sem 0·3) mmol/l, P<0·001), mean glucose (5·6 (sem 0·2) v. 5·1 (sem 0·2) mmol/l, P=0·004), area under the 24 h glucose curve (8102 (sem 243) v. 750 (sem 235) mmol/l per min, P=0·004) and area under the overnight, 8 h glucose curve (2677 (sem 92) v. 2223 (sem 121) mmol/l per min, P=0·01). The present study provides important data on how a simple adjustment to the diet can improve glucose profiles that, if sustained in the long term, would be predicted from epidemiological studies to have a favourable influence on CVD.

Epidemiological studies have indicated that malnutrition during early life may programme chronic degenerative disease in adulthood. In an animal model of fetal malnutrition, rats received an isoenergetic, low-protein (LP) diet during gestation. This reduced fetal β-cell proliferation and insulin secretion. Supplementation during gestation with taurine prevented these alterations. Since proteases are involved in secretion and proliferation, we investigated which proteases were associated with these alterations and their restoration in fetal LP islets. Insulin secretion and proliferation of fetal control and LP islets exposed to different protease modulators were measured. Lactacystin and calpain inhibitor I, but not isovaleryl-l-carnitine, raised insulin secretion in control islets, indicating that proteasome and cysteinyl cathepsin(s), but not μ-calpain, are involved in fetal insulin secretion. Insulin secretion from LP islets responded normally to lactacystin but was insensitive to calpain inhibitor I, indicating a loss of cysteinyl cathepsin activity. Taurine supplementation prevented this by restoring the response to calpain inhibitor I. Control islet cell proliferation was reduced by calpain inhibitor I and raised by isovaleryl-l-carnitine, indicating an involvement of calpain. Calpain activity appeared to be lost in LP islets and not restored by taurine. Most modifications in the mRNA expression of cysteinyl cathepsins, calpains and calpastatin due to maternal protein restriction were consistent with reduced protease activity and were restored by taurine. Thus, maternal protein restriction affected cysteinyl cathepsins and the calpain–calpastatin system. Taurine normalised fetal LP insulin secretion by protecting cysteinyl cathepsin(s), but the restoration of LP islet cell proliferation by taurine did not implicate calpains.

The appetite-modulating peptide ghrelin is predominantly produced and secreted by the stomach and shows a strong growth hormone-releasing activity, which is mediated by the activation of the so-called growth hormone secretagogue type 1a receptor. Ghrelin is involved in the regulation of energy balance by increasing food intake and reducing fat utilization. Additionally, it stimulates lactotroph and corticotroph function, influences the pituitary gonadal axis, inhibits pro-inflammatory cytokine expression, controls gastric motility and acid secretion and influences pancreatic exocrine and endocrine function, as well as impacting on glucose metabolism. This review summarizes the known functions of ghrelin and its role in the regulation of the gut–brain axis.

High plasma level of cholesterol is a well-known risk factor for atherosclerotic diseases. Oxidized LDL induces cellular and nuclear damage that leads to apoptotic cell death. We tested the hypothesis that flavonoids may function as antioxidants with regard to LDL incubated with 5 μm-Cu2+ alone or in combination with human umbilical vein endothelial cells (HUVEC). Cytotoxicity and formation of thiobarbituric acid-reactive substances induced by Cu2+-oxidized LDL were examined in the presence of various subtypes of flavonoid. Flavanols, flavonols and flavanones at a non-toxic dose of 50 μm markedly inhibited LDL oxidation by inhibiting the formation of peroxidative products. In contrast, the flavones luteolin and apigenin had no such effect, with >30 % of cells killed after exposure to 0.1 mg LDL/ml. Protective flavonoids, especially (−)-epigallocatechin gallate, quercetin, rutin and hesperetin, inhibited HUVEC nuclear condensation and fragmentation induced by Cu2+-oxidized LDL. In addition, immunochemical staining and Western blot analysis revealed that anti-apoptotic Bcl-2 expression was enhanced following treatment with these protective flavonoids. However, Bax expression and caspase-3 cleavage stimulated by 18 h incubation with oxidized LDL were reduced following treatment with these protective flavonoids. The down-regulation of Bcl-2 and up-regulation of caspase-3 activation were reversed by the cytoprotective flavonoids, (−)-epigallocatechin gallate, quercetin and hesperetin, at ≥10 μm. These results suggest that flavonoids may differentially prevent Cu2+-oxidized LDL-induced apoptosis and promote cell survival as potent antioxidants. Survival potentials of certain flavonoids against cytotoxic oxidized LDL appeared to stem from their disparate chemical structure. Furthermore, dietary flavonoids may have therapeutic potential for protecting the endothelium from oxidative stress and oxidized LDL-triggered atherogenesis.