This review attempts to delineate the underlying mechanisms leading to the development of hypertension as well as the function of vitamins and minerals in the regulation of blood pressure. Physiological processes that regulate cardiac output and systemic vascular resistance impact on the control of blood pressure. Metabolic abnormalities associated with the tetrad of hypertension, dyslipidaemia, glucose intolerance and obesity share insulin resistance, which might be organ or cell specific, as an underlying feature representing different tissue manifestation of a common cellular ionic defect. As Ca is at the centre of ionic regulation of cellular functions, vitamins involved in Ca regulation have a significant role in the control of blood pressure. The endothelium-dependent vasodilator, NO, is susceptible to oxidative damage. Hence, antioxidant vitamins and related factors regulate blood pressure through protection of NO. Robust evidence for the involvement of vitamin B6 (pyridoxine), vitamin C, vitamin D and vitamin E in the regulation of blood pressure have been reported. The well-known roles of Na, K, Ca, Mg and Cl have been explored further. The action of various vitamins on blood pressure regulation cannot always be explained on the basis of their conventionally recognised “vitamin function”. The non-traditional functions of vitamins and their derivatives can be exploited as an adjunct to available pharmacological modalities in the treatment of hypertension.

HIV-1 (subsequently referred to as HIV) infection may be transmitted to the infant during breast-feeding. The risk of transmission varies with stage of maternal infection, duration of breast-feeding, type of breast-feeding (i.e. exclusive or mixed breast-feeding), and breast pathology. Recent studies support the findings of a meta-analysis (Dunn et al. 1992) and indicate that when breast-feeding is practised for over 2 years, the risk of infection is about 14%. Shorter durations of breast-feeding may therefore minimize the risk of transmission. Although the risk of infection appears to be greatest in the first 6 months this risk needs to be weighed against the excess risk of morbidity and mortality if children are not breast-fed in the first 6 months. In resource-poor settings any policy decision to replace breast-feeding with formula feeding in order to prevent postnatal HIV transmission needs to be balanced against the risks to the infant of malnutrition, morbidity and death if not breast-fed. New information suggests that exclusive breast-feeding, instead of the norm of mixed breast-feeding, may not increase risk of HIV transmission at 6 months and suggests that exclusive breast-feeding with early cessation may be a viable option for some women. The present review suggests options for reducing risk of HIV transmission through breast-feeding. Finally, current knowledge points to the dangers of large-scale replacement feeding programmes in contexts where women will have low education, poor access to water and health services, and strong cultural pressures to breast-feed. Emphasising replacement feeding in these contexts may fuel the mixed breast-feeding practice for mothers who will have no other choice than breast-feeding, yet will try to follow the recommendations applied to replacement feed.

Peripheral blood mononuclear cells (PBMC) accumulate biotin by a Na-dependent energy-requiring transporter. This transporter might be the so-called Na-dependent multivitamin transporter, but kinetic observations suggest the existence of a second, more specific, biotin transporter. PBMC respond to proliferation by increased uptake of biotin; the increase is probably mediated by an increased number of transporters on the cell surface. The inferred increase in the biotin transporter synthesis is relatively specific. The increased uptake of biotin into proliferating PBMC is consistent with the hypothesis that these cells have an increased demand for biotin. Indeed, proliferating PBMC increase expression of genes encoding β-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase, generating a quantitatively significant increased demand for biotin as a coenzyme in newly-synthesized carboxylases. Moreover, expression of the holocarboxylase synthetase gene increases, consistent with the synthesis of new holocarboxylases. In addition, proliferating PBMC increase both the density of biotinylation of histones and the mass of biotinylated histones per cell, suggesting a potential role for biotin in transcription and replication of DNA.

The phasing out of antibiotic compounds as growth promoters from the animal industry means that alternative practices will need to be investigated and the promising ones implemented in the very near future. Fermentation in the gastrointestinal tract (GIT) is being recognized as having important implications for health of the gut and thus of the host animal. Fermentation in single-stomached animals occurs to the largest extent in the large intestine, mainly because of the longer transit time there. The present review examines the micro-ecology of the GIT, with most emphasis on the large intestine as the most important site of fermentative activity, and an attempt is made to clarify the importance of the microfloral activity (i.e. fermentation) in relation to the health of the host. The differences between carbohydrate and protein fermentation are described, particularly in relation to their endproducts. The roles of volatile fatty acids (VFA) and NH3 in terms of their relationship to gut health are then examined. The large intestine has an important function in relation to the development of diarrhoea, particularly in terms of VFA production by fermentation and its role in water absorption. Suggestions are made as to feeds and additives (particularly those which are carbohydrate-based) which could be, or are, added to diets and which could steer the natural microbial population of the GIT. Various methods are described which are used to investigate changes in microbial populations and reasons are given for the importance of measuring the kinetics of fermentation activity as an indicator of microbial activity.

There is now ample epidemiological evidence to show that the wide international variations in the incidence of both adenomatous polyps and colo-rectal cancer are linked to diet, but the mechanisms through which particular dietary constituents influence the onset of neoplasia are poorly understood. The crypt epithelial cells of the human gastrointestinal mucosa are amongst the most rapidly proliferating tissues in the body, and those of the colorectum are particularly vulnerable to neoplasia. Within the crypt, continuous division of basally localized stem cells gives rise to daughter cells that may divide once or twice again, before differentiating and migrating to the mucosal surface. The majority of nascent crypt epithelial cells differentiate, become senescent and are shed into the gut lumen, but a small proportion die by apoptosis soon after cell division. Various lines of evidence suggest that these pathways of programmed cell death provide a protective mechanism against induction of neoplasia by removing genetically damaged stem cells before they can divide further and give rise to precancerous lesions. There is evidence that the short-chain fatty acid butyrate and several different classes of food constituents, including some polyunsaturated fatty acids, flavonoids and glucosinolate breakdown products, can regulate the processes of cell proliferation and death in vitro, and in colorectal crypts in vivo. All three classes of food components suppress the emergence of aberrant crypt foci in animal models of carcinogenesis. The cellular mechanisms underlying these phenomena, and their possible significance for human health, are discussed.

Since pre-history, Cannabis sativa has been exploited for its potent and manifold pharmacological actions. Amongst the most renowned of these actions is a tendency to provoke ravenous eating. The characterization of the psychoactive principals in cannabis (exogenous cannabinoids) and, more recently, the discovery of specific brain cannabinoid receptors and their endogenous ligands (endocannabinoids) has stimulated research into the physiological roles of endocannabinoid systems. In this review, we critically discuss evidence from the literature that describe studies on animals and human subjects to support endocannabinoid involvement in the control of appetite. We describe the hyperphagic actions of the exogenous cannabinoid, Δ9-tetrahydrocannabinol, and the endogenous CB1 ligands, anandamide and 2-arachidonylglycerol, and present evidence to support a specific role of endocannabinoid systems in appetitive processes related to the incentive and reward properties of food. A case is made for more comprehensive and systematic analyses of cannabinoid actions on eating, in the anticipation of improved therapies for disorders of appetite and body weight, and a better understanding of the biopsychological processes underlying hunger.

Space flight is a new experience for man. Tension on the weight-bearing components of the musculo–skeletal system is greatly reduced, as is the work required for movement. The body responds by a reductive remodelling of the musculo–skeletal system. Protein is lost from muscles with anti-gravity functions. The rate of Ca loss from the weight-bearing bones is about 1 % per month. Voluntary dietary intake is reduced during space flight by about 20 %. These adaptations to weightlessness leave astronauts ill-equipped for life with gravity when they return to earth. Rates of energy expenditure are similar to that expected on the ground for comparable activities. Protein intake is adequate in flight but may be limiting after space flight due to substrate competition between repleting muscle and other anabolic processes. The most serious nutritional problem is the inability to maintain energy balance on missions with high exercise requirements. The poor dietary intake is probably a consequence of engineering-imposed environmental constraints. The low levels of lighting in the space vehicle may not be enough to promote vitamin D synthesis. Nevertheless, the evidence suggests that a normal well-balanced diet with plenty of fluids will be as healthy in space as on earth. The long-term goal of the manned space programme is to develop the means of sustaining human life beyond earth. This will involve the development of technologies to grow food, maintain a breathable atmosphere and recycle waste products with the only external input being energy.

The physiologically active form of vitamin B6, pyridoxal 5′-phosphate (PLP), is known to function as a cofactor in many enzymic reactions in amino acid metabolism. Recent studies have shown that, apart from its role as a coenzyme, PLP acts as a modulator of steroid hormone receptor-mediated gene expression. Specifically, elevation of intracellular PLP leads to a decreased transcriptional response to glucocorticoid hormones, progesterone, androgens, and oestrogens. For example, the induction of cytosolic aspartate aminotransferase (cAspAT) in rat liver by hydrocortisone is suppressed by the administration of pyridoxine. The suppression of the cAspAT induction by pyridoxine is caused by a decrease in the expression of the cAspAT gene, which is brought about by inactivation of the binding activity of the glucocorticoid receptor to the glucocorticoid-responsive element in the regulatory region of the cAspAT gene. Vitamin B6 has recently been found to modulate gene expression not only for steroid hormone-responsive or PLP-dependent enzymes but also for steroid- and PLP-unrelated proteins such as serum albumin. Albumin gene expression was found to be modulated by vitamin B6 through a novel mechanism that involves inactivation of tissue-specific transcription factors, such as HNF-1 or C/EBP, by direct interaction with PLP in a similar manner to glucocorticoid receptor. Enhancement of albumin gene expression in the liver by an increased supply of amino acids can be explained by elevated binding of HNF-1 and C/EBP to their DNA-binding sites which, in turn, is caused by a decrease in the intracellular level of PLP by the increased amino acid supply. These findings that vitamin B6 acts as a physiological modulator of gene expression add a new dimension to the hitherto recognized function of vitamin B6 as a cofactor of enzyme action.

Osteoporosis as a worldwide problem is discussed in the present review and the question of improving peak bone mass to reduce the risk of osteoporosis and osteoporotic fracture is addressed. The available evidence points to pre-puberty and puberty as the most opportune periods for intervention, but the potential for achievable increments in bone mass is shown to be small compared with the overwhelming influence of heredity, body composition and hormonal factors on bone. Lean body mass appears to be positively correlated with bone mass, while black–white racial differences in bone mass appear to be related to greater lean mass and lower bone turnover rate in blacks. Within races, twin and parent–offspring models have suggested that 46–80 % of the variance in bone mineral density can be explained by inherited factors; however, the mechanism of the genetic influence on bone density remains poorly understood. Moderate regular exercise seems to maintain bone mass while more vigorous regular exercise increases it in children and young adults. Ca intake has been found to be positively associated with bone mass in many but not all studies, possibly because of a ceiling at about 1300–1500 mg/d for young people. Other nutritional variables, including vitamin D, have been little investigated in relation to childhood and adolescent bone mass. The influence of milk as a source of highly bioavailable Ca and other nutrients has also been less frequently investigated, which is of concern given the cessation of school milk programmes in Western countries over the last three decades. Intervention studies to improve bone health in young people have mainly been based on Ca milk or exercise. The evidence points to the benefits to bone of such interventions, particularly when commenced pre-puberty, and it seems that daily consumption of 200–300 ml milk/d by children and adolescents has no adverse side effects. The benefits to bone are almost universally shown to be lost fairly rapidly after Ca or exercise intervention ceases; there is therefore no justification in terms of bone health for short-term interventions of this nature. The question of withdrawal of milk supplementation has undergone very little examination. Further, very little evidence is available on the effects of long-term interventions of any sort on bone health. Nevertheless, the data obtained so far permit the suggestion that promotion of Ca intake (e.g. at the higher level of current recommendations) and exercise commencing in the pre-pubertal period should be adopted as policy now.

Folic acid is important because supplementation around the time of conception has been proven to lower the risk of having offspring with a neural-tube defect. Furthermore, both dietary folate and folic acid decrease plasma total homocysteine concentrations. Elevated plasma homocysteine concentrations are considered to be an independent risk factor for cardiovascular disease. The aim of the present review is to give an overview of factors influencing bioavailability and bioefficacy (the proportion of ingested nutrient converted to its active form) of food folate and folic acid, and to discuss the functional bioefficacy of folate and folic acid in decreasing plasma homocysteine concentrations. We use the mnemonic SLAMENGHI to group factors influencing bioavailability and bioefficacy: Species of folate; Linkage at molecular level; Amount of folate and folic acid consumed; Matrix; Effect modifiers; Nutrient status; Genetic factors; Host-related factors; mathematical Interactions between the various factors. Bioefficacy of folate from some foods is 50 % that of folic acid. This factor is most probably explained by the matrix factors, encapsulation and binding. However, often such effects cannot be distinguished from factors such as species, chain length of folate in food, effect modifiers and the amount of folate consumed in a meal. Folic acid provided as a supplement is well absorbed. However, the homocysteine-lowering capacity of doses of folic acid >500 μg is limited. It is unclear whether unmetabolised folic acid poses health risks. This factor is of importance, because food fortification is now implemented in many countries and folic acid supplements are freely available. In particular circumstances host-related factors, such as gastrointestinal illness and pH of the jejunum, can influence bioavailability. Genetic factors also deserve attention for future research, because polymorphisms may influence folate bioavailability.

Individuals have varying needs for minerals that are dependent, amongst other things, on their lifestyle, age and genetic makeup. Knowledge of exact individual nutritional requirements should lead to better health, increased quality of life and reduced need for expensive medical care. Bioavailability, nutrient–gene interactions and whole–body metabolism all need to be investigated further if we are to progress towards the goal of defining optimal health and nutritional status. The discussion which follows will critically review the latest developments in the area of metabolism for several of the minerals that are essential for human health: Ca, Zn, Cu and Se. Stable–isotope tracers and mathematical modelling are some of the tools being used to facilitate the greater understanding in uptake, utilisation and excretion of these minerals. Stable isotopes, administered in physiological doses, present little or no risk to volunteers and allow metabolic studies to be carried out in vulnerable population groups such as children and pregnant women. Intrinsic labelling of foodstuffs ensures that the tracer and the native mineral will behave similarly once inside the body. Advances in computing power and software dedicated to solving nutritional problems have made it possible for investigators to use mathematical modelling in their experimental work. Mineral metabolism is ideally suited to a form of modelling known as compartmental analysis, which allows rates of mineral transferand sizes of mineral stores to be calculated accurately without the need for invasive sampling of body tissues

Health benefits for man have been associated with conjugated linoleic acid (CLA) and dairy products are highlighted as offering the best opportunity to increase CLA consumption. CLA is synthesised in the rumen as an intermediate in the biohydrogenation of linoleic acid to stearic acid. The supplies of both intermediates and endproducts of biohydrogenation are affected by the substrate supply and extent of biohydrogenation, thus influencing the CLA content of milk from ruminants. The majority of CLA is present in the rumen in the form of the cis-9,trans-11 isomer. The transfer efficiency of CLA to milk fat is affected by the presence of different isomers of CLA. Ruminant mammary and adipose cells are able to synthesise cis-9,trans-11-CLA from trans-11-18:1 (vaccenic acid) by the action of the Δ9-desaturase enzyme. Plant oils are high in both linoleic and linolenic acids, which results in increased CLA production in the rumen and in the mammary gland. The CLA content of milk increases when cows are offered grazed grass. Many published studies examining the CLA concentration of processed milk were confounded by variations in the concentration of CLA in the raw milk.

Conjugated linoleic acid (CLA) refers to a group of fatty acid isomers of linoleic acid. Recent research shows that CLA affects body composition, lipoprotein metabolism, inflammationand carcinogenesis. Therefore, CLA may have potential as a therapeutic nutrient with respect to many common diseases, including obesity, atherosclerosis, chronic inflammatory diseases and cancer. Animal studies show that CLA is a potent anti-adipogenic nutrient, reducing adipose tissue mass and increasing lean mass. However, the effect of CLA on body composition in human subjects has been less spectacular. Several studies have demonstrated that CLA significantly improves plasma cholesterol and triacylglycerol metabolism in a number of animal models. These studies also showed that CLA inhibits the progression and pathogenesis of atherosclerosis. Whilst CLA has also been shown toimprove triacylglycerol metabolism in human subjects, it has not been determined whether CLA affects atherogenesis. Animal models show that CLA-rich diets modulate the inflammatory response and preliminary trials with human subjects show that CLA affects the cell-mediated immune response. The molecular basis of the health effects of CLA has not been elucidated, but it is probable that CLA mediates its effect in a number of ways including altered eicosanoid or cytokine metabolism and/orby a direct effect of dietary fats on gene transcription. Most of our knowledge is based on in vitro and animal studies; the challenge is to define the nature and molecular basis of any health effects of CLA in human subjects.

Accelerator mass spectrometry (AMS) is an ultrasensitive analytical technique for measuring rare nuclides such as 14C, 26Al and 41Ca. The low detection limit and wide dynamic range of AMS allow long-term and highly sensitive tracer studies in nutrition that cannot be performed with other methods. The present paper is intended to provide a description of AMS to the interested nutritionist and present proven applications. AMS is compared to liquid scintillation counting and stable isotope MS. A description of common AMS methodology is presented that consists of determining the dose, preparing the sample, diluting the sample (if necessary), and measuring the sample. Applications include Ca metabolism, Al uptake from the environment, dietary intake of carcinogens, fat meta-bolism and folate metabolism. Throughout this discussion the experimental advantages (small doses that pose no health risk, extremely long experimental lifetime, small sample sizes and high sensitivity) made possible by the unique analytical capabilities of AMS are emphasized. The future of AMS is discussed. As the number of AMS centres, instruments, and studies increases, the number of nutritional applications that employ AMS will continue to grow. The coupling of AMS with other analytical techniques (e.g. high performance liquid chromatography) will be developed as access to AMS improves.