Bovine milk is known to contain a number of peptide fractions that can affect immune function. The vast majority of immunoregulatory peptides that have been characterised are hydrolysate derivatives of major milk proteins. Recent research has also indicated that the metabolic activity of probiotic lactic acid bacteria can generate de novo immunoregulatory peptides from milk, via enzymatic degradation of parent milk protein molecules. In contrast, relatively little is known of endogenous, preformed immunoregulatory peptides in milk that may be relevant to modulating human health. The natural in vivo role of preformed and enzymatically derived peptides is likely to be one of regulation of the neonatal (bovine) gastrointestinal tract immune system, in order to modulate immune function with respect to the development of immunocompetence and avoidance of undesirable immunological responses (e.g. tolerance, and hypersensitivity to nutrients). There is scope for the further characterisation of both the origin and function of milk-derived immunoregulatory peptides, so that their potential to influence human health can be fully appraised. This review highlights our current knowledge of milk-derived immunoregulatory peptides, and outlines areas that are of relevance for further research.

The present study was designed to study the mechanisms by which dietary conjugated linoleic acids (CLA) decrease serum cholesterol. Hamsters were fed a semi-synthetic diet containing 1 g cholesterol/kg diet with or without supplementation with 20 g linoleic acid (LA) and 20 g CLA/kg diet. After 8 weeks, serum fasting total cholesterol (TC) and triacylglycerol (TG) were significantly lower in the LA-supplemented and CLA-supplemented groups compared with those of the control (CTL) hamsters. In contrast to LA, CLA significantly lowered hepatic cholesterol but it increased the level of adipose tissue cholesterol, suggesting that the hypocholesterolaemic mechanism of CLA is different from that of LA. CLA decreased the activity of intestinal acyl CoA:cholesterol acyltransferase (ACAT) whereas LA had no effect on this enzyme. Consequently, CLA supplementation increased the faecal excretion of total neutral sterols, but it had no or little effect on the faecal acidic sterols. If the ACAT is associated with cholesterol absorption, the part of mechanisms by which CLA decreases serum cholesterol may involve down-regulation of intestinal ACAT activity.

Aliphatic dioic acids have been proposed as alternative nutrients in selected clinical situations. In this study, their possible insulinotropic action was investigated in isolated rat pancreatic islets prepared from fed rats. Azelaic acid, sebacic acid and tridecanedioic acids, when tested at a 10·0 mM CONCENTRATION, WERE FOUND TO AUGMENT INSULIN RELEASE EVOKED BY d-glucose (7·0 mm) in the pancreatic islets. Likewise, glycerol-1,2,3-tris(dodecanoedioate), when used at concentrations close to 1·0 mm, increased the secretory response to the hexose. It is speculated that these findings may extend to insulin-producing cells, the knowledge that aliphatic dioic acids or their esters may act as energy substrates, e.g. in parenteral nutrition.

High blood pressure is a significant public health problem worldwide which is associated with increased risk of cardiovascular disease, stroke, and renal disease. The development of this disease is influenced by genetic and environmental factors. The results of many studies have linked increased consumption of milk and milk products with lower blood pressure and reduced risk of hypertension. The intake of several minerals found in milk has been demonstrated to have an inverse relationship with blood pressure. Peptides formed during the digestion of milk proteins have also been demonstrated to have a blood pressure lowering effect. Other components in milk that have been examined for their effects on blood pressure have been less promising. More recent data indicate that a dietary pattern that is low in fat, with fruits, vegetables, and low fat dairy products can significantly reduce blood pressure and lower risk of developing high blood pressure.

A randomised crossover dietary intervention study was performed to evaluate the effects of replacing meat protein in the diet with a soyabean product, tofu, on blood concentrations of testosterone, dihydrotestosterone, androstanediol glucuronide, oestradiol, sex hormone-binding globulin (SHBG), and the free androgen index (total testosterone concentration/SHBG concentration×100; FAI). Forty-two healthy adult males aged 35–62 years were studied. Diets were isoenergetic, with either 150 g lean meat or 290 g tofu daily providing an equivalent amount of macronutrients, with only the source of protein differing between the two diets. Each diet lasted for 4 weeks, with a 2-week interval between interventions. Fasting blood samples were taken between 07.00 and 09.30 hours. Urinary excretion of genistein and daidzein was significantly higher after the tofu diet (P<0·001). Blood concentrations of sex hormones did not differ after the two diets, but the mean testosterone:oestradiol value was 10 % higher (P=0·06) after the meat diet. SHBG was 3 % higher (P= 0·07), whereas the FAI was 7 % lower (P=0·06), after the tofu diet compared with the meat diet. There was a significant correlation between the difference in SHBG and testosterone:oestradiol and weight change. Adjusting for weight change revealed SHBG to be 8·8 % higher on the tofu diet (mean difference 3 (95 % CI 0·7, 5·2) nmol/l; (P=0·01) and testosterone:oestradiol to be significantly lower, P=0·049). Thus, replacement of meat protein with soyabean protein, as tofu, may have a minor effect on biologically-active sex hormones, which could influence prostate cancer risk. However, other factors or mechanisms may also be responsible for the different incidence rates in men on different diets.

The in vivo evidence of the antimicrobial and antiviral activity of bovine milk and colostrum derived components are reviewed with special emphasis on lactoferrin and lactoperoxidase. Their mode of action and the rationale for their application in efficacy trials with rodents, farm animals, fish and humans, to give protection against infectious agents, are described. A distinction is made between efficacy obtained by oral and non-oral administration of these non-specific defence factors which can be commercially applied in large quantities due to major achievements in dairy technology. From the in vivo studies one can infer that lactoferrin and lactoperoxidase are very promising, naturally occurring antimicrobials for use in fish farming, husbandry, oral hygiene and functional foods. Other promising milk-derived compounds include lipids, from which anti-infective degradation products are generated during digestion, and antimicrobial peptides hidden in the casein molecules.

It was previously shown that a high plasma concentration of non-esterified fatty acids (NEFA) persisted after a fatty breakfast, but not after an isoenergetic carbohydrate breakfast, adversely affecting glucose tolerance. The higher concentration after the fatty breakfast may in part have been a result of different mobilization rates of fatty acids. This factor can be investigated as NEFA mobilized from tissues are monounsaturated to a greater extent than those deposited from a typical meal. Twenty-four middle-aged healthy Caucasian men were given oral glucose tolerance tests (OGTT), and for 28 d isoenergetic breakfasts of similar fat composition but of low (L) or moderate (M) fat content. The composition of NEFA in fasting and postprandial plasma was determined on days 1 and 29. No significant treatment differences in fasting NEFA composition occurred on day 29. During the OGTT and 0–1 h following breakfast there was an increase in plasma long-chain saturated NEFA but a decrease in monounsaturated NEFA (μg/100 μg total NEFA; P<0·001). Between 1 and 3 h following breakfast treatment differences occurred for total saturated and total monounsaturated fatty acids (μg/100 μg total NEFA; P<0·05), expressed as an increase in 18 : 1 and decreases in 16 : 0 and 17 : 0 in treatment M relative to treatment L (P<0·05). Serum insulin attained 35 and 65 mU/l in treatments M and L respectively during this period. Negative correlations were found between 16 : 0 in fasting plasma and both waist:hip circumference (P=0·0009) and insulin response curve area during OGTT (within treatment M, P=0·0001). It is concluded that a normal postprandial insulin response is associated with a rapid change in plasma saturated:monounsaturated NEFA. It is proposed that this change is the result of a variable suppression of fat mobilization, which may partly account for a large difference in postprandial total plasma NEFA between fatty and carbohydrate meals.

The objective of the study was to examine the cariogenic potentials of maltodextrins and glucose syrups (two glucose polymers derived from starch) using a range of techniques in vitro and in laboratory animals. The experimental methods used were: (1) measurement of acid production from glucose syrups and maltodextrins by human dental plaque micro-organisms; (2) evaluation of the role salivary α-amylase in degrading oligosaccharides (degree of polymerisation >3) in the glucose polymers, estimating the products by HPLC; (3) assessment of the fermentability of trioses relative to maltose; (4) measurement of dental caries levels in three large-scale studies in laboratory rats fed on diets containing the glucose polymers. It was found that acid production from the glucose polymers increased as their higher saccharide content fell. Salivary α-amylase rapidly degraded the oligosaccharides (degree of polymerisation >3), mainly to maltose and maltotriose. In the presence of oral micro-organisms, maltotriose took longer to ferment than maltose, but by the end of a 2 h period the total amount of acid produced was the same from both. Incorporated into the diets in solid form, the glucose syrups and maltodextrins were associated with unexpectedly high levels of dental caries. In conclusion, the findings were unforeseen in the light of earlier data that a glucose syrup was less cariogenic than sucrose.

We examined the effects of high-fructose (FR) feeding on the development of diabetic complications in the lens and the kidney of streptozotocin (STZ)-diabetic rats. Male Wistar Furth rats were treated with one of two doses of STZ (HIGH STZ, 55 mg/kg body weight; MOD STZ, 35 mg/kg body weight) or vehicle alone (SHAM) and were then assigned to a control (CNTL) or 400 g FR/kg diet for 12 weeks. At the end of the study, body weight, plasma glucose and insulin concentrations differed among STZ groups (HIGH v. MOD v. SHAM, P<0·001) but did not differ due to diet. Plasma FR concentrations were significantly higher in FR-fed v. CNTL-fed groups (P<0·0001) and in HIGH-STZ groups v. MOD-STZ and SHAM groups (P<0·0004 and P<0·0001 respectively). Focal length variability of the lens, a quantitative measure of cataract formation, was increased in the HIGH STZ, FR group compared with the HIGH STZ, CNTL group (P<0·01). The concentration of H2O2 in kidney microsomes was significantly higher in HIGH STZ, FR rats v. HIGH STZ, CNTL rats (P<0·01). Microalbuminuria was not observed in any of the groups examined, and there was no evidence of extensive histological damage in the kidney from any rats. Under conditions of severe hyperglycaemia, high FR intake promotes the development of cataracts in the lens of the eye, and results in increased concentrations of substances indicative of oxidative stress in the kidney. Although FR has been suggested as a carbohydrate source for diabetics, a high FR diet coupled with hyperglycaemia produces effects that may promote some of the complications associated with diabetes.

The immunoglobulins of bovine colostrum provide the major antimicrobial protection against microbial infections and confer a passive immunity to the newborn calf until its own immune system matures. The concentration in colostrum of specific antibodies against pathogens can be raised by immunising cows with these pathogens or their antigens. Immune milk products are preparations made of such hyperimmune colostrum or antibodies enriched from it. These preparations can be used to give effective specific protection against different enteric diseases in calves and suckling pigs. Colostral immunoglobulin supplements designed for farm animals are commercially available in many countries. Also, some immune milk products containing specific antibodies against certain pathogens have been launched on the market. A number of clinical studies are currently in progress to evaluate the efficacy of immune milks in the prevention and treatment of various human infections, including those caused by antibiotic resistant bacteria. Bovine colostrum-based immune milk products have proven effective in prophylaxis against various infectious diseases in humans. Good results have been obtained with products targeted against rotavirus, Shigella flexneri, Escherichia coli, Clostridium difficile, Streptococcus mutans, Cryptosporidium parvum and Helicobacter pylori. Some successful attempts have been made to use immune milk in balancing gastrointestinal microbial flora. Immune milk products are promising examples of health-promoting functional foods, or nutraceuticals. This review summarises the recent progress in the development of these products and evaluates their potential as dietary supplements and in clinical nutrition.

Marginal Zn deficiency is thought to be prevalent in both developed and developing countries. However, the extent of Zn deficiency is not known, due to the lack of a reliable diagnostic indicator. Blood plasma and erythrocyte concentrations of metallothionein (MT) reflect Zn status, but measurement of MT is dependent on the availability of sensitive immunoassays. Our aim was to show whether measurement of T lymphocyte MT-2A mRNA, using a competitive reverse transcriptase (RT)–polymerase chain reaction (PCR) assay, could indicate Zn status in human subjects in a residential Zn-depletion study. In the study, the Zn intake of seven volunteers was maintained at 13·7 mg/d for 5 weeks (baseline) followed by 4·6 mg/d for 10 weeks (marginal intake) and then 13·7 mg/d (repletion) for 5 weeks. The quantitative assay was developed using standard techniques and concentrations of MT-2A mRNA were normalized by reference to β-actin mRNA which was also measured by competitive RT–PCR assay. An alternative method of measuring the PCR product using capillary electrophoresis with laser-induced fluorescence detection was also evaluated. There was considerable inter-individual variation in MT-2A mRNA concentration and the mean level at the end of the baseline period was 10·3 (SE 3·7) fg MT-2A mRNA/pg β-actin mRNA, which then decreased by 64 % during the low Zn intake period. After repletion, MT-2A mRNA returned to baseline concentrations. In contrast, plasma Zn was unchanged by marginal Zn intake or repletion. The effect of low Zn in all individuals was consistent. We conclude that this assay is a sensitive method of evaluating marginal changes in dietary Zn intake.

Milk is often seen as a potential promotor of atherosclerosis and coronary heart disease because it is a source of cholesterol and saturated fatty acids. But there are several studies indicating that milk and milk products may not affect adversely blood lipids as would be predicted from its fat content and fat composition. There are even factors in milk and milk products which may actively protect from this condition by improving several risk factors. Calcium, bioactive peptides and as yet unidentified components in whole milk may protect from hypertension, and folic acid, vitamin B6 (pyridoxine) and B12 (cyanocobalamin) or other unidentified components of skim milk may contribute to low homocysteine levels. Conjugated linoleic acid may have hypolipidaemic and antioxidative and thus antiatherosclerotic properties. Epidemiological studies suggest that milk and milk products fit well into a healthy eating pattern emphasizing cereals and vegetables.

The purpose of the present study was to determine the effects of Mg deficiency and supplementation on the mechanical properties of the rat common carotid artery. The internal diameter and intra-arterial pressure of carotid artery were measured continuously using an echo-tracking device. Systolic, diastolic and mean intra-arterial pressures were not significantly different in Mg-deficient, -supplemented or control rats. Histological examination showed a larger cross-sectional area, increased intima-media thickness and a greater media:lumen value in carotid artery of Mg-deficient rats, indicating that Mg deficiency may directly stimulate growth and/or proliferation of arterial wall components. In addition, we observed a negative linear relationship between intima-media thickness and plasma Mg concentration, suggesting that increased Mg intake may counteract arterial wall hypertrophy. Neither Mg deficiency nor supplementation modified the arterial distensibility v. intra-arterial pressure curve or the Eincv. wall stress curve, indicating that dietary Mg intake did not modify wall stiffness in young rats. At mean intra-arterial pressure, the stress and Einc values were, however, significantly lower in Mg-deficient rats (P<0·05 in both cases); this finding could be related to the alteration in the geometry of the carotid artery. In conclusion, these findings suggest that Mg deficiency modifies the mechanical properties of the common carotid artery in young rats. Since Mg deficiency is considered a risk factor, these mechanical alterations could contribute to the development of atherosclerosis, hypertension and cardiovascular diseases.

Improved means of cancer prevention and treatment remain key goals of global health programmes. This is particularly true in Western society, where the elderly represent a large proportion of the population, and where the likelihood of tumour development is compounded by risk factors such as poor fibre/high fat diets and environmental pollution. Dietary intervention represents an attractive, non-invasive means of providing anticancer preventative and therapeutic benefits to at-risk individuals. This review focuses on the evidence for anticancer properties of bovine milk and milk-derived components. Evidence of a role for whole milk constituents, as well as purified minor components, in combating tumorigenesis is outlined. Shortcomings in current studies are highlighted, and future opportunities for targeted research to characterize important anticancer properties of milk are discussed.

It has been demonstrated that triacylglycerol (TAG) mobilization from adipose tissue is selective and depends on fatty acid (FA) chain length, unsaturation and positional isomerism. The present study was performed to determine the influence of dietary fat on the composition of TAG stored in rat perirenal and subcutaneous adipose tissues. These results may provide information on the susceptibility of stored TAG to hydrolysis and further mobilization, and may help to establish an interrelationship between dietary composition and the FA efflux from adipose tissue. TAG molecular species and FA composition were determined by HPLC and GLC respectively. No significant differences were found in either FA or TAG composition between perirenal and subcutaneous adipose depots. The major FA in the dietary fats were present in the adipose tissues of the animals; in most cases, in similar proportions. However, differences were found between dietary and adipose tissue content of minor FA, which suggests that dietary FA composition is altered between ingestion and deposition in adipose tissue. The TAG molecular species of rat adipose tissue were enriched with the FA characteristic of each dietary fat. Dietary sunflower oil was responsible for enrichment with the most polar TAG. This finding may suggest easier mobilization of stored TAG. In conclusion, the process of fatty acid and TAG deposition in rat adipose tissue is selective, and depends on the composition of the diet.