A number of authors have argued that only an aquatic-based diet can provide the necessary quantity of DHA to support the human brain, and that a switch to such a diet early in hominin evolution was critical to human brain evolution. This paper identifies the premises behind this hypothesis and critiques them on the basis of clinical literature. Both tissue levels and certain functions of the developing infant brain are sensitive to extreme variations in the supply of DHA in artificial feeding, and it can be shown that levels in human milk reflect maternal diet. However, both the maternal and infant bodies have mechanisms to store and buffer the supply of DHA, so that functional deficits are generally resolved without compensatory diets. There is no evidence that human diets based on terrestrial food chains with traditional nursing practices fail to provide adequate levels of DHA or othern-3 fatty acids. Consequently, the hypothesis that DHA has been a limiting resource in human brain evolution must be considered to be unsupported.

To investigate whether dietary α-linolenic acid (ALA) content alters the effect of β-carotene on mammary carcinogenesis, we conducted a chemically induced mammary tumorigenesis experiment in rats randomly assigned to four nutritional groups (15 rats per group) varying in β-carotene supplementation and ALA content. Two oil formula-enriched diets (15%) were used: one with 6g ALA/kg diet in an essential fatty acids (EFA) ratio of linoleic acid:ALA of 5:1 w/w (EFA 5 diet), the other with 24g ALA/kg diet in an EFA ratio of 1:1 w/w (EFA 1 diet), both designed with a similar linoleic acid content. β-Carotene was either added (10mg/kg diet per d) or not added to these diets. β-Carotene supplementation led to decreased tumour incidence and tumour growth when added to the EFA 5 diet, whereas it had no effect when added to the EFA 1 diet. The decreased tumour growth did not result from an involvement of lipoperoxidation (tumour malondialdehyde content being similar between the groups) or from an inhibition of tumour cell proliferation (as there was an unchanged S phase fraction in the tumours). We concluded that an adequate content of ALA in the diet is required to allow a protective effect of β-carotene in mammary carcinogenesis. Whether such an interaction between ALA and β-carotene influences the risk of breast cancer in women needs to be investigated.

Conjugated linoleic acid (CLA) has protective properties in breast cancer. Here, we studied the mechanisms underlying the effects of CLA on MCF-7 breast cancer cell proliferation, especially in correlation with the involvement of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and protein phosphatase 2A (PP2A). CLA inhibits MCF-7 cell growth in a concentration- and time-dependent manner, without triggering apoptosis. In assessing expression levels of proteins that play obligatory roles in the ERK cascade, we evidenced that CLA down-regulated Raf-1 and decreased levels of phospho-ERK1/2, as well as c-myc expression. Increase in PP2A expression rates were additionally observed after CLA treatment of MCF-7 cells. The above effects, as well as CLA-induced inhibition of cell growth, were reversed by okadaic acid, a specific inhibitor of PP2A. Thus, PP2A likely participates in deactivation of ERK1/2, and its up-regulation may represent a novel mechanism for CLA-induced inhibition of cell proliferation.

Poor growth during parasitic infection may be due to a redistribution of amino acids away from skeletal muscle protein synthesis to the intestinal site of infection. The effect of a Trichostrongylus colubriformis infection on whole-body amino acid kinetics and tissue fractional protein synthesis rates were determined in lambs fed fresh Sulla (Hedysarum coronarium; 800g DM/d). Lambs were dosed with 6000 L3 Trichostrongylus colubriformis larvae daily for 6d (n 6) or kept as parasite-free controls (n 6). On day 45 post-infection, the lambs received an intravenous injection of 2H2O and infusions (8h) of [35S]sulphate to measure the size of the whole-body water and sulphate pools, respectively. On day 48, the lambs were continuously infused for 8h with [3,4-3H]valine into the jugular vein as well as with [1-13C]valine and [35S]cysteine into the abomasum. After the 8h infusions, the lambs were killed and tissue samples collected from the duodenum, ileum, mesenteric lymph nodes, liver, spleen, thymus, muscle and skin. Feed intake (769 v. 689 (sd 47) g DM/d) was not affected by infection, whereas liveweight gains (50 v. −50 (sd 70) g/d) were lower and intestinal worm burdens(240 v. 18 000 (sd 7000) worms) higher in the infected lambs. Parasitic infection increased the fractional protein synthesis rates in the small intestine, mesenteric lymph nodes and liver but did not affect skin and skeletal muscle fractional protein synthesis rates during the established parasitic infection.

The absorption and metabolism in the small intestine of chlorogenic acid (5-0-caffeoylquinic acid), the main phenolic acid in the human diet, and of caffeic acid were studied in rats in order to determine whether chlorogenic acid is directly absorbed or hydrolysed in the small intestine. Chlorogenic and caffeic acids were perfused into a segment of ileum plus jejunum during 45;min (50;μm, 0·75sp;ml/min) using an in situ intestinal perfusion rat model with cannulation of the biliary duct, and were quantified together with their metabolites in perfusion effluent, bile and plasma. The net absorption (influent flux minus effluent flux of phenolic acids and their metabolites) accounted for 19·5% and 8% of the perfused caffeic and chlorogenic acids, respectively. A minor fraction of the perfused caffeic acid was metabolized in the intestinal wall and secreted back into the gut lumen in the form of ferulic acid (0·5% of the perfused flux). Part of the chlorogenic acid (1·2% of the perfused flux) was recovered in the gut effluent as caffeic acid, showing the presence of trace esterase activity in the gut mucosa. No chlorogenic acid was detected in either plasma or bile, and only low amounts of phenolic acids (less than 0·4%) were secreted in the bile. The present results show that chlorogenic acid is absorbed and hydrolysed in the small intestine. In contrast to numerous flavonoids, absorbed phenolic acids are poorly excreted in the bile or gut lumen. Their bioavailability therefore appears to be governed largely by their uptake into the gut mucosa.

The formation of SCFA in rats fed fermented oat fibre concentrates was compared with that of rats fed native oat fibre concentrate. The cultures used were lactic acid bacteria consisting of Lactobacillus bulgaricus and Streptococcus thermophilus (V2), the exopolysaccharide-producing strain Pediococcus damnosus 2.6 (Pd) and L. reuteri (Lr). The materials were incorporated into test diets yielding a concentration of indigestible carbohydrates of 80g/kg (dry weight). Rats fed the V2-fermented fibre-concentrate diet yielded higher caecal and distal concentrations of acetic acid (p<0·01) than rats fed the native fibre concentrate. All the fermented fibre concentrates resulted in a higher propionic acid concentration in the distal colon (p<0·05), while rats fed Pd-fermented fibre concentrate resulted in lower concentration of butyric acid (p<0·05,p <0·01) in all parts of the hindgut as compared with rats fed the native fibre concentrates. Butyrate concentrations ranged between 5–11μmol/g (distal colon) and 6–8;μmol/g (13d faeces). Higher proportions of acetic acid (p<0·05; p<0·01) were observed in the caecum of rats fed the fermented fibre concentrates. Rats fed Pd- and Lr-fermented fibre concentrates produced higher proportions of propionic acid (p<0·05; p<0·01) in the caecum. Changes in SCFA formation in the caecum, distal colon and faeces of rats fed the fermented samples compared with the native sample indicate that these microbes probably survive in the hindgut and that modification of the microflora composition with fermented foods is possible. This may be important for the gastrointestinal flora balance in relation to colonic diseases.

Six subjects exercised for 120;min on a cycle ergometer (65 (se 3) % V˙O2max) when ingesting a placebo or glucose, fructose or galactose (100g in 1000 ml water) labelled with 13C. The oxidation of energy substrates including exogenous hexoses was compared using indirect respiratory calorimetry and 13CO2 production at the mouth. Total carbohydrate progressively decreased and total fat oxidation increased over the 120min exercise period in the four experimental situations. During the 120min of exercise, the amount of fructose oxidized (38·8 (se 2·6) g; 9·0 (se 0·6)% energy yield) was not significantly (approximately 4%) lower than that of exogenous glucose (40·5 (se 3·4) g; 9·2 (se 0·8)% energy yield), while that of galactose (23·7 (se 3·5) g; 5·5 (se 0·9) % energy yield) was only 59% and 61% that of glucose and fructose, respectively. When compared with the placebo, the ingestion and oxidation of the three hexoses did not significantly modify fat oxidation or total carbohydrate oxidation, but it significantly reduced (9–13%) endogenous carbohydrate oxidation. The present data indicate that fructose and exogenous glucose ingested during exercise could be oxidized at a similar rate, but that the oxidation rate of galactose was only approximately 60% that of the exogenous glucose and fructose, presumably because of a preferential incorporation of galactose into liver glycogen (Leloir pathway). The reduction in endogenous carbohydrate oxidation was, however, similar with the three hexoses.

Resveratrol has been widely investigated for its potential health properties, although little is known about its metabolism in vivo Here we investigated the distribution of metabolic products of [3H]trans-resveratrol, following gastric administration. At 2h, plasma concentrations reached 1·7% of the administered dose, whilst liver and kidney concentrations achieved 1·0 and 0·6%, respectively. Concentrations detected at 18h were lower, being only 0·5% in plasma and a total of 0·35% in tissues. Furthermore, whilst kidney and liver concentrations fell to 10 and 25%, respectively, of concentrations at 2h, the brain retained 43% of that measured at 2h. Resveratrol-glucuronide was identified as the major metabolite, reaching 7μm in plasma at 2h. However, at 18h the main form identified in liver, heart, lung and brain was native resveratrol aglycone, indicating that it is the main form retained in the tissues. No phenolic degradation products were detected in urine or tissues, indicating that, unlike flavonoids, resveratrol does not appear to serve as a substrate for colonic microflora. The present study provides additional information about the nature of resveratrol metabolites and which forms might be responsible for its in vivo biological effects.

The physical activity level of an individual can be determined by assigning physical activity ratios (PAR) to different activities. The PAR is the ratio of the energy expended in a particular activity and the BMR, and is thought to be independent of body weight. PAR values of selected activities in Indian male and female subjects were measured and their association with BMI was assessed. The BMR and energy cost of selected activities were measured in thirty male and thirty female subjects in the age group of 20–40 years, who were categorised into different groups of BMI. The PAR values of the underweight male subjects were significantly lower than the overweight subjects for activities such as walking at 3·2 and 4·8km/h and walking at 3·2km/h with a 5kg load. In the female subjects, the underweight subjects had significantly lower PAR values for floor swabbing, and walking at 3·2 and 4·8km/h when compared with overweight females. The mean data of the male and female subjects of the present study were slightly but significantly different to the previously reported FAO, WHO and United Nations University values and other compilations. The BMI was significantly correlated with the PAR value of the studied activities. In India, where a large proportion of the population have BMI below 18·5 and above 25kg/m2, considerations of the influence of body weight and BMI on PAR become important in accurately determining total energy expenditure.

Lactic acid-fermented foods have been shown to increase Fe absorption in human subjects, possibly by lowering pH, activation of phytases, and formation of soluble complexes of Fe and organic acids. We tested the effect of an oat gruel fermented with Lactobacillus plantarum 299v on non-haem Fe absorption from a low-Fe bioavailability meal compared with a pasteurised, fermented oat gruel and non-fermented oat gruels. In a cross-over trial twenty-four healthy women with a mean age of 25 (sd 4) years were served (A) fermented gruel, (B) pasteurised fermented gruel, (C) pH-adjusted non-fermented gruel, and (D) non-fermented gruel with added organic acids. The meals were extrinsically labelled with 55Fe or 59Fe and consumed on 4 consecutive days, for example, in the order ABBA or BAAB followed by CDDC or DCCD in a second period. Fe absorption was determined from isotope activities in blood samples. The fermented gruel with live L. plantarum 299v increased Fe absorption significantly (p<0·0001) compared with the pasteurised and non-fermented gruels. The lactic acid concentration in the fermented gruel was 19% higher than in the pasteurised gruel, but the Fe absorption was increased by 50%. In the gruel with organic acids, the lactic acid concentration was 52% lower than in the pasteurised gruel, with no difference in Fe absorption. The fermented gruel increased non-haem Fe absorption from a phytate-rich meal in young women, indicating a specific effect of live L. plantarum 299v and not only an effect of the organic acids.

The objective of the present study was to compare anthropometry with bioelectrical impedance (BIA) in relation to densitometry (dual-energy X-ray absorptiometry; DEXA) as methods of nutritional assessment and body composition in out-patients with chronic pulmonary obstructive disease (COPD). We conducted a cross-sectional clinical study with sixty-one patients with COPD (forty-two men and nineteen women), mean age of 66·5 (sd 7·9) years and forced expiratory volume in 1s of 1·3 (sd 0·6) litres (52·2 (sd 19·8) % predicted), referred to the Pulmonary Rehabilitation Center. The patients were evaluated regarding nutrition status and body composition as determined by anthropometry, BIA and DEXA. In the results, 34·4% showed mild obstruction, 31·2%, moderate and 34·4%, severe obstruction. According to the BMI (mean 24·5 (sd 4·5) kg/m2), 45·9% of the patients exhibited normal weight, while 27·9% were underweight and 26·2% were obese. Related to fat-free mass (FFM), anthropometry and BIA compared with DEXA presented high correlations (r 0·96 and 0·95 respectively; p<0·001) and high reliability between the methods (α 0·98; p<0·001). Agreement analysis between the methods shows that anthropometry overestimates (0·62 (sd of the difference 2·89) kg) while BIA underestimates FFM (0·61 (sd of the difference 2·82) kg) compared with DEXA. We concluded that according to the nutritional diagnosis, half of our population of patients with COPD showed normal weight, while the other half comprised equal parts obese and underweight patients. Body composition estimated by BIA and anthropometry presented good reliability and correlation with DEXA; the three methods presented satisfactory clinical accuracy despite the great disparity of the limits of agreement.

Young women of reproductive age appear to have a greater capacity than men to convert the essential fatty acid α-linolenic acid to DHA. The purpose of this study was to test the hypothesis that gender-related differences in n-3 PUFA metabolism are reflected in the concentrations of n-3 PUFA in plasma lipids. The subjects were healthy men (n 13) and women (n 23) aged 18–35 years consuming their habitual diet. Dietary habits were assessed by food-frequency questionnaire. Venous blood samples were collected following an overnight fast. For the women, blood collection took place on the tenth day of their menstrual cycle. The fatty acid concentrations of plasma phosphatidylcholine, triacylglycerol, NEFA and cholesteryl esters were determined by gas chromatography. There were no significant differences between men and women in their consumption of protein, carbohydrate, total fat, alcohol, individual fatty acids and selected micronutrients. DHA concentration alone was significantly higher in plasma phosphatidylcholine (31%, p=0·02), triacylglycerol (71%, p=0·02) and NEFA (33%, p=0·01), but not cholesteryl esters, in women compared with men. There were no significant differences between men and women in the concentrations of any other fatty acids measured. Overall, the present data support the suggestion that greater DHA synthesis in women than men results in a higher DHA concentration in plasma lipids.

The effect of long-chain n-3 PUFA on the metabolism of apoB100-containing lipoprotein in diabetic subjects is not fully understood. The objective of the present study was to determine the effect of a daily intake of 1080mg EPA and 720mg DHA for diabetic subjects on the kinetics of apoB100-containing lipoprotein in the fasting state. A kinetic study was undertaken to determine the mechanisms involved in the effects of n-3 fatty acids in terms of a decrease in triacylglycerol level in type 2 diabetic patients. We have studied the effect of fish oils on the metabolism of apoB100 endogenously labelled by [5,5,5–2H3]-leucine in type 2 diabetic patients in the fasting state. The kinetic parameters of apoB100 in VLDL, intermediate-density lipoprotein and LDL were determined by compartmental modelling in five diabetic subjects before and 8 weeks aftern-3 fatty acid treatment. Treatment did not change the plasma cholesterol level (0·801 (sd 0·120)v. 0·793 (sd 0·163) mmol/l) but lowered the plasma triacylglycerol level (1·776 (sd 0·280) v.1·356 (sd 0·595) mmol/l; p<0·05). Treated patients showed a decrease in VLDL apoB100 concentration (0·366 (sd 0·030) v.0·174 (sd 0·036) g/l; v<0·05) related to a decrease in VLDL 1 production (1·49 (sd 0·23) v.0·44 (sd 0·19) mg/kg per h; p<0·05) and an increase in the VLDL conversion rate (0·031 (sd 0·024)v.0·052 (sd 0·040) per h; p<0·05), with no change in fractional catabolic rates. Treatment led to a higher direct production of intermediate-density lipoprotein (0·02 (sd 0·01) v 0·24 (sd 0·12) mg/kg per h; p<0·05). In conclusion, the present study, conducted in the fasting state, showed that supplementation with n-3 fatty acids in type 2 diabetic patients induced beneficial changes in the metabolism of apoB100-containing lipoprotein.

It is essential to have a thorough knowledge of the bioavailability and metabolism of dietary flavonols to understand their role in disease prevention. Lightly fried onions containing 275μmol flavonols, principally quercetin-4′-glucoside and quercetin-3,4′-diglucoside, were fed to healthy human volunteers and plasma and urine were collected over a 24h period. Samples were analysed by HPLC with diode array and tandem mass spectrometric detection. Five flavonol metabolites, quercetin-3′-sulphate, quercetin-3-glucuronide, isorhamnetin-3-glucuronide, a quercetin diglucuronide and a quercetin glucuronide sulphate, were detected in plasma in quantifiable amounts with trace quantities of six additional quercetin metabolites. Sub-micromolar peak plasma concentrations (cmax) of quercetin-3′-sulphate, quercetin-3-glucuronide, isorhamnetin-3-glucuronide and quercetin diglucuronide were observed 0.6–0.8h after ingestion. In contrast, the cmax of quercetin glucuronide sulphate was 2.5h. The elimination half-lives (t1/2) of quercetin-3′-sulphate, quercetin-3-glucuronide and quercetin diglucuronide were 1.71, 2.33 and 1.76h respectively, while the t1/2 of isorhamnetin-3-glucuronide was 5.34h and that of quercetin glucuronide sulphate was 4.54h. The profile of metabolites excreted in urine was markedly different to that of plasma with many of the major urinary components, including quercetin-3′-glucuronide, two quercetin glucoside sulphates and a methylquercetin diglucuronide, absent or present in only trace amounts in the bloodstream indicative of substantial phase II metabolism. Total urinary excretion of quercetin metabolites was 12·9μmol, corresponding to 4·7% of intake. If these samples had been subjected to hydrolysis, as in many previous studies, only quercetin and isorhamnetin would have been detected and quantified. The bioactivity of these metabolites should be considered.

Individuals with diabetes receive more nutrition advice than other population segments yet little is known about how well they comply or differ in nutrient intake from the rest of the population. The present study determined the mean macronutrient intake, glycaemic index (GI), and glycaemic load (GL) of a cohort of 3654 older Australians, with and without diabetes. Fasting pathology tests, including plasma glucose, were obtained for 88% of the 3654 residents, and a 145-item semi-quantitative food-frequency questionnaire was completed by 2900 residents (89%) between 1992 and 1994. In total, 6% of participants had diagnosed diabetes. Valid food-frequency data were available for 2736 without and 164 individuals with diabetes. The GI and GL were calculated from a customised database of Australian foods. Individuals with diabetes consumed significantly more protein (V=0·001) and less sugars (P≤0·001) than the general population. Only seven individuals with diabetes (4·3%) met all macronutrient recommendations and only four (2·4%) met fibre recommendations as well. Those with diabetes had a lower mean GI (55 (sd 5) V57 (sd 4); P=0·007, respectively) and GL (122 (sd 26) V 134 (sd 24); P<0·001, respectively) than the general population. In conclusion, older individuals with diabetes living in Australia in the 1990s chose a diet that had significantly more protein and less sugars than those without diabetes. This difference had little impact on the average GI, but it led to a moderate reduction in the average GL. Only a small percentage, however, was able to meet nutritional recommendations for optimal diabetes management.

The importance of the seasonal variation of calcitropic hormones to growing skeleton has not been established. We studied whether there exists a seasonal variation in calcitropic hormones, bone mineral density (BMD) and bone remodelling markers in early puberty girls. One hundred and ninety-six girls, mean age 11·4 (sd 0·4) years, in Tanner stage 2 (early puberty) and 3 (mid-puberty) were studied during September to March. The BMD was measured from the lumbar vertebrae and the left femur by dual-energy X-ray absoptiometry. Their serum 25-hydroxyvitamin D (S-25-OHD), serum intact parathyroid hormone (S-iPTH), serum osteocalcin, urinary pyridinoline and urinary deoxypyridinoline were analysed from fasting samples. The concentration of S-25-OHD and serum osteocalcin differed among months (p<0·01), reflecting a seasonal variation. The parathyroid hormone correlated negatively with S-25-OHD (r −0·325, p<0·001). Moreover, the BMD in the femur (p=0·047) and to a lesser extent in vertebrae (p=0·057) differed between months in early puberty girls but this was not seen in mid-puberty. Seasonal variation in S-25-OHD and bone remodelling markers accompanied by negative correlation between S-25-OHD and S-iPTH was seen in this cross-sectional study of adolescent girls. In addition, the seasonal rhythm contributed 7·0–7·6% difference in the BMD of lumbar vertebrae and left femur in early puberty girls. This variation should be avoided since it could hamper peak bone mass attainment.

Plantago ovata has been reported to reduce postprandial glucose concentrations in diabetic patients. In the present study, the efficacy and possible modes of action of hot-water extracts of husk of P. ovata were evaluated. The administration of P. ovata (0·5g/kg body weight) significantly improved glucose tolerance in normal, type 1 and type 2 diabetic rat models. When the extract was administered orally with sucrose solution, it suppressed postprandial blood glucose and retarded small intestinal absorption without inducing the influx of sucrose into the large intestine. The extract significantly reduced glucose absorption in the gut during in situ perfusion of small intestine in non-diabetic rats. In 28d chronic feeding studies in type 2 diabetic rat models, the extract reduced serum atherogenic lipids and NEFA but had no effect on plasma insulin and total antioxidant status. No effect of the extract was evident on intestinal disaccharidase activity. Furthermore, the extract did not stimulate insulin secretion in perfused rat pancreas, isolated rat islets or clonal β cells. Neither did the extract affect glucose transport in 3T3 adipocytes. In conclusion, aqueous extracts of P. ovata reduce hyperglycaemia in diabetes via inhibition of intestinal glucose absorption and enhancement of motility. These attributes indicate that P. ovata may be a useful source of active components to provide new opportunities for diabetes therapy.

Dairy Ca intake has been shown to be superior to elemental Ca in increasing the loss of body fat during energy restriction. We questioned whether the mechanisms involved an increase in postprandial energy expenditure, fat oxidation and/or a greater lipolysis. The acute effects of different sources of Ca were examined in eight subjects, aged 47–66 years and BMI 27·6–36·1kg/m2, in a three-way cross-over study. Subjects were randomly provided breakfast meals either low in dairy Ca and vitamin D (LD; control), high in non-dairy Ca (calcium citrate) but low in vitamin D (HC) or high in dairy Ca and vitamin D (HD). Diet-induced thermogenesis, fat oxidation rates (FOR), carbohydrate oxidation rates (COR), insulin, glucose, ΔNEFA and glycerol were measured hourly over a 6h postprandial period. Postprandial data were calculated as a change (Δ) from the fasting value. Results showed that ΔNEFA was significantly different between meals (LD −1·50 (sem 0·26), HC −1·22 (sem 0·32), HD −0·94 (sem 0·27) mmol/l×6h; P=0·035), with a lesser suppression following both high-Ca meals. ΔFOR was significantly higher following the two high-Ca meals (LD −6·5 (sem 2·2), HC 2·93 (sem 2·34), HD 3·3 (sem 2·5) g×6;h; P=0·005), while reciprocally ΔCOR was significantly lower. ΔGlycerol was less suppressed following the high-Ca meals but statistical significance was not achieved. No differences in diet-induced thermogenesis, insulin or glucose were observed. Regardless of source, Ca intake acutely stimulated postprandial fat oxidation; and there was a lesser suppression of NEFA following these meals.