Genistein and folic acid have been reported respectively to protect against the development of cognitive dysfunction; however, the underlying mechanism(s) for this protection remain unknown. In this report, the mechanism(s) contributing to the neuroprotective effects of genistein and folic acid were explored using rat cortical neuron cultures. We found that genistein and folic acid, both separately and collaboratively, increased cell viability and mitochondrial membrane potential in β-amyloid (Aβ) 31-35-treated neurons. Furthermore, reduced percentage of comet cells and shortened tail length were observed in the neurons treated with genistein or folic acid. A more significant reduction in tail length of the comet neurons was observed in the co-administered neurons. RT-PCR analysis of the cultured cortical neurons showed down-regulated expression of p53, bax and caspase-3, but up-regulated expression of bcl-2 in the three neuroprotective treatment groups compared with neurons from the Aβ31-35 solo-treated group. In a nuclear dyeing experiment using Hoechst 33342, we found that both genistein and folic acid prevent neuronal apoptosis. Collectively, these findings suggest that the mechanism underlying the neuroprotection of genistein and folic acid singly or in combination observed in cultured cortical neuron studies might be related to their anti-apoptotic properties.

Chronic low-grade inflammation is a characteristic of ageing that may lead to alterations in health status and quality of life. In addition to intrinsic biological factors, recent data suggest that poor nutritional habits may largely contribute to this condition. The present study aimed at assessing mental and physical components of quality of life and at determining their relationship to vitamin E status, inflammation and tryptophan (TRP) metabolism in the elderly. Sixty-nine elderly subjects recruited from the Three-City cohort study participated in the study. Quality of life was assessed using the medical outcomes study thirty-six-item short-form health survey (SF-36). Biological assays included the measurement of plasma vitamin E (α-tocopherol), inflammatory markers, including IL-6 and C-reactive protein, and TRP metabolism. Results showed that participants with poor physical health status, as assessed by the SF-36, exhibited lower circulating concentrations of α-tocopherol together with increased concentrations of inflammatory markers. Similarly, poor mental health scores on the SF-36 were associated with lower concentrations of α-tocopherol, but also with decreased concentrations of TRP. These findings indicate that nutritional status, notably as it relates to vitamin E, is associated with immune function and quality of life in the elderly.

Within the EURopean micronutrient RECommendations Aligned Network of Excellence (EURRECA), a scoring system was developed to assess the quality of dietary intake validation studies. The scoring system included three steps. The first step was to give each study a quality score, which included five components: sample size, statistics used, data collection procedure, consideration of seasonality and supplement use. Scores ranged from 0 to 7, and validation studies classified as very good ( ≥ 5), good (5–3·5), acceptable/reasonable (3·5–2·5) and poor ( < 2·5). The second and third steps included an adjustment/weighting of the correlation coefficient according to the quality score and moreover a rating of the adjusted/weighted correlation. The scoring system was tested in 124 validation studies that included at least one vitamin. Only 5·6 % of the 124 studies were judged to be of very good quality according to the quality score, 41·9 % of good quality and 16·9 % had a poor rating. When adjusting for the study quality scores, crude and adjusted mean correlations of vitamins A, C, D and E intakes were similar, but the percentage of correlation values classified as poor or very good was higher after adjustment. These results show the importance of considering the quality of studies validating dietary assessment methods and the correlations obtained for the micronutrient of interest when interpreting effects observed in epidemiological studies using dietary assessment methods. Without a doubt, this subject constitutes a key topic for research in nutritional epidemiology.

Adaptive thermogenesis is defined as a greater than predicted change in energy expenditure in response to changes in energy balance. This issue is particularly relevant in the context of a weight-reducing programme in which diminished thermogenesis can be sufficient to compensate for a prescribed decrease in daily energy intake. In the present pilot study, we investigated the adaptive reduction in thermogenesis in resting state that appears to favour resistance to further weight loss. Eight obese men (mean BMI: 33·4 kg/m2, mean age: 38 years) participated in this repeated-measures, within-subject, clinical intervention. They were subjected to a weight-loss programme that consisted of a supervised diet ( − 2930 kJ/d) and exercise clinical intervention. The phases investigated were as follows: (i) baseline, (ii) after 5 (se 1) kg loss of body weight (phase 1), (iii) after 10 (se 1) kg weight loss (phase 2) and (iv) at resistance to further weight loss (plateau). At each phase of the weight-reducing programme, body weight and composition as well as RMR were measured. A regression equation was established in a control population of the same age to predict RMR in obese men at each phase of the weight-loss programme. We observed that body weight and fat mass (FM) were significantly reduced (P < 0·05), while fat-free mass remained unchanged throughout the programme. In phase 1, measured RMR had fallen by 418 kJ/d, more than predicted (P < 0·05), and this difference reached 706 kJ/d at plateau (P < 0·05 v. phase 1). A positive association (r 0·64, P < 0·05) was observed between the reduction in thermogenesis and the degree of FM depletion at plateau. The adaptive reduction in thermogenesis at plateau was substantial and represented 30·9 % of the compensation in energy balance that led to resistance to further lose body weight. In conclusion, these results show that adaptive reduction in thermogenesis may contribute to the occurrence of resistance to lose fat in obese men subjected to a weight-reducing programme.

Recommendations for vitamin A intake are based on maintaining liver stores of ≥ 0·070 μmol/g, which is sufficient to maintain normal vision. We propose that higher levels may be required to maintain normal immune function. To test this hypothesis, we conducted an 8-week residential study among thirty-six healthy Bangladeshi men with low vitamin A stores. Subjects were randomised to receive vitamin A (240 mg in four doses) or placebo during study weeks 2 and 3. Vitamin A stores were estimated by isotopic dilution at week 8. Total T-cells, the naive T-cells:memory T-cells ratio and mitogen-induced lymphocyte proliferation were positively and significantly correlated with vitamin A stores (P < 0·05). Mitogen-stimulated IL-2, IL-4 and TNFα increased significantly (P < 0·05) in the vitamin A but not placebo group after supplementation, while IL-10 production was significantly and negatively correlated with vitamin A stores (P < 0·05). Segmented linear regression analysis revealed that naive T-cell counts and T-cell blastogenesis were positively associated with vitamin A stores above but not below 0·070 μmol/g liver. These data show that increasing vitamin A stores above the level that maintains normal vision enhances some measures of T-cell-mediated immunity, suggesting a difference in requirements for maintaining vision and immune function.

Estimation of whole-grain (WG) food intake in epidemiological and nutritional studies is normally based on general diet FFQ, which are not designed to specifically capture WG intake. To estimate WG cereal intake, we developed a forty-three-item FFQ focused on cereal product intake over the past month. We validated this questionnaire against a 3-d-weighed food record (3DWFR) in thirty-one subjects living in the French-speaking part of Switzerland (nineteen female and twelve male). Subjects completed the FFQ on day 1 (FFQ1), the 3DWFR between days 2 and 13 and the FFQ again on day 14 (FFQ2). The subjects provided a fasting blood sample within 1 week of FFQ2. Total cereal intake, total WG intake, intake of individual cereals, intake of different groups of cereal products and alkylresorcinol (AR) intake were calculated from both FFQ and the 3DWFR. Plasma AR, possible biomarkers for WG wheat and rye intake were also analysed. The total WG intake for the 3DWFR, FFQ1, FFQ2 was 26 (sd 22), 28 (sd 25) and 21 (sd 16) g/d, respectively. Mean plasma AR concentration was 55·8 (sd 26·8) nmol/l. FFQ1, FFQ2 and plasma AR were correlated with the 3DWFR (r 0·72, 0·81 and 0·57, respectively). Adjustment for age, sex, BMI and total energy intake did not affect the results. This FFQ appears to give a rapid and adequate estimate of WG cereal intake in free-living subjects.

We aimed to examine the effect of different doses of lutein supplementation on visual function in subjects with long-term computer display light exposure. Thirty-seven healthy subjects with long-term computer display light exposure ranging in age from 22 to 30 years were randomly assigned to one of three groups: Group L6 (6 mg lutein/d, n 12); Group L12 (12 mg lutein/d, n 13); and Group Placebo (maltodextrin placebo, n 12). Levels of serum lutein and visual performance indices such as visual acuity, contrast sensitivity and glare sensitivity were measured at weeks 0 and 12. After 12-week lutein supplementation, serum lutein concentrations of Groups L6 and L12 increased from 0·356 (sd 0·117) to 0·607 (sd 0·176) μmol/l, and from 0·328 (sd 0·120) to 0·733 (sd 0·354) μmol/l, respectively. No statistical changes from baseline were observed in uncorrected visual acuity and best-spectacle corrected visual acuity, whereas there was a trend toward increase in visual acuity in Group L12. Contrast sensitivity in Groups L6 and L12 increased with supplementation, and statistical significance was reached at most visual angles of Group L12. No significant change was observed in glare sensitivity over time. Visual function in healthy subjects who received the lutein supplement improved, especially in contrast sensitivity, suggesting that a higher intake of lutein may have beneficial effects on the visual performance.

The proposed impact of slowly digestible sources of dietary carbohydrate in reducing the risk of developing obesity and related metabolic disorders remains unclear. The aim of the present study was to compare the postprandial metabolic response to the ingestion of glucose v. trehalose. We hypothesised that the reduced digestion and absorption rate of trehalose is accompanied by an attenuated glycaemic and insulinaemic response, leading to a less inhibited postprandial fat oxidation rate. In a randomised, single-blind, cross-over study, ten overweight subjects ingested two carbohydrate drinks (75 g carbohydrate equivalents of trehalose or glucose) following an overnight fast (08.40 hours) and together with a standardised mixed meal (12.30 hours; 25 % total energy content was provided as either glucose or trehalose). Blood samples were collected before ingestion and every 30 min thereafter for a period of 3 h; substrate use was assessed by indirect calorimetry and expired breath samples were collected. Ingestion of carbohydrates with a mixed meal resulted in a lower peak glucose response and a lower change in area under the curve (ΔAUC) following trehalose when compared with glucose. Differences in peak insulin response and ΔAUC were observed with trehalose when compared with glucose during the morning and afternoon. These differences were accompanied with a reduced carbohydrate oxidation after trehalose when ingested as a drink, whilst no significant differences in fat oxidation between drink were observed.

The diet consumed by urban residents in modern China has become rich in saturated fats and cholesterol. In addition, the diet is high in carbohydrates from white rice and processed wheat starch. The aim of the present study was to determine the effects of replacing white rice and processed wheat starch with wild rice (WR) as the chief source of dietary carbohydrates. Rats fed with the diet patterned after the diet consumed by city residents of modern China showed elevated serum lipid levels comparable with rats consuming a high fat/cholesterol diet known to induce hyperlipidaemia in this species. Meanwhile, rats consuming the city diet with WR as the carbohydrate source suppressed the increase in serum TAG and total cholesterol, and the decrease in HDL cholesterol level. In addition, the rats fed the WR diet suppressed the build-up of oxidative stress by improving antioxidant capacity, increasing superoxide dismutase activity and reducing malondialdehyde concentration, both in the serum and liver. These findings illustrate that WR is effective in suppressing hyperlipidaemia and oxidative stress in rats even when the diet consumed is high in fat and cholesterol.

Previous evidence suggests that the lactase gene C/T− 13910 polymorphism (rs4988235) is associated with avoidance of milk products and lower Ca intake. We examined whether the consumption of milk and milk products and the intakes of milk nutrients differ between the lactase genotypes from childhood to young adulthood. Subjects belong to the Cardiovascular Risk in Young Finns Study where the first cross-sectional surveys were conducted in 1980 (n 3596), with follow-up studies in 1983, 1986, 1989, 1992 and 2001 (n 2620). The same dietary questionnaire was used throughout the follow-up to collect data on habitual consumption of milk and milk products in all subjects, and daily nutrient intakes were assessed with 48 h dietary recalls in 50 % of the subjects. Subjects with the lactase non-persistence (C/C− 13910) genotype consumed less milk since childhood, but the consumption of other milk products did not differ between the genotypes. In adult females, the lactose content of milk products consumed was lower (P = 0·003), and in both sexes low-lactose and milk-free diets were more common in the C/C− 13910 genotype than in the other genotypes. Inadequate Ca intake was most common in females with the C/C− 13910 genotype as early as in childhood (15–63 %), but in males only in adulthood (24 %). In adult females, preference for low-lactose milk and milk products equalised the differences in Ca intake between the genotypes. Thus, in those with the C/C− 13910 genotype, preference for low-lactose milk and milk products may decrease the risk for inadequate Ca intake.

The EURRECA Network of Excellence is working towards the development of aligned micronutrient recommendations across Europe. The purpose of the present study was to define how to identify dietary intake validation studies in adults pertaining to vitamins. After establishing a search strategy, we conducted a MEDLINE and EMBASE literature review. A scoring system was developed to rate the quality of each validation study according to sample size, statistical methods, data collection procedure, seasonality and vitamin supplement use. This produced a quality index with possible scores obtained ranging from 0·5 to 7. Five thousand four-hundred and seventy-six papers were identified. The numbers meeting the inclusion criteria were: for vitamin A, 76; vitamin C, 108; vitamin D, 21; vitamin E, 75; folic acid, 47; vitamin B12, 19; vitamin B6, 21; thiamine, 49; riboflavin, 49; and niacin, 32. The most frequently used method to ascertain dietary intake was the Food Frequency Questionnaire (FFQ), whereas dietary records (DR) and 24-h recalls were the most used reference methods. The correlation coefficients (CC) between vitamin intakes estimated by FFQ and the reference method were weighted according to the study's quality index and ranged from 0·41 to 0·53 when the reference method was the DR and from 0·43 to 0·67 when the reference was 24-h recalls. A minority of studies (n 33) used biomarkers for validation and in these the CC ranged from 0·26 to 0·38. The FFQ is an acceptable method of assessing vitamin intake. The present review provides new insights regarding the characteristics that assessment methods for dietary intake should fulfil.

The hypothesis that increases in the concentration of the anorectic peptide leptin may be responsible for the immune-mediated reduction in feed intake (FI) during gastrointestinal parasitism in sheep was investigated. In a 2 × 2 × 2 factorial design, the first factor was age at the start of infection (5 months old v. 17 months old). The second factor was parasite infection (no infection v. administration of eighty L3 infective Trichostrongylus colubriformis larvae/kg live weight (LW) per d three times per week for 77 d). The third factor was immunosuppressive therapy with a corticosteroid (no therapy or weekly intramuscular injection of 40 mg methylprednisolone acetate/30 kg LW). Relative to their uninfected counterparts, a 20 % reduction in FI per unit LW (FI/LW; g DM/kg LW) was observed in infected non-suppressed 5-month-old lambs from 21 to 63 d post-infection (P < 0·001) but not in comparable17-month-old ewes or in corticosteroid-treated lambs or ewes (P>0·05 for all), allowing the suggestion that the anorexia was a consequence of the developing immune response. The reduction in FI/LW in 5-month-old lambs was not associated with an increase in plasma leptin concentration. Furthermore, plasma leptin concentrations were greater in corticosteroid-treated animals (P < 0·001) and in 17-month-old animals (P < 0·001), none of which displayed an infection-induced reduction in FI/LW. Plasma leptin was positively correlated with carcass fat percentage in both 5-month-old (P = 0·016) and 17-month-old (P < 0·001) animals and did not appear to provide a direct feedback mechanism that restricted energy intake. The results do not support the hypothesis that an increase in circulating leptin is directly responsible for the immune-mediated anorexia in lambs during T. colubriformis infection.

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.

The intake of isoflavones and the resulting equol contents of both plasma and milk of the same red clover-fed cows are reported for the first time in cyclic change-over design study. Cows were fed four different red clover silages and two timothy–meadow fescue silages as controls. The red clover silages contained daidzein, formononetin, biochanin A and genistein, whereas the timothy–meadow fescue silages contained no isoflavones. We found a strong association (y = 0·071x+2·75, R 2 0·71) between the formononetin intake (x) and equol concentration (y) in the plasma, while the formononetin intake and milk equol concentration were weakly associated (y = 0·0035x+0·358, R 2 0·20). This means that a small part of the total formononetin in the silage is secreted into milk as equol. The mean equol contents in plasma and milk of cows fed red clover silage diets were in the range of 4·6–8·4 mg/l and 458–643 μg/l, respectively, while the respective values for the control diets were in the range of 0·8–1·5 mg/l and 171–287 μg/l. We showed that shorter growing periods of red clover resulted in higher silage formononetin contents and plasma and milk equol contents, suggesting that the equol content of milk can be manipulated by varying the harvesting strategy of red clover. We conclude that milk equol is derived from the formononetin of red clover silage and that milk from red clover-fed cows can be considered as a source of equol in human nutrition.

Nutrition during pregnancy and in early life may influence developmental plasticity and alter susceptibility to obesity and adult disease. One mechanism by which this could occur is through epigenetic changes, such as changes in methylation levels, which modify gene expression patterns. Folate intake during pregnancy, as well as maternal methyltetrahydrofolate reductase (MTHFR) C677T genotype, influences the availability of methyl donors for methylation during gestation and therefore may be associated with offspring body composition in childhood. We looked at associations between maternal folic acid supplementation at 18 and 32 weeks of pregnancy, folate intake in the diet (from self-reported FFQ) at 32 weeks of pregnancy and offspring body composition at age 9 years among 5783 children from a population-based birth cohort study in the UK. We also looked at maternal and offspring's MTHFR C677T genotype in relation to offspring body composition. We found no evidence to support the hypothesis that intra-uterine exposure to folate influences childhood body composition.

Conjugated linoleic acid (CLA) isomers have been reported to reduce body weight and beneficially affect glucose metabolism in animals, but the results are inconsistent and seem to depend on animal model and type of CLA isomer. In the present study, feeding male Zucker fa/fa rats diets supplemented with 1 % trans-10, cis-12-CLA for 10 d reduced the liver TAG content without improving the overall adiposity, and enhanced hepatic mitochondrial and peroxisomal β-oxidation. The increased carnitine palmitoyltransferase (CPT)-I activity and mRNA level as well as the increased n-3:n-6 PUFA ratio in liver suggest that trans-10, cis-12-CLA increased the hepatic β-oxidation by stimulation of PPARα. The reduced hepatic TAG content may be partly due to lower activity of stearoyl-CoA desaturase, as the ratios of 18 : 1n-9:18 : 0 and 16 : 1n-7:16 : 0 were reduced in liver. Trans-10, cis-12-CLA increased the CPT-I mRNA in retroperitoneal white adipose tissue (WAT), and increased uncoupling protein-2 mRNA in epididymal and inguinal WAT depots. Leptin mRNA level was decreased in all examined WAT depots, implying reduced insulin sensitivity. The resistin mRNA level was increased in all WAT depots, whereas adiponectin mRNA was reduced in inguinal and retroperitoneal WAT. The present results suggest that dietary supplementation with trans-10, cis-12-CLA may increase the catabolism of lipids in liver and adipose tissue. Moreover, we provide new data suggesting that trans-10, cis-12-CLA modulates the expression of resistin and adiponectin inversely in adipose tissue. Hence, the present results suggest that trans-10, cis-12-CLA may have some beneficial effects on lipid metabolism and adiposity but possibly reduces insulin sensitivity.

The association between trans-fatty acids (TFA) and cancer risk is poorly understood and remains controversial. It is recognised that unique biological effects are associated with specific isoforms within families of fatty acids such as those belonging to the n-3 fatty acids. Furthermore, the interactions between diet and genetic polymorphisms are increasingly recognised for their potential risk-modifying effects on human health and disease. Therefore, the aim of the present review is to evaluate whether specific TFA isomers and genetic polymorphisms differentially modify cancer risk in prostate, colon and breast cancers in animal and human models. Potential mechanisms of action by which TFA may affect cancer development are also reviewed. Overall, across a number of experimental models and human studies, there is insufficient and inconsistent evidence linking specific TFA isomers to cancers of the prostate, colon and breast. A number of methodological limitations and experimental considerations were identified which may explain the inconsistencies observed across these studies. Therefore, further research is warranted to accurately assess the relationship between TFA and cancer risk.

Epidemiological evidence suggests that the intake of prebiotic dietary fibres, for example, inulin, protects against colorectal cancer. However, little is known about cellular responses to complex fermentation samples. Therefore, we prepared a fermentation supernatant fraction of inulin and studied biological properties in human colon cell lines, LT97 and HT29 (representing early and late stages of colon cancer). Inulin enriched with oligofructose (Synergy 1) was incubated under anaerobic conditions with faecal inocula and the supernatant fraction was characterised for content of SCFA and secondary bile acid deoxycholic acid (DCA). A Synergy fermentation supernatant fraction (SFS) and a synthetic fermentation mixture (SFM) mimicking the SFS in SCFA and DCA content were used in the concentration range of 1·25–20 % (v/v) for 24–72 h. The effects on cell growth were determined by quantifying DNA. Effects on apoptosis were analysed by measuring poly(ADP-ribose) polymerase (PARP) cleavage using Western blotting. Compared with the faecal blank, produced without the addition of inulin, the SFS resulted in an almost 2·5-fold increase of SCFA and 3·4-fold decrease of DCA. In comparison with HT29 cells, LT97 cells responded more sensitively to the growth-inhibitory activities. Additionally, a significant increase in PARP cleavage was observed in LT97 cells after incubation with the SFS, demonstrating induction of apoptosis. The present results indicate growth-inhibiting and apoptosis-inducing effects of fermentation supernatant fractions of inulin. Moreover, since early adenoma cells were found to be more sensitive, this may have important implications for chemoprevention when translated to the in vivo situation, because survival of early transformed cells could be reduced.

There is interest in the degree to which fats in dairy foods contribute to CHD. We undertook a systematic review to investigate the effect of dairy consumption on CHD using prospective cohort studies. A systematic search of electronic databases identified studies relating dairy food intake in adulthood to episodes or death from CHD, IHD and myocardial infarction. Included studies were assessed for quality based on study methodology, validity of dietary assessment, success of follow-up, standardised assessment of CHD, IHD or myocardial infarction end points and appropriateness of statistical adjustment. Data from twelve cohorts involving >280 000 subjects were included. Most studies had follow-up of >80 %, adjusted statistically for three or more confounders and used standard criteria to determine end points. About half the studies used a validated FFQ, administered the FFQ more than once or had follow-up of >20 years. Fewer than half the studies involved subjects representative of the general population. Four of the twelve cohorts found no association between dairy intake and CHD. Eight studies reported varying relationships between different dairy foods and CHD or differential associations based on race, sex or over time. Although dairy foods contribute to the SFA composition of the diet, this systematic review could find no consistent evidence that dairy food consumption is associated with a higher risk of CHD. This could be due to the limited sensitivity of the dietary assessment methods to detect an effect of a single food in a mixed diet on complex clinical outcomes.