Molecular determinants and intracellular targets of taurine signalling in pancreatic islet ß-cells.

AIM: Despite its abundance in pancreatic islets of Langerhans and proven antihyperglycemic effects, the impact of the essential amino acid, taurine, on islet ß-cell biology has not yet received due consideration, which prompted the current studies exploring the molecular selectivity of taurine import into ß-cells and its acute and chronic intracellular interactions. METHODS: The molecular aspects of taurine transport were probed by exposing the clonal pancreatic BRIN BD11 ß-cells and primary mouse and human islets to a range of the homologs of the amino acid (assayed at 2-20 mM), using the hormone release and imaging of intracellular signals as surrogate read-outs. Known secretagogues were employed to profile the interaction of taurine with acute and chronic intracellular signals. RESULTS: Taurine transporter TauT was expressed in the islet ß-cells, with the transport of taurine and homologs having a weak sulfonate specificity but significant sensitivity to the molecular weight of the transporter. Taurine, hypotaurine, homotaurine, and ß-alanine enhanced insulin secretion in a glucose-dependent manner, an action potentiated by cytosolic Ca2+ and cAMP. Acute and chronic ß-cell insulinotropic effects of taurine were highly sensitive to co-agonism with GLP-1, forskolin, tolbutamide, and membrane depolarization, with an unanticipated indifference to the activation of PKC and CCK8 receptors. Pre-culturing with GLP-1 or KATP channel inhibitors sensitized or, respectively, desensitized ß-cells to the acute taurine stimulus. CONCLUSION: Together, these data demonstrate the pathways whereby taurine exhibits a range of beneficial effects on insulin secretion and ß-cell function, consistent with the antidiabetic potential of its dietary low-dose supplementation.

NKCC transport mediates the insulinotropic effects of taurine and other small neutral amino acids.

AIMS: Despite its high concentration in pancreatic islets of Langerhans and broad range of antihyperglycemic effects, the route facilitating the import of dietary taurine into pancreatic ß-cell and mechanisms underlying its insulinotropic activity are unclear. We therefore studied the impact of taurine on beta-cell function, alongside that of other small neutral amino acids, L-alanine and L-proline. MAIN METHODS: Pharmacological profiling of insulin secretion was conducted using clonal BRIN BD11 ß-cells, the impact of taurine on the metabolic fate of glucose carbons was assessed using NMR and the findings were verified by real-time imaging of Ca2+ dynamics in the cytosol of primary mouse and human islet beta-cells. KEY FINDINGS: In our hands, taurine, alanine and proline induced secretory responses that were dependent on the plasma membrane depolarisation, import of Ca2+, homeostasis of K+ and Na+ as well as on cell glycolytic and oxidative metabolism. Taurine shifted the balance between the oxidation and anaplerosis towards the latter, in BRIN BD11 beta-cells. Furthermore, the amino acid signalling was significantly attenuated by inhibition of Na+-K+-Cl- symporter (NKCC). SIGNIFICANCE: These data suggest that taurine, like L-alanine and L-proline, acutely induces glucose-dependent insulin-secretory responses by modulating electrogenic Na+ transport, with potential role of intracellular K+ and Cl- in the signal transduction. The acute action delineated would be consistent with antidiabetic potential of dietary taurine supplementation.

A 2-Year Randomized Controlled Trial With Low-Dose B-Vitamin Supplementation Shows Benefits on Bone Mineral Density in Adults With Lower B12 Status.

Folate, vitamins B12, B6, and riboflavin are required for one-carbon metabolism and may affect bone health, but no previous randomized trial has investigated all four nutrients in this context. We investigated the effect of low-dose B-vitamins for 2 years on bone mineral density (BMD) in a dual-centered, 2-year randomized controlled trial (RCT) in adults aged ≥50 years. Eligible participants not consuming B-vitamin supplements or fortified foods >4 times weekly were randomized to receive daily either combined folic acid (200 µg), vitamin B12 (10 µg), vitamin B6 (10 mg), and riboflavin (5 mg), or "active" placebo, whereby both the intervention and placebo groups received vitamin D (10 µg). BMD was assessed before and after intervention using dual-energy X-ray absorptiometry (DXA) scanning of the total hip, femoral neck, and lumbar spine (L1 to L4). Of 205 eligible participants randomized, 167 completed the trial in full. B-vitamin intervention resulted in increases in serum folate (p < 0.001), serum B12 (p < 0.001), and plasma pyridoxal-5-phosphate (p < 0.001) and decreases in functional biomarkers of B-vitamin status, erythrocyte glutathione reductase activation coefficient (p < 0.001), serum methylmalonic acid (MMA; p < 0.001), and serum total homocysteine (p < 0.001). B-vitamin intervention had no overall effect on BMD, which declined in both treatment groups by approximately 1% (ranging from -0.7% to -1.4%). However, in participants with lower baseline B12 status (serum B12 <246 pmol/L or MMA ≥0.22 µmol/L), B-vitamin intervention reduced the 2-year BMD decline versus placebo: adjusted mean (95% confidence interval [CI]) change of -0.003 (-0.008, 0.002) versus -0.015 (-0.021, -0.010) g/cm2 at the total hip and -0.004 (-0.010, 0.001) versus -0.013 (-0.018, -0.007) g/cm2 at the femoral neck. In conclusion, the findings indicate that although low-dose B-vitamin intervention for 2 years had no overall effect on BMD, improving B-vitamin status appears to have specific benefits for bone health in adults with lower B12 status. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The ability of deep eutectic solvent systems to extract bioactive compounds from apple pomace.

The objective of this study was to examine the bioactivity of extracts from apple pomace obtained by non-conventional green extraction methods (DES systems). Bioactivity was antioxidant capacity and ability to stimulate insulin secretion from pancreatic beta-cells. The antioxidant capacity of extracts was examined using the DPPH and the FRAP assay. Impact of the extracts on cell viability and insulin secretion were examined using the BRIN-BD11 cell line. ChCl:EG(1:4) extracts resulted in high antioxidant capacity in the DPPH assay (80.1% inhibition versus 11.3%). Extracts obtained from the classical systems demonstrated an ability to promote insulin secretion significantly higher than the positive control, p < 0.05. ChCl:EG(1:4) extracts stimulated insulin secretion to a lesser extent. Overall, the data provides evidence for the potential of DES systems to extract bioactive compounds from apple pomace that have relevance for metabolic health. Further optimisation of the extraction procedures should be tailored to the desired bioactive properties.

Interindividual variability in response to protein and fish oil supplementation in older adults: a randomized controlled trial.

BACKGROUND: Precision nutrition is highly topical. However, no studies have explored the interindividual variability in response to nutrition interventions for sarcopenia. The purpose of this study was to determine the magnitude of interindividual variability in response to two nutrition supplementation interventions for sarcopenia and metabolic health, after accounting for sources of variability not attributable to supplementation. METHODS: A 24 week, randomized, double-blind, placebo-controlled trial tested the impact of leucine-enriched protein (LEU-PRO), LEU-PRO plus long-chain n-3 PUFA (LEU-PRO+n-3) or control (CON) supplementation in older adults (n = 83, 71 ± 6 years) at risk of sarcopenia. To estimate the true interindividual variability in response to supplementation (free of the variability due to measurement error and within-subject variation), the standard deviation of individual responses (SDR ) was computed and compared with the minimally clinically important difference (MCID) for appendicular lean mass (ALM), leg strength, timed up-and-go (TUG), and serum triacylglycerol (TG) concentration. Clinically meaningful interindividual variability in response to supplementation was deemed to be present when the SDR positively exceeded the MCID. The probability that individual responses were clinically meaningful, and the phenotypic, dietary, and behavioural determinants of response to supplementation were examined. RESULTS: The SDR was below the MCID for ALM (LEU-PRO: -0.12 kg [90% CI: -0.38, 0.35], LEU-PRO+n-3: -0.32 kg [-0.45, 0.03], MCID: 0.21 kg), TUG (LEU-PRO: 0.58 s [0.18, 0.80], LEU-PRO+n-3: 0.73 s [0.41, 0.95], MCID: 0.9 s) and TG (LEU-PRO: -0.38 mmol/L [-0.80, 0.25], LEU-PRO+n-3: -0.44 mmol/L [-0.63, 0.06], MCID: 0.1 mmol/L), indicating no meaningful interindividual variability in response to either supplement. The SDR exceeded the MCID (19 Nm) for strength in response to LEU-PRO (25 Nm [-29, 45]) and LEU-PRO+n-3 (23 Nm [-29, 43]) supplementation but the effect was uncertain, evidenced by wide confidence intervals. In the next stage of analysis, similar proportions of participant responses were identified as very likely, likely, possibly, unlikely, and very unlikely to represent clinically meaningful improvements across the LEU-PRO, LEU-PRO+n-3, and CON groups (P > 0.05). Baseline LC n-3 PUFA status, habitual protein intake, and numerous other phenotypic and behavioural factors were not determinants of response to LEU-PRO or LEU-PRO+n-3 supplementation. CONCLUSIONS: Applying a novel, robust methodological approach to precision nutrition, we show that there was minimal interindividual variability in changes in ALM, muscle function, and TG in response to LEU-PRO and LEU-PRO+n-3 supplementation in older adults at risk of sarcopenia.

Effectiveness of a fortified drink in improving B vitamin biomarkers in older adults: a controlled intervention trial.

BACKGROUND: Older adults are reported to have sub-optimal B vitamin status; targeted food-based solutions may help to address this. The objectives of the OptiAge food intervention study were to develop and investigate the effectiveness of a B vitamin-fortified drink in improving B vitamin biomarkers in older Irish adults with a primary outcome of change in the B vitamin biomarker status. METHODS: A double-blinded randomised controlled trial was performed in parallel at University College Dublin and Ulster University. Participants aged > 50 years were recruited following screening for exclusion criteria (i.e. taking medications known to interfere with B vitamin metabolism, supplements containing B vitamins, consuming > 4 portions of B vitamin-fortified foods per week or diagnosed with gastrointestinal, liver or pulmonary disease). Recruited participants meeting the inclusion criteria were randomised (by sex and study centre) to receive daily for 16 weeks either B vitamin-fortified or placebo drinks as developed by Smartfish, Norway. Each B vitamin-fortified drink (200 ml) contained 200 µg folic acid, 10 µg vitamin B12, 10 mg vitamin B6 and 5 mg riboflavin, while the placebo was an identical, isocaloric formulation without added B vitamins. Fasting blood samples were collected pre- and post-intervention which were used to measure the primary outcome of change in B vitamin biomarker levels. RESULTS: A total of 95 participants were randomised, of which 81 commenced the trial. Of these, 70 completed (37 in the active and 33 in the placebo groups). Intention to treat (ITT) analysis of the B vitamins demonstrated a significant improvement in all B vitamin biomarkers in the active compared to placebo groups: p < 0.01 for each of serum folate, serum vitamin B12 and plasma pyridoxal 5'-phosphate (vitamin B6) and the functional riboflavin biomarker, erythrocyte glutathione reductase activation coefficient (EGRac). Correspondingly, a significant lowering of serum homocysteine from 11.9 (10.3-15.1) µmol/L to 10.6 (9.4-13.0) µmol/L was observed in response to the active treatment (P < 0.001). Similar results were seen in a per-protocol analysis. CONCLUSIONS: The results demonstrate that a B vitamin-fortified drink was effective in optimising B vitamin status, making this a useful intervention option to improve B vitamin status in older adults. Trial registration ISRCTN, ISRCTN61709781-Retrospectively registered, https://www.isrctn.com/ISRCTN61709781.

Leptin Supplementation During Lactation Restores Key Liver Metabolite Levels Malprogrammed by Gestational Calorie Restriction.

INTRODUCTION: Perinatal nutritional factors can program offspring metabolic phenotype and risk to obesity. This study investigates the potential role of leptin supplementation (during lactation) in ameliorating the malprogrammed effects caused by mild maternal calorie restriction during gestation, on young rat offspring liver metabolic response. METHODS AND RESULTS: Untargeted and targeted metabolomics studies on liver samples are performed by NMR and GC-MS, respectively. Global DNA methylation and the expression by RT-PCR of key genes involved in different pathways are also determined. By NMR, 15 liver metabolites are observed to be altered in the offspring of gestational calorie-restricted dams (CR group), at days 25-27 of life. Physiological leptin supplementation during lactation partially reverted the effect of CR condition for most of these metabolites. Moreover, targeted fatty acid analysis by GC-MS shows a significant decrease in the hepatic concentration of certain very long-chain fatty acids (VLCFA) in CR offspring, partially or totally reverted by leptin supplementation. No remarkable changes are found in global DNA methylation or mRNA expression. CONCLUSION: Physiological leptin supplementation during lactation contributes to the reversion of changes caused by maternal mild calorie restriction on the liver metabolome. This agrees with a putative role of leptin supplementation preventing or reversing metabolic disturbances caused by gestational metabolic malprogramming.

Characteristics of participants who benefit most from personalised nutrition: findings from the pan-European Food4Me randomised controlled trial.

Little is known about who would benefit from Internet-based personalised nutrition (PN) interventions. This study aimed to evaluate the characteristics of participants who achieved greatest improvements (i.e. benefit) in diet, adiposity and biomarkers following an Internet-based PN intervention. Adults (n 1607) from seven European countries were recruited into a 6-month, randomised controlled trial (Food4Me) and randomised to receive conventional dietary advice (control) or PN advice. Information on dietary intake, adiposity, physical activity (PA), blood biomarkers and participant characteristics was collected at baseline and month 6. Benefit from the intervention was defined as ≥5 % change in the primary outcome (Healthy Eating Index) and secondary outcomes (waist circumference and BMI, PA, sedentary time and plasma concentrations of cholesterol, carotenoids and omega-3 index) at month 6. For our primary outcome, benefit from the intervention was greater in older participants, women and participants with lower HEI scores at baseline. Benefit was greater for individuals reporting greater self-efficacy for 'sticking to healthful foods' and who 'felt weird if [they] didn't eat healthily'. Participants benefited more if they reported wanting to improve their health and well-being. The characteristics of individuals benefiting did not differ by other demographic, health-related, anthropometric or genotypic characteristics. Findings were similar for secondary outcomes. These findings have implications for the design of more effective future PN intervention studies and for tailored nutritional advice in public health and clinical settings.

Variable Glycemic Responses to Intact and Hydrolyzed Milk Proteins in Overweight and Obese Adults Reveal the Need for Precision Nutrition.

Background: Dietary modifications can contribute to improved pancreatic ß cell function and enhance glycemic control. Objectives: The objectives of this study were as follows: 1) to investigate the potential of milk protein hydrolysates to modulate postprandial glucose response; 2) to assess individual responses; and 3) to explore the inter- and intraindividual reproducibility of the response. Methods: A 14-d randomized crossover study investigated interstitial glucose levels of participants in response to 12% w/v milk protein drinks (intact caseinate and casein hydrolysate A and B) consumed in random order with a 2-d washout between treatments. Milk protein drinks were consumed immediately prior to study breakfast and evening meals. Twenty participants (11 men, 9 women) aged 50 ± 8 y with a body mass index (in kg/m2) of 30.2 ± 3.1 were recruited. Primary outcome was glucose levels assessed at 15-min intervals with the use of glucose monitors. Results: Repeated-measures ANOVA revealed that for breakfast there was a significant difference across the 3 treatment groups (P = 0.037). The ability to reduce postprandial glucose was specific to casein hydrolysate B in comparison with intact caseinate (P = 0.039). However, despite this significant difference, further examination revealed that only 3 out of 18 individuals were classified as responders (P < 0.05). High intraclass correlation coefficients were obtained for glucose response to study meals (intraclass correlation coefficient: 0.892 for breakfast with intact caseinate). The interindividual CVs were higher than the intraindividual CVs. Mean inter- and intraindividual CVs were 19.4% and 5.7%, respectively, for breakfast with intact caseinate. Conclusion: Ingestion of a specific casein hydrolysate successfully reduced the postprandial glucose response; however, at an individual level only 3 participants were classified as responders, highlighting the need for precision nutrition. Exploration of high interindividual responses to nutrition interventions is needed, in combination with the development of precision nutrition, potentially through an n-of-1 approach. This clinical trial was registered as ISRCTN61079365 (https://www.isrctn.com/).

Casein Hydrolysate with Glycemic Control Properties: Evidence from Cells, Animal Models, and Humans.

Evidence exists to support the role of dairy derived proteins whey and casein in glycemic management. The objective of the present study was to use a cell screening method to identify a suitable casein hydrolysate and to examine its ability to impact glycemia related parameters in an animal model and in humans. Following screening for the ability to stimulate insulin secretion in pancreatic beta cells, a casein hydrolysate was selected and further studied in the ob/ob mouse model. An acute postprandial study was performed in 62 overweight and obese adults. Acute and long-term supplementation with the casein hydrolysate in in vivo studies in mice revealed a glucose lowering effect and a lipid reducing effect of the hydrolysate (43% reduction in overall liver fat). The postprandial human study revealed a significant increase in insulin secretion ( p = 0.04) concomitant with a reduction in glucose ( p = 0.03). The area under the curve for the change in glucose decreased from 181.84 ± 14.6 to 153.87 ± 13.02 ( p = 0.009). Overall, the data supports further work on the hydrolysate to develop into a functional food product.

Maternal metabolic response to dietary treatment for impaired glucose tolerance and gestational diabetes mellitus.

BACKGROUND: Dietary advice is a standard component of treatment for pregnant women with impaired glucose tolerance (IGT) and gestational diabetes (GDM), yet few studies report glycemic profiles in response to dietary therapies and the optimal dietary approach remains uncertain. AIM: To assess changes in maternal glycemic profile and pregnancy outcomes among women with diet-controlled IGT and GDM. METHODS: Pregnant women who had one or more elevated values on a 3-h oral glucose tolerance test were enrolled. All participants received dietary advice and glucose monitoring as part of routine clinical care. Fasting and 1-h post-prandial blood samples, collected prior to initiation of clinical treatment and repeated 4-6 weeks later, were analyzed for glucose, insulin, and C-peptide. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Women who required pharmacological therapy for glucose control were excluded from analyses. RESULTS: Participants (N = 93) were of moderately older age (mean 33 years), with a high rate of overweight/obesity (mean body mass index (BMI) = 28.65 kg/m2), and were diagnosed late in gestation (mean 29 weeks). Fasting (mean ± SD 4.82 ± 0.53 to 4.60 ± 0.42 mmol/l; p < 0.001) and post-prandial glucose (7.01 ± 1.19 to 6.47 ± 1.10; p = 0.004) decreased significantly following the intervention. Baseline HOMA-IR was elevated (3.12 ± 1.03) but did not significantly decrease (2.78 ± 1.52; p = 0.066). There were high rates of macrosomia (24.7%) and cesarean delivery (32.3%). CONCLUSIONS: Although improvements in blood glucose levels were observed among women with diet-controlled IGT and GDM, this was insufficient to significantly affect insulin resistance or perinatal outcome. Late diagnosis and treatment of IGT/GDM may have contributed to such outcomes.

Associations of vitamin D status with dietary intakes and physical activity levels among adults from seven European countries: the Food4Me study.

PURPOSE: To report the vitamin D status in adults from seven European countries and to identify behavioural correlates. METHODS: In total, 1075 eligible adult men and women from Ireland, Netherlands, Spain, Greece, UK, Poland and Germany, were included in the study. RESULTS: Vitamin D deficiency and insufficiency, defined as 25-hydroxy vitamin D3 (25-OHD3) concentration of <30 and 30-49.9 nmol/L, respectively, were observed in 3.3 and 30.6% of the participants. The highest prevalence of vitamin D deficiency was found in the UK and the lowest in the Netherlands (8.2 vs. 1.1%, P < 0.05). In addition, the prevalence of vitamin D insufficiency was higher in females compared with males (36.6 vs. 22.6%, P < 0.001), in winter compared with summer months (39.3 vs. 25.0%, P < 0.05) and in younger compared with older participants (36.0 vs. 24.4%, P < 0.05). Positive dose-response associations were also observed between 25-OHD3 concentrations and dietary vitamin D intake from foods and supplements, as well as with physical activity (PA) levels. Vitamin D intakes of ≥5 µg/day from foods and ≥5 µg/day from supplements, as well as engagement in ≥30 min/day of moderate- and vigorous-intensity PA were associated with higher odds (P < 0.05) for maintaining sufficient (≥50 nmol/L) 25-OHD3 concentrations. CONCLUSIONS: The prevalence of vitamin D deficiency varied considerably among European adults. Dietary intakes of ≥10 µg/day of vitamin D from foods and/or supplements and at least 30 min/day of moderate- and vigorous-intensity PA were the minimum thresholds associated with vitamin D sufficiency.

Knowing your genes: does this impact behaviour change?

It is postulated that knowledge of genotype may be more powerful than other types of personalised information in terms of motivating behaviour change. However, there is also a danger that disclosure of genetic risk may promote a fatalistic attitude and demotivate individuals. The original concept of personalised nutrition (PN) focused on genotype-based tailored dietary advice; however, PN can also be delivered based on assessment of dietary intake and phenotypic measures. Whilst dietitians currently provide PN advice based on diet and phenotype, genotype-based PN advice is not so readily available. The aim of this review is to examine the evidence for genotype-based personalised information on motivating behaviour change, and factors which may affect the impact of genotype-based personalised advice. Recent findings in PN will also be discussed, with respect to a large European study, Food4Me, which investigated the impact of varying levels of PN advice on motivating behaviour change. The researchers reported that PN advice resulted in greater dietary changes compared with general healthy eating advice, but no additional benefit was observed for PN advice based on phenotype and genotype information. Within Food4Me, work from our group revealed that knowledge of MTHFR genotype did not significantly improve intakes of dietary folate. In general, evidence is weak with regard to genotype-based PN advice. For future work, studies should test the impact of PN advice developed on a strong nutrigenetic evidence base, ensure an appropriate study design for the research question asked, and incorporate behaviour change techniques into the intervention.

Weekday sunlight exposure, but not vitamin D intake, influences the association between vitamin D receptor genotype and circulating concentration 25-hydroxyvitamin D in a pan-European population: the Food4Me study.

SCOPE: Little is known about diet- and environment-gene interactions on 25-hydroxyvitamin D (25(OH)D concentration. This cross-sectional study aimed to investigate (i) predictors of 25(OH)D concentration and relationships with vitamin D genotypes and (ii) whether dietary vitamin D intake and sunlight exposure modified these relationships. METHODS AND RESULTS: Participants from the Food4Me study (n = 1312; age 18-79) were genotyped for vitamin D receptor (VDR) and vitamin D binding protein at baseline and a genetic risk score was calculated. Dried blood spot samples were assayed for 25(OH)D concentration and dietary and lifestyle information collected. Circulating 25(OH)D concentration was lower with increasing genetic risk score, lower in females than males, higher in supplement users than non-users and higher in summer than winter. Carriage of the minor VDR allele was associated with lower 25(OH)D concentration in participants with the least sunlight exposure. Vitamin D genotype did not influence the relationship between vitamin D intake and 25(OH)D concentration. CONCLUSION: Age, sex, dietary vitamin D intake, country, sunlight exposure, season, and vitamin D genetic risk score were associated with circulating 25(OH)D concentration in a pan-European population. The relationship between VDR genotype and 25(OH)D concentration may be influenced by weekday sunlight exposure but not dietary vitamin D intake.

The effect of the apolipoprotein E genotype on response to personalized dietary advice intervention: findings from the Food4Me randomized controlled trial.

BACKGROUND: The apolipoprotein E (APOE) risk allele (ɛ4) is associated with higher total cholesterol (TC), amplified response to saturated fatty acid (SFA) reduction, and increased cardiovascular disease. Although knowledge of gene risk may enhance dietary change, it is unclear whether ɛ4 carriers would benefit from gene-based personalized nutrition (PN). OBJECTIVES: The aims of this study were to 1) investigate interactions between APOE genotype and habitual dietary fat intake and modulations of fat intake on metabolic outcomes; 2) determine whether gene-based PN results in greater dietary change than do standard dietary advice (level 0) and nongene-based PN (levels 1-2); and 3) assess the impact of knowledge of APOE risk (risk: E4+, nonrisk: E4-) on dietary change after gene-based PN (level 3). DESIGN: Individuals (n = 1466) recruited into the Food4Me pan-European PN dietary intervention study were randomly assigned to 4 treatment arms and genotyped for APOE (rs429358 and rs7412). Diet and dried blood spot TC and ω-3 (n-3) index were determined at baseline and after a 6-mo intervention. Data were analyzed with the use of adjusted general linear models. RESULTS: Significantly higher TC concentrations were observed in E4+ participants than in E4- (P < 0.05). Although there were no significant differences in APOE response to gene-based PN (E4+ compared with E4-), both groups had a greater reduction in SFA (percentage of total energy) intake than at level 0 (mean ± SD: E4+, -0.72% ± 0.35% compared with -1.95% ± 0.45%, P = 0.035; E4-, -0.31% ± 0.20% compared with -1.68% ± 0.35%, P = 0.029). Gene-based PN was associated with a smaller reduction in SFA intake than in nongene-based PN (level 2) for E4- participants (-1.68% ± 0.35% compared with -2.56% ± 0.27%, P = 0.025). CONCLUSIONS: The APOE ɛ4 allele was associated with higher TC. Although gene-based PN targeted to APOE was more effective in reducing SFA intake than standard dietary advice, there was no difference between APOE "risk" and "nonrisk" groups. Furthermore, disclosure of APOE nonrisk may have weakened dietary response to PN. This trial was registered at clinicaltrials.gov as NCT01530139.

Dietary fat intakes in Irish adults in 2011: how much has changed in 10 years?

Imbalances in dietary fat intakes are linked to several chronic diseases. This study describes dietary intakes and food sources of fat and fatty acids in 1051 Irish adults (aged 18-90 years), using data from the 2011 national food consumption survey, the National Adult Nutrition Survey. It also compares current intakes for 18-64-year-olds with those reported in the last such survey in 2001, the North/South Ireland Food Consumption Survey. Dietary fat intakes were estimated using data from 4-d semi-weighed (2011) and 7-d estimated (2001) food diaries. In 2011, intakes for 18-64-year-olds were as follows: total fat, 34·1 (sd 6·1) % total energy (%TE); SFA, 13·3 (sd 3·3) %TE; MUFA, 12·5 (sd 2·6) %TE; PUFA, 6·1 (sd 2·2) %TE; and trans-fat, 0·511 (sd 0·282) %TE. Apart from MUFA, intakes decreased (P65 years had the highest intakes of SFA; however, intakes were typically higher than UK-recommended values for all groups. In contrast, intakes of long-chain n-3 fatty acids were lowest in younger age groups. Intakes of trans-fat were well within UK-recommended levels. Although there have been some improvements in the profile of intakes since 2001, imbalances persist in the quantity and quality of dietary fat consumed by Irish adults, most notably for total and SFA and for younger age groups for long-chain n-3 fatty acids.

α-Tocopherol Stereoisomers in Human Plasma Are Affected by the Level and Form of the Vitamin E Supplement Used.

BACKGROUND: Studies examining vitamin E intake and the percentage of the population meeting dietary guidelines do not distinguish between natural (RRR-α-tocopherol) and synthetic (all-rac-α-tocopherol) intake, even though these different isomeric forms differ in bioactivity. OBJECTIVE: This study aimed to determine the effect of RRR-α-tocopherol vs. all-rac-α-tocopherol intake on the percentage of the population meeting the vitamin E recommendation and on plasma α-tocopherol stereoisomer distribution. METHODS: With the use of data from the Irish National Adult Nutrition Survey (NANS), this study examined the percentage of the Irish population meeting the European Union (EU) RDA for vitamin E of 12 mg/d, correcting for a bioactivity difference in all-rac- vs. RRR-α-tocopherol, where 1 mg of all-rac-α-tocopherol is considered to be equivalent to 1:1.36 (0.74) mg in the EU RDA. In a subcohort of supplement users and nonusers, plasma α- and γ-tocopherol concentrations and α-tocopherol stereoisomer distribution were measured. Receiver operating characteristic (ROC) curve analysis was conducted to determine ability to discriminate supplement user types. RESULTS: Analysis of the NANS showed that 100% of participants still met the recommended intake of 12 mg/d, after all-rac-α-tocopherol intake was corrected for α-tocopherol equivalent bioactivity. In the subcohort analysis, the percentage of plasma RRR-α-tocopherol was significantly lower in high all-rac-α-tocopherol supplement (>11 mg/d) users (82%) compared with nonusers and with high RRR-α-tocopherol supplement (>35 mg/d) users (91% and 93% respectively, P < 0.01). High RRR-α-tocopherol supplement users had a significantly higher plasma α-tocopherol than low all-rac-α-tocopherol supplement (<2.5 mg/d) users (34 vs. 25 µmol/L, P = 0.01). ROC analysis demonstrated an ability to distinguish between RRR- and all-rac-α-tocopherol consumers, which may be useful in investigating the potential effect of RRR- and all-rac-α-tocopherol intake on health. CONCLUSIONS: This study demonstrated that the percentage of the population meeting the vitamin E recommendation was unaffected when all-rac-α-tocopherol intake was corrected for α-tocopherol equivalent bioactivity. all-rac-α-Tocopherol intake led to a decrease in the percentage of plasma RRR-α-tocopherol relative to RRR-α-tocopherol intake.

Effects of the Mediterranean diet supplemented with coenzyme q10 on metabolomic profiles in elderly men and women.

BACKGROUND: Characterization of the variations in the metabolomic profiles of elderly people is a necessary step to understand changes associated with aging. This study assessed whether diets with different fat quality and supplementation with coenzyme Q10 (CoQ) affect the metabolomic profile in urine analyzed by proton nuclear magnetic resonance spectroscopy from elderly people. METHODS: Ten participants received, in a cross-over design, four isocaloric diets for 4-week periods each: Mediterranean diet supplemented with CoQ (Med + CoQ diet); Mediterranean diet; Western diet rich in saturated fat diet; low-fat, high-carbohydrate diet enriched in n-3 polyunsaturated fat. RESULTS: Multivariate analysis showed differences between diets when comparing Med + CoQ diet and saturated fat diet, with greater hippurate urine levels after Med + CoQ diet and higher phenylacetylglycine levels after saturated fat diet in women. Following consumption of Med + CoQ, hippurate excretion was positively correlated with CoQ and ß-carotene plasma levels and inversely related to Nrf2, thioredoxin, superoxide dismutase 1, and gp91(phox) subunit of NADPH oxidase gene expression. After saturated fat diet consumption, phenylacetylglycine excretion was inversely related to CoQ plasma level and positively correlated with isoprostanes urinary level. CONCLUSIONS: The association between hippurate excretion and antioxidant biomarkers along with the relationship between phenylacetylglycine excretion and oxidant biomarkers suggests that the long-term consumption of a Med + CoQ diet could be beneficial for healthy aging and a promising challenge in the prevention of processes related to chronic oxidative stress, such as cardiovascular and neurodegenerative disease.

Metabolic profiling of human peripheral blood mononuclear cells: influence of vitamin d status and gender.

Metabolic profiling of peripheral blood mononuclear cells (PBMC) could serve as a less invasive and more direct alternative to tissue biopsies or serum in metabolomic research. We conducted two exploratory independent studies in order to characterise PBMC's metabolomic profile following short-term vitamin D3 supplementation and to determine gender effects. In the first study, eight healthy males and females aged 40-65 y were randomly selected for profiling of PBMCs after receiving either 15 µg of vitamin D3 or placebo for four weeks. In the second study, twenty younger healthy males and females were studied. Cell metabolites were extracted and deproteinised using methanol/chloroform/water method and analysed by GC-MS. Higher vitamin D status had no effect on the fatty acid profile of PBMCs, but inflammatory biomarkers and adipokines correlated positively with stearic acid levels. In the second study, no gender-specific metabolites were identified. Valine, leucine and aspartic acid were identified as potential BMI-sensitive amino acids. Larger studies are needed to confirm the influence of BMI on these parameters. This work clearly demonstrates the utility of metabolomics profiling of PBMCs and paves the way for future applications of metabolomics in identifying metabolic profiles of blood cells as a measure for dietary intakes or physiological status.

Effect of supplementation with vitamin D2-enhanced mushrooms on vitamin D status in healthy adults.

Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety volunteers (aged 40-65 years) were randomly assigned to one of two 4-week studies: mushroom study (15 µg vitamin D2 or placebo mushroom powder) and capsule study (15 µg vitamin D3 or placebo capsules). Consumption of vitamin D2-enhanced mushrooms increased serum 25-hydroxyvitamin D2 (25(OH)D2) by 128 % from baseline (3·9 (sd 1·9) nmol/l; P < 0·05). Serum 25(OH)D3 increased significantly in the vitamin D3 capsule group (a 55 % increase from a baseline of 44.0 (sd 17·1) nmol/l; P < 0·05). Vitamin D status (25(OH)D) was affected only in the vitamin D3 group. Plasminogen activator inhibitor-1 was lowered by vitamin D2 intake. Vitamin D2 from enhanced mushrooms was bioavailable and increased serum 25(OH)D2 concentration with no significant effect on 25(OH)D3 or total 25(OH)D.