Chemotherapy effects on mitochondrial function in adipose tissue in oesophageal and gastroesophageal junction adenocarcinomas with or without associated cachexia: protocol for a prospective, comparative observational study (ChiFMeOE).

INTRODUCTION: Cachexia is strongly associated with digestive cancers, particularly oesogastric cancer. Mitochondria in adipose tissue are involved in the regulation of metabolism and physiopathology of cancer cachexia in animal studies. Chemotherapeutic regimens used to control tumour development could also alter mitochondrial function in adipose tissue. We hypothesise that cachexia induces an increase in adipose tissue mitochondrial energy metabolism and that chemotherapy can mitigate this. The purpose of the ChiFMeOE study is to identify adipocyte factors involved in the energy imbalance associated with the cachectic process and their response to chemotherapeutic treatments in patients with oesogastric cancer. METHODS AND ANALYSIS: ChiFMeOE is a single-centre observational study that will prospectively include 60 patients referred to chemotherapy and surgery for oesophageal and gastro-oesophageal junction adenocarcinomas at the University Hospital of Clermont-Ferrand, France. Visceral and subcutaneous adipose tissue biopsies will be collected during surgery scheduled before and after neoadjuvant chemotherapy administration, as well as cachexia and nutritional assessment. The primary outcome is the maximum mitochondrial respiration rate (Vmax) measured by high-resolution respirometry. Secondary outcomes are other mitochondrial parameters (ie, enzymatic activities, proteins content and gene expression), tumour characteristics, nutritional status and body composition. ETHICS AND DISSEMINATION: The study was approved by an independent institutional review board on June 2023 (Comité de protection des personnes Sud-Méditerranée V; 2023-A00582-43) and declared to the French regulatory authority for research. Written informed consent will be obtained prior to patient inclusion. The principal investigator will be notified of any changes in patient's health status requiring a modification of his management and/or treatment during the course of the protocol. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT05954117.

Mitochondrial Function in Healthy Human White Adipose Tissue: A Narrative Review.

As ¾ of the global population either have excess or insufficient fat, it has become increasingly critical to understand the functions and dysfunctions of adipose tissue (AT). AT serves as a key organ in energy metabolism, and recently, attention has been focused on white AT, particularly its mitochondria, as the literature evidence links their functions to adiposity. This narrative review provides an overview of mitochondrial functionality in human white AT. Firstly, it is noteworthy that the two primary AT depots, subcutaneous AT (scAT) and visceral AT (vAT), exhibit differences in mitochondrial density and activity. Notably, vAT tends to have a higher mitochondrial activity compared to scAT. Subsequently, studies have unveiled a negative correlation between mitochondrial activity and body mass index (BMI), indicating that obesity is associated with a lower mitochondrial function. While the impact of exercise on AT mitochondria remains uncertain, dietary interventions have demonstrated varying effects on AT mitochondria. This variability holds promise for the modulation of AT mitochondrial activity. In summary, AT mitochondria exert a significant influence on health outcomes and can be influenced by factors such as obesity and dietary interventions. Understanding the mechanisms underlying these responses can offer potential insights into managing conditions related to AT and overall health.

Casein structures differently affect postprandial amino acid delivery through their intra-gastric clotting properties.

We aimed to assess if casein structure affects its digestion and its subsequent amino acid delivery kinetic. Higher nitrogen levels were recovered in dialysates after in vitro digestions of sodium caseinate (SC, formed of small aggregates) compared to micellar casein (MC, native form of casein) and calcium caseinate (CC, intermediate structure). Likewise, plasma indispensable amino-acid concentration peak was higher after SC compared to MC or CC ingestion in healthy volunteers in a randomized, double blind, cross-over study. In pigs, gamma-scintigraphy using labelled meals revealed that SC was mainly localized in the proximal part of the stomach whereas MC was distributed in the whole gastric cavity. Caseins were found in both solid and liquid phases and partly hydrolyzed casein in the solid phase shortly after SC drink ingestion. These data support the concept of slow (MC) and rapid (SC) casein depending of casein structure, likely due to their intra-gastric clotting properties.

Protein intake and bone mineral density: Cross-sectional relationship and longitudinal effects in older adults.

BACKGROUND: There are several mechanisms via which increased protein intake might maintain or improve bone mineral density (BMD), but current evidence for an association or effect is inconclusive. The objectives of this study were to investigate the association between dietary protein intake (total, plant and animal) with BMD (spine and total body) and the effects of protein supplementation on BMD. METHODS: Individual data from four trials that included either (pre-)frail, undernourished or healthy older adults (aged ≥65 years) were combined. Dietary intake was assessed with food records (2, 3 or 7 days) and BMD with dual-energy X-ray absorptiometry (DXA). Associations and effects were assessed by adjusted linear mixed models. RESULTS: A total of 1570 participants [57% women, median (inter-quartile range): age 71 (68-75) years] for which at least total protein intake and total body BMD were known were included in cross-sectional analyses. In fully adjusted models, total protein intake was associated with higher total body and spine BMD [beta (95% confidence interval): 0.0011 (0.0006-0.0015) and 0.0015 (0.0007-0.0023) g/cm2 , respectively]. Animal protein intake was associated with higher total body and spine BMD as well [0.0011 (0.0007-0.0016) and 0.0017 (0.0010-0.0024) g/cm2 , respectively]. Plant protein intake was associated with a lower total body and spine BMD [-0.0010 (-0.0020 to -0.0001) and -0.0019 (-0.0034 to -0.0004) g/cm2 , respectively]. Associations were similar between sexes. Participants with a high ratio of animal to plant protein intake had higher BMD. In participants with an adequate calcium intake and sufficient serum 25(OH)D concentrations, the association between total protein intake with total body and spine BMD became stronger. Likewise, the association between animal protein intake with total body BMD was stronger. In the longitudinal analyses, 340 participants [58% women, median (inter-quartile range): age 75 (70-81) years] were included. Interventions of 12 or 24 weeks with protein supplementation or protein supplementation combined with resistance exercise did not lead to significant improvements in BMD. CONCLUSIONS: An association between total and animal protein intake with higher BMD was found. In contrast, plant protein intake was associated with lower BMD. Research is warranted to further investigate the added value of dietary protein alongside calcium and vitamin D for BMD improvement, especially in osteopenic or osteoporotic individuals. Moreover, more research on the impact of a plant-based diet on bone health is needed.

K-Clique Multiomics Framework: A Novel Protocol to Decipher the Role of Gut Microbiota Communities in Nutritional Intervention Trials.

The availability of omics data providing information from different layers of complex biological processes that link nutrition to human health would benefit from the development of integrated approaches combining holistically individual omics data, including those associated with the microbiota that impacts the metabolisation and bioavailability of food components. Microbiota must be considered as a set of populations of interconnected consortia, with compensatory capacities to adapt to different nutritional intake. To study the consortium nature of the microbiome, we must rely on specially designed data analysis tools. The purpose of this work is to propose the construction of a general correlation network-based explorative tool, suitable for nutritional clinical trials, by integrating omics data from faecal microbial taxa, stool metabolome (1H NMR spectra) and GC-MS for stool volatilome. The presented approach exploits a descriptive paradigm necessary for a true multiomics integration of data, which is a powerful tool to investigate the complex physiological effects of nutritional interventions.

Effects of exercise-induced metabolic and mechanical loading on skeletal muscle mitochondrial function in male rats.

Over the past decades, a growing interest in eccentric (ECC) exercise has emerged, but mitochondrial adaptations to ECC training remain poorly documented. Using an approach for manipulating mechanical and metabolic exercise power, we positioned that for the same metabolic power, training using concentric (CON) or ECC contractions would induce similar skeletal muscle mitochondrial adaptations. Sixty adult rats were randomly assigned to a control (CTRL) or three treadmill training groups running at 15 m·min-1 for 45 min, 5 days weekly for 8 wk at targeted upward or downward slopes. Animals from the CON (+15%) and ECC30 (-30%) groups were trained at iso-metabolic power, whereas CON and ECC15 (-15%) exercised at iso-mechanical power. Assessments were made of vastus intermedius mitochondrial respiration (oxygraphy), enzymatic activities (spectrophotometry), and real-time qPCR for mRNA transcripts. Maximal rates of mitochondrial respiration were 14%-15% higher in CON and ECC30 compared with CTRL and ECC15. Apparent Km for ADP for trained groups was 40%-66% higher than CTRL, with statistical significance reached for CON and ECC30. Complex I and citrate synthase activities were 1.6 (ECC15) to 1.8 (ECC30 and CON) times values of CTRL. Complex IV activity was higher than CTRL (P < 0.05) only for CON and ECC30. mRNA transcripts analyses showed higher TFAM, SLC25A4, CKMT2, and PPID in the ECC30 compared with CTRL. Findings confirm that training-induced skeletal muscle mitochondrial function adaptations are governed by the extent of metabolic overload irrespective of exercise modality. The distinctive ECC30 mRNA transcript pattern may reflect a cytoskeleton damage-repair or ECC adaptive cycle that differs from that of biogenesis.NEW & NOTEWORTHY Anticipating outcomes of eccentric versus concentric training is confounded by differences in mechanical efficiency. Our observations in groups of rats submitted to uphill and downhill running regimens inducing similar levels of metabolic demands or same external power outputs reaffirm that independent of modality, oxygen requirements and not external work governs skeletal muscle mitochondrial function adaptations.

Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women.

BACKGROUNDHigh circulating levels of ceramides (Cer) and sphingomyelins (SM) are associated with cardiometabolic diseases. The consumption of whole fat dairy products, naturally containing such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown.METHODSIn a 4-week randomized controlled trial, 58 postmenopausal women daily consumed milk PL-enriched cream cheese (0, 3, or 5 g of milk PL). Postprandial metabolic explorations were performed before and after supplementation. Analyses included SM and Cer species in serum, chylomicrons, and feces. The ileal contents of 4 ileostomy patients were also explored after acute milk PL intake.RESULTSMilk PL decreased serum atherogenic C24:1 Cer, C16:1 SM, and C18:1 SM species (Pgroup < 0.05). Changes in serum C16+18 SM species were positively correlated with the reduction of cholesterol (r = 0.706), LDL-C (r = 0.666), and ApoB (r = 0.705) (P < 0.001). Milk PL decreased chylomicron content in total SM and C24:1 Cer (Pgroup < 0.001), parallel to a marked increase in total Cer in feces (Pgroup < 0.001). Milk PL modulated some specific SM and Cer species in both ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.CONCLUSIONMilk PL supplementation decreased atherogenic SM and Cer species associated with the improvement of cardiovascular risk markers. Our findings bring insights on sphingolipid metabolism in the gut, especially Cer, as signaling molecules potentially participating in the beneficial effects of milk PL.TRIAL REGISTRATIONClinicalTrials.gov, NCT02099032, NCT02146339.FUNDINGANR-11-ALID-007-01; PHRCI-2014: VALOBAB, no. 14-007; CNIEL; GLN 2018-11-07; HCL (sponsor).

Unveiling the Correlation between Inadequate Energy/Macronutrient Intake and Clinical Alterations in Volunteers at Risk of Metabolic Syndrome by a Predictive Model.

Although lifestyle-based interventions are the most effective to prevent metabolic syndrome (MetS), there is no definitive agreement on which nutritional approach is the best. The aim of the present retrospective analysis was to identify a multivariate model linking energy and macronutrient intake to the clinical features of MetS. Volunteers at risk of MetS (F = 77, M = 80) were recruited in four European centres and finally eligible for analysis. For each subject, the daily energy and nutrient intake was estimated using the EPIC questionnaire and a 24-h dietary recall, and it was compared with the dietary reference values. Then we built a predictive model for a set of clinical outcomes computing shifts from recommended intake thresholds. The use of the ridge regression, which optimises prediction performances while retaining information about the role of all the nutritional variables, allowed us to assess if a clinical outcome was manly dependent on a single nutritional variable, or if its prediction was characterised by more complex interactions between the variables. The model appeared suitable for shedding light on the complexity of nutritional variables, which effects could be not evident with univariate analysis and must be considered in the framework of the reciprocal influence of the other variables.

Vitamin B-6 intake is related to physical performance in European older adults: results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) study.

BACKGROUND: Maintenance of high physical performance during aging might be supported by an adequate dietary intake of niacin, vitamins B-6 and B-12, and folate because these B vitamins are involved in multiple processes related to muscle functioning. However, not much is known about the association between dietary intake of these B vitamins and physical performance. OBJECTIVES: The objectives of this study were to investigate the association between dietary intake of niacin, vitamins B-6 and B-12, and folate and physical performance in older adults and to explore mediation by niacin status and homocysteine concentrations. METHODS: We used baseline data from the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) trial, which included n = 1249 healthy older adults (aged 65-79 y) with complete data on dietary intake measured with 7-d food records and questionnaires on vitamin supplement use and physical performance measured with the short physical performance battery and handgrip dynamometry. Associations were assessed by adjusted linear mixed models. RESULTS: Intake of vitamin B-6 was related to lower chair rise test time [ß: -0.033 ± 0.016 s (log); P = 0.043]. Vitamin B-6 intake was also significantly associated with handgrip strength, but for this association, a significant interaction effect between vitamin B-6 intake and physical activity level was found. In participants with the lowest level of physical activity, higher intake of vitamin B-6 tended to be associated with greater handgrip strength (ß: 1.5 ± 0.8 kg; P = 0.051), whereas in participants in the highest quartile of physical activity, higher intake was associated with lower handgrip strength (ß: -1.4 ± 0.7 kg; P = 0.041). No evidence was found for an association between intake of niacin, vitamin B-12, or folate and physical performance or for mediation by niacin status or homocysteine concentrations. CONCLUSIONS: Vitamin B-6 intake was associated with better chair rise test time in a population of European healthy older adults and also with greater handgrip strength in participants with low physical activity only. Homocysteine concentrations did not mediate these associations. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.

Metabolomics reveals plausible interactive effects between dairy product consumption and metabolic syndrome in humans.

BACKGROUND & AIMS: Metabolic syndrome (MetS) induces major disturbances in plasma metabolome, reflecting abnormalities of several metabolic pathways. Recent evidences have demonstrated that the consumption of dairy products may protect from MetS, but the mechanisms remains unknown. The present study aimed at identify how the consumption of different types of dairy products could modify the changes in plasma metabolome during MetS. METHODS: In this observational study, we analyzed how the consumption of dairy products could modify the perturbations in the plasma metabolome induced by MetS in a sample of 298 participants (61 with MetS) from the French MONA LISA survey. Metabolomic profiling was analyzed with UPLC-MS/MS. RESULTS: Subjects with MetS exhibited major changes in plasma metabolome. Significant differences in plasma levels of branched chain amino acids, gamma-glutamyl amino acids, and metabolites from arginine and proline metabolism were observed between healthy control and Mets subjects. Plasma levels of many lipid species were increased with MetS (mono- and diacylglycerols, eicosanoids, lysophospholipids and lysoplasmalogens), with corresponding decreases in short chain fatty acids and plasmalogens. The consumption of dairy products, notably with a low fat content (milk and fresh dairy products), altered metabolite profiles in plasma from MetS subjects. Specifically, increasing consumption of dairy products promoted accumulation of plasma C15:0 fatty acid and was inversely associated to some circulating lysophospholipids, sphingolipids, gamma-glutamyl amino acids, leukotriene B4 and lysoplasmalogens. CONCLUSIONS: the consumption of low fat dairy products could mitigate some of the variations induced by MetS.

Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay.

OBJECTIVE: To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health. DESIGN: A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients. RESULTS: Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut. CONCLUSION: The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota. TRIAL REGISTRATION NUMBER: NCT02099032 and NCT02146339; Results.

A Dietary Intervention of Bioactive Enriched Foods Aimed at Adults at Risk of Metabolic Syndrome: Protocol and Results from PATHWAY-27 Pilot Study.

Around a quarter of the global adult population have metabolic syndrome (MetS) and therefore increased risk of cardiovascular mortality and diabetes. Docosahexaenoic acid, oat beta-glucan and grape anthocyanins have been shown to be effective in reducing MetS risk factors when administered as isolated compounds, but their effect when administered as bioactive-enriched foods has not been evaluated. OBJECTIVE: The overall aim of the PATHWAY-27 project was to evaluate the effectiveness of bioactive-enriched food consumption on improving risk factors of MetS. A pilot study was conducted to assess which of five bioactive combinations provided within three different food matrices (bakery, dairy or egg) were the most effective in adult volunteers. The trial also evaluated the feasibility of production, consumer acceptability and gastrointestinal tolerance of the bioactive-enriched food. METHOD: The study included three monocentric, parallel-arm, double-blind, randomised, dietary intervention trials without a placebo. Each recruiting centre tested the five bioactive combinations within a single food matrix. RESULTS: The study was completed by 167 participants (74 male, 93 female). The results indicated that specific bioactive/matrix combinations have effects on serum triglyceride or HDL-cholesterol level without adverse effects. CONCLUSION: The study evidenced that bioactive-enriched food offers a promising food-based strategy for MetS prevention, and highlighted the importance of conducting pilot studies.

Impact of Eccentric or Concentric Training on Body Composition and Energy Expenditure.

PURPOSE: To compare the effects of 8-wk eccentric (ECC) versus concentric (CON) training using downhill and uphill running in rats on whole body composition, bone mineral density (BMD), and energy expenditure. METHODS: Animals were randomly assigned to one of the following groups: 1) control (CTRL), 2) +15% uphill-running slope (CON), 3) -15% downhill-running slope (ECC15), and 4) -30% downhill-running slope (ECC30). Those programs enabled to achieve conditions of isopower output for CON and ECC15 and of iso-oxygen uptake (V˙O2) for CON and ECC30. Trained rats ran 45 min at 15 m·min five times per week. Total body mass, fat body mass, and lean body mass (LBM) measured through EchoMRI™, and 24-h energy expenditure including basal metabolic rate (BMR) assessed using PhenoMaster/LabMaster™ cage system were obtained before and after training. At sacrifice, the right femur was collected for bone parameters analysis. RESULTS: Although total body mass increased in all groups over the 8-wk period, almost no change occurred for fat body mass in exercised groups (CON, -4.8 ± 6.18 g; ECC15, 0.6 ± 3.32 g; ECC30, 2.6 ± 6.01 g). The gain in LBM was mainly seen for ECC15 (88.9 ± 6.85 g) and ECC30 (101.6 ± 11.07 g). ECC was also seen to positively affect BMD. An increase in BMR from baseline was seen in exercise groups (CON, 13.9 ± 4.13 kJ·d; ECC15, 11.6 ± 5.10 kJ·d; ECC30, 18.3 ± 4.33 kJ·d) but not in CTRL one. This difference disappeared when BMR was normalized for LBM. CONCLUSIONS: Results indicate that for iso-V˙O2 training, the impact on LBM and BMD is enhanced with ECC as compared with CON, and that for isopower but lower V˙O2 ECC, an important stimulus for adaptation is still observed. This provides further insights for the use of ECC in populations with cardiorespiratory exercise limitations.

Mediterranean-Style Diet Improves Systolic Blood Pressure and Arterial Stiffness in Older Adults.

We aimed to determine the effect of a Mediterranean-style diet, tailored to meet dietary recommendations for older adults, on blood pressure and arterial stiffness. In 12 months, randomized controlled trial (NU-AGE [New Dietary Strategies Addressing the Specific Needs of Elderly Population for Healthy Aging in Europe]), blood pressure was measured in 1294 healthy participants, aged 65 to 79 years, recruited from 5 European centers, and arterial stiffness in a subset of 225 participants. The intervention group received individually tailored standardized dietary advice and commercially available foods to increase adherence to a Mediterranean diet. The control group continued on their habitual diet and was provided with current national dietary guidance. In the 1142 participants who completed the trial (88.2%), after 1 year the intervention resulted in a significant reduction in systolic blood pressure (-5.5 mm Hg; 95% CI, -10.7 to -0.4; P=0.03), which was evident in males (-9.2 mm Hg, P=0.02) but not females (-3.1 mm Hg, P=0.37). The -1.7 mm Hg (95% CI, -4.3 to 0.9) decrease in diastolic pressure after intervention did not reach statistical significance. In a subset (n=225), augmentation index, a measure of arterial stiffness, was improved following intervention (-12.4; 95% CI, -24.4 to -0.5; P=0.04) with no change in pulse wave velocity. The intervention also resulted in an increase in 24-hour urinary potassium (8.8 mmol/L; 95% CI, 0.7-16.9; P=0.03) and in male participants (52%) a reduction in pulse pressure (-6.1 mm Hg; 95% CI, -12.0 to -0.2; P=0.04) and 24-hour urinary sodium (-27.1 mmol/L; 95% CI, -53.3 to -1.0; P=0.04). In conclusion, a Mediterranean-style diet is effective in improving cardiovascular health with clinically relevant reductions in blood pressure and arterial stiffness. Clinical Trial Registration- URL: http://www.clinicialtrials.gov . Unique identifier: NCT01754012.

DHA-Induced Perturbation of Human Serum Metabolome. Role of the Food Matrix and Co-Administration of Oat ß-glucan and Anthocyanins.

Docosahexaenoic acid (DHA) has been reported to have a positive impact on many diet-related disease risks, including metabolic syndrome. Although many DHA-enriched foods have been marketed, the impact of different food matrices on the effect of DHA is unknown. As well, the possibility to enhance DHA effectiveness through the co-administration of other bioactives has seldom been considered. We evaluated DHA effects on the serum metabolome administered to volunteers at risk of metabolic syndrome as an ingredient of three different foods. Foods were enriched with DHA alone or in combination with oat beta-glucan or anthocyanins and were administered to volunteers for 4 weeks. Serum samples collected at the beginning and end of the trial were analysed by NMR-based metabolomics. Multivariate and univariate statistical analyses were used to characterize modifications in the serum metabolome and to evaluate bioactive-bioactive and bioactive-food matrix interactions. DHA administration induces metabolome perturbation that is influenced by the food matrix and the co-presence of other bioactives. In particular, when co-administered with oat beta-glucan, DHA induces a strong rearrangement in the lipoprotein profile of the subjects. The observed modifications are consistent with clinical results and indicate that metabolomics represents a possible strategy to choose the most appropriate food matrices for bioactive enrichment.

Changes in Dietary Intake and Adherence to the NU-AGE Diet Following a One-Year Dietary Intervention among European Older Adults-Results of the NU-AGE Randomized Trial.

BACKGROUND: The Mediterranean Diet has been proposed as an effective strategy to reduce inflammaging, a chronic low grade inflammatory status, and thus, to slow down the aging process. We evaluated whether a Mediterranean-like dietary pattern specifically targeting dietary recommendations of people aged over 65 years (NU-AGE diet) could be effective to shift dietary intake of older adults towards a healthful diet. METHODS: Adults aged 65⁻80 years across five EU-centers were randomly assigned to a NU-AGE diet group or control group. The diet group followed one year of NU-AGE dietary intervention specifying consumption of 15 food groups plus the use of a vitamin D supplement. Participants in the diet group received counselling and individually tailored dietary advice, food products and a vitamin D supplement. Dietary intake was assessed by means of seven-day food records at baseline and one-year follow-up. A continuous NU-AGE index (0⁻160 points) was developed to assess NU-AGE diet adherence. RESULTS: In total 1296 participants were randomized and 1141 participants completed the intervention (571 intervention, 570 control). After one year, the diet group improved mean intake of 13 out of 16 NU-AGE dietary components (p < 0.05), with a significant increase in total NU-AGE index (difference in mean change = 21.3 ± 15.9 points, p < 0.01). CONCLUSIONS: The NU-AGE dietary intervention, based on dietary recommendations for older adults, consisting of individual dietary counselling, free healthy foods and a vitamin D supplement, may be a feasible strategy to improve dietary intake in an aging European population.

Short Telomere Length Is Related to Limitations in Physical Function in Elderly European Adults.

The present study aims to explore the potential influence of leucocyte telomere length (LTL) on both a single indicator and a composite construct of physical functioning in a large European population of elderly men and women across diverse geographical locations. A total of 1,221 adults (65-79 years) were recruited from five European countries within the framework of NU-AGE study. The physical functioning construct was based on the 36-item Short Form Health Survey. Handgrip strength was used as a single indicator of muscle function and LTL was assessed using quantitative real-time PCR. Women had significantly longer (p < 0.05) LTL than men. Participants in Poland had significantly shorter LTL than in the other study centers, whereas participants in the Netherlands had significantly longer LTL than most of the other centers (p < 0.01). An analysis of LTL as a continuous outcome against physical functioning by using linear models revealed inconsistent findings. In contrast, based on an analysis of contrasting telomere lengths (first vs. fifth quintile of LTL), a significant odds ratio (OR) of 1.7 (95% CI: 1.1 - 2.6; p < 0.05) of having functional limitation was observed in those belonging to the first LTL quintile compared to the fifth. Interestingly, having the shortest LTL was still related to a higher likelihood of having physical limitation when compared to all remaining quintiles (OR: 1.5, 95% CI: 1.1 - 2.1; p < 0.05), even after adjustment by study center, age, sex, and overweight status. Collectively, our findings suggest that short LTL is an independent risk factor that accounts for functional decline in elderly European populations. The influence of LTL on functional limitation seems driven by the detrimental effect of having short telomeres rather than reflecting a linear dose-response relationship.

A Mediterranean-like dietary pattern with vitamin D3 (10 µg/d) supplements reduced the rate of bone loss in older Europeans with osteoporosis at baseline: results of a 1-y randomized controlled trial.

Background: The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking. Objective: The aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans. Design: An RCT was undertaken across 5 European centers. Subjects in the intervention group consumed the NU-AGE diet for 1 y by receiving individually tailored dietary advice, coupled with supplies of foods including whole-grain pasta, olive oil, and a vitamin D3 supplement (10 µg/d). Participants in the control group were provided with leaflets on healthy eating available in their country. Results: A total of 1294 participants (mean ± SD age: 70.9 ±4.0 y; 44% male) were recruited to the study and 1142 completed the 1-y trial. The Mediterranean-like dietary pattern had no effect on BMD (site-specific or whole-body); the inclusion of compliance to the intervention in the statistical model did not change the findings. There was also no effect of the intervention on the urinary biomarkers free pyridinoline or free deoxypyridinoline. Serum 25-hydroxyvitamin D significantly increased and parathyroid hormone decreased (P < 0.001) in the MD compared with the control group. Subgroup analysis of individuals with osteoporosis at baseline (site-specific BMD T-score ≤ -2.5 SDs) showed that the MD attenuated the expected decline in femoral neck BMD (n = 24 and 30 in MD and control groups, respectively; P = 0.04) but had no effect on lumbar spine or whole-body BMD. Conclusions: A 1-y intervention of the Mediterranean-like diet together with vitamin D3 supplements (10 µg/d) had no effect on BMD in the normal age-related range, but it significantly reduced the rate of loss of bone at the femoral neck in individuals with osteoporosis. The NU-AGE trial is registered at clinicaltrials.gov as NCT01754012.

Rapeseed oil fortified with micronutrients can reduce glucose intolerance during a high fat challenge in rats.

BACKGROUND: Better choices of dietary lipid sources and substitution of refined by fortified oils could reduce the intake of saturated fatty acids (FA) and increase the intake of omega 3 FA concomitantly to healthy bioactive compounds. METHODS: The development of obesity and metabolic disturbances was explored in rats fed during 11 weeks with a high fat diet (HFD) in which the amount of saturated and polyunsaturated FA was respectively reduced and increased, using rapeseed oil as lipid source. This oil was used in a refined form (R) or fortified (10 fold increase in concentration) with endogenous micronutrients (coenzyme Q10 + tocopherol only (RF) only and also with canolol (RFC)). The effect of substituting palm by rapeseed oil was analysed using a student t test, oil fortification was analysed using ANOVA statistical test. RESULTS: Despite a similar weight gain, diets R, RF and RFC improved glucose tolerance (+ 10%) of the rats compared to a standard HFD with palm and sunflower oils as lipid source. Plasma glucose was lowered in RF and RFC groups (- 15 and 23% respectively), although triacylglycerol level was only reduced in group RFC (- 33%) compared to R. The fortification with canolol promoted the activation of Akt and AMP-activated protein kinase (AMPK) in skeletal muscle and subcutaneous adipose tissue respectively. Canolol supplementation also led to reduce p38 MAPK activation in skeletal muscle. CONCLUSIONS: This study suggests that the presence of endogenous micronutrients in rapeseed oil promotes cellular adaptations to reverse glucose intolerance and improve the metabolism of insulin sensitive tissues.

Dietary canolol protects the heart against the deleterious effects induced by the association of rapeseed oil, vitamin E and coenzyme Q10 in the context of a high-fat diet.

BACKGROUND: Obesity progressively leads to cardiac failure. Omega-3 polyunsaturated fatty acids (PUFA) have been shown to have cardio-protective effects in numerous pathological situations. It is not known whether rapeseed oil, which contains α-linolenic acid (ALA), has a similar protective effect. Omega-3 PUFAs are sensitive to attack by reactive oxygen species (ROS), and lipid peroxidation products could damage cardiac cells. We thus tested whether dietary refined rapeseed oil (RSO) associated with or without different antioxidants (vitamin E, coenzyme Q10 and canolol) is cardio-protective in a situation of abdominal obesity. METHODS: Sixty male Wistar rats were subdivided into 5 groups. Each group was fed a specific diet for 11 weeks: a low-fat diet (3% of lipids, C diet) with compositionally-balanced PUFAs; a high-fat diet rich in palm oil (30% of lipids, PS diet); the PS diet in which 40% of lipids were replaced by RSO (R diet); the R diet supplemented with coenzyme Q10 (CoQ10) and vitamin E (RTC diet); and the RTC diet supplemented with canolol (RTCC diet). At the end of the diet period, the rats were sacrificed and the heart was collected and immediately frozen. Fatty acid composition of cardiac phospholipids was then determined. Several features of cardiac function (fibrosis, inflammation, oxidative stress, apoptosis, metabolism, mitochondrial biogenesis) were also estimated. RESULTS: Abdominal obesity reduced cardiac oxidative stress and apoptosis rate by increasing the proportion of arachidonic acid (AA) in membrane phospholipids. Dietary RSO had the same effect, though it normalized the proportion of AA. Adding vitamin E and CoQ10 in the RSO-rich high fat diet had a deleterious effect, increasing fibrosis by increasing angiotensin-2 receptor-1b (Ag2R-1b) mRNA expression. Overexpression of these receptors triggers coronary vasoconstriction, which probably induced ischemia. Canolol supplementation counteracted this deleterious effect by reducing coronary vasoconstriction. CONCLUSION: Canolol was found to counteract the fibrotic effects of vitamin E + CoQ10 on cardiac fibrosis in the context of a high-fat diet enriched with RSO. This effect occurred through a restoration of cardiac Ag2R-1b mRNA expression and decreased ischemia.