B. van Ommen

Combating inflammaging through a Mediterranean whole diet approach:the NU-AGE project's conceptual framework and design

The development of a chronic, low grade, inflammatory status named inflammaging is a major characteristic of ageing, which plays a critical role in the pathogenesis of age-related diseases. Inflammaging is both local and systemic, and a variety of organs and systems contribute inflammatory stimuli that accumulate lifelong. The NU-AGE rationale is that a one year Mediterranean whole diet (considered by UNESCO a heritage of humanity), newly designed to meet the nutritional needs of the elderly, will reduce inflammaging in fully characterized subjects aged 65-79 years of age, and will have systemic beneficial effects on health status (physical and cognitive). Before and after the dietary intervention a comprehensive set of analyses, including omics (transcriptomics, epigenetics, metabolomics and metagenomics) will be performed to identify the underpinning molecular mechanisms. NU-AGE will set up a comprehensive database as a tool for a systems biology approach to inflammaging and nutrition. NU-AGE is highly interdisciplinary, includes leading research centres in Europe on nutrition and ageing, and is complemented by EU multinational food industries and SMEs, interested in the production of functional and enriched/advanced traditional food tailored for the elderly market, and European Federations targeting policy makers and major stakeholders, from consumers to EU Food & Drink Industries.

Metabolomics of prolonged fasting in humans reveals new catabolic markers

Fasting is one of the simplest metabolic challenges that can be performed in humans. We here report for the first time a comprehensive analysis of the human “fasting metabolome” obtained from analysis of plasma and urine samples in a small cohort of healthy volunteers, using nuclear magnetic resonance (NMR), gas chromatography- and liquid chromatography-mass spectrometry (GC-MS and LC-MS). Intra- and inter-individual variation of metabolites was on measurement of four overnight fasting samples collected from each volunteer over a four week period. One additional sample per volunteer was collected following a prolonged fasting period of 36xa0h. Amongst a total of 377 quantified entities in plasma around 44% were shown to change significantly in concentration when volunteers extended fasting from 12 to 36xa0h. In addition to known markers (plasma free fatty acids, glycerol, ketone bodies) that reflect changes in the body’s fuel management under fasting conditions a wide range of “new” entities such as α-aminobutyrate as well as other amino and keto acids were identified as fasting markers. Based on multiple correlations amongst the metabolites and selected hormones in plasma such as leptin or insulin-like-growth-factor-1 (IGF-1), a robust metabolic network with coherent regulation of a wide range of metabolites could be identified. The metabolomics approach described here demonstrates the plasticity of human metabolism and identifies new and robust markers of the fasting state.

The insulin resistance phenotype (muscle or liver) interacts with the type of diet to determine changes in disposition index after 2 years of intervention: the CORDIOPREV-DIAB randomised clinical trial

AbstractAims/hypothesisThe aim of the study was to determine whether basal insulin resistance (IR) phenotype (muscle and/or liver) determines the effect of long-term consumption of a Mediterranean diet or a low-fat diet on tissue-specific IR and beta cell function.MethodsThe study was performed in 642 patients included in The effect of an olive oil rich Mediterranean diet on type 2 diabetes mellitus risk and incidence study (CORDIOPREV-DIAB). A total of 327 patients were randomised to a Mediterranean diet (35% fat; 22% from monounsaturated fatty acids) and 315 to a low-fat diet (<28% fat). At baseline, the patients were classified into four phenotypes according to the type of IR: (1) no IR; (2) muscle IR; (3) liver IR; (4) muscleu2009+u2009liver IR. The hepatic insulin resistance index (HIRI), muscular insulin sensitivity index (MISI) and disposition index were analysed at baseline and after 2xa0years of follow-up.ResultsAt baseline, 322 patients presented no IR, 106 presented muscle IR, 109 presented liver IR, and 105 presented muscleu2009+u2009liver IR. With both dietary interventions, HIRI decreased in all patients (pu2009<u20090.001) and MISI increased in muscle IR and muscleu2009+u2009liver IR patients (pu2009<u20090.01). Long-term intake of the Mediterranean diet increased the disposition index and insulinogenic index in the muscle IR patients (pu2009=u20090.042 and pu2009=u20090.044, respectively) and the disposition index in the muscleu2009+u2009liver IR patients (pu2009=u20090.048), whereas the low-fat diet increased the disposition index in the liver IR patients (pu2009=u20090.017).Conclusions/interpretationAlthough both diets improve insulin sensitivity, there are differences based on basal IR phenotypes. Moreover, according to insulinogenic and disposition index data, a low-fat diet might be more beneficial to patients with liver IR, whereas patients with muscle IR and muscleu2009+u2009liver IR might benefit more from a Mediterranean diet.n Trial registration ClinicalTrials.gov NCT00924937FundingThe study was supported by the Ministerio de Economia y Competitividad (AGL2012/39615) and by the Ministerio de Ciencia e Innovacion (PIE14/00005 and PI13/00023)

EURRECA: development of tools to improve the alignment of micronutrient recommendations

Approaches through which reference values for micronutrients are derived, as well as the reference values themselves, vary considerably across countries. Harmonisation is needed to improve nutrition policy and public health strategies. The EURRECA (EURopean micronutrient RECommendations Aligned, http://www.eurreca.org) Network of Excellence is developing generic tools for systematically establishing and updating micronutrient reference values or recommendations. Different types of instruments (including best practice guidelines, interlinked web pages, online databases and decision trees) have been identified. The first set of instruments is for training purposes and includes mainly interactive digital learning materials. The second set of instruments comprises collection and interlinkage of diverse information sources that have widely varying contents and purposes. In general, these sources are collections of existing information. The purpose of the majority of these information sources is to provide guidance on best practice for use in a wider scientific community or for users and stakeholders of reference values. The third set of instruments includes decision trees and frameworks. The purpose of these tools is to guide non-scientists in decision making based on scientific evidence. This platform of instruments will, in particular in Central and Eastern European countries, contribute to future capacity-building development in nutrition. The use of these tools by the scientific community, the European Food Safety Authority, bodies responsible for setting national nutrient requirements and others should ultimately help to align nutrient-based recommendations across Europe. Therefore, EURRECA can contribute towards nutrition policy development and public health strategies.

Analyzing metabolomics-based challenge tests

Challenge tests are used to assess the resilience of human beings to perturbations by analyzing responses to detect functional abnormalities. Well known examples are allergy tests and glucose tolerance tests. Increasingly, metabolomics analysis of blood or serum samples is used to analyze the biological response of the individual to these challenges. The information content of such metabolomics challenge test data involves both the disturbance and restoration of homeostasis on a metabolic level and is thus inherently different from the analysis of steady state data. It opens doors to study the variation of resilience between individuals beyond the classical biomarkers; preferably in terms of underlying biological processes. We review challenge tests in which metabolomics was used to analyze the biological response. Specifically, we describe strategies to perform statistical analyses on the responses and we will show some examples of these strategies applied to a postprandial challenge that was used to study a diet with anti-inflammatory properties. Finally we discuss open issues and give recommendation for further research.