Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?

Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.

Claimed effects, outcome variables and methods of measurement for health claims proposed under regulation (EC) 1924/2006 and related to cognitive function in adults.

Some food/food components have been the object of request of authorization to the use of health claims related to cognitive function in adults and compliant with the Regulation (EC) 1924/2006. Most of the requests have received a negative opinion by the European Food Safety Authority (EFSA) also because of the choice of not appropriate outcome variables (OVs) and methods of measurement (MMs) selected in the trials used to substantiate the claim. This manuscript referes to the collection, collation and critical analysis of OVs and MMs related to cognitive function in adults. OVs and MMs were collected from the EFSA Guidance document and the applications for authorization of health claims pursuant to the Articles 13(5). The critical analysis of OVs and MMs, performed by a literature review, was aimed at defining their appropriateness in the context of a specific claimed effect. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims related to cognitive functioning. The information provided in this document may serve to EFSA for updating the guidance on the scientific requirements for health claims related to cognitive functions, but also for a better design of randomized controlled trials aimed at substantiating such health claims.

Claimed effects, outcome variables and methods of measurement for health claims proposed under European Community Regulation 1924/2006 in the framework of protection against oxidative damage and cardiovascular health.

BACKGROUND AND AIMS: The high number of negative opinions from the European Food Safety Authority (EFSA) to the requests for authorization of health claims is largely due to the design of human intervention studies, including the inappropriate choice of outcome variables (OVs) and of their methods of measurement (MMs). The present manuscript reports the results of an investigation aimed to collect, collate and critically analyse the information in relation to claimed effects, OVs and MMs, in the context of protection against oxidative damage and cardiovascular health compliant with Regulation 1924/2006. METHODS AND RESULTS: Claimed effects, OVs and the related MMs were collected from EFSA Guidance documents and applications for authorization of health claims under Articles 13.5 and 14. The OVs and their MMs were evaluated only if the claimed effect was sufficiently defined and was considered beneficial by EFSA. The collection, collation and critical analysis of the relevant scientific literature consisted in the definition of the keywords, the PubMed search strategies and the creation of databases of references. The critical analysis of the OVs and their MMs was performed on the basis of the literature review and was aimed at defining the appropriateness of OVs and MMs in the context of the specific claimed effects. CONCLUSIONS: The information provided in this document could serve to EFSA for the development of further guidance on the scientific requirements for health claims, as well as to the stakeholders for the proper design of human intervention studies aimed to substantiate such health claims.

The ß-cell burden index of food: A proposal.

The quantity and quality of dietary fat and/or carbohydrate may alter one or more of the basic components of the insulin-glucose system, which in turn affect the pathways leading to alterations in glucose homeostasis and, possibly, to cardiovascular disease. This viewpoint article, reviewing some of the currently available tools aiming at quantifying the impact of dietary carbohydrates on the glucose-insulin homeostatic loop, highlights the unmet need of a more thorough assessment of the complex interaction between dietary factors and the glucose-insulin system. A novel index, the "ß-cell burden index", may turn out to be a valuable tool to quantify the role played by the diet in shaping the risk of type 2 diabetes, cardiovascular disease and other metabolic and degenerative disorders, ideally orienting their prevention with strategies based on dietary modifications.

Glycemic index and glycemic load of commercial Italian foods.

BACKGROUND AND AIM: The glycemic index (GI) and glycemic load (GL) are useful parameters in the nutritional classification of carbohydrate foods. Diets characterized by a low GI and/or a low GL have been repeatedly and independently associated with decreased risk of diabetes and other chronic diseases. The aim of this study is to report the GI and GL value of carbohydrate-rich foods available on the Italian market and mostly consumed in Italy. METHODS AND RESULTS: GI values were determined according to FAO/WHO (1997) and ISO (2010). Overall, the 141 commercial foods that were analyzed represent food categories that are the source of >80% carbohydrate intake in Italy. The food items chosen were based mainly on the market share of the brand within each food category and grouped into 13 food categories: 1) beverages: fermented milk drink, juice, smoothie, soft drink; 2) biscuits; 3) breads; 4) bread substitutes; 5) breakfast cereals; 6) cakes and snacks; 7) candy and confectionery; 8) cereals; 9) desserts and ice-creams; 10) marmalade and jam; 11) pasta; 12) pizza; 13) sugar and sweetener. CONCLUSION: This database of commercial Italian foods partly overcomes the lack of information on GI and GL of local foods, contributing to a better understanding of the association between GI/GL and health and providing a more informed choice to Italian consumers and health practitioners.

The use of new technologies for nutritional education in primary schools: a pilot study.

INTRODUCTION: The aim of this study was evaluating if the presence of a humanoid robot could improve the efficacy of a game-based, nutritional education intervention. STUDY DESIGN: This was a controlled, school-based pilot intervention carried out on fourth-grade school children (8-10 years old). A total of 112 children underwent a game-based nutritional educational lesson on the importance of carbohydrates. For one group (n = 58), the lesson was carried out by a nutritional educator, the Master of Taste (MT), whereas for another group, (n = 54) the Master of Taste was supported by a humanoid robot (MT + NAO). A third group of children (n = 33) served as control not receiving any lesson. METHODS: The intervention efficacy was evaluated by questionnaires administered at the beginning and at the end of each intervention. The nutritional knowledge level was evaluated by the cultural-nutritional awareness factor (AF) score. RESULTS: A total of 290 questionnaires were analyzed. Both MT and MT + NAO interventions significantly increased nutritional knowledge. At the end of the study, children in the MT and MT + NAO group showed similar AF scores, and the AF scores of both intervention groups were significantly higher than the AF score of the control group. CONCLUSIONS: This study showed a significant increase in the nutritional knowledge of children involved in a game-based, single-lesson, educational intervention performed by a figure that has a background in food science. However, the presence of a humanoid robot to support this figure's teaching activity did not result in any significant learning improvement.

Assessment of vascular and endothelial dysfunction in nutritional studies.

Vascular and endothelial dysfunction (VED) is emerging as a potential set of early markers of cardiovascular disease risk and tests for its measurement have been widely used in clinical research. The aim of this viewpoint is to describe and discuss the current usage of these measures in well-designed nutritional trials, using the potential relationship between fruit juice intake and VED as example. A search was conducted using the NHS evidence portal including studies published in English between January 1980 and October 2013. Only 10 suitable studies were selected, which investigated the effect of fruit juice intake on VED, among which 4 interventions used flow-mediated dilatation, 2 arterial stiffness, 2 a combination of arterial stiffness and flow-mediated dilatation, 2 carotid intimal media thickness and 1 iontophoresis with laser Doppler. Despite minimal effects reported on classical CVD markers, such as lipids, 8 out of the 10 identified studies reported an effect on endothelial function following juice consumption, indicating that VED tests can be effectively used in human dietary interventions to identify relationships between bioactive compounds from fruit and CVD risk. However, paucity of available data, scarcity of compound bioavailability and metabolism information, strong heterogeneity among experimental methodologies and a number of limitations to study designs, still limit the interpretation of the results obtained through these measures. Future, well-designed studies with greater attention to consider use of VED measures are needed to strengthen the utility of VED tests in nutrition research such as those investigating the impact of polyphenol-rich juices and CVD risk.

Bioaccumulation of resveratrol metabolites in myocardial tissue is dose-time dependent and related to cardiac hemodynamics in diabetic rats.

BACKGROUND AND AIMS: Trans-resveratrol (RSV) is a natural compound occurring in different foods and plants, which in vivo is rapidly conjugated with glucuronic acid and sulfate. Despite its demonstrated cardioprotective activity, the bioaccumulation of RSV or its metabolites in cardiac tissue is still unknown. METHODS AND RESULTS: Diabetic rats were randomized to 1, 3 or 6 weeks of RSV treatment at two different doses (1 or 5 mg/kg/day). A dose and time-dependent accumulation was observed, with no detectable levels of RSV metabolites found in heart tissues after 1 week and significant concentrations of RSV-3-sulfate and RSV-3-glucuronide after 6 weeks of treatment (0.05 nmol/g of tissue and 0.01 nmol/g of tissue, respectively). Tissue accumulation of RSV metabolites was accompanied by an improvement of cardiac function in long-term diabetes, when myocardial morpho-functional damage is more evident, with an almost complete recovery of all hemodynamic parameters, at the highest RSV dose. CONCLUSION: Even if a higher concentration of RSV in tissues cannot be ruled out after constant oral administration, an accumulation coherent with what is usually evaluated in cell based mechanistic studies is largely unattainable and the RSV unconjugated form would not be present in this paradigm. The current investigation provides data on myocardial tissue concentrations of RSV metabolites, after short/medium term RSV treatment. This knowledge constitutes a basic requirement for future studies aimed at reliably defining the molecular pathways underlying RSV-mediated cardioprotective effects and opens up new perspectives for research focused on testing phenolic compounds as adjuvants in degenerative heart diseases.

Unraveling the parahormetic mechanism underlying the health-protecting effects of grapeseed procyanidins.

Proanthocyanidins (PACs), the predominant constituents within Grape Seed Extract (GSE), are intricate compounds composed of interconnected flavan-3-ol units. Renowned for their health-affirming properties, PACs offer a shield against a spectrum of inflammation associated diseases, such as diabetes, obesity, degenerations and possibly cancer. While monomeric and dimeric PACs undergo some absorption within the gastrointestinal tract, their larger oligomeric and polymeric counterparts are not bioavailable. However, higher molecular weight PACs engage with the colonic microbiota, fostering the production of bioavailable metabolites that undergo metabolic processes, culminating in the emergence of bioactive agents capable of modulating physiological processes. Within this investigation, a GSE enriched with polymeric PACs was employed to explore in detail their impact. Through comprehensive analysis, the present study unequivocally verified the gastrointestinal-mediated transformation of medium to high molecular weight polymeric PACs, thereby establishing the bioaccessibility of a principal catabolite termed 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (VL). Notably, our findings, encompassing cell biology, chemistry and proteomics, converge to the proposal of the notion of the capacity of VL to activate, upon oxidation to the corresponding quinone, the nuclear factor E2-related factor 2 (Nrf2) pathway-an intricate process that incites cellular defenses and mitigates stress-induced responses, such as a challenge brought by TNFα. This mechanistic paradigm seamlessly aligns with the concept of para-hormesis, ultimately orchestrating the resilience to stress and the preservation of cellular redox equilibrium and homeostasis as benchmarks of health.

Anti-estrogenic activity of a human resveratrol metabolite.

BACKGROUND AND AIMS: Resveratrol, the most investigated dietary compound in studies aimed at linking wine consumption to human health, is an extremely minor component of this beverage and it is generally studied in vitro as the unconjugated aglycone at concentrations largely exceeding those found in the human circulatory system after dietary intake. Moreover, following intestinal absorption, trans-resveratrol and its glucoside, which are naturally present in wine and other food sources, are converted to sulphate and glucuronide metabolites. An estrogenic activity has previously been documented for resveratrol, yet nothing is known about the activity of its blood-circulating metabolic derivatives. METHODS AND RESULTS: Using a yeast two-hybrid detection system relying on the interaction between the ligand-binding domain of the human oestrogen receptors α and ß and the human coactivator Tif2, we have systematically examined the oestrogen agonist and antagonist activities of the two main resveratrol forms present in planta (trans-resveratrol and trans-resveratrol-3-O-glucoside) and of the three main metabolites found in human plasma (trans-resveratrol-3-O-sulphate, trans-resveratrol-3-O-glucuronide and trans-resveratrol-4'-O-glucuronide). Only resveratrol-3-O-sulphate was found to display a fairly strong and oestrogen receptor α-preferential antagonistic activity, which was confirmed in a human breast adenocarcinoma cell line containing a luciferase reporter gene under the control of an oestrogen-responsive promoter. CONCLUSIONS: We show, for the first time, that resveratrol-3-O-sulphate, but neither of its metabolites, is endowed with anti-estrogenic activity and how human metabolism of phenolic substances plays a pivotal role in modulating their biological effect.

Splicing accuracy varies across human introns, tissues and age.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigated mis-splicing using RNA-sequencing data from ~14K control samples and 42 human body sites, focusing on split reads partially mapping to known transcripts in annotation. We show that mis-splicing occurs at different rates across introns and tissues and that these splicing inaccuracies are primarily affected by the abundance of core components of the spliceosome assembly and its regulators. Using publicly available data on short-hairpin RNA-knockdowns of numerous spliceosomal components and related regulators, we found support for the importance of RNA-binding proteins in mis-splicing. We also demonstrated that age is positively correlated with mis-splicing, and it affects genes implicated in neurodegenerative diseases. This in-depth characterisation of mis-splicing can have important implications for our understanding of the role of splicing inaccuracies in human disease and the interpretation of long-read RNA-sequencing data.

Macrophage polarization: the answer to the diet/inflammation conundrum?

Macrophages, a heterogeneous and ubiquitous cell population representing up to 15% of the cellular content of different types of tissue, are the principal cell mediators in response to pathogens, inflammation process, tissue homeostasis and repair and play a pivotal role in atherosclerosis and insulin resistance because of their capacity to be the major source of inflammatory cytokines, which can function through paracrine and endocrine mechanisms. Recently, differently activated macrophage populations have been described, depending on a large variety of microenvironmental signals, and it is now recognized that their activation plays a crucial role in the development and progression of atherosclerosis. There is good evidence of the ability of conjugated linoleic acids and polyphenolic compounds to modulate inflammation in experimental models involving macrophages. This observation leaves room to the intriguing hypothesis that macrophage polarization could represent one of the unifying mechanisms through which specific food components can exert anti-inflammatory effects in humans, contributing to the prevention of chronic diseases strongly linked to inflammation, such as atherosclerosis. Future studies should be addressed to substantiate this hypothesis, investigating whether or not physiological concentrations of food-derived metabolites can perturb macrophage activation in vitro. On the in vivo side, the evaluation of macrophage populations in tissues, however complex, should be included among the analyses performed in observational and intervention studies, in order to understand if macrophage activation is involved in the anti-inflammatory activity of a specific dietary regimen.

Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population.

BACKGROUND AND AIMS: Oxidative stress has been advocated as a major cause for cardiovascular disease (CVD), and low plasma antioxidant concentrations are associated with endothelial dysfunction, the first step towards atherosclerosis. However, although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD, supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk. The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation (FMD) in volunteers at low cardiovascular risk. METHODS AND RESULTS: In a crossover trial, 24 subjects (13 women, mean age 61 ± 3 years), received, in a randomised order, a 14-day high (HT) and a 14-day low (LT) antioxidant diets, with a 2-week wash-out (WO) in between. Both diets were comparable in daily portions of fruits and vegetables, and in alcohol, fibre and macronutrient intake, but differed in their total antioxidant capacity. Before and after each diet, anthropometrics, blood pressure, fasting plasma glucose, lipid profile, hepatic enzymes, circulating antioxidant concentrations, high sensitivity C-reactive protein (hs-CRP) and FMD were assessed. FMD increased significantly during the HT diet compared to the LT (p < 0.000). FMD values were 2.3% higher after HT compared with LT (p < 0.001) after adjustment for age, gender and diet order. α-tocopherol increased significantly (p < 0.05) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly (p < 0.05 and p < 0.01, respectively) during the HT diet, compared with the LT diet. CONCLUSIONS: A short-term HT diet improves endothelial function in volunteers at low cardiovascular risk, which may further reduce their risk of CVD.

Tuning the catalytic acidity in Al2O3 nanofibers with mordenite nanocrystals for dehydration reactions.

Alumina (Al2O3) is one of the most used supports in the chemical industry due to its exceptional thermal stability, surface area, and acidic properties. Mesoscopic structured alumina with adequate acidic properties is important in catalysis to enhance the selectivity and conversion of certain reactions and processes. This study introduces a synthetic method based on electrospinning to produce Al2O3 nanofibers (ANFs) with zeolite mordenite (MOR) nanocrystals (hereafter, hybrid ANFs) to tune the textural and surface acidity properties. The hybrid ANFs with electrospinning form a non-woven network with macropores. ANF-HMOR, i.e., ANFs containing protonated mordenite (HMOR), shows the highest total acidity of ca. 276 µmol g-1 as determined with infrared spectroscopy using pyridine as a molecular probe (IR-Py). IR-Py results reveal that Lewis acid sites are prominently present in the hybrid ANFs. Brønsted acid sites are also observed in the hybrid ANFs and are associated with the HMOR presence. The functionality of hybrid ANFs is evaluated during methanol dehydration to dimethyl ether (DME). The proof of concept reaction reveals that ANF-HMOR is the more active and selective catalyst with 87% conversion and nearly 100% selectivity to DME at 573 K. The results demonstrate that the textural properties and the acid site type and content can be modulated in hybrid ANF structures, synergistically improving the selectivity and conversion during the methanol dehydration reaction. From a broader perspective, our results promote the utilization of hybrid structural materials as a means to tune chemical reactions selectively.

RNA processing.

Significant progress has been made over the last year in our understanding of the roles that RNA-binding proteins play in pre-mRNA splicing, the components of the spliceosome and how these components relate to the mechanism of splicing. Of particular importance has been the sequence analysis of the first mammalian splicing factors and structural determination of an RNA-binding domain.

Biochemistry and regulation of pre-mRNA splicing.

During the past year, significant advances have been made in the field of pre-mRNA splicing. It is now clear that members of the serine-arginine-rich protein family are key players in exon definition and function at multiple steps in the spliceosome cycle. Novel findings have been made concerning the role of exon sequences, which function as both constitutive and regulated enhancers of splicing, in trans-splicing and as targets for tissue-specific control of splicing patterns. By combining biochemical approaches in human and yeast extracts with genetic analysis, much has been learned about the RNA-RNA and RNA-protein interactions that are necessary to assemble the various complexes that are found along the pathway to the catalytically active spliceosome.

The effect of breakfasts varying in glycemic index and glycemic load on dietary induced thermogenesis and respiratory quotient.

BACKGROUND AND AIM: Glycemic index (GI) and Glycemic Load (GL) are parameters of carbohydrate bioavailability able to influence risk of chronic diseases. GL can be lowered either by reducing carbohydrate intake or by reducing the GI of the carbohydrate moiety of a mixed meal. These two approaches might have a different impact on Dietary-Induced Thermogenesis (DIT) and preferential substrate oxidation in the postprandial period, which are variables known to be involved in the regulation of body weight and body composition. This dietary, crossover intervention trial was designed to evaluate the effect on DIT and Respiratory Quotient (RQ) of three isocaloric breakfasts different in GI and/or GL (high GI and high GL [HGI-HGL] vs. low GI and low GL [LGI-LGL]; vs. high GI and low GL [HGI-LGL]) followed by a standard meal. METHODS AND RESULTS: RQ and DIT were measured in 16 lean young males by indirect calorimetry for 8h. DIT resulted significantly higher after the LGI-LGL compared to the HGI-HGL breakfast (p<0.05). Postprandial changes in RQ differed among all breakfasts (p<0.001). RQ increased from baseline after the two breakfasts with highest carbohydrate content and significantly more after the HGI-HGL than after the LGI-LGL (p<0.02), whereas it decreased after the HGI-LGL breakfast, which contained a higher amount of fat. CONCLUSIONS: Reducing the GL of a meal by reducing GI seems an effective strategy to increase energy expenditure while maintaining a good rate of lipid oxidation. This might be related to different profiles of postprandial hormones affecting substrate oxidation.

[Object and action naming in a sentence context in people with Parkinson's disease free of dementia]. / Denominación de objetos y acciones en un contexto oracional en personas con enfermedad de Parkinson sin demencia.

INTRODUCTION: Difficulties in action language processing (e.g. verbs) have been described in Parkinson's disease (PD). The embodied cognition approach links this difficulty to degenerative motor process. It has also been suggested that frontostriatal dysfunction could involve executive problems for lexical selection, which is generally more demanding for verbs. From this point of view, difficulties should diminish in a supportive context. SUBJECTS AND METHODS: 21 non demented people with PD and 16 control subjects were evaluated in an object and action naming task preceded by a sentence context that could be predictive or not of the target word (e.g. 'When the music started the couple began to…' 'dance'). The mobility of actions and the manipulability of objects were also manipulated. RESULTS: PD patients showed longer response latencies for verbs than the control group. In line with the embodied cognition approach, actions that implied higher mobility were more difficult for the group of people with PD. Moreover, PD patients benefited more from the predictive context for naming objects and actions. CONCLUSIONS: Results suggest that both a disruption at the level of action semantics and a subtle executive dysfunction contribute to lexical access difficulties in people with PD, even in the absence of overt cognitive impairment.

TITLE: Denominación de objetos y acciones en un contexto oracional en personas con enfermedad de Parkinson sin demencia.Introducción. Se han descrito dificultades con el lenguaje de acción (por ejemplo, verbos) en personas con enfermedad de Parkinson (EP). El enfoque de la cognición corpórea ha atribuido esta dificultad al proceso degenerativo motor. Se ha sugerido también que la disfunción frontoestriada podría implicar problemas ejecutivos en el proceso de selección léxica, más demandante en general para verbos. Desde este punto de vista, las dificultades deberían disminuir en un contexto facilitador. Sujetos y métodos. Se evaluó a 21 personas con EP sin demencia y a 16 sujetos control en una tarea de denominación de objetos y acciones precedidos de un contexto oracional que podía ser predictivo o no de la palabra que se debía denominar (por ejemplo, 'Sonó la música y la pareja empezó a…', 'bailar'). Se manipuló también el grado de movilidad de las acciones y el grado de manipulabilidad de los objetos. Resultados. Los pacientes con EP mostraron mayor latencia de respuestas para verbos que el grupo control. En línea con el enfoque de la cognición corpórea, las acciones que implicaban mayor grado de movilidad resultaron más difíciles para el grupo de personas con EP. Asimismo, los pacientes con EP se beneficiaron más del contexto predictivo tanto para objetos como para acciones. Conclusiones. Los resultados apuntan a que tanto una disrupción a nivel de la representación semántica de la acción como una disfunción ejecutiva sutil contribuyen a dificultar el acceso léxico en personas con EP, aun en ausencia de deterioro cognitivo.

Policy mixes to achieve sustainable mobility after the COVID-19 crisis.

The COVID-19 pandemic has the potential to have lasting impacts on energy and the environment at the global scale. Shelter-in-place measures implemented to mitigate the spread of COVID-19 have resulted in expectations for 2020 global energy demand to contract by nearly 5% with related global CO2 emissions declining by as much as 7%. Exactly how long and to what extent we will see continue to see energy demand, CO2 and related greenhouse gas (GHG) emission destruction resulting from COVID-19 is uncertain but dependent on global policy responses to the pandemic. Policy responses targeting the transportation sector, particularly ground-based transportation, can stimulate a sustainable mobility transition that mitigates the potential for long-term environmental damage. This paper reviews and examines social and cultural dynamics of transportation and extends state-of-the-art knowledge to consider how events surrounding the COVID-19 crisis may have created a sustainable mobility opportunity though (1) avoiding unnecessary transportation volume, (2) shifting transportation norms and practices and/or (3) improving the carbon-efficiency of transportation systems. Relevant policies for a low-carbon transportation transition are considered and those most appropriate to the current context are proposed with consideration of key factors that may help or hinder their implementation success.

Polyphenols and health: what compounds are involved?

On the basis of prospective, cross-sectional and intervention studies linking polyphenols to human health, several experimental papers in the literature have tried to evaluate the molecular mechanisms involved in their bioactivity. Polyphenols are reported to in vitro inhibit cancer cell proliferation, reduce vascularisation, protect neurons, stimulate vasodilation and improve insulin secretion, but are often studied as aglycones or as sugar conjugates and at non-physiological concentration. However, it is now well established that polyphenols undergo substantial metabolism after being ingested by humans in dietary relevant amount and that concentrations of plasma metabolites after a normal dietary intake rarely exceed nmol/L. This viewpoint intends to highlight that uncritical judgements made on the basis of the published literature, particularly about toxicity and bioactivity, may sometimes have been misled and misleading and to conclude that i) bioavailability values reported in the literature for phenolic compounds should be strongly reconsidered in the light of the large number of newly identified circulating and excreted metabolites, with particular attention to colonic ring-fission products which are obviously contributing much more than expected to the percentage of their absorption; ii) it is phenolic metabolites, formed in the small intestine and hepatic cells, and low molecular weight catabolic products of the colonic microflora to travel around the human body in the circulatory system or reach body tissues to elicit bioactive effects. Understanding these compounds certainly carries interest for drug-discovery but also for dietary prevention of disease.