Lipidology

Impact drugs targeting cardiometabolic risk on the gut microbiota Purpose of review Alterations in the gut microbiome composition or function are associated with risk factors for cardiometabolic diseases, including hypertension, hyperlipidemia and hyperglycemia. Based on recent evidence that also oral medications used to treat these conditions could alter the gut microbiome composition and function and, vice versa, that the gut microbiome could affect the efficacy of these treatments, we reviewed the literature on these observed interactions. Recent findings While the interaction of metformin with the gut microbiome has been studied most, other drugs that target cardiometabolic risk are gaining attention and often showed associations with alterations in microbiome-related features, including alterations in specific microbial taxa or pathways, microbiome composition or microbiome-derived metabolites, while the gut microbiome was also involved in drug metabolism and drug efficacy. As for metformin, for some of them even a potential therapeutic effect via the gut microbiome is postulated. However, exact mechanisms remain to be elucidated. Summary There is growing interest in clarifying the interactions between the gut microbiome and drugs to treat hypertension, hyperlipidemia and hyperglycemia as well as the first pass effect of microbiome on drug efficacy. While mostly analysed in animal models, also human studies are gaining more and more traction. Improving the understanding of the gut microbiome drug interaction can provide clinical directions for therapy by optimizing drug efficacy or providing new targets for drug development. Correspondence to Max Nieuwdorp, MD, PhD, Department of Internal and Vascular Medicine, Amsterdam Diabetes Center, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, Room D3-211, 1105 AZ Amsterdam, The Netherlands. E-mail: m.nieuwdorp@amsterdamumc.nl Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Impact of ultra-processed food consumption on metabolic health Purpose of review Ultra-processed foods (UPF) have been associated with poor diet quality and adverse health outcomes. Our aim in this review is to summarize recent research assessing the impact of UPF consumption, classified according to the NOVA system, on outcomes related to metabolic health. Recent findings Thirty recent studies with different design, quality and target population have investigated the impact of UPF consumption on parameters related to metabolic health, which were organized into: metabolic syndrome; body weight change and obesity indicators; blood pressure and hypertension; glucose profile, insulin resistance and type 2 diabetes; other metabolic risks and cardiovascular diseases and mortality. Most of the studies demonstrated adverse associations between high UPF consumption and metabolic health, mainly those with robust design and involving adults. Summary Most of the latest findings have revealed an adverse impact of high UPF consumption on metabolic health, including cardiovascular diseases and mortality. Scientific evidence is accumulating towards the necessity of curbing UPF consumption worldwide at different life stages. Nevertheless, other studies are needed to confirm the causality between UPF consumption and metabolic health in diverse scenarios and to better elucidate all likely mechanisms involved in this relationship. Correspondence to Renata Bertazzi Levy, Department of Preventive Medicine, School of Medicine, University of São Paulo, 455 Dr Arnaldo Avenue, 2nd floor, 01246-903 São Paulo-SP, Brazil. Tel: +55 11 3061 8608; e-mail: rlevy@usp.br Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

The COVID-19 pandemic: lifestyle and cardiovascular risk factors No abstract available

Deep dive to the secrets of the PREDIMED trial Purpose of review The aim of this study was to briefly summarize the contribution of the PREDIMED (PREvención con DIeta MEDiterránea) trial on cardiovascular evidence and examine in depth its groundbreaking trajectory. PREDIMED was conducted during 2003–2010 and represented the largest primary prevention trial ever testing the effects of changes in a complete food pattern (namely, the Mediterranean diet) on cardiovascular disease (CVD). Major contributions relied on the relevant changes in the food pattern attained by the behavioural intervention and their robust effect in reducing hard clinical end-points. Given some potential concerns, which were appropriately addressed with supporting analyses, this review is timely and relevant. Recent findings PREDIMED has continued contributing to the existing literature with extensive, robust and abundant new evidence on the benefits of the Mediterranean diet, particularly on cardiovascular health, including recent studies using high-throughput metabolomic techniques. After robustly addressing some controversies, the conclusions of the original trial remained unaltered. Summary The Mediterranean diet represents an effective and robust nutritional strategy against CVD in high cardiovascular risk populations. Recent findings from the PREDIMED have identified a metabolic signature of the Mediterranean diet that can objectively determine dietary adherence and predict CVD risk. This metabolomic signature opens up a new era for nutritional epidemiology and personalized nutrition. Correspondence to Miguel Ruiz-Canela, Department of Preventive Medicine and Public Health, Facultad de Medicina, Irunlarrea 1, 31008 Pamplona, Spain. Tel: +34 948 42 56 00 x806395; fax: +34 948 425 740; e-mail: mcanela@unav.es Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

The role of the molecular circadian clock in human energy homeostasis Purpose of review The aim of this review is to present the latest findings on the role of the circadian clock in the control of metabolism, and the therapeutic potential of chronotherapy to regulate energy homeostasis in humans. Recent findings We summarized the recent advances related to circadian clock regulation of food intake and energy expenditure. In peripheral organs, mitochondrial oxidative capacity and lipolysis show circadian pattern in humans, and rhythms disruption may be involved in the pathogenesis of metabolic diseases. Indeed, circadian desynchrony affects food intake, insulin sensitivity, and increases the risk of developing metabolic disease. Time-targeted strategies, which aim to synchronize external cues with the molecular clock to improve metabolic outcomes, have positive effects on metabolism in humans, with several studies showing that time-targeted feeding improves body weight loss and glucose tolerance. Summary The interest in time-targeted strategies to prevent or manage metabolic disturbances has grown this past year with encouraging health benefits. To maximize the therapeutic effect of these strategies, further research is warranted to delineate the molecular regulation of metabolic processes controlled by the clock and especially its modulation in contexts such as aging, sex differences, or metabolic diseases. Correspondence to Juleen R. Zierath, Department of Molecular Medicine and Surgery, Section of Integrative Physiology, Biomedicum, Solnavägen 9, SE-171 77 Stockholm, Sweden. E-mail: Juleen.zierath@ki.se Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Mendelian randomization as a tool for causal inference in human nutrition and metabolism Purpose of review The current review describes the fundamentals of the Mendelian randomization framework and its current application for causal inference in human nutrition and metabolism. Recent findings In the Mendelian randomization framework, genetic variants that are strongly associated with the potential risk factor are used as instrumental variables to determine whether the risk factor is a cause of the disease. Mendelian randomization studies are less susceptible to confounding and reverse causality compared with traditional observational studies. The Mendelian randomization study design has been increasingly used in recent years to appraise the causal associations of various nutritional factors, such as milk and alcohol intake, circulating levels of micronutrients and metabolites, and obesity with risk of different health outcomes. Mendelian randomization studies have confirmed some but challenged other nutrition-disease associations recognized by traditional observational studies. Yet, the causal role of many nutritional factors and intermediate metabolic changes for health and disease remains unresolved. Summary Mendelian randomization can be used as a tool to improve causal inference in observational studies assessing the role of nutritional factors and metabolites in health and disease. There is a need for more large-scale genome-wide association studies to identify more genetic variants for nutritional factors that can be utilized for Mendelian randomization analyses. Correspondence to Susanna C. Larsson, PhD, Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. E-mail: susanna.larsson@surgsci.uu.se Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Impact of metabolic dysfunction on cognition in humans Purpose of review The current review evaluates the recent literature on the impact of metabolic dysfunction in human cognition, focusing on epidemiological studies and meta-analyses of these. Recent findings Worldwide around 50 million people live with dementia, a number projected to triple by 2050. Recent reports from the Lancet Commission suggest that 40% of dementia cases may be preventable primarily by focusing on well established metabolic dysfunction components and cardiovascular risk factors. Summary There is robust evidence that type 2 diabetes and midlife hypertension increase risk of dementia in late life. Obesity and elevated levels of LDL cholesterol in midlife probably increase risk of dementia, but further research is needed in these areas. Physical activity, diet, alcohol, and smoking might also influence the risk of dementia through their effect on metabolic dysfunction. A key recommendation is to be ambitious about prevention, focusing on interventions to promote healthier lifestyles combating metabolic dysfunction. Only comprehensive multidomain and staff-requiring interventions are however efficient to maintain or improve cognition in at-risk individuals and will be unrealistic economic burdens for most societies to implement. Therefore, a risk score that identifies high-risk individuals will enable a targeted early intensive intervention toward those high-risk individuals that will benefit the most from a prevention against cardiovascular risk factors and metabolic dysfunction. Correspondence to Ruth Frikke-Schmidt, Professor, MD, DMSc, PhD, Chief Physician, Department of Clinical Biochemistry KB 3011, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Tel: +45 3545 4348; fax: +45 3545 2880; e-mail: ruth.frikke-schmidt@regionh.dk Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Liver fat storage pathways: methodologies and dietary effects Purpose of review Nonalcoholic fatty liver is the result of an imbalance between lipid storage [from meal, de novo lipogenesis (DNL) and fatty acid (FA) uptake] and disposal (oxidation and VLDL output). Knowledge on the contribution of each of these pathways to liver fat content in humans is essential to develop tailored strategies to prevent and treat nonalcoholic fatty liver. Here, we review the techniques available to study the different storage pathways and review dietary modulation of these pathways. Recent findings The type of carbohydrate and fat could be of importance in modulating DNL, as complex carbohydrates and omega-3 FAs have been shown to reduce DNL. No effects were found on the other pathways, however studies investigating this are scarce. Summary Techniques used to assess storage pathways are predominantly stable isotope techniques, which require specific expertise and are costly. Validated biomarkers are often lacking. These methodological limitations also translate into a limited number of studies investigating to what extent storage pathways can be modulated by diet. Further research is needed to elucidate in more detail the impact that fat and carbohydrate type can have on liver fat storage pathways and content. Correspondence to Patrick Schrauwen, Department of Nutrition and Movement Sciences, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. Tel: +31 43 388 15 02; e-mail: p.schrauwen@maastrichtuniversity.nl This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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