Omega-3

A meta‐review of “lifestyle psychiatry”: the role of exercise, smoking, diet and sleep in the prevention and treatment of mental disorders

Joseph Firth, Marco Solmi, Robyn E. Wootton +18 more · World Psychiatry · 2020 · 1,011 citations

There is increasing academic and clinical interest in how "lifestyle factors" traditionally associated with physical health may also relate to mental health and psychological well-being. In response, international and national health bodies are producing guidelines to address health behaviors in the prevention and treatment of mental illness. However, the current evidence for the causal role of lifestyle factors in the onset and prognosis of mental disorders is unclear. We performed a systematic meta-review of the top-tier evidence examining how physical activity, sleep, dietary patterns and tobacco smoking impact on the risk and treatment outcomes across a range of mental disorders. Results from 29 meta-analyses of prospective/cohort studies, 12 Mendelian randomization studies, two meta-reviews, and two meta-analyses of randomized controlled trials were synthesized to generate overviews of the evidence for targeting each of the specific lifestyle factors in the prevention and treatment of depression, anxiety and stress-related disorders, schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. Standout findings include: a) convergent evidence indicating the use of physical activity in primary prevention and clinical treatment across a spectrum of mental disorders; b) emerging evidence implicating tobacco smoking as a causal factor in onset of both common and severe mental illness; c) the need to clearly establish causal relations between dietary patterns and risk of mental illness, and how diet should be best addressed within mental health care; and d) poor sleep as a risk factor for mental illness, although with further research required to understand the complex, bidirectional relations and the benefits of non-pharmacological sleep-focused interventions. The potentially shared neurobiological pathways between multiple lifestyle factors and mental health are discussed, along with directions for future research, and recommendations for the implementation of these findings at public health and clinical service levels.

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient

Stephen A. McClave, Beth Taylor, Robert G. Martindale +13 more · Journal of Parenteral and Enteral Nutrition · 2016 · 3,888 citations

This document represents the first collaboration between 2 organizations-the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine-to describe best practices in nutrition therapy in critically ill children. The target of these guidelines is intended to be the pediatric critically ill patient (>1 month and <18 years) expected to require a length of stay >2-3 days in a PICU admitting medical, surgical, and cardiac patients. In total, 2032 citations were scanned for relevance. The PubMed/MEDLINE search resulted in 960 citations for clinical trials and 925 citations for cohort studies. The EMBASE search for clinical trials culled 1661 citations. In total, the search for clinical trials yielded 1107 citations, whereas the cohort search yielded 925. After careful review, 16 randomized controlled trials and 37 cohort studies appeared to answer 1 of the 8 preidentified question groups for this guideline. We used the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluation) to adjust the evidence grade based on assessment of the quality of study design and execution. These guidelines are not intended for neonates or adult patients. The guidelines reiterate the importance of nutrition assessment-particularly, the detection of malnourished patients who are most vulnerable and therefore may benefit from timely intervention. There is a need for renewed focus on accurate estimation of energy needs and attention to optimizing protein intake. Indirect calorimetry, where feasible, and cautious use of estimating equations and increased surveillance for unintended caloric underfeeding and overfeeding are recommended. Optimal protein intake and its correlation with clinical outcomes are areas of great interest. The optimal route and timing of nutrient delivery are areas of intense debate and investigations. Enteral nutrition remains the preferred route for nutrient delivery. Several strategies to optimize enteral nutrition during critical illness have emerged. The role of supplemental parenteral nutrition has been highlighted, and a delayed approach appears to be beneficial. Immunonutrition cannot be currently recommended. Overall, the pediatric critical care population is heterogeneous, and a nuanced approach to individualizing nutrition support with the aim of improving clinical outcomes is necessary.

Systematic Review of Gut Microbiota and Major Depression

Stephanie Cheung, Ariel Goldenthal, Anne‐Catrin Uhlemann +3 more · Frontiers in Psychiatry · 2019 · 593 citations

This systematic review of six human case-control studies found that people with major depressive disorder (MDD) have different gut bacteria compared to healthy controls, but the specific bacteria that differ vary wildly between studies — no single bacterial species or group consistently predicts depression, suggesting that focusing on what bacteria *do* (their metabolic functions) may be more useful than just listing which ones are present.

Mediterranean Diet and Age-Related Cognitive Decline

Cinta Valls‐Pedret, Aleix Sala‐Vila, Mercè Serra‐Mir +9 more · JAMA Internal Medicine · 2015 · 892 citations

Following a Mediterranean diet supplemented with either extra-virgin olive oil or mixed nuts for over six years significantly improved cognitive function and reduced the risk of mild cognitive impairment or dementia in older adults at high cardiovascular risk, suggesting a powerful dietary strategy for brain health.

Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons

Lisa L. Barnes, Klodian Dhana, Xiaoran Liu +17 more · New England Journal of Medicine · 2023 · 298 citations

A rigorous 3-year randomised controlled trial found that the MIND diet did **not** slow cognitive decline more than a healthy control diet in older adults — but both groups improved, and people who already had poor diets at baseline saw the most benefit from the MIND diet. ---

No effect of<i>n</i>-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial

Peter J. Rogers, Katherine M. Appleton, David Keßler +7 more · British Journal Of Nutrition · 2007 · 243 citations

Supplementing with 1.5 g/day of EPA + DHA (fish oil) for 12 weeks produced no meaningful improvement in depressed mood, anxiety, stress, anger, or cognitive function in 190 adults with mild-to-moderate depression, and adding these results to a meta-analysis of previous trials confirmed an overall negligible benefit.

Nutritional assessment and therapy in COPD: a European Respiratory Society statement

Annemie M.W.J. Schols, Ivone Ferreira, Frits M.E. Franssen +9 more · European Respiratory Journal · 2014 · 348 citations

This European Respiratory Society Task Force statement synthesises evidence that nutritional status—especially abnormal body composition (low muscle mass or high fat mass)—is an independent predictor of COPD outcomes, and that targeted nutritional therapy (particularly when combined with exercise) can improve muscle function, exercise capacity, and quality of life in undernourished patients, though the evidence base is strongest for specific metabolic phenotypes rather than all COPD patients.

Effects of<i>n</i>-3 fatty acids, EPA<i>v</i>. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial

Natalie Sinn, Catherine M. Milte, Steven J. Street +4 more · British Journal Of Nutrition · 2011 · 291 citations

Taking high-dose fish oil supplements (either EPA-rich or DHA-rich) for 6 months reduced depressive symptoms in older adults with mild cognitive impairment by about 2–3 points on a 15-point depression scale, compared to a placebo oil, but did not improve memory, executive function, or most quality-of-life measures.

Dietary lysophosphatidylcholine-EPA enriches both EPA and DHA in the brain: potential treatment for depression

Poorna C. R. Yalagala, Sugasini Dhavamani, Sridevi Dasarathi +2 more · Journal of Lipid Research · 2018 · 98 citations

Feeding mice a special form of EPA called lysophosphatidylcholine-EPA (LPC-EPA) increased brain EPA levels more than 100-fold and doubled brain DHA levels, whereas standard EPA supplements had almost no effect on brain omega-3 levels — suggesting that the chemical form of omega-3 supplements matters enormously for brain uptake.

Understanding nutrition, depression and mental illnesses

TS Sathyanarayana Rao, M. R. Asha, Balenahalli Narasingappa Ramesh +1 more · Indian Journal of Psychiatry · 2008 · 401 citations

This comprehensive review synthesizes evidence showing that nutritional deficiencies (especially omega-3s, B vitamins, magnesium, and amino acids) are strongly linked to the onset, severity, and duration of depression and other mental illnesses, suggesting that targeted dietary interventions and supplements can be effective complementary treatments.

Epigenetic clock analysis of diet, exercise, education, and lifestyle factors

Austin Quach, Morgan E. Levine, Toshiko Tanaka +18 more · Aging · 2017 · 871 citations

This observational study found that a diet rich in fruits and vegetables, regular physical activity, higher education, and moderate alcohol consumption are associated with a slower biological aging rate, while obesity and metabolic syndrome are linked to faster aging, suggesting that common healthy lifestyle choices may slow down your "epigenetic clock."

Dietary fat intakes for pregnant and lactating women

Berthold Koletzko, Irene Cetin, J. Thomas Brenna +1 more · British Journal Of Nutrition · 2007 · 386 citations

Consensus recommendations on behalf of the European Commission research projects Perinatal Lipid Metabolism (PeriLip; www.perilip.org ) and Early Nutrition Programming (EARNEST; www.metabolic-programming.org ), developed jointly with representatives of the Child Health Foundation (Stiftung Kindergesundheit; www.kindergesundheit.de ), the Diabetic Pregnancy Study Group (DPSG; www.medfak.uu.se/dpsg ), the European Association of Perinatal Medicine (EAPM; www.europerinatal.com ), the European Society for Clinical Nutrition and Metabolism (ESPEN; www.espen.org ), the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, Committee on Nutrition (ESPGHAN; www.espghan.org ), the International Federation of Placenta Associations (IFPA; http://aculeate.hopto.org/IFPA ) and the International Society for the Study of Fatty Acids and Lipids (ISSFAL; email www.issfal.org.uk ). Members of the Perinatal Lipid Intake Working Group Gioia Alvino, Juliana von Berlepsch, Hans Konrad Biesalski, Tom Clandinin, Hildegard Debertin a , Tamás Decsi, Hans Demmelmair a , Gernot Desoye bc , Veronika Dietz, Peter Dodds, Pauline Emmett, Fabio Facchinetti d , Matthew W. Gillman, Joachim Heinrich, Emilio Herrera b , Irene Hoesli, William C. Heird, Matthew Hyde, Kirsi Laitinen, John Laws, Elvira Larqué Daza, Iliana Lopez-Soldado, Maria Makrides, Kim Fleischer Michaelsen e , Sjurdur Olsen, Henar Ortega, Guy Putet, Imogen Rogers, Paola Roggero, Lubos Sobotka f , Hania Szajewska g , Hope Weiler. (Representing: a Child Health Foundation, b DPSG, c IFPA, d EAPM, e ISSFAL, f ESPEN, g ESPGHAN.) Dietary fat intake in pregnancy and lactation affects pregnancy outcomes and child growth, development and health. The European Commission charged the research project PERILIP, jointly with the Early Nutrition Programming Project, to develop recommendations on dietary fat intake in pregnancy and lactation. Literature reviews were performed and a consensus conference held with international experts in the field, including representatives of international scientific associations. The adopted conclusions include: dietary fat intake in pregnancy and lactation (energy%) should be as recommended for the general population; pregnant and lactating women should aim to achieve an average dietary intake of at least 200 mg DHA/d; intakes of up to 1 g/d DHA or 2·7 g/d n -3 long-chain PUFA have been used in randomized clinical trials without significant adverse effects; women of childbearing age should aim to consume one to two portions of sea fish per week, including oily fish; intake of the DHA precursor, α-linolenic acid, is far less effective with regard to DHA deposition in fetal brain than preformed DHA; intake of fish or other sources of long-chain n -3 fatty acids results in a slightly longer pregnancy duration; dietary inadequacies should be screened for during pregnancy and individual counselling be offered if needed.

2023 Alzheimer's disease facts and figures

V Villemagne, S Burnham, P Bourgeat +97 more · Alzheimer s & Dementia · 2023 · 3,011 citations

This is not an experimental study but an annual statistical report and policy analysis from the Alzheimer's Association, documenting that 6.7 million Americans aged 65+ currently live with Alzheimer's dementia, deaths from the disease increased 145% between 2000 and 2019, and unpaid caregivers provided 18 billion hours of care valued at $339.5 billion in 2022 — with a special focus on whether the healthcare workforce can handle new disease-modifying treatments.

The role of nutrition in children's neurocognitive development, from pregnancy through childhood

Anett Nyaradi, Jianghong Li, Siobhan Hickling +2 more · Frontiers in Human Neuroscience · 2013 · 537 citations

This narrative review of observational studies suggests that individual micronutrients (omega-3s, iron, iodine, zinc, B12, folate, choline) and overall diet quality during pregnancy and childhood are associated with children's cognitive development, but intervention trials testing single nutrients have produced inconsistent results, meaning you should focus on whole-diet patterns rather than isolated supplements for your own or your child's cognitive health.

2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation

José A. Joglar, Mina K. Chung, Anastasia L. Armbruster +50 more · Journal of the American College of Cardiology · 2023 · 703 citations

ESPEN guidelines on nutrition in cancer patients

Jann Arends, Patrick Bachmann, Vickie E. Baracos +19 more · Clinical Nutrition · 2016 · 2,944 citations

ESPEN guideline on clinical nutrition in the intensive care unit

Pierre Singer, Annika Reintam Blaser, Mette M. Berger +12 more · Clinical Nutrition · 2018 · 2,778 citations

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

Jan Steffel, Peter Verhamme, Tatjana Potpara +24 more · European Heart Journal · 2018 · 2,130 citations

The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).

Covid-19 and the Subsequent Lockdown Modified Dietary Habits of Almost Half the Population in an Italian Sample

Federico Scarmozzino, Francesco Visioli · Foods · 2020 · 576 citations

The Covid-19 pandemic led to lockdowns in several parts of the world and, hence, changed some daily habits, including social interactions, the ability to perform sports, and-possibly-diet. The Italian government established and promulgated lockdown policies on 9 March 2020. We aim at assessing the effects of Covid-19-induced confinement policies on self-reported food consumption of self-selected Italians by means of a questionnaire that was created and diffused by the Internet. Nearly half, i.e., 49.6% of responders did not substantially modify their diet during the lockdown; however, 46.1% of them reported that they were eating more during confinement, and 19.5% gained weight. In particular, we report an increase in "comfort food" consumption, notably chocolate, ice-cream, and desserts (42.5%) and salty snacks (23.5%). In addition, 42.7% percent of this cohort attributed this increase to higher anxiety levels. Related to this, 36.8% of responders reported a decrease in alcohol consumption, even though 10.1% of them reported an increase. Interestingly, 21.2% of responders increased their consumption of fresh fruit and vegetables. Only 33.5% of those who declared decreased consumption attributed this change of diet to lower availability and ease of purchasing such items. Equally interesting, over half of responders, i.e., 56.2%, admitted that fruit and vegetables did not appeal to them while in lockdown. Purchases of ready-made meals were reduced by nearly 50%. Future large-scale similar studies should be undertaken worldwide and will help public health authorities shape their reactions to future, unavoidable pandemics.

ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

Authors Task Force Members, Lars Rydén, Peter J. Grant +79 more · European Heart Journal · 2013 · 1,953 citations

This clinical practice guideline synthesises evidence that aggressive management of blood glucose, blood pressure, and lipids in people with diabetes or pre-diabetes reduces cardiovascular events by 10–42% depending on the intervention, but the benefits must be weighed against risks of hypoglycaemia and polypharmacy — for a self-experimenter, the key takeaway is that lifestyle changes (diet, exercise, weight loss) produce comparable or better cardiovascular risk reduction than most medications, with fewer side effects.

Health and disease markers correlate with gut microbiome composition across thousands of people

Ohad Manor, Chengzhen L. Dai, Sergey A. Kornilov +5 more · Nature Communications · 2020 · 838 citations

Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities for targeted interventions that alter the composition of the microbiome to improve host health. By uncovering the interrelationships between host diet and lifestyle factors, clinical blood markers, and the human gut microbiome at the population-scale, our results serve as a roadmap for future studies on host-microbe interactions and interventions.

Canadian Network for Mood and Anxiety Treatments (<scp>CANMAT</scp>) and International Society for Bipolar Disorders (<scp>ISBD</scp>) 2018 guidelines for the management of patients with bipolar disorder

Lakshmi N. Yatham, Sidney H. Kennedy, Sagar V. Parikh +26 more · Bipolar Disorders · 2018 · 1,731 citations

This is a clinical practice guideline—not a single experiment—that synthesises decades of research to rank medications for bipolar disorder by efficacy, safety, and tolerability, providing a clear hierarchy of first-, second-, and third-line treatments for acute mania, acute depression, and long-term maintenance, which matters because it gives clinicians (and informed patients) an evidence-based roadmap for treatment decisions rather than relying on trial-and-error.

2016 ESC/EAS Guidelines for the Management of Dyslipidaemias

Alberico L. Catapano, Ian Graham, Guy De Backer +15 more · Atherosclerosis · 2016 · 1,583 citations

ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit

Pierre Singer, Annika Reintam Blaser, Mette M. Berger +10 more · Clinical Nutrition · 2023 · 576 citations

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013

Lakshmi N. Yatham, Sidney H. Kennedy, Sagar V. Parikh +18 more · Bipolar Disorders · 2012 · 1,214 citations

The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.

IOC consensus statement: dietary supplements and the high-performance athlete

Ronald J. Maughan, Louise M. Burke, Jiří Dvořák +22 more · British Journal of Sports Medicine · 2018 · 933 citations

Nutrition usually makes a small but potentially valuable contribution to successful performance in elite athletes, and dietary supplements can make a minor contribution to this nutrition program. Nonetheless, supplement use is widespread at all levels of sport. Products described as supplements target different issues, including the management of micronutrient deficiencies, supply of convenient forms of energy and macronutrients, and provision of direct benefits to performance or indirect benefits such as supporting intense training regimens. The appropriate use of some supplements can offer benefits to the athlete, but others may be harmful to the athlete's health, performance, and/or livelihood and reputation if an anti-doping rule violation results. A complete nutritional assessment should be undertaken before decisions regarding supplement use are made. Supplements claiming to directly or indirectly enhance performance are typically the largest group of products marketed to athletes, but only a few (including caffeine, creatine, specific buffering agents and nitrate) have good evidence of benefits. However, responses are affected by the scenario of use and may vary widely between individuals because of factors that include genetics, the microbiome, and habitual diet. Supplements intended to enhance performance should be thoroughly trialed in training or simulated competition before implementation in competition. Inadvertent ingestion of substances prohibited under the anti-doping codes that govern elite sport is a known risk of taking some supplements. Protection of the athlete's health and awareness of the potential for harm must be paramount, and expert professional opinion and assistance is strongly advised before embarking on supplement use.

Free Radical Properties, Source and Targets, Antioxidant Consumption and Health

G. Martemucci, Ciro Costagliola, Michele Mariano +3 more · Oxygen · 2022 · 668 citations

Free radicals have acquired growing importance in the fields of biology and medicine. They are produced during many different endogenous and exogenous processes. Mitochondria are the main source of endogenous reactive oxygen species (ROS) produced at cell level. The overproduction of free radicals can damage macromolecules such as nucleic acids, proteins and lipids. This leads to tissue damage in various chronic and degenerative diseases. Antioxidants play a crucial role in the body’s defense against free radicals. This review concerns the main properties of free radicals, their sources and deleterious effects. It highlights the potential role of the dietary supplementation of antioxidants and discusses unsolved problems regarding antioxidant supplements in the prevention and therapy of diseases.

Health Implications of High Dietary Omega-6 Polyunsaturated Fatty Acids

Elaine Patterson, Rebecca Wall, Gerald F. Fitzgerald +2 more · Journal of Nutrition and Metabolism · 2012 · 864 citations

Omega-6 (n-6) polyunsaturated fatty acids (PUFA) (e.g., arachidonic acid (AA)) and omega-3 (n-3) PUFA (e.g., eicosapentaenoic acid (EPA)) are precursors to potent lipid mediator signalling molecules, termed "eicosanoids," which have important roles in the regulation of inflammation. In general, eicosanoids derived from n-6 PUFA are proinflammatory while eicosanoids derived from n-3 PUFA are anti-inflammatory. Dietary changes over the past few decades in the intake of n-6 and n-3 PUFA show striking increases in the (n-6) to (n-3) ratio (~15 : 1), which are associated with greater metabolism of the n-6 PUFA compared with n-3 PUFA. Coinciding with this increase in the ratio of (n-6) : (n-3) PUFA are increases in chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer's disease (AD). By increasing the ratio of (n-3) : (n-6) PUFA in the Western diet, reductions may be achieved in the incidence of these chronic inflammatory diseases.

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies

William S. Harris, Nathan Tintle, Fumiaki Imamura +53 more · Nature Communications · 2021 · 228 citations

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Multifunctional nanoparticle-mediated combining therapy for human diseases

Xiaotong Li, Xiuju Peng, Makhloufi Zoulikha +4 more · Signal Transduction and Targeted Therapy · 2024 · 461 citations

Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment. In preclinical investigations, combined effect of certain known drugs has been well established in treating extensive human diseases. Attributed to synergistic effects by targeting various disease pathways and advantages, such as reduced administration dose, decreased toxicity, and alleviated drug resistance, combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses, such as cancer, atherosclerosis, pulmonary hypertension, myocarditis, rheumatoid arthritis, inflammatory bowel disease, metabolic disorders and neurodegenerative diseases. Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease. Nanoparticle (NP)-mediated drug delivery systems, i.e., liposomal NPs, polymeric NPs and nanocrystals, are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery, extended drug release, and higher drug stability to avoid rapid clearance at infected areas. This review summarizes various targets of diseases, preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases. Ultimately, we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations. This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.

2003 European society of hypertension - European Society of Cardiology guidelines for the management of arterial hypertension

Giuseppe Mancia, E. Agabiti Rosei, Renata Cífková +24 more · Lirias (KU Leuven) · 2003 · 2,605 citations

status: Published

Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017

Makoto Kinoshita, Koutaro Yokote, Hidenori Arai +29 more · Journal of Atherosclerosis and Thrombosis · 2018 · 817 citations

In the subsections on dyslipidemia in the assessment of risk factors, absolute risk of ASCVD, lipid management targets as well as drug therapy and diet therapy in improving lifestyle habits, we created CQs and performed an SR based on the MINDS method. For our SR, we essentially chose the literature published before the end of 2015.

Traffic-Related Air Pollution and Cognitive Function in a Cohort of Older Men

Melinda C. Power, Marc G. Weisskopf, Stacey Alexeeff +3 more · Environmental Health Perspectives · 2010 · 442 citations

BACKGROUND: Traffic-related particles induce oxidative stress and may exert adverse effects on central nervous system function, which could manifest as cognitive impairment. OBJECTIVE: We assessed the association between black carbon (BC), a marker of traffic-related air pollution, and cognition in older men. METHODS: A total of 680 men (mean ± SD, 71 ± 7 years of age) from the U.S. Department of Veterans Affairs Normative Aging Study completed a battery of seven cognitive tests at least once between 1996 and 2007. We assessed long-term exposure to traffic-related air pollution using a validated spatiotemporal land-use regression model for BC. RESULTS: The association between BC and cognition was nonlinear, and we log-transformed BC estimates for all analyses [ln(BC)]. In a multivariable-adjusted model, for each doubling in BC on the natural scale, the odds of having a Mini-Mental State Examination (MMSE) score ≤ 25 was 1.3 times higher [95% confidence interval (CI), 1.1 to 1.6]. In a multivariable-adjusted model for global cognitive function, which combined scores from the remaining six tests, a doubling of BC was associated with a 0.054 SD lower test score (95% CI, -0.103 to -0.006), an effect size similar to that observed with a difference in age of 1.9 years in our data. We found no evidence of heterogeneity by cognitive test. In sensitivity analyses adjusting for past lead exposure, the association with MMSE scores was similar (odds ratio = 1.3; 95% CI, 1.1 to 1.7), but the association with global cognition was somewhat attenuated (-0.038 per doubling in BC; 95% CI, -0.089 to 0.012). CONCLUSIONS: Ambient traffic-related air pollution was associated with decreased cognitive function in older men.

Relation of DASH- and Mediterranean-like dietary patterns to cognitive decline in older persons

Christy Tangney, Hong Li, Yamin Wang +4 more · Neurology · 2014 · 295 citations

OBJECTIVES: We examined whether accordance to the DASH (Dietary Approach to Stop Hypertension) and Mediterranean diets is associated with slower cognitive decline in a prospective Chicago cohort study of older persons, the Memory and Aging Project. METHODS: The sample comprised 826 Memory and Aging Project participants (aged 81.5 ± 7.1 years) who completed a 144-item food frequency questionnaire at baseline and 2 or more cognitive assessments over 4.1 years. Dietary scores were computed for accordance to the DASH diet (0-10) and the Mediterranean diet (MedDietScore) (0-55). For both, higher scores reflect greater accordance. Both patterns share at least 3 common food components. Cognitive function was assessed annually with 19 cognitive tests from which global cognitive scores and summary measures are computed. RESULTS: The mean global cognitive score at baseline was 0.12 (range, -3.23 to 1.60) with an overall mean annual change in score of -0.08 standardized units. Only 13 participants had possible dementia. The mean DASH score was 4.1 (range, 1.0-8.5) and the MedDietScore was 31.3 (range, 18-46). In mixed models adjusted for covariates, a 1-unit difference in DASH score was associated with a slower rate of global cognitive decline by 0.007 standardized units (standard error of estimate = 0.003, p = 0.03). Similarly, a 1-unit-higher MedDietScore was associated with a slower rate of global cognitive decline by 0.002 standardized units (standard error of estimate = 0.001, p = 0.01). CONCLUSIONS: These findings support the hypothesis that both the DASH and Mediterranean diet patterns are associated with slower rates of cognitive decline in the same cohort of older persons.

Mediterranean diet and cognitive health: Initial results from the Hellenic Longitudinal Investigation of Ageing and Diet

Costas A. Anastasiou, Mary Yannakoulia, Mary H. Kosmidis +7 more · PLoS ONE · 2017 · 294 citations

BACKGROUND: The Mediterranean dietary pattern has been associated with a decreased risk of many degenerative diseases and cognitive function in particular; however, relevant information from Mediterranean regions, where the prototype Mediterranean diet is typically adhered to, have been very limited. Additionally, predefined Mediterranean diet (MeDi) scores with use of a priori cut-offs have been used very rarely, limiting comparisons between different populations and thus external validity of the associations. Finally, associations between individual components of MeDi (i.e., food groups, macronutrients) and particular aspects of cognitive performance have rarely been explored. We evaluated the association of adherence to an a priori defined Mediterranean dietary pattern and its components with dementia and specific aspects of cognitive function in a representative population cohort in Greece. METHODS: Participants from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD), an on-going population-based study, exploring potential associations between diet and cognitive performance in a representative sample from Greek regions, were included in this analysis. Diagnosis of dementia was made by a full clinical and neuropsychological evaluation, while cognitive performance was assessed according to five cognitive domains (memory, language, attention-speed, executive functioning, visuospatial perception) and a composite cognitive score. Adherence to MeDi was evaluated by an a priori score (range 0-55), derived from a detailed food frequency questionnaire. RESULTS: Among 1,865 individuals (mean age 73±6 years, 41% male), 90 were diagnosed with dementia and 223 with mild cognitive impairment. Each unit increase in the Mediterranean dietary score (MedDietScore) was associated with a 10% decrease in the odds for dementia. Adherence to the MeDi was also associated with better performance in memory, language, visuospatial perception and the composite cognitive score; the associations were strongest for memory. Fish consumption was negatively associated with dementia and cognitive performance positively associated with non-refined cereal consumption. CONCLUSIONS: Our results suggest that adherence to the MeDi is associated with better cognitive performance and lower dementia rates in Greek elders. Thus, the MeDi in its a priori constructed prototype form may have cognitive benefits in traditional Mediterranean populations.

Combined application of eicosapentaenoic acid and docosahexaenoic acid on depression in women: a meta-analysis of double-blind randomized controlled trials

Xiaohui Qiu, Xue Tian, Jiarun Yang +3 more · Neuropsychiatric Disease and Treatment · 2015 · 23 citations

Taking a combination of the omega-3 fatty acids EPA and DHA (at roughly 1–2 grams total per day) for at least 8 weeks produced a moderate-to-large reduction in depression symptoms in women compared to placebo, with an effect size of 0.65 standard deviations — roughly equivalent to the difference between mild and moderate depression on a standard scale.

Mediterranean Diet and Health Outcomes in the SUN Cohort

Silvia Carlos, Carmen de la Fuente‐Arrillaga, Maira Bes‐Rastrollo +4 more · Nutrients · 2018 · 277 citations

The Mediterranean Dietary (MedDiet) Pattern has been linked to many beneficial health effects. This review summarizes the main findings of a prospective cohort study, the Seguimiento Universidad de Navarra (SUN) cohort, specifically focused on MedDiet and the risk of major chronic disease. It is an open cohort in which 22,786 Spanish university graduates have participated since 1999 until February 2018. Data on diet, lifestyle and clinical diagnosis are collected at baseline and every two years. After reviewing 21 publications from the SUN cohort on the effects of the MedDiet, we conclude that this cohort has provided good evidence that a high MedDiet adherence is associated with a reduced incidence of all-cause mortality, fatal and non-fatal major cardiovascular disease (CVD), type 2 diabetes, weight gain, metabolic syndrome, depression, cognitive decline, and nephrolithiasis. An inverse dose-response relationship was found for many of these associations. The MedDiet was also associated with lower average heart rate, a mitigation of the harmful effects of overweight/obesity on the risk of CVD, and an attenuation of the effects of obesity on type 2 diabetes. A suggestion that the MedDiet may enhance fertility was also found.

Adherence to a Mediterranean Diet, Cognitive Decline, and Risk of Dementia

Catherine Féart · JAMA · 2009 · 754 citations

CONTEXT: Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases, but its association with cognitive decline is unclear. OBJECTIVE: To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 1410 adults (> or = 65 years) from Bordeaux, France, included in the Three-City cohort in 2001-2002 and reexamined at least once over 5 years. Adherence to a Mediterranean diet (scored as 0 to 9) was computed from a food frequency questionnaire and 24-hour recall. MAIN OUTCOME MEASURES: Cognitive performance was assessed on 4 neuropsychological tests: the Mini-Mental State Examination (MMSE), Isaacs Set Test (IST), Benton Visual Retention Test (BVRT), and Free and Cued Selective Reminding Test (FCSRT). Incident cases of dementia (n = 99) were validated by an independent expert committee of neurologists. RESULTS: Adjusting for age, sex, education, marital status, energy intake, physical activity, depressive symptomatology, taking 5 medications/d or more, apolipoprotein E genotype, cardiovascular risk factors, and stroke, higher Mediterranean diet score was associated with fewer MMSE errors (beta = -0.006; 95% confidence interval [CI], -0.01 to -0.0003; P = .04 for 1 point of the Mediterranean diet score). Performance on the IST, BVRT, or FCSRT over time was not significantly associated with Mediterranean diet adherence. Greater adherence as a categorical variable (score 6-9) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort, but among individuals who remained free from dementia over 5 years, the association for the highest compared with the lowest group was significant (adjusted for all factors, for MMSE: beta = -0.03; 95% CI, -0.05 to -0.001; P = .04; for FCSRT: beta = 0.21; 95% CI, 0.008 to 0.41; P =.04). Mediterranean diet adherence was not associated with the risk for incident dementia (fully adjusted model: hazard ratio, 1.12; 95% CI, 0.60 to 2.10; P = .72), although power to detect a difference was limited. CONCLUSIONS: Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests. Higher adherence was not associated with risk for incident dementia.

Fast-food and commercial baked goods consumption and the risk of depression

Almudena Sánchez‐Villegas, Estefanía Toledo, Jokin de Irala +3 more · Public Health Nutrition · 2011 · 272 citations

OBJECTIVE: Whereas the relationship between some components of diet, such as n-3 fatty acids and B-vitamins, and depression risk has been extensively studied, the role of fast-food or processed pastries consumption has received little attention. DESIGN: Consumption of fast food (hamburgers, sausages, pizza) and processed pastries (muffins, doughnuts, croissants) was assessed at baseline through a validated semi-quantitative FFQ. Participants were classified as incident cases of depression if they reported a physician diagnosis of depression or the use of antidepressant medication in at least one of the follow-up questionnaires. Cox regression models were fit to assess the relationship between consumption of fast food and commercial baked goods and the incidence of depression. SETTING: The SUN (Seguimiento Universidad de Navarra - University of Navarra Follow-up) Project, Spain. SUBJECTS: Participants (n 8964) from a Spanish cohort. RESULTS: After a median follow-up of 6·2 years, 493 cases of depression were reported. A higher risk of depression was associated with consumption of fast food (fifth (Q5) v. first quintile (Q1): hazard ratio (HR) = 1·36; 95 % CI 1·02, 1·81; P trend = 0·003). The results did not change after adjustment for the consumption of other food items. No linear relationship was found between the consumption of commercial baked goods and depression. Participants belonging to consumption quintiles Q2-Q5 showed an increased risk of depression compared with those belonging to the lowest level of consumption (Q1; HR = 1·38; 95 % CI 1·06, 1·80). CONCLUSIONS: Fast-food and commercial baked goods consumption may have a detrimental effect on depression risk.

Polycyclic aromatic hydrocarbon exposure and pediatric asthma in children: a case–control study

Nasser M. Al‐Daghri, Majed S. Alokail, Sherif H. Abd-Alrahman +3 more · Environmental Health · 2013 · 252 citations

BACKGROUND: Bronchial asthma is one of the most prevalent diseases in Arab children. Environmental pollution has been suggested to be considered causative of asthma, nasal symptoms and bronchitis in both children and adult. The objectives of this study were to evaluate the association between serum polycyclic aromatic hydrocarbons (PAHs) levels, asthma and allergic outcomes among Saudi children aged up to 15 yrs. We hypothesized that increased serum PAHs are associated with allergy, asthma, or respiratory symptoms. METHODS: A total of 195 Saudi children (98 asthma pediatric patients and 97 healthy controls) were randomly selected from the Riyadh Cohort Study for inclusion. The diagnosis of Asthma was based on established pediatric diagnosis and medications taken. RESULTS: Asthma related markers showed highly significant differences between children with and without asthma. Thus IgE, resistin and IL-4 were significantly increased (p 0.004, 0.001 and 0.003, respectively) in children with asthma compared with non-asthma control subjects. GMCSF, IFN-γ, IL-5, IL-8 and IL-10, on the other hand, were significantly decreased in children with asthma (p 0.003, 0.03, 0.001, 0.004 and 0.03, respectively). Strong associations between serum PAHs levels and biomarkers of childhood asthma were detected in Arabic children. Data confirmed the role of naphthalene, 4H-cyclobenta[def]phenanthrene, 1,2-benzanthracene, chrysene and benzo(e)acephenanthrylene in childhood asthma; levels of these PAHs were correlated with asthma related biomarkers including IgE, resistin, GMCSF and IFN-γ as well as IL-4, IL-5, IL-8 and IL-10 cytokines. CONCLUSIONS: This data highlight the pivotal role of specific PAHs in childhood asthma.

World‐Wide FINGERS Network: A global approach to risk reduction and prevention of dementia

Miia Kivipelto, Francesca Mangialasche, Heather M. Snyder +66 more · Alzheimer s & Dementia · 2020 · 507 citations

Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.

Dietary Fat Intake and the Risk of Depression: The SUN Project

Almudena Sánchez‐Villegas, Lisa D. M. Verberne, Jokin De Irala +4 more · PLoS ONE · 2011 · 243 citations

UNLABELLED: Emerging evidence relates some nutritional factors to depression risk. However, there is a scarcity of longitudinal assessments on this relationship. OBJECTIVE: To evaluate the association between fatty acid intake or the use of culinary fats and depression incidence in a Mediterranean population. MATERIAL AND METHODS: Prospective cohort study (1999-2010) of 12,059 Spanish university graduates (mean age: 37.5 years) initially free of depression with permanently open enrolment. At baseline, a 136-item validated food frequency questionnaire was used to estimate the intake of fatty acids (saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), trans unsaturated fatty acids (TFA) and monounsaturated fatty acids (MUFA) and culinary fats (olive oil, seed oils, butter and margarine) During follow-up participants were classified as incident cases of depression if they reported a new clinical diagnosis of depression by a physician and/or initiated the use of antidepressant drugs. Cox regression models were used to calculate Hazard Ratios (HR) of incident depression and their 95% confidence intervals (CI) for successive quintiles of fats. RESULTS: During follow-up (median: 6.1 years), 657 new cases of depression were identified. Multivariable-adjusted HR (95% CI) for depression incidence across successive quintiles of TFA intake were: 1 (ref), 1.08 (0.82-1.43), 1.17 (0.88-1.53), 1.28 (0.97-1.68), 1.42 (1.09-1.84) with a significant dose-response relationship (p for trend = 0.003). Results did not substantially change after adjusting for potential lifestyle or dietary confounders, including adherence to a Mediterranean Dietary Pattern. On the other hand, an inverse and significant dose-response relationship was obtained for MUFA (p for trend = 0.05) and PUFA (p for trend = 0.03) intake. CONCLUSIONS: A detrimental relationship was found between TFA intake and depression risk, whereas weak inverse associations were found for MUFA, PUFA and olive oil. These findings suggest that cardiovascular disease and depression may share some common nutritional determinants related to subtypes of fat intake.

Impact of sedentarism due to the COVID‐19 home confinement on neuromuscular, cardiovascular and metabolic health: Physiological and pathophysiological implications and recommendations for physical and nutritional countermeasures

Marco Narici, Giuseppe De Vito, Martino V. Franchi +12 more · European Journal of Sport Science · 2020 · 468 citations

Abstract The COVID‐19 pandemic is an unprecedented health crisis as entire populations have been asked to self‐isolate and live in home‐confinement for several weeks to months, which in itself represents a physiological challenge with significant health risks. This paper describes the impact of sedentarism on the human body at the level of the muscular, cardiovascular, metabolic, endocrine and nervous systems and is based on evidence from several models of inactivity, including bed rest, unilateral limb suspension, and step‐reduction. Data form these studies show that muscle wasting occurs rapidly, being detectable within two days of inactivity. This loss of muscle mass is associated with fibre denervation, neuromuscular junction damage and upregulation of protein breakdown, but is mostly explained by the suppression of muscle protein synthesis. Inactivity also affects glucose homeostasis as just few days of step reduction or bed rest, reduce insulin sensitivity, principally in muscle. Additionally, aerobic capacity is impaired at all levels of the O 2 cascade, from the cardiovascular system, including peripheral circulation, to skeletal muscle oxidative function. Positive energy balance during physical inactivity is associated with fat deposition, associated with systemic inflammation and activation of antioxidant defences, exacerbating muscle loss. Importantly, these deleterious effects of inactivity can be diminished by routine exercise practice, but the exercise dose–response relationship is currently unknown. Nevertheless, low to medium‐intensity high volume resistive exercise, easily implementable in home‐settings, will have positive effects, particularly if combined with a 15–25% reduction in daily energy intake. This combined regimen seems ideal for preserving neuromuscular, metabolic and cardiovascular health.

Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression

Jennifer C. Felger, Z Li, Ebrahim Haroon +4 more · Molecular Psychiatry · 2015 · 603 citations

Depression is associated with alterations in corticostriatal reward circuitry. One pathophysiological pathway that may drive these changes is inflammation. Biomarkers of inflammation (for example, cytokines and C-reactive protein (CRP)) are reliably elevated in depressed patients. Moreover, administration of inflammatory stimuli reduces neural activity and dopamine release in reward-related brain regions in association with reduced motivation and anhedonia. Accordingly, we examined whether increased inflammation in depression affects corticostriatal reward circuitry to lead to deficits in motivation and goal-directed motor behavior. Resting-state functional magnetic resonance imaging was conducted on 48 medically stable, unmedicated outpatients with major depression. Whole-brain, voxel-wise functional connectivity was examined as a function of CRP using seeds for subdivisions of the ventral and dorsal striatum associated with motivation and motor control. Increased CRP was associated with decreased connectivity between ventral striatum and ventromedial prefrontal cortex (vmPFC) (corrected P<0.05), which in turn correlated with increased anhedonia (R=-0.47, P=0.001). Increased CRP similarly predicted decreased dorsal striatal to vmPFC and presupplementary motor area connectivity, which correlated with decreased motor speed (R=0.31 to 0.45, P<0.05) and increased psychomotor slowing (R=-0.35, P=0.015). Of note, mediation analyses revealed that these effects of CRP on connectivity mediated significant relationships between CRP and anhedonia and motor slowing. Finally, connectivity between striatum and vmPFC was associated with increased plasma interleukin (IL)-6, IL-1beta and IL-1 receptor antagonist (R=-0.33 to -0.36, P<0.05). These findings suggest that decreased corticostriatal connectivity may serve as a target for anti-inflammatory or pro-dopaminergic treatment strategies to improve motivational and motor deficits in patients with increased inflammation, including depression.

Long-Chain ω-3 Fatty Acids for Indicated Prevention of Psychotic Disorders

G. Paul Amminger, Miriam R. Schäfer, Κωνσταντίνος Παπαγεωργίου +6 more · Archives of General Psychiatry · 2010 · 888 citations

CONTEXT: The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Long-chain omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that omega-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation. OBJECTIVE: To determine whether omega-3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis. DESIGN: Randomized, double-blind, placebo-controlled trial conducted between 2004 and 2007. SETTING: Psychosis detection unit of a large public hospital in Vienna, Austria. PARTICIPANTS: Eighty-one individuals at ultra-high risk of psychotic disorder. INTERVENTIONS: A 12-week intervention period of 1.2-g/d omega-3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months. MAIN OUTCOME MEASURES: The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of omega-6 to omega-3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition. RESULTS: Seventy-six of 81 participants (93.8%) completed the intervention. By study's end (12 months), 2 of 41 individuals (4.9%) in the omega-3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P = .007). The difference between the groups in the cumulative risk of progression to full-threshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). omega-3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P = .01), negative symptoms (P = .02), and general symptoms (P = .01) and improved functioning (P = .002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups. CONCLUSIONS: Long-chain omega-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states. Trial Registration clinicaltrials.gov Identifier: NCT00396643.

2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines

F. Estelle R. Simons, Motohiro Ebisawa, Mario Sánchez‐Borges +8 more · World Allergy Organization Journal · 2015 · 585 citations

The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis provide a unique global perspective on this increasingly common, potentially life-threatening disease. Recommendations made in the original WAO Anaphylaxis Guidelines remain clinically valid and relevant, and are a widely accessed and frequently cited resource. In this 2015 update of the evidence supporting recommendations in the Guidelines, new information based on anaphylaxis publications from January 2014 through mid- 2015 is summarized. Advances in epidemiology, diagnosis, and management in healthcare and community settings are highlighted. Additionally, new information about patient factors that increase the risk of severe and/or fatal anaphylaxis and patient co-factors that amplify anaphylactic episodes is presented and new information about anaphylaxis triggers and confirmation of triggers to facilitate specific trigger avoidance and immunomodulation is reviewed. The update includes tables summarizing important advances in anaphylaxis research.

Vitamin D for Health: A Global Perspective

Arash Hossein‐Nezhad, Michael F. Holick · Mayo Clinic Proceedings · 2013 · 1,290 citations

Food consumption frequency and perceived stress and depressive symptoms among students in three European countries

Rafael Mikolajczyk, Walid El Ansari, Annette E. Maxwell · Nutrition Journal · 2009 · 424 citations

BACKGROUND: Certain foods might be more frequently eaten under stress or when higher levels of depressive symptoms are experienced. We examined whether poor nutritional habits are associated with stress and depressive symptoms and whether the relationships differ by country and gender in a sample from three European countries collected as part of a Cross National Student Health Survey. METHODS: A cross-sectional survey was conducted among first-year students in Germany (N = 696), Poland (N = 489) and Bulgaria (N = 654). Self-administered questionnaires included a 12-item food frequency questionnaire, Cohen's Perceived Stress Scale, and a modified Beck Depression Index. Linear regression analyses were conducted for two outcomes, perceived stress and depressive symptoms. RESULTS: Food consumption frequencies differed by country and gender, as did depressive symptoms and perceived stress. For male students, none of the food consumption groups were associated with perceived stress or depressive symptoms. In females, perceived stress was associated with more frequent consumption of sweets/fast foods and less frequent consumption of fruits/vegetables. Additionally, depressive symptoms were associated with less frequent consumption of fruits/vegetables and meat. CONCLUSION: Our data show consistent associations between unhealthy food consumption and depressive symptoms and perceived stress among female students from three European countries, but not among male students. This suggests that efforts to reduce depressive symptoms and stress among female students may also lead to the consumption of healthier foods and/or vice-versa.

Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway

Li-Ting Guo, Siqi Wang, Jing Su +7 more · Journal of Neuroinflammation · 2019 · 406 citations

BACKGROUND: Baicalin, which is isolated from Radix Scutellariae, possesses strong biological activities including an anti-inflammation property. Recent studies have shown that the anti-inflammatory effect of baicalin is linked to toll-like receptor 4 (TLR4), which participates in pathological changes of central nervous system diseases such as depression. In this study, we explored whether baicalin could produce antidepressant effects via regulation of TLR4 signaling in mice and attempted to elucidate the underlying mechanisms. METHODS: A chronic unpredictable mild stress (CUMS) mice model was performed to explore whether baicalin could produce antidepressant effects via the inhibition of neuroinflammation. To clarify the role of TLR4 in the anti-neuroinflammatory efficacy of baicalin, a lipopolysaccharide (LPS) was employed in mice to specially activate TLR4 and the behavioral changes were determined. Furthermore, we used LY294002 to examine the molecular mechanisms of baicalin in regulating the expression of TLR4 in vivo and in vitro using western blot, ELISA kits, and immunostaining. In the in vitro tests, the BV2 microglia cell lines and primary microglia cultures were pretreated with baicalin and LY292002 for 1 h and then stimulated 24 h with LPS. The primary microglial cells were transfected with the forkhead transcription factor forkhead box protein O 1 (FoxO1)-specific siRNA for 5 h and then co-stimulated with baicalin and LPS to investigate whether FoxO1 participated in the effect of baicalin on TLR4 expression. RESULTS: The administration of baicalin (especially 60 mg/kg) dramatically ameliorated CUMS-induced depressive-like symptoms; substantially decreased the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the hippocampus; and significantly decreased the expression of TLR4. The activation of TLR4 by the LPS triggered neuroinflammation and evoked depressive-like behaviors in mice, which were also alleviated by the treatment with baicalin (60 mg/kg). Furthermore, the application of baicalin significantly increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and FoxO1. The application of baicalin also promoted FoxO1 nuclear exclusion and contributed to the inhibition of the FoxO1 transactivation potential, which led to the downregulation of the expression of TLR4 in CUMS mice or LPS-treated BV2 cells and primary microglia cells. However, prophylactic treatment of LY294002 abolished the above effects of baicalin. In addition, we found that FoxO1 played a vital role in baicalin by regulating the TLR4 and TLR4-mediating neuroinflammation triggered by the LPS via knocking down the expression of FoxO1 in the primary microglia. CONCLUSION: Collectively, these results demonstrate that baicalin ameliorated neuroinflammation-induced depressive-like behaviors through the inhibition of TLR4 expression via the PI3K/AKT/FoxO1 pathway.

α-Synuclein impairs macroautophagy: implications for Parkinson’s disease

Ashley R. Winslow, Chien‐Wen Chen, Silvia Corrochano +10 more · The Journal of Cell Biology · 2010 · 819 citations

Parkinson's disease (PD) is characterized pathologically by intraneuronal inclusions called Lewy bodies, largely comprised of α-synuclein. Multiplication of the α-synuclein gene locus increases α-synuclein expression and causes PD. Thus, overexpression of wild-type α-synuclein is toxic. In this study, we demonstrate that α-synuclein overexpression impairs macroautophagy in mammalian cells and in transgenic mice. Our data show that α-synuclein compromises autophagy via Rab1a inhibition and Rab1a overexpression rescues the autophagy defect caused by α-synuclein. Inhibition of autophagy by α-synuclein overexpression or Rab1a knockdown causes mislocalization of the autophagy protein, Atg9, and decreases omegasome formation. Rab1a, α-synuclein, and Atg9 all regulate formation of the omegasome, which marks autophagosome precursors.