Do sugar-sweetened beverages cause adverse health outcomes in children? A systematic review protocol What do review papers conclude about food and dietary patterns? Sugar-Sweetened Beverage Health Warnings and Purchases: A Randomized Controlled Trial. The 2015 Dutch food-based dietary guidelines Systematic reviews in public health: old chestnuts and new challenges. A conversation with Joseph Lau. Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT). Protocol for systematic reviews of determinants/correlates of obesity-related dietary and physical activity behaviors in young children (preschool 0 to 6 years): evidence mapping and syntheses Systematic Reviews: Synthesis of Best Evidence for Clinical Decisions Taxing sugar-sweetened beverages: a survey of knowledge, attitudes and behaviours. Heart Failure 2012 Dietary Patterns and Cognitive Health in Older Adults: A Systematic Review. A Systematic Review of Single Chinese Herbs for Alzheimer's Disease Treatment Associations Between Periodontal Disease and Systemic Disease: Evaluating the Strength of the Evidence. Improving antiretroviral therapy adherence in resource‐limited settings at scale: a discussion of interventions and recommendations Beta-carotene: a cancer chemopreventive agent or a co-carcinogen? Issues in psychopharmacology. Reporting of Sex Effects by Systematic Reviews on Interventions for Depression, Diabetes, and Chronic Pain Controversies around Xylitol Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines. Sugars and risk of mortality in the NIH-AARP Diet and Health Study.
Background Cardiovascular disease and type 2 diabetes are examples of chronic diseases that impose significant morbidity and mortality in the general population worldwide . Most chronic diseases are associated with underlying preventable risk factors , such as elevated blood pressure , high blood glucose or glucose intolerance , high lipid levels , physical inactivity , excessive sedentary behaviours , and overweight/obesity . The occurrence of intermediate outcomes during childhood increases the risk of disease in adulthood . Sugar-sweetened beverages are known to be significant sources of additional caloric intake , and given recent attention to their contribution in the development of chronic diseases , a systematic review is warranted . We will assess whether the consumption of sugar-sweetened beverages in children is associated with adverse health outcomes and what the potential moderating factors are . Methods / Design Of interest are studies addressing sugar-sweetened beverage consumption , taking a broad perspective . Both direct consumption studies as well as those evaluating interventions that influence consumption ( e.g. school policy , educational ) will be relevant . Non-specific or multi-faceted behavioural , educational , or policy interventions may also be included subject to the level of evidence that exists for the other interventions /exposures . Comparisons of interest and endpoints of interest are pre-specified . We will include r and omized controlled trials , controlled clinical trials , interrupted time series studies , controlled before-after studies , prospect i ve and retrospective comparative cohort studies , case – control studies , and nested case – control design s. The MEDLINE ® , Embase , The Cochrane Library , CINAHL , ERIC , and PsycINFO ® data bases and grey literature sources will be search ed . The processes for selecting studies , abstract ing data , and resolving conflicts are described . We will assess risk of bias using design -specific tools . To determine sets of confounding variables that should be adjusted for , we have developed causal directed acyclic graphs and will use those to inform our risk of bias assessment s. Meta- analysis will be conducted where appropriate ; parameters for exploring statistical heterogeneity and effect modifiers are pre-specified . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach will be used to determine the quality of evidence for outcomes . Systematic review registration PROSPERO CRD42014009641 Nutrients and other bioactive constituents of foods may interact with each other and the surrounding food matrix in complex ways . Therefore , associations between single nutrients and chronic disease may be difficult to identify and interpret , but when dietary patterns ( DPs ) are examined the combination of many food factors will be considered . An explorative literature search of published review articles was conducted to obtain a fuller underst and ing of current DPs in epidemiological research , to discuss pros and cons of DPs in nutrition research , and to identify results of studies linking DPs to chronic disease risk in adults . R and omized feeding trials providing the experimental diets to study participants have repeatedly demonstrated that diets based on current dietary recommendations are associated with important health benefits . Systematic review s of feeding trials and prospect i ve population studies of DPs and chronic disease risk reach similar conclusions regardless of the methodology used to construct DPs . However , to date only a few review articles of DP studies have followed a systematic process using independent review ers with strict inclusion , exclusion , and study quality criteria . Diets with plenty of plants foods , fish , and seafood that preferably include vegetable oils and low-fat dairy products are associated with a lower risk of most chronic diseases . In contrast , Western-type DPs with food products low in essential nutrients and high in energy , like sugar-sweetened beverages , sweets , refined cereals and solid fats ( e.g. butter ) , and high in red and processed meats , are associated with adverse health effects . An emphasis on high- quality original research , and systematic review s following a structured process to objective ly select and judge studies , is needed in order to enforce a strong future knowledge base regarding DPs and chronic disease INTRODUCTION Five U.S. states have proposed policies to require health warnings on sugar-sweetened beverages , but warnings ' effects on actual purchase behavior remain uncertain . This study evaluated the impact of sugar-sweetened beverage health warnings on sugar-sweetened beverage purchases . STUDY DESIGN Participants completed one study visit to a life-sized replica of a convenience store in North Carolina . Participants chose six items ( two beverages , two foods , and two household products ) . One item was r and omly selected for them to purchase and take home . Participants also completed a question naire . Research ers collected data in 2018 and conducted analyses in 2019 . SETTING / PARTICIPANTS Participants were a demographically diverse convenience sample of 400 adult sugar-sweetened beverage consumers ( usual consumption ≥12 ounces/week ) . INTERVENTION Research staff r and omly assigned participants to a health warning arm ( sugar-sweetened beverages in the store displayed a front-of-package health warning ) or a control arm ( sugar-sweetened beverages displayed a control label ) . MAIN OUTCOME MEASURES The primary trial outcome was sugar-sweetened beverage calories purchased . Secondary outcomes included reactions to trial labels ( e.g. , negative emotions ) and sugar-sweetened beverage perceptions and attitudes ( e.g. , healthfulness ) . RESULTS All 400 participants completed the trial and were included in analyses . Health warning arm participants were less likely to be Hispanic and to have overweight/obesity than control arm participants . In intent-to-treat analyses adjusting for Hispanic ethnicity and overweight/obesity , health warnings led to lower sugar-sweetened beverage purchases ( adjusted difference , -31.4 calories ; 95 % CI= -57.9 , -5.0 ) . Unadjusted analyses yielded similar results ( difference , -32.9 calories ; 95 % CI= -58.9 , -7.0 ) . Compared with the control label , sugar-sweetened beverage health warnings also led to higher intentions to limit sugar-sweetened beverage consumption and elicited more attention , negative emotions , thinking about the harms of sugar-sweetened beverage consumption , and anticipated social interactions . Trial arms did not differ on perceptions of sugar-sweetened beverages ' added sugar content , healthfulness , appeal/coolness , or disease risk . CONCLUSIONS Brief exposure to health warnings reduced sugar-sweetened beverage purchases in this naturalistic RCT . Sugar-sweetened beverage health warning policies could discourage sugar-sweetened beverage consumption . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT03511937 The objective of this study was to derive food-based dietary guidelines for the Dutch population . The dietary guidelines are based on 29 systematic review s of English language meta-analyses in PubMed summarizing r and omized controlled trials and prospect i ve cohort studies on nutrients , foods and food patterns and the risk of 10 major chronic diseases : coronary heart disease , stroke , heart failure , diabetes , breast cancer , colorectal cancer , lung cancer , chronic obstructive pulmonary disease , dementia and depression . The committee also selected three causal risk factors for cardiovascular diseases or diabetes : systolic blood pressure , low-density lipoprotein cholesterol and body weight . Findings were categorized as strong or weak evidence , inconsistent effects , too little evidence or effect unlikely for experimental and observational data separately . Next , the committee selected only findings with a strong level of evidence for deriving the guidelines . Convincing evidence was based on strong evidence from the experimental data either or not in combination with strong evidence from prospect i ve cohort studies . Plausible evidence was based on strong evidence from prospect i ve cohort studies only . A general guideline to eat a more plant food-based dietary pattern and limit consumption of animal-based food and 15 specific guidelines have been formulated . There are 10 new guidelines on legumes , nuts , meat , dairy produce , cereal products , fats and oils , tea , coffee and sugar-containing beverages . Three guidelines on vegetables , fruits , fish and alcoholic beverages have been sharpened , and the 2006 guideline on salt stayed the same . A separate guideline has been formulated on  nutrient supplements .  Completely food-based dietary guidelines can be derived in a systematic and transparent way The Bulletin ’s editorial team has decided to encourage systematic review s. This is an important decision and is to be welcomed . However it is possible that it will not be received positively by all . Some may feel that systematic review s are not suitable for answering wider public health questions , and that the new section will simply result in the publication of systematic review s addressing narrowly focused , clinical questions with a focus on r and omized controlled trials alone.1 There is no reason why this should be so , and there are far too many examples of systematic review s of non- clinical interventions ( including government policies ) , which include non-r and omized studies , to list.2 Systematic review s of qualitative research are also becoming more common.3 Nonetheless misconceptions about the scope and flexibility of systematic review s still surface occasionally and it never fails to surprise me when I stumble across one of these hoary old chestnuts . If it really were true that systematic review s were only for simple , individual-level interventions , systematic review ers working in public health would be very concerned . After all , public health problems require us to draw on complex sets of qualitative as well as quantitative evidence ; and some policy interventions have never been subjected to r and omized controlled trials ( RCTs ) but have been evaluated using other approaches ; everything from controlled and uncontrolled before- and -after studies , to time series analyses , to qualitative methods . In such cases , systematic review s that focused on RCTs alone would have little to say and we would end up producing many “ empty review s ” , which contain no studies at all . These would be undoubtedly quicker to do and quicker to read than the typical systematic review , but would be of limited use for making policy . However this is not the case . In public health we already have a wealth of review s that prioritize RCTs where they are available , but which draw upon a range of other evidence where they are appropriate to answering the review question .2 Take , as an example , transport policies , an important social determinant of health.4 Public health decision-makers have been interested in the effects on health of building new roads for decades , but there has never been a r and omized controlled trial , for obvious reasons . Yet it would make no sense to cl aim that there is no evidence to be review ed ; rather , there have been many controlled and uncontrolled studies that have examined the effects of new roads on respiratory symptoms , injuries , community severance , disturbance and a variety of other outcomes of public health importance . These studies have in fact been systematic ally review ed.5 Many other examples of review s of complex interventions that impact on public health could be given , which appear on the Cochrane Data base and elsewhere,6,7 and such review s are the main focus of the recently-established Cochrane Public Health Review Group . It is also worth noting that both the Cochrane and Campbell Collaboration include increasing numbers of review s that are relevant to low- and middle- income countries,8 though there is a particular need for more systematic review s that consider the effects on equity of the interventions that they include.9 Currently systematic review s have a “ utilitarian bias ” – they tend to be concerned more with the effects on population s and average effects than with distributional effects and impacts in disadvantaged subgroups . It is to be hoped that systematic review s su bmi tted to the Bulletin will routinely consider the effects of interventions on health inequities . The Cochrane Health Equity Field ( http://equity.cochrane.org/en/index.html ) was set up explicitly to further this agenda , to encourage systematic review authors to explicitly assess the effects of interventions not only on the whole population , but on the disadvantaged . So where does this leave non- systematic review s ? Should every review be a systematic review ? This is a difficult question to answer in a short editorial . My own view is that not all review s need to be systematic review s ; there is still a place for review papers that provide a broad overview , and that discuss a range of evidence and make a contribution to wider debates about what might work in particular setting s. However , while such discussion s help place evidence in context and suggest how it may be used , they should not be confused with the evidence -based conclusions of a transparent , scientific review , which systematic ally attempts to find all the relevant evidence , appraises its strengths and limitations in a transparent fashion , and draws that evidence together in such a way that the more robust studies are given greater weight . Finally , the challenges are many . Evidence on interventions to improve public health is in short supply , particularly evidence on social determinants . Systematic review ers therefore face a real challenge in making best use of the sometimes poor , often sparse and usually heterogeneous evidence available to them . It is easy to set narrow inclusion criteria for a review and then sift through the evidence before concluding that there is n’t enough – and what there is , is n’t very good anyway . Such “ evidential nihilism ” is probably not helpful to decision-makers , and public health systematic review ers need to continue to develop new methods and better frameworks within which different types of research evidence can be integrated to inform decision-making . Publishing systematic review s in the Bulletin should give an added impetus to this ongoing work . Dr. Joseph Lau is a world-leading expert in meta- analysis and systematic review s. Currently a professor in the Department of Health Services , Policy and Practice and co-director of the Center for Evidence -based Medicine at Brown University , Professor Lau has applied evidence -based methods to a variety of clinical , biomedical and healthcare topics ; has developed reliable and efficient methods and tools to conduct systematic review s and meta-analyses ; and has advanced an underst and ing on the impact of factors that may contribute to differences of results in scientific studies . His past research includes cumulative meta- analysis of r and omized controlled trials , comparison of results from large trials and meta-analyses of small trials , effect of baseline risk in the interpretation of clinical trial results , and empirical evaluation of existing methods of combining data . His current focus is on a Web-based repository of systematic review data , review s of diagnostic tests , nutrition , clinical practice guidelines , and dissemination of evidence -based methods to varied health-care disciplines . This report is a conversation from an adapted version of an interview , more or less chronologically arranged , between Joseph C. Cappelleri as interviewer and Joseph Lau as interviewee , with Meghan Ingerick recording and transcribing the interview Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease ( NAFLD ) to shift into one of the most frequent causes of chronic liver illness in childhood . Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used ; overall it ranges between 3 % and 10 % of pediatric population , increasing up to 70 % in patients with metabolic comorbidities ( Manco M , Bottazzo G , DeVito R et al , J Am Coll Nutr 27:667 - 676 , 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions , including type 2 diabetes ( T2D ) , obesity , and nonalcoholic steatohepatitis ( NASH ) . One of the emerging areas of the study is the link between liver diseases and gut microbiome , which has added new information to the underst and ing of the so-called gut-liver axis . In order to address the role of gut microbiome in NAFLD onset and progression , it is necessary to " decipher " operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and , hence , to address the function of the intestinal microbiome within the gut microbiota-liver axis . Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of  obesity and NAFLD in adults and children . Several r and omized clinical trials ( RCTs ) have been already published on  fecal microbiota transplantation  ( FMT ) , T2D , NASH , and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions , probiotics , symbiotics , and FMT Background The aim of these review s is to inform the design and content of interventions to reduce obesity in young children . The behaviors that are associated with obesity/overweight have been studied extensively ; however , the factors associated with these behaviors in young children ( 0 to 6 years ) have not been systematic ally review ed . Over the past few years the focus of obesity prevention has shifted to preschool children because of the high prevalence of obesity at school entry and recognition that habits formed in early life could track into adulthood . In order to develop effective interventions and change behavior , it is important to underst and the factors that are associated with those behaviors . For example , we need to underst and whether it would be more important to target the family , childcare setting s or the wider environment and identify the most effective way of changing these energy balance related behaviors . Methods / Design Quantitative ( intervention and observational ) and qualitative literature on determinants/correlates of fruit and vegetable intake , sugar sweetened beverage and other unhealthy diet intake , and physical activity and sedentary behaviors in young children will be systematic ally identified , mapped and review ed . A common search strategy ( no language or period restrictions ) will be used to identify papers from eight electronic data bases and this will be supplemented by h and - search ing . Next , studies in developed countries that examine the factors associated with these behaviors in children aged 0 to 6 years ( at baseline ) will be screened and mapped descriptively followed by in-depth data extraction , quality assessment and synthesis . Data from quantitative studies will be summarized using either forest plots or harvest plots and narrative synthesis , and qualitative studies using thematic analysis . Qualitative evidence will be integrated with the quantitative evidence , using a parallel synthesis approach , to provide a deeper underst and ing of effective strategies to influence these energy balance related behaviors . Discussion In addition to updating and mapping current research , these review s will be the first to comprehensively synthesize and integrate both the quantitative and qualitative evidence pertaining to determinants/correlates/barriers/facilitators of obesity related behaviors in this young age group ( 0 to 6 years ) with the aim of informing future interventions . Systematic review registration International Prospect i ve Register for Systematic Review s ( PROSPERO ) Registration number : At the end of a long week in the office , you sink back into your chair , reflecting on some of the more memorable patients you cared for and counseled . Through gentle history taking , you discovered that urinary incontinence is the underlying cause of an elderly patient 's increasing social isolation . During a careful physical examination , you detected bruising on the torso of a woman with chronic headaches and began to explore the longst and ing abusive relationship between the woman and her alcoholic partner . You discontinued procainamide therapy in a 72-year-old man who had asymptomatic premature ventricular contractions after myocardial infa rct ion . To prevent bleeding from esophageal varices , you started -blocker therapy in a woman with long-st and ing cryptogenic cirrhosis and portal hypertension . In couples ' therapy , discussing the future quality of life of a middle-aged gay man with human immunodeficiency virus infection , you journeyed through emotionally intense dialogue about advance directives . You presented the risk factors for major and minor bleeding to a 39-year-old woman who was considering warfarin therapy because of recently diagnosed atrial fibrillation and valvular heart disease . You listened to , made diagnoses for , treated , advised , and comforted many patients . Yet there were some hiccoughs in your practice along the way . You stumbled while debating the pros and cons of breast cancer screening with a healthy 48-year-old woman who has been staying current with information on the Internet . You question ed the merits of a personalized walking program suggested to you by a motivated 66-year-old man with severe claudication . Explaining that you wanted to review the best current evidence on these issues , you resolved to address your uncertainties before these patients made their next office visits , in a week 's time . Sighing deeply , you acknowledge that you have little time to read . You subscribe to three journals , which you browse months after they arrive-either when your journal stack becomes precariously high or when your guilt is sufficiently motivational . You sometimes find the conclusions of individual articles conflicting or confusing . You know that some of the decisions and suggestions you made this week , specifically your decisions about stopping procainamide therapy and starting -blocker therapy and your advice about bleeding risks from anticoagulant therapy , were based on the best current research evidence [ 1 - 3 ] . On the other h and , your patients ' inquiries about breast cancer screening and exercise treatment for claudication highlight your need for a concise , current , rigorous synthesis of the best available evidence on each of these topics : in brief , a systematic review [ 4 , 5 ] . Incorporating Research Evidence into Clinical Decision Making The foregoing scenario is familiar to practitioners . In a typical week , we encounter patients with diverse problems ; exercise numerous clinical , interpersonal , and technical skills ; and make many decisions . The factors that affect these decisions and their outcomes are complex . For instance , each patient has unique sociodemographic characteristics , cultural circumstances , and personal preferences . Each physician has unique knowledge , experiences , and values . Moreover , practitioners and their patients make decisions within the context of a rapidly changing health care system that influences the availability , accessibility , and cost of diagnostic tests and therapies [ 6 ] . Timely , useful evidence from the biomedical literature should be an integral component of clinical decision making . If one treatment has been shown to be better than another , we need to know , so that we can recommend the treatment to the appropriate patients . The worldwide effort to develop new tests and treatments , and to determine their usefulness , has never been stronger , and our patients and their families expect us to be fonts of the knowledge that results from this effort [ 7 ] . Unfortunately , it is easy for current best research evidence to pass us by [ 8 ] . We may lack the time , motivation , and basic skills needed to find , critically appraise , and synthesize information , all of which we must do if we are to integrate the results of original studies into our practice . Fortunately , several potent methods are emerging that can greatly enhance our ability to interpret and apply research evidence ; foremost among them is the systematic review . This article begins a series in Annals that will examine systematic review s in detail and explore their many applications . Systematic review s represent the best chance that most practitioners will have to underst and and accurately apply the key signals arising from the robust and increasingly productive search for solutions to medical problems . A properly conducted systematic review faithfully summarizes the evidence from all relevant studies on the topic of interest , and it does so concisely and transparently . What Is a Systematic Review ? Systematic review s are scientific investigations in themselves , with pre-planned methods and an assembly of original studies as their subjects . They synthesize the results of multiple primary investigations by using strategies that limit bias and r and om error [ 9 , 10 ] . These strategies include a comprehensive search of all potentially relevant articles and the use of explicit , reproducible criteria in the selection of articles for review . Primary research design s and study characteristics are appraised , data are synthesized , and results are interpreted . When the results of primary studies are summarized but not statistically combined , the review may be called a qualitative systematic review . A quantitative systematic review , or meta- analysis , is a systematic review that uses statistical methods to combine the results of two or more studies . The term overview is sometimes used to denote a systematic review , whether quantitative or qualitative . Summaries of research that lack explicit descriptions of systematic methods are often called narrative review s. Review articles are one type of integrative publication ; practice guidelines , economic evaluations , and clinical decision analyses are others . These other types of integrative articles often incorporate the results of systematic review s. For example , practice guidelines are systematic ally developed statements intended to assist practitioners and patients with decisions about appropriate health care for specific clinical circumstances [ 11 ] . Evidence -based practice guidelines are based on systematic review s of the literature , appropriately adapted to local circumstances and values . Economic evaluations compare both the costs and the consequences of different courses of action ; the knowledge of consequences that are considered in these evaluations is often generated by systematic review s of primary studies . Decision analyses quantify both the likelihood and the valuation of the expected outcomes associated with competing alternatives . Differences between Systematic and Narrative Review s All review s , narrative and systematic alike , are retrospective , observational research studies and are therefore subject to systematic and r and om error . Accordingly , the quality of a review - and thus its worth-depends on the extent to which scientific review methods have been used to minimize error and bias . This is the key feature that distinguishes traditional narrative review s from systematic review s ( Table 1 ) . If a review is prepared according to the steps outlined in the right column of Table 1 , it is more likely to be systematic and to provide unbiased conclusions . If review methods approximate those found in the middle column of Table 1 , the article is more likely to be a narrative review , and the conclusions are less likely to be based on an unbiased summary of all relevant evidence . Table 1 . Differences between Narrative Review s and Systematic Review s Systematic review s are generated to answer specific , often narrow , clinical questions in depth . These questions can be formulated explicitly according to four variables : a specific population and setting ( such as elderly out patients ) , the condition of interest ( for example , hypertension ) , an exposure to a test or treatment ( such as pharmacologic management ) , and one or more specific outcomes ( such as cardiovascular and cerebrovascular events and mortality ) [ 12 ] . Thus , an example of a well-formulated , clinical ly relevant question is , Does pharmacologic treatment of hypertension in the elderly prevent strokes and myocardial infa rct ions or delay death ? If the question that is driving the review is not clear from the title , abstract , or introduction , or if no methods section is included , the paper is more likely to be a narrative review than a systematic review [ 13 ] . Most narrative review articles deal with a broad range of issues related to a given topic rather than addressing a particular issue in depth [ 9 ] . For example , a narrative review on diabetes ( such as that which might be found in a textbook chapter ) might include sections on the physiology and pathophysiology of carbohydrate , lipid , and protein metabolism ; the epidemiology of and prognosis associated with diabetes ; diagnostic and screening approaches ; and preventive , therapeutic , rehabilitative , and palliative interventions . Thus , narrative review s may be most useful for obtaining a broad perspective on a topic ; they are less often useful in furnishing quantitative answers to specific clinical questions . Narrative review s are appropriate for describing the history or development of a problem and its management . Narrative review s may better describe cutting-edge developments if research is scant or preliminary or if studies are very limited by flawed design or execution [ 13 ] . They may be particularly useful for discussing data in light of underlying theory and context . Narrative review s can draw analogies and can conceptually integrate two independent fields of research , such as OBJECTIVE To assess current beverage consumption patterns and anticipated reaction to an added 20 % tax on these products . DESIGN A r and om-digit dialled telephone interview lasting 20 min was administered to assess demographics , beverage consumption behaviours and intentions regarding consumption of sugar-sweetened beverages in the event of an additional tax on these beverages . SETTING Respondents were recruited throughout the USA . SUBJECTS The study included 592 adults . RESULTS Sixty-nine per cent of respondents reported consuming at least one pre-packaged sugar-sweetened beverage in the past week ; those who consumed sugar-sweetened beverages averaged seven pre-packaged beverages per week . Ninety-one per cent knew that frequent consumption of soft drinks increases risk of obesity . Thirty-six per cent supported a tax on sugar-sweetened beverages with greatest support among those aged 18 - 24 years , those with BMI < 30 kg/m2 and those with higher levels of education ( P < 0·05 ) . Over one-third of respondents said that they would cut back on their sweetened beverage consumption in the event of an added 20 % tax on these beverages . CONCLUSIONS Our findings suggest that an added tax on these beverages could influence some to cut down on their consumption , reducing their risk of obesity and related illnesses Heart failure has been named “ the growing epidemic . ” Over the last decade , the annual number of heart failure hospitalizations has almost doubled with approximately 50 % of patients being rehospitalized within 6 months of discharge [ 1 ] . The complex array of physiologic , psychological , social , and health care delivery issues makes it a challenging chronic disease to manage . Underst and ing the epidemiology and pathophysiology of the syndrome , identifying the predictors and their strength of association with outcomes , and using the available diagnostic modalities cost-effectively are essential in order to devise effective prevention interventions and implement novel therapeutic approaches to curb this epidemic . In this special issue , we have invited a few papers that address such issues and explain why despite the emergence of novel therapeutic approaches , that promise life prolongation and hospital length reduction , this patient population will still be needing rehospitalization and will often have a poor prognosis . This special issue is the extension of an effort that was initiated in 2011 with the first heart-failure-focused issue [ 2 ] . In the pathophysiology section , S. M. R. Kazemi-Bajestani et al. describe the opportunities and challenges of targeting the angiotensin converting enzyme 2 (ACE2)/Ang II/Ang1–7 and apelin/APJ pathways as novel therapeutic modalities in heart failure [ 3 ] . ACE2 and the apelin/APJ are two important peptide systems which exert diverse effects on the cardiovascular system . Dysregulation of such systems may be involved in the predisposition to cardiovascular diseases whereas enhancing their action may have important therapeutic effects . In the same section , D. Lindner et al. provide a comprehensive review on the protective function of signal transducer and activator of transcription 3 ( STAT3 ) in CVB3-induced myocarditis [ 4 ] . The transcription factor ( STAT3 ) is an important mediator of the inflammatory process , and in this original research the investigators examine the role of STAT3 in viral myocarditis and its possible role in the development to dilated cardiomyopathy . Considering the high mortality rate and the availability of life-saving therapies like transplantation and left ventricular assist devices , accurate prognosis determination in HF is clinical ly important . Taking into account the mediocre performance of current established prediction models , such as the Seattle Heart Failure Model [ 5–7 ] , the work by H. Fukuta et al. [ 8 ] on the prognostic value of left ventricular diastolic dysfunction in patients undergoing cardiac catheterization for coronary artery disease sheds light on this extremely important topic . A shared underst and ing of medical conditions between patients and their health care providers has been shown to improve self-care and outcomes [ 9 ] . In the comorbidity section , we demonstrate how certain comorbid conditions may affect patients ' decision-making capacity and interfere with their ability to comply with treatment requirements , recognize and self-manage disease worsening symptoms . Among others , cognitive impairment is increasingly recognized as a common adverse consequence of HF , whereby phenomena such as microembolism , chronic or intermittent cerebral hypoperfusion , and /or impaired cerebral vessel reactivity may lead to cerebral hypoxia and ischemic brain damage . Cognitive decline in HF is characterized by deficits in one or more cognition domains , including attention , memory , executive function , and psychomotor speed . E. Dardiotis et al. [ 10 ] , in a comprehensive review , underscore the importance for healthcare professionals to become familiar with assessment of cognitive performance using st and ardized screening instruments in their routine evaluations of HF patients . Another comorbidity gaining increasing attention in HF patients is depression . There are several pathophysiological mechanisms as well as behavioral processes linking depression and HF . Equally important is screening for depression and there are several valid and reliable screening tools to identify patients at greater risk . Consultation should be provided by a multidisciplinary team , consisting of cardiologists , psychiatrists , and hospital or community nurses so as to carefully plan , execute , and evaluate medical intervention and implement lifestyle changes . D. Mastrogiannis et al. [ 11 ] systematic ally review the existing knowledge regarding current definitions , prognostic implication s , pathophysiological mechanisms , and current and future treatment options in patients with depression and HF . Evidence from the literature supports the possibility of a pathophysiological relationship between cognitive impairment , depression , and HF . Yet , very few studies have sought to investigate this relationship . The paper by Z. N. Sohani and Z. Samaan review s current literature on the association between depression and cognitive impairment  in persons with HF and explores possible mechanisms explaining this complex triad [ 12 ] . Heart failure through neurohumoral activation induces alterations of cardiac metabolism , such as insulin resistance , and promotes increased utilization of noncarbohydrate substrates for energy production [ 13 , 14 ] . Fasting blood ketone bodies as well as fat oxidation have been shown to be increased in this patient population . The result is depletion of myocardial ATP , phosphocreatine , and creatine kinase , leading to decreased efficiency of mechanical work . A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart . Trimetazidine , perhexiline , and ranolazine directly inhibit fatty acid oxidation and have been used to increase the ischemic threshold in patients with effort angina . Current research is supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with HF . These agents have been shown to improve both glucose metabolism and left ventricular function in diabetic patients with left ventricular dysfunction . In the pharmacotherapy section , we provide a systematic review , in which N. Signoretta et al. [ 15 ] discuss the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilization in patients with HF . In the advanced heart failure section , we provide a thorough review on the current status of mechanical circulatory support in patients with advanced HF . Management of the advanced HF patients with the numerous comorbidities [ 16 , 17 ] requires a significant amount of health care re sources and is becoming a major public health problem . As therapeutical strategies for HF have been refined , the number of patients suffering from the end-stage disease has exp and ed dramatically . Although heart transplantation still represents the gold st and ard therapeutical approach , the shortage of donors universally has made the implantation of mechanical circulatory support devices a well-established management for this disease . The systematic review by K. Spiliopoulos et al. [ 18 ] , outlines the current status of mechanical circulatory support in this patient population . In the chronic follow-up section , we deal with telemonitoring , a novel diagnostic modality that has been suggested to be beneficial for HF patients , targeting optimization of their chronic followup . Telemonitoring is viewed as a means of recording physiological data ( such as body weight , heart rate , arterial blood pressure electrocardiogram recordings , and other data ) by portable devices and transmitting these data remotely ( via a telephone line , a mobile phone , or a computer ) to a server where they can be stored , review ed , and analyzed by the research team . In a systematic review of all r and omized clinical trials evaluating telemonitoring in chronic HF , G. Giamouzis et al. [ 19 ] assess whether telemonitoring provides any substantial benefit in this patient population . We hope that the readers of the journal will find the topics as interesting and important as we did . Gregory Giamouzis George Giannakoulas Javed Butler John A. Elefteriades Carsten Tschope Filippos While the role of diet and nutrition in cognitive health and prevention of dementia  in older adults has attracted much attention , the efficacy of different dietary patterns remains uncertain . Previous review s have mainly focused on the Mediterranean diet , but either omitted other dietary patterns , lacked more recent studies , were based on cross-sectional studies , or combined older and younger population s. We followed PRISMA guidelines , and examined the efficacy of current research from r and omized controlled trials and cohort studies on the effects of different dietary patterns . We review ed the Mediterranean diet , Dietary Approach to Stop Hypertension ( DASH ) diet , the Mediterranean-DASH diet Intervention for Neurodegenerative Delay ( MIND ) diet , Anti-inflammatory diet , Healthy diet recommended by guidelines via dietary index , or Prudent healthy diets generated via statistical approaches , and their impact on cognitive health among older adults . Of 38 studies , the Mediterranean diet was the most investigated with evidence supporting protection against cognitive decline among older adults . Evidence from other dietary patterns such as the MIND , DASH , Anti-inflammatory , and Prudent healthy diets was more limited but showed promising results , especially for those at risk of cardiovascular disease . Overall , this review found positive effects of dietary patterns including the Mediterranean , DASH , MIND , and Anti-inflammatory diets on cognitive health outcomes in older adults . These dietary patterns are plant-based , rich in poly- and mono-unsaturated fatty acids with lower consumption of processed foods . Better underst and ing of the underlying mechanisms and effectiveness is needed to develop comprehensive and practical dietary recommendations against age-related cognitive decline among older adult The objectives here are to provide a systematic review of the current evidence concerning the use of Chinese herbs in the treatment of  Alzheimer 's disease ( AD ) and to underst and their mechanisms of action with respect to the pathophysiology of the disease . AD , characterized microscopically by deposition of amyloid plaques and formation of neurofibrillary tangles in the brain , has become the most common cause of senile dementia . The limitations of western medications have led us to explore herbal medicine . In particular , many Chinese herbs have demonstrated some interesting therapeutic properties . The following data bases were search ed from their inception : MEDLINE ( PUBMED ) , ALT HEALTH WATCH ( EBSCO ) , CINAH and Cochrane Central . Only single Chinese herbs are included . Two review ers independently extracted the data and performed quality assessment . The quality assessment of a clinical trial is based on the Jadad criteria . Seven Chinese herbs and six r and omized controlled clinical trials were identified under the predefined criteria . Ginkgo biloba , Huperzine A ( Lycopodium serratum ) and Ginseng have been assessed for their clinical efficacy with limited favorable evidence . No serious adverse events were reported . Chinese herbs show promise in the treatment of AD in terms of their cognitive benefits and more importantly , their mechanisms of action that deal with the fundamental pathophysiology of the disease . However , the current evidence in support of their use is inconclusive or inadequate . Future research should place emphasis on herbs that can treat the root of the disease Much work has been published on the association between periodontal disease and systemic disease , including original reports , narrative review s , systematic review s , and meta-analyses . Based on the existent work , one can assign an evidence level and grade , using st and ard evidence -based criteria , to the data available in the four major categories of medical outcomes studied : cardiovascular/cerebrovascular , pregnancy , pulmonary , and diabetes . We discuss method ologic and conceptual problems in the study of oral-systemic associations , focusing as an example on the association between periodontal disease and cardiovascular/cerebrovascular disease . We argue that the hierarchical ranking of studies by levels of evidence may be misleading . In particular , while r and omized controlled trials ( RCTs ) are needed to determine the efficacy of periodontal treatment to reduce the risk of cardiovascular events , they may be of limited value in determining the etiologic role of periodontal disease on coronary heart disease and stroke . We discuss limitations of RCTs as well as the limitations of currently available data from epidemiologic studies , including study design and confounding and misclassification errors . We conclude that well- design ed observational studies into the associations between periodontal disease and systemic disease need to remain an integral component of future research efforts in order to fully underst and such associations Abstract Introduction : Successful population ‐level antiretroviral therapy ( ART ) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale‐up and , ultimately , the end of AIDS . Although many people living with HIV are adhering well , others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy . Despite the importance of ART adherence , supportive interventions have generally not been implemented at scale . The objective of this review is to summarize the recommendations of clinical , research , and public health experts for scalable ART adherence interventions in re source ‐limited setting s. Methods : In July 2015 , the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in re source ‐limited setting s. This article summarizes that discussion with recent up date s. It is not a systematic review , but rather provides practical considerations for programme implementation based on evidence from individual studies , systematic review s , meta‐analyses , and the World Health Organization Consoli date d Guidelines for HIV , which include evidence from r and omized controlled trials in low‐ and middle‐income countries . Interventions are categorized broadly as education and counselling ; information and communication technology‐enhanced solutions ; healthcare delivery restructuring ; and economic incentives and social protection interventions . Each category is discussed , including descriptions of interventions , current evidence for effectiveness , and what appears promising for the near future . Approaches to intervention implementation and impact assessment are then described . Results and discussion : The evidence base is promising for currently available , effective , and scalable ART adherence interventions for re source ‐limited setting s. Numerous interventions build on existing health care infrastructure and leverage available re sources . Those most widely studied and implemented to date involve peer counselling , adherence clubs , and short message service ( SMS ) . Many additional interventions could have an important impact on ART adherence with further development , including st and ardized counselling through multi‐media technology , electronic dose monitoring , de central ized and differentiated models of care , and livelihood interventions . Optimal targeting and tailoring of interventions will require improved adherence measurement . Conclusions : The opportunity exists today to address and resolve many of the challenges to effective ART adherence , so that they do not limit the potential of ART to help bring about the end of AIDS Evidence from both epidemiological and experimental observations have fueled the belief that the high consumption of fruits and vegetables rich in carotenoids may help prevent cancer and heart disease in humans . Because of its well-documented antioxidant and antigenotoxic properties , the carotenoid beta-carotene ( betaCT ) gained most of the attention in the early 1980s and became one of the most extensively studied cancer chemopreventive agents in population -based trials supported by the National Cancer Institute . However , the results of three r and omized lung cancer chemoprevention trials on betaCT supplementation unexpectedly contradicted the large body of epidemiological evidence relating to the potential benefits of dietary carotenoids . Not only did betaCT show no benefit , it was associated with significant increases in lung cancer incidence , cardiovascular diseases , and total mortality . These findings aroused widespread scientific debate that is still ongoing . It also raised the suspicion that betaCT may even possess co-carcinogenic properties . In this review , we summarize the current data on the co-carcinogenic properties of betaCT that is attributed to its role in the induction of carcinogen metabolizing enzymes and the over-generation of oxidative stress . The data presented provide convincing evidence of the harmful properties of this compound if given alone to smokers , or to individuals exposed to environmental carcinogens , as a micronutrient supplement . This has now been directly verified in a medium-term cancer transformation bioassay . In the context of public health policies , while the benefits of a diet rich in a variety of fruits and vegetables should continue to be emphasized , the data presented here point to the need for consideration of the possible detrimental effects of certain isolated dietary supplements , before mass cancer chemoprevention clinical trials are conducted on human subjects . This is especially important for genetically predisposed individuals who are environmentally or occupationally exposed to mutagens and carcinogens , such as those found in tobacco smoke and in industrial setting Although pharmacologic treatment remains a critical element in the short- and long-term management of schizophrenia  , the past decade has been a challenging time in terms of real progress . Despite the introduction of several new medications as well as the conduct of larger and more diverse clinical trials , there remains considerable debate as to how far we have progressed in addressing some of the fundamental unmet needs in treating this disorder . A theme in this issue of Schizophrenia Bulletin addresses a number of topics in this context . Although the notion of careful , systematic , and critical summaries of all relevant r and omized controlled trials is not a new one , the Cochrane Schizophrenia Group is relatively young . Clive Adams , one of its founders , and colleagues provide the rationale and history of the group as well as review ing its methods and contributions . The Bulletin also carries a “ Cochrane Corner ” in each issue to alert the field to schizophrenia-related review s. Systematic meta-analyses are playing an increasingly important role in informing both the research agenda and clinical practice . The work of the Cochrane collaboration has been enormously valuable in this process . In recent years , the field of schizophrenia research has benefited from the application of various clinical trial method ologies to enhance the study of treatment outcomes and determine generalizability . Large effectiveness trials have provided data to exp and our knowledge base beyond that which is provided by traditional efficacy trials . Stroup and Geddes provide examples of each type of trial to illustrate their relative advantages and disadvantages . Within the context of different trial design s , Leucht et al provide an overview addressing critical aspects of trial design , potential population sampling bias , endpoint choices and definitions , quality of assessment s , data analysis and reporting , as well as , other potential sources of bias or confounds relevant to the interpretation of clinical trials data in schizophrenia . One of the most difficult challenges in the design , conduct , analysis , and interpretation of clinical trials is the problem of dropouts — those individuals who do not complete the trial , often for unknown reasons . A variety of statistical techniques have been developed and applied in order to address this issue ; however , none is entirely satisfactory . Rabinowitz and Davidov discuss the association of dropout and outcome in trials of antipsychotic medication and its implication s for strategies to address missing data . Another strategy to minimize dropouts in acute treatment trials would be to shorten the length of the trial , particularly when placebo control groups are included . Addressing this issue and drawing on recent meta- analysis suggesting that a substantial proportion of antipsychotic drug response occurs within the first 2 weeks , McMahon and colleagues present an exploratory analysis from short-term placebo controlled clinical trial data suggesting the potential feasibility of reducing the duration of such trials . Much more work needs to be done to determine the benefits and risks of such an approach , but this is a very valuable first step . In the final article , we provide a review of unanswered questions in the pharmacologic treatment of schizophrenia .  Despite numerous trials being conducted with antipsychotic medication , there are many clinical decisions that must be made on a day-to-day basis for which sufficient data are not available to provide an adequate evidence base . We hope that these articles will provide a snapshot of current challenges and opportunities for further progress in the design , conduct , and interpretation of psychopharmacologic trials in schizophrenia Differences in disease prevalence , clinical manifestations , and health outcomes exist between men and women . Sources for this variation range from biological differentiation at the cellular level to behavioral differences influenced by societal gender norms . Typically , biologically based differences between men and women are called sex differences , whereas gender differences describe health differences related , at least in part , to societal constructs of gender ( 13 ) . For example , biological events unique to women , such as pregnancy and menopause , are probably associated with sex differences in occurrence of certain conditions or in response to some medical therapies ( 48 ) . Gender differences probably exist in health-related perceptions and behaviors for women and men with medical conditions that are prevalent for both sexes ( for example , heart disease and chronic pain ) ( 9 –16 ) . Although sex and gender differences are theoretically distinct , they remain difficult to disentangle when differences between men and women in health outcomes and treatment effectiveness are being examined . For this reason , and for brevity , we hereafter refer to sex and gender differences collectively as sex effects . In the past 2 decades , recognition of the importance of sex effects for health outcomes and treatment heterogeneity has been growing . Beginning in 1993 , the National Institutes of Health has issued policies requiring the inclusion of women and minorities in all clinical research and trial design s with valid analysis of sex effects or differences between racial and ethnic groups ( 17 , 18 ) . Since then , the inclusion of women in clinical trials has increased ( 19 , 20 ) , and sex effects have been identified for medications , such as nicotine replacement therapy , analgesics , and aspirin ( 13 , 14 , 21 ) . Recently , sex effects in adverse reactions led to sex-specific dosage recommendations for a widely used sedative ( 7 ) . Despite this progress , representation of women in clinical studies remains inadequate for many conditions ( 22 ) . Further , published clinical trials infrequently report sex effects or discuss the appropriateness of sex-specific analyses ( 19 , 20 , 23 ) . To advance the clinical evidence base and improve health outcomes for women , clinical research must include adequate numbers of women , appropriately conduct sex-specific analyses , and consistently report sex effects . Systematic review s ( SRs ) are a key source of information for clinicians , research ers , and guideline panels . By synthesizing the overall body of evidence for key clinical and research questions , SRs could potentially make a unique contribution to the evaluation of sex effects . To our knowledge , however , the reporting of sex effects by SRs has not been previously examined . Here , we use evidence mapping to systematic ally evaluate the reporting of sex effects by SRs examining a diverse set of interventions for chronic conditions common to women ( that is , depression , diabetes , and chronic pain ) . Evidence mapping is an emerging approach that describes key characteristics of studies for a broad area of medicine ( 2426 ) . Our evidence map addresses the volume and characteristics of eligible SRs , including the representation of women in primary studies , whether and how review s reported sex effects , and findings about sex effects . Methods This work was part of a larger report for the Veterans Health Administration ( VHA ) Evidence -based Synthesis Program ( ESP ) . The complete technical report is available online ( www.hsrd . research .va.gov/publications/esp ) and includes additional information on our methods . We focused on SRs to determine the reporting of sex effects , provide high-level information about the volume of current clinical evidence , and summarize information about actual sex effects . Prioritization of Conditions for Inclusion We used forced-ranking prioritization ( 27 ) with our VHA stakeholders to determine our conditions of interest . These stakeholders included representatives from the Health Services Research & Development Center for the Study of Healthcare Innovation , Implementation and Policy ; Health Services Research & Development Women 's Health Research Network ; Women 's Health Research in the Office of Research & Development ; Women 's Health Services ; and Mental Health Services . We initially selected 34 conditions ( Appendix Table 1 ) based on disease prevalence in women , disease burden in women , availability and breadth of effective treatments for men or women , and women veterans ' priorities for gender-specific care . Stakeholders ranked this initial set of conditions , discussed the rankings , and reranked conditions that initially received intermediate priority rankings . After 2 rounds of iterative prioritization , the following conditions were selected : depressive disorders , type 2 diabetes mellitus , and chronic pain ( that is , chronic low back pain , fibromyalgia , and chronic knee pain due to osteoarthritis ) . Appendix Table 1 . Conditions Presented to Stakeholders for Prioritization * Data Sources and Search es In collaboration with an expert reference librarian , we search ed PubMed and Cochrane Data base of Systematic Review s to identify eligible SRs published after 1 October 2009 through 31 October 2014 for depression , 13 February 2015 for diabetes , and 27 February 2015 for chronic pain . Search strategies used Medical Subject Headings and free-text terms for the conditions of interest , eligible interventions , and SRs ( Appendix Table 2 ) . We restricted the search to the past 6 years because SRs are typically out date d within 5 years of publication ( 28 ) , and our goal was to describe the current state of the clinical literature . In addition to electronic search ing , we screened published review s of review s for eligible articles . Appendix Table 2 . Search Strategies Study Selection and Quality Assessment Eligible SRs evaluated interventions in several broad categories ( that is , medications , behavioral interventions , supervised exercise , and quality improvement or organizational interventions ) . We also included condition-specific interventions , such as bariatric surgery for diabetes . Review s that evaluated mixed conditions or multiple interventions must have reported results separately for at least 1 eligible condition or intervention . We included review s of interventions in any setting , with any type of active or inactive comparator , and with any duration of follow-up . Detailed inclusion and exclusion criteria are provided in Appendix Table 3 . Appendix Table 3 . Detailed Inclusion and Exclusion Criteria for Review Eligibility Two investigators screened citations for eligibility , and citations that were considered to be relevant by either person were retained for full-text review . Full-text articles were review ed by 2 investigators , and disagreements were resolved through discussion or adjudicated by a third person . Formal assessment of review quality was beyond the scope of this project . However , we noted whether review s originated from organizations known for high- quality review s ( that is , Cochrane Collaboration , Agency for Healthcare Research and Quality Evidence -based Practice Centers , and VHA ESP ) . For review s reporting sex effects , we also assessed industry funding and whether statistical power was considered . Data Abstract ion Data were abstract ed by 1 investigator and review ed by a second person . Disagreements were resolved by discussion or by a third review er . Abstract ed data included the analysis method ( that is , qualitative synthesis , meta- analysis , network meta- analysis , or individual-patient data [ IPD ] meta- analysis ) ; clinical conditions ; interventions ; main outcomes ; number and design of primary studies ( for example , r and omized , controlled trials [ RCTs ] or observational cohorts ) ; proportion of women in the included primary studies ; and if sex effects were part of the study aims , analysis plan , or results . For review s reporting sex effects , we also recorded the number of primary studies used for sex-specific analyses , effect estimates , and the method used ( for example , metaregression , subgroup analysis , or IPD meta- analysis ) . All eligible review s on depressive disorders and chronic pain conditions were fully abstract ed . All diabetes review s of nonpharmacologic interventions were also fully abstract ed . For eligible diabetes medication review s ( n= 120 ) , we applied an additional prioritization procedure before full abstract ion . We prioritized review s that examined multiple classes of medications or evaluated a single class of medications when 6 or fewer eligible review s were identified . For SRs evaluating a single class ( > 6 eligible review s were identified ) , we used additional prioritization criteria ( for example , the most recent review published in a high-impact journal or work done by an organization known for high- quality review s ) . The remaining unselected but eligible review s ( n= 58 ) had a keyword text search for sex effects and were fully abstract ed only when this search yielded positive results ( n= 13 ) . Data Synthesis and Analysis of SRs We grouped eligible review s by intervention category and described the overall volume of clinical literature for interventions addressing each condition of interest . We also determined the number of review s reporting sex effects and summarized these results . Time trends for the proportion of these review s were examined for depression and diabetes . Examination of Primary RCTs for Selected Interventions We anticipated that some interventions for each condition would have few or no eligible SRs that addressed sex effects . Thus , for a subset of interventions for each condition , we evaluated primary RCTs to determine the feasibility of conducting a future review to evaluate sex effects . Specifically , we examined  quality improvement interventions and psychotherapy for depression ; diet , physical activity , and culturally tailored psychoeducation for diabetes ; behavioral interventions for chronic low back pain ; and exercise interventions Xylitol research has been conducted since the early 70 ’s ; at the beginning of 2009 there were almost 500 PubMed - indexed papers on “ xylitol and dental ” . Xylitol research was initiated in Finl and , but nowadays the majority of papers are published by non-Finnish authors . Xylitol studies have been criticized mainly by European research ers . This criticism is reflected for example in the most recent textbook of cariology , Dental Caries – The Disease and its Clinical Management ( 2008 ) , used by students in all Nordic countries . It shows a figure with reduction in caries occurrence in the Turku Sugar Studies as an example , not of the effect of total substitution of dietary sugars with xylitol , but rather “ indicating the importance of removal of sugar from the diet , rather than starch , in caries control “ . Moreover , a frequently cited review in Caries Research in 2004 came to the conclusion that “ there is no evidence for a caries-therapeutic effect of xylitol”.1 Xylitol studies are easy to criticize especially by authors who have never been involved in field trials . For example , to avoid exchange of test products between children of the same class r and omisation has to be done by schools or school classes . This is rarely recognized by the critics of xylitol studies . In addition , it is hard to find volunteers to comply with 2–3 years chewing of a hard and tasteless gum base , which is the control often suggested for chewing gum trials . Polyols like maltitol and sorbitol are by no means inert and are thus not valid controls for xylitol . Fortunately , US dental experts have critically , but positively , conducted research and review ed the literature on xylitol.2–5 One consequence of practical problems associated with field trials is that in systematic review s of methods for caries control and prevention the strict exclusion criteria leave only few xylitol studies for evaluation . For example , the inclusion criteria for a Swedish systematic review on methods of caries prevention ( SBU ; www.sbu.se ) were so strict that hardly any recommendations concerning caries prevention could be made . This also applied to xylitol : according to the report , the evidence on the clinical efficacy for xylitol was inconclusive . In a critical evaluation of the SBU report , the following question was asked “ where does this leave the confused dental practitioner , who has to offer chairside advice to patients , but can not wait of further ( good- quality ) research to be conducted and published , providing a more solid evidence -base ? ” ( Stillman-Lowe , 2005 ) . On the other h and , xylitol has been recommended for use in caries control and prevention by several dental associations . Also the European Food Safety Authority evaluated the literature on xylitol in 2008 and came to the conclusion that “ xylitol chewing gum reduces the risk of caries in children ” . The cl aim had to be reformulated since chewing gum is not a medicine and can thus not be cl aim ed to reduce the risk of a disease , caries . In Europe , there is a strong interest not to give xylitol a better status than for other polyol sweeteners . Xylitol differs from other polyols as is obvious to all experts familiar with microbiology . Xylitol has beneficial effects on the oral flora not shared by other polyols . The evidence so far supports specific xylitol-effects on oral bacteria , but not on saliva .  Xylitol can not be metabolized by plaque bacteria , contrary to sorbitol and other 6-carbon polyols , and may thus favour mineralization . The accumulated evidence suggests that 1 ) mutans streptococci are the target organisms of xylitol in vivo , 2 ) mutans streptococci are reduced and stay on a lower level even during long-term xylitol consumption as long as the consumption lasts , 3 ) xylitol consumption reduces the accumulation of plaque , 4 ) xylitol consumed by mothers reduces the mother-child transmission of mutans streptococci and consequently , caries occurrence in their children,6,7 and 5 ) xylitol consumption reduces the risk of caries in children.4 In clinical trials on xylitol mostly chewing gum with high xylitol concentrations has been used . Studies with low daily doses of xylitol are known as a rule to fail to show any caries-preventive effects . To obtain beneficial xylitol-effects on mutans streptococci , on plaque and caries occurrence xylitol must be consumed three times or more per day , with a daily dose of 5–6 grams.4,7 When using chewing gums or pastilles , saliva stimulation always occurs due to chewing or sucking . Some authors have cl aim ed that the beneficial effects of xylitol are solely based on saliva stimulation and that all sugar-free gums are similar in this respect . In fact , in conditions where caries occurrence is high , even sorbitol gum can prevent caries.8 A recent study elegantly shows caries prevention with xylitol without any saliva stimulation . In this study fifteen-month-old children were given xylitol or sorbitol syrup with a syringe for 12 months.9 The xylitol syrup prevented  early childhood caries  effectively , while sorbitol had no effect . In spite of the abundant literature still more studies are needed on the action of xylitol . Biofilm models could be very useful in xylitol research . There is a clear need for properly design ed , r and omized , controlled , clinical trials to demonstrate 1 ) the feasibility of  xylitol prevention in different population s with different dietary and oral hygiene habits , 2 ) suitable vehicles to deliver xylitol , 3 ) the extent to which xylitol can be “ diluted ” with other polyols without losing the caries preventive effects , and 4 ) the minimum daily xylitol dose and frequency of xylitol are needed to obtain the expected xylitol-effects on mutans streptococci , plaque and most importantly , on caries occurrence . Clinical trials often aim to improve treatment methods . When several clinical trials give similar results , clinicians can be given treatment guidelines based on findings verified by research . In this way research serves the clinicians in treating patients according to evidence -based solid information . Systematic review s are currently required to up date guidelines for caries prevention . As such , critical evaluation of the existing literature is a positive goal , but if it leads to a situation where no treatment guidelines can be given , something is wrong . This also applies to xylitol studies . Though strict inclusion criteria prevent conclusions based on systematic review s of the literature , evidence -based treatment guidelines can still be given for the use of xylitol . Xylitol is a useful adjunct to traditional methods for caries control and prevention . Caries prevention with xylitol has been cl aim ed to be expensive , but if true primary prevention is obtained , as demonstrated in the mother-child study , 6,7 it may be worth it Non-alcoholic fatty liver disease ( NAFLD ) is the most common liver disorder in Western industrialized countries , affecting 20 - 40 % of the general population . Large population -based surveys in China , Japan , and Korea indicate that the prevalence of NAFLD is now 12 % to 24 % in population subgroups , depending on age , gender , ethnicity , and location ( urban versus rural ) . There is strong evidence that the prevalence of NAFLD has increased recently in parallel with regional trends in obesity , type 2 diabetes , and metabolic syndrome ; and that further increases are likely . The relationship between NAFLD , central obesity , diabetes , and metabolic syndrome is clearly evident in retrospective and prospect i ve Asian studies , but the strength of association with these metabolic risk factors is only appreciated when regional definitions of anthropometry are used . Pathological definition of NAFLD , particularly its activity and the extent of liver fibrosis , requires histological examination , but liver biopsy is often not appropriate in this disorder for logistic reasons . An alternative set of operational definitions is proposed here . Clinicians need guidelines as how best to diagnose and manage NAFLD and its associated metabolic disorders in countries with scant healthcare re sources . The Asia-Pacific Working Party ( APWP ) for NAFLD was convened to collate evidence and deliberate these issues . Draft proposals were presented and discussed at Asia-Pacific Digestive Week at Cebu , Philippines , in late November 2006 , and are published separately in this issue of the Journal as an Executive Summary . The present document review s the reasoning and evidence behind the APWP-NAFLD proposals for definition , assessment , and management of NAFLD in the Asia-Pacific region BACKGROUND Although previous studies have linked intake of sugars with incidence of cancer and other chronic diseases , its association with mortality remains unknown . OBJECTIVE We investigated the association of total sugars , added sugars , total fructose , added fructose , sucrose , and added sucrose with the risk of all-cause , cardiovascular disease , cancer , and other-cause mortality  in the NIH-AARP Diet and Health Study . DESIGN The participants ( n = 353,751 ) , aged 50 - 71 y , were followed for up to 13 y. Intake of individual sugars over the previous 12 mo was assessed at baseline by using a 124-item NIH Diet History Question naire . RESULTS In fully adjusted models ( fifth quartile compared with first quartile ) , all-cause mortality was positively associated with the intake of total sugars [ HR ( 95 % CI ) : 1.13 ( 1.06 , 1.20 ) ; P-trend < 0.0001 ] , total fructose [ 1.10 ( 1.04 , 1.17 ) ; P-trend < 0.0001 ] , and added fructose [ 1.07 ( 1.01 , 1.13 ) ; P-trend = 0.005 ) in women and total fructose [ 1.06 ( 1.01 , 1.10 ) ; P-trend = 0.002 ] in men . In men , a weak inverse association was found between other-cause mortality and dietary added sugars  ( P-trend = 0.04 ) , sucrose ( P-trend = 0.03 ) , and added sucrose ( P-trend = 0.006 ) . Investigation of consumption of sugars by source showed that the positive association with mortality risk was confined only to sugars from beverages , whereas the inverse association was confined to sugars from solid foods . CONCLUSIONS In this large prospect i ve study , total fructose intake was weakly positively associated with  all-cause mortality in both women and men , whereas added sugar , sucrose , and added sucrose intakes were inversely associated with other-cause mortality in men . In our analyses , intake of added sugars was not associated with an increased risk of mortality . The NIH-AARP Diet and Health Study was registered at clinical trials.gov as NCT00340015
We conclude based on high quality evidence from r and omized controlled trials ( RCT ) , systematic review s and meta-analyses of cohort studies that singling out added sugars as unique culprits for metabolically based diseases such as obesity , diabetes and cardiovascular disease appears inconsistent with modern , high quality evidence and is very unlikely to yield health benefits .
While it is prudent to consume added sugars in moderation , the reduction of these components of the diet without other reductions of caloric sources seems unlikely to achieve any meaningful benefit
Added sugars are a controversial and hotly debated topic .
Consumption of added sugars has been implicated in increased risk of a variety of chronic diseases including obesity , cardiovascular disease , diabetes and non-alcoholic fatty liver disease ( NAFLD ) as well as cognitive decline and even some cancers .
Support for these putative associations has been challenged , however , on a variety of fronts .
The purpose of the current review is to summarize high impact evidence including systematic review s , meta-analyses , and r and omized controlled trials ( RCTs ) , in an attempt to provide an overview of current evidence related to added sugars and health considerations .
This paper is an extension of a symposium held at the Experimental Biology 2015 conference entitled " Sweeteners and Health : Current Underst and ings , Controversies , Recent Research Findings and Directions for Future Research " .