Health Impact of Alcohol Use in the United States

Health Impact of Alcohol Use in the United States | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Health Impact of Alcohol Use in the United States Kevin Shield, Katherine Keyes, Priscilla Martinez, Adam J. Milam, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4224612/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Alcohol is consumed by an estimated 137.4 million people in the United States 12 years of age and older, and, as a result, is estimated to have caused about 140 thousand deaths among people 20 to 64 years of age each year from 2015 up to and including 2019. Methods The proposed proposed review of the evidence on alcohol’s impact to health aims to produce conclusions to inform the Dietary Guidelines for Americans, 2026–2030 . A multi-method approach will be utilized to formulate conclusions on (i) weekly (i.e., average) thresholds to minimize long-term and short-term risks of morbidity and mortality, (ii) daily thresholds to minimize the short-term risk of injury or acute illness due to per occasion drinking, (iii) alcohol use among vulnerable populations (e.g., pregnant women), and (iv) situations and circumstances that are hazardous for alcohol use. To inform expert discussions, this project will also include a systematic review of existing low-risk drinking guidelines, a systematic review of meta-analyses which examine alcohol’s impact on key attributable disease and mortality outcomes, and of estimates of the lifetime absolute risk of alcohol-attributable mortality and morbidity based on a person’s sex and average level of alcohol use. The preliminary conclusions produced as a result of this project will undergo public consultation, and data from these consultations will be analyzed using both quantitative and qualitative methods. The results of the public consultations will be used to further revise and refine the project’s conclusions. Discussion This project will establish a scientific consensus concerning alcohol’s impact on health. This consensus is imperative for informing the upcoming Dietary Guidelines for Americans, 2026–2030 , and for better informing individuals about the health risks associated with alcohol use. Alcohol Guidelines Public Health Risk United States Figures Figure 1 Figure 2 BACKGROUND Alcohol is a psychoactive substance used by about 137.4 million people residing in households in the United States who are 12 years of age and older ( 1 ). Indeed, based on a 2022 nationwide representative survey, 48.7% of people 12 years of age and older consumed alcohol in the past month, 61.2 million people (44.5 percent of current drinkers) engaged in binge drinking in the past month, and 29.5 million people (10.5 percent of people 12 years of age and older) had an alcohol use disorder ( 1 ). Alcohol use has been shown to be linked to over 200 health conditions as defined by the three-digit codes of the International Statistical Classification of Diseases and Related Health Problems, 10th revision, (ICD-10) ( 2 ), including infectious diseases, malignant neoplasms, cardiovascular diseases, digestive diseases, mental and behavioral disorders, metabolic disorders, and injuries. At the population level, from 2015 to 2019, alcohol consumption in the United States among people 20 to 64 years of age caused an estimated annual mean of 140 thousand deaths (97 thousand deaths among men and 43 thousand deaths among women), representing 5.0% of all deaths among this age group (6.8 of all deaths among men, and 3.2 of all deaths among women) ( 3 ). National drinking guidelines usually have prescribed specific guidance on (i) thresholds (usually expressed as a maximum number of drinks per week or drinks per day) to minimize the relative long-term and short-term risks of serious morbidity and mortality caused by the consumption of alcohol over a number of years (e.g., liver disease, some cancers), (ii) per occasion thresholds to minimize the short-term risks of injury or acute illness due to per occasion consumption, (iii) consumption among vulnerable populations (e.g., youth and pregnant women (see ( 4 )), and (iv) situations and circumstances that are particularly hazardous (e.g., driving ( 5 , 6 )). In order to provide information on the health impact of alcohol use, the U.S. Department of Agriculture and the U.S. Department of Health and Human Services issued the Dietary Guidelines for Americans, 2020–2025 which provided health-based recommendations regarding alcohol use ( 7 ). (Similar documents have been published by other countries ( 8 – 13 )). The United States’ recommendations provide guidance on drinking initiation, per occasion alcohol use, and which individuals should not consume alcohol, namely: “If adults age 21 years and older choose to drink alcoholic beverages, drinking less is better for health than drinking more.” “To help Americans move toward a healthy dietary pattern and minimize risks associated with drinking, adults of legal drinking age can choose not to drink or to drink in moderation by limiting intakes to 2 drinks or less in a day for men and 1 drink or less in a day for women, on days when alcohol is consumed.” “There are also some people who should not drink at all, such as if they are pregnant or might be pregnant; under the legal age for drinking; if they have certain medical conditions or are taking certain medications that can interact with alcohol; and if they are recovering from an alcohol use disorder or if they are unable to control the amount they drink.” At the individual level, the impact of alcohol use on health is complex and multifactorial. For example, with respect to injuries and the majority of diseases, alcohol use has no protective effect on health at any level of consumption ( 14 , 15 ). For ischemic heart disease and ischemic stroke, the health effects of low-level or moderate alcohol consumption have been mixed ( 16 ); however, for people who engage in binge drinking (i.e., consuming 5 and 4 standard drinks (14 grams of ethanol) or more during at least one drinking occasion for men and women, respectively, alcohol is thought to have detrimental health effects ( 17 , 18 ). Furthermore, with respect to diabetes, there is thought to be a protective effect on disease occurrence and mortality for women who consume low amounts of alcohol ( 19 ). Due to the health impacts of alcohol use at the population level in the United States, there is a need for consumption recommendations which are grounded in science, focused on public health, and consider the complexities of how alcohol use impacts health generally, and impacts the health of vulnerable populations specifically. The Dietary Guidelines for Americans, 2020–2025 , which were published in 2020, aimed to provide consumption recommendations to Americans; the mandate of the U.S. Department of Agriculture and the U.S. Department of Health and Human Services is to update this guidance every five years to keep abreast of current alcohol research. Accordingly, the proposed review of the evidence on alcohol’s impact on health will produce conclusions to assist the Interagency Coordinating Committee for the Prevention of Underage Drinking to inform the Dietary Guidelines for Americans, 2026–2030 . METHODS The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach will be utilized to formulate conclusions on how alcohol impacts health ( 20 – 22 ). Project oversight will be performed by the U.S. Department of Agriculture and the U.S. Department of Health and Human Services (who formulated the project’s “Terms of Reference”). Furthermore, to achieve the project’s “Terms of Reference”, a Technical Advisory Panel has been formulated to oversee the project. The project will determine the health impacts caused by ethanol in alcoholic beverages, and, therefore, will not distinguish between harms caused by beer, wine, spirits, and other alcoholic beverages. Harms caused by beer, wine, spirits, and other alcoholic beverages are based mainly on ethanol content, regardless of the form in which the ethanol is consumed, with the exception of alcohol poisonings which are caused predominately by the consumption of spirits ( 23 ) and some other forms of unintentional injury where there is evidence of a higher risk due to the consumption of spirits ( 24 ). A systematic review of existing guidelines on alcohol and health as well as individual modelling projects will be performed to generate conclusions on (i) weekly thresholds to minimize long-term and short-term risks of morbidity and mortality, (ii) per occassion thresholds to minimize the short-term risks of injury or acute illness due to per occasion drinking, (iii) alcohol use among vulnerable populations, and (iv) situations and individual circumstances that are hazardous. An overview of the proposed methodology and data sources are outlined in Table 1 and the supplemental material. Table 1 Methodology and data sources Conclusions on alcohol’s impact on health Methodology used to reach conclusions Underlying data sources Weekly / daily thresholds to minimize long-term and short-term risks of morbidity and mortality Conclusions based on nominal group interviews Lifetime risk of alcohol-attributable mortality and morbidity at different drinking levels Per occasion thresholds to minimize the short-term risks of injury or acute illness due to per occasion drinking Conclusions based on nominal group interviews Systematic review of meta-analyses which summarize how drinking patterns affect the risk of disease and injury occurrence Results from a reanalysis of United States’ emergency room case-cross-over studies Results from roadside survey studies Alcohol use among vulnerable populations Conclusions based on nominal group interviews Systematic review of previously published guidelines Situations and individual circumstances that are hazardous Systematic review of previous guidelines on alcohol and health A 2016 systematic review highlighted differences in alcohol guidelines across 37 countries ( 8 ), but did not assess their scientific quality or the methodologies used to produce these guidelines. Therefore, this review is of limited value for the development of future guidelines. Accordingly, a systematic literature search of country-level guidance on alcohol and health will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and will be preregistered with PROSPERO ( 25 , 26 ). Guidance on alcohol and health will be identified through websites of countries' health ministries using an internet search (i.e., ‘[country] AND health ministry’), and/or using the World Health Organization’s Global Information System on Alcohol and Health ( 27 ). A list of all country names will be obtained from the World Health Organization ( https://www.who.int/countries ). In addition to searching websites of countries' health ministries, a peer-reviewed literature search for guidance documents will be performed. Articles will be identified through a systematic search of PubMed, PsycInfo, and Web of Science based on keywords and subject headings. As an example, the search strategy for PubMed is outlined in Table S7 (see supplemental material). Searches will be piloted and refined with the aid of a research librarian. No publication year or language restrictions will be applied. References contained in the articles included will be examined for relevant publications. The processes used for the screening of articles, data extraction, and standardization are outlined in the supplemental material (see Table S8). Each guideline on alcohol and health will be evaluated according to its methodological rigor; the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument is the most commonly used guideline appraisal and consistency evaluation tool in the GRADE protocol and will be used here ( 28 , 29 ). The review will summarize advice on (i) weekly thresholds to minimize long-term and short-term risks of morbidity and mortality, (ii) daily thresholds to minimize the short-term risks of injury or acute illness due to per occasion drinking, (iii) vulnerable populations, and (iv) situations and individual circumstances that are hazardous. Collecting and generating evidence on weekly thresholds to minimize health risks Two methods can be used to generate evidence on weekly thresholds to minimize health risks associated with different levels of average alcohol consumption: (i) the examination of all-cause absolute risk curves from cohort studies (which include deaths from all causes, including conditions from which a causal relationship with alcohol use has not been determined), and (ii) the modelling of lifetime all-cause absolute alcohol-attributable mortality and morbidity risk curves by combining data on cause-specific relative risks with corresponding data on absolute mortality risks for lifetime abstainers. Based on the positives and negatives of each method, it was decided to proceed with the modelling of lifetime all-cause absolute alcohol-attributable mortality and morbidity risk curves (i.e., method (ii)) to align with the current practices of the Centers for Disease Control and Prevention, the World Health Organization, and the Institute for Health Metrics and Evaluation for estimating the burden of disease attributable to alcohol use ( 30 – 33 ), and with other recently released guidance documents on alcohol and health ( 11 – 13 , 34 ). Mathematical modelling will be used to estimate the lifetime risk of death and disability for different levels of average alcohol consumption. The risk curves generated will be based on the average amount of pure alcohol (i.e., ethanol). “People who consumed alcohol” will be defined as those individuals who consumed at least one standard drink (14 grams of alcohol) in the past year. The mathematical modelling will specifically examine the following outcomes: deaths, premature deaths (i.e., deaths that occur among those < 70 years of age), years of life lost (YLL), years lived with disability (YLD: a measure of disease occurrence and the disability caused by the disease), disease and injury incidence, and disability adjusted years of life lost (a combination of both YLL and YLD). The inclusion of diseases and injuries in the modelling of alcohol-attributable deaths and disability will be based on three criteria: (i) the disease or injury has to be causally related to alcohol use, (ii) a dose-response risk function needs to be available for the risk relationship between alcohol consumption (measured in grams per day) and the disease or injury of interest, and (iii) either death or disability needs to be measured specifically for the disease or injury causally related to alcohol use. Multiple data sources will be used to establish causality for this review. Causality can be assumed in all causes of death that are solely (100%) attributable to alcohol use (e.g., alcoholic cardiomyopathy). Furthermore, this review will use information from the World Health Organization’s Global Status Report on Alcohol and Health (GSRAH) ( 30 ), the Institute for Health Metrics and Evaluation’s Global Burden of Disease study ( 28 ), and the World Cancer Research Fund’s (WCRF’s) Continuous Update Project ( 35 – 37 ), all of which have assessed which diseases and injuries are causally related to alcohol consumption. A sensitivity analysis will be performed in which causality will be based on conditions included in the Alcohol-Related Disease Impact application of the Centers for Disease Control and Prevention ( 38 ). Systematic Review of Meta-analyses This study also aims to conduct a systematic review of all relevant meta-analyses that have investigated diseases causally associated with alcohol use. Relative Risk (RR) estimates for each included disease category and injury will be obtained from systematic reviews identified in the evidence review process. The RRs in the reviews will have used people who are lifetime abstainers as a reference group. In cases where lifetime abstainers were not the reference group, these RRs will be rescaled so that the lifetime abstainers are the reference group. PubMed (including MEDLINE and Life Science Journals) and Web of Science will be searched for relevant articles based on keywords and subject headings. The search strategy for MEDLINE, as an example, is outlined in Table S9 in the supplemental matrial. Searches will be piloted and refined with the aid of a research librarian. No language restrictions will be applied. A publication restriction of 2010 and later will be applied to ensure that only recent summaries of the epidemiological evidence are included in the review. References contained in the articles included will be examined for relevant publications. Subject experts will be contacted to identify relevant publications. Previous systematic reviews, the International Agency for Research on Cancer Monographs, and the WCRF’s Continuous Update Project reports will be searched for relevant publications. All systematic reviews will be evaluated for quality using the criteria from A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) and from the Risk of Bias in Systematic Reviews (ROBIS) tool ( 39 , 40 ). Quality assessments will consider study design and adjustments for confounding factors, among other criteria. In addition these quality assessments will take into account factors specific to alcohol epidemiological studies. For example, biases in exposure and outcome measurements, such as the use of current abstainers instead of lifetime abstainers as the risk reference group (i.e., allowing the misclassification of former drinkers as lifetime abstainers), and how representative the cohorts are of the US general population ( 41 ). The systematic review will be pre-registered with PROSPERO, and conducted in accordance with the PRISMA guidelines ( 42 ). Selection of Meta-analyses Meta-analyses used in the modelling process will be selected by panels of nominal group interview experts in the distinct areas of (i) cancer, (ii) cardiovascular diseases, (iii) digestive conditions, (iv) neurological disorders, (v) infectious diseases, and (vi) injuries who will be consulted to determine the RR estimates for each condition considered to be causally related to alcohol use. The sampling frame of experts will be decided based on the authors who have published the largest number of first and last author publications concerning the above-noted disease areas (as determined by performing a PubMed Search) in the past 10 years. These authors will be asked to participate in the nominal group interview panels. Quota sampling will also be used to establish nominal group interview panels which ensure diversity and representation based on geographic location, sex, race and ethnicity, which will be reported by the potential participants before they are included in the nominal group interview panels. Specifically, the following parameters will be established: (i) a minimum of 90% of the experts will be United States-based, (ii) a minimum of 40% of the experts will identify as female, with a goal of 50%, and (iii) no more than 80% of the experts will be non-Hispanic White, with a goal of no more than 60% of participants being non-Hispanic White. Experts will be required to have no potential conflicts of interest. Once the panels of experts have been established, a nominal group process will be used to determine the most appropriate meta-analyses to use in the modelling study. The nominal group interview allows for the selection of meta-analyses avoiding group think (as compared to group interviews), and reduces random error in decision making by increasing the number of people whose opinions are considered (e.g., ( 43 )). All panels will also provide input on the magnitude of the underreporting of alcohol consumption in medical observation studies, as well as input on vulnerable populations and situations and individual circumstances where the consumption of alcohol is hazardous. In the first round, each expert will be provided with the results of the preregistered systematic scoping review, and will be asked to provide free-text comments on the interpretation of these studies. When necessary, experts will be contacted to clarify their answers. The project team will analyze answers to identify potential underlying patterns and prepare a draft consensus position. Each expert will also be asked the degree to which they hypothesize alcohol use to be misestimated in population surveys (what fraction is due to spillage and wastage, and what fraction is due to survey and response biases) and in cohort studies. In the second round of interviews, based on feedback regarding the results of round 1, the consolidated information will be provided to the expert participants. During these interviews, experts will interact and clarify their positions in small group virtual meetings. At the end of the second round of interviews, all experts will be asked to complete a questionnaire which will be used to build a consensus on which meta-analyses to include in the modelling study. In the event that this process proves too time consuming, selection of meta-analysis will be modified and streamlined. The streamlined approach will involve selecting the meta-analysis for modeling based on its performance on the AMSTAR 2 and ROBIS tools, prioritizing the study with the least potential risk of bias. Data sources: Mortality and Alcohol Exposure A comparative risk method (i.e., the systematic evaluation of changes in population health that would be avoided in the absence of a risk factor) will be used to estimate the alcohol-attributable burden of disease. For this method, the reference group of lifetime abstainers will be utilized − thus determining the number of deaths and the burden of disability that would not occur if alcohol consumption was eliminated (see: ( 11 – 13 , 44 )). Lifetime risk curves will be based on an exposure of average grams of pure alcohol (i.e., ethanol) consumed per week. Data on the number of deaths that occurred in the United States by age, sex, and cause will be obtained from the National Vital Statistics System ( 45 , 46 ). Data on population by age and sex will be obtained from the Census Bureau of the United States ( 47 ). Data on disease incidence and YLD will be obtained from the Institute for Health Metrics and Evaluation’s Global Burden of Disease study ( 48 ). Life tables by sex will be obtained from the Centers for Disease Control and Prevention, National Center for Health Statistics ( 49 ). Relative risks from the systematic review of meta-analyses will be combined with estimates of the risk of mortality and morbidity for lifetime abstainers to estimate lifetime risk curves. A comparative risk assessment methodology will be used to estimate the risk of mortality and morbidity for lifetime abstainers (see supplemental material). Lifetime risk curves will be calculated by estimating alcohol-attributable mortality and morbidity risk by cause, age, and sex. The life-year specific alcohol-attributable mortality risks will be multiplied by the YLL for each cause of death. The lifetime risk curves will also account for competing causes of death (i.e., deaths which occur that are not attributable to alcohol use). Seesupplemental material for further details regarding the lifetime risk methodology. The lifetime risk curves for alcohol-attributable mortality and morbidity risks will be provided to members of all nominal group interview panels. We will then use the nominal group interview process, including all members from all panels, to establish conclusions on weekly and/or daily alcohol use thresholds. Collecting and generating evidence on per occasion alcohol use thresholds to minimize short-term health risks Per occasion alcohol use is based on consumption during particular times or occasions, (as compared to average consumption which is determined by dividing total consumption by time). As such, per occasion consumption is related to consumption patterns, and provides a proxy measure for blood alcohol concentrations that might be achieved based on a particular level of per occasion consumption. High per occasion consumption resulting in high blood alcohol concentrations is strongly associated with “acute” disease processes such as injuries ( 50 ), but also is associated with the risk of infectious diseases ( 51 ), breast cancer ( 52 ), ischemic heart disease and ischemic stroke ( 53 ), diabetes ( 54 ), epilepsy ( 55 , 56 ), and liver cirrhosis ( 57 ). Multiple sources of data will be used to reach conclusions on the health impacts of per occasion alcohol use, namely: (i) results from the systematic review of meta-analyses and systematic reviews which summarize how drinking patterns affect the risk of disease and injury occurrence, (ii) results from a reanalysis of United States’ emergency room case-cross-over studies which examined the relationship between alcohol use and injury occurrence ( 50 ), and (iii) results from roadside survey studies where the blood alcohol content of road injury decedents was compared to that of drivers randomly selected from the same road on the same day and at the same hour as the fatal crash case ( 58 , 59 ). Based on these data sources, the expert groups will reach public health conclusions on the maximum number of drinks people should consume during one drinking occasion. The nominal group interviews will follow a two round structure that will also be used to determine the best RR functions to be used in the modelling of the health impacts of alcohol use. Collecting and generating evidence on the effects of alcohol use among vulnerable populations, and situations and individual circumstances where consuming alcohol is hazardous The planned study will build upon previous guidelines (identified through the previously noted systematic review) using nominal group interviews to provide conclusions with respect to evidence on the effects of alcohol use among vulnerable populations (e.g., pregnant persons, underage youth), and situations and individual circumstances where consuming alcohol is hazardous. The experts selected from the nominal group surveys will review evidence of individuals in vulnerable populations or who are subject to situations and individual circumstances where consuming alcohol is hazardous to determine if these considerations should be included in the conclusions of the study. In addition, experts who are part of the nominal group interviews will be invited to identify vulnerable populations and situations and individual circumstances which have not been previously noted in any other guidelines, but where current research supports that these vulnerable populations and/or situations and individual circumstances should be added to alcohol and health guidance documents, as well as any relevant peer-reviewed research documents which support their addition. The structure of these nominal group interviews will follow a two round structure that will also be used to determine the best RR functions to be used in the modelling of the health impacts of alcohol use. Collecting and generating evidence on the public’s understanding and reaction to conclusions on alcohol consumption and health To understand how conclusions regarding the health impacts of alcohol use align with the alcohol consumption of the general public, we will examine alcohol use in the general population using data from the National Alcohol Survey, National Survey on Drug Use and Health (NSDUH), National Health Interview Survey (NHIS), The National Epidemiologic Survey on Alcohol and Related Conditions - III (NESARC-III), and Behavioral Risk Factor Surveillance System (BRFSS) in order to obtain data on alcohol exposure in the United States (see Tables S1 to S6 in supplemental materal). These population surveys, which have differing sampling frames, response rates, and validation of self-reporting of alcohol use, provide comprehensive data on alcohol consumption patterns and allow estimations of the prevalences of different levels of alcohol use in the population. To gain an understanding of the public’s understanding and reaction to the conclusions on alcohol and health produced by this project, we will engage in public consultations using a mixed methods (quantitative and quantitative) approach. Public consultation recruitment will be performed using a convenience sampling methodology. Specifically, the consultation process will be promoted through institutional websites, mass emails, social media, and national and regional digital news media advertisements. All residents of the United States will be eligible to participate. Individuals who do participate will be asked categorical and open-ended questions (in English) about: their demographics, including geographic location; their profession; their current sources of information on health and, more specifically, on the impacts of alcohol consumption on health; current and previous health conditions; their awareness of the Dietary Guidelines for Americans, 2020–2025 ; their alcohol use and whether they are trying to follow the alcohol consumption guidance in the Dietary Guidelines for Americans, 2020–2025 and their reasons for following or not following the guidelines; their requirements for and expectations of the Dietary Guidelines for Americans, 2026–2030 ; what information they found useful about the project’s conclusions on alcohol and health; and what challenges they had in interpreting the project’s conclusions on alcohol and health. Aggregate information on the demographics of participants will be examined, published and compared to United States Census data to assess whether participants in the consultation process are representative of the general population ( 47 ). A thematic analysis will be performed on responses to open-ended questions to identify common themes between respondents’ answers to each of the questions. As the information obtained from an analysis of the findings of the consultation process is to be used to revise and refine the research conclusions, both a semantic and latent coding approach and analysis will be employed. Furthermore, to analyse the qualitative data, Braun and Clarke's six phases of thematic analysis approach will be utilized ( 60 ). DISCUSSION Given the magnitude of the burden of disease caused by alcohol use in the United States, it is imperative to provide up-to-date public health information on the health consequences of alcohol use. The Dietary Guidelines for Americans, 2026–2030 represent an opportunity to provide the public with updated information on how alcohol use impacts health. The information derived from the project will provide conclusions on alcohol and health to directly inform the Dietary Guidelines for Americans, 2026–2030 . The proposed project differs from the project used to inform the Dietary Guidelines for Americans, 2020–2025 in numerous appreciable ways ( 7 ). First, the proposed project will include many new components, including a systematic review of other low-risk drinking guidelines, public consultations, and arriving at decisions through the use of nominal group interviews of systematically chosen panels of scientific experts. The use of nominal group interviews is a particularly important improvement on previous efforts which informed the Dietary Guidelines for Americans, 2020–2025 , as this project relies on independent judgements of numerous experts, which previous research shows can vary over relatively short time spans, between experts, and within an individual expert due to systematic and random error ( 61 ). Second, with regards to assessing the impact of average alcohol intake on health, the 2020 Dietary Guideline Advisory Committee’s systematic review focused on relationships between alcohol and all-cause mortality. As previously mentioned, the Centers for Disease Control and other organizations agree that modelling risk curves using a cause-specific approach is more accurate than using all-cause mortality risk estimates from cohort studies. This is mainly due to the fact that all-cause mortality RRs are estimated based on large, non-representative cohort studies which are over-representative of the middle class and include a number of causes of death. Indeed, deaths caused by cardiovascular diseases are overrepresented in such cohorts, and individuals with risk factors which synergistically interact with alcohol use (such as tobacco smoking and obesity) are under-represented ( 62 , 63 ). The use of cause-specific RRs when modelling lifetime alcohol-attributable mortality and morbidity will avoid this problem as it utilizes death data from the United States. Furthermore, the use of all-cause mortality risk curves is susceptible to a greater degree of confounding compared to a cause-specific approach. The use of cause-specific RRs when modelling lifetime alcohol-attributable mortality and morbidity will only be susceptible to confounding for causes of death which are considered casually related to alcohol, whereas cohort studies which assess the risk relationship between alcohol use and all-cause mortality are susceptible to confounding from all causes of death. The success of the Dietary Guidelines for Americans, 2026–2030 will depend upon the conclusions of this review, the dissemination and clarity of the guidelines, and upon the American public’s knowledge of how much beer, wine, or spirits constitutes a standard drink. The lack of knowledge of what constitutes a standard drink, especially compared to what constitutes a standard pour at home or at a restaurant or bar, may impede the effectiveness of the Dietary Guidelines for Americans, 2026–2030 in conveying the health impact of alcohol use. For example, a systematic review published in 2017 found that of 17 published studies comparing a standard pour (alcoholic beverages were poured by the participant) with a standard drink, 11 studies reported overpouring, one study reported evidence of underpouring, and six studies showed evidence of both over- and underpouring, with under- and overpouring dependent upon gender, drinking history, and type of alcoholic beverage ( 64 ). Further, while information on the impact of alcohol use on health may promote people’s desire to change their alcohol consumption, additional tools may be needed to actively promote changes in alcohol use, and to maintain such reductions. First, people who are heavy continuous drinkers may experience withdrawal symptoms when reducing their alcohol use, with these symptoms being potentially life threatening ( 65 ). Such individuals should not reduce their alcohol use without first consulting a physician. For people who do not experience withdrawal when reducing their alcohol use, tools are available to assist in facilitating goal setting, to aid people in developing specific strategies for change, and to recognize situations and triggers that have frequently led in the past to alcohol use or hazardous drinking ( 66 ). Accordingly, from a public health perspective, there is a need to help the public in obtaining, and healthcare systems in providing, tools to assist people in changing their alcohol use. Limitations There are multiple limitations to the proposed project. First, the evidence review, with few exceptions of short term outcomes, will not capture randomized control trials. Thus, the included studies will be observational. Although observational studies inherently may be exposed to threats to their validity, including confounding and selection bias, these studies will be valuable in providing needed information for assessing the outcomes resulting from alcohol consumption. Moreover, there is increasing acknowledgment that causal effects may be estimated using observational studies ( 67 , 68 ). Second, the outcomes focused upon in the current update will be limited to health conditions that result in mortality and morbidity. Numerous adverse health outcomes and social harms will not be directly incorporated. Third, due to the use of evidence examining and reporting population averages, it is important to note that the conclusions arising from the study will not necessarily be tailored to the individual and will not encapsulate other risk and protective factors which influence the use of alcohol and its related outcomes. For example, while studies have shown that consuming one drink a day is sufficient to increase the risk of liver cirrhosis ( 69 ), in the absence of other risk factors, consuming one drink a day may be insufficient to cause liver cirrhosis from a pathological standpoint. However, in the presence of other risk factors, such as obesity or Hepatitis B or C infection, alcohol use may further the progress of liver disease leading to cirrhosis or death ( 70 , 71 ). CONCLUSION Alcohol use causes a substantial amount of harm in the United States, both at the population level and at the individual level. As such, there is a need for public health guidance documents on alcohol and health. Accordingly, the proposed project will build upon the 2020 Dietary Guideline Advisory Committee’s report by establishing scientific consensus on the conclusions of peer-reviewed literature concerning alcohol’s impact on health. Abbreviations AGREE Appraisal of Guidelines for Research and Evaluation AMSTAR 2 A Measurement Tool to Assess Systematic Reviews GSRAH Global Status Report on Alcohol and Health GRADE Grading of Recommendations, Assessment, Development and Evaluation ICD-10 International Statistical Classification of Diseases and Related Health Problems, 10th revision PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses ROBIS Risk of Bias in Systematic Reviews RR Relative Risk YLD years lived with disability YLL years of life lost WCRF World Cancer Research Fund Declarations Ethics approval and consent to participate: Not applicable Consent for publication: Not applicable Availability of data and materials: Not applicable Competing interests: None to declare Funding: Funding for this manuscript was provided by Syergy Enterpises Inc. Authors' contributions: KS: was involved in study conceptualization, design of the work, drafted the manuscript, and substantively revised the manuscript. KK: was involved in study conceptualization, design of the work, and substantively revised the manuscript. PM: was involved in study conceptualization, design of the work, and substantively revised the manuscript. AJM: was involved in study conceptualization, design of the work, and substantively revised the manuscript. JR: was involved in study conceptualization, design of the work, and substantively revised the manuscript. TSN: was involved in study conceptualization, design of the work, and substantively revised the manuscript. All authors read and approved the final manuscript. Acknowledgements: We would like to thank Dr. Alicia Sparks for her contributions to the protocol and her feedback on the revised protocol. Conflict of Interest declaration: This study is funded by the United States’ Substance Abuse and Mental Health Services Administration References Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2022 National Survey on Drug Use and Health (HHS Publication No. PEP23-07-01-006. NSDUH Series H-58. Rockville, USA; 2023. Rehm J, Gmel Sr GE, Gmel G, Hasan OS, Imtiaz S, Popova S, et al. The relationship between different dimensions of alcohol use and the burden of disease—an update. Addiction. 2017;112(6):968–1001. Esser MB, Leung G, Sherk A, Bohm MK, Liu Y, Lu H, Naimi TS. Estimated deaths attributable to excessive alcohol use among US adults aged 20 to 64 years, 2015 to 2019. JAMA Netw open. 2022;5(11):e2239485–e. National Health Service. Drinking alcohol while pregnant: National Health Service. 2023 [ https://www.nhs.uk/pregnancy/keeping-well/drinking-alcohol-while-pregnant/ . 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Why does society accept a higher risk for alcohol than for other voluntary or involuntary risks? BMC Med. 2014;12:189. Department of Health [United Kingdom]. UK Chief Medical Officers’ Low Risk Drinking Guidelines. London, UK: Department of Health [United Kingdom]; 2016. Santé publique France. Alcool et santé: améliorer les connaissances et réduire les risques. France: Saint-Maurice; 2019. Alcohol Guidelines Project Team. Australian guidelines to reduce health risks from drinking alcohol. Canberra: Commonwealth of Australia; 2020. Taylor B, Irving H, Kanteres F, Room R, Borges G, Cherpitel C, et al. The more you drink, the harder you fall: a systematic review and meta-analysis of how acute alcohol consumption and injury or collision risk increase together. Drug Alcohol Depend. 2010;110(1–2):108–16. Rehm J, Gmel GE, Sr., Gmel G, Hasan OSM, Imtiaz S, Popova S, et al. The relationship between different dimensions of alcohol use and the burden of disease-an update. 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Are lifetime abstainers the best control group in alcohol epidemiology? On the stability and validity of reported lifetime abstention. Am J Epidemiol. 2008;168(8):866–71. Moher D, Liberati A, Tetzlaff J, Altman DG, Group TP. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement: e1000097. PLoS Med. 2009;6(7). Rehm JT, Gadenne V. Intuitive predictions and professional forecasts: Cognitive processes and social consequences. Amsterdam, Netherlands: Elsevier; 2013. Shield KD, Gmel G, Gmel G, Mäkelä P, Probst C, Room R, Rehm J. Life-time risk of mortality due to different levels of alcohol consumption in seven European countries: implications for low‐risk drinking guidelines. Addiction. 2017;112(9):1535–44. Ahmad FB, Cisewski JA, Anderson RN. Provisional mortality data—United States, 2021. Morb Mortal Wkly Rep. 2022;71(17):597. Ahmad FB, Cisewski JA, Xu J, Anderson RN. Provisional mortality data—United States, 2022. Morb Mortal Wkly Rep. 2023;72(18):488. United States Census Bureau. Data. Suitland, United States of America; 2023. Institute of Health Metrics and Evaluation. GBD Results Tool. Seattle, USA: Institute of Health Metrics and Evaluation; 2021. Arias E, Xu J. Division of Vital Statistics. U.S. State Life Tables, 2020. Natl Vital Stat Rep. 2022;71(1). Cherpitel CJ, Witbrodt J, Ye Y, Korcha R. A multi-level analysis of emergency department data on drinking patterns, alcohol policy and cause of injury in 28 countries. Drug Alcohol Depend. 2018;192:172–8. Romeo J, Wärnberg J, Marcos A. Drinking pattern and socio-cultural aspects on immune response: an overview. Proceedings of the Nutrition Society. 2010;69(3):341-6. Shield KD, Soerjomataram I, Rehm J. Alcohol use and breast cancer: a critical review. Alcoholism: Clin Experimental Res. 2016;40(6):1166–81. Roerecke M, Rehm J. Alcohol consumption, drinking patterns, and ischemic heart disease: a narrative review of meta-analyses and a systematic review and meta-analysis of the impact of heavy drinking occasions on risk for moderate drinkers. BMC Med. 2014;12:182. Holst C, Becker U, Jørgensen ME, Grønbæk M, Tolstrup JS. Alcohol drinking patterns and risk of diabetes: a cohort study of 70,551 men and women from the general Danish population. Diabetologia. 2017;60:1941–50. Alldredge BK, Lowenstein DH. Status epilepticus related to alcohol abuse. Epilepsia. 1993;34(6):1033–7. Samokhvalov AV, Irving H, Mohapatra S, Rehm J. Alcohol consumption, unprovoked seizures, and epilepsy: A systematic review and meta-analysis. Epilepsia. 2010;51(7):1177–84. Llamosas-Falcón L, Tran A, Jiang H, Rehm J. Liver holidays? A meta‐analysis of drinking the same amount of alcohol daily or non‐daily and the risk for cirrhosis. Drug Alcohol Rev. 2023;42(1):119–24. Romano E, Torres-Saavedra PA, Calderón Cartagena HI, Voas RB, Ramírez A. Alcohol-related risk of driver fatalities in motor vehicle crashes: comparing data from 2007 and 2013–2014. J Stud Alcohol Drug. 2018;79(4):547–52. Kelley-Baker T, Lacey JH, Voas RB, Romano E, Yao J, Berning A. Drinking and driving in the United States: Comparing results from the 2007 and 1996 National Roadside Surveys. Traffic Inj Prev. 2013;14(2):117–26. Clarke V, Braun V. Thematic analysis. J Posit Psychol. 2017;12(3):297–8. Kahneman D, Sibony O, Sunstein CR. Noise: a flaw in human judgment. Boston, United States: Hachette Group; 2021. Rehm J. Alcohol consumption and mortality. What do we know and where should we go? Addiction. 2000;95(7):989–95. Rehm J, Gmel G, Sempos C, Trevisan M. Alcohol-related mortality and morbidity. Alcohol Res Health. 2003;27(1):39–51. Schultz NR, Kohn CS, Schmerbauch M, Correia CJ. A systematic review of the free-pour assessment: Implications for research, assessment and intervention. Exp Clin Psychopharmacol. 2017;25(3):125. Wolf C, Curry A, Nacht J, Simpson SA. Management of alcohol withdrawal in the emergency department: current perspectives. Open Access Emerg Med. 2020:53–65. Center for Substance Abuse Treatment. A Guide to Substance Abuse Services for Primary Care Clinicians. Report No.: (SMA) 97-3139. Rockville, USA; 1997. Hilton Boon M, Burns J, Craig P, Griebler U, Heise TL, Vittal Katikireddi S, et al. Value and challenges of using observational studies in systematic reviews of public health interventions. American Public Health Association; 2022. pp. 548–52. Hernán MA. The C-word: scientific euphemisms do not improve causal inference from observational data. Am J Public Health. 2018;108(5):616–9. Roerecke M, Vafaei A, Hasan OSM, Chrystoja BR, Cruz M, Lee R, et al. Alcohol consumption and risk of liver cirrhosis: a systematic review and meta-analysis. Am J Gastroenterol. 2019;114(10):1574–86. Llamosas-Falcón L, Shield KD, Gelovany M, Manthey J, Rehm J. Alcohol use disorders and the risk of progression of liver disease in people with hepatitis C virus infection–a systematic review. Subst Abuse Treat Prev Policy. 2020;15(1):1–9. Åberg F, Färkkilä M, editors. Drinking and obesity: alcoholic liver disease/nonalcoholic fatty liver disease interactions. Seminars in liver disease. Thieme Medical; 2020. Additional Declarations No competing interests reported. Supplementary Files AIHProtocolAppendixRevised20240405.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4224612","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":290378211,"identity":"8df93d76-168d-42f0-a440-9ea2332c5272","order_by":0,"name":"Kevin Shield","email":"data:image/png;base64,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","orcid":"","institution":"Centre for Addiction and Mental Health","correspondingAuthor":true,"prefix":"","firstName":"Kevin","middleName":"","lastName":"Shield","suffix":""},{"id":290378215,"identity":"3ac3f9a4-44e2-4b9d-9747-49345b495256","order_by":1,"name":"Katherine Keyes","email":"","orcid":"","institution":"Columbia University","correspondingAuthor":false,"prefix":"","firstName":"Katherine","middleName":"","lastName":"Keyes","suffix":""},{"id":290378220,"identity":"2c16651a-0b12-4339-84b0-8ae462fc5ea8","order_by":2,"name":"Priscilla Martinez","email":"","orcid":"","institution":"Alcohol Research Group, Public Health Institute","correspondingAuthor":false,"prefix":"","firstName":"Priscilla","middleName":"","lastName":"Martinez","suffix":""},{"id":290378225,"identity":"6afc11c6-730f-477b-a5d9-16706498528a","order_by":3,"name":"Adam J. Milam","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Adam","middleName":"J.","lastName":"Milam","suffix":""},{"id":290378229,"identity":"cc823dd5-4ea1-4146-b8cc-e3a28a96f799","order_by":4,"name":"Jürgen Rehm","email":"","orcid":"","institution":"Centre for Addiction and Mental Health","correspondingAuthor":false,"prefix":"","firstName":"Jürgen","middleName":"","lastName":"Rehm","suffix":""},{"id":290378231,"identity":"5c590428-c313-415c-8544-77efe026b5e7","order_by":5,"name":"Timothy S. Naimi","email":"","orcid":"","institution":"Canadian Institute for Substance Use Research","correspondingAuthor":false,"prefix":"","firstName":"Timothy","middleName":"S.","lastName":"Naimi","suffix":""}],"badges":[],"createdAt":"2024-04-05 19:29:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4224612/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4224612/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54994057,"identity":"ba12d4ea-aced-4dc5-8b1e-2311bfb9eb69","added_by":"auto","created_at":"2024-04-19 17:44:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":44740,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart for formulating conclusions on how alcohol impacts health\u003c/p\u003e","description":"","filename":"Figure111.png","url":"https://assets-eu.researchsquare.com/files/rs-4224612/v1/99edccb0e21eeb3b93e9de67.png"},{"id":54994056,"identity":"ca8b6550-ed01-400c-8b1d-1ecac5c368d1","added_by":"auto","created_at":"2024-04-19 17:44:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":29068,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart for estimating the relationship between average volume of alcohol consumed and health consequences\u003c/p\u003e","description":"","filename":"Figure28.png","url":"https://assets-eu.researchsquare.com/files/rs-4224612/v1/176b43e2717bd54f9a9be26f.png"},{"id":64082586,"identity":"4af8a75e-78cf-4f1f-b423-752155952b33","added_by":"auto","created_at":"2024-09-06 10:51:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":669466,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4224612/v1/764d1c37-015d-471a-8902-ce02eb09982f.pdf"},{"id":54994058,"identity":"5756b18f-67d2-4c9d-96ad-cb2b9dcaca0a","added_by":"auto","created_at":"2024-04-19 17:44:54","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":97034,"visible":true,"origin":"","legend":"","description":"","filename":"AIHProtocolAppendixRevised20240405.docx","url":"https://assets-eu.researchsquare.com/files/rs-4224612/v1/ae7ebdb056ef612ea9aa43fc.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Health Impact of Alcohol Use in the United States","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eAlcohol is a psychoactive substance used by about 137.4\u0026nbsp;million people residing in households in the United States who are 12 years of age and older (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Indeed, based on a 2022 nationwide representative survey, 48.7% of people 12 years of age and older consumed alcohol in the past month, 61.2\u0026nbsp;million people (44.5 percent of current drinkers) engaged in binge drinking in the past month, and 29.5\u0026nbsp;million people (10.5 percent of people 12 years of age and older) had an alcohol use disorder (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Alcohol use has been shown to be linked to over 200 health conditions as defined by the three-digit codes of the International Statistical Classification of Diseases and Related Health Problems, 10th revision, (ICD-10) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), including infectious diseases, malignant neoplasms, cardiovascular diseases, digestive diseases, mental and behavioral disorders, metabolic disorders, and injuries. At the population level, from 2015 to 2019, alcohol consumption in the United States among people 20 to 64 years of age caused an estimated annual mean of 140 thousand deaths (97 thousand deaths among men and 43 thousand deaths among women), representing 5.0% of all deaths among this age group (6.8 of all deaths among men, and 3.2 of all deaths among women) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNational drinking guidelines usually have prescribed specific guidance on (i) thresholds (usually expressed as a maximum number of drinks per week or drinks per day) to minimize the relative long-term and short-term risks of serious morbidity and mortality caused by the consumption of alcohol over a number of years (e.g., liver disease, some cancers), (ii) per occasion thresholds to minimize the short-term risks of injury or acute illness due to per occasion consumption, (iii) consumption among vulnerable populations (e.g., youth and pregnant women (see (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)), and (iv) situations and circumstances that are particularly hazardous (e.g., driving (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)).\u003c/p\u003e \u003cp\u003eIn order to provide information on the health impact of alcohol use, the U.S. Department of Agriculture and the U.S. Department of Health and Human Services issued the \u003cem\u003eDietary Guidelines for Americans, 2020\u0026ndash;2025\u003c/em\u003e which provided health-based recommendations regarding alcohol use (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). (Similar documents have been published by other countries (\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)). The United States\u0026rsquo; recommendations provide guidance on drinking initiation, per occasion alcohol use, and which individuals should not consume alcohol, namely:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e\u0026ldquo;If adults age 21 years and older choose to drink alcoholic beverages, drinking less is better for health than drinking more.\u0026rdquo;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e\u0026ldquo;To help Americans move toward a healthy dietary pattern and minimize risks associated with drinking, adults of legal drinking age can choose not to drink or to drink in moderation by limiting intakes to 2 drinks or less in a day for men and 1 drink or less in a day for women, on days when alcohol is consumed.\u0026rdquo;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e\u0026ldquo;There are also some people who should not drink at all, such as if they are pregnant or might be pregnant; under the legal age for drinking; if they have certain medical conditions or are taking certain medications that can interact with alcohol; and if they are recovering from an alcohol use disorder or if they are unable to control the amount they drink.\u0026rdquo;\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eAt the individual level, the impact of alcohol use on health is complex and multifactorial. For example, with respect to injuries and the majority of diseases, alcohol use has no protective effect on health at any level of consumption (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). For ischemic heart disease and ischemic stroke, the health effects of low-level or moderate alcohol consumption have been mixed (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e); however, for people who engage in binge drinking (i.e., consuming 5 and 4 standard drinks (14 grams of ethanol) or more during at least one drinking occasion for men and women, respectively, alcohol is thought to have detrimental health effects (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Furthermore, with respect to diabetes, there is thought to be a protective effect on disease occurrence and mortality for women who consume low amounts of alcohol (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDue to the health impacts of alcohol use at the population level in the United States, there is a need for consumption recommendations which are grounded in science, focused on public health, and consider the complexities of how alcohol use impacts health generally, and impacts the health of vulnerable populations specifically. The \u003cem\u003eDietary Guidelines for Americans, 2020\u0026ndash;2025\u003c/em\u003e, which were published in 2020, aimed to provide consumption recommendations to Americans; the mandate of the U.S. Department of Agriculture and the U.S. Department of Health and Human Services is to update this guidance every five years to keep abreast of current alcohol research. Accordingly, the proposed review of the evidence on alcohol\u0026rsquo;s impact on health will produce conclusions to assist the Interagency Coordinating Committee for the Prevention of Underage Drinking to inform the \u003cem\u003eDietary Guidelines for Americans, 2026\u0026ndash;2030\u003c/em\u003e.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThe Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach will be utilized to formulate conclusions on how alcohol impacts health (\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Project oversight will be performed by the U.S. Department of Agriculture and the U.S. Department of Health and Human Services (who formulated the project\u0026rsquo;s \u0026ldquo;Terms of Reference\u0026rdquo;). Furthermore, to achieve the project\u0026rsquo;s \u0026ldquo;Terms of Reference\u0026rdquo;, a Technical Advisory Panel has been formulated to oversee the project.\u003c/p\u003e \u003cp\u003eThe project will determine the health impacts caused by ethanol in alcoholic beverages, and, therefore, will not distinguish between harms caused by beer, wine, spirits, and other alcoholic beverages. Harms caused by beer, wine, spirits, and other alcoholic beverages are based mainly on ethanol content, regardless of the form in which the ethanol is consumed, with the exception of alcohol poisonings which are caused predominately by the consumption of spirits (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) and some other forms of unintentional injury where there is evidence of a higher risk due to the consumption of spirits (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). A systematic review of existing guidelines on alcohol and health as well as individual modelling projects will be performed to generate conclusions on (i) weekly thresholds to minimize long-term and short-term risks of morbidity and mortality, (ii) per occassion thresholds to minimize the short-term risks of injury or acute illness due to per occasion drinking, (iii) alcohol use among vulnerable populations, and (iv) situations and individual circumstances that are hazardous. An overview of the proposed methodology and data sources are outlined in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and the supplemental material.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMethodology and data sources\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConclusions on alcohol\u0026rsquo;s impact on health\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMethodology used to reach conclusions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnderlying data sources\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeekly / daily thresholds to minimize long-term and short-term risks of morbidity and mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConclusions based on nominal group interviews\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLifetime risk of alcohol-attributable mortality and morbidity at different drinking levels\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePer occasion thresholds to minimize the short-term risks of injury or acute illness due to per occasion drinking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eConclusions based on nominal group interviews\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSystematic review of meta-analyses which summarize how drinking patterns affect the risk of disease and injury occurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eResults from a reanalysis of United States\u0026rsquo; emergency room case-cross-over studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eResults from roadside survey studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol use among vulnerable populations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eConclusions based on nominal group interviews\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSystematic review of previously published guidelines\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSituations and individual circumstances that are hazardous\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u0026lt; Insert Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e about here \u0026gt;\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSystematic review of previous guidelines on alcohol and health\u003c/h2\u003e \u003cp\u003eA 2016 systematic review highlighted differences in alcohol guidelines across 37 countries (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), but did not assess their scientific quality or the methodologies used to produce these guidelines. Therefore, this review is of limited value for the development of future guidelines. Accordingly, a systematic literature search of country-level guidance on alcohol and health will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and will be preregistered with PROSPERO (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Guidance on alcohol and health will be identified through websites of countries' health ministries using an internet search (i.e., \u0026lsquo;[country] AND health ministry\u0026rsquo;), and/or using the World Health Organization\u0026rsquo;s Global Information System on Alcohol and Health (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). A list of all country names will be obtained from the World Health Organization (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/countries\u003c/span\u003e\u003cspan address=\"https://www.who.int/countries\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). In addition to searching websites of countries' health ministries, a peer-reviewed literature search for guidance documents will be performed. Articles will be identified through a systematic search of PubMed, PsycInfo, and Web of Science based on keywords and subject headings. As an example, the search strategy for PubMed is outlined in Table S7 (see supplemental material). Searches will be piloted and refined with the aid of a research librarian. No publication year or language restrictions will be applied. References contained in the articles included will be examined for relevant publications. The processes used for the screening of articles, data extraction, and standardization are outlined in the supplemental material (see Table S8).\u003c/p\u003e \u003cp\u003eEach guideline on alcohol and health will be evaluated according to its methodological rigor; the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument is the most commonly used guideline appraisal and consistency evaluation tool in the GRADE protocol and will be used here (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). The review will summarize advice on (i) weekly thresholds to minimize long-term and short-term risks of morbidity and mortality, (ii) daily thresholds to minimize the short-term risks of injury or acute illness due to per occasion drinking, (iii) vulnerable populations, and (iv) situations and individual circumstances that are hazardous.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCollecting and generating evidence on weekly thresholds to minimize health risks\u003c/h2\u003e \u003cp\u003eTwo methods can be used to generate evidence on weekly thresholds to minimize health risks associated with different levels of average alcohol consumption: (i) the examination of all-cause absolute risk curves from cohort studies (which include deaths from all causes, including conditions from which a causal relationship with alcohol use has not been determined), and (ii) the modelling of lifetime all-cause absolute alcohol-attributable mortality and morbidity risk curves by combining data on cause-specific relative risks with corresponding data on absolute mortality risks for lifetime abstainers. Based on the positives and negatives of each method, it was decided to proceed with the modelling of lifetime all-cause absolute alcohol-attributable mortality and morbidity risk curves (i.e., method (ii)) to align with the current practices of the Centers for Disease Control and Prevention, the World Health Organization, and the Institute for Health Metrics and Evaluation for estimating the burden of disease attributable to alcohol use (\u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), and with other recently released guidance documents on alcohol and health (\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMathematical modelling will be used to estimate the lifetime risk of death and disability for different levels of average alcohol consumption. The risk curves generated will be based on the average amount of pure alcohol (i.e., ethanol). \u0026ldquo;People who consumed alcohol\u0026rdquo; will be defined as those individuals who consumed at least one standard drink (14 grams of alcohol) in the past year. The mathematical modelling will specifically examine the following outcomes: deaths, premature deaths (i.e., deaths that occur among those\u0026thinsp;\u0026lt;\u0026thinsp;70 years of age), years of life lost (YLL), years lived with disability (YLD: a measure of disease occurrence and the disability caused by the disease), disease and injury incidence, and disability adjusted years of life lost (a combination of both YLL and YLD).\u003c/p\u003e \u003cp\u003eThe inclusion of diseases and injuries in the modelling of alcohol-attributable deaths and disability will be based on three criteria: (i) the disease or injury has to be causally related to alcohol use, (ii) a dose-response risk function needs to be available for the risk relationship between alcohol consumption (measured in grams per day) and the disease or injury of interest, and (iii) either death or disability needs to be measured specifically for the disease or injury causally related to alcohol use. Multiple data sources will be used to establish causality for this review. Causality can be assumed in all causes of death that are solely (100%) attributable to alcohol use (e.g., alcoholic cardiomyopathy). Furthermore, this review will use information from the World Health Organization\u0026rsquo;s Global Status Report on Alcohol and Health (GSRAH) (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e), the Institute for Health Metrics and Evaluation\u0026rsquo;s Global Burden of Disease study (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), and the World Cancer Research Fund\u0026rsquo;s (WCRF\u0026rsquo;s) Continuous Update Project (\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e), all of which have assessed which diseases and injuries are causally related to alcohol consumption. A sensitivity analysis will be performed in which causality will be based on conditions included in the Alcohol-Related Disease Impact application of the Centers for Disease Control and Prevention (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSystematic Review of Meta-analyses\u003c/h2\u003e \u003cp\u003eThis study also aims to conduct a systematic review of all relevant meta-analyses that have investigated diseases causally associated with alcohol use. Relative Risk (RR) estimates for each included disease category and injury will be obtained from systematic reviews identified in the evidence review process. The RRs in the reviews will have used people who are lifetime abstainers as a reference group. In cases where lifetime abstainers were not the reference group, these RRs will be rescaled so that the lifetime abstainers are the reference group.\u003c/p\u003e \u003cp\u003ePubMed (including MEDLINE and Life Science Journals) and Web of Science will be searched for relevant articles based on keywords and subject headings. The search strategy for MEDLINE, as an example, is outlined in Table S9 in the supplemental matrial. Searches will be piloted and refined with the aid of a research librarian. No language restrictions will be applied. A publication restriction of 2010 and later will be applied to ensure that only recent summaries of the epidemiological evidence are included in the review. References contained in the articles included will be examined for relevant publications. Subject experts will be contacted to identify relevant publications. Previous systematic reviews, the International Agency for Research on Cancer Monographs, and the WCRF\u0026rsquo;s Continuous Update Project reports will be searched for relevant publications.\u003c/p\u003e \u003cp\u003eAll systematic reviews will be evaluated for quality using the criteria from A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) and from the Risk of Bias in Systematic Reviews (ROBIS) tool (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Quality assessments will consider study design and adjustments for confounding factors, among other criteria. In addition these quality assessments will take into account factors specific to alcohol epidemiological studies. For example, biases in exposure and outcome measurements, such as the use of current abstainers instead of lifetime abstainers as the risk reference group (i.e., allowing the misclassification of former drinkers as lifetime abstainers), and how representative the cohorts are of the US general population (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe systematic review will be pre-registered with PROSPERO, and conducted in accordance with the PRISMA guidelines (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eSelection of Meta-analyses\u003c/h2\u003e \u003cp\u003eMeta-analyses used in the modelling process will be selected by panels of nominal group interview experts in the distinct areas of (i) cancer, (ii) cardiovascular diseases, (iii) digestive conditions, (iv) neurological disorders, (v) infectious diseases, and (vi) injuries who will be consulted to determine the RR estimates for each condition considered to be causally related to alcohol use. The sampling frame of experts will be decided based on the authors who have published the largest number of first and last author publications concerning the above-noted disease areas (as determined by performing a PubMed Search) in the past 10 years. These authors will be asked to participate in the nominal group interview panels. Quota sampling will also be used to establish nominal group interview panels which ensure diversity and representation based on geographic location, sex, race and ethnicity, which will be reported by the potential participants before they are included in the nominal group interview panels. Specifically, the following parameters will be established: (i) a minimum of 90% of the experts will be United States-based, (ii) a minimum of 40% of the experts will identify as female, with a goal of 50%, and (iii) no more than 80% of the experts will be non-Hispanic White, with a goal of no more than 60% of participants being non-Hispanic White. Experts will be required to have no potential conflicts of interest.\u003c/p\u003e \u003cp\u003eOnce the panels of experts have been established, a nominal group process will be used to determine the most appropriate meta-analyses to use in the modelling study. The nominal group interview allows for the selection of meta-analyses avoiding group think (as compared to group interviews), and reduces random error in decision making by increasing the number of people whose opinions are considered (e.g., (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e)). All panels will also provide input on the magnitude of the underreporting of alcohol consumption in medical observation studies, as well as input on vulnerable populations and situations and individual circumstances where the consumption of alcohol is hazardous. In the first round, each expert will be provided with the results of the preregistered systematic scoping review, and will be asked to provide free-text comments on the interpretation of these studies. When necessary, experts will be contacted to clarify their answers. The project team will analyze answers to identify potential underlying patterns and prepare a draft consensus position. Each expert will also be asked the degree to which they hypothesize alcohol use to be misestimated in population surveys (what fraction is due to spillage and wastage, and what fraction is due to survey and response biases) and in cohort studies.\u003c/p\u003e \u003cp\u003eIn the second round of interviews, based on feedback regarding the results of round 1, the consolidated information will be provided to the expert participants. During these interviews, experts will interact and clarify their positions in small group virtual meetings. At the end of the second round of interviews, all experts will be asked to complete a questionnaire which will be used to build a consensus on which meta-analyses to include in the modelling study.\u003c/p\u003e \u003cp\u003eIn the event that this process proves too time consuming, selection of meta-analysis will be modified and streamlined. The streamlined approach will involve selecting the meta-analysis for modeling based on its performance on the AMSTAR 2 and ROBIS tools, prioritizing the study with the least potential risk of bias.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eData sources: Mortality and Alcohol Exposure\u003c/h2\u003e \u003cp\u003eA comparative risk method (i.e., the systematic evaluation of changes in population health that would be avoided in the absence of a risk factor) will be used to estimate the alcohol-attributable burden of disease. For this method, the reference group of lifetime abstainers will be utilized \u0026minus; thus determining the number of deaths and the burden of disability that would not occur if alcohol consumption was eliminated (see: (\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e)). Lifetime risk curves will be based on an exposure of average grams of pure alcohol (i.e., ethanol) consumed per week.\u003c/p\u003e \u003cp\u003eData on the number of deaths that occurred in the United States by age, sex, and cause will be obtained from the National Vital Statistics System (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e). Data on population by age and sex will be obtained from the Census Bureau of the United States (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). Data on disease incidence and YLD will be obtained from the Institute for Health Metrics and Evaluation\u0026rsquo;s Global Burden of Disease study (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). Life tables by sex will be obtained from the Centers for Disease Control and Prevention, National Center for Health Statistics (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRelative risks from the systematic review of meta-analyses will be combined with estimates of the risk of mortality and morbidity for lifetime abstainers to estimate lifetime risk curves. A comparative risk assessment methodology will be used to estimate the risk of mortality and morbidity for lifetime abstainers (see supplemental material). Lifetime risk curves will be calculated by estimating alcohol-attributable mortality and morbidity risk by cause, age, and sex. The life-year specific alcohol-attributable mortality risks will be multiplied by the YLL for each cause of death. The lifetime risk curves will also account for competing causes of death (i.e., deaths which occur that are not attributable to alcohol use). Seesupplemental material for further details regarding the lifetime risk methodology.\u003c/p\u003e \u003cp\u003e\u0026lt; Insert Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e about here \u0026gt;\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe lifetime risk curves for alcohol-attributable mortality and morbidity risks will be provided to members of all nominal group interview panels. We will then use the nominal group interview process, including all members from all panels, to establish conclusions on weekly and/or daily alcohol use thresholds.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCollecting and generating evidence on per occasion alcohol use thresholds to minimize short-term health risks\u003c/h2\u003e \u003cp\u003ePer occasion alcohol use is based on consumption during particular times or occasions, (as compared to average consumption which is determined by dividing total consumption by time). As such, per occasion consumption is related to consumption patterns, and provides a proxy measure for blood alcohol concentrations that might be achieved based on a particular level of per occasion consumption. High per occasion consumption resulting in high blood alcohol concentrations is strongly associated with \u0026ldquo;acute\u0026rdquo; disease processes such as injuries (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e), but also is associated with the risk of infectious diseases (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e), breast cancer (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e), ischemic heart disease and ischemic stroke (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e), diabetes (\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e), epilepsy (\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e), and liver cirrhosis (\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMultiple sources of data will be used to reach conclusions on the health impacts of per occasion alcohol use, namely: (i) results from the systematic review of meta-analyses and systematic reviews which summarize how drinking patterns affect the risk of disease and injury occurrence, (ii) results from a reanalysis of United States\u0026rsquo; emergency room case-cross-over studies which examined the relationship between alcohol use and injury occurrence (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e), and (iii) results from roadside survey studies where the blood alcohol content of road injury decedents was compared to that of drivers randomly selected from the same road on the same day and at the same hour as the fatal crash case (\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e). Based on these data sources, the expert groups will reach public health conclusions on the maximum number of drinks people should consume during one drinking occasion. The nominal group interviews will follow a two round structure that will also be used to determine the best RR functions to be used in the modelling of the health impacts of alcohol use.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCollecting and generating evidence on the effects of alcohol use among vulnerable populations, and situations and individual circumstances where consuming alcohol is hazardous\u003c/b\u003e \u003c/p\u003e \u003cp\u003e The planned study will build upon previous guidelines (identified through the previously noted systematic review) using nominal group interviews to provide conclusions with respect to evidence on the effects of alcohol use among vulnerable populations (e.g., pregnant persons, underage youth), and situations and individual circumstances where consuming alcohol is hazardous. The experts selected from the nominal group surveys will review evidence of individuals in vulnerable populations or who are subject to situations and individual circumstances where consuming alcohol is hazardous to determine if these considerations should be included in the conclusions of the study. In addition, experts who are part of the nominal group interviews will be invited to identify vulnerable populations and situations and individual circumstances which have not been previously noted in any other guidelines, but where current research supports that these vulnerable populations and/or situations and individual circumstances should be added to alcohol and health guidance documents, as well as any relevant peer-reviewed research documents which support their addition. The structure of these nominal group interviews will follow a two round structure that will also be used to determine the best RR functions to be used in the modelling of the health impacts of alcohol use.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCollecting and generating evidence on the public\u0026rsquo;s understanding and reaction to conclusions on alcohol consumption and health\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTo understand how conclusions regarding the health impacts of alcohol use align with the alcohol consumption of the general public, we will examine alcohol use in the general population using data from the National Alcohol Survey, National Survey on Drug Use and Health (NSDUH), National Health Interview Survey (NHIS), The National Epidemiologic Survey on Alcohol and Related Conditions - III (NESARC-III), and Behavioral Risk Factor Surveillance System (BRFSS) in order to obtain data on alcohol exposure in the United States (see Tables S1 to S6 in supplemental materal). These population surveys, which have differing sampling frames, response rates, and validation of self-reporting of alcohol use, provide comprehensive data on alcohol consumption patterns and allow estimations of the prevalences of different levels of alcohol use in the population.\u003c/p\u003e \u003cp\u003eTo gain an understanding of the public\u0026rsquo;s understanding and reaction to the conclusions on alcohol and health produced by this project, we will engage in public consultations using a mixed methods (quantitative and quantitative) approach. Public consultation recruitment will be performed using a convenience sampling methodology. Specifically, the consultation process will be promoted through institutional websites, mass emails, social media, and national and regional digital news media advertisements. All residents of the United States will be eligible to participate. Individuals who do participate will be asked categorical and open-ended questions (in English) about:\u003c/p\u003e \u003cp\u003e\u003col style=\"list-style-type:lower-roman;\"\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003etheir demographics, including geographic location;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003etheir profession;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003etheir current sources of information on health and, more specifically, on the impacts of alcohol consumption on health;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ecurrent and previous health conditions;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003etheir awareness of the \u003cem\u003eDietary Guidelines for Americans, 2020\u0026ndash;2025\u003c/em\u003e;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003etheir alcohol use and whether they are trying to follow the alcohol consumption guidance in the \u003cem\u003eDietary Guidelines for Americans, 2020\u0026ndash;2025\u003c/em\u003e and their reasons for following or not following the guidelines;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003etheir requirements for and expectations of the \u003cem\u003eDietary Guidelines for Americans, 2026\u0026ndash;2030\u003c/em\u003e;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ewhat information they found useful about the project\u0026rsquo;s conclusions on alcohol and health; and\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ewhat challenges they had in interpreting the project\u0026rsquo;s conclusions on alcohol and health.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e \u003cp\u003eAggregate information on the demographics of participants will be examined, published and compared to United States Census data to assess whether participants in the consultation process are representative of the general population (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). A thematic analysis will be performed on responses to open-ended questions to identify common themes between respondents\u0026rsquo; answers to each of the questions. As the information obtained from an analysis of the findings of the consultation process is to be used to revise and refine the research conclusions, both a semantic and latent coding approach and analysis will be employed. Furthermore, to analyse the qualitative data, Braun and Clarke's six phases of thematic analysis approach will be utilized (\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eGiven the magnitude of the burden of disease caused by alcohol use in the United States, it is imperative to provide up-to-date public health information on the health consequences of alcohol use. The \u003cem\u003eDietary Guidelines for Americans, 2026\u0026ndash;2030\u003c/em\u003e represent an opportunity to provide the public with updated information on how alcohol use impacts health. The information derived from the project will provide conclusions on alcohol and health to directly inform the \u003cem\u003eDietary Guidelines for Americans, 2026\u0026ndash;2030\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eThe proposed project differs from the project used to inform the \u003cem\u003eDietary Guidelines for Americans, 2020\u0026ndash;2025\u003c/em\u003e in numerous appreciable ways (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). First, the proposed project will include many new components, including a systematic review of other low-risk drinking guidelines, public consultations, and arriving at decisions through the use of nominal group interviews of systematically chosen panels of scientific experts.\u003c/p\u003e \u003cp\u003eThe use of nominal group interviews is a particularly important improvement on previous efforts which informed the \u003cem\u003eDietary Guidelines for Americans, 2020\u0026ndash;2025\u003c/em\u003e, as this project relies on independent judgements of numerous experts, which previous research shows can vary over relatively short time spans, between experts, and within an individual expert due to systematic and random error (\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e). Second, with regards to assessing the impact of average alcohol intake on health, the 2020 Dietary Guideline Advisory Committee\u0026rsquo;s systematic review focused on relationships between alcohol and all-cause mortality. As previously mentioned, the Centers for Disease Control and other organizations agree that modelling risk curves using a cause-specific approach is more accurate than using all-cause mortality risk estimates from cohort studies. This is mainly due to the fact that all-cause mortality RRs are estimated based on large, non-representative cohort studies which are over-representative of the middle class and include a number of causes of death. Indeed, deaths caused by cardiovascular diseases are overrepresented in such cohorts, and individuals with risk factors which synergistically interact with alcohol use (such as tobacco smoking and obesity) are under-represented (\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e). The use of cause-specific RRs when modelling lifetime alcohol-attributable mortality and morbidity will avoid this problem as it utilizes death data from the United States. Furthermore, the use of all-cause mortality risk curves is susceptible to a greater degree of confounding compared to a cause-specific approach. The use of cause-specific RRs when modelling lifetime alcohol-attributable mortality and morbidity will only be susceptible to confounding for causes of death which are considered casually related to alcohol, whereas cohort studies which assess the risk relationship between alcohol use and all-cause mortality are susceptible to confounding from all causes of death.\u003c/p\u003e \u003cp\u003eThe success of the \u003cem\u003eDietary Guidelines for Americans, 2026\u0026ndash;2030\u003c/em\u003e will depend upon the conclusions of this review, the dissemination and clarity of the guidelines, and upon the American public\u0026rsquo;s knowledge of how much beer, wine, or spirits constitutes a standard drink. The lack of knowledge of what constitutes a standard drink, especially compared to what constitutes a standard pour at home or at a restaurant or bar, may impede the effectiveness of the \u003cem\u003eDietary Guidelines for Americans, 2026\u0026ndash;2030\u003c/em\u003e in conveying the health impact of alcohol use. For example, a systematic review published in 2017 found that of 17 published studies comparing a standard pour (alcoholic beverages were poured by the participant) with a standard drink, 11 studies reported overpouring, one study reported evidence of underpouring, and six studies showed evidence of both over- and underpouring, with under- and overpouring dependent upon gender, drinking history, and type of alcoholic beverage (\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurther, while information on the impact of alcohol use on health may promote people\u0026rsquo;s desire to change their alcohol consumption, additional tools may be needed to actively promote changes in alcohol use, and to maintain such reductions. First, people who are heavy continuous drinkers may experience withdrawal symptoms when reducing their alcohol use, with these symptoms being potentially life threatening (\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e). Such individuals should not reduce their alcohol use without first consulting a physician. For people who do not experience withdrawal when reducing their alcohol use, tools are available to assist in facilitating goal setting, to aid people in developing specific strategies for change, and to recognize situations and triggers that have frequently led in the past to alcohol use or hazardous drinking (\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e). Accordingly, from a public health perspective, there is a need to help the public in obtaining, and healthcare systems in providing, tools to assist people in changing their alcohol use.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eThere are multiple limitations to the proposed project. First, the evidence review, with few exceptions of short term outcomes, will not capture randomized control trials. Thus, the included studies will be observational. Although observational studies inherently may be exposed to threats to their validity, including confounding and selection bias, these studies will be valuable in providing needed information for assessing the outcomes resulting from alcohol consumption. Moreover, there is increasing acknowledgment that causal effects may be estimated using observational studies (\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e). Second, the outcomes focused upon in the current update will be limited to health conditions that result in mortality and morbidity. Numerous adverse health outcomes and social harms will not be directly incorporated. Third, due to the use of evidence examining and reporting population averages, it is important to note that the conclusions arising from the study will not necessarily be tailored to the individual and will not encapsulate other risk and protective factors which influence the use of alcohol and its related outcomes. For example, while studies have shown that consuming one drink a day is sufficient to increase the risk of liver cirrhosis (\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e), in the absence of other risk factors, consuming one drink a day may be insufficient to cause liver cirrhosis from a pathological standpoint. However, in the presence of other risk factors, such as obesity or Hepatitis B or C infection, alcohol use may further the progress of liver disease leading to cirrhosis or death (\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e, \u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e).\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eAlcohol use causes a substantial amount of harm in the United States, both at the population level and at the individual level. As such, there is a need for public health guidance documents on alcohol and health. Accordingly, the proposed project will build upon the 2020 Dietary Guideline Advisory Committee\u0026rsquo;s report by establishing scientific consensus on the conclusions of peer-reviewed literature concerning alcohol\u0026rsquo;s impact on health.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAGREE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAppraisal of Guidelines for Research and Evaluation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAMSTAR 2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eA Measurement Tool to Assess Systematic Reviews\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGSRAH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlobal Status Report on Alcohol and Health\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGRADE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGrading of Recommendations, Assessment, Development and Evaluation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICD-10\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Statistical Classification of Diseases and Related Health Problems, 10th revision\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePRISMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePreferred Reporting Items for Systematic Reviews and Meta-Analyses\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROBIS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRisk of Bias in Systematic Reviews\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRelative Risk\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eYLD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eyears lived with disability\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eYLL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eyears of life lost\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWCRF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Cancer Research Fund\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eNone to declare\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eFunding for this manuscript was provided by Syergy Enterpises Inc.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eKS: was involved in study conceptualization, design of the work, drafted the manuscript, and substantively revised the manuscript. KK: was involved in study conceptualization, design of the work, and substantively revised the manuscript. PM: was involved in study conceptualization, design of the work, and substantively revised the manuscript. AJM: was involved in study conceptualization, design of the work, and substantively revised the manuscript. JR: was involved in study conceptualization, design of the work, and substantively revised the manuscript. TSN: was involved in study conceptualization, design of the work, and substantively revised the manuscript.\u0026nbsp;All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe would like to thank Dr. Alicia Sparks for her contributions to the protocol and her feedback on the revised protocol.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConflict of Interest declaration:\u0026nbsp;\u003c/strong\u003eThis study is funded by the United States\u0026rsquo; Substance Abuse and Mental Health Services Administration\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSubstance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2022 National Survey on Drug Use and Health (HHS Publication No. PEP23-07-01-006. NSDUH Series H-58. 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Alcohol use disorders and the risk of progression of liver disease in people with hepatitis C virus infection\u0026ndash;a systematic review. Subst Abuse Treat Prev Policy. 2020;15(1):1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Aring;berg F, F\u0026auml;rkkil\u0026auml; M, editors. Drinking and obesity: alcoholic liver disease/nonalcoholic fatty liver disease interactions. Seminars in liver disease. Thieme Medical; 2020.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Alcohol, Guidelines, Public Health, Risk, United States","lastPublishedDoi":"10.21203/rs.3.rs-4224612/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4224612/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAlcohol is consumed by an estimated 137.4\u0026nbsp;million people in the United States 12 years of age and older, and, as a result, is estimated to have caused about 140 thousand deaths among people 20 to 64 years of age each year from 2015 up to and including 2019.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe proposed proposed review of the evidence on alcohol\u0026rsquo;s impact to health aims to produce conclusions to inform the \u003cem\u003eDietary Guidelines for Americans, 2026\u0026ndash;2030\u003c/em\u003e. A multi-method approach will be utilized to formulate conclusions on (i) weekly (i.e., average) thresholds to minimize long-term and short-term risks of morbidity and mortality, (ii) daily thresholds to minimize the short-term risk of injury or acute illness due to per occasion drinking, (iii) alcohol use among vulnerable populations (e.g., pregnant women), and (iv) situations and circumstances that are hazardous for alcohol use. To inform expert discussions, this project will also include a systematic review of existing low-risk drinking guidelines, a systematic review of meta-analyses which examine alcohol\u0026rsquo;s impact on key attributable disease and mortality outcomes, and of estimates of the lifetime absolute risk of alcohol-attributable mortality and morbidity based on a person\u0026rsquo;s sex and average level of alcohol use. The preliminary conclusions produced as a result of this project will undergo public consultation, and data from these consultations will be analyzed using both quantitative and qualitative methods. The results of the public consultations will be used to further revise and refine the project\u0026rsquo;s conclusions.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eThis project will establish a scientific consensus concerning alcohol\u0026rsquo;s impact on health. This consensus is imperative for informing the upcoming \u003cem\u003eDietary Guidelines for Americans, 2026\u0026ndash;2030\u003c/em\u003e, and for better informing individuals about the health risks associated with alcohol use.\u003c/p\u003e","manuscriptTitle":"Health Impact of Alcohol Use in the United States","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-19 17:44:49","doi":"10.21203/rs.3.rs-4224612/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6643cf59-a8a2-4543-a41c-ee6ee78235a1","owner":[],"postedDate":"April 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-06T10:43:44+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-19 17:44:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4224612","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4224612","identity":"rs-4224612","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}