Advances in Nutrition

دسترسی یکساله به بیش از ۵۰۰ ژورنال روز جهان موجود در سامانه

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سفارش

Perspective: Nutritional Status as a Biological Variable (NABV): Integrating Nutrition Science into Basic and Clinical Research and Care

Daniel J Raiten, Gerald F Combs, Jr, Alison L Steiber, Andrew A Bremer

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1599–1609

The field of nutrition has evolved from one focused primarily on discovery of the identities, metabolic functions, and requirements for essential nutrients to one focused on the application of that knowledge to the development and implementation of dietary recommendations to promote health and prevent disease. This evolution has produced a deeper appreciation of not only the roles of nutrients, but also factors affecting their functions in increasingly complex global health contexts. The intersection of nutrition with an increasingly more complex global health context necessitates a view of nutritional status as a biological variable (NABV), the study of which includes an appreciation that nutritional status is: 1) not limited to dietary exposure; 2) intimately and inextricably involved in all aspects of human health promotion, disease prevention, and treatment; and 3) both an input and an outcome of health and disease. This expanded view of nutrition will inform future research by facilitating considerations of the contexts and variability associated with the many interacting factors affecting and affected by nutritional status. It will also demand new tools to study multifactorial relations to the end of increasing precision and the development of evidence-based, safe, and effective standards of health care, dietary interventions, and public health programs.

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Perspective: Planning and Conducting Statistical Analyses for Human Nutrition Randomized Controlled Trials: Ensuring Data Quality and Integrity

Kristina S Petersen, Penny M Kris-Etherton, George P McCabe, Gowri Raman, Joshua W Miller, Kevin C Maki

doi : 10.1093/advances/nmab045

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1610–1624

Appropriate planning, execution, and reporting of statistical methods and results is critical for research transparency, validity, and reproducibility. This paper provides an overview of best practices for developing a statistical analysis plan a priori, conducting statistical analyses, and reporting statistical methods and results for human nutrition randomized controlled trials (RCTs). Readers are referred to the other NURISH (NUtrition inteRventIon reSearcH) publications for detailed information about the preparation and conduct of human nutrition RCTs. Collectively, the NURISH series outlines best practices for conducting human nutrition research.

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Perspective: Milk microRNAs as Important Players in Infant Physiology and Development

Christine Leroux, Mathilde Lea Chervet, J Bruce German

doi : 10.1093/advances/nmab059

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1625–1635

Evolutionary selective pressure on lactation has resulted in milk that provides far more than simply essential nutrients, delivering a complex repertoire of agents from hormones to intact cells. Human infants are born with low barrier integrity of their gut, which means that many of the complex biopolymer components of milk enter and circulate in lymph and blood, reaching organs throughout the body. Due to this state of gut maturation, all components of milk are potentially part of the crosstalk between mother and infants. This article highlights the functions of milk's complex biopolymers, more specifically the potential role of microRNAs (miRNAs) contained in extracellular vesicles in human milk. miRNAs are key effectors in the regulation of many biological processes during early-age development, and consequently milk-sourced miRNAs must be considered to provide unique biological assets to the infant during breastfeeding. This article interprets the evidence of the potential action of human milk miRNAs on infant development, taking into account their abundance in milk based on the literature and current knowledge. Human milk miRNAs appear to influence lipid and glucose metabolism, gut maturation, neurogenesis, and immunity. We also show growing evidence that human milk miRNAs are epigenetic modulators that play a pivotal role in the regulation of tissue-specific gene expression throughout life. Furthermore, this article addresses the ongoing debate regarding the potential influence of human milk miRNAs on viral infection as a new research area. This article highlights that these bioactive molecules are now being incorporated into our overall understanding of nutrient needs for healthy infant development, preparing each individual infant to succeed as a healthy and protected adult throughout its life. In essence, miRNAs are a new language in the Rosetta stone of health that is mammalian lactation.

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Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis

Asma Kazemi, Vida Mohammadi, Sahar Keshtkar Aghababaee, Mahdieh Golzarand, Cain C T Clark, Siavash Babajafari

doi : 10.1093/advances/nmab012

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1636–1658

This systematic review was conducted to summarize and clarify the evidence on the association between 25-hydroxyvitamin-D [25(OH)D] concentrations and coronavirus disease 2019 (COVID-19) risk and outcomes. PubMed, Scopus, and Web of Science databases and Google Scholar were searched up to 26 November 2020. All retrospective and prospective cohort, cross-sectional, case-control, and randomized controlled trial studies that investigated the relation between 25(OH)D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity were included. Thirty-nine studies were included in the current systematic review. In studies that were adjusted (OR: 1.77; 95% CI: 1.24, 2.53; I2: 44.2%) and nonadjusted for confounders (OR: 1.75; 95% CI: 1.44, 2.13; I2: 33.0%) there was a higher risk of SARS-CoV-2 infection in the vitamin D deficiency (VDD) group. Fifteen studies evaluated associations between VDD and composite severity. In the studies that were adjusted (OR: 2.57; 95% CI: 1.65, 4.01; I2 = 0.0%) and nonadjusted for confounders (OR: 10.61; 95% CI: 2.07, 54.23; I2 = 90.8%) there was a higher severity in the VDD group. Analysis of studies with crude OR (OR: 2.62; 95% CI: 1.13, 6.05; I2: 47.9%), and adjusted studies that used the Cox survival method (HR: 7.67; 95% CI: 3.92, 15.03; I2: 0.0%) indicated a significant association of VDD with mortality, while in adjusted studies that used logistic regression, no relation was observed (OR: 1.05; 95% CI: 0.63, 1.75; I2: 76.6%). The results of studies that examined relations between VDD and intensive care unit (ICU) admission, pulmonary complications, hospitalization, and inflammation were inconsistent. In conclusion, although studies were heterogeneous in methodological and statistical approach, most of them indicated a significant relation between 25(OH)D and SARS-CoV-2 infection, COVID-19 composite severity, and mortality. With regard to infection, caution should be taken in interpreting the results, due to inherent study limitations. For ICU admission, inflammation, hospitalization, and pulmonary involvement, the evidence is currently inconsistent and insufficient.

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Dietary Diversity Indicators and Their Associations with Dietary Adequacy and Health Outcomes: A Systematic Scoping Review

Eric O Verger, Agnes Le Port, Augustin Borderon, Gabriel Bourbon, Mourad Moursi, Mathilde Savy, François Mariotti, Yves Martin-Prevel

doi : 10.1093/advances/nmab009

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1659–1672

Dietary diversity has long been recognized as a key component of diet quality and many dietary diversity indicators (DDIs) have been developed. This systematic scoping review aimed to present a comprehensive inventory of DDIs and summarize evidence linking DDIs and dietary adequacy or health outcomes in adolescents and adults. Two search strategies were developed to identify peer-reviewed articles published in English up until June 2018 and were applied to Medline, Web of Science, and Scopus. A 2-stage screening process was used to select the studies to be reviewed. Four types of DDIs were identified among 161 articles, the majority of them belonging to the food group–based indicator type (n = 106 articles). Fifty studies indicated that DDIs were proxies of nutrient adequacy, but there was a lack of evidence about their relation with nutrients to limit. Associations between DDIs and health outcomes were largely inconsistent among 137 studies, especially when the outcomes studied were body weight (n = 60) and noncommunicable diseases (n = 41). We conclude that the ability of DDIs to reflect diet quality was found to be principally limited to micronutrient adequacy and that DDIs do not readily relate to health outcomes. These findings have implications for studies in low- and lower-middle-income economies where DDIs are often used to assess dietary patterns and overall diet quality.

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Ultra-processed Foods and Cardiovascular Diseases: Potential Mechanisms of Action

Filippa Juul, Georgeta Vaidean, Niyati Parekh

doi : 10.1093/advances/nmab049

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1673–1680

Ultra-processed foods are industrially manufactured ready-to-eat or ready-to-heat formulations containing food additives and little or no whole foods, in contrast to processed foods, which are whole foods preserved by traditional techniques such as canning or pickling. Recent epidemiological studies suggest that higher consumption of ultra-processed food is associated with increased risk of cardiovascular disease (CVD). However, epidemiological evidence needs to be corroborated with criteria of biological plausibility. This review summarizes the current evidence on the putative biological mechanisms underlying the associations between ultra-processed foods and CVD. Research ranging from laboratory-based to prospective epidemiological studies and experimental evidence suggest that ultra-processed foods may affect cardiometabolic health through a myriad of mechanisms, beyond the traditionally recognized individual nutrients. Processing induces significant changes to the food matrix, for which ultra-processed foods may affect health outcomes differently than unrefined whole foods with similar nutritional composition. Notably, the highly degraded physical structure of ultra-processed foods may affect cardiometabolic health by influencing absorption kinetics, satiety, glycemic response, and the gut microbiota composition and function. Food additives and neo-formed contaminants produced during processing may also play a role in CVD risk. Key biological pathways include altered serum lipid concentrations, modified gut microbiota and host–microbiota interactions, obesity, inflammation, oxidative stress, dysglycemia, insulin resistance, and hypertension. Further research is warranted to clarify the proportional harm associated with the nutritional composition, food additives, physical structure, and other attributes of ultra-processed foods. Understanding how ultra-processing changes whole foods and through which pathways these foods affect health is a prerequisite for eliminating harmful processing techniques and ingredients.

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The Dietary Inflammatory Index and Human Health: An Umbrella Review of Meta-Analyses of Observational Studies

Wolfgang Marx, Nicola Veronese, Jaimon T Kelly, Lee Smith, Meghan Hockey, Sam Collins, Gina L Trakman, Erin Hoare, Scott B Teasdale, Alexandra Wade, Melissa Lane, Hajara Aslam, Jessica A Davis, Adrienne O'Neil, Nitin Shivappa, James R Hebert, Lauren C Blekkenhorst, Michael Berk, Toby Segasby, Felice Jacka

doi : 10.1093/advances/nmab037

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1681–1690

Numerous observational studies have investigated the role of the Dietary Inflammatory Index (DII®) in chronic disease risk. The aims of this umbrella review and integrated meta-analyses were to systematically synthesize the observational evidence reporting on the associations between the DII and health outcomes based on meta-analyses, and to assess the quality and strength of the evidence for each associated outcome. This umbrella review with integrated meta-analyses investigated the association between the DII and a range of health outcomes based on meta-analyses of observational data. A credibility assessment was conducted for each outcome using the following criteria: statistical heterogeneity, 95% prediction intervals, evidence for small-study effect and/or excess significance bias, as well as effect sizes and P values using calculated random effects meta-analyses. In total, 15 meta-analyses reporting on 38 chronic disease-related outcomes were included, incorporating a total population of 4,360,111 subjects. Outcomes (n = 38) were examined through various study designs including case-control (n = 8), cross-sectional (n = 5), prospective (n = 5), and combination (n = 20) study designs. Adherence to a pro-inflammatory dietary pattern had a significant positive association with 27 (71%) of the included health outcomes (P value < 0.05). Using the credibility assessment, Class I (Convincing) evidence was identified for myocardial infarction only, Class II (Highly suggestive) evidence was identified for increased risk of all-cause mortality, overall risk of incident cancer, and risk of incident site-specific cancers (colorectal, pancreatic, respiratory, and oral cancers) with increasing (more pro-inflammatory) DII score. Most outcomes (n = 31) presented Class III (Suggestive) or lower evidence (Weak or No association). Pro-inflammatory dietary patterns were nominally associated with an increased risk of many chronic disease outcomes. However, the strength of evidence for most outcomes was limited. Further prospective studies are required to improve the precision of the effect size.

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Higher Mushroom Consumption Is Associated with Lower Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies

Djibril M Ba, Paddy Ssentongo, Robert B Beelman, Joshua Muscat, Xiang Gao, John P Richie, Jr

doi : 10.1093/advances/nmab015

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1691–1704

Mushrooms are rich in bioactive compounds. The potential health benefits associated with mushroom intake have gained recent research attention. We thus conducted a systematic review and meta-analysis to assess the association between mushroom intake and risk of cancer at any site. We searched MEDLINE, Web of Science, and Cochrane Library to identify relevant studies on mushroom intake and cancer published from 1 January, 1966, up to 31 October, 2020. Observational studies (n = 17) with RRs, HRs, or ORs and 95% CIs of cancer risk for ?2 categories of mushroom intake were eligible for the present study. Random-effects meta-analyses were conducted. Higher mushroom consumption was associated with lower risk of total cancer (pooled RR for the highest compared with the lowest consumption groups: 0.66; 95% CI: 0.55, 0.78; n = 17). Higher mushroom consumption was also associated with lower risk of breast cancer (pooled RR for the highest compared with the lowest consumption groups: 0.65; 95% CI: 0.52, 0.81; n = 10) and nonbreast cancer (pooled RR for the highest compared with the lowest consumption groups: 0.80; 95% CI: 0.66, 0.97; n = 13). When site-specific cancers were examined, a significant association with mushroom consumption was only observed with breast cancer; this could be due to the small number of studies that were conducted with other cancers. There was evidence of a significant nonlinear dose–response association between mushroom consumption and the risk of total cancer (P-nonlinearity = 0.001; n = 7). Limitations included the potential for recall and selection bias in case-control designs, which comprised 11 out of the 17 studies included in this meta-analysis, and the large variation in the adjustment factors used in the final models from each study. The association between higher mushroom consumption and lower risk of cancer, particularly breast cancer, may indicate a potential protective role for mushrooms in the diet.

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Potato Consumption and Risk of Site-Specific Cancers in Adults: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies

Manije Darooghegi Mofrad, Hadis Mozaffari, Mohammad Reza Askari, Mohammad Reza Amini, Alireza Jafari, Pamela J Surkan, Leila Azadbakht

doi : 10.1093/advances/nmab024

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1705–1722

The etiology of cancer type may vary significantly due to anatomy, embryology, and physiology of the cancer site. Although the association between potato consumption and colorectal cancer (CRC) was summarized in a 2018 meta-analysis of 5 cohort studies, to the best of our knowledge, no meta-analysis has evaluated potato consumption in relation to multiple cancer sites in adults. Medline/PubMed, ISI Web of Knowledge, Scopus, and the Cochrane Database of Systematic Reviews were searched for relevant publications through August 2020. We selected cohort or case-control studies conducted in adults that reported risk estimates (relative risk [RRs], HRs, and ORs) of potato intake for any cancer type. Random effects meta-analyses compared high and low intake categories. Twenty prospective cohort studies (total n = 785,348) including 19,882 incident cases, and 36 case-control studies (21,822 cases; 66,502 controls) were included. Among cohort studies, we did not find an association between high versus low intake of total potato (white and yellow) consumption and overall cancers: 1.04 (95% CI: 0.96, 1.11; tau2 = 0.005, n = 18). We found no relation between total potato consumption (high compared with low intake) and risk of CRC, pancreatic cancer, colon, gastric, breast, prostate, kidney, lung, or bladder cancer in cohort or case-control studies. We did not find an association between high versus low consumption of potato preparations (boiled/fried/mashed/roasted/baked) and risk of gastrointestinal-, sex-hormone-, or urinary-related cancers in cohort or case-control studies. Certainty of the evidence was low for total cancer, CRC, colon, rectal, renal, pancreatic, breast, prostate, and lung cancer and very low for gastric and bladder cancer. In conclusion, potato intake or potato preparations were not associated with multiple cancer sites when comparing high and low intake categories. This finding was consistent with the findings from the 2018 meta-analysis regarding potato intake and risk of CRC.

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Dietary Intake and Circulating Concentrations of Carotenoids and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Observational Studies

yi-Wen Jiang, Zhong-Han Sun, Wen-Wei Tong, Kun yang, Kun-Quan Guo, Gang Liu, An Pan

doi : 10.1093/advances/nmab048

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1723–1733

Previous meta-analysis studies have indicated inverse associations between some carotenoids and risks of metabolic syndrome, cardiovascular disease, cancer, and all-cause mortality. However, the results for associations between carotenoids and type 2 diabetes (T2D) remain inconsistent and no systematic assessment has been done on this topic. We conducted a systematic review and meta-analysis to examine the associations of dietary intakes and circulating concentrations of carotenoids with risk of T2D. We searched PubMed and Ovid Embase from database inception to July 2020. Prospective observational studies of carotenoids and T2D risk were included. Random-effects models were used to summarize the RRs and 95% CIs. Thirteen publications were included. Dietary intake of ?-carotene was inversely associated with the risk of T2D, and the pooled RR comparing the highest with the lowest categories was 0.78 (95% CI: 0.70, 0.87; I2 = 13.7%; n = 6); inverse associations were also found for total carotenoids (n = 2), ?-carotene (n = 4), and lutein/zeaxanthin (n = 4), with pooled RRs ranging from 0.80 to 0.91, whereas no significant associations were observed for ?-cryptoxanthin and lycopene. Circulating concentration of ?-carotene was associated with a lower risk of T2D, and the pooled RR comparing extreme categories was 0.60 (95% CI: 0.46, 0.78; I2 = 56.2%; n = 7); inverse associations were also found for total carotenoids (n = 3), lycopene (n = 4), and lutein (n = 2), with pooled RRs ranging from 0.63 to 0.85, whereas no significant association was found for circulating concentrations of ?-carotene and zeaxanthin when comparing extreme categories. Dose-response analysis indicated that nonlinear relations were observed for circulating concentrations of ?-carotene, ?-carotene, lutein, and total carotenoids (all P-nonlinearity < 0.05), but not for other carotenoids or dietary exposures. In conclusion, higher dietary intakes and circulating concentrations of total carotenoids, especially ?-carotene, were associated with a lower risk of T2D. More studies are needed to confirm the causality and explore the role of foods rich in carotenoids in prevention of T2D.

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A Systematic Review of Dietary Influences on Fecal Microbiota Composition and Function among Healthy Humans 1–20 Years of Age

Andrew M Dinsmoor, Miriam Aguilar-Lopez, Naiman A Khan, Sharon M Donovan

doi : 10.1093/advances/nmab047

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1734–1750

Diet is a key modulator of fecal microbiota composition and function. However, the influence of diet on the microbiota from toddlerhood to adolescence and young adulthood is less well studied than for infancy and adulthood. We aimed to complete a qualitative systematic review of the impacts of diet on the fecal microbiota of healthy humans 1–20 y of age. English-language articles, published after 2008, indexed in the PubMed/MEDLINE, Cochrane, Web of Science, and Scopus databases were searched using keywords and Medical Subject Headings terms. Quality assessment of included studies was conducted using the Quality Criteria Checklist derived from the Nutrition Evidence Library of the Academy of Nutrition and Dietetics. A total of 973 articles were identified through database searching and 3 additional articles were included via cross-reference. Subsequent to de-duplication, 723 articles were screened by title and abstract, of which 709 were excluded based on inclusion criteria established a priori. The remaining 14 studies were independently screened by 2 reviewers for final inclusion. Included studies were published between 2010 and 2019 and included 8 comparative cross-sectional studies, 4 cross-sectional studies, 1 randomized crossover study, and 1 substudy of a randomized 2-period crossover trial. Associations of a diet rich in indigestible plant polysaccharides with Prevotella, or with an enterotype dominated by this genus, often comprised of the species Prevotella copri, were observed. In addition, associations of a high-fat and -sugar diet with Bacteroides, or with an enterotype dominated by this genus, were observed predominantly in comparative cross-sectional and cross-sectional studies spanning the ages of 1–15 y. This review identified a gap in the literature for ages 16–20 y. In addition, randomized controlled trials for dietary intervention are needed to move from association-based observations to causal relations between diet and microbiota composition and function.

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Association between the Urinary Sodium to Potassium Ratio and Blood Pressure in Adults: A Systematic Review and Meta-Analysis

Rhoda N Ndanuko, Rukayat Ibrahim, Retno A Hapsari, Elizabeth P Neale, David Raubenheimer, Karen E Charlton

doi : 10.1093/advances/nmab036

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1751–1767

While sodium and potassium are individually important for blood pressure (BP) regulation, the relative contribution of sodium to potassium intake has not been sufficiently investigated. This study aimed to evaluate the association between urinary sodium to potassium ratio (UNa: K) and systolic and diastolic BP in adults. A systematic review (PROSPERO; CRD42016035296) was conducted and was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Three scientific databases (MEDLINE, Scopus, Web of Science) were searched to March 2020 while reference lists of included articles were further hand-searched. Randomized controlled trials (RCT), cohort and cross-sectional studies that assessed 24-h urinary excretion in adults were included. Data from eligible studies were extracted and summarized. Random effects meta-analysis was conducted on RCT data to assess standardized mean differences (SMD) in systolic and diastolic BP according to 24-h UNa: K. Thirty-nine studies were included. Meta-analysis of 5 RCTs found a lower UNa: K ratio to be associated with a significantly greater reduction in systolic and diastolic BP compared with a higher UNa: K ratio [SMD: ?1.09 (95% CI: ?1.91, ?0.28) mmHg and ?1.42 (95% CI: ?2.24, ?0.59) mmHg, respectively]. Heterogeneity between RCTs was observed in systolic and diastolic BP (I2 = 97%, P < 0.0001 and I2 = 98%, P < 0.0001, respectively). The current body of evidence demonstrates that a lower 24-h UNa: K ratio is associated with lower BP in adults. Dietary strategies to achieve an increase in potassium while at the same time lowering sodium would be beneficial in lowering BP.

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A Systematic Review of Salt Reduction Initiatives Around the World: A Midterm Evaluation of Progress Towards the 2025 Global Non-Communicable Diseases Salt Reduction Target

Joseph Alvin Santos, Dejen Tekle, Emalie Rosewarne, Nadia Flexner, Laura Cobb, Ayoub Al-Jawaldeh, Warrick Junsuk Kim, Joao Breda, Stephen Whiting, Norm Campbell, Bruce Neal, Jacqui Webster, Kathy Trieu

doi : 10.1093/advances/nmab008

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1768–1780

In 2013, the WHO recommended that all member states aim to reduce population salt intake by 30% by 2025. The year 2019 represents the midpoint, making it a critical time to assess countries’ progress towards this target. This review aims to identify all national salt reduction initiatives around the world in 2019, and to quantify countries’ progress in achieving the salt reduction target. Relevant data were identified through searches of peer-reviewed and gray literature, supplemented with responses from prefilled country questionnaires sent to known country leads of salt reduction or salt champions, WHO regional representatives, and international experts to request further information. Core characteristics of each country's strategy, including evaluations of program impact, were extracted and summarized. A total of 96 national salt reduction initiatives were identified, representing a 28% increase in the number reported in 2014. About 90% of the initiatives were multifaceted in approach, and 60% had a regulatory component. Approaches include interventions in settings (n= 74), food reformulation (n = 68), consumer education (n = 50), front-of-pack labeling (n = 48), and salt taxation (n = 5). Since 2014, there has been an increase in the number of countries implementing each of the approaches, except consumer education. Data on program impact were limited. There were 3 countries that reported a substantial decrease (>2 g/day), 9 that reported a moderate decrease (1–2 g/day), and 5 that reported a slight decrease (<1 g/day) in the mean salt intake over time, but none have yet met the targeted 30% relative reduction in salt intake from baseline. In summary, there has been an increase in the number of salt reduction initiatives around the world since 2014. More countries are now opting for structural or regulatory approaches. However, efforts must be urgently accelerated and replicated in other countries and more rigorous monitoring and evaluation of strategies is needed to achieve the salt reduction target.

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Dietary Assessment Methods to Estimate (Poly)phenol Intake in Epidemiological Studies: A Systematic Review

Yifan Xu, Melanie Le Sayec, Caroline Roberts, Sabine Hein, Ana Rodriguez-Mateos, Rachel Gibson

doi : 10.1093/advances/nmab017

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1781–1801

Nutritional epidemiological studies have frequently reported associations between higher (poly)phenol intake and a decrease in the risk or incidence of noncommunicable diseases. However, the assessment methods that have been used to quantify the intakes of these compounds in large-population samples are highly variable. This systematic review aims to characterize the methods used to assess dietary (poly)phenol intake in observational studies, report the validation status of the methods, and give recommendations on method selection and data reporting. Three databases were searched for publications that have used dietary assessment methods to measure (poly)phenol intake and 549 eligible full texts were identified. Food-frequency questionnaires were found to be the most commonly used tool to assess dietary (poly)phenol intake (73%). Published data from peer-reviewed journals were the major source of (poly)phenol content data (25%). An increasing number of studies used open-access databases such as Phenol-Explorer and USDA databases on flavonoid content since their inception, which accounted for 11% and 23% of the data sources, respectively. Only 16% of the studies reported a method that had been validated for measuring the target (poly)phenols. For future research we recommend: 1) selecting a validated dietary assessment tool according to the target compounds and target period of measurement; 2) applying and combining comprehensive (poly)phenol content databases such as USDA and Phenol-Explorer; 3) detailing the methods used to assess (poly)phenol intake, including dietary assessment method, (poly)phenol content data source; 4) follow the Strengthening the Reporting of Observational Studies in Epidemiology—Nutritional Epidemiology (STROBE-nut) framework; and 5) complementing dietary intake assessment based on questionnaires with measurement of (poly)phenols in biofluids using appropriate and validated analytical methods.

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Pro-biomics: Omics Technologies To Unravel the Role of Probiotics in Health and Disease

Despoina Eugenia Kiousi, Marina Rathosi, Margaritis Tsifintaris, Pelagia Chondrou, Alex Galanis

doi : 10.1093/advances/nmab014

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1802–1820

The comprehensive characterization of probiotic action has flourished during the past few decades, alongside the evolution of high-throughput, multiomics platforms. The integration of these platforms into probiotic animal and human studies has provided valuable insights into the holistic effects of probiotic supplementation on intestinal and extraintestinal diseases. Indeed, these methodologies have informed about global molecular changes induced in the host and residing commensals at multiple levels, providing a bulk of metagenomic, transcriptomic, proteomic, and metabolomic data. The meaningful interpretation of generated data remains a challenge; however, the maturation of the field of systems biology and artificial intelligence has supported analysis of results. In this review article, we present current literature on the use of multiomics approaches in probiotic studies, we discuss current trends in probiotic research, and examine the possibility of tailor-made probiotic supplementation. Lastly, we delve deeper into newer technologies that have been developed in the last few years, such as single-cell multiomics analyses, and provide future directions for the maximization of probiotic efficacy.

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Effects of Foods Fortified with Zinc, Alone or Cofortified with Multiple Micronutrients, on Health and Functional Outcomes: A Systematic Review and Meta-Analysis

Becky L Tsang, Erin Holsted, Christine M McDonald, Kenneth H Brown, Robert Black, Mduduzi N N Mbuya, Frederick Grant, Laura A Rowe, Mari S Manger

doi : 10.1093/advances/nmab065

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1821–1837

Seventeen per cent of the world's population is estimated to be at risk of inadequate zinc intake, which could in part be addressed by zinc fortification of widely consumed foods. We conducted a review of efficacy and effectiveness studies to ascertain the effect of zinc fortification [postharvest fortification of an industrially produced food or beverage; alone or with multiple micronutrients (MMN)] on a range of health outcomes. Previous reviews have required that the effect of zinc be isolated; because zinc is always cofortified with MMN in existing fortification programs, we did not impose this condition. Outcomes assessed were zinc-related biomarkers (plasma or serum, hair or urine zinc concentrations, comet assay, plasma fatty acid concentrations, and the proportion of and total zinc absorbed in the intestine from the diet), child anthropometry, morbidity, mortality, cognition, plasma or serum iron and copper concentrations, and for observational studies, a change in consumption of the food vehicle. Fifty-nine studies were included in the review; 54 in meta-analyses, totaling 73 comparisons. Zinc fortification with and without MMN increased plasma zinc concentrations (efficacy, n = 27: 4.68 ?g/dL; 95% CI: 2.62–6.75; effectiveness, n = 13: 6.28 ?g/dL; 95% CI: 5.03–7.77 ?g/dL) and reduced the prevalence of zinc deficiency (efficacy, n = 11: OR: 0.76, 95% CI: 0.60–0.96; effectiveness, n = 10: OR: 0.45, 95% CI: 0.31–0.64). There were statistically significant increases in child weight (efficacy, n = 11: 0.43 kg, 95% CI: 0.11–0.75 kg), improvements in short-term auditory memory (efficacy, n = 3: 0.32 point, 95% CI: 0.13–0.50 point), and decreased incidence of diarrhea (efficacy, n = 3: RR: 0.79, 95% CI: 0.68–0.92) and fever (efficacy, n = 2: RR: 0.85, 95% CI: 0.74–0.97). However, these effects cannot be solely attributed to zinc. Our review found that zinc fortification with or without MMN reduced the prevalence of zinc deficiency and may provide health and functional benefits, including a reduced incidence of diarrhea.

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Ethnic Differences in Iron Status

Wanhui Kang, Alexa Barad, Andrew G Clark, Yiqin Wang, Xu Lin, Zhenglong Gu, Kimberly O O'Brien

doi : 10.1093/advances/nmab035

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1838–1853

Iron is unique among all minerals in that humans have no regulatable excretory pathway to eliminate excess iron after it is absorbed. Iron deficiency anemia occurs when absorbed iron is not sufficient to meet body iron demands, whereas iron overload and subsequent deposition of iron in key organs occur when absorbed iron exceeds body iron demands. Over time, iron accumulation in the body can increase risk of chronic diseases, including cirrhosis, diabetes, and heart failure. To date, only ?30% of the interindividual variability in iron absorption can be captured by iron status biomarkers or iron regulatory hormones. Much of the regulation of iron absorption may be under genetic control, but these pathways have yet to be fully elucidated. Genome-wide and candidate gene association studies have identified several genetic variants that are associated with variations in iron status, but the majority of these data were generated in European populations. The purpose of this review is to summarize genetic variants that have been associated with alterations in iron status and to highlight the influence of ethnicity on the risk of iron deficiency or overload. Using extant data in the literature, linear mixed-effects models were constructed to explore ethnic differences in iron status biomarkers. This approach found that East Asians had significantly higher concentrations of iron status indicators (serum ferritin, transferrin saturation, and hemoglobin) than Europeans, African Americans, or South Asians. African Americans exhibited significantly lower hemoglobin concentrations compared with other ethnic groups. Further studies of the genetic basis for ethnic differences in iron metabolism and on how it affects disease susceptibility among different ethnic groups are needed to inform population-specific recommendations and personalized nutrition interventions for iron-related disorders.

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Validity of Body-Composition Methods across Racial and Ethnic Populations

Malia N M Blue, Grant M Tinsley, Eric D Ryan, Abbie E Smith-Ryan

doi : 10.1093/advances/nmab016

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1854–1862

Multi-compartment body-composition models that divide the body into its multiple constituents are the criterion method for measuring body fat percentage, fat mass, and fat-free mass. However, 2- and 3-compartment body-composition devices such as air displacement plethysmography (ADP), DXA, and bioelectrical impedance devices [bioelectrical impedance analysis (BIA)] are more commonly used. Accurate measures depend on several assumptions, including constant hydration, body proportion, fat-free body density, and population characteristics. Investigations evaluating body composition in racial and ethnic minorities have observed differences in the aforementioned components between cohorts. Consequently, for racial/ethnic minority populations, estimates of body composition may not be valid. The purpose of this review was to comprehensively examine the validity of common body-composition devices in multi-ethnic samples (samples including >1 race/ethnicity) and in African-American, Hispanic, Asian, and Native American populations. Based on the literature, DXA produces valid results in multi-ethnic samples and ADP is valid for Hispanic and African American males when utilizing race-specific equations. However, for DXA and ADP, there is a need for validity investigations that include larger, more racially diverse samples, specifically including Hispanic/Latinx, Asian, Native American adults, and African-American females. Technology has advanced significantly since initial validity studies were conducted; therefore, conclusions are based on outdated models and software. For BIA, body-composition measures may be valid in a multi-ethnic sample, but the literature demonstrates disparate results between races/ethnicities. For BIA and ADP, the majority of studies have utilized DXA or hydrostatic weighing as the criterion to determine validity; additional studies utilizing a multi-compartment model criterion are essential to evaluate accuracy. Validity studies evaluating more recent technology in larger, more racially/ethnically diverse samples may improve our ability to select the appropriate method to accurately assess body composition in each racial/ethnic population.

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Protein Intake from Birth to 2 Years and Obesity Outcomes in Later Childhood and Adolescence: A Systematic Review of Prospective Cohort Studies

Alexandra Stokes, Karen J Campbell, Hong-Jie Yu, Ewa A Szymlek-Gay, Gavin Abbott, Qi-Qiang He, Miaobing Zheng

doi : 10.1093/advances/nmab034

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1863–1876

Emerging evidence shows an association between protein intake during infancy and later obesity risk, and that association may differ by protein sources. This systematic review summarized and evaluated prospective cohort studies assessing the long-term association of total protein intake and protein sources during infancy (from birth to 2 y) with subsequent obesity outcomes in childhood or adolescence. Literature searches were conducted in Embase, Medline, Scopus, and Web of Science. Sixteen studies that reported associations between total protein intake and/or protein intake from different sources from birth to 2 y and ?1 obesity outcomes in childhood or adolescence from 9 cohorts were identified. Most studies (11/16) were rated as high quality. The most frequently reported association was total protein intake and BMI (up to 10 y) with 6 out of 7 cohorts showing significant positive associations. Similar associations were found for animal protein, but not for plant protein. Limited studies examined the association between protein intake (both total and sources) and body composition (body fat, fat mass, and fat-free mass) and revealed inconsistent findings. Overall, higher intakes of total and animal protein during infancy were associated with higher BMI in childhood and adolescence. Future studies investigating the contribution of protein sources in long-term obesity development are needed. This review was registered at PROSPERO as CRD42020166540.

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Nutritional Status Impacts Epigenetic Regulation in Early Embryo Development: A Scoping Review

Shuang Cai, Shuang Quan, Guangxin Yang, Meixia Chen, Qianhong Ye, Gang Wang, Haitao Yu, Yuming Wang, Shiyan Qiao, Xiangfang Zeng

doi : 10.1093/advances/nmab038

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1877–1892

With the increasing maternal age and the use of assisted reproductive technology in various countries worldwide, the influence of epigenetic modification on embryonic development is increasingly notable and prominent. Epigenetic modification disorders caused by various nutritional imbalance would cause embryonic development abnormalities and even have an indelible impact on health in adulthood. In this scoping review, we summarize the main epigenetic modifications in mammals and the synergies among different epigenetic modifications, especially DNA methylation, histone acetylation, and histone methylation. We performed an in-depth analysis of the regulation of various epigenetic modifications on mammals from zygote formation to cleavage stage and blastocyst stage, and reviewed the modifications of key sites and their potential molecular mechanisms. In addition, we discuss the effects of nutrition (protein, lipids, and one-carbon metabolism) on epigenetic modification in embryos and emphasize the importance of various nutrients in embryonic development and epigenetics during pregnancy. Failures in epigenetic regulation have been implicated in mammalian and human early embryo loss and disease. With the use of reproductive technologies, it is becoming even more important to establish developmentally competent embryos. Therefore, it is essential to evaluate the extent to which embryos are sensitive to these epigenetic modifications and nutrition status. Understanding the epigenetic regulation of early embryo development will help us make better use of reproductive technologies and nutrition regulation to improve reproductive health in mammals.

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Putting ATM to BED: How Adipose Tissue Macrophages Are Affected by Bariatric Surgery, Exercise, and Dietary Fatty Acids

Laurent Turner, Sylvia Santosa

doi : 10.1093/advances/nmab011

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1893–1910

With increasing adiposity in obesity, adipose tissue macrophages contribute to adipose tissue malfunction and increased circulating proinflammatory cytokines. The chronic low-grade inflammation that occurs in obesity ultimately gives rise to a state of metainflammation that increases the risk of metabolic disease. To date, only lifestyle and surgical interventions have been shown to be somewhat effective at reversing the negative consequences of obesity and restoring adipose tissue homeostasis. Exercise, dietary interventions, and bariatric surgery result in immunomodulation, and for some individuals their effects are significant with or without weight loss. Robust evidence suggests that these interventions reduce chronic inflammation, in part, by affecting macrophage infiltration and promoting a phenotypic switch from the M1- to M2-like macrophages. The purpose of this review is to discuss the impact of dietary fatty acids, exercise, and bariatric surgery on cellular characteristics affecting adipose tissue macrophage presence and phenotypes in obesity.

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Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity

Felix Hadtstein, Misha Vrolijk

doi : 10.1093/advances/nmab033

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1911–1929

Vitamin B-6 in the form of pyridoxine (PN) is commonly used by the general population. The use of PN-containing supplements has gained lots of attention over the past years as they have been related to the development of peripheral neuropathy. In light of this, the number of reported cases of adverse health effects due to the use of vitamin B-6 have increased. Despite a long history of study, the pathogenic mechanisms associated with PN toxicity remain elusive. Therefore, the present review is focused on investigating the mechanistic link between PN supplementation and sensory peripheral neuropathy. Excessive PN intake induces neuropathy through the preferential injury of sensory neurons. Recent reports on hereditary neuropathy due to pyridoxal kinase (PDXK) mutations may provide some insight into the mechanism, as genetic deficiencies in PDXK lead to the development of axonal sensory neuropathy. High circulating concentrations of PN may lead to a similar condition via the inhibition of PDXK. The mechanism behind PDXK-induced neuropathy is unknown; however, there is reason to believe that it may be related to ?-aminobutyric acid (GABA) neurotransmission. Compounds that inhibit PDXK lead to convulsions and reductions in GABA biosynthesis. The absence of central nervous system-related symptoms in PDXK deficiency could be due to differences in the regulation of PDXK, where PDXK activity is preserved in the brain but not in peripheral tissues. As PN is relatively impermeable to the blood–brain barrier, PDXK inhibition would similarly be confined to the peripheries and, as a result, GABA signaling may be perturbed within peripheral tissues, such as sensory neurons. Perturbed GABA signaling within sensory neurons may lead to excitotoxicity, neurodegeneration, and ultimately, the development of peripheral neuropathy. For several reasons, we conclude that PDXK inhibition and consequently disrupted GABA neurotransmission is the most plausible mechanism of toxicity.

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Ready-to-Use Therapeutic Food (RUTF) Containing Low or No Dairy Compared to Standard RUTF for Children with Severe Acute Malnutrition: A Systematic Review and Meta-Analysis

Isabel Potani, Carolyn Spiegel-Feld, Garyk Brixi, Jaden Bendabenda, Nandi Siegfried, Robert H J Bandsma, André Briend, Allison I Daniel

doi : 10.1093/advances/nmab027

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1930–1943

Ready-to-use therapeutic food (RUTF) containing less dairy may be a lower-cost treatment option for severe acute malnutrition (SAM). The objective was to understand the effectiveness of RUTF containing alternative sources of protein (nondairy), or <50% of protein from dairy products, compared with standard RUTF in children with SAM. The Cochrane Library, MEDLINE, Embase, CINAHL, and Web of Science were searched using terms relating to RUTF. Studies were eligible if they included children with SAM and evaluated RUTF with <50% of protein from dairy products compared with standard RUTF. Meta-analysis and meta-regression were completed to assess the effectiveness of intervention RUTF on a range of child outcomes. The quality of the evidence across outcomes was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A total of 5868 studies were identified, of which 8 articles of 6 studies met the inclusion criteria evaluating 7 different intervention RUTF recipes. Nondairy or lower-dairy RUTF showed less weight gain (standardized mean difference: ?0.20; 95% CI: ?0.26, ?0.15; P < 0.001), lower recovery (relative risk ratio: 0.93; 95% CI: 0.87, 1.00; P = 0.046), and lower weight-for-age z scores (WAZ) near program discharge (mean difference: ?0.10; 95% CI: ?0.20, 0.0; P = 0.047). Mortality, time to recovery, default (consecutive absences from outpatient therapeutic feeding program visits), nonresponse, and other anthropometric measures did not differ between groups. The certainty of evidence was high for weight gain and ranged from very low to moderate for other outcomes. RUTF with lower protein from dairy or dairy-free RUTF may not be as effective as standard RUTF for treatment of children with SAM based on weight gain, recovery, and WAZ evaluated using meta-analysis, although further research is required to explore the potential of alternative formulations. This review was registered at https://www.crd.york.ac.uk/prospero/ as CRD42020160762.

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Healthy Food Prescription Programs and their Impact on Dietary Behavior and Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis

Saiuj Bhat, Daisy H Coyle, Kathy Trieu, Bruce Neal, Dariush Mozaffarian, Matti Marklund, Jason H Y Wu

doi : 10.1093/advances/nmab039

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1944–1956

The enormous burden of diet-related chronic diseases has prompted interest in healthy food prescription programs. Yet, the impact of such programs remains unclear. The aim of this study was to conduct a systematic review of healthy food prescription programs and evaluate their impact on dietary behavior and cardiometabolic parameters by meta-analysis. A systematic search was carried out in Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials databases since their inception to 3 January, 2020 without language restriction. A systematic search of interventional studies investigating the effect of healthy food prescription on diet quality and/or cardiometabolic risk factors including BMI, systolic (SBP) and diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), or blood lipids was carried out. Thirteen studies were identified for inclusion, most of which were quasi-experimental (pre/post) interventions without a control group (n = 9). Pooled estimates revealed a 22% (95% CI: 12, 32; n = 5 studies, n = 1039 participants; I2 = 97%) increase in fruit and vegetable consumption, corresponding to 0.8 higher daily servings (95% CI: 0.2, 1.4; I2 = 96%). BMI decreased by 0.6 kg/m2 (95% CI: 0.2, 1.1; I2 = 6.4%) and HbA1c by 0.8% (95% CI: 0.1, 1.6; I2 = 92%). No significant change was observed in other cardiometabolic parameters. These findings should be interpreted with caution in light of considerable heterogeneity, methodological limitations of the included studies, and moderate to very low certainty of evidence. Our results support the need for well-designed, large, randomized controlled trials in various settings to further establish the efficacy of healthy food prescription programs on diet quality and cardiometabolic health.

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Simulation Modeling for the Economic Evaluation of Population-Based Dietary Policies: A Systematic Scoping Review

Karl M F Emmert-Fees, Florian M Karl, Peter von Philipsborn, Eva A Rehfuess, Michael Laxy on behalf of the Policy Evaluation Network (PEN) Consortium

doi : 10.1093/advances/nmab028

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1957–1995

Simulation modeling can be useful to estimate the long-term health and economic impacts of population-based dietary policies. We conducted a systematic scoping review following the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guideline to map and critically appraise economic evaluations of population-based dietary policies using simulation models. We searched Medline, Embase, and EconLit for studies published in English after 2005. Modeling studies were mapped based on model type, dietary policy, and nutritional target, and modeled risk factor–outcome pathways were analyzed. We included 56 studies comprising 136 model applications evaluating dietary policies in 21 countries. The policies most often assessed were reformulation (34/136), taxation (27/136), and labeling (20/136); the most common targets were salt/sodium (60/136), sugar-sweetened beverages (31/136), and fruit and vegetables (15/136). Model types included Markov-type (35/56), microsimulation (11/56), and comparative risk assessment (7/56) models. Overall, the key diet-related risk factors and health outcomes were modeled, but only 1 study included overall diet quality as a risk factor. Information about validation was only reported in 19 of 56 studies and few studies (14/56) analyzed the equity impacts of policies. Commonly included cost components were health sector (52/56) and public sector implementation costs (35/56), as opposed to private sector (18/56), lost productivity (11/56), and informal care costs (3/56). Most dietary policies (103/136) were evaluated as cost-saving independent of the applied costing perspective. An analysis of the main limitations reported by authors revealed that model validity, uncertainty of dietary effect estimates, and long-term intervention assumptions necessitate a careful interpretation of results. In conclusion, simulation modeling is widely applied in the economic evaluation of population-based dietary policies but rarely takes dietary complexity and the equity dimensions of policies into account. To increase relevance for policymakers and support diet-related disease prevention, economic effects beyond the health sector should be considered, and transparent conduct and reporting of model validation should be improved.

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Toward a Healthy and Environmentally Sustainable Campus Food Environment: A Scoping Review of Postsecondary Food Interventions

Kirsten M Lee, Goretty M Dias, Karla Boluk, Steffanie Scott, Yi-Shin Chang, Tabitha E Williams, Sharon I Kirkpatrick

doi : 10.1093/advances/nmab026

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 1996–2022

Interventions are urgently needed to transform the food system and shift population eating patterns toward those consistent with human health and environmental sustainability. Postsecondary campuses offer a naturalistic setting to trial interventions to improve the health of students and provide insight into interventions that could be scaled up in other settings. However, the current state of the evidence on interventions to support healthy and environmentally sustainable eating within postsecondary settings is not well understood. A scoping review of food- and nutrition-related interventions implemented and evaluated on postsecondary campuses was conducted to determine the extent to which they integrate considerations related to human health and/or environmental sustainability, as well as to synthesize the nature and effectiveness of interventions and to identify knowledge gaps in the literature. MEDLINE (via PubMed), CINAHL, Scopus, and ERIC were searched to identify articles describing naturalistic campus food interventions published in English from January 2015 to December 2019. Data were extracted from 38 peer-reviewed articles, representing 37 unique interventions, and synthesized according to policy domains within the World Cancer Research Foundation's NOURISHING framework. Most interventions were focused on supporting human health, whereas considerations related to environmental sustainability were minimal. Interventions to support human health primarily sought to increase nutrition knowledge or to make complementary shifts in food environments, such as through nutrition labeling at point of purchase. Interventions to support environmental sustainability often focused on reducing food waste and few emphasized consumption patterns with lower environmental impacts. The implementation of integrated approaches considering the complexity and interconnectivity of human and planetary health is needed. Such approaches must go beyond the individual to alter the structural determinants that shape our food system and eating patterns.

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Synergizing Mouse and Human Studies to Understand the Heterogeneity of Obesity

Penny Gordon-Larsen, John E French, Naima Moustaid-Moussa, Venkata S Voruganti, Elizabeth J Mayer-Davis, Christopher A Bizon, Zhiyong Cheng, Delisha A Stewart, John W Easterbrook, Saame Raza Shaikh

doi : 10.1093/advances/nmab040

Advances in Nutrition, Volume 12, Issue 5, September 2021, Pages 2023–2034

Obesity is routinely considered as a single disease state, which drives a “one-size-fits-all” approach to treatment. We recently convened the first annual University of North Carolina Interdisciplinary Nutrition Sciences Symposium to discuss the heterogeneity of obesity and the need for translational science to advance understanding of this heterogeneity. The symposium aimed to advance scientific rigor in translational studies from animal to human models with the goal of identifying underlying mechanisms and treatments. In this review, we discuss fundamental gaps in knowledge of the heterogeneity of obesity ranging from cellular to population perspectives. We also advocate approaches to overcoming limitations in the field. Examples include the use of contemporary mouse genetic reference population models such as the Collaborative Cross and Diversity Outbred mice that effectively model human genetic diversity and the use of translational models that integrate -omics and computational approaches from pre-clinical to clinical models of obesity. Finally, we suggest best scientific practices to ensure strong rigor that will allow investigators to delineate the sources of heterogeneity in the population with obesity. Collectively, we propose that it is critical to think of obesity as a heterogeneous disease with complex mechanisms and etiologies, requiring unique prevention and treatment strategies tailored to the individual.

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