Perspective: Advancing Dietary Guidance for Cognitive Health-Focus On Solutions to Harmonize Test Selection, Implementation, and Evaluation.

This perspective article is a product of a workshop of experts convened by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS), a nonprofit organization that brings together scientists from government, academia, and industry to catalyze science relevant to food and nutrition for public benefit. An expert group was convened in March 2022 to discuss the current issues surrounding cognitive task selection in nutrition research, with a focus on solutions toward informing dietary guidance for cognitive health, to address a gap identified in the 2020 United States Dietary Guidelines Advisory Committee report, specifically the "considerable variation in testing methods used, [and] inconsistent validity and reliability of cognitive testing methods." To address this issue, we first undertook an umbrella review of relevant reviews already undertaken; these indicate agreement on some of the issues that affect heterogeneity in task selection, and on many of the fundamental principles underlying the selection of cognitive outcome measures. However, resolving the points of disagreement is critical to ensuring a meaningful impact on the issue of heterogeneity in task selection; these issues hamper the evaluation of existing data for informing dietary guidance. This summary of the literature is therefore followed by the expert group's perspective in the form of a discussion of potential solutions to these challenges, with the aim of building on the work of previous reviews in the area and advancing dietary guidance for cognitive health. Registered on PROSPERO: CRD42022348106. Data described in the manuscript, code book, and analytic code will be made publicly and freely available without restriction at doi.org/10.17605/OSF.IO/XRZCK.

The Challenge of Measuring Sweet Taste in Food Ingredients and Products for Regulatory Compliance: A Scientific Opinion.

The Codex Alimentarius Commission, a central part of the joint Food and Agricultural Organization/World Health Organizations Food Standards Program, adopts internationally recognized standards, guidelines, and code of practices that help ensure safety, quality, and fairness of food trade globally. Although Codex standards are not regulations per se, regulatory authorities around the world may benchmark against these standards or introduce them into regulations within their countries. Recently, the Codex Committee on Nutrition and Foods for Special Dietary Uses (CCNFSDU) initiated a draft revision to the Codex standard for follow-up formula (FUF), a drink/product (with added nutrients) for young children, to include requirements for limiting or measuring the amount of sweet taste contributed by carbohydrates in a product. Stakeholders from multiple food and beverage manufacturers expressed concern about the subjectivity of sweetness and challenges with objective measurement for verifying regulatory compliance. It is a requirement that Codex standards include a reference to a suitable method of analysis for verifying compliance with the standard. In response, AOAC INTERNATIONAL formed the Ad Hoc Expert Panel on Sweetness in November 2020 to review human perception of sweet taste, assess the landscape of internationally recognized analytical and sensory methods for measuring sweet taste in food ingredients and products, deliver recommendations to Codex regarding verification of sweet taste requirements for FUF, and develop a scientific opinion on measuring sweet taste in food and beverage products beyond FUF. Findings showed an abundance of official analytical methods for determining quantities of carbohydrates and other sweet-tasting molecules in food products and beverages, but no analytical methods capable of determining sweet taste. Furthermore, sweet taste can be determined by standard sensory analysis methods. However, it is impossible to define a sensory intensity reference value for sweetness, making them unfit to verify regulatory compliance for the purpose of international food trade. Based on these findings and recommendations, the Codex Committee on Methods of Analysis and Sampling agreed during its 41st session in May 2021 to inform CCNFSDU that there are no known validated methods to measure sweetness of carbohydrate sources; therefore, no way to determine compliance for such a requirement for FUF.

Workshop report: Toward the development of a human whole stool reference material for metabolomic and metagenomic gut microbiome measurements.

INTRODUCTION: To date, there has been little effort to develop standards for metabolome-based gut microbiome measurements despite the significant efforts toward standard development for DNA-based microbiome measurements. OBJECTIVES: The National Institute of Standards and Technology (NIST), The BioCollective (TBC), and the North America Branch of the International Life Sciences Institute (ILSI North America) are collaborating to extend NIST's efforts to develop a Human Whole Stool Reference Material for the purpose of method harmonization and eventual quality control. METHODS: The reference material will be rationally designed for adequate quality assurance and quality control (QA/QC) for underlying measurements in the study of the impact of diet and nutrition on functional aspects of the host gut microbiome and relationships of those functions to health. To identify which metabolites deserve priority in their value assignment, NIST, TBC, and ILSI North America jointly conducted a workshop on September 12, 2019 at the NIST campus in Gaithersburg, Maryland. The objective of the workshop was to identify metabolites for which evidence indicates relevance to health and disease and to decide on the appropriate course of action to develop a fit-for-purpose reference material. RESULTS: This document represents the consensus opinions of workshop participants and co-authors of this manuscript, and provides additional supporting information. In addition to developing general criteria for metabolite selection and a preliminary list of proposed metabolites, this paper describes some of the strengths and limitations of this initiative given the current state of microbiome research. CONCLUSIONS: Given the rapidly evolving nature of gut microbiome science and the current state of knowledge, an RM (as opposed to a CRM) measured for multiple metabolites is appropriate at this stage. As the science evolves, the RM can evolve to match the needs of the research community. Ultimately, the stool RM may exist in sequential versions. Beneficial to this evolution will be a clear line of communication between NIST and the stakeholder community to ensure alignment with current scientific understanding and community needs.

Advancements in Personalized Nutrition Technologies: Guiding Principles for Registered Dietitian Nutritionists.

Individualized nutrition counseling and care is a cornerstone of practice for registered dietitian nutritionists (RDNs). The term personalized nutrition (PN) refers to "individual-specific information founded in evidence-based science to promote dietary behavior change that may result in measurable health benefits." PN technologies, which include the "omics" approaches, may offer the potential to improve specificity of nutrition care through assessment of molecular-level data, such as genes or the microbiome, in order to determine the course for nutrition intervention. These technologies are evolving rapidly, and for many RDNs, it is unclear whether, when, or how these technologies should be incorporated into the nutrition care process. In order to provide guidance in these developing PN fields, International Life Sciences Institute North America convened a multidisciplinary panel to develop guiding principles for PN approaches. The objective of this article is to inform RDN practice decisions related to the implementation of PN technologies by examining the alignment of proposed PN guiding principles with the Code of Ethics for the Nutrition and Dietetics Profession, as well as Scope and Standards of Practice. Guiding principles are described as they apply to each stage of the nutrition care process and include identifying potential beneficiaries, communicating effects transparently, and protecting individual privacy. Guiding principles for PN augment standard guidance for RDNs to pose relevant questions, raise potential concerns, and guide evaluation of supporting evidence for specific PN technologies. RDNs have a responsibility to think critically about the application of PN technologies, including appropriateness and potential effectiveness, for the individual served.

Perspective: Guiding Principles for the Implementation of Personalized Nutrition Approaches That Benefit Health and Function.

Personalized nutrition (PN) approaches have been shown to help drive behavior change and positively influence health outcomes. This has led to an increase in the development of commercially available PN programs, which utilize various forms of individual-level information to provide services and products for consumers. The lack of a well-accepted definition of PN or an established set of guiding principles for the implementation of PN creates barriers for establishing credibility and efficacy. To address these points, the North American Branch of the International Life Sciences Institute convened a multidisciplinary panel. In this article, a definition for PN is proposed: "Personalized nutrition uses individual-specific information, founded in evidence-based science, to promote dietary behavior change that may result in measurable health benefits." In addition, 10 guiding principles for PN approaches are proposed: 1) define potential users and beneficiaries; 2) use validated diagnostic methods and measures; 3) maintain data quality and relevance; 4) derive data-driven recommendations from validated models and algorithms; 5) design PN studies around validated individual health or function needs and outcomes; 6) provide rigorous scientific evidence for an effect on health or function; 7) deliver user-friendly tools; 8) for healthy individuals, align with population-based recommendations; 9) communicate transparently about potential effects; and 10) protect individual data privacy and act responsibly. These principles are intended to establish a basis for responsible approaches to the evidence-based research and practice of PN and serve as an invitation for further public dialog. Several challenges were identified for PN to continue gaining acceptance, including defining the health-disease continuum, identification of biomarkers, changing regulatory landscapes, accessibility, and measuring success. Although PN approaches hold promise for public health in the future, further research is needed on the accuracy of dietary intake measurement, utilization and standardization of systems approaches, and application and communication of evidence.

Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions.

On December 17, 2018, the North American branch of the International Life Sciences Institute (ILSI North America) convened a workshop "Can We Begin to Define a Healthy Gut Microbiome Through Quantifiable Characteristics?" with >40 invited academic, government, and industry experts in Washington, DC. The workshop objectives were to 1) develop a collective expert assessment of the state of the evidence on the human gut microbiome and associated human health benefits, 2) see if there was sufficient evidence to establish measurable gut microbiome characteristics that could serve as indicators of "health," 3) identify short- and long-term research needs to fully characterize healthy gut microbiome-host relationships, and 4) publish the findings. Conclusions were as follows: 1) mechanistic links of specific changes in gut microbiome structure with function or markers of human health are not yet established; 2) it is not established if dysbiosis is a cause, consequence, or both of changes in human gut epithelial function and disease; 3) microbiome communities are highly individualized, show a high degree of interindividual variation to perturbation, and tend to be stable over years; 4) the complexity of microbiome-host interactions requires a comprehensive, multidisciplinary research agenda to elucidate relationships between gut microbiome and host health; 5) biomarkers and/or surrogate indicators of host function and pathogenic processes based on the microbiome need to be determined and validated, along with normal ranges, using approaches similar to those used to establish biomarkers and/or surrogate indicators based on host metabolic phenotypes; 6) future studies measuring responses to an exposure or intervention need to combine validated microbiome-related biomarkers and/or surrogate indicators with multiomics characterization of the microbiome; and 7) because static genetic sampling misses important short- and long-term microbiome-related dynamic changes to host health, future studies must be powered to account for inter- and intraindividual variation and should use repeated measures within individuals.

Moving the Needle on Hypertension: What Knowledge Is Needed?

This review highlights the gaps in knowledge and methodological challenges discussed during the Experimental Biology 2019 expert panel session titled "Moving the Needle on Hypertension: What Knowledge Is Needed?" Hypertension is a critical public health burden. Despite a demonstrated benefit of blood pressure reduction on measures of hypertension-related morbidity and mortality, rates for successful blood pressure control remain low. Dietary sodium reduction has been shown to reduce both systolic blood pressure by approximately 3.2 mm Hg and diastolic blood pressure by 2.3 mm Hg, depending on baseline blood pressure and degree of sodium reduction. The updated Dietary Reference Intakes for adults released by the National Academies of Sciences, Engineering, and Medicine include a Chronic Disease Risk Reduction sodium intake level of 2300 mg/d, highlighting the importance of dietary sodium intake in reducing elevated blood pressure and indicating that reducing intakes to this level is expected to reduce blood pressure and risk of cardiovascular disease. The average US daily sodium intake of 3400 mg/d is well above the Chronic Disease Risk Reduction of 2300 mg/d, suggesting that dietary sodium reduction has the potential to significantly improve public health. Although the National Academies of Sciences, Engineering, and Medicine report presents intake recommendations based on a systematic, comprehensive, and thorough evaluation of the evidence, several challenges to moving the needle on hypertension remain. Success will require a more advanced understanding of sodium and potassium physiology, as well as development of the tools needed to effectively address existing research gaps and reduce barriers to sodium intake reduction.

New Opportunities for Breastfeeding Promotion and Support in WIC: Review of WIC Food Packages, Improving Balance and Choice.

Although breastfeeding (BF) is the recommended way to feed infants, this may be difficult for the low-income women served by the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). The 2017 recommended revisions to the WIC food packages provide substantial support to both exclusively and partially BF dyads, remove barriers to partial BF choices within the first 30 days postpartum, and increase flexibility in determining the amount of formula offered to partially breastfed infants. When combined with adequate support and tailored counseling, these changes are intended to make it easier for women served by WIC to choose to breastfeed.

Postnatal growth in preterm infants and later health outcomes: a systematic review.

UNLABELLED: In preterm infants, poor postnatal growth is associated with adverse neurocognitive outcomes; conversely, rapid postnatal growth is supposedly harmful for future development of metabolic diseases. CONCLUSION: In this systematic review, observational studies reported consistent positive associations between postnatal weight or head growth and neurocognitive outcomes; however, there was limited evidence from the few intervention studies. Evidence linking postnatal weight gain to later adiposity and other cardiovascular disease risk factors in preterm infants was also limited.

Criteria for validation and selection of cognitive tests for investigating the effects of foods and nutrients.

This review is an output of the International Life Sciences Institute (ILSI) Europe Marker Initiative, which aims to identify evidence-based criteria for selecting adequate measures of nutrient effects on health through comprehensive literature review. Experts in cognitive and nutrition sciences examined the applicability of these proposed criteria to the field of cognition with respect to the various cognitive domains usually assessed to reflect brain or neurological function. This review covers cognitive domains important in the assessment of neuronal integrity and function, commonly used tests and their state of validation, and the application of the measures to studies of nutrition and nutritional intervention trials. The aim is to identify domain-specific cognitive tests that are sensitive to nutrient interventions and from which guidance can be provided to aid the application of selection criteria for choosing the most suitable tests for proposed nutritional intervention studies using cognitive outcomes. The material in this review serves as a background and guidance document for nutritionists, neuropsychologists, psychiatrists, and neurologists interested in assessing mental health in terms of cognitive test performance and for scientists intending to test the effects of food or food components on cognitive function.

Brain imaging and human nutrition: which measures to use in intervention studies?

The present review describes brain imaging technologies that can be used to assess the effects of nutritional interventions in human subjects. Specifically, we summarise the biological relevance of their outcome measures, practical use and feasibility, and recommended use in short- and long-term nutritional studies. The brain imaging technologies described consist of MRI, including diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI, as well as electroencephalography/magnetoencephalography, near-IR spectroscopy, positron emission tomography and single-photon emission computerised tomography. In nutritional interventions and across the lifespan, brain imaging can detect macro- and microstructural, functional, electrophysiological and metabolic changes linked to broader functional outcomes, such as cognition. Imaging markers can be considered as specific for one or several brain processes and as surrogate instrumental endpoints that may provide sensitive measures of short- and long-term effects. For the majority of imaging measures, little information is available regarding their correlation with functional endpoints in healthy subjects; therefore, imaging markers generally cannot replace clinical endpoints that reflect the overall capacity of the brain to behaviourally respond to specific situations and stimuli. The principal added value of brain imaging measures for human nutritional intervention studies is their ability to provide unique in vivo information on the working mechanism of an intervention in hypothesis-driven research. Selection of brain imaging techniques and target markers within a given technique should mainly depend on the hypothesis regarding the mechanism of action of the intervention, level (structural, metabolic or functional) and anticipated timescale of the intervention's effects, target population, availability and costs of the techniques.

ILSI Brazil International Workshop on Functional Foods: a narrative review of the scientific evidence in the area of carbohydrates, microbiome, and health.

To stimulate discussion around the topic of 'carbohydrates' and health, the Brazilian branch of the International Life Sciences Institute held the 11th International Functional Foods Workshop (1-2 December 2011) in which consolidated knowledge and recent scientific advances specific to the relationship between carbohydrates and health were presented. As part of this meeting, several key points related to dietary fiber, glycemic response, fructose, and impacts on satiety, cognition, mood, and gut microbiota were realized: 1) there is a need for global harmonization of a science-based fiber definition; 2) low-glycemic index foods can be used to modulate the postprandial glycemic response and may affect diabetes and cardiovascular outcomes; 3) carbohydrate type may influence satiety and satiation; glycemic load and glycemic index show links to memory, mood, and concentration; 4) validated biomarkers are needed to demonstrate the known prebiotic effect of carbohydrates; 5) negative effects of fructose are not evident when human data are systematically reviewed; 6) new research indicates that diet strongly influences the microbiome; and 7) there is mounting evidence that the intestinal microbiota has the ability to impact the gut-brain axis. Overall, there is much promise for development of functional foods that impact the microbiome and other factors relevant to health, including glycemic response (glycemic index/glycemic load), satiety, mood, cognition, and weight management.

The confusing world of dietary sugars: definitions, intakes, food sources and international dietary recommendations.

Government and health organizations worldwide have issued dietary guidelines for sugars. These guidelines vary considerably in the recommended or suggested intakes and the types of sugars specified. Despite access to the same published literature, recommendations vary greatly and create confusion for nutrition practitioners who offer dietary guidance. Some of the confusion in this field is linked to differences in definitions for sugar and methods to measure total sugars. Additionally, although dietary guidance typically recommends foods high in sugar, fruits and dairy products, other advice suggests strict limits on intake of "added sugar". Added sugar cannot be analytically determined and must be calculated so nutrient databases generally contain values for total sugar and do not differentiate between sugars naturally occurring in foods and those added in processing. This review defines sugars, provides the sugar content of major food sources, summarizes health concerns about dietary sugars, and compiles dietary guidelines for sugars issued by various organizations. Dietary recommendations from various health organizations are based on different means of assessment, and thus vary considerably. In general, the use of added sugars is cautioned, especially when it contributes to calories in excess of needs for an individual.

Fructose malabsorption and intolerance: effects of fructose with and without simultaneous glucose ingestion.

Concern exists that increasing fructose consumption, particularly in the form of high-fructose corn syrup, is resulting in increasing rates of fructose intolerance and aggravation of clinical symptoms in individuals with irritable bowel syndrome. Most clinical trials designed to test this hypothesis have used pure fructose, a form not commonly found in the food supply, often in quantities and concentrations that exceed typical fructose intake levels. In addition, the amount of fructose provided in tests for malabsorption, which is thought to be a key cause of intolerance, often exceeds the normal physiological absorption capacity for this sugar. To help health professionals accurately identify and treat this condition, this article reviews clinical data related to understanding fructose malabsorption and intolerance (i.e., malabsorption that manifests with symptoms) relative to usual fructose and other carbohydrate intake. Because simultaneous consumption of glucose attenuates fructose malabsorption, information on the fructose and glucose content of foods, beverages, and ingredients representing a variety of food categories is provided.

Refining the threshold of toxicological concern (TTC) for risk prioritization of trace chemicals in food.

Due to ever-improving analytical capabilities, very low levels of unexpected chemicals can now be detected in foods. Although these may be toxicologically insignificant, such incidents often garner significant attention. The threshold of toxicological concern (TTC) methodology provides a scientifically defensible, transparent approach for putting low-level exposures in the context of potential risk, as a tool to facilitate prioritization of responses, including potential mitigation. The TTC method supports the establishment of tiered, health-protective exposure limits for chemicals lacking a full toxicity database, based on evaluation of the known toxicity of chemicals which share similar structural characteristics. The approach supports the view that prudent actions towards public health protection are based on evaluation of safety as opposed to detection chemistry. This paper builds on the existing TTC literature and recommends refinements that address two key areas. The first describes the inclusion of genotoxicity data as a way to refine the TTC limit for chemicals that have structural alerts for genotoxicity. The second area addresses duration of exposure. Whereas the existing TTC exposure limits assume a lifetime of exposure, human exposure to unintended chemicals in food is often only for a limited time. Recommendations are made to refine the approach for less-than-lifetime exposures.

Folate deficiency does not alter the usefulness of the serum transferrin receptor concentration as an index for the detection of iron deficiency in mexican women during early lactation.

The purpose of this study was to investigate the usefulness of soluble serum transferrin receptor (TfR) concentration, TfR index and log TfR:ferritin ratio (TfR outcomes) in detecting tissue Fe deficiency among breast-feeding Otomi women residing in Capulhuac, Mexico (2800 m above sea level) and to determine whether folate deficiency modifies the interpretation of these data. Lactating women (n = 68) provided blood samples at 22 +/- 13 d (mean +/- SD) postpartum. Using the 3-index Fe assessment model with and without Hb, 2 women (3%) had Fe-deficient erythropoiesis, 24 (36%) Fe deficiency anemia, and 19 (29%) indeterminate Fe status; 29 (43%) and 5 (7.5%) women had plasma and erythrocyte folate concentrations below normative cutoff values, respectively. Mean values for TfR outcomes were higher among women classified as Fe deficient than those who were Fe sufficient, but did not differ with low or normal blood folate concentrations. Similarly, TfR outcomes did not differ among women with normocytic or macrocytic erythrocytes. Receiver-operating characteristic (ROC) curves generated for TfR outcomes yielded areas under the curve from 0.62 to 0.68, indicating that each of these measures, on its own, is a poor predictor of tissue Fe deficiency in lactating women. In conclusion, low blood folate concentrations or the presence of macrocytosis in Otomi women from Capulhuac, Mexico (moderate altitude) did not influence the utility of TfR outcomes for the detection of Fe deficiency during early lactation. Further, on their own, TfR, TfR index, and TfR:ferritin ratio were poor predictors of tissue Fe deficiency for any given individual.

Milk folate but not milk iron concentrations may be inadequate for some infants in a rural farming community in San Mateo, Capulhuac, Mexico.

BACKGROUND: We were interested in identifying possible nutritional reasons for growth faltering among breastfed infants in the rural farming community of San Mateo, Capulhuac, Mexico (2800 m above sea level). OBJECTIVE: We examined the prevalence of inadequate iron and folate status among lactating Otomi women and determined to what extent their iron and folate nutriture influenced the milk concentrations of these nutrients. DESIGN: Lactating women (n = 71) provided blood and milk samples and dietary information at a mean (+/- SD) of 22 +/- 13 d postpartum. Blood indexes included hemoglobin, hematocrit, serum iron, total-iron-binding capacity, ferritin, transferrin receptor, mean cell volume, plasma folate, and erythrocyte folate. RESULTS: Approximately 62% and 58% of the women had nutritional anemia defined as a hemoglobin concentration