Unraveling Links between Chronic Inflammation and Long COVID: Workshop Report.

As COVID-19 continues, an increasing number of patients develop long COVID symptoms varying in severity that last for weeks, months, or longer. Symptoms commonly include lingering loss of smell and taste, hearing loss, extreme fatigue, and "brain fog." Still, persistent cardiovascular and respiratory problems, muscle weakness, and neurologic issues have also been documented. A major problem is the lack of clear guidelines for diagnosing long COVID. Although some studies suggest that long COVID is due to prolonged inflammation after SARS-CoV-2 infection, the underlying mechanisms remain unclear. The broad range of COVID-19's bodily effects and responses after initial viral infection are also poorly understood. This workshop brought together multidisciplinary experts to showcase and discuss the latest research on long COVID and chronic inflammation that might be associated with the persistent sequelae following COVID-19 infection.

Research is still limited on nutrition and quality of life among older adults.

Introduction: Globally, the number of older adults is growing exponentially. Yet, while living longer, people are not necessarily healthier. Nutrition can positively impact healthy aging and quality of life (QoL). Two decades ago, nutrition and diet were rarely viewed as key QoL domains, were not part of QoL screening, and QoL studies frequently used unvalidated tools. It is unclear how the nutrition and QoL research area may have since evolved. Methods: A scoping review was conducted in Pubmed of research with community-living older adults (aged ≥65) from developed economies that included 1 of 29 common, valid QoL instruments, nutrition indices, and was published between 1/2000-12/2022. The review followed published methodology guidance and used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram to document identified studies and record number of included/excluded studies (based on scoping review's pre-specified criteria). Results: Of 258 studies identified initially, 37 fully met scoping review inclusion criteria; only 2 were QoL studies, 30 focused on nutrition, 3 on measurement tool validation/testing, and 2 were other study types. Most studies (n = 32) were among populations outside of North America; majority were conducted in Europe (n = 22) where the EuroQol 5 Dimension (Eq5D) was used in >1/2 the studies. Of 5 North American studies, the 36-Item Short Form Survey (SF-36) was most frequently used (n = 4). Myriad nutrition indices described various aspects of eating, dietary intake, and nutrition status, making comparability between studies difficult. Studies included several different nutrition questionnaires; Mini Nutritional Assessment (MNA) (n = 8) or Mini Nutritional Assessment Short Form (MNA-SF) (n = 5) were used most frequently. The most frequent anthropometric measure reported was Body Mass Index (BMI) (n = 28). Nutrition-related biochemical indices were reported infrequently (n = 8). Discussion: The paucity of studies over the last two decades suggests research on nutrition and QoL among community-living older adults remains underdeveloped. Valid QoL instruments and nutrition indices are now available. To ensure greater comparability among studies it is important to develop consensus on core indices of QoL and particularly nutrition. Greater agreement on these indices will advance further research to support healthy aging and improve QoL for community-dwelling older adults.

Major Gaps in Understanding Dietary Supplement Use in Health and Disease.

Precise dietary assessment is critical for accurate exposure classification in nutritional research, typically aimed at understanding how diet relates to health. Dietary supplement (DS) use is widespread and represents a considerable source of nutrients. However, few studies have compared the best methods to measure DSs. Our literature review on the relative validity and reproducibility of DS instruments in the United States [e.g., product inventories, questionnaires, and 24-h dietary recalls (24HR)] identified five studies that examined validity (n = 5) and/or reproducibility (n = 4). No gold standard reference method exists for validating DS use; thus, each study's investigators chose the reference instrument used to measure validity. Self-administered questionnaires agreed well with 24HR and inventory methods when comparing the prevalence of commonly used DSs. The inventory method captured nutrient amounts more accurately than the other methods. Reproducibility (over 3 months to 2.4 years) of prevalence of use estimates on the questionnaires was acceptable for common DSs. Given the limited body of research on measurement error in DS assessment, only tentative conclusions on these DS instruments can be drawn at present. Further research is critical to advancing knowledge in DS assessment for research and monitoring purposes.

Perspectives on the Use of Proprietary Blends in Dietary Supplements.

This paper discusses the rationale for use of proprietary blends on dietary supplement labels, and their implications for researchers and consumers. The Dietary Supplement Health Education Act of 1994 allows the listing of nonnutrient dietary ingredients as proprietary blends on dietary supplement labels for companies to protect their unique formulas. The weight of the blend and names of the ingredients within the blends must be declared, but not the amounts of the individual ingredients within the proprietary blend. Thus, from label information, the amount of a dietary ingredient in a proprietary blend is not available for calculating exposures in assessments of intakes or for determining doses in clinical trials.

Critical data at the crossroads: the National Health and Nutrition Examination Survey faces growing challenges.

NHANES needs urgent attention to ensure its future, which is facing emerging challenges associated with data collection, stagnant funding that has undercut innovation, and the increased call for granular data for subpopulations and groups at risk. The concerns do not rest merely on securing more funding but focus on the need for a constructive review of the survey to explore new approaches and identify appropriate change. This white paper, developed under the auspices of the ASN's Committee on Advocacy and Science Policy (CASP), is a call to the nutrition community to advocate for and support activities to prepare NHANES for future success in a changing nutrition world. Furthermore, because NHANES is much more than a nutrition survey and serves the needs of many in health fields and even commercial arenas, effective advocacy must be grounded in alliances among the survey's diverse stakeholders so that the full range of expertise and interests can engage. This article highlights the complicated nature of the survey along with key overarching challenges to underscore the importance of a measured, thoughtful, comprehensive, and collaborative approach to considering the future of NHANES. Starting-point questions are identified for the purposes of focusing dialog, discussion forums, and research. In particular, the CASP calls for a National Academies of Sciences, Engineering, and Medicine study on NHANES to articulate an actionable framework for NHANES going forward. With a well-informed and integrated set of goals and recommendations that could be provided by such a study, a secure future for NHANES is more readily achievable.

A narrative review of nutrient based indexes to assess diet quality and the proposed total nutrient index that reflects total dietary exposures.

A priori dietary indices provide a standardized, reproducible way to evaluate adherence to dietary recommendations across different populations. Existing nutrient-based indices were developed to reflect food/beverage intake; however, given the high prevalence of dietary supplement (DS) use and its potentially large contribution to nutrient intakes for those that use them, exposure classification without accounting for DS is incomplete. The purpose of this article is to review existing nutrient-based indices and describe the development of the Total Nutrient Index (TNI), an index developed to capture usual intakes from all sources of under-consumed micronutrients among the U.S. population. The TNI assesses U.S. adults' total nutrient intakes relative to recommended nutrient standards for eight under-consumed micronutrients identified by the Dietary Guidelines for Americans: calcium, magnesium, potassium, choline, and vitamins A, C, D, E. The TNI is scored from 0 to 100 (truncated at 100). The mean TNI score of U.S. adults (≥19 y; n = 9,954) based on dietary data from NHANES 2011-2014, was 75.4; the mean score for the index ignoring DS contributions was only 69.0 (t-test; p < 0.001). The TNI extends existing measures of diet quality by including nutrient intakes from all sources and was developed for research, monitoring, and policy purposes.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1967872.

Have safety and efficacy assessments of bioactives come of age?

This article describes why the safety and efficacy assessment of non-nutrient bioactives for reducing chronic disease risk is so complicated, especially for dietary supplements and traditional medicines. Scientists, regulators, and the public have different and sometimes opposing perspectives about bioactives. Drug, food, and traditional medicine models used for bioactive safety assessment are based on different assumptions and use different processes. Efficacy assessment is seldom based on clinical trials of boactives' effects in reducing chronic disease risk. It usually consists of application of quality assurance measures and evaluation of label claims and commercial speech about ingredients or products to ensure conformity to regulations. Harmonization of safety and efficacy assessment on a global basis is difficult because of differences within and between regulatory systems. The recommendations provided may open the way for bioactives to play a larger health role in the future, fill gaps in data needed for crafting authoritative dietary guidance on intakes, and speed harmonization of global standards.

Trends in Overall and Micronutrient-Containing Dietary Supplement Use in US Adults and Children, NHANES 2007-2018.

BACKGROUND: Dietary supplement (DS) use is widespread in the United States and contributes large amounts of micronutrients to users. Most studies have relied on data from 1 assessment method to characterize the prevalence of DS use. Combining multiple methods enhances the ability to capture nutrient exposures from DSs and examine trends over time. OBJECTIVES: The objective of this study was to characterize DS use and examine trends in any DS as well as micronutrient-containing (MN) DS use in a nationally representative sample of the US population (≥1 y) from the 2007-2018 NHANES using a combined approach. METHODS: NHANES obtains an in-home inventory with a frequency-based dietary supplement and prescription medicine questionnaire (DSMQ), and two 24-h dietary recalls (24HRs). Trends in the prevalence of use and selected types of products used were estimated for the population and by sex, age, race/Hispanic origin, family income [poverty-to-income ratio (PIR)], and household food security (food-secure vs. food-insecure) using the DSMQ or ≥ 1 24HR. Linear trends were tested using orthogonal polynomials (significance set at P < 0.05). RESULTS: DS use increased from 50% in 2007 to 56% in 2018 (P = 0.001); use of MN products increased from 46% to 49% (P = 0.03), and single-nutrient DS (e.g., magnesium, vitamins B-12 and D) use also increased (all P < 0.001). In contrast, multivitamin-mineral use decreased (70% to 56%; P < 0.001). In adults (≥19 y), any (54% to 61%) and MN (49% to 54%) DS use increased, especially in men, non-Hispanic blacks and Hispanics, and low-income adults (PIR ≤130%). In children (1-18 y), any DS use remained stable (∼38%), as did MN use, except for food-insecure children, whose use increased from 24% to 31% over the decade (P = 0.03). CONCLUSIONS: The prevalence of any and MN DS use increased over time in the United States. This may be partially attributed to increased use of single-nutrient products. Population subgroups differed in their DS use.

Malnutrition-related conditions and interventions in US state/territorial Older Americans Act aging plans.

BACKGROUND: Factors that decrease independence and increase morbidity must be reduced to improve the nutrition, health, and other challenges confronting older adults. In the United States (US), the Older Americans Act (OAA) requires each state/territory develop multi-year aging plans for spending federal funds that foster healthy aging (including support of congregate/home delivered meals programs) and separately requires grant applications for nutrition service programs supporting older Native Americans. Malnutrition (particularly protein-energy undernutrition), sarcopenia, frailty, and obesity can all result in disability but are potentially changeable. The study goal was to collect baseline information on mentions of these malnutrition-related conditions and interventions that address them in US state/territorial OAA program multi-year aging plans. METHODS: OAA program multi-year aging plans available on the ADvancing States website in February 2021 (n = 52) were searched for number of mentions of defined nutrition terms including malnutrition, sarcopenia, frailty, obesity, and whether terms were included in plans' goals/objectives, strategies/actions, or solely in the narrative. RESULTS: Malnutrition, sarcopenia, frailty, and obesity were mentioned infrequently in US state/territorial OAA program multi-year aging plans. 33% of plans mentioned malnutrition but only 8% as goals/objectives and 15% as strategies/actions. 62% mentioned frailty; 6% (goals/objectives), 15% (strategies/actions). None mentioned sarcopenia whereas in contrast, 21% mentioned obesity; 2% (goals/objectives), 2% (strategies/actions). Nutrition intervention mentions were nearly nil. There were no significant differences in frequency of term mentions by US region or by states with higher percentages of older adults or obese adults. CONCLUSIONS: Clearly specifying definitions of malnutrition-related conditions and incorporating them into measurable goals/objectives, defined strategies/actions, and outcomes may help improve future state/territorial OAA program multi-year aging plans to better support healthy aging.

An Updated Framework for Industry Funding of Food and Nutrition Research: Managing Financial Conflicts and Scientific Integrity.

Although the food and beverage industry plays a critical role in advancing food and nutrition science, industry-funded research is subject to intense scrutiny as a result of various perceived and real biases related to funding sources. To address this, the Institute for the Advancement of Food and Nutrition Sciences (IAFNS) Assembly on Scientific Integrity has updated its Guiding Principles for Funding Food Science and Nutrition Research to provide a modernized framework for minimizing bias and promoting integrity in industry-funded research. Existing best practices for managing conflicts and maintaining trust in science, as well as coverage related to conflicts in industry-funded research, were reviewed to inform the development of the updated Guiding Principles. The updated Guiding Principles continue to provide conflict-of-interest guidelines to protect the integrity and credibility of the scientific record. These updates provide clarification, strengthen the guardrails that separate the funding from the science, and reflect the shift within the scientific community toward increased transparency and open science. If the principles are followed as intended, there should be little reason to dispute the results of industry-funded studies, other than to debate the science itself. This article issues a challenge to the research community to strive for just that.

Do Multivitamin/Mineral Dietary Supplements for Young Children Fill Critical Nutrient Gaps?

BACKGROUND: Nearly a third of young US children take multivitamin/mineral (MVM) dietary supplements, yet it is unclear how formulations compare with requirements. OBJECTIVE: Describe the number and amounts of micronutrients contained in MVMs for young children and compare suggested amounts on product labels to micronutrient requirements. DESIGN: Cross-sectional. SETTING: All 288 MVMs on the market in the United States in the National Institutes of Health's Dietary Supplement Label Database in 2018 labeled for children 1 to <4 years old. MAIN OUTCOME MEASURES: Number of MVM products and amounts per day of micronutrients in each product suggested on labels compared with requirements represented by age-appropriate Daily Values (DV). Micronutrients of public health concern identified by the Dietary Guidelines for Americans (DGA) 2015-2020 (DGA 2015) and DGA 2020-2025 (DGA 2020) or those of concern for exceeding the upper tolerable intake levels. STATISTICAL ANALYSES: Number of products and percent DV per day provided by each micronutrient in each product. RESULTS: The 288 MVMs contained a mean of 10.1 ± 2.27 vitamins and 4.59 ± 2.27 minerals. The most common were, in rank order, vitamins C, A, D, E, B6, B12; zinc, biotin, pantothenic acid, iodine, and folic acid. For micronutrients denoted by the DGA 2015 and DGA 2020 of public health concern, 56% of the 281 products containing vitamin D, 4% of the 144 with calcium, and none of the 60 containing potassium provided at least half of the DV. The upper tolerable intake level was exceeded by 49% of 197 products with folic acid, 17% of 283 with vitamin A, and 14% of 264 with zinc. Most MVMs contained many of 16 other vitamins and minerals identified in national surveys as already abundant in children's diets. CONCLUSIONS: A reexamination of the amounts and types of micronutrients in MVMs might consider formulations that better fill critical gaps in intakes and avoid excess.

The Total Nutrient Index is a Useful Measure for Assessing Total Micronutrient Exposures Among US Adults.

BACKGROUND: Most dietary indices reflect foods and beverages and do not include exposures from dietary supplements (DS) that provide substantial amounts of micronutrients. A nutrient-based approach that captures total intake inclusive of DS can strengthen exposure assessment. OBJECTIVES: We examined the construct and criterion validity of the Total Nutrient Index (TNI) among US adults (≥19 years; nonpregnant or lactating). METHODS: The TNI includes 8 underconsumed micronutrients identified by the Dietary Guidelines for Americans: calcium; magnesium; potassium; choline; and vitamins A, C, D, and E. The TNI is expressed as a percentage of the RDA or Adequate Intake to compute micronutrient component scores; the mean of the component scores yields the TNI score, ranging from 0-100. Data from exemplary menus and the 2003-2006 (≥19 years; n = 8861) and 2011-2014 NHANES (≥19 years; n = 9954) were employed. Exemplary menus were used to determine whether the TNI yielded high scores from dietary sources (women, 31-50 years; men ≥ 70 years). TNI scores were correlated with Healthy Eating Index (HEI) 2015 overall and component scores for dairy, fruits, and vegetables; TNI component scores for vitamins A, C, D, and E were correlated with respective biomarker data. TNI scores were compared between groups with known differences in nutrient intake based on the literature. RESULTS: The TNI yielded high scores on exemplary menus (84.8-93.3/100) and was moderately correlated (r = 0.48) with the HEI-2015. Mean TNI scores were significantly different for DS users (83.5) compared with nonusers (67.1); nonsmokers (76.8) compared with smokers (70.3); and those living with food security (76.6) compared with food insecurity (69.1). Correlations of TNI vitamin component scores with available biomarkers ranged from 0.12 (α-tocopherol) to 0.36 (serum 25-hydroxyvitamin D), and were significantly higher than correlations obtained from the diet alone. CONCLUSIONS: The evaluation of validity supports that the TNI is a useful construct to assess total micronutrient exposures of underconsumed micronutrients among US adults.

Proposed Nutrient Standards for Plant-Based Beverages Intended as Milk Alternatives.

Background: Plant-based beverages (PBB) that are marketed as alternatives to cow milk are gaining in popularity worldwide. Nutrient quality of PBB can be highly variable. Objective: To develop a set of voluntary or mandatory nutrient standards for the PBB product category in order to assist innovation and guide product development and reformulation. Methods: The present goal was to develop standards for PBB energy content, minimum protein content and quality, maximum content for added fat, sugar, and salt, and to suggest fortification levels for selected vitamins and minerals. The standards were based on dietary recommendations and guidelines and current practices of federal agencies in the US. Results: The proposed energy and nutrient content for PBB milk alternatives are maximum 85-100 kcal energy per 100 g; a minimum for 2.2/100 g of high-quality protein, low content of saturated fat (<0.75/100 g) and added sugar (5.3-6.25/100 g) and consistent fortification with calcium, vitamins A, D, B-2, and B-12 at levels comparable to those found in cow milk (1%). Ideally, the protein content ought to be increased (2.8/100 g) and added sugar content reduced even further (2.7-3.1/100 g) for "best of class" products. These proposed standards were applied to the 641 existing PBB products listed in the 2018 version of the USDA Branded Food Products Database (BFPDB). The standards were met by <5% of the PBB on the US market. Conclusion: Often viewed as equivalent to milk in nutritional value, many PBB are often low in protein and are fortified with varying amounts of calcium, and vitamins A and D. Nutrient standards for this category should be adopted by the food industry, by public health regulatory authorities, and by standardization bodies such as the Codex Alimentarius.

Metabolic Regulation of Inflammation and Its Resolution: Current Status, Clinical Needs, Challenges, and Opportunities.

Metabolism and inflammation have been viewed as two separate processes with distinct but critical functions for our survival: metabolism regulates the utilization of nutrients, and inflammation is responsible for defense and repair. Both respond to an organism's stressors to restore homeostasis. The interplay between metabolic status and immune response (immunometabolism) plays an important role in maintaining health or promoting disease development. Understanding these interactions is critical in developing tools for facilitating novel preventative and therapeutic approaches for diseases, including cancer. This trans-National Institutes of Health workshop brought together basic scientists, technology developers, and clinicians to discuss state-of-the-art, innovative approaches, challenges, and opportunities to understand and harness immunometabolism in modulating inflammation and its resolution.

Dietary Protein Intake Is Positively Associated with Appendicular Lean Mass and Handgrip Strength among Middle-Aged US Adults.

BACKGROUND: Sarcopenia, a progressive loss of skeletal muscle mass and strength, can begin in the 4th decade of life. Protein intake predicts skeletal muscle mass and strength among older adults, but knowledge of similar associations among middle-aged adults is lacking. OBJECTIVES: We aimed to assess associations between protein intake and skeletal muscle mass, characterized by appendicular lean mass adjusted for BMI [in kg/m2 (ALMBMI)], and muscle strength, represented by handgrip strength adjusted for BMI (GSMAXBMI), among middle-aged adults. METHODS: We analyzed cross-sectional data from 1209 men and 1208 women aged 40-59 y in the 2011-2014 NHANES. Protein intake per kilogram actual body weight (BW), assessed by two 24-h recalls, was examined as continuous and categorical parameters [low (

Modernization of the National Institutes of Health Dietary Supplement Label Database.

Launched in 2008, NIH's DSLD (https://dsld.nlm.nih.gov/dsld/) currently catalogs information printed on over 125,000 (historical and current) labels of dietary supplement products sold in the U.S.. The database is maintained and updated continuously, and new versions deployed regularly. The new home page includes a prominent search bar and counter that displays the number of searchable labels in the database. The redesigned website yields near-instantaneous label retrieval, a more attractive layout of information, tailored search filters and download options, and the ability to view data in pictorial formats resulting in a much-improved user experience. The modernization of the DSLD ensures that this NIH resource has new forms of data delivery to meet the needs of App developers and data scientists, and improved performance for users. The DSLD is updated frequently to reflect the products sold in the rapidly evolving U.S. dietary supplement market.

Using the Google™ Search Engine for Health Information: Is There a Problem? Case Study: Supplements for Cancer.

We assessed the quality of online health and nutrition information using a Google™ search on "supplements for cancer". Search results were scored using the Health Information Quality Index (HIQI), a quality-rating tool consisting of 12 objective criteria related to website domain, lack of commercial aspects, and authoritative nature of the health and nutrition information provided. Possible scores ranged from 0 (lowest) to 12 ("perfect" or highest quality). After eliminating irrelevant results, the remaining 160 search results had median and mean scores of 8. One-quarter of the results were of high quality (score of 10-12). There was no correlation between high-quality scores and early appearance in the sequence of search results, where results are presumably more visible. Also, 496 advertisements, over twice the number of search results, appeared. We conclude that the Google™ search engine may have shortcomings when used to obtain information on dietary supplements and cancer.

Association of food insecurity with dietary intakes and nutritional biomarkers among US children, National Health and Nutrition Examination Survey (NHANES) 2011-2016.

BACKGROUND: Food insecurity is associated with poorer nutrient intakes from food sources and lower dietary supplement use. However, its association with total usual nutrient intakes, inclusive of dietary supplements, and biomarkers of nutritional status among US children remains unknown. OBJECTIVE: The objective was to assess total usual nutrient intakes, Healthy Eating Index-2015 (HEI-2015) scores, and nutritional biomarkers by food security status, sex, and age among US children. METHODS: Cross-sectional data from 9147 children aged 1-18 y from the 2011-2016 NHANES were analyzed. Usual energy and total nutrient intakes and HEI-2015 scores were estimated using the National Cancer Institute method from 24-h dietary recalls. RESULTS: Overall diet quality was poor, and intakes of sodium, added sugars, and saturated fat were higher than recommended limits, regardless of food security status. Food-insecure girls and boys were at higher risk of inadequate intakes for vitamin D and magnesium, and girls also had higher risk for inadequate calcium intakes compared with their food-secure counterparts, when total intakes were examined. Choline intakes of food-insecure children were less likely to meet the adequate intake than those of their food-secure peers. No differences by food security status were noted for folate, vitamin C, iron, zinc, potassium, and sodium intakes. Food-insecure adolescent girls aged 14-18 y were at higher risk of micronutrient inadequacies than any other subgroup, with 92.8% (SE: 3.6%) at risk of inadequate intakes for vitamin D. No differences in biomarkers for vitamin D, folate, iron, and zinc were observed by food security status. The prevalence of iron deficiency was 12.7% in food-secure and 12.0% in food-insecure adolescent girls. CONCLUSIONS: Food insecurity was associated with compromised intake of some micronutrients, especially among adolescent girls. These results highlight a need for targeted interventions to improve children's overall diet quality, including the reduction of specific nutrient inadequacies, especially among food-insecure children. This study was registered at clinicaltrials.gov as NCT03400436.

Perspective: Framework for Developing Recommended Intakes of Bioactive Dietary Substances.

Dietary bioactives are food substances that promote health but are not essential to prevent typical deficiency conditions. Examples include lutein and zeaxanthin, omega-3 fatty acids, and flavonoids. When quality evidence is available, quantified intake recommendations linking dietary bioactives with specific health benefits will enable health professionals to provide evidence-based information to consumers. Without evidence-based recommendations, consumers use information from available sources that often lack standards and rigor. This article describes a framework to develop guidance based on quality evidence fully vetted for efficacy and safety by qualified experts, and designed to communicate the amounts of specific dietary bioactive compounds with identified health benefits. The 4-step Framework described here can be adapted by credible health organizations to work within their guideline development process. Standards of practice used in clinical guidelines are adapted to quantify dietary bioactive intake recommendations from foods consumed by the general public, by taking into account that side effects and trade-offs are often needed for medical treatments but are not acceptable for dietary bioactives. In quantifying dietary bioactive recommendations, this Framework establishes 4 decision-making steps: 1) characterize the bioactive, determine amounts in specific food sources, and quantify intakes; 2) evaluate safety; 3) quantify the causal relation between the specific bioactive and accepted markers of health or normal function via systematic evidence reviews; and 4) translate the evidence into a quantified bioactive intake statement. This Framework provides a working model that can be updated as new approaches are advanced.