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.

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.

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.

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.

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.

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.

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.

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.

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 (

Comparison of 4 Methods to Assess the Prevalence of Use and Estimates of Nutrient Intakes from Dietary Supplements among US Adults.

BACKGROUND: Accurate and reliable methods to assess prevalence of use of and nutrient intakes from dietary supplements (DSs) are critical for research, clinical practice, and public health monitoring. NHANES has been the primary source of DS usage patterns using an in-home inventory with a frequency-based DS and Prescription Medicine Questionnaire (DSMQ), but little is known regarding DS information obtained from 24-h dietary recalls (24HRs). METHODS: The objectives of this analysis were to compare results from 4 different methods for measuring DS use constructed from two data collection instruments (i.e., DSMQ and 24HR) and to determine the most comprehensive method for measuring the prevalence of use and estimating nutrient intakes from DS for selected nutrients. NHANES 2011-2014 data from US adults (aged ≥19 y; n = 11,451) were used to examine the 4 combinations of methods constructed for measuring the prevalence of use of and amount of selected nutrients from DSs (i.e., riboflavin, vitamin D, folate, magnesium, calcium): 1) DSMQ, 2) 24HR day 1, 3) two 24HRs (i.e., mean), and 4) DSMQ or at least one 24HR. RESULTS: Half of US adults reported DS use on the DSMQ (52%) and on two 24HRs (mean of 49%), as compared with a lower prevalence of DS use when using a single 24HR (43%) and a higher (57%) prevalence when combining the DSMQ with at least one 24HR. Mean nutrient intake estimates were highest using 24HR day 1. Mean supplemental calcium from the DSMQ or at least one 24HR was 372 mg/d, but 464 mg/d on the 24HR only. For vitamin D, the estimated intakes per consumption day were higher on the DSMQ (46 µg) and the DSMQ or at least one 24HR (44 µg) than those on the 24HR day 1 (32 µg) or the mean 24HR (31 µg). Fewer products were also classed as a default or reasonable match on the DSMQ than on the 24HR. CONCLUSIONS: A higher prevalence of use of DSs is obtained using frequency-based methods, whereas higher amounts of nutrients are reported from a 24HR. The home inventory results in greater accuracy for products reported. Collectively, these findings suggest that combining the DSMQ with at least one 24HR (i.e., DSMQ or at least one 24HR) is the most comprehensive method for assessing the prevalence of and estimating usual intake from DSs in US adults.This trial was registered at clinicaltrials.gov as NCT03400436.

Imaging inflammation and its resolution in health and disease: current status, clinical needs, challenges, and opportunities.

Inflammation is a normal process in our body; acute inflammation acts to suppress infections and support wound healing. Chronic inflammation likely leads to a wide range of diseases, including cancer. Tools to locate and monitor inflammation are critical for developing effective interventions to arrest inflammation and promote its resolution. To identify current clinical needs, challenges, and opportunities in advancing imaging-based evaluations of inflammatory status in patients, the U.S. National Institutes of Health convened a workshop on imaging inflammation and its resolution in health and disease. Clinical speakers described their needs for image-based capabilities that could help determine the extent of inflammatory conditions in patients to guide treatment planning and undertake necessary interventions. The imaging speakers showcased the state-of-the-art in vivo imaging techniques for detecting inflammation in different disease areas. Many imaging capabilities developed for 1 organ or disease can be adapted for other diseases and organs, whereas some have promise for clinical utility within the next 5-10 yr. Several speakers demonstrated that multimodal imaging measurements integrated with serum-based measures could improve in robustness for clinical utility. All speakers agreed that multiple inflammatory measures should be acquired longitudinally to comprehend the dynamics of unresolved inflammation that leads to disease development. They also agreed that the best strategies for accelerating clinical translation of imaging inflammation capabilities are through integration between new imaging techniques and biofluid-based biomarkers of inflammation as well as already established imaging measurements.-Liu, C. H., Abrams, N. D., Carrick, D. M., Chander, P., Dwyer, J., Hamlet, M. R. J., Kindzelski, A. L., PrabhuDas, M., Tsai, S.-Y. A., Vedamony, M. M., Wang, C., Tandon, P. Imaging inflammation and its resolution in health and disease: current status, clinical needs, challenges, and opportunities.

Older adults with obesity have higher risks of some micronutrient inadequacies and lower overall dietary quality compared to peers with a healthy weight, National Health and Nutrition Examination Surveys (NHANES), 2011-2014.

OBJECTIVE: To evaluate total usual intakes and biomarkers of micronutrients, overall dietary quality and related health characteristics of US older adults who were overweight or obese compared with a healthy weight. DESIGN: Cross-sectional study. SETTING: Two 24-h dietary recalls, nutritional biomarkers and objective and subjective health characteristic data were analysed from the National Health and Nutrition Examination Survey 2011-2014. We used the National Cancer Institute method to estimate distributions of total usual intakes from foods and dietary supplements for eleven micronutrients of potential concern and the Healthy Eating Index (HEI)-2015 score. PARTICIPANTS: Older adults aged ≥60 years (n 2969) were categorised by sex and body weight status, using standard BMI categories. Underweight individuals (n 47) were excluded due to small sample size. RESULTS: A greater percentage of obese older adults compared with their healthy-weight counterparts was at risk of inadequate Mg (both sexes), Ca, vitamin B6 and vitamin D (women only) intakes. The proportion of those with serum 25-hydroxyvitamin D < 40 nmol/l was higher in obese (12 %) than in healthy-weight older women (6 %). Mean overall HEI-2015 scores were 8·6 (men) and 7·1 (women) points lower in obese than in healthy-weight older adults. In addition, compared with healthy-weight counterparts, obese older adults were more likely to self-report fair/poor health, use ≥ 5 medications and have limitations in activities of daily living and cardio-metabolic risk factors; and obese older women were more likely to be food-insecure and have depression. CONCLUSIONS: Our findings suggest that obesity may coexist with micronutrient inadequacy in older adults, especially among women.

Beat osteoporosis - nourish and exercise skeletons (BONES): a group randomized controlled trial in children.

BACKGROUND: Lifelong healthy habits developed during childhood may prevent chronic diseases in adulthood. Interventions to promote these habits must begin early. The BONES (Beat Osteoporosis - Nourish and Exercise Skeletons) project assessed whether early elementary school children participating in a multifaceted health behavior change, after-school based intervention would improve bone quality and muscular strength and engage in more bone-strengthening behaviors. METHODS: The 2-year BONES (B) intervention included bone-strengthening physical activity (85 min/week), educational materials (2 days/week), and daily calcium-rich snacks (380 mg calcium/day) delivered by after-school program leaders. BONES plus Parent (B + P) included an additional parent education component. From 1999 to 2004, n = 83 after-school programs (N = 1434 children aged 6-9 years) in Massachusetts and Rhode Island participated in a group randomized trial with two intervention arms (B only, n = 25 programs; B + P, n = 33) and a control arm (C, n = 25). Outcome measures (primary: bone quality (stiffness index of the calcaneus) and muscular strength (grip strength and vertical jump); secondary: bone-strengthening behaviors (calcium-rich food knowledge, preference, and intake; and physical activity level (metabolic equivalent time (MET) score, and weight-bearing factor (WBF) score)) were recorded at baseline, and after years one and two. Analyses followed an intent-to-treat protocol, and focused on individual subjects' trajectories along the three time points adjusting for baseline age and race via a mixed-effects regression framework. Analyses were performed with and without sex stratification. RESULTS: Children in B + P increased bone stiffness compared to C (p = 0.05); No significant changes were observed in muscle strength, food knowledge, or vertical jump. Children in B + P showed significant improvement in their MET and WBF scores compared to C (p < 0.01) with a stronger effect in boys in both B and B + P (all p < 0.01). CONCLUSION: After-school programs, coupled with parental engagement, serving early elementary school children are a potentially feasible platform to deliver bone-strengthening behaviors to prevent osteoporosis in adulthood, with some encouraging bone and physical activity outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00065247. Retrospectively registered. First posted July 22, 2003.

Screening Community-Living Older Adults for Protein Energy Malnutrition and Frailty: Update and Next Steps.

Protein-energy malnutrition (PEM)/undernutrition and frailty are prevalent, overlapping conditions impacting on functional and health outcomes of older adults, but are frequently unidentified and untreated in community settings in the United States. Using the World Health Organization criteria for effective screening programs, we reviewed validity, reliability, and feasibility of data-driven screening tools for identifying PEM and frailty risk among community-dwelling older adults. The SCREEN II is recommended for PEM screening and the FRAIL scale is recommended as the most promising frailty screening tool, based on test characteristics, cost, and ease of use, but more research on both tools is needed, particularly on predictive validity of favorable outcomes after nutritional/physical activity interventions. The Malnutrition Screening Tool (MST) has been recommended by one expert group as a screening tool for all adults, regardless of age/care setting. However, it has not been tested in US community settings, likely yields large numbers of false positives (particularly in community settings), and its predictive validity of favorable outcomes after nutritional interventions is unknown. Community subgroups at highest priority for screening are those at increased risk due to prior illness, certain demographics and/or domiciliary characteristics, and those with BMI < 20 kg/m2 or < 22 if > 70 years or recent unintentional weight loss > 10% (who are likely already malnourished). Community-based health professionals can better support healthy aging by increasing their awareness/use of PEM and frailty screening tools, prioritizing high-risk populations for systematic screening, following screening with more definitive diagnoses and appropriate interventions, and re-evaluating and revising screening protocols and measures as more data become available.

Trends in Mean Nutrient Intakes of US Infants, Toddlers, and Young Children from 3 Feeding Infants and Toddlers Studies (FITS).

BACKGROUND: Many updates to young child feeding recommendations have been published over the past decade, but concurrent intake trends have not been assessed. OBJECTIVE: The aim of this study was to evaluate adequacy and trends in energy and nutrient intakes of US infants and children aged 0-47.9 mo through use of Feeding Infants and Toddlers Study (FITS) data from 2002, 2008, and 2016. METHODS: FITS are cross-sectional surveys of parents/caregivers of infants and young children (FITS 2002, n = 2962; FITS 2008, n = 3276; FITS 2016, n = 3235). Dietary intakes were assessed by telephone with trained interviewers using the Nutrition Data System for Research. Mean ± SE nutrient intakes were calculated. Diet adequacy was assessed with the nutrient adequacy ratio (NAR) for 17 nutrients and the corresponding mean adequacy ratio. RESULTS: Energy and macronutrient intakes were generally stable across surveys, but significant decreases for saturated fat and total sugars and an increase in fiber were observed among 6-11.9-mo-olds and 12-23.9-mo-olds (P-trend < 0.0001). Mean sodium intakes exceeded Adequate Intakes (AI) for all ages, whereas fiber intakes were universally below the AI. Nutrients with the lowest NAR values were vitamin D (range 0.41-0.67/1.00) and vitamin E (range 0.60-0.79/1.00 for 2008 and 2016). For iron, infants aged 6-11.9 mo had the lowest NAR values at 0.77-0.88/1.00, compared to 0.85-0.89/1.00 for 12-47.9-mo-olds. Potassium was low from 12 to 47.9 mo (NAR range 0.55-0.63/1.00 across survey years). The nutrients with the greatest decline in mean intakes were iron and vitamins D and E among 6-11.9-mo-olds, and vitamin D and potassium among 12-23.9-mo-olds in 2016 compared to 2002. CONCLUSIONS: The diets of US infants and young children were generally adequate for most micronutrients and stable over time, but sodium intakes were too high, and nutrient gaps still existed, especially for vitamins D, E, and fiber across ages and for iron among infants.

The Chemical Forms of Iron in Commercial Prenatal Supplements Are Not Always the Same as Those Tested in Clinical Trials.

In the US, 70% of pregnant women use an iron-containing prenatal supplement product; however, only 2.6% of pregnant women have iron-deficiency anemia and 16.3% are iron deficient. Yet, published data on the amounts and chemical forms of iron used in formulating these products are not available, although they are known to affect bioavailability. This information is especially important in comparing commercially available products with those that were tested in clinical trials. Our examination of nonprescription and prescription iron-containing prenatal supplement products in NIH's Dietary Supplement Label Database (DSLD) and DailyMed found the labeled amount of elemental iron ranged between 9 and 60 mg/serving in 148 nonprescription supplements and between 4.5 and 106 mg/serving in 101 prescription supplements. Ferrous fumarate was the preferred chemical form used in these products. In contrast, ferrous sulfate was the preferred chemical form of iron reported in the clinical trials summarized in a 2015 Cochrane Systematic review assessing the effects of daily oral iron supplements for pregnant women. Ferrous sulfate was not found on any prenatal supplement product label in the DSLD or DailyMed. The chemical forms of products on the market and those tested in clinical trials are dissimilar, and we believe this may have clinical implications. The findings raise several questions. Do outcomes in clinical trials correlate with the benefits and risks that might adhere to iron supplements with different iron formulations? Should the differences in chemical forms, their bioavailability, and safety profiles, be considered in greater depth when evaluating the effect of the various formulations on maternal iron nutriture? Should new clinical trials for pregnant and lactating women in the US use a form of iron not found in prenatal supplements sold in the US or should a more common form be used?

Dietary Supplement Use among Infants and Toddlers Aged <24 Months in the United States, NHANES 2007-2014.

BACKGROUND: Limited nationally representative data are available on dietary supplement (DS) use and resulting nutrient exposures among infants and toddlers. OBJECTIVE: This study evaluated DS use among US infants and toddlers to characterize DS use, estimate nutrient intake from DSs, and assess trends in DS use over time. METHODS: Using nationally representative data from NHANES (2007-2014) and trends over time (1999-2014), we estimated prevalence of DS use and types of products used for US infants and toddlers aged <2 y (n = 2823). We estimated median daily intakes of vitamins and minerals consumed via DSs for all participants aged <2 y, by age groups (0-11.9 mo and 12.0-23.9 mo), and by feeding practices for infants 0-5.9 mo. RESULTS: Overall, 18.2% (95% CI: 16.2%, 20.3%) of infants and toddlers used ≥1 DS in the past 30 d. Use was lower among infants (0-5.9 mo: 14.6%; 95% CI: 11.5%, 18.1%; 6-11.9 mo: 11.6%; 95% CI: 8.8%, 15.0%) than among toddlers (12-23.9 mo: 23.3%; 95% CI: 20.4%, 26.3%). The most commonly reported DSs were vitamin D and multivitamin infant drops for those <12 mo, and chewable multivitamin products for toddlers (12-23.9 mo). The nutrients most frequently consumed from DSs were vitamins D, A, C, and E for those <2 y; for infants <6 mo, a higher percentage of those fed breast milk than those fed formula consumed these nutrients via DSs. DS use remained steady for infants (6-11.9 mo) and toddlers from 1999-2002 to 2011-2014, but increased from 7% to 20% for infants aged 0-5.9 mo. CONCLUSIONS: One in 5 infants and toddlers aged <2 y use ≥1 DS. Future studies should examine total nutrient intake from foods, beverages, and DSs to evaluate nutrient adequacy overall and by nutrient source.

Best Practices for Dietary Supplement Assessment and Estimation of Total Usual Nutrient Intakes in Population-Level Research and Monitoring.

The use of dietary supplements (DS) is pervasive and can provide substantial amounts of micronutrients to those who use them. Therefore when characterizing dietary intakes, describing the prevalence of inadequacy or excess, or assessing relations between nutrients and health outcomes, it is critical to incorporate DS intakes to improve exposure estimates. Unfortunately, little is known about the best methods to assess DS, and the structure of measurement error in DS reporting. Several characteristics of nutrients from DS are salient to understand when comparing to those in foods. First, DS can be consumed daily or episodically, in bolus form and can deliver discrete and often very high doses of nutrients that are not limited by energy intakes. These characteristics contribute to bimodal distributions and distributions severely skewed to the right. Labels on DS often provide nutrient forms that differ from those found in conventional foods, and underestimate analytically derived values. Finally, the bioavailability of many nutrient-containing DS is not known and it may not be the same as the nutrients in a food matrix. Current methods to estimate usual intakes are not designed specifically to handle DS. Two temporal procedures are described to refer to the order that nutrient intakes are combined relative to usual intake procedures, referred to as a "shrinking" the distribution to remove random error. The "shrink then add" approach is preferable to the "add then shrink" approach when users and nonusers are combined for most research questions. Stratifying by DS before usual intake methods is another defensible option. This review describes how to incorporate nutrient intakes from DS to usual intakes from foods, and describes the available methods and fit-for-purpose of different analytical strategies to address research questions where total usual intakes are of interest at the group level for use in nutrition research and to inform policy decisions. Clinical Trial Registry: NCT03400436.