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.

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.

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.

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.

Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives.

The increased utilization of metrology resources and expanded application of its' approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects.

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.

Perspective: Time to Resolve Confusion on Folate Amounts, Units, and Forms in Prenatal Supplements.

Folate-containing prenatal supplements are commonly consumed in the United States, but inconsistencies in units of measure and chemical forms pose challenges for providing authoritative advice on recommended amounts. New regulations require folate to be declared as micrograms of dietary folate equivalents (DFE) on product labels, whereas intake recommendations for reducing the risk of neural tube defects (NTDs) and the Tolerable Upper Intake Level are expressed as micrograms of folic acid. Today, >25% of prenatal supplements contain folate as synthetic salts of L-5-methyltetrahydrofolate (L-5-MTHF), but recommendations do not include this form of the vitamin. Harmonizing units of measure and addressing newer forms of folate salts in intake recommendations and in the prevention of NTDs would resolve the confusion.

Harmonizing Micronutrient Intake Reference Ranges for Dietary Guidance and Menu Planning in Complementary Feeding.

There are no published harmonized nutrient reference values for the complementary feeding period. The aim of the study was to develop proposals on adequate and safe intake ranges of micronutrients that can be applied to dietary guidance and menu planning. Dietary intake surveys from 6 populous countries were selected as pertinent to the study and reviewed for data on micronutrients. The most frequently underconsumed micronutrients were identified as iron, zinc, calcium, magnesium, phosphorus, potassium, and vitamins A, B6, B12, C, D, E, and folate. Key published reference values for these micronutrients were identified, compared, and reconciled. WHO/FAO values were generally identified as initial nutrient targets and reconciled with nutrient reference values from the Institute of Medicine and the European Food Standards Authority. A final set of harmonized reference nutrient intake ranges for the complementary feeding period is proposed.

Dietary Supplement Use and Its Micronutrient Contribution During Pregnancy and Lactation in the United States.

OBJECTIVE: To estimate the prevalence of use and the micronutrient contribution of dietary supplements among pregnant, lactating, and nonpregnant and nonlactating women in the United States. METHODS: Cross-sectional data from 1,314 pregnant, 297 lactating, and 8,096 nonpregnant and nonlactating women (aged 20-44 years) in the 1999-2014 National Health and Nutrition Examination Survey were combined to produce statistically reliable, nationally representative estimates. Information about dietary supplements used in the past 30 days was collected through an interviewer-administered questionnaire and in-home inventory. The prevalence of nutrient-specific supplement use, mean daily nutrient intakes from supplements among users, and motivations for supplement use were assessed. Differences by age, income, and trimester within pregnant women were also tested. RESULTS: Seventy-seven percent of pregnant women and 70% of lactating women used one or more dietary supplements, whereas 45% of nonpregnant and nonlactating women used supplements. In particular, 64% of pregnant and 54% of lactating women used prenatal supplements. Mean intakes of thiamin, riboflavin, niacin, folic acid, vitamins B6, B12, and C, iron, and zinc from supplements alone were at or above their respective recommended dietary allowances (RDAs) among pregnant and lactating supplement users. About half of pregnant and 40% of lactating women took supplements based on the recommendation of a health care provider. Among pregnant women, those in their first trimester, aged 20-34 years, or in a lower-income family were less likely to use supplements compared with their counterparts. CONCLUSION: The majority of pregnant and lactating women used dietary supplements, which contributed many nutrients in doses above the RDAs. Although inadequate Intakes of folate and iron are of concern among pregnant women who are not using supplements, supplement users often consumed high doses, suggesting a potential need of health care providers to discuss dietary supplement use and the recommended doses of nutrients during pregnancy and lactation.

Disintegration and Dissolution Testing of Green Tea Dietary Supplements: Application and Evaluation of United States Pharmacopeial Standards.

Approved performance quality tests are lacking in the United States Pharmacopeia (USP) for dietary supplements (DSs) containing green tea extracts. We evaluated the applicability of USP <2040 > general chapter protocols for disintegration and dissolution testing of botanicals to GT DSs. Of 28 single-ingredient GT DSs tested in 2 to 4 lots, 9 (32.1%) always passed the disintegration test, 8 (28.6%) always failed, and 11 (39.3%) showed inconsistent results. Of 34 multi-ingredient DSs tested in 2 lots, 21 (61.8%) passed and 8 (23.5%) failed in both lots, and 5 (14.7%) exhibited inconsistent performance. When stronger destructive forces were applied (disk added), all of the capsules that had failed initially, but not the tablets, passed. In dissolution testing, for the release of epigallocatechin-3-gallate (EGCG), only 6 of 20 single-ingredient DSs passed. Unexpectedly, with the addition of pepsin (prescribed by USP), only one additional DS passed. These results raise concerns that EGCG was not released properly from GT DS dosage forms. However, the general USP protocols may be inadequate for this botanical. More biorelevant destructive forces may be needed to break down capsules and tablets strengthened by the EGCG's interaction with shell material and to overcome the inhibition of digestive enzymes by EGCG.

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.

Total Usual Micronutrient Intakes Compared to the Dietary Reference Intakes among U.S. Adults by Food Security Status.

This study examined total usual micronutrient intakes from foods, beverages, and dietary supplements (DS) compared to the Dietary Reference Intakes among U.S. adults (≥19 years) by sex and food security status using NHANES 2011-2014 data (n = 9954). DS data were collected via an in-home interview; the NCI method was used to estimate distributions of total usual intakes from two 24 h recalls for food and beverages, after which DS were added. Food security status was categorized using the USDA Household Food Security Survey Module. Adults living in food insecure households had a higher prevalence of risk of inadequacy among both men and women for magnesium, potassium, vitamins A, B6, B12, C, D, E, and K; similar findings were apparent for phosphorous, selenium, and zinc in men alone. Meanwhile, no differences in the prevalence of risk for inadequacy were observed for calcium, iron (examined in men only), choline, or folate by food security status. Some DS users, especially food secure adults, had total usual intakes that exceeded the Tolerable Upper Intake Level (UL) for folic acid, vitamin D, calcium, and iron. In conclusion, while DS can be helpful in meeting nutrient requirements for adults for some micronutrients, potential excess may also be of concern for certain micronutrients among supplement users. In general, food insecure adults have higher risk for micronutrient inadequacy than food secure adults.

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.