Challenges in Reporting Adverse Events from Dietary Supplements.

In 2008, the Institute of Medicine (IOM) Committee on Dietary Supplement Use by Military Personnel recommended the development of service wide military policies (e.g., education or regulations) to guide commanders in management practices for safe use of dietary supplements (DS). This review summarizes the activities the military has undertaken to advance the safe use of DS by Service Members and develop best practices on reporting adverse events across the Department of Defense (DoD). In March 2022, the Department of Defense issued a DoD Instruction (DoDI) regarding the use of DS by members of the U S. military. This DoDI provides guidelines to establish an official list of prohibited substances. The DoDI also identifies Operation Supplement Safety (OPSS) at CHAMP as DoD's "go to" program for DS use and information about DS and ingredients. Noted are a number of gaps in the reporting of adverse events from DS that need to be addressed by multiple constituencies.

Select Dietary Supplement Ingredients for Preserving and Protecting the Immune System in Healthy Individuals: A Systematic Review.

Immune health products represent approximately 10% of all US dietary supplement sales. Claims made on products to support or boost the immune system are attractive to the otherwise healthy consumer who may or may not be experiencing certain life stressors. The purpose of this systematic review is to critically evaluate the purported benefits and/or potential harms of select dietary supplement ingredients frequently listed on the labels of products having immune health or related market claims. With a focus on resilience, research questions were related to whether dietary supplement ingredients are efficacious in preserving and protecting immune health in healthy individuals; and when faced with a stressor, whether taking a supplement prophylactically can assist in maintaining health and resisting or bouncing back more quickly. Thirty-nine randomized controlled studies involving populations including children, adults and seniors exposed to stressors, such as air travel, intense exercise, academic stress, and/or exposure to winter weather, met eligibility criteria. The studies included eight of the 27 supplement ingredients identified through a market-driven scoping review. Those ingredients used in single ingredient products were echinacea, elderberry, garlic, vitamin A, vitamin C, vitamin D, vitamin E, and zinc. Whereas some studies may point to evidence for benefit, specific gaps preclude the authors from making firm statements with regard to the overall evidence-base for these products and ingredients and in answering the research questions. As we move toward a vision of health promotion and resilience rather than a sole focus on disease prevention and treatment, further work in this area of dietary supplements is of utmost importance.

Recommendation on an updated standardization of serum magnesium reference ranges.

PURPOSE: Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization. METHODS: We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide. RESULTS: Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD. CONCLUSIONS: Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

Protective effects of dietary curcumin and astaxanthin against heat-induced ROS production and skeletal muscle injury in male and female C57BL/6J mice.

AIMS: This study aimed to: 1) investigate sex differences in heat-induced mitochondrial dysfunction, ROS production, and skeletal muscle injury in mice; 2) evaluate whether curcumin and astaxanthin, alone or together, would prevent those heat-induced changes. MAIN METHODS: Male and female C57BL/6J mice were treated with curcumin and astaxanthin for 10 days, then exposed to 39.5 °C heat for up to 3 h. Heat-induced hyperthermia, changes in mitochondrial morphology and function, and oxidative damage to skeletal muscle were evaluated. KEY FINDINGS: Although female mice had a slightly higher basal core body temperature (Tc) than male mice, peak Tc during heat exposure was significantly lower in females than in males. Heat increased ROS levels in skeletal muscle in both sexes; interestingly, the increases in ROS were greater in females than in males. Despite the above-mentioned differences, heat induced similar levels of mitochondrial fragmentation and membrane potential depolarization, caspase 3/7 activation, and injury in male and female skeletal muscle. Individual treatment of curcumin or astaxanthin did not affect basal and peak Tc but prevented heat-induced mitochondrial dysfunction, ROS increases, and apoptosis in a dose-dependent manner. Moreover, a low-dose combination of curcumin and astaxanthin, which individually showed no effect, reduced the heat-induced oxidative damage to skeletal muscle. SIGNIFICANCE: Both male and female mice can develop mitochondrial dysfunction and oxidative stress in skeletal muscle when exposed to heat stress. High doses of either curcumin or astaxanthin limit heat-induced skeletal muscle injury, but a low-dose combination of these ingredients may increase their efficacy.

Beyond Nutrient Deficiency-Opportunities to Improve Nutritional Status and Promote Health Modernizing DRIs and Supplementation Recommendations.

The US Dietary Guidelines for Americans (DGA) provide dietary recommendations to meet nutrient needs, promote health, and prevent disease. Despite 40 years of DGA, the prevalence of under-consumed nutrients continues in the US and globally, although dietary supplement use can help to fill shortfalls. Nutrient recommendations are based on Dietary Reference Intakes (DRIs) to meet the nutrient requirements for nearly all (97 to 98 percent) healthy individuals in a particular life stage and gender group and many need to be updated using current evidence. There is an opportunity to modernize vitamin and mineral intake recommendations based on biomarker or surrogate endpoint levels needed to 'prevent deficiency' with DRIs based on ranges of biomarker or surrogate endpoints levels that support normal cell/organ/tissue function in healthy individuals, and to establish DRIs for bioactive compounds. We recommend vitamin K and Mg DRIs be updated and DRIs be established for lutein and eicosapentaenoic and docosahexaenoic acid (EPA + DHA). With increasing interest in personalized (or precision) nutrition, we propose greater research investment in validating biomarkers and metabolic health measures and the development and use of inexpensive diagnostic devices. Data generated from such approaches will help elucidate optimal nutrient status, provide objective evaluations of an individual's nutritional status, and serve to provide personalized nutrition guidance.

Magnesium Depletion Score (MDS) Predicts Risk of Systemic Inflammation and Cardiovascular Mortality among US Adults.

BACKGROUND: Kidney reabsorption of magnesium (Mg) is essential for homeostasis. OBJECTIVES: We developed and validated models with the kidney reabsorption-related magnesium depletion score (MDS) to predict states of magnesium deficiency and disease outcomes. METHODS: MDS was validated in predicting body magnesium status among 77 adults (aged 62 ± 8 y, 51% men) at high risk of magnesium deficiency in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (registered at clinicaltrials.gov as NCT01105169) using the magnesium tolerance test (MTT). We then validated MDS for risk stratification and for associations with inflammation and mortality among >10,000 US adults (weighted: aged 48 ± 0.3 y, 47% men) in the NHANES, a nationally representative study. A proportional hazards regression model was used for associations between magnesium intake and the MDS with risks of total and cardiovascular disease (CVD) mortality. RESULTS: In the PPCCT, the area under the receiver operating characteristic (ROC) curve (AUC) for magnesium deficiency was 0.63 (95% CI: 0.50, 0.76) for the model incorporating the MDS with sex and age compared with 0.53 (95% CI: 0.40, 0.67) for the model with serum magnesium alone. In the NHANES, mean serum C-reactive protein significantly increased with increasing MDS (P-trend < 0.01) after adjusting for age and sex and other covariates, primarily among individuals with magnesium intake less than the Estimated Average Requirement (EAR; P-trend < 0.05). Further, we found that low magnesium intake was longitudinally associated with increased risks of total and CVD mortality only among those with magnesium deficiency predicted by MDS. MDS was associated with increased risks of total and CVD mortality in a dose-response manner only among those with magnesium intake less than the EAR. CONCLUSIONS: The MDS serves as a promising measure in identifying individuals with magnesium deficiency who may benefit from increased intake of magnesium to reduce risks of systemic inflammation and CVD mortality. This lays a foundation for precision-based nutritional interventions.

Effectively Prescribing Oral Magnesium Therapy for Hypertension: A Categorized Systematic Review of 49 Clinical Trials.

Trials and meta-analyses of oral magnesium for hypertension show promising but conflicting results. An inclusive collection of 49 oral magnesium for blood pressure (BP) trials were categorized into four groups: (1) Untreated Hypertensives; (2) Uncontrolled Hypertensives; (3) Controlled Hypertensives; (4) Normotensive subjects. Each group was tabulated by ascending magnesium dose. Studies reporting statistically significant (p < 0.05) decreases in both systolic BP (SBP) and diastolic BP (DBP) from both baseline and placebo (if reported) were labeled "Decrease"; all others were deemed "No Change." Results: Studies of Untreated Hypertensives (20 studies) showed BP "Decrease" only when Mg dose was >600 mg/day; <50% of the studies at 120-486 mg Mg/day showed SBP or DBP decreases but not both while others at this Mg dosage showed no change in either BP measure. In contrast, all magnesium doses (240-607 mg/day) showed "Decrease" in 10 studies on Uncontrolled Hypertensives. Controlled Hypertensives, Normotensives and "magnesium-replete" studies showed "No Change" even at high magnesium doses (>600 mg/day). Where magnesium did not lower BP, other cardiovascular risk factors showed improvement. Conclusion: Controlled Hypertensives and Normotensives do not show a BP-lowering effect with oral Mg therapy, but oral magnesium (≥240 mg/day) safely lowers BP in Uncontrolled Hypertensive patients taking antihypertensive medications, while >600 mg/day magnesium is required to safely lower BP in Untreated Hypertensives; <600 mg/day for non-medicated hypertensives may not lower both SBP and DBP but may safely achieve other risk factor improvements without antihypertensive medication side effects.

Perspective: Characterization of Dietary Supplements Containing Calcium and Magnesium and Their Respective Ratio-Is a Rising Ratio a Cause for Concern?

Low magnesium intakes coupled with high calcium intakes and high calcium-to-magnesium (Ca:Mg) intake ratios have been associated with increased risk for multiple chronic conditions such as cardiovascular disease and metabolic syndrome, as well as some cancers (colorectal, prostate, esophageal), and total mortality. A high dietary Ca:Mg ratio (>2.60) may affect body magnesium status while, on the other hand, high intakes of magnesium could adversely impact individuals with an exceedingly low dietary Ca:Mg ratio (<1.70). Thus, a Ca:Mg ratio range of 1.70-2.60 (weight to weight) has been proposed as an optimum range. Data from NHANES surveys have shown the mean Ca:Mg intake ratio from foods alone for US adults has been >3.00 since 2000. One-third of Americans consume a magnesium supplement with a mean dose of 146 mg/d, and 35% of Americans consume a calcium supplement with a mean dose of 479 mg/d. Our review of Ca:Mg ratios in dietary supplements sold in the United States and listed in NIH's Dietary Supplement Label Database (DSLD) found a mean ratio of 2.90 across all calcium- and magnesium-containing products, with differences by product form. The ratios ranged from a low of 0.10 in liquid products to a high of 48.5 in powder products. Thirty-one percent of products fell below, 40.5% fell within, and 28.3% fell above the ratio range of 1.70-2.60. Our findings of calculated Ca:Mg ratios from dietary supplements coupled with food-intake data suggest that, in individuals with high calcium intakes from diet and/or supplements, magnesium supplementation may be warranted to establish a more favorable dietary Ca:Mg ratio in their total diet. Additional research may provide greater insight into whether the Ca:Mg ratio is a biomarker of interest for moderating chronic disease and which population groups may derive benefit from moderating that ratio.

Capturing the Use of Dietary Supplements in Electronic Medical Records: Room for Improvement.

Of importance to federal agencies that administer health care facilities is capturing patient use of dietary supplements (DS) to avoid potential drug - supplement interactions. Digital technologies, such as use of the electronic medical record and the electronic health record (EHR) are key to monitoring health care. The particular electronic software package and the health care professional using this software influences how this documentation is recorded. A survey was conducted to determine how information on DS is being collected, recorded, and processed in EHR across federal agencies. Four federal agencies providing direct health care services to large numbers of men and women in the US were surveyed on current practices regarding the recording and processing of information on DS use either on outpatient or inpatient basis. A point of contact for each of the following federal agencies was identified, and a 13-question survey was sent to each for completion: NIH Clinical Center, Department of Defense (DoD) Military Nutrition Committee, Veterans Health Administration (VHA) Office of Specialty Care Services, and the Indian Health Service (IHS), Office of Information Technology. All four agency representatives completed the survey. No agency used the same EHR software reporting system. Most EHR have searchable fields that are in a structured format, but some information is free text and allowed entry by multiple members of the health-care team. Three different medication formulary or drug knowledge databases were utilized across the agencies. Most agencies using EHR management systems have adequately described procedures for entering and charting information on DS. The responsibility for charting, however, varies across agencies whether captured by the admitting doctor, nurse, dietitian, or pharmacist. Direct linkage between the pharmacy system and the drug knowledge database is a feature of the EHR for several but not all federal agencies. An unmet need still exists in the EHR to implement DS/drug interaction checks as many DS products have multiple active ingredients and when taken with other DS or prescription drugs increase the likelihood of an adverse event. Establishing common EHR practices could facilitate monitoring the use and potential interactions of DS with prescribed drugs.

Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial.

Background: Previous in vitro and in vivo studies indicate that enzymes that synthesize and metabolize vitamin D are magnesium dependent. Recent observational studies found that magnesium intake significantly interacted with vitamin D in relation to vitamin D status and risk of mortality. According to NHANES, 79% of US adults do not meet their Recommended Dietary Allowance of magnesium. Objectives: The aim of this study was to test the hypothesis that magnesium supplementation differentially affects vitamin D metabolism dependent on baseline 25-hydroxyvitamin D [25(OH)D] concentration. Methods: The study included 180 participants aged 40-85 y and is a National Cancer Institute independently funded ancillary study, nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), which enrolled 250 participants. The PPCCT is a double-blind 2 × 2 factorial randomized controlled trial conducted in the Vanderbilt University Medical Center. Doses for both magnesium and placebo were customized based on baseline dietary intakes. Subjects were randomly assigned to treatments using a permuted-block randomization algorithm. Changes in plasma 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2 [25(OH)D2], 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by liquid chromatography-mass spectrometry. Results: The relations between magnesium treatment and plasma concentrations of 25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 were significantly different dependent on the baseline concentrations of 25(OH)D, and significant interactions persisted after Bonferroni corrections. Magnesium supplementation increased the 25(OH)D3 concentration when baseline 25(OH)D concentrations were close to 30 ng/mL, but decreased it when baseline 25(OH)D was higher (from ∼30 to 50 ng/mL). Magnesium treatment significantly affected 24,25(OH)2D3 concentration when baseline 25(OH)D concentration was 50 ng/mL but not 30 ng/mL. On the other hand, magnesium treatment increased 25(OH)D2 as baseline 25(OH)D increased. Conclusion: Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status. This trial was registered at clinicaltrials.gov as NCT03265483.

The Dietary Supplement Label Database: Recent Developments and Applications.

Objective: To describe the history, key features, recent enhancements, and common applications of the Dietary Supplement Label Database (DSLD). Background and History: Although many Americans use dietary supplements, databases of dietary supplements sold in the United States have not been widely available. The DSLD, an easily accessible public-use database was created in 2008 to provide information on dietary supplement composition for use by researchers and consumers. Rationale: Accessing current information easily and quickly is crucial for documenting exposures to dietary supplements because they contain nutrients and other bioactive ingredients that may have beneficial or adverse effects on human health. This manuscript details recent developments with the DSLD to achieve this goal and provides examples of how the DSLD has been used. Recent Developments: With periodic updates to track changes in product composition and capture new products entering the market, the DSLD currently contains more than 71,000 dietary supplement labels. Following usability testing with consumer and researcher user groups completed in 2016, improvements to the DSLD interface were made. As of 2017, both a desktop and mobile device version are now available. Since its inception in 2008, the use of the DSLD has included research, exposure monitoring, and other purposes by users in the public and private sectors. Future Directions: Further refinement of the user interface and search features to facilitate ease of use for stakeholders is planned. Conclusions: The DSLD can be used to track changes in product composition and capture new products entering the market. With over 71,000 DS labels it is a unique resource that policymakers, researchers, clinicians, and consumers may find valuable for multiple applications.

Using the Dietary Supplement Label Database to Identify Potentially Harmful Dietary Supplement Ingredients.

Over half of young adults, athletes, and Military Service Members self-report using at least one dietary supplement (DS) 1 or more times per week. DS may be consumed to improve health, provide more energy, increase muscle strength, and/or enhance performance. The United States Food and Drug Administration (FDA) has raised concerns regarding adulteration, safety, and adverse events associated with DS marketed for brain health and bodybuilding. Some DS products may compromise health as well as lead to a serious adverse event. The National Institutes of Health (NIH) Dietary Supplement Label Database (DSLD), available at https://dsld.nlm.nih.gov/, can be freely accessed and used by researchers, providers, and consumers alike to screen for potentially harmful DS. It was developed to serve the research community and as a resource for health care providers and the public. Herein we provide two examples of how the database can be used to identify DS ingredients of concern in products marketed for brain health and bodybuilding. The search for DS marketed for brain health returned 49 unique DS, and the search on DS marketed for bodybuilding returned 18 unique DS. Search results were cross-referenced with the Operation Supplement Safety High-Risk Supplement List, the FDA Tainted Products Marketed as Dietary Supplements list, the Natural Medicines database, and NIH Office of Dietary Supplements Fact Sheets. Three ingredients found in DS marketed for brain health and two ingredients in DS marketed for bodybuilding were identified as "of concern". Educational tools, including the DSLD, can help consumers and providers make informed decisions regarding DS.

Dietary Supplement Ingredient Database (DSID) and the Application of Analytically Based Estimates of Ingredient Amount to Intake Calculations.

OBJECTIVE: We describe the purpose of the Dietary Supplement Ingredient Database (DSID), the statistical methodology underlying online calculators of analytically verified supplement content estimates, and the application and significance of DSID label adjustments in nutritional epidemiology. BACKGROUND AND HISTORY: During dietary supplement (DS) manufacturing, many ingredients are added at higher than declared label amounts, but overages are not standardized among manufacturers. As a result, researchers may underestimate nutrient intakes from DSs. The DSID provides statistical tools on the basis of the results of chemical analysis to convert label claims into analytically predicted ingredient amounts. These adjustments to labels are linked to DS products reported in NHANES. RATIONALE: Tables summarizing the numbers of NHANES DS products with ingredient overages and below label content show the importance of DSID adjustments to labels for accurate intake calculations. RECENT DEVELOPMENTS: We show the differences between analytically based estimates and labeled content for vitamin D, calcium, iodine, caffeine, and omega-3 (n-3) fatty acids and their potential impact on the accuracy of intake assessments in large surveys. Analytical overages >20% of label levels are predicted for several nutrients in 50-99% of multivitamin-mineral products (MVMs) reported in NHANES: for iodine and selenium in adult MVMs, for iodine and vitamins D and E in children's MVMs, and for iodine, chromium, and potassium in nonprescription prenatal MVMs. Predicted overages of 10-20% for calcium can be applied to most MVMs and overages >10% for folic acid in the vast majority of adult and children's MVMs. FUTURE DIRECTIONS: DSID studies are currently evaluating ingredient levels in prescription prenatal MVMs and levels of constituents in botanical DSs. CONCLUSIONS: We estimate that the majority of MVM products reported in NHANES have significant overages for several ingredients. It is important to account for nonlabeled additional nutrient exposure from DSs to better evaluate nutritional status in the United States.

Characteristics and Challenges of Dietary Supplement Databases Derived from Label Information.

Launched in 2008, the Dietary Supplement Label Database (DSLD) permits the search of any term that appears anywhere on product labels. Since then, the database's search and download features have been periodically improved to enhance use for researchers and consumers. In this review, we describe how to customize searches and identify products and ingredients of interest to users in the DSLD, and provide the limitations of working with information derived from dietary supplement product labels. This article describes how data derived from information printed on product labels are entered and organized in the DSLD. Among the challenges are determining the chemical forms, types of extract, and amounts of dietary ingredients, especially when these are components of proprietary blends. The FDA announced new dietary supplement labeling regulations in May 2016. The 2017 DSLD has been updated to reflect them. These new regulations and examples cited in this article refer to this redesigned version of the DSLD. Search selection characteristics such as for product type and intended user group are as described in FDA guidance and regulations for dietary supplements. For this reason, some age groups (such as teens and seniors) and marketing recommendations for use (e.g., weight loss, performance, and other disease- or condition-specific claims) are not included in the search selections. The DSLD user interface features will be revised periodically to reflect regulatory and technologic developments to enhance user experience. A comprehensive database derived from analytically verified data on composition would be preferable to label data, but is not feasible for technical, logistic, and financial reasons. Therefore, a database derived from information printed on product labels is the only practical option at present for researchers, clinicians, and consumers interested in the composition of these products.

Interpreting magnesium status to enhance clinical care: key indicators.

PURPOSE OF REVIEW: To update advances in identifying factors affecting magnesium (Mg) status that assist in providing improved evidence-based clinical decision-making for assessing Mg status. RECENT FINDINGS: Findings from recent cohort studies, small randomized control trials, and multiple meta-analyses reinforce earlier work that serum Mg concentrations, urinary Mg excretion, and Mg dietary intakes are inversely associated with cardiovascular disease, chronic kidney disease, and diabetes. These studies indicate that the reference range for serum Mg needs updating, and that individuals with serum Mg in the range of 0.75-0.85 mmol/l and displaying changes in other factors associated with a low Mg status may be Mg deficient. Individuals with serum Mg concentrations below this range most likely are Mg deficient and, above this range, are most likely Mg sufficient. SUMMARY: The combined determination of serum Mg concentration, 24-h urinary Mg excretion, and dietary Mg intake is currently the most practical method to obtain a sound assessment of Mg status. The strong correlations of Mg deficiency with increased risk of several chronic diseases, some of which exist as comorbidities, indicate that Mg status should be ascertained in patients presenting such disorder.

Is Nutrient Content and Other Label Information for Prescription Prenatal Supplements Different from Nonprescription Products?

BACKGROUND: Prenatal supplements are often recommended to pregnant women to help meet their nutrient needs. Many products are available, making it difficult to choose a suitable supplement because little is known about their labeling and contents to evaluate their appropriateness. OBJECTIVE: To determine differences between prescription and nonprescription prenatal supplements available in the United States regarding declared nutrient and nonnutrient ingredients and the presence of dosing and safety-related information. DESIGN: Using two publicly available databases with information about prenatal supplement products, information from prescription and nonprescription product labels were extracted and evaluated. For the 82 prescription and 132 nonprescription products, declared label amounts of seven vitamins and minerals, docosahexaenoic acid (DHA), the presence of other nonnutrient components, and the presence of key safety and informational elements as identified in two Department of Health and Human Services Office of Inspector General (OIG)'s 2003 reports were compiled and compared. RESULTS: Compared with nonprescription products, prescription products contained significantly fewer vitamins (9±0.2 vs 11±0.3; P≤0.05) and minerals (4±0.1 vs 8±0.3; P≤0.05). Declared amounts of folic acid were higher in prescription products, whereas vitamin A, vitamin D, iodine, and calcium were higher in the nonprescription products. Amounts of iron, zinc, and DHA were similar. Virtually all products contained levels of one or more nutrients that exceeded the Recommended Dietary Allowances for pregnant and/or lactating women. Product type also influenced ingredients added. Fewer prescription products contained botanical ingredients (6% prescription vs 33% nonprescription) and probiotics (2% prescription vs 8% nonprescription). Only prescription products contained the stool softener docusate sodium. CONCLUSIONS: Our analysis of prenatal supplements indicates that prescription and nonprescription supplements differ in terms of declared composition and nutrient strength, but have labels that are similarly sparse regarding aspects of use such as dosing information.