Perspective: Call for Re-evaluation of the Tolerable Upper Intake Level for Magnesium Supplementation in Adults.

In 1997, the US Institute of Medicine (IOM) dietary reference intakes (DRI) Committee established a magnesium (Mg) tolerable upper intake level (UL) for adults of 350 mg/d from supplemental intake alone. Diarrhea was the limiting factor. The safety of oral Mg dietary supplements exceeding the UL is currently in debate. Increasing the UL may result in more Mg supplementation, decreasing the prevalence of undernutrition for this nutrient and thus providing additional protection against numerous chronic diseases. This perspective aims to show that more recent and comprehensive evidence-based data on the occurrence of diarrhea indicate that the Mg UL for adults should be re-evaluated. To update the literature base to re-evaluate setting the Mg UL, a PubMed search was conducted to identify intervention studies published between 1997 and 2022 that used single-ingredient Mg products reporting a priori diarrhea adverse events among adults. The Food and Drug Administration Center for Food Safety and Adverse Event Reporting System (CAERS) was also searched for adverse events caused by Mg supplementation. The PubMed search identified 10 studies, including 5 meta-analyses and 5 randomized controlled trials, that met the search criteria. Seven studies (Mg intakes of 128-1200 mg/d) found no significant differences in diarrhea occurrence between the intervention and control groups. One meta-analysis found only minor differences in gastrointestinal disturbances between groups given placebo versus 520 mg Mg/d, but withdrawals were not significantly different between groups. Another meta-analysis found that 3 of 13 studies (120-973 mg/d) reported diarrhea that led to study withdrawal, but the treatment arm was not specified in 2 studies. The CAERS search, when limited to single-ingredient suspect Mg products, found only 40 attributable cases of gastrointestinal adverse events. Only one-third of these 40 cases noted a complaint of diarrhea. These updated data indicate that doses above the current UL for Mg supplements can be consumed without adverse events.

Calcium and vitamin D for increasing bone mineral density in premenopausal women.

BACKGROUND: Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life. OBJECTIVES: To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 12 April 2022. SELECTION CRITERIA: We included randomised controlled trials in healthy premenopausal women (with or without calcium or vitamin D deficiency) comparing supplementation of calcium or vitamin D (or both) at any dose and by any route of administration versus placebo for at least three months. Vitamin D could have been administered as cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Outcomes included total hip bone mineral density (BMD), lumbar spine BMD, quality of life, new symptomatic vertebral fractures, new symptomatic non-vertebral fractures, withdrawals due to adverse events, serious adverse events, all reported adverse events and additional withdrawals for any reason. MAIN RESULTS: We included seven RCTs with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Mean age ranged from 18.1 to 42.1 years. Studies reported results for total hip or lumbar spine BMD (or both) and withdrawals for various reasons, but none reported fractures or withdrawals for adverse events or serious adverse events. Results for the reported outcomes are presented for the three comparisons: calcium versus placebo, vitamin D versus placebo, and calcium plus vitamin D versus placebo. In all comparisons, there was no clinical difference in outcomes, and the certainty of the evidence was moderate to low. Most studies were at risk of selection, performance, detection, and reporting biases. Calcium versus placebo Four studies compared calcium versus placebo (138 participants in the calcium group and 123 in the placebo group) with mean ages from 18.0 to 47.3 years. Calcium supplementation may have little to no effect on total hip or lumbar spine BMD after 12 months in three studies and after six months in one study (total hip BMD: mean difference (MD) -0.04 g/cm2, 95% confidence interval (CI) -0.11 to 0.03; I2 = 71%; 3 studies, 174 participants; low-certainty evidence; lumbar spine BMD: MD 0 g/cm2, 95% CI -0.06 to 0.06; I2 = 71%; 4 studies, 202 participants; low-certainty evidence). Calcium alone supplementation does not reduce or increase the withdrawals in the trials (risk ratio (RR) 0.78, 95% CI 0.52 to 1.16; I2 = 0%; 4 studies, 261 participants: moderate-certainty evidence). Vitamin D versus placebo Two studies compared vitamin D versus placebo (110 participants in the vitamin D group and 79 in the placebo group), with mean ages from 18.0 to 32.7 years. These studies reported lumbar spine BMD as a mixture of MDs and percent of change and we were unable to pool the results. In the original studies, there were no differences in lumbar BMD between groups. Vitamin D alone supplementation does not reduce or increase withdrawals for any reason between groups (RR 0.74, 95% CI 0.46 to 1.19; moderate-certainty evidence). Calcium plus vitamin D versus placebo Two studies compared calcium plus vitamin D versus placebo (271 participants in the calcium plus vitamin D group and 270 in the placebo group; 220 participants from Woo 2007 and 50 participants from Islam 2010). The mean age range was 18.0 to 36 years. These studies measured different anatomic areas, one study reported total hip BMD and the other study reported lumbar spine BMD; therefore, data were not pooled for this outcome. The individual studies found no difference between groups in percent of change on total hip BMD (-0.03, 95% CI -0.06 to 0; moderate-certainty evidence), and lumbar spine BMD (MD 0.01, 95% CI -0.01 to 0.03; moderate-certainty evidence). Calcium plus vitamin D supplementation may not reduce or increase withdrawals for any reason (RR 0.82, 95% CI 0.29 to 2.35; I2 = 72%; 2 studies, 541 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non-vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful.

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.

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.

Prioritized research recommendations and potential solutions: addressing gaps surrounding dietary supplement ingredients for boosting brain health and optimizing cognitive performance.

In the market of dietary supplements, a low level of certainty exists in the state of the science, coupled with not always knowing what is in the product. Together these issues make weighing benefits/risks difficult and hinder the ability to guide evidence-based practice decisions. The authors sought to identify priorities and develop potential solutions to address research gaps so that information disseminated, can ultimately, be relied upon, when trying to make appropriate and safe decisions. Using a modified-Delphi process, 8 panelists reviewed evidence, provided from systematic review, on dietary supplement ingredients for brain health, and prioritized gaps identified and offered potential solutions. Research gaps specific to dietary supplements research included the need for quality testing of products, the question of bioavailability and absorption of ingredients, and optimal composition and standardization of supplements under investigation. Other gaps related to populations studied; a general sense of bias towards focusing research on diseased rather than maintaining or optimizing performance in healthy populations. Additionally, the lack of uniform cognitive performance measures and metrics used across research is a gap, as well as whether the metrics are accurate representations of or even generalizable to "real-life" participants wishing to optimize their performance. Methodological quality and ethical concerns in the conduct and reporting of science encompass all issues. If resources map to potential solutions outlined in this paper, then these proposed next steps offered will help facilitate meaningful research, move evidence into practice recommendations, and ultimately develop better decision-making tools for consumers to trust and rely upon for making safe supplement decisions.

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.

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.

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.

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.

Dietary Supplements for Musculoskeletal Pain: Science Versus Claims.

Special Operations Forces (SOF) face unique challenges that manifest themselves both mentally and physically. The extremes of training and combat can affect the readiness to perform at peak levels, especially when confronted with musculoskeletal pain. Many SOF Operators turn to dietary supplements in hopes of gaining an edge. Although some supplements are now being marketed for pain, decisions to use these products need to be driven by information that is evidence based. We describe SOF-specific evidence-based recommendations for the use of dietary ingredients for pain that emerged from a rigorous scientific evaluation. These recommendations are compared with the label claims made in the commercial market by companies selling products to combat musculoskeletal pain. This information can be used by the SOF medical community to assist Operators in making informed decisions when considering or selecting dietary supplements for maintaining and optimizing performance.

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.

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.

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.

Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association.

Multiple randomized controlled trials (RCTs) have assessed the effects of supplementation with eicosapentaenoic acid plus docosahexaenoic acid (omega-3 polyunsaturated fatty acids, commonly called fish oils) on the occurrence of clinical cardiovascular diseases. Although the effects of supplementation for the primary prevention of clinical cardiovascular events in the general population have not been examined, RCTs have assessed the role of supplementation in secondary prevention among patients with diabetes mellitus and prediabetes, patients at high risk of cardiovascular disease, and those with prevalent coronary heart disease. In this scientific advisory, we take a clinical approach and focus on common indications for omega-3 polyunsaturated fatty acid supplements related to the prevention of clinical cardiovascular events. We limited the scope of our review to large RCTs of supplementation with major clinical cardiovascular disease end points; meta-analyses were considered secondarily. We discuss the features of available RCTs and provide the rationale for our recommendations. We then use existing American Heart Association criteria to assess the strength of the recommendation and the level of evidence. On the basis of our review of the cumulative evidence from RCTs designed to assess the effect of omega-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events, we update prior recommendations for patients with prevalent coronary heart disease, and we offer recommendations, when data are available, for patients with other clinical indications, including patients with diabetes mellitus and prediabetes and those with high risk of cardiovascular disease, stroke, heart failure, and atrial fibrillation.

Safety and performance benefits of arginine supplements for military personnel: a systematic review.

CONTEXT: Dietary supplements are widely used by military personnel and civilians for promotion of health. OBJECTIVE: The objective of this evidence-based review was to examine whether supplementation with l-arginine, in combination with caffeine and/or creatine, is safe and whether it enhances athletic performance or improves recovery from exhaustion for military personnel. DATA SOURCES: Information from clinical trials and adverse event reports were collected from 17 databases and 5 adverse event report portals. STUDY SELECTION: Studies and reports were included if they evaluated the safety and the putative outcomes of enhanced performance or improved recovery from exhaustion associated with the intake of arginine alone or in combination with caffeine and/or creatine in healthy adults aged 19 to 50 years. DATA EXTRACTION: Information related to population, intervention, comparator, and outcomes was abstracted. Of the 2687 articles screened, 62 articles meeting the inclusion criteria were analyzed. Strength of evidence was assessed in terms of risk of bias, consistency, directness, and precision. RESULTS: Most studies had few participants and suggested risk of bias that could negatively affect the results. l-Arginine supplementation provided little enhancement of athletic performance or improvements in recovery. Short-term supplementation with arginine may result in adverse gastrointestinal and cardiovascular effects. No information about the effects of arginine on the performance of military personnel was available. CONCLUSIONS: The available information does not support the use of l-arginine, either alone or in combination with caffeine, creatine, or both, to enhance athletic performance or improve recovery from exhaustion. Given the information gaps, an evidence-based review to assess the safety or effectiveness of multi-ingredient dietary supplements was not feasible, and therefore the development of a computational model-based approach to predict the safety of multi-ingredient dietary supplements is recommended.