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.

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).

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.

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.

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.

The Circulating Concentration and 24-h Urine Excretion of Magnesium Dose- and Time-Dependently Respond to Oral Magnesium Supplementation in a Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Accurate determination of Mg status is important for improving nutritional assessment and clinical risk stratification. OBJECTIVE: We aimed to quantify the overall responsiveness of Mg biomarkers to oral Mg supplementation among adults without severe diseases and their dose- and time responses using available data from randomized controlled trials (RCTs). METHODS: We identified 48 Mg supplementation trials (n = 2131) through searches of MEDLINE and the Cochrane Library up to November 2014. Random-effects meta-analysis was used to estimate weighted mean differences of biomarker concentrations between intervention and placebo groups. Restricted cubic splines were used to determine the dose- and time responses of Mg biomarkers to supplementation. RESULTS: Among the 35 biomarkers assessed, serum, plasma, and urine Mg were most commonly measured. Elemental Mg supplementation doses ranged from 197 to 994 mg/d. Trials ranged from 3 wk to 5 y (median: 12 wk). Mg supplementation significantly elevated circulating Mg by 0.04 mmol/L (95% CI: 0.02, 0.06) and 24-h urine Mg excretion by 1.52 mmol/24 h (95% CI: 1.20, 1.83) as compared to placebo. Circulating Mg concentrations and 24-h urine Mg excretion responded to Mg supplementation in a dose- and time-dependent manner, gradually reaching a steady state at doses of 300 mg/d and 400 mg/d, or after ~20 wk and 40 wk, respectively (all P-nonlinearity ≤ 0.001). The higher the circulating Mg concentration at baseline, the lower the responsiveness of circulating Mg to supplementation, and the higher the urinary excretion (all P-linearity < 0.05). In addition, RBC Mg, fecal Mg, and urine calcium were significantly more elevated by Mg supplementation than by placebo (all P-values < 0.05), but there is insufficient evidence to determine their responses to increasing Mg doses. CONCLUSIONS: This meta-analysis of RCTs demonstrated significant dose- and time responses of circulating Mg concentration and 24-h urine Mg excretion to oral Mg supplementation.

A select review reporting the quality of studies measuring endothelial dysfunction in randomised diet intervention trials.

A quality assessment of the primary studies reported in the literature carried out using select dietary ingredients (DI) purported to affect vascular endothelial function was conducted through a systematic PubMed search from January 2000 to August 2012. A total of seventy randomised controlled trials with defined DI (folic acid (fifteen), n-3 fatty acids (twenty), cocoa (fifteen) and isoflavones (twenty)) and standardised measures of vascular endothelial function were evaluated. Jadad scores, quality scoring parameters for DI and flow-mediated dilation (FMD) methodology used were ascertained. A total of 3959 randomised subjects, mean age 51 (se 0·21) years (range 9-79 years), were represented in the dataset. The mean Jadad scores did not differ statistically among the DI studies, with the majority of the studies being of good quality. Higher DI quality scores were achieved by studies using the botanical ingredients cocoa and isoflavones than by those using the nutrient ingredients folic acid and n-3 fatty acids. The mean DI quality scores were 4·13 (se 0·34), 5·20 (se 0·47), 6·13 (se 0·41) and 6·00 (se 0·59) for the folic acid, n-3 fatty acid, cocoa and isoflavone intervention studies, respectively (and significantly different). The mean Corretti FMD scores were 7·27 (se 0·56), 7·46 (se 0·79), 6·29 (se 0·61) and 7·11 (se 0·56) for the folic acid, n-3 fatty acid, cocoa and isoflavone intervention studies, respectively (NS). FMD studies failed to adequately describe the equipment used and more than half failed to provide an adequate description of the procedures used for vascular image acquisition and measurement. DI can be utilised for dietary intervention studies; however, the methodology should be clearly reported using the guidelines for assessment for both DI and FMD.

The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature.

A systematic review was conducted using Samueli Institute's Rapid Evidence Assessment of the Literature (REAL) process to determine the evidence base for melatonin as an agent to optimize sleep or improve sleep quality, and generalize the results to a military, civilian, or other healthy, active, adult population. Multiple databases were searched yielding 35 randomized controlled trials (RCTs) meeting the review's inclusion criteria, which were assessed for methodological quality as well as for melatonin effectiveness. The majority of included studies were high quality (83.0%). Overall, according to Grading Recommendations, Assessment Development and Evaluation (GRADE) methodology, weak recommendations were made for preventing phase shifts from jet lag, for improving insomnia in both healthy volunteers and individuals with a history of insomnia, and for initiating sleep and/or improving sleep efficacy. Based on the literature to date, no recommendations for use in shift workers or to improve hormonal phase shift changes in healthy people can be made at this time. Larger and longer-duration RCTs utilizing well characterized products are needed to warrant melatonin recommendations in young, healthy adults.

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.

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.

Conceptualizing a resilience research framework at The National Institutes of Health.

The National Institutes of Health (NIH) have recently gathered internal and external input towards a shared understanding of resilience in the wide context of human health and the biomedical sciences that would help accelerate advances in human health and its maintenance. This shared view is that resilience refers in general to a system's capacity to recover, grow, adapt, or resist perturbation from a challenge or stressor. Over time, a system's response to a challenge might show varied degrees of reactions that likely fluctuate in response to the type of challenge (internal and/or external), severity of the challenge, the length of time exposed to the challenge, other external factors and/or biological factors (innate and/or external). We have embarked on this special issue as an opportunity to explore commonalities amongst viewpoints on the science of resilience covered by the various NIH Institutes, Centers, and Offices (ICOs) with respect to the characterization of various systems, stressors, outcomes measures and metrics, and interventions and/or protective factors that are shared within each domain and across multiple domains. Here, resilience is characterized broadly by four areas of scientific study: molecular/cellular, physiologic, psychosocial and spiritual, and environmental/community resilience. Each area or domain provides general frameworks for designing studies that may help advance the science of resilience within the context of health maintenance. This special issue will also acknowledge the remaining gaps that impede advancement of the science of resilience and offer considerations for potential next steps towards addressing the research gaps.

Next steps: Operationalizing resilience research.

The National Institutes of Health have recently gathered internal and external input towards a shared understanding of resilience in the wide context of human health and the biomedical sciences that would help accelerate advances in human health and its maintenance. We suggest the current view that resilience refers in general to a system's capacity to recover, grow, adapt, or resist perturbation from a challenge or stressor. To help harmonize the design and reporting of resilience research studies across multiple domains we have developed and are proposing a Resilience Research Design (ResD) Tool. Researchers can use the Resilience ResD Tool to proceed through a flowchart of six questions that will guide identification of key features in a resilience research study. Through this special supplement, we have shown the application of the Resilience ResD Tool and suggest opportunities and gaps with respect to next steps towards operationalizing resilience research.

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.

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.