Total Force Fitness: Making Holistic, Integrated Whole-Person Research a DoD Priority.

Total Force Fitness (TFF) was conceived as a holistic framework for building and sustaining Human Performance Optimization for Warfighters and their families. As such, TFF research must also be holistic in nature. During the research breakout, group barriers and challenges to TFF research were discussed, and critical research focus areas were prioritized. The top approaches discussed were (1) using big data to identify best practices and health trajectories; (2) applying community-based participatory research principles to military units; (3) focusing on "Whole-Person," integrative research (physical, behavioral, spiritual, and biological) across the Department of Defense; and, finally, (4) prioritizing key opportunities to advance TFF across the active duty and Reserve/Guard enterprises and their families. The research group noted that coordinated action would be needed to move the prioritized agenda forward. Finally, translating research into action is essential because TFF is a way of honoring our service members as whole persons with careers, goals, and families.

Total Force Fitness Summit 2021: Maximizing the Health and Well-being of Service Members and Their Families.

Total Force Fitness (TFF) is a multidomain, holistic framework that provides the Department of Defense (DoD) with the capability to assess, promote, and sustain human performance optimization across the full spectrum of components key to meeting mission requirements. On September 14 and 15, 2021, in Bethesda, MD, The Consortium for Health and Military Performance convened a second TFF Summit with the goal of promoting the mission of optimizing the health and well-being of our service members across their careers. Participants included scientists, clinicians, educators, public health professionals, and military leaders from all the services. The current operating picture of TFF within the DoD was described, and then working groups were convened to address issues related to (1) delivering full spectrum health and performance services; (2) advocacy, awareness, and empowerment; (3) research; (4) education; and (5) standardization, branding, and metrics. The outcomes of the summit included recommendations that operational leadership and a consolidated and joint approach are required for TFF to be successful, and TFF must be regarded as an integral part of the National Defense, Security, and Military Strategy. To that end, TFF should be aligned within OUSD(P&R), not the Military Health System, so it extends beyond the medical setting and fully supports mission readiness and performance. Importantly, we must be proactive and teach new recruits about the TFF holistic approach to sustain optimal performance across their careers.

Omega-3 Index improves after increased intake of foods with omega-3 polyunsaturated fatty acids among US service academy cadets.

The inclusion of omega-3 fatty acids in our dietary intake is important for performance and recovery and may reduce the risk of various health issues. Studies have shown the omega-3 fatty acid status of US service members is low. The purpose of this study was to evaluate whether offering fish and omega-3-enhanced foods would increase the Omega-3 Index (O3I). We hypothesize cadets will increase O3I with enhanced omega-3 options more than fish alone. Food service venues at 3 US service academies offered fish and other omega-3 foods to cadets for 12 weeks. Questionnaires were used to collect information on the dietary habits and omega-3 food intake of participants. The O3I of each participant was measured at baseline, mid- (6 weeks), and after data collection (12 weeks) time points. Following the 12 weeks, we found a significant increase in O3I. More specifically, the intake of other omega-3 foods, smoothies (3 per week) and toppings (3 per week), increased O3I in cadets. This study identified a strategy encouraging omega-3 food intake and improving O3I among cadets. These results help us understand how we can more effectively impact military service member nutrition for optimal health and performance.

Mitochondrial Fission as a Therapeutic Target for Metabolic Diseases: Insights into Antioxidant Strategies.

Mitochondrial fission is a crucial process in maintaining metabolic homeostasis in normal physiology and under conditions of stress. Its dysregulation has been associated with several metabolic diseases, including, but not limited to, obesity, type 2 diabetes (T2DM), and cardiovascular diseases. Reactive oxygen species (ROS) serve a vital role in the genesis of these conditions, and mitochondria are both the main sites of ROS production and the primary targets of ROS. In this review, we explore the physiological and pathological roles of mitochondrial fission, its regulation by dynamin-related protein 1 (Drp1), and the interplay between ROS and mitochondria in health and metabolic diseases. We also discuss the potential therapeutic strategies of targeting mitochondrial fission through antioxidant treatments for ROS-induced conditions, including the effects of lifestyle interventions, dietary supplements, and chemicals, such as mitochondrial division inhibitor-1 (Mdivi-1) and other mitochondrial fission inhibitors, as well as certain commonly used drugs for metabolic diseases. This review highlights the importance of understanding the role of mitochondrial fission in health and metabolic diseases, and the potential of targeting mitochondrial fission as a therapeutic approach to protecting against these conditions.

Omega-3 Fatty Acids: Benefits for Performance and Recovery.

Full-spectrum human performance optimization (HPO) is essential for Special Operations Forces (SOF). Nutrition is one part of HPO and is important for all aspects of performance. One area of increased interest in this regard is omega-3 polyunsaturated fatty acids (omega-3). Research has indicated that Servicemembers (SM), including SOF, do not eat the recommended 2 to 3 servings per week of fatty fish and have low omega-3 levels. Therefore, alternative approaches are warranted. The purpose of this article is to highlight the potential mental and physical health and performance benefits of omega-3. Consuming omega-3 on a regular basis would not only be beneficial for the health of SOF but also for their training and overall performance.

Acute heat stress-indued apoptosis in mouse skeletal muscle is not associated with alteration of glutamine homeostasis.

We previously demonstrated that exposing mice to heat causes functional and ultrastructural mitochondrial alterations and apoptosis in skeletal muscle. Emerging evidence indicates that glutamine (Gln) deprivation may increase cell susceptibility to apoptosis whereas Gln supplementation may protect cells against heat stress. In this study, we investigated the effect of short-term Gln treatment on heat-induced changes in mouse skeletal muscle. Male mice received vehicle, low-dose Gln (100 mg/kg/d) or high-dose Gln (300 mg/kg/d) through daily gavage for 10 days before a heat exposure test. During heat exposure, mice displayed a hyperthermic response and no significant differences in peak core body temperature were noted across the three groups. Neither heat exposure nor pretreatment with low-dose or high-dose Gln significantly affected Gln concentrations in plasma and gastrocnemius muscles. Heat-exposed mice had significantly higher caspase 3/7 levels in gastrocnemius muscle compared to unexposed controls. Heat exposure significantly increased ROS production and mitochondrial fragmentation and decreased mitochondrial membrane potential in flexor digitorum brevis muscle. These changes were not affected by low- or high-dose Gln pretreatment. Together, acute heat stress did not disrupt Gln homeostasis in mouse skeletal muscle and Gln supplementation did not protect mouse skeletal muscle against heat-induced injury. The results of this study do not support a role of Gln in heat-induced skeletal muscle apoptosis.

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.

Analysis of Select Dietary Supplement Products Marketed to Support or Boost the Immune System.

Importance: Cold, flu, and immunity dietary supplement product sales have skyrocketed since the start of the COVID-19 pandemic. Supporting or boosting the immune system has become an important reason for using dietary supplements, and many consumers are purchasing products through online platforms. Objectives: To examine whether select dietary supplement products advertised as supporting or boosting the immune system are accurately labeled according to the Supplement Facts label of listed ingredients and to qualitatively describe the product labels' characteristics in terms of claims made. Design, Setting, and Participants: In this case series, 30 featured immune health dietary supplements were selected and purchased from Amazon.com in May 2021. Product analysis was performed using liquid chromatography-mass spectrometry. The list of ingredients detected through analysis for each product was compared with the ingredients on the product's Supplement Facts label to determine whether the product's label was accurate. Claims made on product labels were also evaluated by using the Operation Supplement Safety Scorecard's set of questions to describe the labels' characteristics. Results: A total of 30 select dietary supplement products were evaluated. Thirteen of the 30 products had accurate labels based on the product analysis. Of the 17 products with inaccurate labels, 13 had ingredients listed on the labels that were not detected through analysis, such that their labels were misbranded. Nine products had substances detected that were not claimed on the product labels, some of which may be considered adulterated. Five were misbranded and contained additional components not claimed on the label. No product had third-party certification seals present on the packaging. Ten of the 13 products with accurate labels received a score of 4 or more when applying the Operation Supplement Safety Scorecard, meaning the product was "likely okay/less risky." Conclusions and Relevance: In this case series study, most of the products tested had inaccurate labels and claims that were inconsistent with requirements the US Food and Drug Administration has put forward for dietary supplements. Quality control measures seem to be insufficient for most of these select products, and claims made on labels may be misleading consumers who purchase products.

Optimization of Omega-3 Index Levels in Athletes at the US Naval Academy: Personalized Omega-3 Fatty Acid Dosage and Molecular Genetic Approaches.

The Dietary Guidelines for Americans recommend increasing the intake of omega-3 polyunsaturated fatty acids. The Omega-3 Index (O3I) is one marker used to assess omega-3 status. The O3I national average is 4.3%, which translates into a high risk for developing cardiovascular disease. Research has reported an association between variants in the two desaturase encoding genes, fatty acid desaturase 1 and fatty acid desaturase 2 (FADS1/2), and the concentration of O3I. The aim of this study was to assess whether a personalized dosage of omega-3 supplementation would lead to an O3I ≥ 8%. A secondary aim was to identify if changes in O3I levels would be associated with either of the two FADS1/2 variants. METHODS: This interventional study had a pre- and post-intervention design to assess changes in O3I. Ninety participants completed demographic, biometrics, O3I, and genetic testing. Participants were provided a personalized dose of omega-3 supplements based on their baseline O3I. RESULTS: The majority (63%) of participants were 20 year old white males with an average O3I at baseline of 4.6%; the post-supplementation average O3I was 5.6%. The most frequent genetic variants expressed in the full sample for FADS1/2 were GG (50%) and CA/AA (57%). CONCLUSIONS: O3I was significantly increased following omega-3 supplementation. However, it was not possible to conclude whether the two FADS1/2 variants led to differential increases in OI3 or if a personalized dosage of omega-3 supplementation led to an O3I ≥ 8%, due to our study limitations.

The Effects of Berry Extracts on Oxidative Stress in Cultured Cardiomyocytes and Microglial Cells: A Potential Cardioprotective and Neuroprotective Mechanism.

Oxidative stress is a key underlying factor in cognitive decline and atherosclerosis. Oxidative stress occurs at the cellular level with an imbalance between reactive oxygen species and reactive nitrogen species and a deficiency in antioxidants. Mounting evidence suggests that berry flavonoids may promote cellular health by exerting antioxidant properties. Black currant and various berry extracts were tested in microglia (BV-2) and cardiomyocyte (HL-1) cell lines to study their biological effects. The principal ingredients in black currant and cranberry extract-delphinidin 3-rutinoside (D3R) and cyanidin 3-glucoside (C3G), were also assessed. A menadione-induced oxidative stressor was used, and its output was quantified to detect oxidative stress (CellROXTM). Black currant extract had similar antioxidant effects as N-acetylcysteine (NAC) in HL-1 cells with regard to cellular protection, whereas cranberry extract was ineffective. In contrast, cranberry extract was comparable in effectiveness to black currant extract in BV-2 cells. D3R and C3G also reduced oxidative stress similarly to whole berry extracts, which indicates that these ingredients may confer the antioxidant effects of berries. Black currant and cranberry extracts inhibit oxidative stress in microglial and cardiomyocyte cell lines. Black currant extract was more effective in reducing oxidative stress in the HL-1 cells, whereas cranberry extract was comparable in reducing oxidative stress in the BV-2 cells. The results suggest that berry flavonoids exert neuro- and cardioprotective effects.

Relative safety and quality of various dietary supplement products U.S. Service Members ask about.

CONTEXT: The purpose of this project was to determine types of dietary supplement products U.S. Service Members frequently ask about and identify risks associated with select products that consumers should be aware of when considering their use. METHODS: Forty-one dietary supplement products frequently asked about through the Operation Supplement Safety's (OPSS.org) Ask-the-Expert portal were selected. Product analysis was performed to verify whether select products were accurately labeled and to identify any risky ingredients contained in these products. Operation Supplement Safety Risk Assessment Scorecard criteria were additionally used as a screening tool to assess a product's relative safety potential. RESULTS: Among the select dietary supplements, 12 (29.3%) were marketed as pre-workout products; 14 (34.1%) for weight loss; four (9.8%) for male enhancement/testosterone boosters; and 11 (26.8%) as body building supplements. Eleven (26.8%) products had accurate labels; only eight of these had accurate labels plus no risky ingredients listed on the labels. Twenty-six (63.4%) products were misbranded; 10 (24.4%) were adulterated, and six (14.6%) were both misbranded and adulterated. Risky ingredients appeared on 23 (56%) of all product labels. Eight of these 23 products also had additional risky ingredients not listed on the labels but detected through analysis. According to the Scorecard based on label claims, 35 (85.4%) received a rating of "no-go/risky". CONCLUSIONS: U.S. Service Members and the public at large should be aware that dietary supplements may contain risky ingredients and know how to identify ingredients on the label to evaluate potential risk.

Hydrolyzed whey protein enriched with glutamine dipeptide attenuates skeletal muscle damage and improves physical exhaustion test performance in triathletes.

Purpose: To investigate the effects of hydrolyzed whey protein enriched with glutamine dipeptide on the percentage of oxygen consumption, second ventilatory threshold, duration and total distance covered, and skeletal muscle damage during an exhaustion test in elite triathletes. Methods: The study was a randomized, double-blinded, placebo-controlled, crossover trial. Nine male triathletes performed a progressive incremental test on a treadmill ergometer (1.4 km h-1·3 min-1) 30 min after ingesting either 50 g of maltodextrin plus four tablets of 700 mg hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide diluted in 250 ml of water (MGln) or four tablets of 700 mg maltodextrin plus 50 g maltodextrin diluted in 250 ml of water (M). Each athlete was submitted to the two dietary treatments and two corresponding exhaustive physical tests with an interval of one week between the interventions. The effects of the two treatments were then compared within the same athlete. Maximal oxygen consumption, percentage of maximal oxygen consumption, second ventilatory threshold, and duration and total distance covered were measured during the exhaustion test. Blood was collected before and immediately after the test for the determination of plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration (also measured 6, 10, and 15 min after the test). Plasma cytokines (IL-6, IL-1ß, TNF-α, IL-8, IL-10, and IL-1ra) and C-reactive protein levels were also measured. Results: A single dose of MGln increased the percentage of maximal oxygen consumption, second ventilatory threshold duration, and total distance covered during the exhaustion test and augmented plasma lactate levels 6 and 15 min after the test. MGln also decreased plasma LDH and CK activities indicating muscle damage protection. Plasma cytokine and C-reactive protein levels did not change across the study periods. Conclusion: Conditions including overnight fasting and a single dose of MGln supplementation resulted in exercising at a higher percentage of maximal oxygen consumption, a higher second ventilatory threshold, blood lactate levels, and reductions in plasma markers of muscle damage during an exhaustion test in elite triathletes. These findings support oral glutamine supplementation's efficacy in triathletes, but further studies require.

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.

Effects of training service dogs on service members with PTSD: A pilot-feasibility randomized study with mixed methods.

This pilot-feasibility randomized control trial examined effects of an adjunctive short-term service dog training program (SDTP) for service members in out-patient treatment for PTSD. Twenty-nine volunteer participants were randomly assigned to either the SDTP (n = 12) or waitlist (n = 17); 20 participants were available for post-treatment evaluation. SDTP protocol consisted of six structured one-hour sessions with a dog-trainer conducted over two weeks, intended to train a service dog to help a fellow Veteran. SMs completed symptom questionnaires (PTSD, insomnia, stress, depression, anxiety), and the SDTP group completed a post-intervention quantitative interview. Most effect sizes demonstrated moderate symptom reductions, both between-groups and within the SDTP group. Between-group effects were strongest for intrusive thoughts (Hedge's g = -0.66; 95%CI: -1.72, 0.23) and overall PTSD symptoms (g = -0.45; 95%CI: -1.47, 0.45); within-SDTP group effects were strongest for stress (d = -1.31, 95%CI: -2.17, -0.42), intrusive thoughts (d = -0.78, 95%CI: -1.55, 0.01) and hypervigilance (d = -0.77, 95%CI: -1.48, -0.04). Qualitative analyses indicated participants found SDTP in some ways challenging yet beneficial in multiple aspects of personal and social lives. Future work should examine optimal treatment parameters (e.g., duration, "dosing") when training dogs as an adjunct to other PTSD treatment.

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.

Dietary Supplement Ingredients for Optimizing Cognitive Performance Among Healthy Adults: A Systematic Review.

Background: Dietary supplements promoted for brain health and enhanced cognitive performance are widely available. Claims made for these products are directed not only to the elderly wishing to prevent or mitigate cognitive decline, but also young healthy populations looking to boost their cognitive performance. It is unclear whether these claims made on product bottles and through advertising match the science. Objectives: To explore the evidence on the efficacy and safety of single dietary supplement ingredients frequently marketed with claims of enhanced cognitive performance among healthy adults. Design: A systematic review. Results: Nine of 54 dietary supplement ingredients identified through a scoping review met the eligibility criteria with at least 3 published studies identified per ingredient, yielding 69 unique publications. Ingredients evaluated included Bacopa monnieri, choline, creatine, omega-3 fatty acids, Ginkgo biloba, ginseng, Rhodiola rosea, tyrosine, and valerian root, all in supplement form and compared with a placebo, at various serving sizes and durations of use. Conclusions: The low level of certainty in the state of the science, coupled with not always knowing what is in a dietary supplement product, make weighing risks and benefits difficult; these data hinder the ability to develop recommendations about using such ingredients for consumers interested in boosting their cognitive performance. Whereas certain trends regarding promising serving sizes or duration for use, are pointed to in this synthesis, when combined, studies are inconsistent and imprecise, and many are methodologically flawed. Potential solutions to address research gaps are offered, for future research next steps, which is needed to strengthen the evidence and inform decisions.

A Threat to Military Combat Power: Dietary Supplements.

BACKGROUND: The use of dietary supplements by young warfighters is pervasive and comes with a readiness cost, especially in the deployed setting. Predatory targeting and marketing by various unscrupulous companies put this population at risk for a higher than baseline risk for adverse events. METHODS: We report on 6 serious adverse events experienced by warfighters while deployed in Kuwait and Afghanistan. Presented is a discussion of current practice gaps and solutions, as well as details regarding how polypharmacy contributes to the seriousness of the threat posed by problematic supplements. RESULTS: The morbidity associated with the 6 cases of dietary supplement adverse events compromised mission readiness and was costly in terms of health and health care expenditures. CONCLUSION: The military dietary supplement issue needs exposure, review, and action at the highest levels of government.

Aligning and Assessing Core Attributes of Spiritual Fitness for Optimizing Human Performance.

The United States Special Operations Command (SOCOM)'s Preservation of the Force and Family Program (POTFF) identifies spiritual performance (SP) as a key pillar for holistically caring for and optimizing the performance of all Special Operations Forces (SOF) and their families. Enhancing SP is key to sustaining core spiritual beliefs, values, awareness, relationships and experiences. The SOCOM Spiritual Fitness Scale (SSFS) enables religious support teams in SOF communities and beyond to reliably measure SP according to POTFF's definition of SP and the Chairman of the Joint Chiefs of Staff Instruction (CJCSI) on Spiritual Fitness (SF). The three subscales of the SSFS relate to core attributes of SP/SF, which were identified through factor analysis during iterations of the tool's development. Directly aligning SP/SF programs with the core attributes of SSFS will allow chaplains to support both theists and nontheists and to retain certain traditional chaplain activities which no longer have universal connection to religious ministry in the public discourse. Chaplains are also empowered to immediately begin conducting relevant and spiritual assessments. We will illustrate how a chaplain can align SP initiatives with the three core attributes of SP/SF and leverage the SSFS to assess baseline unit needs, conceive and develop evidence-based initiatives, conduct rolling program assessments, and articulate program efficacy to key leaders and collaborators.

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

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