Environmental challenges such as rising atmospheric carbon dioxide (CO) levels, changes in climate patterns, and heightened frequency and severity of extreme weather events are presenting multifaceted and compounding threats to nutrition and nutrition-related health outcomes. This perspective paper identifies the following three critical research gaps at the intersection of dietary supplements and environmental challenges: 1) addressing nutrient deficiencies caused by environmental threats; 2) enhancing biological resilience to environmental stressors; and 3) altering environmental impacts through changes in dietary patterns and industry practices. We discuss methodological challenges and emphasize interdisciplinary collaboration. By addressing these gaps, we can better understand how dietary supplements might contribute to nutrition security and health in the United States amid changing environmental conditions. This knowledge will inform public health policies and interventions, while considering the complex interplay between dietary supplements, nutrition, and environmental factors. Statement of Significance: Rigorous dietary supplements research in the context of environmental challenges is severely underrepresented in nutrition, environmental, and public health literature. This perspective paper summarizes relevant literature, identifies research gaps, and proposes an interdisciplinary and collaborative research agenda to address the complex intersection of dietary supplements, nutrition security, resilience, and environmental challenges.

The role of dietary fat in type 2 diabetes (T2D) development remains debated. Fatty acid (FA) biomarkers may better reflect bioavailable FAs than self-reported dietary intake.

Nutritional deficiencies are prevalent in populations across the world. Fortification of staple foods has been used as an alternative to supplementation to address many deficiencies. One such staple is salt, which has long been fortified with iodine, but more recently with iron, folate, and other micronutrients. Our objective was to determine the effects of fortified salt on nutritional and health outcomes among children, adolescents, and adults. We conducted a systematic review of published and unpublished literature using a pre-defined search strategy. Abstracts and full texts were screened for randomized trials, quasi-randomized trials, and pre- post-designs of double or multiple fortified salt. We calculated weighted pooled effect sizes for effects of fortified salt on nutritional and health outcomes. Of the 395 studies identified, 33 (including 37 intervention-control comparisons) fit our inclusion criteria. Of these comparisons, 26 studied the effects of salt fortified with iron and iodine (DFS), two studied the effects of salt fortified with folic acid and iodine (FISFA), one studied the effect of triple-fortified salt (TFS), one studied the effect of quadruple-fortified salt (QFS), and seven studied the effects of multiple micronutrient fortified salt (MMFS; fortified with at least five nutrients). Pooled effect sizes indicated positive effects from all iron-containing fortified salt on hemoglobin concentration [standardized mean difference (95% CI): DFS 0.36 (0.22, 0.50), n=26 comparisons; TFS 1.56 (1.42, 1.70), n=1; QFS 0.33 (0.02, 0.63), n=1; MMFS 0.23 (0.03, 0.43), N=6]. DFS and MMFS reduced the odds of anemia and iron deficiency anemia. MMFS improved serum folate and reduced the odds of iron deficiency. Pooled effects on biomarkers of vitamin B12, vitamin A, and zinc status varied by type of salt, but were largely not significant. Fortification of salt with iodine and iron, with and without other nutrients, is effective in increasing hemoglobin and reducing the odds of anemia and iron deficiency in population-based studies.

It is unclear whether various obesity phenotypes are differently associated with cognitive disorders. The aim of this study was to examine the associations of general obesity [measured by body mass index (BMI)], central obesity [measured by waist circumference (WC), waist-to-hip ratio (WHR)], or body fat percentage (BFP), and visceral obesity with cognitive disorders in older adults using meta-analysis and Mendelian randomization (MR) approaches. We identified observational studies published from the inception of 4 (PubMed, Embase, Medline, and Web of Science) databases until November 2024. A random-effects model was employed to construct the pooled odds ratio (OR) and 95% confidence interval (CI) for exploring the associations of general, central, and visceral obesity with cognitive impairment. The mean, median, or range age of participants is ≥60 y. Subsequently, a 2-sample MR analysis was performed using genetic variation data to investigate the potential causal relationships of general, central, and visceral obesity with cognitive impairment. A total of 70 studies comprising 2,810,410 participants were included. In meta-analysis, general obesity (measured by BMI) showed an inverse association with cognitive disorders. Compared with normal BMI, the pooled ORs (95% CIs) were 1.29 (1.21, 1.38) for underweight, 0.87 (0.84, 0.90) for overweight, and 0.88 (0.85, 0.91) for obesity. In contrast, no significant association was observed for central obesity (WC or WHR) or visceral obesity. Subgroup analyses by sex, study design, region, and disease type produced results consistent with the overall findings. In MR analyses, higher BMI, BFP, WC, and WHR were associated with a reduced risk of cognitive impairment, with WHR also inversely related to mild cognitive impairment. No causal association was observed for dementia or Alzheimer's disease. The research results indicate that there might be a negative correlation between obesity (especially generalized obesity) and cognitive impairment in the elderly.

Fermented foods represent a diverse category of products shaped by microbial metabolism, offering distinctive sensory qualities and potential health benefits. Although prior reviews have explored the nutritional and microbial aspects of fermented foods or focused on specific health outcomes and mechanisms of action, few recent narrative reviews have integrated clinical and epidemiologic evidence across diverse health domains. This review addresses that gap by critically evaluating observational and interventional studies linking fermented food consumption with metabolic, cardiovascular, oncologic, and neuropsychological outcomes, while summarizing associated biomarkers that may underpin these effects. Emphasis is placed on clinical studies of fermented foods containing live microbes. Through mapping current evidence to noncommunicable disease outcomes, the review identifies consistent protective associations, methodological limitations, and key knowledge gaps, and outlines priorities to advance the field and its translation into dietary guidance. It further underscores the need for standardized product characterization and well-powered clinical trials to establish causality. Overall, this work provides the most current and integrative assessment of fermented foods and human health, highlighting their potential as a valuable yet underutilized component of strategies for chronic disease prevention and public health policy.

Given the global rise in type 2 diabetes mellitus (T2D), the Mediterranean diet (MedDiet) has gained attention as a promising preventive dietary pattern.

Radiotherapy plays a vital role in cancer treatment, yet its effects on patients' nutritional status can precipitate muscle loss, with significant implications for treatment tolerance and outcomes. Evidence from high-income countries increasingly links radiation-induced muscle loss to adverse clinical outcomes. In contrast, low- and middle-income countries face a stark evidence gap, despite the heightened vulnerability of cancer patients in these settings due to delayed diagnosis, limited access to care, and high rates of co-morbidities. This paper highlights the critical gaps in nutritional care for radiotherapy patients in low- and middle-income countries.

Childhood overweight/obesity have emerged as pressing public health concerns globally, and the impact of the food environment on children's diets and health outcomes have gained heightened attention. Comprehensive and child-specific monitoring systems are critical for guiding targeted interventions and policies. This review aims to synthesize recent literature on food environment indicators associated with children overweight/obesity using the 4A framework, including food availability, accessibility, affordability, and appeal. We conducted a systematic search of peer-reviewed literature (2020-2025). This systematic review is guided by PRISMA and involved narrative synthesis and framework-based classification (CRD420251116187). A total of 75 observational and 6 intervention studies are included. Indicators related to availability (e.g., home food supply and fast-food outlet density) and accessibility (e.g., proximity to healthy food stores) are most commonly studied, while affordability and appeal indicators (e.g., food pricing and marketing exposure) are less frequently addressed. Current evidence underscores deficiencies in the measurement and monitoring of food environment for children, which is important to prevent and manage childhood overweight/obesity using integrated indicators at home, schools, communities, and society. Moreover, there is a necessity existed to develop standardized, child-centered food environment monitoring system, facilitating prompt, equity-sensitive policy action to address children overweight/obesity on a worldwide scale, which also supports global sustainable development. This systematic review paper will be useful to choose indicators for the construction of food environment monitoring system. STATEMENTS OF SIGNIFICANCE: This systematic review addresses an important gap, as no previous review has comprehensively synthesized evidence on food environment indicators associated with childhood overweight/obesity. Using the 4A framework (food availability, food accessibility, food affordability, and food appeal) to organize existing evidence, this study provides a structured foundation for identifying key indicators that can inform the development of food environment monitoring systems and guide multi-level interventions across home, school, and community settings, thereby offering a practical reference for advancing food environment development initiatives worldwide.

Food biodiversity is receiving increased attention because of global food systems being a major contributor to biodiversity loss. Food biodiversity, defined as the diversity of plants, animals, and other organisms used for food, may benefit both human and planetary health. Despite this potential, little is known about the association between food biodiversity and the healthiness of human diets. This systematic scoping review presents an overview of the nexus between food biodiversity, diet quality, health outcomes, and environmental impact. Three search strategies were performed in Scopus and PubMed Central, to identify English articles published up until December 2024 on food biodiversity in relation to diet quality, health outcomes, and environmental impact. Eight studies reported on the association between food biodiversity and diet quality, and 4 on the association between food biodiversity and health outcomes. No studies reported on the association between food biodiversity and environmental impact. The studies quantified food biodiversity using Nutritional Functional Diversity, Dietary Species Richness (DSR), Simpson Diversity Index, Shannon Diversity Index, Berger-Parker Index, or a combination of these. One study compared the latter 4 metrics by calculating Hill numbers. Despite using different metrics, all studies showed significant positive associations between food biodiversity and nutritional adequacy, a reduced risk of total and cause-specific mortality, or a reduced risk of gastrointestinal cancers. One study reported a nonsignificant association between DSR and body fat percentage. In conclusion, limited available studies consistently find a positive association between food biodiversity, diet quality, and decreased health risks, highlighting the potential of food biodiversity to improve the healthiness of diets. Currently, DSR is proposed to be the most feasible metric to quantify food biodiversity. Future studies should focus on the added value of food biodiversity over dietary diversity in relation to human and planetary health, which is currently unclear.

Although plant-rich dietary patterns like the Mediterranean and Mediterranean-DASH Intervention for Neurodegenerative Delay diets have been linked to cognitive benefits, the role of predominantly plant-based diets is less understood. This systematic review aimed to evaluate the association between plant-based diets and cognitive outcomes. A literature search was conducted in Medline and Embase using keywords related to plant-based diets (e.g., "vegetarian diet") and cognitive outcomes (e.g., "dementia"). Studies of any design were eligible. Reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale. Meta-analyses were conducted on prospective studies that examined the same dietary exposure and cognitive outcome, using fixed-effects regression models. Twenty-two studies were included, with considerable variability in methodologies and outcomes. Plant-based diets were defined either categorically (e.g., vegetarian compared with nonvegetarian), or using indices of adherence, such as the healthful plant-based diet index (hPDI), with higher scores reflecting higher adherence. Two meta-analyses, each based on 2 high-quality prospective cohort studies, examined associations between plant-based diet indices and cognitive outcomes. For cognitive impairment, pooled odds ratios (95% confidence interval) for highest compared with lowest quartiles were 0.61 (0.55, 0.68; I = 97.1%) for plant-based diet index (PDI) and 0.68 (0.62, 0.75; I = 84.3%) for hPDI. For dementia, pooled hazard ratios were 1.03 (0.91, 1.17; I = 0%) for PDI, 0.85 (0.75, 0.97; I = 0%) for hPDI, and 1.17 (1.03, 1.33; I = 60.3%) for unhealthful PDI. These findings suggest that dietary patterns emphasizing healthful plant-based foods and limiting less healthful plant foods and animal products are associated with lower odds of cognitive impairment and risk of dementia. However, findings across individual studies were inconsistent, highlighting the need for further high-quality research. This review was registered at PROSPERO as CRD42022380055.

Globally, nonsugar sweeteners (NSSs) are commonly used in foods and beverages to enhance sweetness without added calories. NSSs have been the subject of numerous in vitro and animal studies to assess their potential carcinogenic risk to humans. As a complement to a larger systematic evaluation of the epidemiology evidence of NSSs and cancer, here we present a comprehensive review of the available experimental evidence from animal and mechanistic studies for the NSSs acesulfame-K (Ace-K), advantame, aspartame, cyclamate, neotame, saccharin, steviol glycosides, and sucralose within the context of ingredient safety. For this evaluation, we focused on genotoxicity, other potential cancer modes of action (MoAs), and carcinogenicity. Overall, high-quality studies have not shown evidence for carcinogenicity in animal models, except for saccharin, which causes bladder tumors in rats via a mechanism not relevant to humans. There is also no consistent or compelling evidence for any biologically plausible MoA by which any of these NSSs could cause cancer in humans. The results of this evaluation are consistent with the results of epidemiology studies, which have shown no consistent associations between NSS intake and cancer risk. Taken together, the body of available evidence supports previous conclusions by authoritative and regulatory bodies that Ace-K, advantame, aspartame, cyclamate, neotame, saccharin, steviol glycosides, and sucralose do not pose a genotoxic or carcinogenic risk to humans.

This third article in the series presenting reference values (RVs) for nutrients in human milk describes the values for B vitamins. The mothers, infants, and lactation quality (MILQ) and early-MILQ studies, conducted at sites in Bangladesh, Brazil, Denmark, and The Gambia, were designed to measure human milk nutrient concentrations of well-nourished mothers during the first 8.5 mo of lactation. Applying ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) to analyze multiple B vitamins simultaneously produced RVs for vitamin B2, B3, pantothenic acid, B6, and biotin. Choline was analyzed separately by UPLC-MS/MS, vitamin B1 by high-performance liquid chromatography-fluorescence detection, and vitamin B12 by competitive chemiluminescence enzyme immunoassay. Measured milk B-vitamin concentrations from the MILQ study were compared with those used by the Institute of Medicine (IOM) for setting recommendations for nutrient requirements of infants. MILQ estimates were substantially lower (<60% of the concentrations used by the IOM) for vitamins B1, B2, and B6; 60%-100% of concentrations used by the IOM for vitamin B3, vitamin B12, and choline; and consistent or slightly (100%-125%) higher than concentrations used by the IOM for pantothenic acid and biotin. Total daily median B-vitamin intakes from 1 to 6 mo were 29%-45% of IOM adequate intakes (AIs) for vitamins B1 and B2, 60%-75% of AIs for vitamins B3, B6, B12, and choline, and 118%-128% of AIs for pantothenic acid and biotin. The MILQ B-vitamin concentrations are provided as percentile curves to enable comparison and interpretation of data from other studies.

Despite being established public health practice for >80 y, community water fluoridation continues to attract assertions of harm, and continued scrutiny of the evidence is required to inform policy. A rapid systematic literature review was conducted to examine human nondental health outcomes from fluoride exposure through drinking water. A protocol was developed a priori and registered on the Open Science Framework. Literature searches were conducted in Medline, CINAHL, Web of Science, Embase, PubMed, Campbell Collaboration, Cochrane Library, and Scopus databases. Gray literature and citation searches were also undertaken. Quality assessment was performed using the Mixed Methods Appraisal Tool (MMAT). Meta-analysis was judged not feasible due to the heterogeneous nature of the included studies. A total of 1143 unique records were identified, of which 130 full-text studies were reviewed and 58 were selected for final inclusion. Among these, 37 were cross-sectional studies, 15 were cohort studies, 4 were case-control studies, and 2 were ecological studies. Most studies were judged to be of acceptable quality using MMAT. The most common risk of bias was insufficient control of confounders. Health outcomes studied included blood pressure, neurological outcomes, bone cancers, thyroid function, skeletal outcomes, low birth weight/preterm birth, and metabolic outcomes. In children, some evidence of adverse effects on neurological outcomes and thyroid function was observed. In adults, some evidence was identified of adverse effects on blood pressure, thyroid function, and skeletal structure. In general, these effects occurred at drinking water fluoride concentrations >1.5 mg/L. No evidence of adverse effects was found at concentrations <1.0 mg/L in both children and adults. The nature of study designs and methodological limitations precluded causal inference. No convincing evidence of harm was identified from community water fluoridation at concentrations between 0.7 and 1.0 mg/L, whereas uncertainty remains at higher concentrations. Significant methodological limitations highlight the need for more rigorous future studies. A protocol was developed a priori and registered on the Open Science Framework (Registration DOI: https://doi.org/10.17605/OSF.IO/JH245).

This second article in the series establishing reference values (RVs) for nutrients in human milk describes RVs for protein, carbohydrate, fat, and energy. To establish RVs, the mothers, infants, and lactation quality (MILQ) and early-MILQ studies collected human milk samples throughout the first 8.5 mo of lactation in 1242 well-nourished women in Bangladesh, Brazil, Denmark, and The Gambia. Macronutrients were measured by near-infrared spectroscopy. Protein concentrations decreased from 12.4 g/L at 4-17 d to a 7.7-7.9 g/L plateau by 4-5 mo. Carbohydrate concentrations were stable throughout lactation, ranging from 68.2 to 70.1 g/L. Fat concentrations decreased from 37.0 g/L at 4-17 d to 31.2-32.8 g/L after 2-3 mo. Energy density mirrored fat trends, decreasing from 665 kcal/L at 4-17 d to 597-602 kcal/L by 3-4 mo. Compared with estimates used by the Institute of Medicine (IOM)--renamed the National Academy of Medicine (NAM) in 2015--to set nutrient intake recommendations for infants, MILQ values were ∼90% of concentrations used for carbohydrate and energy, and 70%-80% for protein and fat. Total daily median intakes (concentrations × milk volumes) from 1 to 6 mo were on par with IOM adequate intakes (AIs) for carbohydrate and energy, 65% of the AI for protein, and 84% of the AI for fat. These RVs offer a critical resource for understanding the nutritional contributions of human milk and informing public health practices to support infant growth and development.

The World Health Organization recommends exclusive breastfeeding for the first 6 mo of life and continued breastfeeding for 2 y or beyond. However, limited reliable, representative data on nutrient concentrations in milk from well-nourished mothers are available. Furthermore, there is a lack of data integrating human milk nutrient concentrations with the volume of milk transferred to infants during progressive stages of lactation. Accurate quantification of nutrient concentrations and milk volume is essential for setting macro- and micronutrient intake recommendations for infants and women's additional requirements for lactation. This first article in a series of 7 in this Supplement describes the Mothers, Infants, and Lactation Quality (MILQ) study conducted at sites in Bangladesh, Brazil, Denmark, and The Gambia. The MILQ study measured human milk nutrient concentrations and quantified milk volume throughout the first 8.5 mo of lactation. Validated analytical methodologies were used for nutrient quantification. The stable isotope dilution dose-to-mother method was used for milk volume measurement. A total of 1242 mother-infant dyads participated in the MILQ study. Milk volumes, milk nutrient concentrations, percentile curves, and total nutrient intakes (concentration times milk volume at each time point) are presented in the series of articles in this supplement. Comparisons are made between values in the MILQ study and those used by the Institute of Medicine (now renamed the National Academy of Medicine) to set nutrient intake recommendations for infants and lactating women, and with other selected studies. Data from the MILQ study provide a valuable resource for updating existing nutrient intake recommendations, evaluating and improving infant nutrition strategies, and assessing interventions to optimize maternal and infant nutritional status and health.

Human milk from healthy, well-nourished women is the optimal nutrition for infants and young children, and exclusive breastfeeding is recommended for the first 6 mo. In the context of poor diets, the quality of milk may be compromised, and understanding the relationships between maternal diet, human milk nutrient concentrations, and milk intakes in young infants is important for guiding policy. The Mothers, Infants, and Lactation Quality (MILQ) study collected human milk samples from 1 to 8.5 mo of lactation in 558 well-nourished but unsupplemented women in Bangladesh, Brazil, Denmark, and The Gambia. Milk intakes were measured at 3 visits postnatally (1-3.49 mo, 3.5-5.99 mo, and 6.0-8.5 mo). Milk intakes were assessed in 3 sites (Bangladesh, Brazil, and The Gambia) using the stable isotope dilution dose-to-mother method. In Denmark, intakes were measured by test weighing, and volume data were corrected by a factor of 1.05 to account for insensible water losses. The mean ± standard deviation human milk intake across sites and time points was 781 ± 193 g/d. Milk intakes were comparable among sites early in lactation, but as intakes decreased across lactation, between-site differences emerged as nonmilk feeds were introduced. Exclusively breastfed infants consumed greater volumes of milk each day than mixed-fed infants. When expressed against infant body weight, a gradual decrease in milk intake was observed across lactation. Milk nutrient concentrations were largely unrelated to daily milk intakes. Therefore, correlations between milk nutrient concentrations and total daily intake of nutrients were mostly positive and strong. Mean milk intake in the MILQ study was consistent with previously published global data, although variability was observed across lactation and between contexts. Infants consuming greater milk volumes had greater daily intakes of milk nutrients. The implications for infant status and recommended nutrient intakes require further investigation.

Iron deficiency anaemia (IDA) is the most common form of anaemia and the leading cause of years lived with disabilities (YLD) and disability-adjusted life years (DALYs) among adolescents. Recently, various iron-rich snacks have been developed as interventions to improve iron status among adolescents. This review aimed to evaluate the efficacy of natural, non-commercially fortified iron-rich snacks in improving iron status among adolescent girls aged 10-19 years. A systematic review of randomized controlled trials and quasi-experiments was conducted, focusing on iron status indicators including hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TSAT), and soluble transferrin receptors (sTfR). Searches were performed in PubMed, ScienceDirect, EBSCO, Research4Life, and Google Scholar. Risk of bias was assessed using Cochrane tools, and study quality was evaluated with GRADE. Ten studies (five RCTs and five quasi-experiments) involving 24 to 211 participants were included. Nine studies had moderate risk of bias, mainly due to performance, detection, and reporting issues; one had high selection bias. Iron content of snacks varied, with nine studies out of ten reported Hb increases ranging from 0.45 to 2.28 g/dL. Only one study reported improvements in serum iron (from 25.482 ± 0.036 g/dL to 41.511 ± 0.033 g/dL) and ferritin (from 10.827 ± 0.192 ng/mL to 14.016 ± 0.103 ng/mL). These results indicate the potential of locally developed snacks to improve iron and Hb levels in adolescents. This review synthesizes evidence on food-based interventions, focusing on natural, non-fortified iron-rich snacks for adolescent girls. The findings demonstrate promising potential for these snacks to improve iron status and haemoglobin concentrations, underscoring their value as culturally acceptable, cost-effective, and sustainable complement to existing nutrition strategies. Although results are promising, more rigorously designed trials with comprehensive iron biomarkers are needed to confirm efficacy and support integration into adolescent nutrition programs.