Translation of preclinical findings on the efficacy of dietary interventions for metabolic disease to human clinical studies is challenging due to the predominant use of male rodents in animal research. Our objective was to evaluate a combined high-fat (HF) diet and low-dose streptozotocin (STZ) model for induction of type-2 diabetes (T2D) in male and female C57BL/6J mice. We hypothesized that T2D biomarkers would differ significantly between sexes. Mice were administered either a low-fat (LF) diet (10% kcal from fat), or HF diet (60% kcal from fat) + STZ injections (30 mg/kg/d for 3 days). Both sexes gained weight and developed impaired postprandial oral glucose tolerance on the HF+STZ treatment compared to LF. Only male mice on HF + STZ developed fasting hyperglycemia, fasting hyperinsulinemia and insulin resistance, suggesting that the underlying causes of postprandial hyperglycemia differed between sexes. Principal component analysis of measures such as body weights, glucose and insulin concentrations indicated metabolic derangement for males only on HF+STZ treatment, while LF group males and both groups of females significantly overlapped. Based on our data, we accept our hypothesis that the combined high-fat diet and low-dose STZ model for T2D phenotypes differs significantly in its effect on mice based on sex. The HF diet + low-dose STZ model is not useful for studying insulin resistance in females. Other models are needed to model T2D, and study the effects of dietary interventions in this disease, in females. Sexual dimorphism remains a significant challenge for both preclinical and clinical research.

The primary objective of this study was to examine the association between iron overload (IO), metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatic fibrosis. We hypothesized that there is a significant association. Data from the NHANES (2017-2020) were analyzed to explore IO's impact on MASLD and hepatic fibrosis in U.S. adults. We assessed serum ferritin, controlled attenuation parameter (CAP), liver stiffness measurement (LSM), and various covariates. Gene expression data were sourced from the FerrDb V2 and GEO databases. Differential gene expression analysis, Protein-Protein Interaction (PPI) Network construction, and Gene Ontology (GO) and KEGG pathway enrichment analyses were performed. The study verified the link between MASLD, hepatic fibrosis, and iron overload hub genes. This study of 5927 participants, averaging 46.78 years of age, revealed significant correlations between serum ferritin and CAP, LSM, after adjusting for covariates. Threshold effect analysis indicated nonlinear associations between serum ferritin and CAP, LSM, with distinct patterns observed by age and gender. Moreover, the area under the ROC curve for serum ferritin with MASLD and hepatic fibrosis was 0.8272 and 0.8376, respectively, demonstrating its performance in assessing these conditions. Additionally, molecular analyses identified potential hub genes associated with iron overload and MASLD, and hepatic fibrosis, revealing the underlying mechanisms. Our study findings reveal an association between iron overload, MASLD, and hepatic fibrosis. Additionally, the hub genes may be implicated in iron overload and subsequently contribute to the progression of MASLD and hepatic fibrosis. These findings support precision nutrition strategies.

Randomized controlled trials (RCT) demonstrate that whole wheat consumption improves glycemia. However, substantial inter-individual variation is often observed, highlighting that dietary whole grain recommendations may not support the health of all persons. The objective of this report is to describe the rationale and design of a planned RCT aimed at establishing the gut microbiota and metabolome signatures that predict whole wheat-mediated improvements in glucose tolerance in adults with prediabetes. It is hypothesized that a controlled diet containing wheat bread (WHEAT; 160 g/day) compared with refined bread (WHITE) will improve glucose tolerance in a gut microbiota-mediated manner. Biospecimens will be collected before and after each 2-week study arm. Testing for oral glucose tolerance and gastrointestinal permeability will be performed post-intervention. Assessments will include oral glucose tolerance (primary outcome) and secondary outcomes including gut microbiota, targeted and untargeted metabolomics of fecal and plasma samples, intestinal and host inflammatory responses, and intestinal permeability. WHEAT is predicted to alleviate glucose intolerance by shifting microbiota composition to increase short-chain fatty acid-producing bacteria while reducing populations implicated in intestinal inflammation, barrier dysfunction, and systemic endotoxemia. Further, benefits from WHEAT are anticipated to correlate with gut-level and systemic metabolomic responses that can help to explain the expected inter-individual variability in glucose tolerance. Thus, knowledge gained from integrating multi-omic responses associating with glucose tolerance could help to establish a precision nutrition-based framework that can alleviate cardiometabolic risk. This framework could inform novel dietary whole grain recommendations by enhancing our understanding of inter-individual responsiveness to whole grain consumption.

Alpha-linolenic acid (C18:3n-3 [ALA]) intake may have a beneficial effect in reducing cancer risk; however, its association with colorectal cancer (CRC) risk remains conflicted. Additionally, ALA was emphasized as being associated with mucins, an important glycoproteins family within the intestine. Thus, we hypothesized that a higher dietary ALA intake may reduce the risk of CRC and this preventive effect has an interaction with mucin 4 (MUC4) rs2246901. We conducted a case-control study at the National Cancer Center in Korea, involving 1039 cases and 1982 controls, aiming to determine the interaction of the MUC4 rs2246901 polymorphism and ALA intake in CRC risk. Dietary ALA intake was collected via semiquantitative food frequency questionnaire (SQFFQ), categorizing by 4 quartiles. We evaluated the odds ratios (ORs) and 95% confidence intervals (CIs) through unconditional logistic regression models. Higher dietary ALA intake was found to be inversely associated with CRC risk (adjusted OR = 0.58; 95% CI, 0.45-0.75, P for trend < .001). No significant association between MUC4 rs2246901 polymorphism and CRC risk was found. In a recessive model, MUC4 rs2246901 seemed to modify this association; participants with at least 1 major allele and higher ALA intake had a significantly lower CRC risk than those who had a lower intake (adjusted OR = 0.56; 95% CI, 0.43-0.72; P interaction = .047). A higher dietary ALA was proposed as a potential protective nutrient against CRC. Moreover, this association might be influenced by presence of the MUC4 rs2246901 polymorphism.

To make healthy food choices, consumers need to be aware of the sugar content of foods. Units act as an environmental cue that might influence sugar content estimation accuracy. The present study (1) tested whether estimations of sugar content are more accurate in sugar cubes vs grams, (2) compared accuracy of sugar content to estimations of the foods' weight and energy content, and (3) investigated gender, education, and body mass index as potential correlates. A sample of 886 adults was randomly assigned to estimating the sugar content of 10 common foods in grams or cubes. Estimations of sugar content diverged considerably from actual values in both groups (0.22 ≤ Cohen's ds ≤ 1.20; 0.20 ≤ Cohen's ds ≤ 1.10), but were more pronounced for sugar content estimations in grams in 7 out of 10 foods (ts ≥ 4.04, Ps < .001, Cohen's ds ≥ 0.14). Sugar content misestimation was somewhat more pronounced than misestimation of weight (0.05 ≤ Cohen's ds ≤ 1.43) and energy content (0.04 ≤ Cohen's ds ≤ 1.19). Relationships between sugar content misestimation and gender (0.00 ≤ Cohen's ds ≤ 0.33), education (-0.07 ≤ r ≤ 0.11), and body mass index (-0.08 ≤ r ≤ 0.06) were mostly negligible. Although sugar content estimations were somewhat more accurate in sugar cubes vs grams, estimation accuracy is generally low. In addition to promoting consumers' knowledge through labeling and education, additional avenues for interventions might need to be explored for sizeable effects on food choices.

Evidence is limited regarding the association of plasma niacin with the risk of hyperlipidemia in participants with diabetes. We aimed to determine the relationship between plasma niacinamide/nicotinic acid and hyperlipidemia in participants with/without diabetes. Plasma niacinamide/nicotinic acid concentrations were measured using high-performance liquid chromatography-tandem mass spectroscopy. Multivariable logistic regression analyses were performed to evaluate the association between plasma niacin and hyperlipidemia in participants with diabetes and nondiabetes in a cross-sectional study. Compared to the first quartile, plasma nicotinamide, nicotinic acid, and niacin (nicotinamide plus nicotinic acid) were associated with a 54%, 50%, and 52% lower risk of hyperlipidemia in diabetic participants, respectively, but no significant association was observed in nondiabetic participants. These inverse associations persisted across subgroups stratified by sex, age, body mass index, smoking status, alcohol consumption, and physical activity. In addition, the fully adjusted odds ratios (95% confidence intervals) for hypercholesterolemia and hypertriglyceridemia among diabetic participants were 0.54 (0.38, 0.77) and 0.61 (0.44, 0.85), respectively, when comparing to the first quartile of plasma niacin concentrations (all P < .001). This study of 2647 participants observed that plasma niacin was inversely associated with hyperlipidemia in those with diabetes.

Prediabetes and type 2 diabetes mellitus are growing global health concerns, predisposing individuals to various vascular complications. Lifestyle modifications, including dietary interventions, offer promising avenues for prevention and management. Using a multivariable-adjusted model, we analyzed the cross-sectional associations between plasma proportions (% of total fatty acids) of omega-3 polyunsaturated fatty acids (n3 PUFA, including total n3 PUFA, docosahexaenoic acid [DHA], non-DHA n3 PUFA), and glycated hemoglobin A1c (HbA1c) as well as the prevalence of prediabetes in a sample from the UK Biobank cohort. Our hypothesis was that proportions of n3 PUFA, especially DHA, would by inversely associated with the prediabetes prevalence. The sample (n = 92,762; 54.5% females) had an average age of 56 years and was overweight (mean body mass index = 27). The mean plasma DHA proportion in the sample was 2.03% (standard deviation [SD] = 0.67%), non-DHA n3 PUFA was 2.41% (SD = 1.02%) and total n3 PUFA was 4.43% (SD = 1.56%). Prediabetic individuals were identified by blood HbA1c proportions between 5.7% and 6.4% (39-46 mmol/mol) according to American Diabetes Association criteria. Each of the three n3 PUFA biomarkers was inversely associated with HbA1c proportions. In particular, DHA showed the strongest inverse association, with an OR of 0.62 (95% confidence intervals: 0.58, 0.67; P < .001) when comparing quintiles 5 to 1 in a fully adjusted model. These findings suggest a potential protective role of n3 PUFA, particularly DHA, in mitigating the risk of having prediabetes. Further prospective investigations are needed to clarify whether long-chain n3 PUFA could function as modifiable factors for prediabetes.

Chemotherapy-related cognitive impairment (CRCI) and affective symptoms negatively impact quality of life in breast cancer survivors. The aim of this study was to determine the efficacy of high eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA) and low sucrose diets to alleviate these symptoms in a mouse model of chemotherapy. Potential mechanisms involving insulin resistance were explored. We hypothesized that diets enriched in EPA+DHA and low amounts of sucrose would protect against the impact of chemotherapy on measures of CRCI. Female C57Bl/6 mice were randomized to 1 of 4 diets (2% kcal eicosapentaenoic acid + docosahexaenoic acid [EPA+DHA]/high or low sucrose, low omega-3/high or low sucrose) for 6 weeks and treated with two injections of doxorubicin-based chemotherapy or vehicle during week 2 and 4. Behavioral tests were performed 7 days after second injection. Chemotherapy increased serum insulin and decreased body weight, locomotion and exploratory behavior (all p < .05). Low sucrose consumption resulted in better long-term memory regardless of chemotherapy or vehicle injection (p < .05). 2% EPA+DHA consumption lessened insulin resistance (p < .05); however, controlling for body weight attenuated this effect (p = .08). There were no significant differences by diet or injection on liver lipid content; however, liver lipid content was positively correlated with insulin resistance scores (p < .05). Low sucrose diets may protect long-term memory during chemotherapy. The effect of EPA+DHA on insulin resistance and affective side effects during chemotherapy requires further investigation.

Modulation of the gut microbiota through specific dietary interventions shows potential for maintenance and optimization of health. A dietary fiber diet and fermented foods diet appear to alter the gut microbiota, but evidence is limited. Therefore, we designed the Gut Health Enhancement by Eating Favorable Food study, a 21-week randomized controlled trial studying effects of dietary fibers and fermented foods on gut microbiota diversity and composition, while also stimulating dietary behavior changes through a citizen science (CS) approach. We hypothesized that a high-fermented food diet would increase microbial diversity, whereas a high-dietary fiber diet would stimulate the growth of specific fiber-degrading bacteria. The following elements of CS were adopted: education on the gut microbiota, tailored dietary intervention, remote data collection by participants, sharing of personal gut microbiota outcomes with participants, and vlogs by participants for dissemination of results. Here we describe the study protocol and report the flow of participants, baseline characteristics, and compliance rates. Completed in March 2024, the trial included 147 healthy adults randomized to a high-dietary fiber intervention, high-fermented food intervention, or control group. Each group received an additional study product after 2 weeks: dried chicory root, a fermented beverage, or maltodextrin (placebo). A 3-month follow-up assessed the participants' ability to sustain dietary changes. The recruitment of participants was successful, reflected by 1448 applications. The compliance with the dietary guidelines and study products was >90%. This study shows that including elements of CS in an randomized controlled trial is feasible and may help recruitment and compliance.

Maternal nutrition during the perinatal stage is critical to offspring brain development. Egg yolks are a balanced and nutrient-dense food that is rich in bioactive components crucial to optimal neurodevelopment early in life. Egg consumption is often recommended to pregnant women to enhance both maternal and fetal health. We hypothesized that maternal intake of egg yolk from late gestation and throughout lactation would enhance functional organization and cognitive developmental outcomes in offspring using a pig model. Sows were fed a control diet (n = 6) or a diet containing egg yolks (n = 5, 350 mg egg yolk powder/kg BW/day, equivalent to ∼3 eggs/day for humans) from late gestation through lactation. At weaning, piglet offspring (n = 2/sow, total n = 22) underwent structural magnetic resonance imaging (MRI) and resting-state-functional MRI. Piglets underwent novel object recognition testing to assess hippocampal-dependent learning and memory. Functional MRI results demonstrated that egg yolk significantly increased functional activation in the executive network (p = 0.0343) and cerebellar network (p = 0.0253) in piglets when compared to control. Diffusion tensor imaging analysis showed that perinatal intake of egg yolks significantly increased white matter fiber length in the hippocampus (p = 0.0363) and cerebellum (p = 0.0287) in piglet offspring compared to control piglets. Furthermore, piglets from egg yolk-fed sows spent significantly more proportional frequency exploring the novel object than the familiar object in novel object recognition testing (p = 0.0370). The findings from this study support egg yolk-altered activation of specific brain networks may be associated with functional cognitive outcomes in weaning piglets.

Plant-based diets are recognized for their health benefits. However, evidence on the association between plant-based diet quality and aging in the US population is limited. This study aimed to investigate the association between different plant-based diet indices, phenotypic age acceleration (PhenoAgeAccel), and biological age acceleration (BioAgeAccel). We hypothesized that healthful plant-based diets would negatively affect PhenoAgeAccel and BioAgeAccel in US adults. The cross-sectional analysis included 22,363 participants, and information was obtained from the National Health and Nutrition Examination Survey database. The quality of plant-based diet was assessed using 3 indices: overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). Phenotypic age (PA) and biological age (BA) was calculated based on a linear combination of chronological age and 12 multi-system clinical chemistry biomarkers in accordance with the previously established method. PhenoAgeAccel and BioAgeAccel are the residuals of the PA and BA. Weighted linear regression analyses were performed to evaluate the relationships between PDI, hPDI and uPDI, and PhenoAgeAccel and BioAgeAccel. After adjusting for all covariates, we observed that a 10-unit higher PDI score was associated with 0.80 years lower PhenoAgeAccel (β: -0.80, 95% confidence interval [CI]: -0.94, -0.67), and 1.91 years lower BioAgeAccel (β: -1.91, 95% CI: -2.42,-1.40). A 10-unit higher hPDI score was associated with 0.83 years lower PhenoAgeAccel (β: -0.83, 95% CI: -0.96, -0.70), and 1.76 years lower BioAgeAccel (β: -1.76, 95% CI: -2.18, -1.34). Conversely, a 10-unit higher uPDI score was associated with 0.77 years higher PhenoAgeAccel (β: 0.77, 95% CI: 0.66, 0.89) and 1.21 years higher BioAgeAccel (β: 1.21, 95% CI: 0.80, 1.62). These findings suggest that US adults may be able to slow the aging process by increasing adherence to a healthy plant-based diet.

The role of the gut microbiota in the association between high-fat diet and cognition is not clear. We hypothesized that a high-fat diet may influence cognition by altering the intestinal microbiota. Fecal microbiota isolated from male C57BL/6J mice feeding on various high-fat diets and a control basic diet were transplanted to antibiotic-treated recipient mice. The measurement of weight and plasma lipids, novel object recognition test, 16S rRNA gene sequencing of feces, and hematoxylin-eosin staining of the hippocampal cornu ammonis 1 and cornu ammonis 3 areas were performed for all mice. Compared with those in the control and n-3 polyunsaturated fatty acid (n-3 PUFA) groups, donor obese mice fed with diets high in long-chain saturated fatty acids, n-6 polyunsaturated fatty acids (n-6 PUFAs), and trans fatty acids exhibited significant cognitive impairment (all P < .05). There were fewer neurons in the hippocampal area in the n-6 PUFA group than in the n-3 PUFA group (P < .05). Similar effect on cognition and neurons in hippocampal area in corresponding recipient mice were revealed after fecal microbiota transplantation. In addition, the composition of intestinal microbiota differed among recipient mice after fecal microbiota transplantation from donor mice. According to these results, it was concluded that diets rich in long-chain saturated fatty acids, n-6 PUFAs, and trans fatty acids may lead to cognitive impairment by damaging the structure of the hippocampus through influencing the intestinal microbiota in mice, whereas a diet high in n-3 PUFAs may exhibit a beneficial effect.

Recent studies suggest a link between periodontitis and the Dietary Inflammatory Index (DII). We hypothesize that a more proinflammatory diet is associated with periodontitis risk in pregnant women with gestational diabetes mellitus (GDM). This study aimed to explore the association between DII scores and periodontitis risk in GDM women. In this cross-sectional study, 302 eligible GDM women from a Maternal and Child Health Hospital were enrolled between February and July 2023. DII scores were calculated based on dietary intake data collected using a validated semiquantitative food frequency questionnaire. Periodontal health was assessed through periodontal parameters including bleeding on probing, probing depth, and clinical attachment loss. Logistic regression models were employed to evaluate the odds ratios (ORs) for periodontitis risk across DII tertiles. Our study found that the prevalence of periodontitis across the DII tertiles 1, 2, and 3 was 34.7%, 56.4%, and 54.0%, respectively. Comparing the highest DII tertile (tertile 3) with the lowest (tertile 1), a significant association was found between higher DII scores and periodontitis risk (univariate OR: 2.21; 95% CI: 1.25, 3.90; P = .006), which remained significant in the fully adjusted model (adjusted OR: 2.30; 95% CI: 1.21, 4.37; P = .011). In conclusion, elevated DII scores are associated with an increased risk of periodontitis, underscoring the crucial role of a proinflammatory diet in periodontitis progression. Future well-designed experimental studies are needed to verify if tailored dietary strategies can effectively reduce periodontitis risk among pregnant women with GDM.

Consumption of oats is associated with lowered risks of type 2 diabetes and obesity. However, many oat-based products (e.g., breakfast cereals) use finely milled flours but are associated with health claims based on oats of larger particle sizes. The objective of this study was to test the hypothesis that increasing oat flour particle size will result in lower postprandial glycemia and appetite. Using a randomized-controlled, crossover design, 20 participants (10 males, 10 females; age: 25.3 ± 1.0 years; body mass index: 23.2 ± 0.6 kg/m) consumed a serving of porridge made using 40 g of coarse (675.7 ± 19.6 µm), whole (443.3 ± 36.2 µm), fine (96.0 ± 2.1 µm), or a commercial (375.9 ± 14.8 µm) oat flour unmatched in available carbohydrate, protein, and dietary fiber content. After a 12-hour overnight fast, blood glucose, insulin, and appetite were measured at 15 to 30-minute intervals over 120 minutes posttreatment consumption. Coarse and whole flours led to lower blood glucose between 30 and 60 minutes (P < .02). Blood glucose area under the curve (AUC) was lower after coarse than fine and commercial oat flours (P < 0.03), and after whole than fine oat flour (P < .002). Both coarse and whole oat flours resulted in lower insulin AUC than finer flours (P < .05). Appetite AUC was lower after the commercial than coarse flour (P < .007). Controlling milling to produce coarser oat flour to add to common foods may have health benefits. This study was registered at ClinicalTrials.gov (NCT05291351).

This pilot dose-escalation study evaluated the absorption and metabolism of a novel fasting mimetic formulation containing spermidine, nicotinamide, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) taken as oral supplements in young adults. Five healthy men consumed a standardized breakfast, followed by control (wheat flour) or low, medium, or high doses of supplements containing spermidine, nicotinamide, PEA, and OEA 2 hours later. Blood was drawn at 0, 1, 2, and 4 hours after the supplement (2, 3, 4, and 6 hours postprandial). Plasma concentrations of spermidine, 1-methylnicotinamide, PEA and OEA were quantified by liquid chromatography-mass spectrometry. The secretion of tumor necrosis factor alpha and production of reactive oxygen species by stimulated macrophages incubated with plasma, and cholesterol efflux capacity of plasma were analyzed. Plasma 1-methylnicotinamide, PEA, and OEA concentrations increased after supplement intake (P < .05). Spermidine concentrations decreased in the control arm (P < .05) but not the supplement arms. Net incremental area under the curve for tumor necrosis factor alpha and reactive oxygen species in stimulated macrophages decreased when incubated with plasma following supplement intake (P < .05). Intake of the combined supplements showed they were bioavailable and increased in plasma in a dose-dependent manner and provide preliminary data showing enhanced plasma anti-inflammatory and antioxidant functions. This trial was registered at clinicaltrials.gov (NCT05017428).

Oxidative and nitrosative stress play pivotal roles in normal physiological processes and the pathogenesis of metabolic disorders. Previous studies from our lab demonstrated insulin resistance (IR), and dyslipidemia in iNOS mice, emphasizing the importance of maintaining optimal redox balance. These mice exhibited altered gut microbiota with decreased Lactobacillus. Therefore, we hypothesized that Lactobacillus supplementation could mitigate metabolic disturbances in iNOS mice. To test this hypothesis, iNOS mice and wild-type (WT) mice were divided into four groups: iNOS with or without Lactobacillus supplementation, WT with or without Lactobacillus supplementation and glucose tolerance, insulin resistance, gluconeogenesis, lipids, gene expression related to glucose and lipid metabolism (qPCR), fecal gut microbiota (16S rRNA sequencing), and serum and caecum metabolomics (LC-MS) were monitored. IR and dyslipidemic iNOS mice exhibited reduced microbial diversity, diminished presence of Lactobacillus, and altered serum metabolites, indicating metabolic dysregulation. Lactobacillus supplementation in iNOS mice effectively reversed glucose intolerance, IR, dyslipidemia, and associated metabolic irregularities compared to WT. These improvements correlated with changes in gene expression related to fatty acid synthesis in liver and adipose tissue, lipid oxidation in liver, and lipid efflux in intestinal tissue as compared to untreated iNOS mice. Despite the positive effects on metabolic markers, Lactobacillus supplementation did not reduce body weight or rectify disrupted energy balance, as evidenced by reduced VCO production, heat generation, and metabolic rates in iNOS mice. The results suggest that Lactobacillus supplementation ameliorates metabolic disturbances but did not fully restore disrupted energy balance, highlighting complex interactions between the gut microbiome and metabolism.

Antioxidant intake is inversely associated with different health outcomes; however, its association with insulin resistance (IR) has not been well documented. We hypothesized that the Dietary Antioxidant Index (DAI) is inversely associated with IR in Mexican children and adolescents. A cross-sectional analysis was performed using data from the Health Workers Cohort Study. A total of 830 children and adolescents aged 7 to 18 years were enrolled. The DAI was evaluated in three categories defined by tertiles using a semiquantitative food frequency questionnaire. IR was defined using previously reported cutoff points in the homeostasis model assessment. This association was evaluated using a multiple logistic regression model. Stratified analysis was performed using body mass index and sex. The prevalence of IR based on the DAI categories (low, medium, high) was 23.8%, 24.2%, and 15.3%, respectively. The IR odds ratio (OR) for participants in the highest DAI category was 0.49 (95% confidence interval [CI]: 0.30-0.80). Notably, female Children and Adolescents in the highest DAI category had significantly lower odds of developing IR than those in the lowest DAI category (OR 0.54, 95% CI 0.29-0.98). Participants with overweight/obesity showed a similar association (OR 0.37, 95% CI 0.18-0.76). These results suggest that the DAI is inversely associated with IR, particularly in females, highlighting the potential role of antioxidants in preventing IR. This underscores the need to establish recommendations for antioxidant consumption in female children and adolescents.

Heavy metals are pervasive in the environment, and exposure to these metals may contribute to obesity in children and adolescents. We hypothesized that metal exposures are associated with obesity in children and adolescents. Data were drawn from children and adolescents aged 6 to 19 years from the 2007 to 2018 National Health and Nutrition Examination Survey. We employed weighted multivariate logistic regression and restricted cubic spline to explore the effects of individual metal exposures on obesity, and weighted quantile sum regression, quantile g-computed regression, and Bayesian kernel machine regression to explore the effects of mixed metal exposures on obesity. Subgroup analyses by gender were also performed. All models were adjusted for age, gender, race, poverty to income ratio, and serum cotinine. Among the 3,650 children and adolescents studied, 21.04% had obesity. Logistic regression revealed positive associations between barium (OR = 1.23, 95% CI: 1.07-1.40) and thallium (OR = 1.55, 95% CI: 1.23-2.15) with obesity, while cadmium (OR = 0.74, 95% CI: 0.61-0.89), cobalt (OR = 0.51, 95% CI: 0.41-0.62), and lead (OR = 0.70, 95% CI: 0.57-0.86) were negatively associated with obesity. Restricted cubic spline indicated a nonlinear relationship between lead and thallium and obesity. Quantile g-computed regression demonstrated that mixed metal exposure was negatively associated with obesity (OR = 0.50, 95% CI: 0.42-0.59). Subgroup analyses revealed a gender-specific effect for mercury (P for interaction = 0.03), which was negatively associated with obesity in females (OR = 0.83, 95% CI: 0.69-0.99). In conclusion, metal exposures are associated with obesity in children and adolescents, with gender differences.

Accumulating evidence has demonstrated that medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA) positively affect cognitive function. However, it remains unclear whether the improvement is related to the alterations of gut microbiota and inflammation and the impact of the combined intervention. In this study, we hypothesized that the supplementation of MCTs combined with DHA could modulate gut microbiota, inflammation, and improve cognitive function in APPswe/PS1De9 model mice and senescence-accelerated mouse-prone-8, which are two different mouse models used in neurodegeneration research. The mice were divided into four groups: Control group, MCTs group, DHA group, and MCTs + DHA group. The study assessed cognitive function, inflammatory cytokines, and gut microbiota composition. The results showed that supplementation of MCTs + DHA improved spatial learning ability, memory capacity, exploratory behavior; decreased the relative abundance of Proteobacteria; reduced the ratio of Firmicutes/Bacteroidetes; decreased the concentrations of serum interleukin (IL)-2, IL-6, monocyte chemotactic protein-1, tumor necrosis factor-alpha, while increasing the concentration of IL-10. Furthermore, supplementation with MCTs + DHA exhibited significantly superior effects compared to MCTs or DHA alone in reducing inflammation, optimizing gut microbiota composition, and improving cognitive function. In conclusion, supplementation with MCTs + DHA improved cognition function, accompanied with favorable alterations in gut microbiota and inflammation in APPswe/PS1De9 and senescence-accelerated mouse-prone-8 mice.

Diet during pregnancy is crucial to maternal metabolism and fetal development, so exploring the most potent food risk factor could improve maternal and child health. In this study, we investigated the diet and lifestyle of 833 healthy pregnant women in the second trimester from November 2020 to August 2021. Based on the Tianjin Antenatal Care System in China, we followed up with these women and recorded their gestational weight gain (GWG) and newborn birth weight. We conducted a dietary survey through FFQ based on the food groups recommended by the Chinese Dietary Guidelines and included common ultra-processed foods. We collected 219 semi-quantitative FFQs and 614 self-reported FFQs for analysis. According to the consumption frequency of 12 food groups, 4 dietary patterns were extracted by principal component analysis. We analyzed the associations of food energy, consumption frequency, and dietary patterns with GWG and birth weight, especially GWG in the first and second trimesters (f-GWG). The results showed that f-GWG was positively correlated with food energy. Beverage consumption was associated with f-GWG (r = 0.288, P = .026) in obese pregnant women. A dietary pattern that favors high consumption of ultra-processed foods (fried foods, baked desserts, and sweet beverages) was associated with increased GWGs. Non-obesity women with high consumption of baked desserts and sweet beverages had higher GWGs (P < .05). After adjusting for confounding factors (including total energy, physical activity, and sleep quality), only sweet beverage consumption was associated with f-GWG (β 0.498, 95%CI 0.153-0.843) and birth weight (β 0.124, 95%CI 0.009-0.240). Sweet beverage consumption is a key adjustable risk factor for prenatal care.

This study represents the first investigation into the safety of a novel, high-purity spermidine trihydrochloride supplement (hpSPD) in humans. Spermidine, a natural compound found in various foods, has demonstrated potential health benefits in animal and epidemiological studies. However, evidence from clinical trials and safety evaluations of spermidine supplements is limited because pure spermidine for human administration has not been available. In this randomized, double-blind, within-subject and placebo-controlled trial, 37 healthy men (age 50-70 years; body mass index, 18.5-28 kg/m) were administered either hpSPD or a placebo. We hypothesized that 7-day and 28-day dosing of 40 mg/day of hpSPD would have minimal effects on safety, although metabolic and polyamine homeostasis has not previously been examined at this dosage level. Consistent with our hypothesis, 40 mg/day hpSPD did not result in any significant changes in clinical, lipids, chemistry, or hematological parameters compared to placebo. Compliance was high, and no study product-related adverse events were reported. Substantial changes in serum and urine polyamine concentrations were not observed following hpSPD supplementation, suggesting effective homeostatic control of full-dose highly purified spermidine supplements with no evidence of adaptation of spermidine metabolism at 40 mg/day. These findings suggest that hpSPD at 40 mg/day for up to 28 days is safe and well-tolerated in healthy older men. The study is consistent with preclinical results and provides important evidence supporting the safety of high-purity spermidine supplementation, enabling further research with single-molecule spermidine to investigate its potential biology for improving human health. This trial was registered at clinicaltrials.gov (NCT05459961).