Journal of the American Nutrition Association最新文献

Background: Riboflavin, which is mainly obtained from dietary sources, plays a role mainly in energy metabolism and antioxidants, and has been used for the prevention and treatment of several diseases. However, the epidemiological and molecular mechanisms linking riboflavin to chronic kidney disease (CKD) are unclear.

Methods: Epidemiological studies were conducted using data from the National Health and Nutrition Examination Survey. Logistic regression models and restricted cubic spline were used to assess the association between riboflavin and CKD. Mediation analyses were applied to explore the effects of inflammatory factors. In addition, molecular mechanism studies were conducted using multiple publicly available databases. STRING, Cytoscape and microarray data were used to screen the genes. Clinical relevance and distribution of targets in the kidney were explored using the Nephroseq v5 online platform and single-cell RNA sequencing. The binding activity of riboflavin to target proteins was investigated by molecular docking.

Results: The weighted prevalence of CKD was 14.8%. High riboflavin intake is associated with a reduced risk of CKD (especially early CKD). Mediation analysis showed that alkaline phosphatase mediated riboflavin to reduce CKD prevalence with a mediation ratio of 10.5%. 74 potential targets of riboflavin against CKD were obtained through data mining. The possible mechanisms of riboflavin against CKD are related to apoptosis, PI3K/Akt signaling, MAPK signaling and IL17 signaling pathway, among which 9 hub genes (MYC, TP53, BCL2, AKT1, TNF, JUN, IL1B, IL6 and CASP3) are mainly related to MAPK signaling. In CKD patients, IL1B expression levels were increased, mainly in renal macrophages, and correlated with decreased renal function, while signals such as VISFATIN and SPP1 were highly expressed. Molecular docking verified that riboflavin has good binding potential to IL1B protein.

Conclusions: This study highlights the clinical potential of riboflavin in preventing CKD, and explores its epidemiological and preventive mechanisms.

Objectives: Low-calorie diet (LCD) interventions can lead to remission of type 2 diabetes (T2D), but the underlying mechanisms are not well understood. As a diet-sensitive regulator of gene expression, DNA methylation may reveal pathways underlying remission. However, whether individuals with different responses to LCD-induced T2D remission and weight loss exhibit distinct DNA methylation patterns remains unclear.

Methods: A 3-month intensive weight loss intervention (815-835 kcal/d) and a following 3-month weight loss maintenance phase were conducted among participants with T2D. DNA methylation was measured using the Infinium Methylation EPIC BeadChip (935K) at 4 timepoints. Differentially methylated cytosine-phosphate-guanine (CpG) sites and regions were analyzed to identify changes between those who achieved T2D remission and weight loss >12 kg and those who did not. Predictive models based on DNA methylation profiles at baseline and week 1 were developed to forecast individual responses to LCD.

Results: Seventeen individuals (mean age 36.8 [8.5] years, 29.4% women) were included, and 11 of them achieved T2D remission. Of the 784,965 CpG sites, the microarray identified 8 and 13 CpG sites differentially methylated for T2D remission and weight loss status, respectively, mapping to 9 gene regions, including PKFP, PON1, and SERINC5. Pathway analysis mapped these genes to glucose and lipid metabolism pathways. Methylation-inferred scores showed a greater improvement in predicting T2D remission and weight loss status following the LCD intervention than the base models (area under curve ranges: 0.86-0.88 vs. 0.73-0.80).

Conclusions: Variation in DNA methylation profiles across individuals with differing responses to the LCD, highlighting the epigenetic roles in the effects of the LCD on weight loss and T2D remission. Baseline DNA methylation status may serve as a predictor of T2D remission in response to LCD intervention.

Clinical trial registry number and website: This trial was registered at the https://clinicaltrials.gov/study/NCT05472272?cond=NCT05472272&rank=1 as NCT05472272.

Objective: This study aimed to determine the glycemic index of conventional and biofortified cowpeas, their effects on healthy individuals' appetite, and their anti-inflammatory and antioxidant effects in RAW 264.7 cells.

Methods: Iron biofortified (BRS Aracê, BRS Tumucumaque, and BRS Xiquexique) and conventional (BRS Pajeú) cowpeas were cooked and their chemical composition was analyzed. Eutrophic adults (n = 11) consumed each cowpea and control glucose and post-prandial glucose and appetite responses were obtained over 120 min. In vitro, the study used RAW 264.7 cells stimulated with lipopolysaccharide-LPS (1 µML) and treated with digested cowpea beans (1 mg/mL). Total antioxidant capacity (TAC), nitric oxide, superoxide dismutase (SOD), TNF-α, and IL-10 were analyzed in the cell and culture medium, and NF-κB by immunohistochemistry. The data were analyzed by ANOVA and post-hoc of Tukey (p < 0.05).

Results: All cowpeas had a lower incremental area under the glycemic curve (iAUC) than glucose. In appetite responses, Pajeú had the lowest "hunger sensation" and higher "satiety sensation" (p < 0.05). In vitro analysis showed that Pajeú and Tumucumaque improved TAC and biofortified cowpeas reduced the activation and translocation of NF-κB to nuclei. However, the cowpeas had no effects on SOD activity, nitric oxide, TNF-α, and IL-10 released and production into cells (p > 0.05).

Conclusions: Cowpea, biofortified or not, presents benefits in reducing the glycemic index, but has a moderate impact on induced inflammation, being a sustainable option for human intake and health.

Clinical trial registration: Brazilian Clinical Trials Registry (ReBEC), number RBR-7ntftdv.

Objective: The aim of this research was to clarify the relationship between the Dietary Index for Gut Microbiota (DI-GM) and the severity of chronic kidney disease (CKD), renal function, and the prevalence of sarcopenia in patients with CKD, as well as the role of the Systemic Immune-Inflammation Index (SII) therein.

Method: Using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018, the study included 2169 participants with CKD. DI-GM was calculated on a scale of 0 to 13, with higher scores indicating a healthier gut microbiome. CKD severity was categorized by estimated glomerular filtration rate (eGFR), and sarcopenia was defined using appendicular lean mass adjusted for body mass index. Statistical analyses included weighted regression models, restricted cubic spline, subgroup analysis, and mediation analysis.

Results: Higher DI-GM scores were associated with lower CKD severity (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78-0.94; p = .001), improved renal function (eGFR, β = 1.078, p = .020; serum creatinine, β = -1.548, p = .026; blood urea nitrogen, β = -0.091, p = .026), and reduced sarcopenia prevalence (OR, 0.70; 95% CI, 0.57-0.87; p = .002). SII score partially mediated the association between DI-GM score and sarcopenia in CKD, accounting for 12.11% of the effect (p < .001). No significant associations were found between DI-GM score and all-cause or cardiovascular mortality among the population with CKD.

Conclusions: Findings suggest that dietary interventions targeting gut microbiota may have benefits in managing CKD severity, improving renal function, and reducing sarcopenia risk.

Background: Medicinal plants form the foundation of healthcare systems and modern medicine, offering powerful therapeutic potential to combat a wide range of chronic metabolic disorders.

Objective: The present study evaluates the safety of Withania somnifera leaf extracts using rodent modeling for 56 days. It also explores the molecular docking interactions of Withania somnifera (WS) leaf phytoconstituents with the dipeptidyl peptidase-4 (DPP-4) receptor.

Methodology: A total of 20 rats were divided into 5 groups (G0: Normal diet, G1: 0.25% WS leaves Extract, G3: 0.5% WS leaves Extract, G4: 0.5% WS leaves powder, and G5: 1% WS leaves powder) for 56 days. The organ-to-body weight ratio, LFTs, RFTs, and hematological profile were determined in the 4th and 8th weeks. On the other hand, the structures of compounds identified from the methanolic extract of W. somnifera leaves were modified into PDBQT format to perform molecular docking.

Results: The results showed that all parameters varied within normal ranges. The hematological parameters were higher in G2 after the 28th day compared to the values after the 56th day. The maximum values of serum glucose and lipid parameters were found in the G3 group as compared to other groups, while hepato-renal markers were high in G0. Molecular docking revealed the binding affinity of w-02, w-03, w-04, w-05, and w-07 with DPP-4 receptors; moreover, w-04 had the highest binding affinity of -6.4 kcal/mol.

Conclusion: The 0.5% leaves extract of W. somnifera revealed positive effect on hematological and biochemical profile of rats without causing any adverse effects.

Background: Perimenopausal women often experience dysmenorrhea, menstrual cramps, hormonal imbalances and vasomotor symptoms (VMS), significantly affecting their quality of life. In Ayurveda, Asparagus racemosus (Shatavari) root extract has been used for female reproductive health. This study evaluated the safety and efficacy of CL22205, a standardized A. racemosus root extract, in managing perimenopausal symptoms.

Methods: This randomized, double-blind, placebo-controlled trial was conducted on 50 perimenopausal women (age: 40-50 years) experiencing mild to moderate climacteric symptoms. Participants received either CL22205 (200 mg/day) or placebo over a period of 120 consecutive days. Primary outcome measure was Menopausal Rating Scale (MRS) scores. Secondary measures assessed Hot Flash Weekly Weighted Score (HFWWS), Menstrual Symptom Questionnaire (MSQ), ovarian follicular number using ultrasonography, serum Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), Anti-Müllerian Hormone (AMH), and 17β-Estradiol (E2), skin and hair quality, and patient satisfaction using Integrative Medicine Patient Satisfaction & Outcome Scales (IMPSS & IMOS). Serum biochemistry, hematology, and urine analysis were performed for safety evaluation.

Results: CL22205 significantly reduced (p < 0.001) total MRS scores and HFWWS vs. placebo and baseline after 120 days of treatment, menstrual symptoms (congestive and spasmodic dysmenorrhea) were improved (p < 0.001). CL22205 decreased serum FSH (56.3%), LH (34.3%), and increased AMH (188.1%, p < 0.001) levels. Skin and hair quality improved significantly (p < 0.001), with no adverse events.

Conclusion: CL22205 effectively reduces VMS, menstrual discomfort, and hormonal imbalances while improving skin and hair health, offering a safe and natural alternative for perimenopausal symptoms management.

Objective: This study aimed to investigate the effects of acute caffeine (CAF) intake on heart rate, time to exhaustion, and cardiac autonomic modulation during a constant-load exercise test in patients with chronic obstructive pulmonary disease (COPD).

Methods: A counterbalanced, randomized, double-blind, placebo-controlled, and crossover design was adopted in the present study. Eleven patients diagnosed with COPD initially performed a maximal incremental exercise test on a cycle ergometer, and from 72 to 96 h later, a constant-load exercise test (60% of the peak power achieved in the maximal incremental exercise test) after ingestion of CAF (5 mg.kg^-1) or placebo (cellulose, PLA) 60 min before the test. Heart rate (HR) and heart rate variability (HRV) were continuously monitored beat-to-beat throughout the test and recovery using a portable HR monitor.

Results: During exercise, the response of HR showed a significant effect of time (p < 0.001), but there was no main effect of condition (p = 0.76) or a time x condition interaction (p = 0.74). CAF ingestion increased time to exhaustion during the constant-load exercise test compared to PLA (p = 0.04). The CAF ingestion also reduced the magnitude of HR recovery 60 s post-exercise in comparison with PLA (p = 0.02). No other significant differences were found for HR recovery in further time points or HRV indices (p > 0.05).

Conclusion: In conclusion, acute CAF ingestion increased time to exhaustion in a constant-load exercise test in patients with COPD. There was no main effect of CAF on HR during exercise. Although CAF reduced HR recovery at the beginning of recovery, CAF did not seem to induce more prolonged changes on cardiac autonomic modulation post-exercise. These findings suggest CAF could be safety used as an effective ergogenic aid to optimize the endurance performance of patients with COPD.

Efforts to improve dietary patterns often focus on the nutritional composition and associated health effects of individual foods in isolation. This reductionist type of approach has been traditionally applied across nutrition science, leading to a weakened understanding of the complex interplay of how food affects human health. Emerging evidence suggests that many foods may exert indirect effects on overall diet quality by acting as a vehicle that increases co-consumption of other foods. Thus, the term "carrier food" is intended to describe such foods that, regardless of its direct effect (i.e. nutritional contribution), indirectly impacts diet quality by serving as a vehicle for increasing co-consumption of other foods or food groups, during a snacking or eating occasion. In this context, the "companion food" is consumed due to its relationship with consumption of the carrier food. Carrier foods can be classified into four types - positive, offset, gateway, and reverse - each exerting a unique impact on overall diet quality. This editorial defines and contextualizes the term carrier food, explores examples and methods from existing nutrition research, and outlines implications for public health messaging, food formulation, and dietary assessment. By shifting focus from individual nutrients to patterns of co-consumption, the concept of a carrier food offers a more nuanced and actionable approach to dietary assessment and intervention. As food and nutrition science continues to evolve, integrating this term into research, policy, and practice may help better align nutritional recommendations with real-world eating behavior.

Objective: Inpatients undergoing stroke rehabilitation experience high malnutrition rates, requiring strict dietary management. However, manual and time-pressured dietary provision can cause errors in diet composition, highlighting the need for innovation. Therefore, we aimed to evaluate whether GPT-4o can accurately identify dietary errors in hospital-based stroke rehabilitation menus, analyze differences in AI vs. expert rationale for decisions, and explore AI's potential role in clinical workflows through a structured collaboration framework.

Methods: A TRIPOD-compliant validation study analyzing 264 hospital-based menus designed for stroke rehabilitation inpatients requiring specialized diets (e.g., dysphagia, diabetes). GPT-4o's dietary compliance classifications were assessed using a structured 0-error, 1-error, and 2+ error framework, with expert dietitians as ground-truth in a rehabilitation hospital nutrition department, where expert dietitians selected menus from existing clinical practices for inpatients on specialized diets. AI-expert agreement, overall accuracy, sensitivity, and specificity in dietary error classification were assessed. AI vs. expert justifications were analyzed thematically to identify differences in decision rationale. Cohen's Kappa (95% CI) measured inter-rater reliability. Overall accuracy, sensitivity, and specificity were calculated using a 3 × 3 confusion matrix, comparing AI classifications (0-error, 1-error, 2+ error) to the expert-labeled ground truth. Thematic analysis categorized AI vs. expert justifications for flagged dietary errors.

Results: Out of 264 menus (1,000+ food items), 26 (9.8%) had discrepancies. Among these, 57.7% (15 cases) were PAS-based dysphagia diets, followed by diabetic (19.2%, 5 cases) and allergen-related (15.4%, 4 cases) diets. The remaining two cases involved low-sodium and low-fat diets. Cohen's Kappa: 0.892 (95% CI: 0.845-0.939, p < 0.001). 0-errors: Sensitivity 94.3%, specificity 100%; 1-error: Sensitivity 86.2%, specificity 96.6%; 2+-errors: Sensitivity 97.8%, specificity 92.6%. Thematic analysis revealed GPT-4o followed strict rule-based interpretations, whereas dietitians incorporated patient tolerance and food preparation considerations.

Conclusion: GPT-4o demonstrated high accuracy but over-flagged violations, supporting its role as a prescreening tool with expert collaboration.