Nutrients

27 pages, 2213 KB

Open AccessReview

Edible Bird’s Nest as a Multi-Component Functional Food for Brain Aging: From Single-Bioactive Actions to Network-Regulatory Mechanisms

by Wenjuan Gong, Xintong Wang, Wen Zhang, Huihui Wang, Wei Xiong, Yixuan Li, Pengcheng Wen and Yanan Sun

Nutrients 2026, 18(4), 671; https://doi.org/10.3390/nu18040671 - 18 Feb 2026

Abstract

Functional food research has long emphasized isolated bioactive compounds, yet such single-target strategies often show limited efficacy against complex, multifactorial processes such as brain aging. In this review, we examine edible bird’s nest (EBN) as a representative multi-component functional food and discuss how [...] Read more.

Functional food research has long emphasized isolated bioactive compounds, yet such single-target strategies often show limited efficacy against complex, multifactorial processes such as brain aging. In this review, we examine edible bird’s nest (EBN) as a representative multi-component functional food and discuss how its complex food matrix may exert coordinated neuroprotective effects. We summarize the major bioactive constituents of EBN, including sialic acid, functional glycoproteins, and bioactive peptides, and organize their actions into functional modules related to oxidative stress, neuroinflammation, apoptosis, synaptic maintenance, and neurotrophic support. Emerging evidence on the prebiotic potential of EBN and its modulation of the gut–brain axis is also integrated, highlighting interactions between peripheral metabolic regulation and central nervous system function. By comparing EBN with conventional functional ingredients such as vitamins C and E, coenzyme Q10, curcumin, and omega-3 fatty acids, we propose that EBN represents a distinctive “network-regulatory” food system in which nutritional support and pathway modulation are intrinsically linked. Overall, this review provides a conceptual framework for understanding how complex food matrices can be rationally applied to support brain health and reduce age-related neurodegenerative risk. Full article

(This article belongs to the Special Issue Food Functional Factors and Nutritional Health)

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15 pages, 894 KB

Open AccessArticle

Xanthophyll-Rich Extracts from Garcinia dulcis Pulp as Potential Anti-Hepatocellular Carcinoma Functional Food

by Ulfa Kholili, Aji Bayu Wicaksono, Amal Arifi Hidayat, Ugroseno Yudho Bintoro, Soetjipto Soetjipto, Aryati Aryati, Muhammad Zulfikar Fiko Defianto and Muhammad Miftahussurur

Nutrients 2026, 18(4), 670; https://doi.org/10.3390/nu18040670 - 18 Feb 2026

Abstract

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a leading cause of cancer-related mortality worldwide. Despite recent advances in immunotherapy and targeted agents, treatment efficacy is frequently limited by tumor heterogeneity, drug resistance, and systemic toxicity. Natural products, [...] Read more.

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a leading cause of cancer-related mortality worldwide. Despite recent advances in immunotherapy and targeted agents, treatment efficacy is frequently limited by tumor heterogeneity, drug resistance, and systemic toxicity. Natural products, particularly carotenoid-derived compounds, have emerged as promising multi-target anticancer agents. Xanthophylls, a class of oxygenated carotenoids, exhibit pleiotropic biological activities that are relevant to cancer therapy; however, their potential against HCC remains incompletely explored. This study aimed to systematically evaluate the anti-HCC potential of xanthophyll-rich extracts from Garcinia dulcis pulp using integrated metabolomic, in silico, and in vitro approaches. Methods: Xanthophyll-rich extracts from G. dulcis pulp were prepared using microwave-assisted extraction. Phytochemical profiling was performed using UHPLC–ESI–MS/MS. In silico analyses included bioactivity prediction, ADMET profiling, target identification, network pharmacology, pathway enrichment, and molecular docking against key HCC-related proteins (EGFR, BCL-2, and mTOR). In vitro antiproliferative activity was assessed using MTT assays on HepG2 and Huh7 hepatocellular carcinoma cell lines, with THLE-2 normal hepatocytes used as controls. Results: Metabolomic analysis revealed a xanthophyll-dominated profile, with zeaxanthin and lutein as the major constituents, alongside fucoxanthin, astaxanthin, β-cryptoxanthin, β-carotene, and canthaxanthin. In silico predictions demonstrated high antineoplastic and pro-apoptotic activities, with strong involvement in the HIF-1, EGFR, PD-1/PD-L1, JAK–STAT, and mTOR signaling pathways. Molecular docking confirmed stable and high-affinity interactions of xanthophylls with EGFR, BCL-2, and mTOR. In vitro assays showed selective cytotoxicity against HCC cells, with IC₅₀ values of 42.8 ± 3.6 µg/mL (HepG2) and 58.4 ± 4.9 µg/mL (Huh7), while exhibiting significantly lower toxicity toward normal hepatocytes. Conclusions: Xanthophyll-rich extracts from Garcinia dulcis pulp exhibit potent and selective anti-hepatocellular carcinoma activity through multi-target mechanisms involving oncogenic signaling, apoptosis regulation, and tumor metabolism. These findings support the translational potential of G. dulcis xanthophylls as promising natural candidates for further development in HCC therapy. Full article

(This article belongs to the Special Issue Nutritional Attributes and Health Implications of Novel, Non-Conventional, and Reformulated Foods)

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18 pages, 383 KB

Open AccessArticle

Substitution of White Meat for Red Meat and Diabetes Risk: A Prospective Cohort Study Stratified by Red Meat Intake

by Langrun Wang, Jie Guo, Yiran Guan, Chao Zhang, Ran Wang, Keji Li, Ruixin Zhu and Jingjing He

Nutrients 2026, 18(4), 669; https://doi.org/10.3390/nu18040669 - 18 Feb 2026

Abstract

Background/Objectives: Current evidence on the diabetes prevention benefit of substituting red meat with white meat remains inconsistent and is predominantly based on Western populations. This research examined whether the benefits of such dietary substitution depend on habitual red meat intake levels. Methods [...] Read more.

Background/Objectives: Current evidence on the diabetes prevention benefit of substituting red meat with white meat remains inconsistent and is predominantly based on Western populations. This research examined whether the benefits of such dietary substitution depend on habitual red meat intake levels. Methods: This prospective analysis included 12,143 adults from the China Health and Nutrition Survey (2004–2015). Dietary intake was assessed by multiple 24 h recalls supplemented by a household food inventory. Incident diabetes was identified via self-report and supplementary biochemical data. Estimates of hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained through Cox proportional hazards modeling. Dose–response relationships were examined using restricted cubic splines. Substitution effects were evaluated within strata defined by baseline red meat intake (<75 vs. ≥75 g/day). Results: During 83,046 person-years of follow-up, 687 incident diabetes cases occurred. U-shaped associations were identified for both red meat (lowest risk at 75 g/day) and white meat (lowest risk at 60 g/day) consumption in relation to diabetes risk (p-nonlinearity < 0.0001). Substitution was not associated with diabetes risk in the low-intake stratum (<75 g/day, p = 0.107). Conversely, in the high-intake stratum (≥75 g/day), replacing 50 g/day of red meat with white meat was associated with a 34% lower diabetes risk (HR: 0.66; 95% CI: 0.51, 0.86; p = 0.002). Conclusions: Meat intake shows a nonlinear association with diabetes risk in Chinese adults. The potential benefit of substituting white meat for red meat is conditional, with a more pronounced effect observed among individuals with high habitual red meat consumption, which may support the development of targeted dietary guidance for this subgroup. Full article

(This article belongs to the Special Issue Dietary Patterns and Population Health)

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19 pages, 5165 KB

Open AccessArticle

In Vitro Effects of Twelve Food Additives on Gut Microbiome and Its Fibre Fermentation Capacity in Adults with Crohn’s Disease in Remission and Healthy Controls

by Hanoof Alessa, Molly Elizabeth Quinn, Linah Alhomidan, Cameron Ross, Stefanos Kainadas, Emily Brownson, Jonathan MacDonald, John Paul Seenan, Ben Nichols, Athanasios Koutsos and Konstantinos Gerasimidis

Nutrients 2026, 18(4), 668; https://doi.org/10.3390/nu18040668 - 18 Feb 2026

Abstract

Background/Objectives: Animal studies have shown that food additives may adversely affect the gut microbiome. However, the effect of food additives on the microbiome in adults with Crohn’s disease (CD) remains less explored. This study investigated the impact of food additives on gut microbiome [...] Read more.

Background/Objectives: Animal studies have shown that food additives may adversely affect the gut microbiome. However, the effect of food additives on the microbiome in adults with Crohn’s disease (CD) remains less explored. This study investigated the impact of food additives on gut microbiome and fibre fermentation capacity in adults with CD and healthy controls (HCs) using in vitro faecal fermentations. Methods: Faeces from 6 HCs and 6 patients with CD in clinical remission (Harvey Bradshaw Index < 5) were used for in vitro fermentation of a fibre mix with one of 12 food additives (calcium propionate, carboxymethylcellulose, carrageenan kappa, cinnamaldehyde, maltodextrin, polysorbate-80, potassium sorbate, sodium benzoate, sodium sulphite, titanium dioxide, turmeric, and xanthan gum). Short-chain fatty acids (SCFAs) were measured using gas chromatography, the microbiome was profiled with 16S rRNA amplicon sequencing and total bacterial load was measured with qPCR. Results: Maltodextrin increased acetate production in both groups. In HCs, turmeric increased acetate and butyrate production, sodium sulphite reduced acetate production, and maltodextrin reduced butyrate production. Microbiome Shannon α-diversity increased with titanium dioxide (both groups), and with carrageenan kappa only in patients with CD. In both groups, the addition of maltodextrin and polysorbate-80 induced significant shifts in microbiome structure (β-diversity). Significant shifts were seen with maltodextrin (HC: R² = 6.8%, p = 0.001; CD: R² = 5.1%, p = 0.004) and sodium sulphite (HC: R² = 6.9%, p = 0.001). Maltodextrin significantly decreased the estimated absolute abundance of Escherichia–Shigella in patients CD; sodium benzoate, potassium sorbate, and calcium propionate did so in HCs. Faecalibacterium decreased in the presence of polysorbate-80 in the HC and CD groups, as well as in the presence of maltodextrin in the CD group. Total bacterial load decreased with polysorbate-80, potassium sorbate, maltodextrin and calcium propionate in both groups. Xanthan gum decreased total bacterial load in HCs. Conclusion: Certain food additives significantly affected fibre fermentation capacity and microbiome structure, with only modest differences observed according to participants’ health status. Full article

(This article belongs to the Special Issue Diet in the Pathogenesis and Management of Inflammatory Bowel Disease)

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34 pages, 832 KB

Open AccessArticle

Machine Learning to Tailor Intermittent Fasting for Blood Pressure Improvement

by Shula Shazman

Nutrients 2026, 18(4), 667; https://doi.org/10.3390/nu18040667 - 18 Feb 2026

Abstract

Background/Objectives: Intermittent fasting (IF) has shown feature effectiveness in reducing blood pressure, highlighting the need for personalized intervention strategies. Methods: To address this, a machine learning framework was developed to predict the likelihood of blood pressure improvement (≥5 mmHg systolic reduction) across different [...] Read more.

Background/Objectives: Intermittent fasting (IF) has shown feature effectiveness in reducing blood pressure, highlighting the need for personalized intervention strategies. Methods: To address this, a machine learning framework was developed to predict the likelihood of blood pressure improvement (≥5 mmHg systolic reduction) across different IF and calorie restriction protocols in premenopausal women without diagnosed hypertension. Results: The model achieved 77% accuracy and an AUC of 0.8 in distinguishing responders from non-responders. Logistic regression analysis identified dietary intervention type as the strongest predictor of success, with Intermittent Energy and Carbohydrate Restriction + free Protein and Fat (IECR + FF) and Intermittent Energy and Carbohydrate Restriction + free Protein and Fat (IECR) protocols showing the highest effectiveness (coefficients 0.55 and 0.41 respectively). Decision tree analysis revealed age in years as a critical stratification factor, with younger patients (≤47 years) responding optimally to IECR + FF combinations, while older patients benefited from IECR, Continuous Energy Restriction (CER), or Intermittent Energy Restriction (IER) approaches. Notably, waist-to-hip ratio emerged as the strongest negative predictor, indicating that central adiposity significantly impedes blood pressure improvement regardless of intervention type. Higher baseline HDL positively predicted success, while elevated LDL and the DER diet were associated with poor outcomes. The complementary analytical approaches demonstrated that logistic regression and decision tree methods highlight different aspects of the data, with the former identifying independent linear associations and the latter suggesting potential non-linear interactions and candidate thresholds involving age years, dietary intervention type, baseline blood pressure, and metabolic markers. Conclusions: This exploratory, hypothesis-generating analysis was conducted in a cohort of premenopausal women without diagnosed hypertension and is not intended to inform clinical decision-making. The observed patterns should be interpreted as preliminary and may reflect sample-specific effects or model instability. Confirmation in larger, independent, and more diverse populations is essential before any clinical relevance can be inferred. Full article

(This article belongs to the Section Nutritional Epidemiology)

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16 pages, 2333 KB

Open AccessReview

Evaluating the Efficacy of Probiotics on Inflammatory Cytokines in Alcoholic Liver Disease: A Focus on IL-6 and IL-10

by Jiadila Bahetiyaer, Jie Cui, Wenhui Li, Jian Zhang, Ye Sun, Chunqing Ai, Shuying Liu, Shuaiming Jiang, Chengcheng Zhang and Jinchi Jiang

Nutrients 2026, 18(4), 666; https://doi.org/10.3390/nu18040666 - 18 Feb 2026

Abstract

Background: While probiotics may offer therapeutic benefits for alcoholic liver disease (ALD), their impact on inflammatory markers in ALD patients is still uncertain. Objective: This study aims to investigate the effects of probiotic supplementation on inflammatory biomarkers in patients with alcoholic liver disease, [...] Read more.

Background: While probiotics may offer therapeutic benefits for alcoholic liver disease (ALD), their impact on inflammatory markers in ALD patients is still uncertain. Objective: This study aims to investigate the effects of probiotic supplementation on inflammatory biomarkers in patients with alcoholic liver disease, particularly examining its role in modulating interleukin-6 (IL-6) levels. Methods: A comprehensive search was performed across PubMed, Embase, and Web of Science to identify randomized controlled trials investigating probiotic interventions in patients with alcoholic liver disease. Seven independent comparisons were chosen for meta-analysis to evaluate probiotics’ effects on inflammatory markers, with subgroup analyses examining the impact of region, formulation type, and gender. Results: The findings demonstrated that probiotics led to a significant reduction in IL-6 levels (SMD = −0.68, 95% CI [−1.15; −0.20], p = 0.005). No statistically significant effect of probiotics on interleukin-1β (IL-1β) (SMD = −0.35, 95% CI [−0.87, 0.17], p = 0.18) or tumor necrosis factor alpha (TNF-α) levels (SMD = −0.73, 95% CI [−1.68, 0.21], p = 0.13) was observed. Notably, probiotics were associated with a significant increase in interleukin-10 (IL-10) levels (SMD = 0.93,95% CI [−0.02; 1.87], p = 0.05). Subgroup analyses further revealed that the efficacy of probiotics in reducing IL-6 levels was more pronounced in studies characterized by higher proportions of Asian participants, solid dosage forms, and male subjects. Conclusions: Probiotics have notably reduced IL-6 levels by altering the gut microbiota and increased IL-10 levels, with limited impact on IL-1β and TNF-α. These results suggest probiotics could be used to treat ALD and emphasize the need for personalized probiotic approaches for different populations. Full article

(This article belongs to the Section Prebiotics, Probiotics and Postbiotics)

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16 pages, 3349 KB

Open AccessArticle

A Combination of Amaranth Protein Hydrolysate and Korean Mint Extract Ameliorates Cisplatin-Induced Nephrotoxicity and Cachexia in CT26 Tumor-Bearing BALB/c Mice

by Junhee Lee, Yeeun Kim, Mi-Bo Kim, Ju Hyun Park, Daedong Kim, Dong-Woo Lee and Jae-Kwan Hwang

Nutrients 2026, 18(4), 665; https://doi.org/10.3390/nu18040665 - 18 Feb 2026

Abstract

Background/Objectives: Cancer cachexia involves progressive skeletal muscle and adipose tissue loss, which is further aggravated by cisplatin chemotherapy via increased systemic inflammation, tissue catabolism, and renal toxicity. The present study aimed to evaluate whether a combination of amaranth protein hydrolysate and Agastache rugosa [...] Read more.

Background/Objectives: Cancer cachexia involves progressive skeletal muscle and adipose tissue loss, which is further aggravated by cisplatin chemotherapy via increased systemic inflammation, tissue catabolism, and renal toxicity. The present study aimed to evaluate whether a combination of amaranth protein hydrolysate and Agastache rugosa extract (AKE) could attenuate cisplatin-associated cachexia and nephrotoxicity in CT26 tumor-bearing mice. Methods: Cancer cachexia was induced by subcutaneous CT26 cell inoculation in 6-week-old male BALB/c mice, followed by a 7-day tumor establishment period. Cisplatin was then administered intraperitoneally, and AKE (125 or 250 mg/kg/day) was given daily by oral gavage for 14 days. Results: AKE administration significantly alleviated cisplatin-induced body weight loss and systemic inflammation, accompanied by preservation of skeletal muscle and adipose tissue mass, as well as increased myofiber cross-sectional area and adipocyte size. AKE markedly reduced serum inflammatory cytokines, blood urea nitrogen, and creatinine levels, indicating protection against cisplatin-induced renal injury. Mechanistically, AKE suppressed renal apoptosis through inhibition of mitogen-activated protein kinase signaling. In skeletal muscle, AKE attenuated muscle atrophy by modulating protein turnover pathways, including downregulation of muscle-specific ubiquitin ligases and restoration of Akt/mTOR and FoxO3a signaling. Furthermore, AKE mitigated adipose tissue wasting by suppressing AMP-activated protein kinase-dependent browning and restoring adipogenic signaling involved in lipid storage and differentiation. Conclusions: These findings demonstrate that AKE confers comprehensive protection against cisplatin-induced cachexia and nephrotoxicity by coordinately preserving muscle and adipose tissue and attenuating renal injury, suggesting its potential as a functional nutritional strategy to alleviate chemotherapy-associated tissue wasting. Full article

(This article belongs to the Special Issue Botanicals and Nutritional Approaches in Metabolic Disorders)

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13 pages, 262 KB

Open AccessReview

Unusual Micronutrient Deficiencies as Causes of Anemia

by Ananya Datta Mitra and Ralph Green

Nutrients 2026, 18(4), 664; https://doi.org/10.3390/nu18040664 - 18 Feb 2026

Abstract

Anemia due to micronutrient deficiencies has received little attention in public health and modern-day clinical practice. Increasing numbers of persons, mainly in low- and middle-income nations, are faced with malnutrition and malabsorption syndromes, giving rise to various micronutrient deficiencies that can lead to [...] Read more.

Anemia due to micronutrient deficiencies has received little attention in public health and modern-day clinical practice. Increasing numbers of persons, mainly in low- and middle-income nations, are faced with malnutrition and malabsorption syndromes, giving rise to various micronutrient deficiencies that can lead to anemias refractory to treatment with iron, folate or vitamin B12. Though relatively uncommon, such underlying nutrient deficiencies may be difficult to recognize as they can coexist with more common causes and there may be few or no specific clinical characteristics pinpointing a particular micronutrient. The main examples of these micronutrients contributing to a small but important burden of anemia are other B-group vitamins, pyridoxine and thiamine, ascorbic acid, the fat-soluble vitamins, A and E and other trace elements such as copper, zinc and selenium. The following review highlights the current state of knowledge and the relevance of these micronutrient deficiencies in the broader context of nutritional anemia. Full article

(This article belongs to the Section Micronutrients and Human Health)

19 pages, 1497 KB

Open AccessArticle

Circadian Timing, Rather than Hydration Status, Determines Metabolic Adaptation to Ramadan-like Fasting in Diet-Induced Obese Rats

by Noof M. Alshahrani, Maha H. Alhussain, Mohammed F. Alahmed, Ahmad T. Almnaizel and Ahmed S. BaHammam

Nutrients 2026, 18(4), 663; https://doi.org/10.3390/nu18040663 - 18 Feb 2026

Abstract

Background: Ramadan fasting involves daily abstinence from food and water between dawn and sunset, but human studies cannot readily disentangle the effects of fasting timing, circadian alignment, and hydration status on metabolic regulation. Objective: To determine whether fasting timing or hydration status exerts [...] Read more.

Background: Ramadan fasting involves daily abstinence from food and water between dawn and sunset, but human studies cannot readily disentangle the effects of fasting timing, circadian alignment, and hydration status on metabolic regulation. Objective: To determine whether fasting timing or hydration status exerts a stronger influence on metabolic outcomes in diet-induced obese rats under controlled Ramadan-like conditions. Methods: Forty diet-induced obese rats were assigned to four Ramadan-like fasting groups differing by timing and hydration: dry morning (DM), wet morning (WM), dry night (DN), or wet night (WN) fasting, in addition to healthy control (HC) and obese control (OC) groups (n = 8 each). Because rats are nocturnal, morning fasting restricted food during the inactive (light) phase, whereas night fasting restricted food during the active (dark) phase. Body weight, glucose, insulin, HOMA-IR, lipid profile, adipokines, and electrolytes were assessed after four weeks. Results: Morning fasting significantly reduced body-weight gain (F(5,42) = 10.72, p < 0.0001; η² = 0.56) and improved insulin sensitivity, reflected by lower insulin (F(5,30) = 2.98, p = 0.027; η² = 0.33) and HOMA-IR (F(5,30) = 3.76, p = 0.0092; η² = 0.39), independent of hydration status. Serum glucose differed across groups (F(5,42) = 5.82, p = 0.00036). After body-weight adjustment, total cholesterol and triglycerides were reduced in fasting groups, whereas hydration primarily influenced fluid and electrolyte parameters without materially altering core metabolic outcomes. Conclusions: Under controlled conditions, fasting timing exerted a stronger influence on metabolic regulation than hydration status. Fasting aligned with the inactive circadian phase was associated with more favorable metabolic outcomes, highlighting circadian alignment as a key determinant of fasting-related metabolic adaptation in obesity. Full article

(This article belongs to the Section Nutrition and Metabolism)

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4 pages, 175 KB

Open AccessEditorial

Nutritional Requirements During Pregnancy and Lactation: An Editorial

by Antonios Siargkas, Panagiota Kripouri, Antigoni Tranidou, Themistoklis Dagklis and Ioannis Tsakiridis

Nutrients 2026, 18(4), 662; https://doi.org/10.3390/nu18040662 - 18 Feb 2026

Abstract

As we navigate the landscape of nutritional science in 2026, global efforts remain steadfast in their commitment to optimizing maternal and offspring health, which was reinforced at the 78th World Health Assembly in Geneva, where the World Health Organization (WHO) reaffirmed its global [...] Read more.

As we navigate the landscape of nutritional science in 2026, global efforts remain steadfast in their commitment to optimizing maternal and offspring health, which was reinforced at the 78th World Health Assembly in Geneva, where the World Health Organization (WHO) reaffirmed its global nutrition targets, placing renewed emphasis on maternal dietary intake [...] Full article

(This article belongs to the Special Issue Nutritional Requirements of Pregnant and Lactating Women)

12 pages, 243 KB

Open AccessArticle

Exploring Beverage Intake and Dietary Timing Patterns in Medication-Induced Xerostomia: A Cross-Sectional Pilot Study

by Alhanoof K. Alarfaj, Abdul B. Barmak, Waldir M. Filho and Szilvia Arany

Nutrients 2026, 18(4), 661; https://doi.org/10.3390/nu18040661 - 18 Feb 2026

Abstract

Background: Xerostomia, or the subjective sensation of dry mouth, is a prevalent side effect of medications. While its impact on oral function is well documented, limited research has examined how xerostomia influences beverage consumption and the timing of food intake, especially in non-cancer, [...] Read more.

Background: Xerostomia, or the subjective sensation of dry mouth, is a prevalent side effect of medications. While its impact on oral function is well documented, limited research has examined how xerostomia influences beverage consumption and the timing of food intake, especially in non-cancer, middle-aged populations. Objectives: To examine associations between beverage intake, meal timing, and subjective and objective measures of salivary gland function in individuals with medication-induced xerostomia. Methods: This cross-sectional pilot study included 90 adults aged 45–66 taking anticholinergic medications. Salivary function was assessed via unstimulated whole saliva (UWS), minor salivary flow (MSF), and the Xerostomia Inventory (XI). Validated questionnaires evaluated habitual water and beverage intake, and meal timing. Multivariable models were adjusted for demographics, medication use, and comorbidities. Results: Hyposalivation (UWS ≤ 0.3 mL/min) was associated with higher XI scores (p = 0.033) and greater anticholinergic medication burden (p = 0.024). The later timing of last intake and last snack was independently associated with greater xerostomia severity. Total beverage and water intake were not associated with salivary flow or XI scores. Nighttime eating was correlated with higher anticholinergic burden. Conclusions: The timing of intake, rather than fluid volume, may better reflect symptom burden in medication-induced xerostomia, underscoring the behavioral adaptations to oral dryness. Full article

(This article belongs to the Section Nutrition and Public Health)

20 pages, 580 KB

Open AccessArticle

A Maturation-Aware Machine Learning Framework for Screening the Nutritional Status of Adolescents

by Hatem Ghouili, Zouhaier Farhani, Narimen Yousfi, Halil İbrahim Ceylan, Amel Dridi, Andrea de Giorgio, Nicola Luigi Bragazzi, Noomen Guelmami, Ismail Dergaa and Anissa Bouassida

Nutrients 2026, 18(4), 660; https://doi.org/10.3390/nu18040660 - 17 Feb 2026

Abstract

Background: Malnutrition in adolescents remains a significant public health issue worldwide, with undernutrition and overweight often coexisting. Accurate nutritional screening during adolescence is complicated by variability in biological maturation and class imbalance, particularly among underweight adolescents. Objective: This study aims to develop and [...] Read more.

Background: Malnutrition in adolescents remains a significant public health issue worldwide, with undernutrition and overweight often coexisting. Accurate nutritional screening during adolescence is complicated by variability in biological maturation and class imbalance, particularly among underweight adolescents. Objective: This study aims to develop and validate machine learning models for classifying the nutritional status of adolescents, accounting for class imbalance and biological maturation, and to evaluate model stability and variable importance at different stages of peak height velocity (PHV). Methods: In this cross-sectional study, 4232 adolescents aged 11 to 18 years were recruited from nine educational institutions in Tunisia. Their nutritional status was classified according to the International Obesity Task Force (IOTF) BMI thresholds into three categories: underweight (14.4%), normal weight (68.3%), and overweight (17.2%). Ten anthropometric, behavioral, and maturation-related predictors were analyzed. Six supervised machine learning algorithms were evaluated using a 70/30 stratified split between training and test sets, with five-fold cross-validation. Class imbalance was addressed by ROSE combined with cost-sensitive learning. Model performance was assessed using accuracy, Cohen’s kappa coefficient, macro F1 score, sensitivity, specificity, and AUC. Results: The cost-sensitive Random Forest (RF) model achieved the best overall performance, with an accuracy of 0.830, a macro F1 score of 0.767, a macro-AUC of 0.921, and a macro- sensitivity of 0.743. The class-specific sensitivities were 0.70 (underweight), 0.91 (normal weight), and 0.62 (overweight), with no major misclassification between the extreme categories. Performance remained stable across the different maturation phases (accuracy from 0.823 to 0.839), with optimal discrimination in the pre-PHV (macro-AUC = 0.936; sensitivity for underweight = 0.82) and post-PHV (macro-AUC = 0.931) periods. Body mass was the main predictor (importance = 1.00), followed by waist circumference (0.34–0.53). The importance of age for classifying underweight increased significantly from the pre-PHV (0.10) to the post-PHV (0.75) period. A two-stage hierarchical model further improved underweight detection (stage 1 AUC = 0.911; sensitivity = 0.732). Conclusions: A cost-sensitive RF model, combined with ROSE, provides robust classification of adolescents’ nutritional status maturation, significantly improving underweight detection while preserving overall accuracy. This approach is particularly well-suited to public health screening in schools as a first-stage assessment that requires clinical confirmation and promotes a maturation-aware interpretation of nutritional risk among adolescents. Full article

(This article belongs to the Special Issue Nutrition-Based Counseling and Interventions for Chronic Disease Prevention)

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22 pages, 1787 KB

Open AccessArticle

Effects of Dietary Highland Barley at Different Inclusion Levels on Normobaric Hypoxia Tolerance, Oxidative Stress, Energy Metabolism, and Gut Microbiota in Mice

by Liangxing Zhao, Luman Sang, Yan Liu, Baicheng Lai, Qingyu Zhao, Liang Zou and Qun Shen

Nutrients 2026, 18(4), 659; https://doi.org/10.3390/nu18040659 - 17 Feb 2026

Abstract

Background: Normobaric acute hypoxia models are widely applied to assess tolerance to acute hypoxic stress. Highland barley is a cereal crop originating from and traditionally cultivated in high-altitude regions; however, the dose–response relationship underlying its effects on hypoxia tolerance remains unclear. Methods: Male [...] Read more.

Background: Normobaric acute hypoxia models are widely applied to assess tolerance to acute hypoxic stress. Highland barley is a cereal crop originating from and traditionally cultivated in high-altitude regions; however, the dose–response relationship underlying its effects on hypoxia tolerance remains unclear. Methods: Male ICR mice were randomly allocated to five groups (n = 8 per group) and fed an AIN-93M basal diet or experimental diets supplemented with 20%, 40%, 60%, or 80% highland barley for 13 weeks. Hypoxia survival time was evaluated using a normobaric asphyxial hypoxia model, in which oxygen is progressively depleted in a sealed chamber by continuous respiration with carbon dioxide absorbed by soda lime. Hematological parameters, indices of oxidative stress and energy metabolism, and gut microbiota composition were also assessed. Results: Compared with the control group, dietary supplementation with 20% highland barley was associated with a longer hypoxia survival time (mean difference: 9.49 min; 95% CI: −2.05 to 21.02), whereas the 80% group exhibited the shortest survival time (approximately 40.6 min). In the 20% group, red blood cell count and hemoglobin concentration increased by 41.6% and 42.1%, respectively. ATP content and superoxide dismutase activity in brain tissue increased by 33.2% and 28.4%, respectively, with similar trends observed in heart tissue. In addition, gut microbiota α-diversity was increased in the 20% highland barley group, and distinct separation of microbial community structures was observed among groups receiving different supplementation levels. Conclusions: Overall, the data suggest that moderate dietary supplementation with highland barley (20%) is associated with a favorable physiological and microbiota profile under normobaric asphyxial hypoxic challenge, suggesting the presence of a potentially effective intake range for highland barley-based nutritional intervention. Full article

(This article belongs to the Special Issue Gut Microbiota in Components of Grain and Host Health)

23 pages, 3734 KB

Open AccessArticle

Metagenomics and Machine Learning Identify TMA-Producing Serratia Induced by High-Fat/Choline Diet: A Novel Obesity Target for TMA

by Zhuo Wang, Jiaying Wei, Zixin Huang, Xiang Liu, Shanshan Li, Zhengfeng Fang, Liang Hu, Ran Li, Lisi Tao, Cheng Li and Hong Chen

Nutrients 2026, 18(4), 658; https://doi.org/10.3390/nu18040658 - 17 Feb 2026

Abstract

Background: High-fat diet-induced metabolic disorders are associated with trimethylamine (TMA)/trimethylamine N-oxide (TMAO), whose production is linked to gut microbial choline metabolism. However, changes in specific gut microbiota under a high-fat diet and the relationship between these changes and choline in TMA/TMAO production [...] Read more.

Background: High-fat diet-induced metabolic disorders are associated with trimethylamine (TMA)/trimethylamine N-oxide (TMAO), whose production is linked to gut microbial choline metabolism. However, changes in specific gut microbiota under a high-fat diet and the relationship between these changes and choline in TMA/TMAO production remain unclear. Methods: A total of 48 7-week-old male C57BL/6J mice were subjected to one-week acclimatization feeding, and then randomly divided into four groups (12 mice per group) to establish a 2 × 2 factorial design animal experiment: the control group (CON, basal diet), the choline-supplemented control group (CON + C, basal diet supplemented with 1% choline), the high-fat diet group (HF, high-fat diet), and the high-fat plus choline group (HF + C, high-fat diet supplemented with 1% choline). The experiment lasted for 9 weeks, during which dynamic monitoring of TMAO levels in mice was performed in the first 4 weeks. At the ninth week, the mice were sacrificed and samples were collected for subsequent assays, including the concentrations of TMA and TMAO in serum, colonic contents and feces; the pathological morphology of liver tissue, adipocyte staining characteristics and serum biochemical parameters; and the expression levels of key genes and proteins in liver, small intestine and colon tissues. Meanwhile, metagenomic analysis was conducted on colonic contents, combined with machine learning to predict the correlation between gut microbiota and TMA. In addition, gene cloning, multiple sequence alignment, molecular simulation and in vitro culture experiments were carried out to verify the TMA-producing function of the target strain. Results: This study elucidated that high-fat diet and high choline exert a significant interaction in TMA/TMAO production through a 2 × 2 animal experiment; meanwhile, the significantly increased TMA/TMAO levels co-induced by the two factors further exacerbate metabolic disorders. Notably, through combined metagenomics and machine learning, we identified Serratia marcescens as the primary TMA-producing microorganism under high-fat/choline diet induction. In vitro cultures simulating the intestinal environment revealed that the TMA conversion ability of Serratia marcescens is time-dependent, reaching 60 ± 2.49% after 24 h of anaerobic culture with choline chloride. Multiple sequence alignment and molecular simulation further demonstrated that the CutC enzyme of Serratia marcescens has a conserved amino acid sequence and high affinity for choline. Conclusions: We uncovered a two-factor synergistic effect of a high-fat/choline diet on TMA/TMAO, and for the first time identified the genus Serratia as a TMA-producing bacterium. These findings provide a new potential target for intervening in metabolic disorders mediated by high-fat diet-induced TMAO elevation. Full article

(This article belongs to the Section Nutrigenetics and Nutrigenomics)

13 pages, 1574 KB

Open AccessArticle

Comparing Acute Effects of Caffeine Delivery Forms on Cross-Training Performance: A Randomized Placebo-Controlled Crossover Trial

by Salvador Vargas-Molina, Diego A. Bonilla, Manuel García-Sillero, Sergio Iglesias-Placed, Mora Murri, Fernando Martín-Rivera and Javier Benítez-Porres

Nutrients 2026, 18(4), 657; https://doi.org/10.3390/nu18040657 - 17 Feb 2026

Abstract

Background/Objectives: The aim of this study was to compare the different forms of caffeine (CAF) administration in CrossFit^® participants. The countermovement jump (CMJ), the rate of perceived exertion (RPE), the total number of repetitions, and the maximum (HR_max) and [...] Read more.

Background/Objectives: The aim of this study was to compare the different forms of caffeine (CAF) administration in CrossFit^® participants. The countermovement jump (CMJ), the rate of perceived exertion (RPE), the total number of repetitions, and the maximum (HR_max) and mean heart rate (HR_mean) were evaluated. Methods: Fourteen males with more than six months of continuous CrossFit^® training (30.9 [5.62] years, 179 [1.33] cm, 78 [5.75] kg, 24.3 [1.33] kg·m⁻²) participated in this randomized, placebo-controlled, crossover study. Participants were randomized in a repeated measures design using caffeine capsule (CC), caffeine chewing gum (CCG), and caffeine mouth rinse (CMR) protocols, along with a placebo group (PG). Participants were unaware of whether any of the delivery methods contained caffeine. A 7-day washout period before each crossover was used. To ensure ecological validity, we replicated the real-world practice of CAF ingestion 30 min prior to training, mirroring typical athlete pre-workout routines. The participants of CrossFit^® performed the ‘Cindy’ protocol, and the CMJ as a primary outcome was measured pre- and post-intervention, while the RPE, HR, and the number of repetitions were tracked at the end of the workout for comparisons. Results: No significant differences were found between CAF forms in internal load measures (RPE, HR_max, HR_mean) or the number of repetitions. While no changes were observed with other CAF forms, CMR significantly improved the CMJ performance compared to the baseline (Δ: +3.5; Cohen’s d_unb: 0.51], which exceeded the estimated SWC by approximately three-fold. However, the inferential analysis revealed no significant main effects of the caffeine administration method on any measured outcomes. Conclusions: While CAF delivery forms did not improve internal load measures or performance parameters, such as the RPE, HR, or the total number of repetitions, the caffeine mouth rinse (CMR) showed a potentially meaningful improvement in CMJ performance after CrossFit^® training in participants with a certain level of experience. Full article

(This article belongs to the Section Sports Nutrition)

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16 pages, 283 KB

Open AccessArticle

Food Agency and Intentions to Improve Cooking Skills Among Korean Young Adults: Demographic Differences and Motivators

by So-Young Kim, Ji Yu Choi and Min Hyun Maeng

Nutrients 2026, 18(4), 656; https://doi.org/10.3390/nu18040656 - 17 Feb 2026

Abstract

Background/Objectives: This study aimed to examine levels of food agency and intentions to improve cooking skills among Korean young adults in their 20s, and to identify demographic differences and underlying motivators. Subjects/Methods: An online survey was administered from February 18 to [...] Read more.

Background/Objectives: This study aimed to examine levels of food agency and intentions to improve cooking skills among Korean young adults in their 20s, and to identify demographic differences and underlying motivators. Subjects/Methods: An online survey was administered from February 18 to 25, 2021, targeting Korean adults aged 20–29 years (n = 1102; 579 men, 523 women). Food agency was assessed using the Cooking and Food Provisioning Action Scale (CAFPAS), comprising three subscales: self-efficacy (13 items), attitude (10 items), and structure (5 items). Participants also reported their intentions to improve cooking skills and the motivators behind those intentions. Reliability of multi-item measures was confirmed using Cronbach’s alpha. Descriptive statistics were calculated for all study variables. Demographic differences in food agency and intentions were analyzed using independent t-tests and one-way ANOVA. Open-ended responses were analyzed using qualitative content analysis to explore key motivators. Statistical analyses were performed using SPSS Statistics 28.0 (α = 0.05). Results: Food agency scores were significantly lower among university graduates, employed individuals, and those from lower-income households. Single-person households reported significantly higher self-efficacy and attitude scores, while structure scores were significantly lower in this group. Lower structure scores were also observed among women; university graduates or individuals with higher levels of education; employed respondents; and those belonging to the low-income group. Intentions to improve cooking skills were significantly higher among women and single-person households. Qualitative analysis identified media influence and the demands of independent living as primary motivational drivers. Conclusions: These findings highlight the need for targeted interventions to enhance structural capacity for food agency, particularly among women, employed individuals, those with higher education, and people in the low-income range. Efforts should focus on leveraging media influence and supporting individuals adapting to independent living to promote cooking skill development. Full article

(This article belongs to the Section Nutritional Policies and Education for Health Promotion)

20 pages, 858 KB

Open AccessArticle

Exploring the Association Between DTC Obesity-Related Gene Polymorphisms and Obesity Risk Factors in Koreans: Focus on BDNF

by Jiha Kim, Soyoun Lee and Myoungsook Lee

Nutrients 2026, 18(4), 655; https://doi.org/10.3390/nu18040655 - 16 Feb 2026

Abstract

Background/Objectives: Among more than 300 candidate genes for obesity, FTO, MC4R, and BDNF have been approved for DTC genetic testing. However, population-specific evidence supporting their relevance to obesity-related phenotypes in Koreans remains limited. Methods: A total of 231 healthy adults aged [...] Read more.

Background/Objectives: Among more than 300 candidate genes for obesity, FTO, MC4R, and BDNF have been approved for DTC genetic testing. However, population-specific evidence supporting their relevance to obesity-related phenotypes in Koreans remains limited. Methods: A total of 231 healthy adults aged 19–64 years were recruited between March and May 2024. Anthropometric and clinical measurements, genotyping, dietary intake, and questionnaires on socioeconomic status, family history, and lifestyle behaviors were obtained. Associations between genotypes and obesity-related phenotypes were evaluated using ANOVA and ANCOVA, multivariable-adjusted models and multicollinearity analysis-based stepwise regression. Results: In Koreans, MAFs for FTO (3 SNPs), MC4R rs17782313 and BDNF rs6265 were 13–16%, 27.1% and 47.4%, respectively. OB frequency (%) differed significantly between BDNF GG and A allele carriers (p < 0.05). Compared to GG, BDNF A allele carriers showed higher WHR, ALT, HbA1c and sodium intake (p < 0.05). BDNF A allele carriers were observed to have higher drinking frequency and elevated ALT levels. Significant genotype–obesity interactions were identified for RMR/BW status, dietary fiber, Vit E, folate, P, K, cholesterol, and PUFA (p < 0.05). Among A allele carriers, OB-related indicators (BMI, RMR, WHR) were independently associated with age, sex, RMR, SBP, ALT, leptin, and dietary intakes of Vit A and sugars. Conclusions: These findings support the relevance of BDNF rs6265 in obesity phenotypes among Korean adults and provide Korean-specific evidence for genotype-based nutrition strategies. Given the cross-sectional study, the interpretation of personalized nutrition approaches for genetic risk carriers should be made with caution. Full article

(This article belongs to the Special Issue Advances in Gene–Diet Interactions and Human Health)

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18 pages, 2156 KB

Open AccessArticle

Impact of Polycystic Ovary Syndrome Status on Changes in Reproductive Function During a Hypocaloric Dietary Intervention

by Jie Zhang, Joy Y. Kim, Ryan Levine, Catherine Cho, Hannah Lee, Eli Thoma, Faith E. Carter, Brittany Y. Jarrett, Bailey Smith, Heidi Vanden Brink and Marla E. Lujan

Nutrients 2026, 18(4), 654; https://doi.org/10.3390/nu18040654 - 16 Feb 2026

Abstract

Background/Objectives: Lifestyle interventions are first-line treatment for women with polycystic ovary syndrome (PCOS) to improve metabolic health. Impacts on reproductive function are less clear. Previous research has been limited by inconsistencies in evaluation of ovulatory function and lack of comparisons between women [...] Read more.

Background/Objectives: Lifestyle interventions are first-line treatment for women with polycystic ovary syndrome (PCOS) to improve metabolic health. Impacts on reproductive function are less clear. Previous research has been limited by inconsistencies in evaluation of ovulatory function and lack of comparisons between women with and without PCOS. Methods: The present study implemented a prospective clinical trial of 28 women (PCOS, N = 10 and Non-PCOS Control, N = 18) undergoing a 1-month baseline assessment followed by a 6-month hypocaloric dietary intervention. Results: Both groups reached clinically meaningful weight loss with the intervention (PCOS group: 6.5 ± 5.5%; Non-PCOS Control group: 10.0 ± 4.7%). Largest follicle diameter and growth rate of ovulatory dominant follicle, menstrual cycle length and luteal phase length did not change during the intervention in either group (all p > 0.05). The Non-PCOS Control group had increased mid-luteal phase progesterone levels and secretory phase maximum endometrial thickness during the intervention (all p < 0.05), whereas the PCOS group showed a reduction in follicular phase length (p < 0.05). Additionally, changes in ovulatory function and endometrial development were not associated with the rate of weight loss (all p > 0.05). Conclusions: This study demonstrates that women with PCOS are unlikely to experience changes in menstrual cyclicity and endometrial development with a short-term hypocaloric dietary intervention. The shortening of the follicular phase suggests that women with PCOS may need a longer intervention to achieve clinically meaningful improvements in ovulatory function and endometrial health. Full article

(This article belongs to the Special Issue Diet in Women with Polycystic Ovary Syndrome)

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14 pages, 3771 KB

Open AccessBrief Report

PPAR-γ Activation Alleviates Intestinal Dysfunction and Lactose Malabsorption in Experimental Food Allergy Rats

by Yuyang Hao, Lu Yao, Yuxin Jin, Sheng Yin, Zhiwei He and Huilian Che

Nutrients 2026, 18(4), 653; https://doi.org/10.3390/nu18040653 - 16 Feb 2026

Abstract

Background/Objectives: Food allergy-induced intestinal inflammation can impair lactose digestion and absorption by damaging the epithelium, leading to secondary lactase deficiency with no effective treatments. The immunometabolism nuclear receptor PPAR-γ regulates gut epithelial function and nutrient absorption. This study aimed to determine whether PPAR-γ [...] Read more.

Background/Objectives: Food allergy-induced intestinal inflammation can impair lactose digestion and absorption by damaging the epithelium, leading to secondary lactase deficiency with no effective treatments. The immunometabolism nuclear receptor PPAR-γ regulates gut epithelial function and nutrient absorption. This study aimed to determine whether PPAR-γ activation can preserve lactose digestion and absorption during allergic inflammation and to elucidate the underlying mechanisms. Methods: In an ovalbumin-sensitized Brown Norway rat model of food allergy, animals were treated with either the PPAR-γ agonist rosiglitazone or the antagonist GW9662. Lactose absorption was assessed by in vivo lactose tolerance tests (blood glucose monitoring) and intestinal transit measurements. Jejunal tissues were analyzed for lactase gene expression, lactase enzyme activity, and SGLT1/GLUT2 transporter levels. Results: Allergic rats exhibited reduced weight gain, delayed intestinal transit, and lactose malabsorption (lower blood glucose after lactose challenge), accompanied by sharply decreased jejunal lactase mRNA, enzyme activity, and SGLT1/GLUT2 levels. Rosiglitazone treatment restored intestinal PPAR-γ expression and markedly improved lactose absorption, normalizing the lactose tolerance curve. Rosiglitazone also increased lactase gene expression and enzyme activity, and upregulated SGLT1 levels. In contrast, PPAR-γ inhibition with GW9662 further reduced lactase and transporter levels and failed to improve absorption. Conclusions: PPAR-γ signaling maintains intestinal lactose digestive capacity of rats during allergic inflammation by sustaining lactase production and monosaccharide transporter expression. Our findings verify an immunometabolism mechanism linking nuclear receptor activation to enhanced nutrient absorption and highlight PPAR-γ agonism as a promising therapeutic strategy to alleviate food allergy-associated lactose malabsorption. Full article

(This article belongs to the Special Issue Food Intake and Inflammatory Bowel Disease)

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