Nutrients

22 pages, 1565 KB

Open AccessArticle

Protective Effects of Vitamin D Against Doxorubicin Chemotherapy–Induced Hepatotoxicity in Wistar Albino Rats: Evidence from ⁹⁹mTc-Pyrophosphate Scintigraphy and Oxidative–Inflammatory Pathways

by Murat Kalın, Haluk Kerim Karakullukcu, Mina Karakullukcu, Aylin Arslan, Serdar Savaş Gül, Reyhan Toyran, Ömer Faruk Özkan, Gülçin Ercan and Hatice Aygun

Nutrients 2026, 18(7), 1097; https://doi.org/10.3390/nu18071097 (registering DOI) - 29 Mar 2026

Abstract

Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and [...] Read more.

Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU/kg), Vitamin D (60,000 IU/kg), Doxorubicin, DOX + Vitamin D (5000 IU/kg), and DOX + Vitamin D (60,000 IU/kg). Vitamin D₃ (cholecalciferol) was administered orally either as a daily dose (5000 IU/kg for 12 days) or as a single bolus dose (60,000 IU/kg). Doxorubicin (6 mg/kg/day, cumulative dose 18 mg/kg) was administered intraperitoneally on days 10–12. Hepatic injury was evaluated using ⁹⁹mTc-pyrophosphate (⁹⁹mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10). Results: Doxorubicin markedly increased hepatic ⁹⁹mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-α, IL-6, and IL-1β levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p < 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 ± 2.7 vs. 74.1 ± 3.8 and 69.3 ± 3.2 ng/mL for the 5000 and 60,000 IU/kg groups, respectively; p < 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, ⁹⁹mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses. Full article

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

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27 pages, 671 KB

Open AccessReview

Vitamin D: Nutritional Programming During the First 1000 Days of Life

by Costanza Sortino, Maurizio Carta, Cristina Bonacasa, Eva Candela, Veronica Notarbartolo, Laura Maria Sollena and Mario Giuffrè

Nutrients 2026, 18(7), 1096; https://doi.org/10.3390/nu18071096 (registering DOI) - 29 Mar 2026

Abstract

Background: The first 1000 days of life represent a critical window for developmental programming, during which specific nutritional exposures, such as vitamin D levels, may influence long-term health trajectories. Vitamin D plays a central role in skeletal development, but increasing evidence also supports [...] Read more.

Background: The first 1000 days of life represent a critical window for developmental programming, during which specific nutritional exposures, such as vitamin D levels, may influence long-term health trajectories. Vitamin D plays a central role in skeletal development, but increasing evidence also supports its possible involvement in immune, metabolic, and neurodevelopmental processes during early life. In this narrative review, we summarize current evidence on the biological functions of vitamin D across the first 1000 days, focusing on its roles in skeletal, immune, metabolic, and neurodevelopmental processes, and its potential role as a programming factor. Methods: We conducted our research using the PubMed, Scopus, and Cochrane databases. We included systematic reviews, randomized controlled trials, and high-quality observational studies published from 2015 onward, focusing on pregnancy, neonatal life, and early childhood. Results: Vitamin D acts through placental, epigenetic, skeletal, immune, metabolic, and neurodevelopmental pathways that are particularly active during early development. Low maternal or early-life vitamin D status has been associated with adverse birth outcomes and impaired bone health. It has also been linked to increased susceptibility to infections and allergic diseases, altered metabolic trajectories, and mild neurodevelopmental differences. Evidence from supplementation trials remains heterogeneous, with benefits appearing more consistent in populations with baseline deficiency. Conclusions: Vitamin D fulfills several biological plausibility criteria for a potential early-life programming factor, although current human evidence remains heterogeneous. Full article

(This article belongs to the Special Issue Nutrition in the Early Years: Feeding Challenges and Their Health Implications)

11 pages, 373 KB

Open AccessReview

Endothelial Cells as Active Lipid Gatekeepers: Vascular Control of Lipid Handling and Metabolic Homeostasis

by Takeshi Kanda and Hidonori Urai

Nutrients 2026, 18(7), 1095; https://doi.org/10.3390/nu18071095 (registering DOI) - 29 Mar 2026

Abstract

Endothelial cells have emerged as critical peripheral nutrient sensors that actively regulate systemic lipid metabolism rather than serving as passive conduits. Endothelial peroxisome proliferator-activated receptor γ maintains redox balance, supports nitric oxide-dependent perfusion, and preserves insulin sensitivity during high-fat feeding, while ghrelin signaling [...] Read more.

Endothelial cells have emerged as critical peripheral nutrient sensors that actively regulate systemic lipid metabolism rather than serving as passive conduits. Endothelial peroxisome proliferator-activated receptor γ maintains redox balance, supports nitric oxide-dependent perfusion, and preserves insulin sensitivity during high-fat feeding, while ghrelin signaling through endothelial GHS-R promotes triglyceride clearance and lipid uptake into white adipose tissue through an endothelial peroxisome proliferator-activated receptor γ-dependent program. These pathways reveal that the endothelium integrates hormonal and metabolic cues to tune lipid trafficking, vectorial fatty acid delivery, and depot-specific energy storage. The concept that the endothelial phenotype, rather than circulating lipid levels alone, determines organ-level lipid exposure reframes endothelial lipid sensing as a key regulator of whole-body metabolic homeostasis. Understanding how endocrine and transcriptional pathways shape endothelial lipid handling may reveal new therapeutic targets for the treatment of obesity, dyslipidemia, and related metabolic diseases. Full article

(This article belongs to the Special Issue Exploring the Nutrient Sensing Mechanisms and Metabolic Regulatory Networks of Metabolic Diseases)

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11 pages, 481 KB

Open AccessArticle

Effects of Extended-Release Cornstarch Supplementation on Glycemic Stability and Metabolic Parameters in Korean Patients with Glycogen Storage Disease

by Jungyun Han, Minjy Kim, Na Yeon Lee and Yunkoo Kang

Nutrients 2026, 18(7), 1094; https://doi.org/10.3390/nu18071094 (registering DOI) - 29 Mar 2026

Abstract

Background/Objectives: Patients with hepatic glycogen storage disease (GSD) require frequent nighttime intake of uncooked corn starch (UCCS) to prevent fasting hypoglycemia, which imposes a substantial burden. Glycosade, an extended-release cornstarch, was developed to prolong overnight glucose availability. However, data regarding South Korean patients [...] Read more.

Background/Objectives: Patients with hepatic glycogen storage disease (GSD) require frequent nighttime intake of uncooked corn starch (UCCS) to prevent fasting hypoglycemia, which imposes a substantial burden. Glycosade, an extended-release cornstarch, was developed to prolong overnight glucose availability. However, data regarding South Korean patients are limited. Therefore, we aimed to evaluate the efficacy and safety of Glycosade in South Korean patients with hepatic GSD. Methods: In this single-center prospective observational study, patients with hepatic GSD underwent laboratory evaluations before and 1 month after Glycosade administration. Continuous glucose monitoring (CGM) was performed during UCCS and Glycosade administration periods. The nocturnal mean glucose, coefficient of variation, time in range (70–180 mg/dL), and time below the range (<70 and <54 mg/dL) were compared between the periods using paired analyses. Results: No significant differences were observed in the nocturnal CGM metrics between the treatment periods. However, time-aligned CGM profiles revealed distinct temporal patterns, with a decline in glucose levels approximately 3–4 h after UCCS intake, whereas Glycosade showed a more sustained glucose profile over an extended period. Liver enzyme and lipid levels improved significantly after 1 month of Glycosade supplementation. Conclusions: In a cohort of South Korean patients with hepatic GSD, Glycosade maintained nocturnal glycemic stability comparable to that of conventional cornstarch without increasing the risk of hypoglycemia. Glycosade was also associated with improved biochemical parameters, supporting its role in nighttime dietary management. Full article

(This article belongs to the Special Issue Featured Papers on Dietary Carbohydrates and Human Health)

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24 pages, 1740 KB

Open AccessReview

A Narrative Review on Pseudocereals and Cardiometabolic Health: Biological Mechanisms and Evidence from Human Studies

by Yesim Oztekin and Zehra Buyuktuncer

Nutrients 2026, 18(7), 1093; https://doi.org/10.3390/nu18071093 (registering DOI) - 29 Mar 2026

Abstract

Background/Objectives: Demand for functional foods is growing due to the desire to prevent cardiometabolic disorders. Pseudocereals, particularly quinoa, buckwheat, and amaranth, stand out for their functional properties related to cardiometabolic health. The dietary fiber, plant proteins, vitamins, minerals, and phytochemicals in pseudocereals [...] Read more.

Background/Objectives: Demand for functional foods is growing due to the desire to prevent cardiometabolic disorders. Pseudocereals, particularly quinoa, buckwheat, and amaranth, stand out for their functional properties related to cardiometabolic health. The dietary fiber, plant proteins, vitamins, minerals, and phytochemicals in pseudocereals primarily help to regulate glycemic response and lipid profile, as well as blood pressure. The aim of this review is to briefly explain the role of pseudocereals in biological mechanisms underlying cardiometabolic effects and evaluate the findings of human studies. Methods: The biological mechanisms that emphasize potential cardiometabolic effects of pseudocereals were summarized based on preclinical studies. Human studies were searched on Web of Science, PubMed, and ScienceDirect between June and December 2025. Findings of human studies on potential cardiometabolic health benefits of pseudocereals, including their anti-hyperlipidemic, anti-hyperglycemic, anti-obesity, and anti-hypertensive effects, are discussed. Results: The revealed mechanisms in preclinical studies and current outcomes of thirty-three human studies included in this review indicated that pseudocereals, especially quinoa and buckwheat, might be a part of healthy nutrition to assist the prevention and management of cardiometabolic disorders. In human studies, the most notable improvements were reported in plasma triglyceride and total cholesterol levels. Nevertheless, the number of human studies is limited, and existing studies have methodological variations to state cumulative and evidence-based consumption recommendations. Conclusions: Despite the potential protective effects of pseudocereals on cardiometabolic health, well-designed, controlled human studies are needed to elucidate the outcomes and provide clear evidence of the role of pseudocereals in relation to cardiometabolic effects. Full article

(This article belongs to the Special Issue Featured Papers on Dietary Carbohydrates and Human Health)

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10 pages, 499 KB

Open AccessCommunication

Short-Term Associations Between Fat-Free Mass Preservation and Glycaemic Markers During Tirzepatide Therapy: A Secondary Exploratory Analysis

by Luigi Schiavo, Biagio Santella, Monica Mingo, Gianluca Rossetti, Marcello Orio, Luigi Cobellis, Francesco Cobellis and Vincenzo Pilone

Nutrients 2026, 18(7), 1092; https://doi.org/10.3390/nu18071092 (registering DOI) - 29 Mar 2026

Abstract

Background/Objectives: Tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, induces substantial weight loss in patients with obesity; however, pharmacologically induced weight reduction may be accompanied by losses in fat-free mass (FFM), muscle strength (MS), and resting metabolic rate (RMR), [...] Read more.

Background/Objectives: Tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, induces substantial weight loss in patients with obesity; however, pharmacologically induced weight reduction may be accompanied by losses in fat-free mass (FFM), muscle strength (MS), and resting metabolic rate (RMR), potentially influencing metabolic health. The metabolic implications of short-term preservation of metabolically active tissue during TZP therapy remain incompletely characterized. Methods: We performed a secondary, exploratory analysis of a previously published 12-week prospective, non-randomized comparative study including 60 patients with obesity treated with TZP (n = 30 TZP+Low Energy Ketogenic Therapy [LEKT]; n = 30 TZP+Low Calorie Diet [LCD]). Body weight (BW), fat mass (FM), FFM, MS, and RMR were assessed at baseline and week 12. Glycaemic parameters included fasting glucose, insulin, hemoglobin A1c (HbA1c), and HOMA-IR. All analyses were exploratory and hypothesis-generating. Results: Both groups achieved comparable reductions in BW after 12 weeks. FM decreased in both groups, while relative preservation of FFM, MS, and RMR was observed in one dietary context. Short-term changes in HbA1c, insulin, and HOMA-IR were statistically associated with concurrent changes in FFM, MS, and RMR, whereas no consistent associations were observed with changes in total BW or FM. Baseline glycaemic values were largely within the normoglycemic range. Conclusions: In this short-term secondary exploratory analysis, preservation of metabolically active tissue during TZP therapy was associated with concurrent glycaemic profiles, whereas no consistent associations were observed with total weight loss magnitude. These findings do not imply causality and should be interpreted as hypothesis-generating, warranting confirmation in larger, randomized, long-term studies. Full article

(This article belongs to the Special Issue Nutritional Support of GLP-1 Therapy: From Diabetes and Obesity Management to Cardiovascular Prevention)

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27 pages, 615 KB

Open AccessReview

Ketogenic Diet and Brain Health: Cerebrovascular Mechanisms, Neuroprotection, and Translational Implications

by Noémi Mózes, Ágnes Fehér, Tamás Csípő, Vince Fazekas-Pongor, Ágnes Lipécz, Dávid Major, Andrea Lehoczki, Norbert Dósa, Kata Pártos, Boglárka Csík, Hung Wei Yi, Csilla Kaposvári, Krisztián Horváth and Mónika Fekete

Nutrients 2026, 18(7), 1091; https://doi.org/10.3390/nu18071091 (registering DOI) - 29 Mar 2026

Abstract

Background: Ketogenic dietary therapies (KDTs), characterized by substantial carbohydrate restriction and increased dietary fat intake, were originally developed for the treatment of drug-resistant epilepsy but have recently attracted broader scientific interest. In the context of population aging and the increasing prevalence of cognitive [...] Read more.

Background: Ketogenic dietary therapies (KDTs), characterized by substantial carbohydrate restriction and increased dietary fat intake, were originally developed for the treatment of drug-resistant epilepsy but have recently attracted broader scientific interest. In the context of population aging and the increasing prevalence of cognitive impairment and dementia, their potential relevance for brain health has received growing attention. Experimental and emerging clinical evidence suggests that ketogenic metabolism may influence biological processes involved in brain aging, including cerebrovascular regulation, neuroinflammatory signaling, and cerebral energy metabolism. Objective: This narrative review aims to synthesize current evidence on the relationship between ketogenic dietary therapies and brain health, with particular emphasis on cerebrovascular mechanisms, neuroinflammatory pathways, and neuroprotective processes relevant to aging. The review also briefly introduces the Semmelweis Study as an example of a translational research framework for evaluating nutrition-related interventions in real-world preventive settings. Methods: A narrative literature review was conducted using structured searches of major scientific databases to identify experimental and human studies investigating ketogenic dietary interventions, cerebrovascular mechanisms, and neuroprotective outcomes. Publications related to the Semmelweis Study were included solely to illustrate implementation-oriented research approaches and not as evidence supporting dietary efficacy. Results: Available evidence indicates that ketogenic dietary interventions may modulate several biological pathways relevant to brain health, including cerebral energy metabolism, mitochondrial function, oxidative stress regulation, and inflammatory signaling. However, the current evidence base is dominated by preclinical studies and short-term human investigations, and direct evidence linking ketogenic dietary therapies to long-term cerebrovascular or cognitive outcomes remains limited. Conclusions: Ketogenic dietary therapies represent metabolically distinct dietary strategies with potential relevance for cerebrovascular and neuroprotective mechanisms. Nevertheless, human evidence remains heterogeneous and insufficient to support broad clinical recommendations. Future research should prioritize well-designed long-term human studies with clearly defined metabolic, cerebrovascular, and cognitive endpoints. Translational research frameworks may facilitate the evaluation of feasibility, safety, and implementation of ketogenic interventions in aging populations. Full article

(This article belongs to the Special Issue Food as Medicine for Brain and Other Tissues)

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23 pages, 2591 KB

Open AccessArticle

Post-Chemotherapy Changes and Agreement of CT-Derived Body Composition at L3 and T12 in Older Patients with Metastatic Colorectal Cancer: Associations with Nutritional Indices and Outcomes

by Anıl Yıldız, Melin Aydan Ahmed, Nihan Nizam Eren, Abdulmunir Azizy, Selay Artan, Simay Çokgezer, Bedirhan Ulufer, Ozan Deniz Aygörmez, Gündüz Karaoğlan, Şirin Zelal Şahin Tırnova, Gulistan Bahat, Mustafa Durmaz, İnci Kızıldağ Yırgın, Senem Karabulut, Burak Sakar, Mehmet Akif Karan and Didem Taştekin

Nutrients 2026, 18(7), 1090; https://doi.org/10.3390/nu18071090 (registering DOI) - 28 Mar 2026

Abstract

Background: Age- and cancer-related sarcopenia and malnutrition are common in older patients with colorectal cancer (CRC) and may negatively influence treatment tolerance and prognosis. However, the comparative prognostic value of post-chemotherapy changes in CT-based body composition parameters at the third lumbar vertebra (L3) [...] Read more.

Background: Age- and cancer-related sarcopenia and malnutrition are common in older patients with colorectal cancer (CRC) and may negatively influence treatment tolerance and prognosis. However, the comparative prognostic value of post-chemotherapy changes in CT-based body composition parameters at the third lumbar vertebra (L3) and the twelfth thoracic vertebra (T12) levels, and their associations with nutritional indices, remain unclear. This study aimed to examine and compare the prognostic relevance of post-chemotherapy body composition changes at L3 and T12 and to assess their relationship with nutritional indices in older patients with metastatic CRC (mCRC). Methods: This retrospective study included 87 older patients with mCRC. Baseline and ~3-month follow-up CT scans were analyzed at L3 and T12 using 3D Slicer to quantify skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), visceral-to-subcutaneous fat ratio (VSR), and intramuscular adipose tissue index (IMATI). Changes (Δ) in CT-derived body composition after chemotherapy were calculated as percentage change using ((follow-up − baseline)/baseline) × 100. Prognostic Nutritional Index (PNI) and Geriatric Nutritional Index (GNRI), which are established nutritional assessment tools, were calculated from baseline laboratory/anthropometric data. Agreement between T12 and L3 was assessed, and associations with grade ≥3 toxicity, progression-free survival (PFS), and overall survival (OS) were evaluated using multivariable models and ROC analyses. Results: Mean age was 69.0 ± 4.5 years (59 male/28 female), and 26.4% developed grade ≥3 adverse events. Over 3 months, mean SMI declined significantly at both L3 (46.7 ± 8.8 → 42.8 ± 9.8 cm²/m²) and T12 (34.6 ± 8.2 → 31.6 ± 8.1 cm²/m²) (p < 0.001 for both), accompanied by decreases in VATI and VSR; T12-IMATI increased significantly. Baseline PNI showed a weak positive correlation with L3-SMI (r = 0.302, p = 0.033), whereas GNRI showed moderate correlations with SMI at L3 (r = 0.502, p < 0.001) and T12 (r = 0.317, p = 0.025) and was associated with longitudinal changes in muscle metrics. T12-SMI consistently yielded lower values than L3-SMI, and agreement varied by compartment (best for SATI; weakest for VSR). Lower GNRI and greater L3-SMI loss were independently associated with grade ≥3 toxicity; ΔL3-SMI showed the highest discrimination (AUC = 0.79, 95% CI = 0.69–0.87, p < 0.001; cut-off >5.1% loss). All patients progressed (median PFS 7.6 months); mortality was 82.8% (median follow-up: 25 months). In multivariable analysis, PFS, CRP, GNRI, and ΔL3-SMI remained independently associated with OS. ΔL3-SMI provided the strongest mortality discrimination (AUC = 0.85, 95% CI = 0.74–0.94, p < 0.001; cut-off >10.4% loss), while ΔIMATI was also informative (AUC = 0.71, 95% CI = 0.59–0.82, p = 0.023). Conclusions: In older patients with mCRC, early post-chemotherapy skeletal muscle loss—particularly at the L3 level—showed the strongest prognostic association with severe toxicity and mortality. GNRI provided complementary prognostic information as a marker of baseline immunonutritional reserve. Although T12-derived measurements were correlated with L3-derived values, systematic bias suggests that they should not be interpreted interchangeably for longitudinal risk stratification. Full article

(This article belongs to the Special Issue Nutrition and Dietary Guidelines for Colorectal Cancer Patients)

17 pages, 592 KB

Open AccessArticle

Hair Manganese as a Marker of Cardiometabolic Status Rather than Coronary Artery Disease Severity—An Exploratory Pilot Study

by Ewelina A. Dziedzic, Aleksandra Czernicka, Agnieszka Mazur-Jax, Andrzej Osiecki, Jakub S. Gąsior, Jakub Marek Baran, Łukasz Dudek and Wacław Kochman

Nutrients 2026, 18(7), 1089; https://doi.org/10.3390/nu18071089 (registering DOI) - 28 Mar 2026

Abstract

Background: Manganese (Mn) is an essential trace element with antioxidant properties; however, excessive exposure may contribute to inflammation and vascular dysfunction. Hair analysis provides an indicator of long-term Mn exposure. This study evaluated the relationship between hair Mn levels, acute coronary syndrome (ACS), [...] Read more.

Background: Manganese (Mn) is an essential trace element with antioxidant properties; however, excessive exposure may contribute to inflammation and vascular dysfunction. Hair analysis provides an indicator of long-term Mn exposure. This study evaluated the relationship between hair Mn levels, acute coronary syndrome (ACS), coronary artery disease (CAD) severity, and cardiovascular risk factors, with particular emphasis on metabolic status in a cardiometabolic population. Methods: Hair Mn concentration was measured using inductively coupled plasma optical emission spectrometry (ICP-OES) in 80 patients (mean age 67 ± 11 years; 28.8% women) undergoing coronary angiography for suspected ACS. Final diagnoses included stable CAD (N = 42) and ACS [ST-elevation myocardial infarction (STEMI) N = 17, non-ST-elevation myocardial infarction (NSTEMI) N = 12, and unstable angina (UA) N = 9]. CAD severity was quantified using the SYNTAX score and the Coronary Artery Surgery Study Score (CASSS). Associations with clinical variables were assessed using non-parametric tests and Spearman correlations. The median SYNTAX score was 13.8 (range 0.0–68.5), and the median hair Mn concentration was 0.22 ppm (range 0.01–1.65). Results: SYNTAX scores were higher in ACS than in stable CAD (p = 0.027), with the highest values observed in NSTEMI. Hair Mn levels did not differ among diagnostic groups and showed no association with CASSS or SYNTAX (R = −0.11; p = 0.348). No differences were detected with respect to sex, smoking, prior myocardial infarction, hypertension, hyperlipidemia, or type 2 diabetes. A modest inverse correlation was observed between hair Mn and body mass index (BMI) in unadjusted analysis (R = −0.25; p = 0.03), but this association was not robust after correction for multiple comparisons, suggesting a potential exploratory link between manganese homeostasis and cardiometabolic status. Conclusions: Although hair Mn concentration was not associated with angiographic indices of CAD severity or ACS subtypes, the observed relationship with BMI may indicate a role of Mn homeostasis in cardiometabolic regulation. Larger prospective studies are required to clarify these associations. Full article

(This article belongs to the Special Issue Micronutrients in Cardiovascular Diseases: Mechanisms, Biomarkers, and Therapeutic Perspectives)

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10 pages, 230 KB

Open AccessArticle

Association Between the Dietary Index for Gut Microbiota (DI-GM) and Colorectal Cancer in the PLCO Cohort

by Bezawit E. Kase, Angela D. Liese, Jiajia Zhang, Elizabeth Angela Murphy and Susan E. Steck

Nutrients 2026, 18(7), 1088; https://doi.org/10.3390/nu18071088 (registering DOI) - 28 Mar 2026

Abstract

Objectives: The study aimed to examine the association between a dietary index for gut microbiota (DI-GM) and the risk of incident colorectal cancer (CRC). Clarifying the role of diet-induced alterations in the composition and function of gut microbiota on the development of CRC [...] Read more.

Objectives: The study aimed to examine the association between a dietary index for gut microbiota (DI-GM) and the risk of incident colorectal cancer (CRC). Clarifying the role of diet-induced alterations in the composition and function of gut microbiota on the development of CRC can contribute to prevention efforts. Methods: Participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial enrolled in the intervention arm and who completed baseline assessments were included in the analysis (n = 55,685). The DI-GM is a literature-derived index used to score diet quality in terms of maintaining healthy gut microbiota. A time-dependent Cox model stratified by follow-up years (<5 and ≥5 person-years) was used to evaluate the relationships between the dietary patterns and risk of incident CRC. Results: A total of 735 incident CRC were identified over 650,470 person-years of follow-up. During < 5 years of follow-up, those with higher diet quality (DI-GM scores above 67th percentile) had an 18% lower risk of incident CRC (HR_adjusted = 0.82, 95% CI: 0.63, 1.07) compared with those with lower diet quality (DI-GM scores below the 67th percentile), though effect estimates were imprecise. During ≥ 5 years of follow-up, there was no association between incident CRC and DI-GM (HR_adjusted = 1.01, 95% CI: 0.80, 1.26). Conclusions: Diet quality measured using the DI-GM was associated with the risk of CRC in the first five years of follow-up in a large prospective cohort study. A diet that enhances the composition and function of gut microbiota may contribute to reduction in CRC risk. Full article

(This article belongs to the Section Nutritional Epidemiology)

15 pages, 290 KB

Open AccessArticle

Dietary Patterns, Hepatic Fat Fraction, and the Role of Genotype

by Kyle Salmon, Catherine C. Cohen, Leslie Lange, Dana Dabelea and Wei Perng

Nutrients 2026, 18(7), 1087; https://doi.org/10.3390/nu18071087 (registering DOI) - 28 Mar 2026

Abstract

Background/Objectives: We aimed to identify eating habits associated with hepatic fat fraction (HFF) and assess effect modification by an established genetic variant for fatty liver disease, PNPLA3 rs738409, among 381 general-risk adolescents. Methods: Dietary intake was assessed using the Block Kids [...] Read more.

Background/Objectives: We aimed to identify eating habits associated with hepatic fat fraction (HFF) and assess effect modification by an established genetic variant for fatty liver disease, PNPLA3 rs738409, among 381 general-risk adolescents. Methods: Dietary intake was assessed using the Block Kids Food Frequency Questionnaire and HFF was measured via magnetic resonance imaging (MRI) at age ~16 years. We first characterized naturally occurring dietary patterns using principal component analysis followed by reduced-rank regression with HFF as the response variable to identify a dietary pattern that is both relevant to the population and associated with HFF. Next, we investigated associations of the dietary pattern with HFF using linear regression models that accounted for maternal gestational diabetes, education, and prenatal smoking and child sex, age, Tanner stage, and BMI. Finally, we tested for a dietary pattern and PNPLA3 rs738409 interaction and stratified by genotype if P-interaction < 0.05. Results: The participants were 16.7 ± 1.2 years (range: 12.6–19.6 years). Half were female (50.4%) and 52.0% identified as non-Hispanic White. The dietary pattern of interest was composed of vegetables, fruit, nuts and seeds, oatmeal, sports bars, crackers and sandwiches, and beef, and was inversely associated with HFF (−0.48 [95% CI: −0.81, −0.16]). Stratified analyses revealed the strongest inverse association observed between the diet pattern score and HFF in the high-risk-variant (GG) group (−2.19 [−4.35, −0.03]), followed by the intermediate-risk (CG) group (−0.43 [−0.77, −0.10]), but not the low-risk (CC) group (−0.32 [−0.77, 0.13]). Conclusions: A diet high in vegetables, fruit, nuts and seeds, oatmeal, sports bars, crackers and sandwiches, and beef—potentially capturing an active, on-the-go lifestyle—is associated with lower HFF during adolescence, especially among individuals at genetic risk. Full article

(This article belongs to the Special Issue Associations Between Eating Patterns and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease)

18 pages, 2547 KB

Open AccessArticle

The Flavonoid Apigenin Modulates Oligodendroglial Plasticity and Has a Neuroprotective Effect in Cerebellar Slice Cultures with Oxygen Glucose Deprivation

by Rodrigo Barreto Carreira, Cleonice Creusa dos Santos, Juciele Valeria Ribeiro de Oliveira, Nivia Nonato Silva, Victor Diogenes Amaral da Silva, Mauricio Moraes Victor, Arthur Morgan Butt and Silvia Lima Costa

Nutrients 2026, 18(7), 1086; https://doi.org/10.3390/nu18071086 (registering DOI) - 28 Mar 2026

Abstract

Background: Apigenin, as a flavonoid, can be protective against oxidative damage in hypoxic events due to its antioxidant properties. Here, we have investigated the neuroprotective effects of apigenin in an ex vivo model of ischemic damage, using cerebellar slices from postnatal day (P)8–12 [...] Read more.

Background: Apigenin, as a flavonoid, can be protective against oxidative damage in hypoxic events due to its antioxidant properties. Here, we have investigated the neuroprotective effects of apigenin in an ex vivo model of ischemic damage, using cerebellar slices from postnatal day (P)8–12 reporter mice to identify oligodendrocytes (SOX10-EGFP) and astrocytes (GFAP-EGFP). Methods: Apigenin (10 and 20 μM) was administered preventively at 60 min prior to and during inducing ischemic damage by oxygen and glucose deprivation (OGD); controls were maintained with glucose and normoxia (OGN). Results: OGD induced a marked retraction of oligodendroglial processes without reducing the oligodendrocyte number. This structural disruption was prevented by apigenin; notably, 10 μM apigenin blocked process retraction, whereas 20 μM did not, indicating a dose-dependent effect on the oligodendroglial morphology. Consistent with this, MBP and NF70 immunofluorescence analyses of axonal myelination demonstrated that OGD caused a significant loss of myelin sheaths, and this was prevented by pre-treatment with apigenin. In addition, apigenin prevented astrocyte reactivity induced by OGD, as assessed by increased GFAP-EGFP expression and decreased expression of glutamine synthetase. Moreover, immunofluorescence for calbindin indicated that apigenin protected Purkinje neurons from ischemic damage. Conclusions: These results demonstrate that apigenin is neuroprotective in ischemia and this is associated with modulation of astrocyte reactivity and maintenance of oligodendrocyte and myelin integrity. Full article

(This article belongs to the Special Issue The Possible Role of Bioactive Compounds in Food in the Prevention of Neurodegenerative Diseases)

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15 pages, 303 KB

Open AccessArticle

Exploring the Association Between Internet Use and Dietary Habits of Adolescents and University Students in Greece: A Pilot Study

by Christina Stavraki, Nikolaos Georgiadis, Eleni Kornarou, Artemis K. Tsitsika, Theodoros N. Sergentanis and Tonia Vassilakou

Nutrients 2026, 18(7), 1085; https://doi.org/10.3390/nu18071085 (registering DOI) - 28 Mar 2026

Abstract

Background/Objectives: Adolescents and university students appear to be at increased risk for internet addiction (IA), while disordered eating behavior (DEB) is common in these age groups. At the same time, adherence to the Mediterranean diet (MD) has declined in many countries. This study [...] Read more.

Background/Objectives: Adolescents and university students appear to be at increased risk for internet addiction (IA), while disordered eating behavior (DEB) is common in these age groups. At the same time, adherence to the Mediterranean diet (MD) has declined in many countries. This study aimed to explore the potential association between IA, DEB and MD compliance among high school and university students. Methods: A total of 212 students aged 15–24 years participated in this cross-sectional study conducted in Greece. Data were collected via an online questionnaire including the Internet Addiction Test (IAT), KIDMED, and EAT-26 scales. Descriptive statistics, chi-square tests, and univariate and multivariate logistic regression analyses were performed. Results: Most participants demonstrated normal internet use (69.8%), while 23.1% showed mild IA and 7.1% moderate IA. Regarding dietary habits, 9.4% had low MD adherence, 52.8% moderate and 37.7% high adherence. A total of 15.6% scored above the EAT-26 cut-off, indicating risk for disordered eating behavior. IA was only significantly associated with urbanization (p = 0.014). MD adherence was not associated with gender, urbanization, financial or education status. Multivariate logistic regression showed that female gender (OR = 9.28, 95% CI: 2.10–40.91, p = 0.003) and moderate IA (OR = 6.70, 95% CI: 1.71–26.35, p = 0.006) were significant predictors of disordered eating, while educational status and MD adherence were not significant predictors. Conclusions: Moderate IA and female gender were strongly associated with an increased risk for disordered eating. Further qualitative and clinical studies are needed to better understand the interaction between IA, eating behaviors, and dietary patterns in young people. Full article

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

14 pages, 414 KB

Open AccessArticle

Firmicutes/Bacteroidetes Ratio as an Insufficient Indicator of Metabolic Status in Mexican Young Adults

by Ana Teresa Nez-Castro, Luis Guillermo González-Olivares, Laura Berenice Olvera-Rosales, Edwin Gualberto Barrón-Calva, Edwin Alonso Chávez-Mejía, Arianna Omaña-Covarrubias, Carlos Manuel Franco-Abuín and Alicia del Carmen Mondragón-Portocarrero

Nutrients 2026, 18(7), 1084; https://doi.org/10.3390/nu18071084 (registering DOI) - 28 Mar 2026

Abstract

Background: The Firmicutes/Bacteroidetes (F/B) ratio has been proposed as a microbial biomarker of obesity and metabolic alterations; however, its reliability remains controversial, particularly in young populations. Methods: This study evaluated the relationship between the F/B ratio, body fat percentage, and metabolic markers in [...] Read more.

Background: The Firmicutes/Bacteroidetes (F/B) ratio has been proposed as a microbial biomarker of obesity and metabolic alterations; however, its reliability remains controversial, particularly in young populations. Methods: This study evaluated the relationship between the F/B ratio, body fat percentage, and metabolic markers in 70 university students aged 18–25 years, classified as normal weight (29.5%), overweight (27.4%), or obese (43.2%). Anthropometric measurements and biochemical parameters (glucose, triglycerides, total cholesterol, and HDL-C) were obtained using standard methods, and stool samples were analyzed to determine the F/B ratio. Results: Mean glucose and cholesterol were within normal ranges, whereas triglycerides showed high variability, and HDL-C was lower in men. Although the F/B ratio increased across nutritional groups, regression analyses showed weak correlations (R < 0.5) and no significant associations (p > 0.05). Conclusions: The F/B ratio is not an adequate standalone indicator of metabolic status in Mexican young adults. Full article

(This article belongs to the Section Nutrition and Obesity)

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21 pages, 5293 KB

Open AccessArticle

Prenatal Edible Bird’s Nest Supplementation Attenuates Offspring Skin Pigmentation via Dual Inhibition of CREB and ERK Signaling to Downregulate MITF-TYR Axis

by Wenrui Zhang, Yijia Zhang, Xinyuan Wang, Yujuan Chen, Liqin Chen, Jie Gao, Yixuan Li, Dongliang Wang and Yanan Sun

Nutrients 2026, 18(7), 1083; https://doi.org/10.3390/nu18071083 (registering DOI) - 28 Mar 2026

Abstract

Background/Objectives: Edible bird’s nest (EBN) benefits skin, but its transgenerational effects are unknown. This study investigated whether maternal EBN or its key component, sialic acid (SA), could program offspring skin pigmentation and antioxidant capacity. Methods: Pregnant Sprague-Dawley rats were supplemented with EBN or [...] Read more.

Background/Objectives: Edible bird’s nest (EBN) benefits skin, but its transgenerational effects are unknown. This study investigated whether maternal EBN or its key component, sialic acid (SA), could program offspring skin pigmentation and antioxidant capacity. Methods: Pregnant Sprague-Dawley rats were supplemented with EBN or equi-sialic acid SA. Offspring skin brightness (L*, ITA°), melanin content, and key molecular targets (e.g., MITF, TYR, TRP1/2, PMEL, RAB27A, p-CREB, p-ERK, CAT, GCS, MDA) were assessed at postnatal days 0–21. Results: Maternal EBN induced a dose-dependent skin-brightening effect in offspring. High-dose EBN increased skin L* by 10.46% and ITA° by 14.28%, while reducing total melanin by 26.77%. This was mediated by downregulation of the MITF-TYR/TRP axis and its upstream CREB/ERK signaling, suppression of melanosome transport proteins (PMEL, RAB27A), and enhancement of antioxidant defenses (increased CAT/GCS, decreased MDA). SA alone showed similar but weaker effects. Conclusions: This study demonstrates that maternal EBN intake programs offspring skin towards a lighter phenotype and enhanced antioxidant status through multi-faceted regulation of melanogenesis. The superior efficacy of whole EBN over pure SA highlights the value of the intact food matrix, suggesting EBN as a promising functional food for maternal nutrition. Full article

(This article belongs to the Section Nutrition and Metabolism)

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15 pages, 567 KB

Open AccessReview

The Broad Effect of Iodine in Graves’ Hyperthyroidism and Its Relationship with the Gut Microbiota

by Elsbeth R. P. C. van Wees-Jansen, Barbara A. Hutten and Max Nieuwdorp

Nutrients 2026, 18(7), 1082; https://doi.org/10.3390/nu18071082 (registering DOI) - 27 Mar 2026

Abstract

Thyroid disorders are among the most common endocrine disorders worldwide and are classified as noncommunicable diseases. These disorders are associated with significant morbidity, impaired quality of life, and considerable socioeconomic burden. Like other noncommunicable diseases, thyroid disorders arise from complex interactions between genetic [...] Read more.

Thyroid disorders are among the most common endocrine disorders worldwide and are classified as noncommunicable diseases. These disorders are associated with significant morbidity, impaired quality of life, and considerable socioeconomic burden. Like other noncommunicable diseases, thyroid disorders arise from complex interactions between genetic susceptibility and environmental factors, including diet and lifestyle. Despite growing interest in lifestyle-based approaches to noncommunicable disease prevention and management, thyroid disorders have received comparatively limited attention in this context. Graves’ disease, the most common cause of hyperthyroidism, is a relevant condition for exploring dietary interventions. Current treatment strategies—anti-thyroid drugs, radioactive iodine and thyroidectomy—have remained largely unchanged for decades. Long-term remission following drug therapy is achieved in no more than approximately 50% of patients, while all treatment modalities carry potential adverse effects. These limitations underscore the need for alternative or adjunctive therapeutic strategies. Iodine intake plays a central role in thyroid hormone synthesis. Indeed, observational studies have shown inverse associations between iodine intake and remission rates, as well as achievement of euthyroidism, medication requirements and thyroid autoantibody titers. These findings suggest that dietary iodine restriction may enhance treatment efficacy and reduce medication-related risks. Beyond its direct effects on thyroid hormone synthesis, iodine may influence Graves’ disease through indirect mechanisms involving the lipid profile and the gut–thyroid axis. Autoimmune thyroid diseases are associated with a dyslipidemic profile and with gut microbiota dysbiosis; the latter characterized by increased potentially pathogenic bacteria and reduced beneficial bacteria such as Lactobacillus and Bifidobacterium. Full article

(This article belongs to the Special Issue Application of New Metabolomics Approaches in Studying the Nutrition-Microbiome Reciprocal Interaction)

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15 pages, 1036 KB

Open AccessReview

The Ketogenic Diet and Potential Micronutrient Risks in Drug-Resistant Epilepsy Management: A Literature Review

by Bhavini Singh, Paige Botten, Katherine P. Richardson, Chaston Weaver and Sharad Purohit

Nutrients 2026, 18(7), 1081; https://doi.org/10.3390/nu18071081 - 27 Mar 2026

Abstract

The ketogenic diet (KD) is a critical, evidence-based intervention within medical nutrition therapy for managing neurological disorders. In this article, we reviewed the published research on the efficacy of the ketogenic diet and its variations in treating epilepsy, particularly for patients unresponsive to [...] Read more.

The ketogenic diet (KD) is a critical, evidence-based intervention within medical nutrition therapy for managing neurological disorders. In this article, we reviewed the published research on the efficacy of the ketogenic diet and its variations in treating epilepsy, particularly for patients unresponsive to anti-epileptic drugs. The literature review was performed on PubMed between 2022 and 2025. The review of clinical studies across various age groups reveals that, while the KD is effective for both focal and generalized seizures, infants often achieve higher rates of seizure freedom compared to adults, potentially due to better dietary compliance. Despite its success, the restrictive nature of the diet presents significant challenges for individuals suffering from epilepsy. The key challenges that reduce compliance over time include side effects, such as gastrointestinal issues, potential for malnutrition, and a high risk of micronutrient deficiencies. The role of the registered dietitian is paramount in this interdisciplinary approach, ensuring personalized education by monitoring growth and adjusting nutritional plans to optimize health outcomes for children unresponsive to anti-epileptic drugs. Ultimately, integrating MNT with traditional pharmacological or surgical treatments offers the most promising path for significant seizure reduction and improved quality of life for epileptic patients. Full article

(This article belongs to the Section Pediatric Nutrition)

33 pages, 5068 KB

Open AccessReview

The Potential of Plant-Derived Foods to Treat Glaucoma: A Review

by Jinze Liu and Zhongmei He

Nutrients 2026, 18(7), 1080; https://doi.org/10.3390/nu18071080 - 27 Mar 2026

Abstract

Glaucoma, characterized by progressive retinal ganglion cell degeneration and optic nerve damage, is the leading cause of irreversible blindness worldwide. Multiple risk factors influence the pathogenesis and progression of glaucoma. Food-derived bioactive components have emerged as a new area of interest to overcome [...] Read more.

Glaucoma, characterized by progressive retinal ganglion cell degeneration and optic nerve damage, is the leading cause of irreversible blindness worldwide. Multiple risk factors influence the pathogenesis and progression of glaucoma. Food-derived bioactive components have emerged as a new area of interest to overcome the limitations of current standard treatments due to their antioxidant and anti-inflammatory activities and multi-target mechanisms. In this context, various plant-derived foods, such as Lycium barbarum, Ganoderma lucidum, Cryptotanshinone, Scutellaria baicalensis, Silybum marianum, Astragalus membranaceus, Ginkgo biloba, Panax ginseng, Crocus sativus, and resveratrol, have shown potential mechanisms for treating glaucoma. These bioactive components may address oxidative damage, neuroinflammation, and elevated intraocular pressure, which may be due to the modulation of multiple signaling pathways, including JAK2/STAT3, PI3K/AKT, MEK/ERK/CREB, cAMP/PKA/CREB, and others. However, further clinical trials are needed to validate dosage, bioavailability, and long-term safety. This review highlights the potential of bioactive components from plant-derived foods, offering a reference for further investigation into their effects on glaucoma. Full article

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

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46 pages, 1664 KB

Open AccessReview

Ginger Bioactives as Multi-Target Therapeutics: Mechanisms, Delivery Innovation, and Human Health Impact

by Pasquale Simeone, Francesca Martina Filannino, Antonia Cianciulli, Maria Ida de Stefano, Melania Ruggiero, Teresa Trotta, Antonella Compierchio, Tarek Benameur, Rosa Calvello, Amal Ferchichi, Chiara Porro and Maria Antonietta Panaro

Nutrients 2026, 18(7), 1079; https://doi.org/10.3390/nu18071079 - 27 Mar 2026

Abstract

Background/Objectives: Ginger has a long history as both a culinary and medicinal plant and is widely recognized in traditional medicine for its ability to promote health and well-being. The principal bioactive compounds of ginger are present in fresh and dried forms and have [...] Read more.

Background/Objectives: Ginger has a long history as both a culinary and medicinal plant and is widely recognized in traditional medicine for its ability to promote health and well-being. The principal bioactive compounds of ginger are present in fresh and dried forms and have been largely studied for their therapeutic potential. These compounds exhibit a wide range of biological activities mediated through various mechanisms. Advances in nanotechnology have enabled the development of innovative delivery systems, thereby enhancing the bioavailability and therapeutic efficacy of ginger-derived compounds in modern medical applications. Methods: A comprehensive literature review was conducted to evaluate the characteristics of ginger and its potential role in disease prevention. Relevant studies were identified through the main research databases, publication screening, manual reference checks, and author consensus was conducted. Results: This narrative review provides an overview of the therapeutic potential of bioactive compounds in ginger for the management and prevention of cardiovascular, arthritis, neurodegenerative, and gastrointestinal diseases, with particular emphasis on the molecular mechanisms. In addition, their potential anti-aging properties are extensively discussed. The evidence reported is predominantly preclinical (in vitro and in vivo models), with more limited and heterogeneous clinical data. Recent studies have also highlighted the role of artificial intelligence (AI) in accelerating the discovery and evaluation of bioactive agents with therapeutic relevance across diverse biological systems. Conclusions: This review highlights the emerging applications of ginger extracts in human health and suggests their applications in both traditional medicine and contemporary drug discovery. Full article

(This article belongs to the Special Issue Bioactive Ingredients in Plants Related to Human Health—2nd Edition)

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