Nutrients

3 pages, 147 KB

Open AccessEditorial

Bioactive Compounds and Functional Foods in Human Health—Bridging Mechanisms and Applications for Future Nutrition

by Vassilis Athanasiadis and Stavros I. Lalas

Nutrients 2025, 17(22), 3586; https://doi.org/10.3390/nu17223586 (registering DOI) - 17 Nov 2025

The role of bioactive compounds in the diet has moved from the periphery to the center of scientific and societal debate in both research and public health [...] Full article

(This article belongs to the Special Issue Bioactive Compounds and Functional Foods in Human Health)

16 pages, 411 KB

Open AccessArticle

The Influence of Berberine on Vascular Function Parameters, Among Them VEGF, in Individuals with MAFLD: A Double-Blind, Randomized, Placebo-Controlled Trial

by Anna Koperska, Ewa Miller-Kasprzak, Agnieszka Seraszek-Jaros, Katarzyna Musialik, Paweł Bogdański and Monika Szulińska

Nutrients 2025, 17(22), 3585; https://doi.org/10.3390/nu17223585 (registering DOI) - 16 Nov 2025

Abstract

Background: Metabolically Associated Fatty Liver Disease (MAFLD) is a prevalent liver disorder closely tied to metabolic dysfunction, insulin resistance, and chronic low-grade inflammation. Vascular Endothelial Growth Factor (VEGF) may have a dual interesting role in MAFLD pathophysiology—supporting vascular repair in early stages, but [...] Read more.

Background: Metabolically Associated Fatty Liver Disease (MAFLD) is a prevalent liver disorder closely tied to metabolic dysfunction, insulin resistance, and chronic low-grade inflammation. Vascular Endothelial Growth Factor (VEGF) may have a dual interesting role in MAFLD pathophysiology—supporting vascular repair in early stages, but potentially contributing to fibrosis in later stages. In this study, berberine (BBR), a plant-derived isoquinoline alkaloid, exhibits multiple beneficial properties, including anti-inflammatory, antioxidant, and endothelial-protective effects, on the study group, perhaps by influencing VEGF concentration. Objective: This study aimed to investigate the effectiveness of BBR in addressing vascular function parameters linked to MAFLD, particularly its impact on serum VEGF levels and arterial stiffness. Methods: This randomized, double-blind, placebo-controlled clinical trial enrolled seventy individuals with MAFLD who were overweight or obese. Participants were randomly assigned in a 1:1 ratio to receive either BBR (1500 mg/day) or a placebo orally for 12 weeks. The following parameters were assessed pre- and post-intervention: VEGF, brachial SBP (Systolic Blood Pressure)/DBP (Diastolic Blood Pressure), MAP (Mean Arterial Pressure), AIx (Augmentation Index), AP (Aortic Pressure), number of waveforms, Pulse Pressure (PP), PWV (Pulse Wave Velocity), and PWA-SP/PWA-DP (Pulse Wave Analysis Systolic/Diastolic Pressure). The results for the metabolic parameters—FLI (Fatty Liver Index)—and anthropometric parameters—BMI (Body Mass Index), fat mass corp—and laboratory parameters, among them, hsCRP (high-sensitivity C-reactive protein), were published by us earlier. Results: In the BBR-treated cohort, VEGF concentrations demonstrated a statistically significant increase following the intervention, rising from a baseline mean of 456.23 ± 307.61 pg/mL to 561.22 ± 389.77 pg/mL (p < 0.0001). In the BBR group, a significant reduction in PWA-SP was observed after 12 weeks of supplementation (134.85 ± 16.26 vs. 124.46 ± 13.47 mmHg, p < 0.0001). No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups. In the BBR group, delta VEGF correlated negatively with delta FLI; no such associations were observed in the placebo group. Changes in PWV were consistent and significantly correlated with changes in brachial SBP/DBP, PWA-SP, PWA-DP, and MAP. No serious adverse events were reported, and BBR was well tolerated. Conclusions: BBR appears to be a safe and promising adjunct in MAFLD therapy, potentially exerting reparative effects through VEGF modulation and vascular support. Further research is warranted to confirm its long-term impact and elucidate underlying protective mechanisms. Full article

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

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24 pages, 1397 KB

Open AccessReview

Vitamin D in Atopic Dermatitis: Role in Disease and Skin Microbiome

by Karolina Blady, Bartosz Pomianowski, Miłosz Strugała, Leon Smółka, Karolina Kursa and Agata Stanek

Nutrients 2025, 17(22), 3584; https://doi.org/10.3390/nu17223584 (registering DOI) - 16 Nov 2025

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with immune dysregulation, skin barrier dysfunction, and microbial dysbiosis characterized by Staphylococcus aureus overcolonization and reduced bacterial diversity. Beyond its classical role in calcium homeostasis, Vitamin D (VD) influences skin immunity and microbial [...] Read more.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with immune dysregulation, skin barrier dysfunction, and microbial dysbiosis characterized by Staphylococcus aureus overcolonization and reduced bacterial diversity. Beyond its classical role in calcium homeostasis, Vitamin D (VD) influences skin immunity and microbial composition. This review summarizes current knowledge on VD metabolism, its immunological pathways in AD, and its interactions with the skin microbiome. Recent evidence positions the skin as an active immunological organ rather than a passive barrier. Commensal bacteria such as Staphylococcus epidermidis not only inhibit pathogens by producing bacteriocins and modulins but also generate ceramides and short-chain fatty acids (SCFAs) that stabilize the lipid barrier. Moreover, dermal fibroblasts and preadipocytes produce antimicrobial peptides, while resident γδ T cells release growth factors like fibroblast growth factor 7 (FGF7), linking host defense with tissue regeneration. VD modulates AD by suppressing T helper 2 cells/T helper 17 cell responses, enhancing regulatory T cell development, inducing antimicrobial peptides, and strengthening skin and gut barrier integrity. Its interaction with the microbiome and pathways such as SCFA and aryl hydrocarbon receptor (AhR) signaling supports its potential as an adjunctive therapy in AD management. Evidence from mechanistic studies and animal models suggests that VD supplementation may modulate inflammation and microbial diversity. Clinical implications, therapeutic perspectives, and future research directions highlight the potential of VD as a therapeutic adjunct in AD management. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Skin, Hair and Nail Conditions)

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17 pages, 1033 KB

Open AccessArticle

Newborn Screening Alone Cannot Prevent Most Cases of Severe Vitamin B12 Deficiency in the First Year of Life

by Christina Kaufman, Julian Margreitter, Marion Herle, Walter Bonfig, Corinne Däster, Bianka Heinrich, Daniela Karall, Hubert Kogler, Vassiliki Konstantopoulou, Alexander Laemmle, Reta Malär, Pascal Müller, Veronika Pöll, Martin Poms, Franziska Righini-Grunder, Rotraud K. Saurenmann, Susanna Sluka, Nicolas von der Weid, Maximilian Zeyda, Matthias R. Baumgartner and Martina Huemer Show full author list Hide full author list

Nutrients 2025, 17(22), 3583; https://doi.org/10.3390/nu17223583 (registering DOI) - 16 Nov 2025

Abstract

Background/Objectives: Vitamin B12 (B12) is essential for the provision of methyl groups for numerous essential pathways. Infant B12 deficiency (B12D) can lead to severe, even irreversible neurological abnormalities. Maternal B12 status in pregnancy and during the breastfeeding period correlates significantly with the child’s [...] Read more.

Background/Objectives: Vitamin B12 (B12) is essential for the provision of methyl groups for numerous essential pathways. Infant B12 deficiency (B12D) can lead to severe, even irreversible neurological abnormalities. Maternal B12 status in pregnancy and during the breastfeeding period correlates significantly with the child’s B12 status. B12D is a target disease in some newborn screening (NBS) programs. This study investigates whether infants that were clinically symptomatic and diagnosed with B12D in their first year of life could be retrospectively detected by the Austrian NBS algorithm. Methods: Data from infants with clinically diagnosed B12D in their first year of life between 2012 and 2022 were retrospectively collected in Austria (B12-related NBS implemented in 2018) and Switzerland (B12-related NBS not implemented). NBS data were retrospectively analysed, and clinical information was collected by a survey. Correlations between clinical symptoms, NBS data, biochemical parameters at diagnosis, maternal medical history and B12 status were analysed. Results: Four/forty-eight cases were retrospectively detected by the first-tier NBS parameters. From two children material for second-tier testing was available and B12D was confirmed by elevated total homocysteine (tHcy), resulting in a detection rate between 4.3 and 9.3%. The numbers of neurological and haematological symptoms correlated with low B12 and elevated levels of tHcy and methylmalonic acid. Although the detection rate of symptomatic B12D by NBS was low, fewer infants with symptomatic B12D were observed in the period after implementation of B12-related NBS (Austria). A history of B12D-relevant maternal disease such as pernicious anaemia was reported in 12 cases. Conclusions: B12D causes severe clinical symptoms in infants. NBS has a very limited retrospective detection rate of infants with severe B12D but seems to correlate with a reduction in cases due to not yet precisely quantified mechanisms. The workup triggered by NBS recalls is costly and often challenging for families. Maternal B12D increases the risk of infant B12D but also of other pregnancy-related health risks. To increase the efficacy of the prevention of infant B12D, to promote a healthy pregnancy and breastfeeding period, and to reduce the frequency of NBS recalls, pregnant women should be screened for B12D to be counselled and treated. Full article

(This article belongs to the Section Pediatric Nutrition)

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17 pages, 1273 KB

Open AccessArticle

Effect of Exogenous Ketones as an Adjunct to Low-Calorie Diet on Metabolic Markers

by Eliza J. Roeth, Genevieve Parker, Ella F. Cooper-Leavitt, Colson G. Beus, Cameron R. Braithwaite, Madeline D. Morris, Asher P. Reynolds, Ethan P. Evans, Jack H. Radford, Fischer D. Davis, Paul R. Reynolds, R. Ryley Parrish and Benjamin T. Bikman

Nutrients 2025, 17(22), 3582; https://doi.org/10.3390/nu17223582 (registering DOI) - 16 Nov 2025

Abstract

Background/Objectives: Overweight and obesity affect a majority of adults, contributing to metabolic disorders. Caloric restriction often leads to undesirable lean mass loss alongside fat reduction. This study investigated whether exogenous β-hydroxybutyrate (BHB) supplementation, as an adjunct to a hypocaloric diet, improves body composition [...] Read more.

Background/Objectives: Overweight and obesity affect a majority of adults, contributing to metabolic disorders. Caloric restriction often leads to undesirable lean mass loss alongside fat reduction. This study investigated whether exogenous β-hydroxybutyrate (BHB) supplementation, as an adjunct to a hypocaloric diet, improves body composition and metabolic markers in overweight and obese adults by preferentially reducing fat mass while preserving lean mass. Methods: In this 8-week randomized, double-blind, placebo-controlled trial, 51 adults were assigned to receive either racemic BHB mineral salts or placebo (maltodextrin) twice daily, alongside modest caloric restriction. Assessments at baseline and week 8 included dual-energy X-ray absorptiometry for body composition, indirect calorimetry for resting metabolic rate (RMR), and venous blood analyses for cardiometabolic biomarkers (e.g., lipids, HOMA-IR, uric acid, liver enzymes). Results: Body mass decreased in both groups over the intervention (p < 0.01 within placebo and p < 0.001 within BHB). Within the BHB group, fat mass decreased significantly (−2 kg; p < 0.05 vs. baseline), body fat percentage improved (p < 0.01 vs. baseline), and lean-to-fat mass ratio increased (p < 0.05 vs. baseline); no such significant changes were observed within the placebo group. Group × time interactions were not significant for these body composition variables (p > 0.05). Furthermore, lean mass was largely preserved, with no declines in RMR. Within the BHB group, LDL cholesterol was reduced (p < 0.05 vs. baseline), while other lipids, HOMA-IR, and uric acid remained stable, with liver enzymes showing a positive change. Conclusions: Exogenous BHB supplementation may enhance the quality of diet-induced weight loss through within-group improvements in fat mass reduction and lean mass preservation, with no adverse metabolic impacts. Full article

(This article belongs to the Special Issue The Ketogenic Diet: Biochemical Mechanisms and Clinical Applications)

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15 pages, 2346 KB

Open AccessArticle

Effects of Sleeve Gastrectomy on Blood Pressure Reduction in Diet-Induced Obese Hypertensive Rats: A Potential Role of Prouroguanylin

by Naoki Matsuda, Yuichi Yoshida, Koro Gotoh, Satoshi Nagai, Ryo Kurimoto, Kentaro Sada, Takaaki Noguchi, Miho Suzuki, Shotaro Miyamoto, Yoshinori Ozeki, Takashi Ozaki, Akiko Kudo, Takeshi Nakata, Akihiro Fukuda, Takayuki Masaki and Hirotaka Shibata

Nutrients 2025, 17(22), 3581; https://doi.org/10.3390/nu17223581 (registering DOI) - 16 Nov 2025

Abstract

Background/Objectives: Sleeve gastrectomy (SG) is the most commonly performed bariatric surgery worldwide. It results in significant weight loss and improves metabolic disorders such as hypertension. Weight loss is thought to be the main factor contributing to blood pressure (BP) reduction after SG. Small-intestinal [...] Read more.

Background/Objectives: Sleeve gastrectomy (SG) is the most commonly performed bariatric surgery worldwide. It results in significant weight loss and improves metabolic disorders such as hypertension. Weight loss is thought to be the main factor contributing to blood pressure (BP) reduction after SG. Small-intestinal hormones may also mediate the antihypertensive effects of SG. We aimed to investigate the mechanisms underlying the antihypertensive effects of SG through small-intestinal hormones independently of weight loss. Methods: This study involved male Sprague–Dawley rats that underwent a sham operation or SG, followed by a dietary intervention involving a standard diet, a high-fat and high-salt diet, or pair-feeding with SG. Results: Three weeks postoperatively, SG significantly reduced systolic blood pressure (SBP) and increased urinary sodium excretion. RNA sequencing of the small intestine revealed upregulation of the gene encoding prouroguanylin (proUGN). proUGN is a small-intestinal hormone that inhibits renal sodium reabsorption by converting sodium/hydrogen ion exchanger type 3 (NHE3) in the proximal tubules into the inactive phosphorylated form at Ser552 (pS552-NHE3). Furthermore, SG significantly increased proUGN levels in the ileum and plasma, as well as the levels of pS552-NHE3 in the renal cortex. The administration of exogenous uroguanylin, which is converted from proUGN, resulted in increased renal pS552-NHE3, increased urinary sodium excretion, and decreased SBP without body weight reduction. These effects were similar to those observed with SG. Conclusions: SG increases proUGN secretion from the small intestine, leading to increased blood concentration. This inhibits NHE3 activity in the proximal tubules, promotes natriuresis and reduces BP. Full article

(This article belongs to the Special Issue Featured Articles on Nutrition and Obesity Management (3rd Edition))

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Graphical abstract

20 pages, 490 KB

Open AccessArticle

The Association of Unhealthy Eating Behaviors with Sleep Quality Outcomes Among University Students: A Cross-Sectional Study

by Maha Al-Jawarneh, Shalini Chauhan, Ildikó Csölle and Szimonetta Lohner

Nutrients 2025, 17(22), 3580; https://doi.org/10.3390/nu17223580 (registering DOI) - 15 Nov 2025

Abstract

Background: This study examined the association between specific unhealthy eating behaviors and sleep quality among university students. Understanding how dietary habits affect sleep during significant lifestyle transitions associated with university experience can inform health promotion strategies. Methods: A cross-sectional design was [...] Read more.

Background: This study examined the association between specific unhealthy eating behaviors and sleep quality among university students. Understanding how dietary habits affect sleep during significant lifestyle transitions associated with university experience can inform health promotion strategies. Methods: A cross-sectional design was employed using a self-reported questionnaire to assess eating behaviors, timing of meals, and sleep-related behavior among a sample of international university students. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) tool. Statistical analyses were used to assess the relationship between eating patterns, overall sleep quality, and its components. Results: More than half of the students had poor sleep quality (51.7%). Daytime dysfunction was significantly more common in females than in males (27.9% vs. 8.3%, respectively; p < 0.001). Conversely, poor sleep efficiency was more prevalent among males than females (27.5% vs. 15.8%; p = 0.008). Multivariate logistic regression revealed that, compared to students who did not frequently consume heavy evening meals, those who did were more likely to experience poor sleep quality (OR = 2.73, 95% CI: 1.575–4.731). Similarly, those who frequently substitute snacks for main meals were more likely to experience poor sleep quality than those who did not (OR = 2.68, 95% CI: 1.465–4.895). Finally, students who ate within three hours of bedtime had higher odds of poor sleep quality compared to those who had their last meal more than three hours before bedtime (OR = 2.06, 95% CI: 1.173–3.629). Conclusions: Unhealthy dietary habits, such as consuming heavy evening meals, substituting snacks for main meals, and having a short meal-to-bedtime interval, were significantly associated with poor sleep quality. Interventions promoting healthier dietary patterns and appropriate meal timing could help improve sleep in this population. Full article

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

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23 pages, 6248 KB

Open AccessArticle

Radix Rehmanniae Praeparata Extract Enhances Liver Regeneration Through AMPK-Driven Metabolic Reprogramming

by Changmeng Li, Qi Zheng, Fanghong Li, Yinhao Zhang, Shuwen Duan, Jia Liu, Qi Han and Runping Liu

Nutrients 2025, 17(22), 3579; https://doi.org/10.3390/nu17223579 (registering DOI) - 15 Nov 2025

Abstract

Background: Liver regeneration is essential for restoring hepatic mass after injury or resection, with metabolic reprogramming as a critical driver. Radix Rehmanniae Praeparata (RRP), a traditional Chinese medicine for chronic liver diseases, regulates glucose and lipid metabolism. This study evaluated the effects of [...] Read more.

Background: Liver regeneration is essential for restoring hepatic mass after injury or resection, with metabolic reprogramming as a critical driver. Radix Rehmanniae Praeparata (RRP), a traditional Chinese medicine for chronic liver diseases, regulates glucose and lipid metabolism. This study evaluated the effects of RRP on liver regeneration and explored the underlying mechanisms. Methods: A 70% partial hepatectomy (PHx) mouse model was employed, and integrated transcriptomic and metabolomic analyses were conducted to characterize the global features of RRP-induced metabolic reprogramming and its association with hepatocyte proliferation. To further validate these findings, the AML12 hepatocyte cell line and primary mouse hepatocytes were used to identify key targets of RRP. Results: RRP significantly enhanced liver regeneration, as evidenced by the upregulation of hepatocyte proliferation markers. Transcriptomic, metabolomic, and biochemical analyses showed that RRP promoted lipid catabolism and H3K27ac remodeling-dependent hepatocyte proliferation by increasing acetyl-CoA flux. RRP also enhanced carbohydrate consumption and pentose phosphate pathway, as well as protecting mitochondrial integrity, which contribute to both energy production and nucleotide synthesis during cell cycle progression. Notably, RRP-induced AMPK activation was involved in these metabolic reprogramming events, since pharmacological inhibition of AMPK with Compound C attenuated the promotive effects of RRP on liver regeneration. Conclusions: RRP promotes liver regeneration by enhancing metabolic reprogramming mediated by AMPK activation, highlighting its therapeutic potential for metabolic adaptation and postoperative recovery in compromised liver. Full article

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

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18 pages, 362 KB

Open AccessArticle

Implications for Dietary Guideline Policy of a Cultural Adaptation of the US Dietary Guidelines for Women of Mexican Descent: A Pilot Study

by Norma Garfias-Avila, Ching-Yun Wang, Johanna W Lampe, Jason A. Mendoza, Jean De Dieu Tapsoba, Norma J Alcalá, Lisa Levy and Marian L. Neuhouser

Nutrients 2025, 17(22), 3578; https://doi.org/10.3390/nu17223578 (registering DOI) - 15 Nov 2025

Abstract

Background/Objectives: This study aims to evaluate whether the Dietary Guidelines for Americans (DGA) are effective for maintaining a healthy diet among Mexican-descent populations in the US or if a more culturally tailored policy approach is warranted. Methods: As a first outcome, [...] Read more.

Background/Objectives: This study aims to evaluate whether the Dietary Guidelines for Americans (DGA) are effective for maintaining a healthy diet among Mexican-descent populations in the US or if a more culturally tailored policy approach is warranted. Methods: As a first outcome, 20 healthy women of Mexican descent from the Seattle area participated in a pilot randomized controlled trial. They were randomly assigned (10 participants each) to either a group receiving instruction on the standard 2015 DGA or a group receiving an adaptation of the DGA focused on traditional Mexican cuisine and culture. In this 12-week study (with follow-ups at 3 and 6 months), participants’ acceptability of the cultural adaptation of the DGA was compared with that of the standard DGA with end-of-study surveys. Ten blood-based metabolic biomarkers were assessed at baseline and 3 months. Dietary changes at 3 months were assessed with a Food Frequency Questionnaire (FFQ) that was translated into Spanish but not culturally adapted. The secondary outcome was dietary change at 6 months. Results: The primary findings at 3 months showed that serum free fatty acids were reduced for the standard DGA arm. Carbohydrate consumption was reduced in the standard DGA arm only. The end-of-study survey results suggested that both interventions were well received by participants. Conclusions: The preliminary findings from this small sample size suggest that depending on a person’s priorities, either intervention could be offered, with each arm showing slightly different dietary and biomarker outcomes. Full article

(This article belongs to the Special Issue Food Fortification and Nutritional Policies)

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14 pages, 261 KB

Open AccessArticle

Hepatic Steatosis and Diet in Adult Celiac Disease: A Cross-Sectional Study

by Míra Zsófia Peresztegi, Zsolt Szakács, Nelli Farkas, Gábor Szekeres, Nándor Faluhelyi, Krisztina Hagymási, Gyula Pásztor, Zsófia Vereczkei, Petra Fülöp, Szilvia Lada, Sarolta Dakó, Eszter Dakó and Judit Bajor

Nutrients 2025, 17(22), 3577; https://doi.org/10.3390/nu17223577 (registering DOI) - 15 Nov 2025

Abstract

Background: Celiac disease (CD) is a chronic immune-mediated enteropathy that is treated exclusively with a lifelong gluten-free diet (GFD). Hepatic involvement, including hepatic steatosis (HS), is common in both newly diagnosed and long-term GFD-treated CD patients. Limited data exist regarding HS prevalence [...] Read more.

Background: Celiac disease (CD) is a chronic immune-mediated enteropathy that is treated exclusively with a lifelong gluten-free diet (GFD). Hepatic involvement, including hepatic steatosis (HS), is common in both newly diagnosed and long-term GFD-treated CD patients. Limited data exist regarding HS prevalence and risk factors in CD, and the effects of dietary patterns, including GFD and the Mediterranean diet (MD), remain unclear. Objective: This study investigated the prevalence and severity of HS in newly diagnosed, pre-GFD and GFD-treated CD patients compared to non-celiac control subjects, while assessing the influence of dietary adherence. Methods: In a nested cross-sectional study within the ARCTIC trial (NCT05530070), 290 Hungarian adults were enrolled (60 pre-GFD CD, 156 CD on GFD, and 74 control subjects). HS was assessed by ultrasonography, and dietary adherence was evaluated using the Standardized Dietitian Evaluation and Mediterranean Diet Score (MDS). Binary regression models were applied to identify predictors of HS. Results: HS was diagnosed in 34% of participants, most frequently in pre-GFD CD patients. BMI was the strongest predictor of HS both overall and within the CD cohort (OR = 1.27; 95% CI: 1.16, 1.42; p < 0.001). Neither adherence to GFD nor overall MD adherence significantly influenced the prevalence of HS. Severity of HS correlated with higher BMI, older age, and diabetes prevalence, while individual MD components, including olive oil consumption, were associated with milder HS. Conclusions: HS is more prevalent in CD patients, particularly pre-GFD patients, and is strongly associated with BMI. While overall dietary patterns did not significantly impact HS, certain diet components may modulate severity. Full article

(This article belongs to the Special Issue Dietary Patterns, Lipid Metabolism and Fatty Liver Disease)

14 pages, 306 KB

Open AccessArticle

Challenging the Wine Component in Mediterranean Diet Scores: Cognitive Outcomes in Portuguese Adults at High Risk of Dementia

by Andreia Mesquita, Daniela de Sousa, Patrícia Padrão, Ana Rute Costa and Pedro Moreira

Nutrients 2025, 17(22), 3576; https://doi.org/10.3390/nu17223576 (registering DOI) - 15 Nov 2025

Abstract

Introduction: The Mediterranean diet (MD) has been linked to better cognition, but evidence in older adults at high dementia risk is limited. Moreover, the traditional Mediterranean Diet Adherence Screener (MEDAS) counts daily wine consumption as a beneficial component, which may distort genuine diet–cognition [...] Read more.

Introduction: The Mediterranean diet (MD) has been linked to better cognition, but evidence in older adults at high dementia risk is limited. Moreover, the traditional Mediterranean Diet Adherence Screener (MEDAS) counts daily wine consumption as a beneficial component, which may distort genuine diet–cognition relationships. Objective: Evaluate whether MD adherence, as measured with the original MEDAS (MEDAS-O) versus a version that reverses the wine item (MEDAS-R), is associated with cognitive function in Portuguese adults aged 55–85 years at increased dementia risk. Methodology: The sample comprised 75 participants from the NUTRIMIND randomised controlled trial (mean age 70.5 ± 7.0 years). MD adherence was evaluated using the original version of MEDAS (MEDAS-O) and an adapted version with a reverse score in the wine question (MEDAS-R). Cognitive function was assessed via the Montreal Cognitive Assessment (MoCA), Addenbrooke’s Cognitive Examination Revised (ACE-R) and Mini-Mental State Examination (MMSE). Statistical analysis was performed using Analysis of Covariance (ANCOVA) models adjusted for age, sex, BMI, education, and physical activity. Results: MEDAS-R was positively associated with better MMSE performance (p = 0.043) and showed a borderline association with the MoCA (p = 0.051), but not with the ACE-R score (p = 0.356). No association was found between MEDAS-O and cognitive function. Better cognitive scores were more frequently observed among participants with higher education (p < 0.001). Conclusions: Reversing the wine item changes how MEDAS relates to cognitive function. These findings support re-evaluating how wine is scored in MD adherence measures. Full article

(This article belongs to the Special Issue Nutrition and Brain Health Across the Lifespan: Insights into Mental, Cognitive, and Sleep Outcomes in Health and Disease)

21 pages, 376 KB

Open AccessArticle

Evaluating the Impact of Indonesia’s National School Feeding Program (ProGAS) on Children’s Nutrition and Learning Environment: A Mixed-Methods Approach

by Indriya Laras Pramesthi, Luh Ade Ari Wiradnyani, Roselynne Anggraini, Judhiastuty Februhartanty, Wowon Widaryat, Bambang Hadi Waluyo, Agung Tri Wahyunto, Muchtaruddin Mansyur and Umi Fahmida

Nutrients 2025, 17(22), 3575; https://doi.org/10.3390/nu17223575 (registering DOI) - 15 Nov 2025

Abstract

Background: Nutrition problems among primary school children increase the risk of illness, reduce school attendance, and impair academic performance. The Indonesian national school feeding program (ProGAS—Program Gizi Anak Sekolah) was developed to address these issues through the provision of healthy breakfast, nutrition education, [...] Read more.

Background: Nutrition problems among primary school children increase the risk of illness, reduce school attendance, and impair academic performance. The Indonesian national school feeding program (ProGAS—Program Gizi Anak Sekolah) was developed to address these issues through the provision of healthy breakfast, nutrition education, and character building. Methods: This study employed a mixed-methods design involving 454 primary school students aged 8–14 years from 24 schools across four provinces. Data collection included structured questionnaires, 24 h dietary recalls, and anthropometric measurements. In-depth interviews with school principals, teachers, cooking teams, parents, students, nutritionists, and district education office staff were conducted to capture experiences and opinions on the ProGAS implementation. Results: ProGAS significantly improved students’ dietary diversity, meal frequency, handwashing with soap, and nutrition knowledge, alongside a positive trend in school attendance. Improvements included higher mean dietary diversity, increased proportion of students eating ≥3 meals/day, greater correct responses on balanced nutrition, and higher rates of handwashing before meals (all p < 0.01). Children also developed positive behaviors such as praying before meals, queuing, and taking responsibility for cleaning dishes. However, students’ breakfast habits did not significantly improve, the delivery of nutrition education was suboptimal, and no significant changes were observed in nutrient intakes or nutritional status based on BMI-for-age. While the energy and protein contributions of the ProGAS menu met the recommended 25–30% of daily requirements for breakfast, its micronutrient contributions remained below the recommended levels. Key management gaps include the delivery of nutrition education to students and the monitoring of implementation by local and national authorities. Conclusions: ProGAS demonstrated positive impacts on some dietary and hygiene practices as well as learning environment. To achieve greater improvements in breakfast habits, nutrient intake and nutritional status, it is recommended to strengthen the school feeding menus not only for dietary diversity but also for nutrient density, enhance capacity building for teachers, deliver regular and engaging nutrition education, and reinforce program monitoring. Full article

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

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12 pages, 238 KB

Open AccessArticle

Associations Between Frailty, Sarcopenia, and Nutritional Status in Older Adults Living in Nursing Homes

by Serap İncedal Irgat and Gül Kızıltan

Nutrients 2025, 17(22), 3574; https://doi.org/10.3390/nu17223574 (registering DOI) - 15 Nov 2025

Abstract

Background/Objectives: Increasing awareness of factors that put the population at high risk of frailty is essential to prevent frailty and minimize its adverse consequences. Methods: In this cross-sectional study, participants were over the age of 65 and living in nursing homes. The Edmonton [...] Read more.

Background/Objectives: Increasing awareness of factors that put the population at high risk of frailty is essential to prevent frailty and minimize its adverse consequences. Methods: In this cross-sectional study, participants were over the age of 65 and living in nursing homes. The Edmonton Frailty Scale was used to determine frailty, the Sarcopenia Rapid Screening Test (SARC-F) was used to assess sarcopenia, and the Mini Nutritional Assessment (MNA) questionnaire and 7-day 24-h dietary recall were used to determine the nutritional status of the older adult population. Data were analyzed by SPSS 25.0 for Windows (Statistical Package for Social Sciences). Results: The frailty scale score of gender was statistically significant (p < 0.05). There was a statistically significant difference in sarcopenia status and malnutrition based on the distribution of the frailty status among the participants (p < 0.05). There was a statistically significant difference in vitamin C intake adequacy according to the distribution of frailty status among older adults (p < 0.05). There was a positive correlation between frailty status and sarcopenia (r = 0.773; p < 0.05). Frailty and nutritional status were significantly negatively correlated (r = −0.496; p < 0.05). There was a significant positive correlation between the sarcopenia status and malnutrition status of the participants (r = 0.489; p < 0.005). Conclusions: Older adults living in nursing homes are at risk for frailty syndrome, malnutrition, and sarcopenia. Evaluating older adults in terms of all these factors and implementing daily nutrition plans and support according to these results is of great importance for promoting a healthy life. Full article

(This article belongs to the Section Geriatric Nutrition)

22 pages, 419 KB

Open AccessReview

Rethinking Vitamin D Deficiency: Controversies and Practical Guidance for Clinical Management

by Manuel Sosa-Henríquez, Óscar Torregrosa-Suau, María Jesús Gómez de Tejada-Romero, María Jesús Cancelo-Hidalgo, Francisco José Tarazona-Santabalbina, Iñigo Etxebarria-Foronda, Guillermo Martínez Díaz-Guerra and Carmen Valdés-Llorca

Nutrients 2025, 17(22), 3573; https://doi.org/10.3390/nu17223573 (registering DOI) - 15 Nov 2025

Abstract

Vitamin D (VD), due to its hormonal action, plays a crucial role in calcium homeostasis and bone metabolism, and its deficiency has been associated with musculoskeletal disorders such as osteoporosis, fractures, and osteomalacia, as well as a growing attention of chronic conditions and [...] Read more.

Vitamin D (VD), due to its hormonal action, plays a crucial role in calcium homeostasis and bone metabolism, and its deficiency has been associated with musculoskeletal disorders such as osteoporosis, fractures, and osteomalacia, as well as a growing attention of chronic conditions and certain cancers. Despite its physiological relevance and widespread prevalence, particularly among older individuals, patients with chronic diseases, institutionalized populations and pregnant or lactating women, clinical approaches to diagnosing and managing vitamin D deficiency (VDD) remain heterogeneous across guidelines and healthcare settings. This reflects a lack of consensus regarding the benefits and limitations of universal versus selective screening, the definition of adequate serum concentrations, and the clinical indications for supplementation across different patient profiles. This narrative review explores key controversies in the clinical management of VDD, including current perspectives on screening strategies and target populations, indications for empirical supplementation, criteria for biochemical monitoring, and therapeutic goals in bone-related outcomes. In particular, the review discusses the rationale for adopting a 30 ng/mL (75 nmol/L) threshold for adequate serum 25(OH) concentrations in skeletal health, the role of vitamin D and calcium in osteoporosis treatment, and the pharmacological advantages of cholecalciferol compared to other vitamin D compounds. Through a synthesis of available evidence and expert consensus, the review aims to support clinical decision-making in the prevention and treatment of VDD and to identify areas that require further clarification or research. This review aims to support evidence-based clinical decision-making. Full article

(This article belongs to the Special Issue Assessment of Vitamin Deficiency and Benefits of Vitamin Supplementation for Human Health)

22 pages, 1822 KB

Open AccessArticle

by María P. Jarrín-Orozco, María Romo-Vaquero, Concepción Carrascosa, Miriam Pertegal, José Berná, Julio Puigcerver, Adrián Saura-Sanmartín, Isabel Espinosa-Salinas, María García-Nicolás, María Á. Ávila-Gálvez and Juan C. Espín

Nutrients 2025, 17(22), 3572; https://doi.org/10.3390/nu17223572 (registering DOI) - 15 Nov 2025

Abstract

Background/Objectives: Interindividual variability in polyphenol metabolism may help explain the inconsistent effects of polyphenol intake on health outcomes. This study compared, for the first time, (i) polyphenol-related gut microbiota metabotypes (urolithins: UM0, UMA, UMB; equol: EP, ENP; lunularin: LP, LNP) and their [...] Read more.

Background/Objectives: Interindividual variability in polyphenol metabolism may help explain the inconsistent effects of polyphenol intake on health outcomes. This study compared, for the first time, (i) polyphenol-related gut microbiota metabotypes (urolithins: UM0, UMA, UMB; equol: EP, ENP; lunularin: LP, LNP) and their clusters (MCs) in non-medicated premenopausal (Pre-M) and postmenopausal (Post-M) women and (ii) the impact of an 8-week intake of a polyphenol-rich plant extract mixture (PPs) on the quality of life (QoL) of Post-M. Methods: Polyphenol metabotypes were determined in urine via UPLC-QTOF-MS after a 3-day intake of PPs containing resveratrol, pomegranate (ellagitannins and ellagic acid), and red clover (isoflavones) in Pre-M (n = 120) and Post-M (n = 90) women. QoL was assessed with the short-form Cervantes Scale in a randomized, placebo-controlled crossover trial (8-week PPs vs. placebo), completed by 78 Post-M participants. Results: At baseline, Pre-M and Post-M women showed only minor differences in metabotype and MC distributions linked to menopausal status. MC3 (UMA+EP+LP) predominated in Pre-M, while MC7 (UMA+EP+LNP) was most frequent in Post-M. PPs intake in Post-M women led to modest shifts in metabotype and MC distributions toward Pre-M patterns. Quantitative metabolite production was comparable between groups, except for equol, which showed a median 2.8-fold increase after PPs intake in EP Post-M women. Clinically meaningful improvements (score reduction ≥ 6.7 points) in QoL were observed in the Psychic domain in EP women (28%, p = 0.039) and in the Menopause and Health domain, specifically in EP (24.1%, p = 0.004), MC3 (22.5%, p = 0.043), and MC4 (UMB+EP+LP; 41.3%, p = 0.022), were mainly driven by a reduction in hot flashes (p = 0.001). Conclusions: These findings support metabotyping as a tool to guide targeted dietary strategies and enhance QoL through precision health in Post-M women. Full article

(This article belongs to the Special Issue Precision Nutrition: A Personalised Approach to Health and Age Management)

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21 pages, 9555 KB

Open AccessArticle

Rutin as a Circadian Modulator Preserves Skeletal Muscle Mitochondrial Function and Reduces Oxidative Stress to Protect Against D-Galactose-Induced Aging In Vitro and In Vivo

by Yoonha Choi, Suhyeon Lee and Eunju Kim

Nutrients 2025, 17(22), 3571; https://doi.org/10.3390/nu17223571 (registering DOI) - 15 Nov 2025

Abstract

Background: Skeletal muscle aging is characterized by impaired myogenic differentiation, disrupted circadian rhythms, elevated oxidative stress, and mitochondrial dysfunction. Rutin, a natural flavonoid with antioxidant properties, has been suggested to mitigate aging processes; however, its effects on circadian regulation and muscle homeostasis remain [...] Read more.

Background: Skeletal muscle aging is characterized by impaired myogenic differentiation, disrupted circadian rhythms, elevated oxidative stress, and mitochondrial dysfunction. Rutin, a natural flavonoid with antioxidant properties, has been suggested to mitigate aging processes; however, its effects on circadian regulation and muscle homeostasis remain unclear. Methods: In vitro, differentiated C2C12 myotubes were treated with D-galactose (D-gal, 20 g/L) with or without rutin (20 μM). In vivo, C57BL/6 mice were supplemented with rutin (100 mg/kg b.w.) via oral gavage in a D-gal-induced aging mouse model (150 mg/kg b.w., i.p.). Results: D-gal induced cellular senescence, impaired myogenic differentiation, disrupted circadian oscillations, increased oxidative stress, and compromised mitochondrial function. Rutin treatment restored myotube formation, enhanced circadian rhythmicity of differentiation-related genes, and corrected the antiphase patterns of Per2 and Rorc. It also reduced reactive oxygen species and malondialdehyde levels; increased superoxide dismutase, catalase, and glutathione peroxidase activity; improved ATP production and membrane potential; and decreased mitochondrial oxidative aging, as confirmed by pMitoTimer imaging. Furthermore, rutin reinstated the rhythmic expression of oxidative phosphorylation proteins and Pgc1α. In vivo, rutin supplementation enhanced muscle performance (prolonged hanging time) and oxidative capacity, particularly at night (ZT14–ZT16), without altering muscle fiber-type distribution, and normalized circadian rhythmicity of core clock genes. Conclusions: Rutin attenuates D-gal-induced cellular senescence by modulating circadian rhythms, reducing oxidative stress, and improving mitochondrial function. Importantly, its in vivo effects on muscle performance and circadian regulation suggest that rutin is a promising therapeutic strategy to counteract skeletal muscle aging and sarcopenia. Full article

(This article belongs to the Special Issue Role of Bioactive Compounds in Oxidative Stress and Inflammation)

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20 pages, 13781 KB

Open AccessArticle

Longitudinal Microbiome and Metabolome Shifts After Successful Intervention in Impending Stunting in Indonesian Infants

by Conny Tanjung, Ryohei Shibata, Bahrul Fikri, Titis Prawitasari, Andi Alfian Zainuddin, Aidah Juliaty, Dwi Sora Yullyana, Tonny Sundjaya, Hedi Kuswanto, Jessica Clarensia, Naoki Shimojo, Berthold Koletzko, Hiroshi Ohno and Nasrum Massi

Nutrients 2025, 17(22), 3570; https://doi.org/10.3390/nu17223570 - 14 Nov 2025

Abstract

Background/Objectives: Stunting and weight faltering (WF) remain pressing public health challenges in low- and middle-income countries, with long-term consequences for child growth, development, and survival. While the role of gut health in early growth is increasingly recognized, evidence on how the gut [...] Read more.

Background/Objectives: Stunting and weight faltering (WF) remain pressing public health challenges in low- and middle-income countries, with long-term consequences for child growth, development, and survival. While the role of gut health in early growth is increasingly recognized, evidence on how the gut microbiome and metabolome respond to nutritional interventions in WF infants is scarce. This study explored gut microbiome and metabolome changes in Indonesian infants aged 6–12 months who overcame WF following a one-month intervention. Methods: Infants were assigned to either a Nutritional Advice (NA) group or a Nutritional Advice plus Oral Nutritional Supplements (NAONS) group. Stool samples were collected before and after the intervention for microbiome (16S rRNA sequencing) and metabolome (LC-MS) analysis. Results: Significant shifts in gut microbial composition (beta diversity) and species richness (Chao1 index) were observed in both groups, suggesting enhanced microbial diversity and gut resilience. Within-group analysis revealed increases in beneficial genera such as Faecalibacterium and Peptostreptococcus, and a reduction in pro-inflammatory Fusobacterium in the NA group. The NAONS group showed a notable decrease in Proteus, a potentially pathogenic genus. Between-group comparisons indicated higher abundances of Lactococcus and Leuconostoc in the NAONS group, likely reflecting the influence of milk protein-rich supplements on microbial colonization, favoring lactic acid bacteria over SCFA-producing taxa, leading to better gut health. Metabolome analysis revealed significant changes in the NA group, increases in metabolites like Threonine, Tryptophan, and Xylose pointed to improved energy metabolism and gut health, while a decrease in Oxalic Acid suggested better metabolic efficiency. In contrast, the NAONS group, while benefiting from rapid weight gain, displayed a distinct metabolic profile influenced by high milk protein intake. No significant correlations were found between microbiome and metabolome changes, highlighting the complexity of gut-host interactions, suggesting that the interventions led to independent shifts in the aforementioned profiles. Conclusions: Overall, the findings suggest that nutritional interventions may enhance gut health and support recovery from weight faltering, providing insights into strategies that may contribute to restoring healthy growth trajectories and preventing stunting by modulating gut health. Full article

(This article belongs to the Section Pediatric Nutrition)

16 pages, 572 KB

Open AccessArticle

Early Pregnancy Nutritional Adequacy and Subsequent Gestational Diabetes Risk by Body Mass Index: A Prospective Cohort Study of 2227 Korean Women

by Hye-Ji Han, Hyun Jung Lee, Jin Woo Kim, Su Ji Yang, Ju Yeon Kim, Yong Jun Choi, Seoyeon Kim, Nari Kim, Young Ran Kim, Sang Hee Jung, Ji Hyon Jang, Youjeong Hwang, Min Hyoung Kim, Moon Young Kim, Ji Hyae Lim and Hyun Mee Ryu

Nutrients 2025, 17(22), 3569; https://doi.org/10.3390/nu17223569 - 14 Nov 2025

Abstract

Background/Objectives: This study evaluated the association between nutrient intake adequacy during early pregnancy and gestational diabetes mellitus (GDM) risk through a prospective cohort study of Korean pregnant women. Methods: A total of 2227 singleton pregnant women were included in this study. Dietary assessment [...] Read more.

Background/Objectives: This study evaluated the association between nutrient intake adequacy during early pregnancy and gestational diabetes mellitus (GDM) risk through a prospective cohort study of Korean pregnant women. Methods: A total of 2227 singleton pregnant women were included in this study. Dietary assessment was conducted once during early pregnancy enrollment using the 24 h dietary recall method. The collected dietary data were analyzed using the CAN-Pro Korean food composition database to calculate nutrient-specific intake levels. Nutrient Adequacy Ratio (NAR) for each nutrient and Mean Adequacy Ratio (MAR), which integrates individual NARs, were calculated based on intake levels. GDM diagnosis was determined using oral glucose tolerance test (OGTT) results conducted between 24 and 28 weeks of gestation. Relative risk (RR) for each individual nutrient was calculated, and logistic regression analysis was performed to estimate odds ratios (OR) for GDM risk according to MAR quartiles. Results: Among 2227 participants, 157 women developed GDM. Compared to the highest MAR quartile, women in the lowest quartile showed significantly increased GDM risk (OR = 1.82, 95% CI: 1.10–2.99), with the second lowest quartile demonstrating similarly elevated risk (OR = 1.75, 95% CI: 1.06–2.88). Among individual nutrients, inadequate vitamin D intake was associated with the highest GDM risk (RR = 3.84), followed by insufficient intakes of vitamin K (RR = 1.89), vitamin B₆ (RR = 1.62), niacin (RR = 1.54), and calcium (RR = 1.39). Body mass index-stratified analysis revealed that the association between low nutritional adequacy and GDM risk was particularly pronounced in women with BMI ≥ 25.0 kg/m², showing up to a four-fold increased risk in the lowest adequacy groups. Conclusions: These findings suggest that low overall dietary adequacy and nutritional imbalance during early pregnancy are associated with increased GDM risk. The results underscore the importance of ensuring adequate and balanced nutrition during early pregnancy for GDM prevention. Full article

(This article belongs to the Section Nutrition in Women)

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8 pages, 1373 KB

Open AccessBrief Report

A Longitudinal Study of Adolescent Mental Health and Quality of Life as Predictors of College Physical Health, Mental Health, and Gluten-Free Diet Adherence in Celiac Disease

by Tierra L. Mosher, Lilly Jill Su, Javier A. López-Rivera, Ritu Verma, Kate Keenan and Hilary Jericho

Nutrients 2025, 17(22), 3568; https://doi.org/10.3390/nu17223568 (registering DOI) - 14 Nov 2025

Abstract

Background/Objectives: To determine whether adolescent (T1) mental health, quality of life, and adjustment to celiac disease (CeD) are associated with college-age (T2) perceived physical and mental health and gluten-free diet (GFD) adherence. Methods: In 2015, adolescents with CeD (n = 101, T1) [...] Read more.

Background/Objectives: To determine whether adolescent (T1) mental health, quality of life, and adjustment to celiac disease (CeD) are associated with college-age (T2) perceived physical and mental health and gluten-free diet (GFD) adherence. Methods: In 2015, adolescents with CeD (n = 101, T1) completed standardized surveys assessing mental health (CSI-4), quality of life (PedsQL), and adjustment to CeD (CDDUX). Five years later, participants ≥18 years self-reported GFD adherence and physical and mental health perception in college (n = 59, T2). Patients who were current or recent college students that provided complete data at both time points were analyzed (n = 43) using Kendall’s tau to test: concurrent associations among T2 perceived physical/mental health and GFD adherence; and prospective associations between T1 measures and T2 perceived outcomes. Results: Higher T1 CSI-4 and PedsQL scores were negatively correlated with T2 perceived physical health (τ = −0.31, p = 0.02 and τ = −0.28, p = 0.04, respectively). There was trending association between T1 PedsQL and T2 mental health perception (τ = −0.23, p = 0.06). T2 physical and mental health perception were positively correlated (τ = 0.41, p = 0.001). No significant associations emerged between T1 measures and T2 GFD adherence, nor between T2 health perception and GFD adherence, although T2 physical health perception positively trended with GFD adherence (p = 0.78). Conclusions: Adolescents with CeD reporting more depressive symptoms or lower quality of life feel less physically and mentally healthy when in college. In college, feeling physically healthy aligns with feeling mentally healthy, although neither clearly predicts GFD adherence. Early mental health screening in adolescents with CeD may support transitions to independent dietary management. Full article

(This article belongs to the Special Issue Diet on Gut Health and Celiac Disease)

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