Nutrients

8 pages, 802 KB

Open AccessArticle

Using Dose–Response Correlation Re-Analyzing to Distinguish Placebo from Standardized Rose-Hip Powder (Lito) in a Clinical Trial on Osteoarthritis Where Data Initially Looked Identical

by Alzahraa Mahmoud Motawei, Kristian Marstrand Warholm and Kaj Winther

Nutrients 2026, 18(2), 331; https://doi.org/10.3390/nu18020331 (registering DOI) - 20 Jan 2026

Abstract

Background: Large positive responses to placebo are common in clinical trials and pose a major challenge when evaluating different treatments, including new foods. Standard between-group comparisons may fail to detect true effects when placebo improvements are significant. We aimed to demonstrate how a [...] Read more.

Background: Large positive responses to placebo are common in clinical trials and pose a major challenge when evaluating different treatments, including new foods. Standard between-group comparisons may fail to detect true effects when placebo improvements are significant. We aimed to demonstrate how a simple dose–response correlation method can help differentiate genuine positive responses from those experienced with placebo through secondary analysis of a randomized controlled clinical trial of powdered Rosa-canina fruits. Methods: Data were reanalyzed from a multicenter, double-blind, randomized, placebo-controlled trial (N = 120; ClinicalTrials.gov NCT01459939) evaluating the effects of standardized Rosa-canina powder in hip and knee osteoarthritis (OA). Participants received fixed doses, leading to variability in mg/kg exposure due to different body weights. Pearson correlations between dose/kg and changes in WOMAC pain and function at 6 and 12 weeks were calculated separately for the active and placebo groups. Standard between-group comparisons were also performed. Results: Both groups showed significant improvement, over 50%, with no statistically significant differences between them in WOMAC pain or function. However, only the active group, which received a food supplement, exhibited a consistent negative correlation between body weight and symptom improvement at 6 and 12 weeks, suggesting greater benefit with higher dose per kilogram of body weight. No dose–response relationship was observed in the placebo recipients. Therefore, weight-stratified plots revealed an exposure–response gradient in the active group. Conclusions: Dose–response correlation analysis uncovered positive effects of Rosa-canina as a nutrient that were not detectable through standard between-group comparisons. This is consistent with findings from earlier rose-hip research. This low-cost, easy-to-implement method may help distinguish active effects from placebo responses in trials with large nonspecific improvements. Incorporating such analyses could improve the identification of nutrients containing biologically active preparations and support dose selection in future clinical research. Full article

(This article belongs to the Special Issue The Role of Health Benefits of Plant Extracts in Reduction of Rescue Medication)

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19 pages, 1215 KB

Open AccessArticle

Bioinformatic Insights into the Carotenoids’ Role in Gut Microbiota Dynamics

by Helena R. Rocha, Pedro Ribeiro, Pedro Miguel Rodrigues, Ana M. Gomes, Manuela Pintado and Marta C. Coelho

Nutrients 2026, 18(2), 330; https://doi.org/10.3390/nu18020330 (registering DOI) - 20 Jan 2026

Abstract

Background/Objectives: Carotenoids are bioactive pigments with well-established antioxidant and immunomodulatory properties, yet their impact on gut microbiota remains poorly understood from a chemical standpoint. This study explores how carotenoid structure and gastrointestinal stability shape microbial responses combining in vitro fermentation with bioinformatic analyses. [...] Read more.

Background/Objectives: Carotenoids are bioactive pigments with well-established antioxidant and immunomodulatory properties, yet their impact on gut microbiota remains poorly understood from a chemical standpoint. This study explores how carotenoid structure and gastrointestinal stability shape microbial responses combining in vitro fermentation with bioinformatic analyses. Methods: Individual carotenoids (beta (β)-carotene, lutein, lycopene) and combined carotenoids, as well as algal-derived extracts were subjected to 48 h in vitro fermentation, and microbial composition and activity were assessed through sequencing and computational analysis. Results: β-carotene and lycopene promoted acid-tolerant taxa such as Escherichia-Shigella, whereas lutein, due to its higher polarity, supported more transient fluctuations. Mixtures and algal carotenoids exhibited synergistic effects, sustaining beneficial genera including Bifidobacterium and Bacteroides and promoting structured ecological trajectories. Conclusions: These findings provide a chemistry-driven perspective on how carotenoids act as modulators of microbial ecosystems, with direct implications for the formulation of carotenoid-enriched functional foods and dietary interventions. Full article

(This article belongs to the Special Issue Dietary Carotenoids for Human Health)

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20 pages, 5312 KB

Open AccessArticle

Dietary Supplementation with Chrysanthemum morifolium Ramat cv. ‘Hangju’ Flower Extract Alleviates Skin Photoaging in SKH-1 Hairless Mice

by Yujie Lao, Ruixuan Geng, Mengjie Li, Seong-Gook Kang, Kunlun Huang, Bin Deng, Huiji Zhou, Rong Luo and Tao Tong

Nutrients 2026, 18(2), 329; https://doi.org/10.3390/nu18020329 (registering DOI) - 20 Jan 2026

Abstract

Background/Objectives: Skin photoaging represents a predominant form of extrinsic aging, characterized by structural and functional impairment of the skin barrier. In severe cases, it may precipitate dermatological diseases and even tumors. Given the prevalence and detrimental effects of skin photoaging, strategies for its [...] Read more.

Background/Objectives: Skin photoaging represents a predominant form of extrinsic aging, characterized by structural and functional impairment of the skin barrier. In severe cases, it may precipitate dermatological diseases and even tumors. Given the prevalence and detrimental effects of skin photoaging, strategies for its effective prevention and mitigation have garnered significant research interest. Chrysanthemum morifolium Ramat cv. ‘Hangju’ contains diverse bioactive compounds, including flavonoids, phenylpropanoids, phenolic acids, and polysaccharides, which have been proven to exhibit antioxidant and anti-inflammatory effects. Methods: This study employed a UVB-induced mouse model of skin photoaging to evaluate the potential of dietary supplementation with Chrysanthemum morifolium Ramat cv. ‘Hangju’ flower extract (CME) in vivo. Results: In the photoaged skin of female SKH-1 hairless mice, dietary supplementation with CME significantly increased skin moisture content, reduced wrinkle formation, suppressed epidermal hyperplasia, enhanced collagen density, and suppressed the senescence marker expression and DNA damage marker expression. Analysis of the skin transcriptome suggested that CME could alter gene expression patterns and potentially modulate critical signaling pathways involved in skin homeostasis. Moreover, 16S rRNA sequencing indicated that CME mitigated UVB-induced gut microbiota dysbiosis. Conclusions: These preclinical findings reveal the anti-photoaging property of dietary CME supplementation and point to its potential application as a functional dietary supplement for promoting skin health. Full article

(This article belongs to the Special Issue Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases (2nd Edition))

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17 pages, 299 KB

Open AccessReview

Coffee Versus Caffeine as Ergogenic Aids: Biological and Methodological Distinctions with Implications for Exercise Performance and Recovery

by Przemysław Domaszewski

Nutrients 2026, 18(2), 328; https://doi.org/10.3390/nu18020328 (registering DOI) - 20 Jan 2026

Abstract

Background: Caffeine is a well-established ergogenic aid, yet most experimental evidence is based on isolated caffeine, whereas habitual intake in both the general and physically active populations occurs mainly through coffee. This gap between experimental models and everyday practice complicates the interpretation [...] Read more.

Background: Caffeine is a well-established ergogenic aid, yet most experimental evidence is based on isolated caffeine, whereas habitual intake in both the general and physically active populations occurs mainly through coffee. This gap between experimental models and everyday practice complicates the interpretation of existing findings. Objective: This review compares coffee and isolated caffeine as ergogenic aids, focusing on biological mechanisms, methodological differences, tolerability, and context-dependent use in sport and exercise. Methods: A narrative review of human studies examining the effects of coffee and isolated caffeine on exercise performance, fatigue, and post-exercise recovery was conducted, with attention being paid to dosing accuracy, bioavailability, inter-individual variability, and the influence of the coffee matrix. Results: Isolated caffeine consistently improves performance under controlled conditions. Coffee can produce similar ergogenic effects, particularly in endurance exercise, although responses are more variable due to differences in caffeine content and individual sensitivity. Emerging evidence suggests that coffee, especially when consumed with carbohydrates, may support post-exercise glycogen resynthesis. Coffee also appears to be better tolerated by many individuals and provides additional bioactive compounds with antioxidant and anti-inflammatory properties. Conclusions: Coffee and isolated caffeine should not be viewed as interchangeable ergogenic strategies. While isolated caffeine remains useful in experimental settings, coffee represents a more ecologically relevant and potentially safer source of caffeine in applied practice. Further direct comparative studies are needed to clarify their context-specific roles. Full article

(This article belongs to the Section Sports Nutrition)

16 pages, 421 KB

Open AccessArticle

Dietary Patterns During Weight Loss Maintenance vs. Weight Regain: A Secondary Analysis of the Look AHEAD Trial

by Mary Catherine Prater, Frank L. Greenway and Ursula White

Nutrients 2026, 18(2), 327; https://doi.org/10.3390/nu18020327 - 20 Jan 2026

Abstract

Background/Objectives: Limited information exists on how dietary patterns change in adults who experience weight regain vs. those who maintain weight loss after lifestyle interventions. Methods: Five hundred fifty-two adults (60 ± 1.0 years, 33.8 ± 0.4 kg/m²) with type [...] Read more.

Background/Objectives: Limited information exists on how dietary patterns change in adults who experience weight regain vs. those who maintain weight loss after lifestyle interventions. Methods: Five hundred fifty-two adults (60 ± 1.0 years, 33.8 ± 0.4 kg/m²) with type 2 diabetes mellitus from the Look AHEAD Trial achieved ≥ 7% weight loss after Year 1, completed follow-up visits through Year 4, and provided three 134-item food frequency questionnaires. Weight “regain” (WLR) was defined as regaining ≥ 50% of the initial weight lost. Dietary patterns were determined using established DASH diet scores (scale: 0–9) and principal component analysis (PCA; higher scores = more adherent). Repeated measures linear mixed models assessed group and sex differences in dietary patterns. Results: Dietary patterns were similar between groups during weight loss (baseline to Year 1). WLR DASH scores decreased more from Year 1 to Year 4 compared to “maintain” (WLM) (WLR: Y1: 5.66 ± 0.14, Y4: 4.60 ± 0.14; WLM: Y1: 5.49 ± 0.13, Y4: 4.92 ± 0.13; difference-p < 0.01). Of the two PCA-derived dietary patterns, Pattern 1 (vegetable, fruit, and fish) decreased more in WLR (WLR: Y1: 0.12 ± 0.16, Y4: −0.14 ± 0.16, WLM: Y1: 0.06 ± 0.14, Y4: 0.25 ± 0.15; difference-p < 0.01), while Pattern 2 (low-fiber grains and high-fat animal proteins) increased in WLR (WLR: Y1: 0.40 ± 0.11, Y4: 0.61 ± 0.11, WLM: Y1: 0.34 ± 0.10, Y4: 0.21 ± 0.10, difference-p < 0.01). Sex differences showed that only WLR women and WLM men increased sweets from Y1 to Y4 (WLR women Y1: 0.26 ± 0.04, Y4: 0.41 ± 0.04; p < 0.01; WLM men: Y1: 0.23 ± 0.04, Y4: 0.38 ± 0.04; p < 0.01). Conclusions: These data demonstrate that differences in dietary patterns between WLR and WLM emerge after the initial weight loss intervention with some sex differences. This suggests that longer-term shifts in dietary patterns after lifestyle interventions may influence weight loss maintenance. Full article

(This article belongs to the Section Nutrition and Obesity)

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13 pages, 2331 KB

Open AccessArticle

Vitamin D Status in Rheumatology Patients with Inflammatory Compared with Non-Inflammatory Diagnoses: Inflammatory and Autoimmune Markers Are Not Associated with Vitamin D Levels

by Arne Schäfer, Magdolna Szilvia Kovacs, Axel Nigg and Martin Feuchtenberger

Nutrients 2026, 18(2), 326; https://doi.org/10.3390/nu18020326 - 20 Jan 2026

Abstract

Background/Objectives: Vitamin D levels tend to be lower in patients with inflammatory rheumatic diseases (IRDs), including rheumatoid arthritis (RA), but there are minimal data on vitamin D levels in rheumatology patients with inflammatory vs. non-inflammatory diagnoses. Methods: In this retrospective, observational study, we [...] Read more.

Background/Objectives: Vitamin D levels tend to be lower in patients with inflammatory rheumatic diseases (IRDs), including rheumatoid arthritis (RA), but there are minimal data on vitamin D levels in rheumatology patients with inflammatory vs. non-inflammatory diagnoses. Methods: In this retrospective, observational study, we used electronic health record data from patients presenting for their first visit at a large rheumatology clinic to assess vitamin D levels and deficiency based on diagnosis, and to evaluate the association between vitamin D and inflammatory markers (including C-reactive protein [CRP]) or autoimmune markers (including rheumatoid factor [RF], anti-citrullinated peptide antibody, and anti-nuclear antibodies). Logistic regression analysis with 13 clinical variables was used to evaluate the association between vitamin D levels and IRD diagnosis, and linear regression was used to evaluate the association between vitamin D levels and CRP or RF. Results: The patient cohort included 4979 patients; 1385 (27.8%) had an IRD. Vitamin D levels were significantly lower in the IRD vs. non-inflammatory subgroup (mean [SD] of 26.6 [13.3] vs. 27.7 [14.3]; p = 0.009), but the difference was not clinically relevant given the small effect size. Vitamin D deficiency rates (<20 ng/mL) were not significantly different between the subgroups, and vitamin D was not associated with an IRD diagnosis in logistic regression analysis. In linear regression analysis, vitamin D was not associated with CRP or RF in the full patient cohort or in the subgroup with RA (n = 539). Conclusions: We conclude that vitamin D levels do not differ substantially based on IRD versus non-inflammatory diagnosis, CRP levels, or RF levels in this clinical cohort. Full article

(This article belongs to the Special Issue Prevalence and Risk Factors of Vitamin D Deficiency)

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14 pages, 390 KB

Open AccessArticle

The Impact of Malnutrition Risk and Perioperative Complications in Gastrointestinal Cancer Patients Undergoing Elective Major Surgery: A Prospective Observational Multicenter Study

by Manuel Durán-Poveda, Gil Rodríguez Caravaca, Alejandro Suárez-de-la-Rica, Diego Rodríguez Villar, Andrés Sánchez Pernaute, Emilia Cancer Minchot, Julia Ocón Bretón, Tamara Díaz-Vico and Brezo Martínez-Amores

Nutrients 2026, 18(2), 325; https://doi.org/10.3390/nu18020325 - 20 Jan 2026

Abstract

Background/Objectives: The study aimed to characterize perioperative complications and their relationship with nutritional risk in gastrointestinal cancer patients undergoing surgical treatment. Methods: An observational, prospective, and multicenter study was carried out in 469 patients with gastrointestinal malignancies undergoing elective major abdominal surgical procedures [...] Read more.

Background/Objectives: The study aimed to characterize perioperative complications and their relationship with nutritional risk in gastrointestinal cancer patients undergoing surgical treatment. Methods: An observational, prospective, and multicenter study was carried out in 469 patients with gastrointestinal malignancies undergoing elective major abdominal surgical procedures in public hospitals throughout Spain. Complications developed during hospitalization and at 30 days after surgery were recorded, and the patients’ nutritional status was evaluated using the MUST screening tool. Results: Colorectal and gastric cancer were the most common tumors. Complications during hospitalization occurred in 146 patients (rate 31.1%). Infections accounted for 68.5% of complications, in particular surgical site infections (SSIs), followed by paralytic ileus (40.4%). At 30 days, the complication rate was 9%, with infections as the most common events. In patients with severe nutritional risk at discharge (MUST score ≥ 2), the percentage of patients with complications was 24.7% as compared to 9.2% in patients without complications (p < 0.0001). Conclusions: Clinicians should be aware of the high frequency of SSIs and that complications are higher among patients with severe nutritional risk. These findings emphasize the need for routine nutritional screening and targeted perioperative support in cancer patients undergoing gastrointestinal cancer surgery. Full article

(This article belongs to the Special Issue Dietary and Nutritional Guidelines for Cancer Patient)

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13 pages, 1607 KB

Open AccessArticle

A Comparison of Marine and Non-Marine Magnesium Sources for Bioavailability and Modulation of TRPM6/TRPM7 Gene Expression in a Caco-2 Epithelial Cell Model

by Olusoji A. Demehin, Michelle Ryan, Tommy Higgins, Breno Moura Motta, Tim Jähnichen and Shane O’Connell

Nutrients 2026, 18(2), 324; https://doi.org/10.3390/nu18020324 - 20 Jan 2026

Abstract

Background/Objectives: Magnesium (Mg²⁺) supplements can contain different types of Mg²⁺ salts, which influence their bioavailability. A highly bioavailable and bioaccessible Mg²⁺ source is essential to meet requirements for many physiological processes that are fundamental to human health. The objective [...] Read more.

Background/Objectives: Magnesium (Mg²⁺) supplements can contain different types of Mg²⁺ salts, which influence their bioavailability. A highly bioavailable and bioaccessible Mg²⁺ source is essential to meet requirements for many physiological processes that are fundamental to human health. The objective of this study was to compare the bioavailability of Mg²⁺ from different sources, with different composition and chemical structure, namely, Aquamin Mg Soluble (seawater), magnesium oxide, commercial magnesium bisglycinate 1, and analytical grade magnesium bisglycinate 2. In addition, the influence of the different Mg²⁺ sources on transported Mg²⁺ and expression of TRPM6 and TRPM7 genes in Caco-2 cell monolayers was also evaluated to estimate bioavailability. TRPM6 and TRPM7 are members of the transient receptor potential melastatin subfamily characterized as Mg²⁺ permeable channels. Method: The study involved analyzing bioavailability of the Mg²⁺ sources predigested with and without food using the Infogest model prior to application to a Caco-2 cell monolayer in transwells for assessing transport. Mg²⁺ concentration on the basolateral side was analyzed by ICP-MS, and expression of TRPM6 and TRPM7 genes in the monolayer was analyzed using real-time qPCR. Results: Aquamin Mg Soluble showed significantly higher bioavailability compared to magnesium bisglycinate 2 (p = 0.016) when digested with food prior to application to the Caco-2 monolayer. In the digestion without food prior to the Caco-2 monolayer, there was no significant difference between Mg²⁺ bioavailability among the tested supplements. The TRPM6 gene was significantly downregulated in Caco-2 monolayers exposed to Aquamin Mg Soluble compared to untreated Caco-2 cells (p < 0.001). Conclusions: The INFOGEST digestion model showed that Aquamin Mg Soluble provides a highly bioavailable form of Mg²⁺, while the Caco-2 monolayer model also demonstrated its increased bioavailability by the modulation of TRPM6 gene expression. Full article

(This article belongs to the Special Issue Magnesium in Aging, Health and Diseases)

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14 pages, 1306 KB

Open AccessArticle

A Molecular and Functional Investigation of the Anabolic Effect of an Essential Amino Acids’ Blend Which Is Active In Vitro in Supporting Muscle Function

by Lorenza d’Adduzio, Melissa Fanzaga, Maria Silvia Musco, Marta Sindaco, Paolo D’Incecco, Giovanna Boschin, Carlotta Bollati and Carmen Lammi

Nutrients 2026, 18(2), 323; https://doi.org/10.3390/nu18020323 - 20 Jan 2026

Abstract

Background/Objectives: Essential amino acids’ (EAAs) biological effects depend on both gastrointestinal stability and intestinal bioavailability. A commercially available EAA blend has previously shown to be highly bioaccessible and able to inhibit the DPP-IV enzyme both directly and at a cellular level following [...] Read more.

Background/Objectives: Essential amino acids’ (EAAs) biological effects depend on both gastrointestinal stability and intestinal bioavailability. A commercially available EAA blend has previously shown to be highly bioaccessible and able to inhibit the DPP-IV enzyme both directly and at a cellular level following simulated digestion in vitro. In light with this consideration, the present study aimed to evaluate the intestinal in vitro bioavailability of GAF subjected to INFOGEST digestion (iGAF) and to investigate the metabolic effects of its bioavailable fraction on muscle cells using an integrated Caco-2/C2C12 co-culture model. Methods: Differentiated Caco-2 cell lines were treated with iGAF, and amino acid transport was quantified by ion-exchange chromatography. The basolateral fraction containing bioavailable EAAs was used to treat differentiated C2C12 myotubes for 24 h. Western blot analyses were performed to assess the activation of anabolic and metabolic pathways, including mTOR, Akt, GSK3, AMPK and GLUT-4. Results: More than 50% of each EAA present in iGAF crossed the Caco-2 monolayer, with BCAAs and phenylalanine particularly enriched in the basolateral fraction. Exposure of C2C12 myotubes to the bioavailable iGAF stimulated mTORC1 activation and increased the phosphorylation of Akt and GSK3, indicating an enhanced anabolic response. At a cellular level, iGAF also elevated the p-AMPK/AMPK ratio, suggesting activation of energy-sensing pathways. Moreover, GLUT4 protein levels and glucose uptake were significantly increased. Conclusions: The study focuses exclusively on a cellular model, and results suggested that iGAF is highly bioavailable in vitro and that its absorbed fraction activates key anabolic and metabolic pathways of skeletal muscle cells, enhancing both protein synthesis signaling and glucose utilization in vitro. Full article

(This article belongs to the Section Proteins and Amino Acids)

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19 pages, 2280 KB

Open AccessArticle

Maternal Protein Restriction and Branched-Chain Amino Acid Supplementation Differentially Affect Maternal Energy Balance and Impair Offspring Growth

by Daniela Redrovan, Souvik Patra, Md Tareq Aziz, Matthew W. Gorton, Emily A. Chavez, Scott Frederiksen, Joshua Rowe, Adel Pezeshki and Prasanth K. Chelikani

Nutrients 2026, 18(2), 322; https://doi.org/10.3390/nu18020322 - 20 Jan 2026

Abstract

Background: The increasing prevalence of low-birth-weight (LBW) offspring from obese mothers underscores the need for dietary strategies to mitigate the transgenerational propagation of metabolic diseases. Objectives: We determined whether dietary protein restriction under obesogenic conditions altered maternal energy balance and led to LBW [...] Read more.

Background: The increasing prevalence of low-birth-weight (LBW) offspring from obese mothers underscores the need for dietary strategies to mitigate the transgenerational propagation of metabolic diseases. Objectives: We determined whether dietary protein restriction under obesogenic conditions altered maternal energy balance and led to LBW offspring and whether branched-chain amino acid (BCAA) supplementation improved maternal energy balance and mitigated weight and craniofacial skeletal deficits in offspring. Methods: High-fat-fed obese pregnant Sprague Dawley rats (~8–10 weeks of age, n = 8–11/group) were randomized in study 1 to control high-fat diet (20% protein; HFD), low-protein diet (LP; 5% protein), and LP + BCAA diet (100% BCAA requirements) and in study 2 to control HFD (20% protein), LP (10% protein), and LP + 2BCAA diet (200% BCAA requirements). Post-weaning offspring were fed HFD until 8 weeks of age. Results: Protein restriction promoted hyperphagia and energy expenditure, whereas BCAA supplementation attenuated such hyperphagic effects in pregnancy but not in lactation. Protein restriction reduced maternal body weight in lactation, and although BCAA supplementation did not reverse the weight loss, it enhanced insulin sensitivity and paradoxically reduced offspring survival. Maternal protein restriction reduced offspring body weight and craniofacial bone growth that persisted into adulthood, but BCAA supplementation did not rescue such deficits. Conclusions: Maternal protein restriction in obese dams enhanced maternal energy expenditure but impaired offspring growth and development. Although BCAA supplementation improved maternal energy balance, it was insufficient to reverse the adverse effects of maternal protein restriction on offspring growth under obesogenic conditions. Full article

(This article belongs to the Topic Maternal Nutrition from Preconception, Through Pregnancy and Lactation)

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33 pages, 798 KB

Open AccessReview

Gut Microbiota and Short-Chain Fatty Acids in Cardiometabolic HFpEF: Mechanistic Pathways and Nutritional Therapeutic Perspectives

by Antonio Vacca, Gabriele Brosolo, Stefano Marcante, Sabrina Della Mora, Luca Bulfone, Andrea Da Porto, Claudio Pagano, Cristiana Catena and Leonardo A. Sechi

Nutrients 2026, 18(2), 321; https://doi.org/10.3390/nu18020321 - 20 Jan 2026

Abstract

Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of the cases of HF worldwide. Among the different phenotypes, cardiometabolic HFpEF has the highest prevalence. Cumulative insults related to cardiometabolic comorbidities—obesity, hypertension and type 2 diabetes—create a milieu of metabolic [...] Read more.

Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of the cases of HF worldwide. Among the different phenotypes, cardiometabolic HFpEF has the highest prevalence. Cumulative insults related to cardiometabolic comorbidities—obesity, hypertension and type 2 diabetes—create a milieu of metabolic derangements, low-grade systemic inflammation (i.e., metainflammation), endothelial dysfunction, and coronary microvascular disease. Emerging data indicate that the gut–heart axis is a potential amplifier of this process. Cardiometabolic comorbidities promote gut dysbiosis, loss of short-chain fatty acid (SCFA)-producing taxa, and disruption of the intestinal barrier, leading to endotoxemia and upregulation of pro-inflammatory pathways such as TLR4- and NLRP3-mediated signaling. Concomitantly, beneficial gut-derived metabolites (acetate, propionate, butyrate) decrease, while detrimental metabolites increase (e.g., TMAO), potentially fostering myocardial fibrosis, diastolic dysfunction, and adverse remodeling. SCFAs—acetate, propionate, and butyrate—may exert pleiotropic actions that directly target HFpEF pathophysiology: they may provide a CPT1-independent energy substrate to the failing myocardium, may improve lipid and glucose homeostasis via G protein-coupled receptors and AMPK activation, and may contribute to lower blood pressure and sympathetic tone, reinforce gut barrier integrity, and act as anti-inflammatory and epigenetic modulators through the inhibition of NF-κB, NLRP3, and histone deacetylases. This review summarizes current evidence linking gut microbiota dysfunction to cardiometabolic HFpEF, elucidates the mechanistic role of SCFAs, and discusses nutritional approaches aimed at enhancing their production and activity. Targeting gut–heart axis and SCFAs pathways may represent a biologically plausible and low-risk approach that could help attenuate inflammation and metabolic dysfunctions in patients with cardiometabolic HFpEF, offering novel potential therapeutic targets for their management. Full article

(This article belongs to the Section Clinical Nutrition)

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4 pages, 153 KB

Open AccessEditorial

Towards Precision and Balance in Selenium Nutrition: From Innovation to Application

by Jiaqiang Huang and Kongdi Zhu

Nutrients 2026, 18(2), 320; https://doi.org/10.3390/nu18020320 - 20 Jan 2026

Abstract

Selenium (Se) is an essential trace element for human health, primarily functioning through its incorporation into selenoproteins, which play critical roles in antioxidant defense, immune regulation, and thyroid hormone metabolism [...] Full article

(This article belongs to the Special Issue Selenium-Rich Products: Their Development and Regulation of Human Health)

19 pages, 4111 KB

Open AccessArticle

The Effects of Chinese Dwarf Cherry (Cerasus humilis) Kernel Oil on Defecation and the Gut Microbiota in Constipated Mice

by Jingyu Gao, Yumin Dai, Zhe Liang, Nan Chen, Xilong Li, Xin Wen, Yuanying Ni and Mo Li

Nutrients 2026, 18(2), 319; https://doi.org/10.3390/nu18020319 - 19 Jan 2026

Abstract

Background: The Chinese dwarf cherry (CDC) has been valued for over 2000 years for its medicinal and nutritional properties, particularly its kernels. Despite its recognition as a rich source of oil, the potential health benefits of CDC kernel oil remain unclear. Method: Initially, [...] Read more.

Background: The Chinese dwarf cherry (CDC) has been valued for over 2000 years for its medicinal and nutritional properties, particularly its kernels. Despite its recognition as a rich source of oil, the potential health benefits of CDC kernel oil remain unclear. Method: Initially, we evaluated the preventive effectiveness of CDC in a mouse model of constipation induced by loperamide. Results: The findings indicated that CDC kernel oil alleviated constipation by reducing the first black fecal defecation time and increasing the fecal number, wet weight, water content and gastrointestinal transit rate in model mice. Additionally, CDC kernel oil reduced inhibitory neurotransmitters and increased excitability neurotransmitters, two anti-oxidases’ activity and fecal short-chain fatty acid (SCFA) content. Histological analysis revealed an improved mucus cell morphology in the intestinal tract. Furthermore, CDC kernel oil increased the abundance of some beneficial bacteria. It was identified that the gut microbiota was associated with neurotransmitters, mediators of inflammation and SCFAs. Conclusion: The findings offer a scientific foundation for considering CDC kernel oil as a potential functional food for the alleviation of constipation. Full article

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

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15 pages, 1806 KB

Open AccessArticle

Inverse Associations of Acetic Acid Intake with Carbohydrate, Sugar, and Saturated Fat Intakes Among Japanese Adults Aged 20 to 69 Years

by Risako Yamamoto-Wada, Joto Yoshimoto, Yoshino Kodaira, Kanako Deguchi, Yuto Aoki, Mikiya Kishi and Katsumi Iizuka

Nutrients 2026, 18(2), 318; https://doi.org/10.3390/nu18020318 - 19 Jan 2026

Abstract

Background: Acetic acid has been suggested to have health benefits. Our previous exploratory study linked acetic acid intake to higher protein and vitamin consumption, but relationships with age and sex remained unclear. Objective: This study examined associations between acetic acid intake, age, and [...] Read more.

Background: Acetic acid has been suggested to have health benefits. Our previous exploratory study linked acetic acid intake to higher protein and vitamin consumption, but relationships with age and sex remained unclear. Objective: This study examined associations between acetic acid intake, age, and sex, and explored nutrient correlates after adjusting for age, sex, and energy intake. Methods: Dietary data from 12,074 Japanese adults aged 20–69 years, collected via the Asken food-tracking app, were analyzed. Two-way ANOVA assessed effects of age, sex, and their interaction on acetic acid intake. Multiple linear regressions examined associations between acetic acid intake and nutrient intakes. Model 1 adjusted for age and sex; Model 2 additionally adjusted for total energy intake. Results: Participants included 3038 men (47.8 ± 11.9 y) and 9036 women (42.4 ± 11.8 y). Acetic acid intake was higher among men and older participants (sex: F = 11.0, p < 0.001; age: F = 9.1, p < 0.001). In Model 1, acetic acid intake correlated positively with most nutrients. After adjusting for energy (Model 2), negative associations were found with carbohydrates, sugars, starches, saturated fat, and butyric acid (all p < 0.05). Conclusions: Individuals with higher acetic acid intake tended to consume fewer carbohydrates and saturated fats, even at equivalent energy intake. These findings suggest that acetic acid-containing diets may reduce the intake of starches and saturated fatty acids, potentially contributing to obesity prevention. Full article

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

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18 pages, 2772 KB

Open AccessReview

Dietary (−)-Epigallocatechin Gallate (EGCG): State-of-the-Art Advances in Bioactivities, Bioavailability Enhancement Strategies, and Applications in Nutrition and Health

by Li Niu, Yisi Luo, Weiwen Xie, Chao Wang and Zhonghua Liu

Nutrients 2026, 18(2), 317; https://doi.org/10.3390/nu18020317 - 19 Jan 2026

Abstract

(−)-Epigallocatechin gallate (EGCG), a major polyphenolic compound in tea leaves, exhibits potent antioxidant, anti-inflammatory, and anticancer properties. Despite its therapeutic potential, poor bioavailability limits clinical efficacy. This review comprehensively examines the sources, and multifunctional bioactivities of EGCG, including its antioxidant, anti-inflammatory, anticancer, cardiovascular [...] Read more.

(−)-Epigallocatechin gallate (EGCG), a major polyphenolic compound in tea leaves, exhibits potent antioxidant, anti-inflammatory, and anticancer properties. Despite its therapeutic potential, poor bioavailability limits clinical efficacy. This review comprehensively examines the sources, and multifunctional bioactivities of EGCG, including its antioxidant, anti-inflammatory, anticancer, cardiovascular protective, metabolic regulatory, neuroprotective, gut microbiota-modulating, and antimicrobial properties. Traditional and emerging applications of EGCG are summarized from different perspectives. Strategies to enhance bioavailability such as nanotechnology, chemical modification, and combination drug regimens are highlighted. Based on existing human clinical trials, recommendations for effective and safe dosage ranges of EGCG intake are provided. By analyzing the current situation, providing reasonable opinions and making outlooks, the clinical value of EGCG will be fully released, which will ultimately promote human health. Full article

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

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20 pages, 775 KB

Open AccessFeature PaperArticle

Healthful Plant-Based Diets and Cognitive Function in Older Adults: Mediation by Nutritional Status and Modification by Urban–Suburban Location and Gender in a Shanghai Community-Based Study

by Zishuo Huang, Gonghang Qiu, Borui Yang, Ye Shao, Shuna Lin, Huimin Zhou, Liang Sun and Ying Wang

Nutrients 2026, 18(2), 316; https://doi.org/10.3390/nu18020316 - 19 Jan 2026

Abstract

Background and aims: Amid global aging, the role of diet in cognitive health is crucial. The healthful plant-based diet index (hPDI) is linked to cardiometabolic benefits, but its association with cognitive function in older adults, particularly through nutritional status and across different socio-geographic [...] Read more.

Background and aims: Amid global aging, the role of diet in cognitive health is crucial. The healthful plant-based diet index (hPDI) is linked to cardiometabolic benefits, but its association with cognitive function in older adults, particularly through nutritional status and across different socio-geographic contexts, remains unclear. This study investigated the association between hPDI and multidimensional cognitive function, the mediating role of nutritional status, and potential associated modifications by urban–suburban location and gender. Methods: A community-based cross-sectional study was conducted in Shanghai, China, involving 2079 older adults (aged ≥60). Dietary intake was assessed by a validated food frequency questionnaire (FFQ) to calculate hPDI. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment-Basic (MoCA-B), and Clinical Dementia Rating (CDR). Nutritional status was measured by the Mini Nutritional Assessment (MNA). Hierarchical regression, interaction, and mediation analyses were performed, adjusting for comprehensive covariates based on social determinants of health (SDoH). Results: Higher hPDI was significantly associated with better cognitive scores (MMSE: β = 0.083, p < 0.001; MoCA-B: β = 0.069, p < 0.001) and lower odds of worse CDR (OR = 0.944, p < 0.001) in fully adjusted models. In the cross-sectional mediation analysis, MNA statistically mediated a significant proportion of the observed associations (MMSE: 41.25%; MoCA-B: 53.68%; CDR: 38.98%). The protective association was consistent across urban and suburban areas. However, a significant three-way interaction (hPDI × Gender × Area, p < 0.01) was found, with no cognitive benefit observed for males in suburban areas. Conclusions: Adherence to a healthful plant-based diet is associated with better cognitive function in older adults, partly statistically mediated by improved nutritional status. While this association is geographically equitable in Shanghai, suburban males do not appear to benefit, highlighting the need for gender- and context-sensitive dietary interventions. Full article

(This article belongs to the Section Geriatric Nutrition)

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24 pages, 5453 KB

Open AccessArticle

Neuroprotective Effects of Desert Milk Exosomes in LPS-Induced Cognitive Decline: Role of Microglial M2 Polarization and AMPK Signaling

by Yujie Li, Wei Lu, Wentao Qian, Xinyuan Liao, Pengjie Wang, Yi Wang, Wenya Jiao, Menghui Wang, Jingru Zhao, Jinhui Yang, Haina Gao and Hongliang Li

Nutrients 2026, 18(2), 315; https://doi.org/10.3390/nu18020315 - 19 Jan 2026

Abstract

Background/Objectives: Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes, as bioactive extracellular vesicles, have underexplored potential in regulating brain neuroinflammatory responses. This study aimed to characterize desert milk exosomes (D-Exo) and investigate their neuroprotective and anti-neuroinflammatory effects in [...] Read more.

Background/Objectives: Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes, as bioactive extracellular vesicles, have underexplored potential in regulating brain neuroinflammatory responses. This study aimed to characterize desert milk exosomes (D-Exo) and investigate their neuroprotective and anti-neuroinflammatory effects in LPS-induced HNF mice model and an LPS-stimulated BV2 microglia. Methods: Exosomes were isolated from desert and non-desert milk (ND-Exo) for proteomic analysis. After pretreating BV2 cells with exosomes and stimulating with LPS, their inflammatory responses and polarization were assessed by RT-PCR. Balb/c mice were orally gavaged with D-Exo or 0.9% NaCl for 28 days before LPS injection. Cognitive function was assessed via behavioral tests, with microglial/astrocyte activation analyzed by immunofluorescence. Results: D-Exo exhibited superior stability and a unique proteomic profile enriched with proteins linked to neuroinflammation and blood-brain barrier (BBB) integrity, notably within the AMPK signaling pathway. In vitro, D-Exo shifted LPS-stimulated microglia from the M1 to the M2 phenotype. In vivo, it alleviated HNF and cognitive decline, reduced Aβ_1-42 and Tau deposition, elevated BDNF and MAP2, and suppressed neuroinflammation and glial activation. Conclusions: D-Exo is enriched with specific proteins, attenuates neuroinflammation and cognitive decline by regulating microglial M1/M2 polarization and AMPK pathway, highlighting its preventive potential. Full article

(This article belongs to the Special Issue Animal-Originated Food and Food Compounds in Health and Disease)

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20 pages, 1108 KB

Open AccessArticle

Variability in the Composition and Antioxidant Status of Milk of Polish Women Breastfeeding up to 2 Years

by Agnieszka Chrustek, Elena Sinkiewicz-Darol, Katarzyna Łubiech, Dorota Olszewska-Słonina and Agnieszka Dombrowska-Pali

Nutrients 2026, 18(2), 314; https://doi.org/10.3390/nu18020314 - 19 Jan 2026

Abstract

Background/Objectives: Breastfeeding has accompanied women since the beginning of time and, according to anthropological research, naturally ends between the age of 2 and 6. WHO (World Health Organization) recommends exclusive breastfeeding for about the first 6 months, with continued breastfeeding along with introducing [...] Read more.

Background/Objectives: Breastfeeding has accompanied women since the beginning of time and, according to anthropological research, naturally ends between the age of 2 and 6. WHO (World Health Organization) recommends exclusive breastfeeding for about the first 6 months, with continued breastfeeding along with introducing appropriate complementary foods for up to 2 years of age or longer. Despite the increasing promotion of breastfeeding, women do not comply with the WHO guidelines and give up exclusive breastfeeding quickly, and long-term breastfeeding mothers still struggle with a lack of understanding in society. Methods: This work aims to expand the knowledge on the composition and antioxidant status of the milk of mothers breastfeeding past 12 months. Results: The basic composition of human milk changes depending on the stage of lactation. In women breastfeeding for more than a year, an increase in fat (p < 0.001) and magnesium (p < 0.001) was observed. A decreased concentration of leptin (p = 0.001), iron (p < 0.001), and iron-reducing capacity (p < 0.001) was also observed compared to milk from the initial stage of lactation. Conclusions: The milk of women breastfeeding for more than 12 months is a valuable food for the baby, maintaining its protection against free radicals and providing adequate nutrients. Full article

(This article belongs to the Section Pediatric Nutrition)

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22 pages, 435 KB

Open AccessReview

The Multidirectional Biological Activity of Resveratrol: Molecular Mechanisms, Systemic Effects and Therapeutic Potential—A Review

by Łukasz Kogut, Czesław Puchalski, Danuta Katryńska and Grzegorz Zaguła

Nutrients 2026, 18(2), 313; https://doi.org/10.3390/nu18020313 - 19 Jan 2026

Abstract

Background/Objectives: Resveratrol is a multi-target polyphenolic stilbene widely studied for its antioxidant, anti-inflammatory, cardioprotective, hepatoprotective, neuroprotective, immunomodulatory and anticancer properties. This review summarizes current evidence on its molecular mechanisms, therapeutic potential, metabolic interactions and biological implications, with particular emphasis on bioavailability, signaling pathways [...] Read more.

Background/Objectives: Resveratrol is a multi-target polyphenolic stilbene widely studied for its antioxidant, anti-inflammatory, cardioprotective, hepatoprotective, neuroprotective, immunomodulatory and anticancer properties. This review summarizes current evidence on its molecular mechanisms, therapeutic potential, metabolic interactions and biological implications, with particular emphasis on bioavailability, signaling pathways and organ-specific actions. Methods: A comprehensive literature review was conducted focusing on recent in vitro, in vivo and clinical studies evaluating resveratrol’s biochemical activity, molecular targets and physiological effects. Special attention was given to oxidative stress regulation, inflammatory signaling, mitochondrial function, metabolic pathways, gut microbiota interactions, and its influence on chronic diseases. Results: Resveratrol modulates several key signaling pathways including NF-κB, SIRT1, AMPK, MAPK, Nrf2 and PI3K/AKT/mTOR. It reduces oxidative stress, inhibits inflammatory cytokines, regulates apoptosis, improves mitochondrial performance, and activates endogenous antioxidant systems. The compound demonstrates protective effects in cardiovascular diseases, hepatic steatosis, neurodegenerative disorders, metabolic dysfunction, and various cancers through anti-inflammatory, anti-proliferative and anti-fibrotic mechanisms. Additionally, resveratrol beneficially alters gut microbiota composition and microbial metabolites, contributing to improved metabolic homeostasis. Despite high intestinal absorption, systemic bioavailability remains low; however, novel nanoformulations significantly enhance its stability and plasma concentrations. Conclusions: Resveratrol exhibits broad therapeutic potential driven by its capacity to regulate oxidative, inflammatory, metabolic and apoptotic pathways at multiple levels. Its pleiotropic activity makes it a promising candidate for prevention and complementary treatment of chronic diseases. Advances in delivery systems and microbiota-derived metabolites may further enhance its clinical applicability. Full article

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

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