Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007
The Functional Foods in Health and Disease (FFHD) is a peer-reviewed, open-access international journal which serves as the journal of the Academic Society for Functional Foods and Bioactive Compounds (ASFFBC). Journal Citation and Indexing The FFHD journal has been indexed in the Web of Science since 2011 with a current Impact Factor of 1.04. In addition, FFHD is indexed in the Emerging Sources Citation Index (ESCI) since 2015 and in Scopus since 2020. All articles from 2011 on have been accepted and indexed in web of Science. The acceptance into both Scopus and Web of Science shows the strength of the journal and the authors as well as helps to expand the reach of our published articles. The articles we publish include cutting-edge biomedical research and development of functional foods. The goal is to provide research that can lead to the development of functional food products. The actual definition for these functional foods, as provided by the Functional Food Center (FFC) is as follows: “Natural or processed foods that contain biologically-active compounds, which, in defined, effective, non-toxic amounts, provide a clinically proven and documented health benefit utilizing specific biomarkers, to promote optimal health and reduce the risk of chronic/viral diseases and manage their symptoms." The journal also serves as an excellent resource for Ph.D. students, professors, public health professionals, medical doctors, dieticians, nutritionists, government representatives (FDA, NIH, USDA), and the general public for information regarding the latest advancements for promoting optimal health and reducing the risk of chronic/viral diseases and managing their symptoms using functional foods and bioactive compounds including antioxidants, vitamins, and many more. The FFHD journal has been published under the title Functional Foods in Health and Disease since February 2011. You can submit your manuscripts and cover letter here or directly to the Editorial Office at editor@ffhdj.com as an e-mail attachment. Additional information about submission guidelines can be found here and an example cover letter can be found here. Scopus Metrics: [Functional Foods in Health and Disease - Scopus Page] The FFHD journal is also indexed in the following databases: Scopus, CrossRef, Index Copernicus International (ICI), Chemical Abstract, EBSCO, and Google Scholar. Functional Food in Health and Disease journal has been indexed in the following databases: Scopus, Index Copernicus, CrossRef, and Google Scholar. The FFHD journal has been indexed in Scopus since 2020 with a current CiteScore of 3.1 (Calculated on December 5th, 2025). Journal H-index is 30. While SJR currently lists FFHD in Quartile 3 (Q3), a direct search on the Scopus website shows that the journal is now ranked in Quartile 2 (Q2), reflecting recent citation improvements.
Authors retain the copyright of their articles and grant the Functional Food Center (FFC) and its journals the right of first publication under the terms of the Creative Commons Attribution 4.0 International License. This license permits unrestricted use, distribution, and reproduction in any medium, including commercial use, provided the original author(s) and source are properly credited. Authors may post and share their published work freely, provided that the original publication in this journal is acknowledged. By submitting to this journal, authors confirm that their manuscripts are original, not under consideration elsewhere, and that they hold the necessary rights to grant this license. The Functional Food Center encourages open scientific exchange and allows derivative and extended works, provided attribution to the original publication is maintained.
Assessment of the anti-diabetic potential of resveratrol in streptozotocin-induced diabetic animal models through modulation of oxidative stress and inflammation
Background: Resveratrol (RES) is well known for its various biological properties, including anti-inflammatory and antioxidant activities, making it a valuable therapeutic approach for treating numerous pathological disorders. Objectives: The aim of this study was to assess the anti-diabetic effects of RES in streptozotocin (STZ)-induced diabetic rats. Methods: A total of thirty-two male rats, weighing 160-175g, were randomly allocated into four experimental groups (n = 8 per group): normal untreated controls, diabetic controls, diabetic rats receiving resveratrol treatment, and diabetic rats treated with glibenclamide as a positive control. Following completion of the treatment, blood samples were collected for biochemical investigations. Animals were then sacrificed, and renal histopathological analysis was performed to evaluate renal tissue architecture, and IL-6 expression was examined by immunohistochemistry. Results: The treatment with RES significantly elevated insulin levels, decreased blood glucose, total triglyceride (TG) and cholesterol (TC) levels, reduced inflammation, lowered the levels of inflammatory markers, and improved the activities of antioxidant enzymes in diabetic rats. RES lessened diabetes-induced renal damage, including inflammation, congestion, and fibrosis. In addition, RES markedly suppressed interleukin-6 (IL-6) expression in kidney tissues compared with the diabetes control group. Conclusion: These outcomes suggest that RES is a potent therapeutic agent for diabetes and related complications. Novelty of the study: This study demonstrates that RES not only improves glycemic control, lipid metabolism, and insulin levels, but also attenuates oxidative stress and inflammation in diabetic rats. Notably, RES protects renal tissue architecture and markedly downregulates IL-6 expression. These findings highlight RES as a multi-target bioactive compound with potential therapeutic in diabetes management. Keywords: Resveratrol, anti-diabetic potential, oxidative stress, inflammation
Copyright (c) 2026 Riyadh Omar Nasser Alfahed, Walleed Khaled Aljafen, Mohammed Sulaiman Alduraibi, Arshad Husain Rahmani https://creativecommons.org/licenses/by/4.0
Utilising the omega-3 index to assess the relative bioimpact of a whole
Background: Epidemiological studies indicate chronic global underconsumption of dietary omega-3 fatty acids with an increased risk of adverse health outcomes. Omega-3 supplements are frequently used to address this deficit. However, whole fish contains an array of other fatty acids with additional putative health benefits. The health outcomes of omega-3 supplementation trials have been highly variable, in contrast to trials assessing regular fish consumption. Objective: Our goal was to evaluate the biological impact (bioimpact) of a whole salmon oil (OmeGo) compared to a commonly used, concentrated omega-3 oil. OmeGo is produced from fresh salmon using a patented protease hydrolysis process, leaving the salmon oil’s natural food matrix intact. This could feasibly improve the oil’s bioavailability and bioimpact. Methods: In this randomized, active-controlled interventional study, 84 healthy subjects were randomized to receive OmeGo or an omega-3 supplement for 14 weeks to assess changes in red blood cell eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) quantified as the omega-3 index (O3I). Inflammatory biomarkers and sleep quality, two important determinants of well-being, were also assessed. Results: Despite OmeGo containing 2.5-fold less EPA and DHA, the increase in O3I from baseline was 1.7-fold greater than the active comparator, corresponding to a 4.3-fold greater increase in O3I per 100mg of EPA+DHA (p = 0.001). High-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) all decreased to a greater extent in the OmeGo group, with between-group differences reaching statistical significance for hsCRP (p < 0.01) and TNF-α (p < 0.05). Conclusion: The findings of this study indicate that a fish oil retaining its intact food matrix and natural omega-3 fatty acids levels is more bioavailable and better replicates the health benefits of regular fish consumption compared to a commonly used concentrated EPA/DHA supplement. Novelty of Study: This study challenges the prevailing assumption that concentrated omega-3 supplementation is the most effective strategy for compensating for inconsistent fish consumption and attaining the health benefits associated with regular fish intake. Keywords: omega-3 index; salmon oil, polyunsaturated fatty acids; eicosapentaenoic acid; docosahexaenoic acid; C-reactive protein; tumour necrosis factor-α; interleukin-6.
Copyright (c) 2026 Crawford Currie, Tor Åge Myklebust, Christian Bjerknes, Bomi Framroze https://creativecommons.org/licenses/by/4.0
Anti-aging effects of active medicinal-food homologous complex nutrients in zebrafish
Background: Aging is a complex biological process characterized by progressive cellular and molecular deterioration, including oxidative stress accumulation, telomere attrition, and cellular senescence. Active medicinal–food homologous complex nutrients (AMCN) are bioactive compounds derived from natural sources with potential anti-aging effects, but their mechanisms remain poorly understood. Objective: To investigate the anti-aging effects of AMCN and their underlying molecular mechanisms using a zebrafish aging model. Methods: Zebrafish were subjected to an aging model and treated with varying concentrations of AMCN. Aging biomarkers were assessed, including β-galactosidase activity, intracellular reactive oxygen species (ROS), telomerase protein concentration, and telomere length. Results: AMCN treatment significantly decreased β-galactosidase staining intensity as well as ROS levels in a dose-dependent manner. Telomerase protein concentration was elevated, and telomere length was partially restored, particularly at moderate and higher AMCN concentrations. Novelty of Study: This study demonstrates, for the first time in a whole-organism vertebrate model, that active medicinal–food homologous complex nutrients (AMCN) exert coordinated, multi-target anti-aging effects in a zebrafish model by reducing oxidative stress, attenuating cellular senescence, and preserving telomere integrity. By establishing a functional association between redox regulation and telomere maintenance, this study provides mechanistic evidence supporting the role of AMCN in modulating key processes involved in aging. The use of zebrafish as a translational vertebrate model enables in vivo evaluation of these effects and enhances the physiological relevance of AMCN, supporting their application in the development of nutraceuticals and functional foods aimed at mitigating age-related decline and maintaining physiological homeostasis. These findings highlight AMCN as a promising multi-component dietary intervention targeting interconnected hallmarks of aging. Conclusions: AMCN exerts protective effects against aging-related cellular dysfunction by reducing oxidative stress, suppressing senescence, and maintaining telomere stability. These results provide scientific support for the potential use of AMCN as a functional dietary intervention to promote healthy aging and prevent age-related functional decline. Keywords: Active medicinal–food homologous complex nutrients, functional food, zebrafish model, anti-aging, reactive oxygen species, telomerase, telomere, oxidative stress , cellular senescence
Copyright (c) 2026 Yinan Yuan, Fuqiao Xu, Hanluo Li, Sini Kang, Yiming Wen, Heng Liu, Xiaoze Ren, Lan Yuan https://creativecommons.org/licenses/by/4.0
Impact of a functional food–oriented self-care educational program on physical activity and treatment tolerance in lung cancer patients undergoing chemotherapy
Background: Cancer-related fatigue and reduced treatment tolerance are among the most debilitating consequences of chemotherapy in lung cancer patients. Emerging evidence highlights the role of functional foods and bioactive dietary components in modulating inflammation, oxidative stress, and metabolic dysfunction—key mechanisms underlying fatigue and physical decline during cancer treatment. Objectives: To evaluate the impact of a functional food–based self-care educational program on physical activity, fatigue, and chemotherapy tolerance among lung cancer patients. Methods: A quasi-experimental pre–post study was conducted among 100 lung cancer patients undergoing chemotherapy. Participants received a structured self-care educational program emphasizing functional food principles, including antioxidant-rich foods, omega-3 fatty acids, and high-quality protein sources, alongside guidance on physical activity and symptom management. Outcomes related to physical activity, fatigue severity, and chemotherapy-related symptoms were assessed before and after the intervention. Results: The intervention resulted in significant improvements in physical activity engagement and health-related behaviors. Notable reductions were observed in chemotherapy-related fatigue, gastrointestinal symptoms, peripheral neuropathy, and analgesic use (p < 0.05). Improved treatment tolerance was accompanied by enhanced dietary practices consistent with functional food recommendations. Novelty of the Study: This study provides region-specific evidence from Iraq on the clinical impact of a structured functional food–oriented educational intervention in lung cancer patients, linking bioactive dietary principles with symptom reduction and improved chemotherapy tolerance. Conclusion: A functional food–based self-care educational program significantly improved physical activity levels, reduced treatment-related symptoms, and enhanced chemotherapy tolerance in lung cancer patients. These findings support the integration of functional nutrition strategies into supportive oncology care to improve clinical and functional outcomes. Keywords: Functional foods; Bioactive compounds; Lung cancer; Chemotherapy tolerance; Cancer-related fatigue; Physical activity.
Copyright (c) 2026 Arjuman Mohamed Aziz, Yousif Mohammed Younus, Jangi sh. Salai https://creativecommons.org/licenses/by/4.0
Effects of oral intake of collagen peptides on lower back discomfort: a randomized, double-blind, placebo-controlled, parallel-group comparison study
Background: Lower back pain is a widespread problem that limits daily activities and lowers quality of life for many people. Collagen peptides, which support joint and tissue health, may help relieve this kind of discomfort. Objectives: This study aimed to evaluate the effects of collagen peptide intake on lower back discomfort in healthy middle-aged and older adults reporting subjective symptoms of lower back discomfort. Methods: We conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study. Following screening, 49 healthy Japanese individuals experiencing lower back discomfort were randomized to receive either 10 g of a collagen peptide-containing drink (collagen group; n = 24) or a placebo drink (placebo group; n = 25) once daily for 12 weeks. The Japan low back pain evaluation questionnaire (JLEQ) was administered at baseline and at the end of the intervention. Results: Overall, 48 participants were included. The collagen group demonstrated significant improvement in JLEQ items, such as "How difficult has it been for you to put on underwear and stockings in the past few days because of your back pain?" and "During the past month, have you avoided going out to your neighborhood because of your back pain?". Conclusions: Collagen peptide ingestion may alleviate lower back discomfort and improve daily functioning. Novelty of the Study: This randomized controlled trial demonstrates that collagen peptide intake improves functional limitations associated with lower back discomfort in healthy individuals. The study indicates that utilizing collagen peptides can enhance quality of life by alleviating lower back discomfort. Trial registration: The study protocol was registered with UMIN-CTR (ID: UMIN000055421). Keywords: Collagen peptides, Bioactive peptides, Lower back discomfort, Musculoskeletal health, Functional food intervention, Randomized controlled trial, Biomarkers of pain, Quality of life
Copyright (c) 2026 Eriko Saito, Takumi Yamaguchi, Mariko Ito, Rina Takayanagi, Hiroko Maruki-Uchida, Eisaku Nishimura, Takashi Koikeda, Naoki Iemoto https://creativecommons.org/licenses/by/4.0
Efficacy and safety of a multi-ingredient dietary supplement (Glucocil®) in prediabetics: A randomized, double-blind, placebo-controlled study
Background: Interest in natural food supplements as effective alternative therapeutics for managing dysglycemia has grown substantially over the past decade owing to their minimal side effects and holistic health rejuvenation. Objective: In the present randomized, double-blind, placebo-controlled 90-day study, the efficacy of Glucocil®, a proprietary formulation of 14 natural ingredients, was investigated in a cohort of 37 pre-diabetic individuals (21 experimental and 16 placebo). Materials and Methods: Glucocil® was bio-engineered using a proprietary manufacturing technology utilizing safety-affirmed ingredients and progressive high-shear wet milling operation with sequential addition of selected phytoconstituents, vitamins and other ingredients. Subjects were advised to consume 4,800 mg of either placebo (soybean oil; 1,200 mg/ soft gel) or Glucocil® soft gels (1,200 mg/soft gel) each day over a period of 90 consecutive days. Either at the end of the study or at intermittent intervals of 30 and 60 days, fasting blood glucose, oral glucose tolerance, fasting insulin, glycated hemoglobin levels as well as lipid profile were assessed to ascertain the efficacy of the formulation. Anthropogenic parameters were also determined to ascertain the visible changes (if any) inflicted by the formulation. Lastly, safety of the formulation was assessed in terms of cardiovascular parameters and liver function parameters. Results: HbA1c decreased from 6.44 to 5.80 in the Glucocil® group with significant within-group improvement (p=0.0002), whereas placebo decreased from 6.22 to 6.06 without significant within-group change (p=0.2930). The mean HbA1c change was greater with Glucocil® (−0.64) than placebo (−0.17), with a significant between-group difference (p=0.0301). OGTT 2-hour glucose decreased significantly within the Glucocil® group (−24.11 mg/dL; p=0.0131), but not significantly versus placebo between groups (p=0.5406). However, both fasting insulin and fasting blood glucose didn’t undergo an equally appreciable drop. Consumption of Glucocil® did not bring about any appreciable change in body weight or other anthropometric factors. No noticeable change was found in lipid profile of the individuals in the treatment group as compared to the placebo group, except for a slight increase in HDL effected by consumption of Glucocil®. Safety assessment of this formulation was carried out in terms of assessment of cardiovascular (pulse rate, systolic and diastolic blood pressure) and liver function parameters. Conclusion: This investigation provided valuable insights in evaluation of safety and efficacy of Glucocil®, a novel antidiabetic supplement made fully from natural ingredients and free from any noticeable side effects. Keywords: Glucocil®- A novel phytonutrient formulation; Clinical trial; Pre-Diabetics; Blood glucose; HbA1c; Metabolic health; Safety
Copyright (c) 2026 Amit Bobde, Sayali Kale, Sonal Raote, Lee Zhong, Marvin Heuer, Sanjoy Chakraborty, Debasis Bagchi https://creativecommons.org/licenses/by/4.0
Piceatannol enhances contractile force in 3D engineered skeletal muscle tissues
Background: Skeletal muscle underpins movement, metabolic homeostasis, and overall health. Age- and disease-related declines in muscle function lead to disability and increased healthcare burden. Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, has shown antioxidant and metabolic effects in muscle cells. However, its direct impact on contractile force remains unclear. Three-dimensional (3D) engineered skeletal muscle provides a physiologically relevant in vitro model that enables direct measurement of contractile force. Objective: We investigated the effects of PIC on contractile force in 3D engineered skeletal muscle and the underlying molecular pathways. Methods: 3D engineered tissues were generated from C2C12 myoblasts embedded in type I collagen and differentiated in serum-reduced medium. Constructs were treated with 50 or 100 µM PIC or vehicle. Contractile force was measured at baseline (pre-treatment) and at weeks 1 and 2 post-treatment using electrical pulse stimulation, by tracking displacement of flexible pillars. RNA-seq was performed on two-dimensional (2D) cultured myotubes to identify genes differentially expressed following PIC treatment, and key findings were validated by RT-qPCR. Results: PIC increased contractile force relative to vehicle in the 3D skeletal muscle tissues. At 50 µM, contractile force was significantly higher than vehicle at week 2; at 100 µM, it was significantly higher at both weeks 1 and 2. Transcriptomic analysis revealed enrichment of pathways related to carbohydrate metabolism, particularly glycolysis and glucose handling. RT-qPCR confirmed increased expression of G/ut4 and glycolytic enzymes, including Hk2, Pfkm, and Pkm. Conclusion: In 3D engineered skeletal muscle, PIC enhanced contractile force and upregulated genes related to glucose uptake and glycolysis. These preclinical findings support and inform the development of PIC-containing functional foods aimed at preserving muscle function. Novelty of the Study: This study is the first to demonstrate, in a physiologically relevant 3D engineered skeletal muscle model that overcomes 2D culture limitations, that PIC increases contractile force measured directly. It further implicates glycolytic activation as the underlying mechanism. Keywords: muscle function; contractile force; skeletal muscle; glycolysis; piceatannol; polyphenol; 3D engineered skeletal muscle tissues
Copyright (c) 2026 Haruka Kimura, Naoko Matsui, Kaoru Ishihara, Ryouichi Ito, Shinpei Kawakami, Yukihiro Oritani, Naoki Iemoto https://creativecommons.org/licenses/by/4.0
Reliability and validity of a Hebrew-language short screening questionnaire for highly processed foods (HsQ-HPF)
Background: Ultraprocessed food consumption has been linked to adverse health outcomes and is traditionally assessed through labor-intensive dietary intake methods. To facilitate efficient assessment, the short screening questionnaire of highly processed food consumption (sQHPF) was previously developed and validated in Spanish populations. Objective: To translate, culturally adapt, and validate a Hebrew version of the sQHPF (HsQHPF) for use among Israeli adults. Methods: In this cross-sectional study, adult participants completed a 24-hour dietary recall, the HsQHPF, and the Israel Mediterranean Diet Screener (IMEDAS). A subgroup repeated the HsQHPF after three weeks to evaluate reliability. Associations between HsQHPF scores, NOVA group 4 food items from the dietary recall, and IMEDAS scores were examined. Internal consistency, correlations, and intraclass correlation coefficients (ICC) were calculated. Results: Forty-three adults participated (median age 25 years; 72.7% female). The HsQHPF exhibited excellent internal consistency (Cronbach’s α = 0.74). HsQHPF scores correlated strongly and significantly with the number of NOVA group 4 items from the 24-hour recall (rho = 0.727, p < 0.001), supporting construct validity. No significant associations were found with IMEDAS scores. Test–retest reliability was high (ICC = 0.81; 95% CI 0.58–0.92; p < 0.001). Higher HsQHPF tertiles were associated with significantly greater saturated fat intake and a higher number of NOVA group 4 foods. Conclusion: The HsQHPF is a valid and reliable tool for evaluating ultra-processed food consumption in the Israeli adult population. Its use may streamline data collection in future studies examining associations between ultra-processed food intake and health outcomes. Novelty of the study: The present study is the first to validate a tool for evaluating the intake of ultra-processed foods in adults in the Israeli population Keywords: Validity; highly processed foods; questionnaire; methods
Copyright (c) 2026 Mona Boaz, Abigail Navaro, Shahar Reut Nahmany, Vered Kaufman-Shriqui https://creativecommons.org/licenses/by/4.0
Activation of tryptophan metabolism in cardiometabolic disorders: Prognostic role of IDO and TDO enzymes
Background: Cardiometabolic disorders, including cardiovascular disease and type 2 diabetes mellitus (T2DM), represent a major global health burden and are closely associated with metabolic abnormalities such as obesity, dyslipidemia, and impaired glucose regulation. Disease progression is strongly influenced by chronic low-grade inflammation and dysregulated immune responses. Tryptophan, an essential amino acid, plays an important role in immune regulation and maintenance of inflammatory homeostasis. Overactivation of the kynurenine pathway leads to the accumulation of toxic metabolites, which promote inflammation and increase the risk of atherosclerosis, pulmonary arterial hypertension (PAH), and non-alcoholic fatty liver disease (NAFLD). Methods: This study was conducted between October 2024 and February 2025 and included total 150 participants. Ninety patients with cardiometabolic disorders were enrolled, including 30 patients with coronary artery disease (CAD) combined with T2DM, 30 patients with CAD combined with PAH, and 30 patients with CAD combined with NAFLD. Sixty apparently healthy individuals served as a control group. Venous blood samples were collected from all participants. Hematological parameters were evaluated using an automated complete blood count analyzer. Serum levels of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) were determined using enzyme-linked immunosorbent assay techniques. CD8+ T cell expression was determined using flow cytometry. All patients had angiographically confirmed coronary artery disease. Results: Serum IDO levels were significantly elevated in patients with CAD combined with T2DM (4.85 ± 1.21 ng/mL), CAD combined with PAH (4.32 ± 1.08 ng/mL), and CAD combined with NAFLD (5.01 ± 1.34 ng/mL) compared to the control group (2.13 ± 0.74 ng/mL; P < 0.01). Similarly, serum TDO levels were significantly higher in CAD + T2DM (3.76 ± 0.98 ng/mL), CAD + PAH (3.54 ± 0.87 ng/mL), and CAD + NAFLD (3.92 ± 1.05 ng/mL) than in controls (1.89 ± 0.63 ng/mL; P < 0.01). CD8⁺ T-cell proportions were also significantly increased in CAD + T2DM (32.4 ± 5.8%), CAD + PAH (30.7 ± 5.1%), and CAD + NAFLD (31.9 ± 6.0%) compared to healthy controls (21.3 ± 4.2%; P < 0.01). Novelty of the Study: This study is among the first to simultaneously evaluate CD8⁺ T cell expression and IDO and TDO enzyme activity in several cardiometabolic disorders, highlighting their combined prognostic significance in inflammation-driven metabolic pathology. Conclusions: These findings suggest that inflammation-related activation of tryptophan metabolism through the kynurenine pathway plays an important role in immune disturbances and disease progression in cardiometabolic disorders. IDO and TDO enzymes may serve as valuable diagnostic biomarkers and potential therapeutic targets in inflammation-induced metabolic diseases. Keywords: Chronic inflammation; Tryptophan metabolism; IDO and TDO enzymes; Kynurenine pathway; Cardiometabolic disorders; Functional food biomarkers
Copyright (c) 2026 Anwar Jasib Almzaiel, Jihad Yaser Kshash https://creativecommons.org/licenses/by/4.0
Co-ingestion of soy isoflavones and lactobionic acid improves facial stratum corneum hydration: a randomized, placebo-controlled trial
Background: Low-dose soy isoflavones (<30 mg/day) alone often show limited effects on skin hydration; co-ingestion with lactobionic acid may enhance absorption and equol bioconversion, potentially improving corneum hydration. Objective: To evaluate whether co-ingesting soy isoflavones (25 mg aglycone equivalents) with lactobionic acid (250 mg) improves stratum corneum water content compared with isoflavones alone or placebo. Methods: This randomized, placebo-controlled, parallel-group trial aimed to determine the effects of 12-week consumption of soy isoflavones alone (Iso, 25 mg soy isoflavone aglycone equivalents), soy isoflavones and lactobionic acid (Iso+LAB, 25 mg soy isoflavone (aglycone equivalents) and 250 mg lactobionic acid), or placebo (no soy isoflavone or lactobionic acid) on the stratum corneum water content and urinary isoflavone concentration in 33 healthy adult women. Results: The stratum corneum water content of the left cheek significantly increased in the Iso+LAB group at 12 weeks, whereas no significant improvement was observed in the Iso group compared with the placebo group. Among equol producers, the Iso+LAB group exhibited significantly higher urine equol levels at 4 weeks compared with the Iso group. Among equol non-producers, the urinary daidzein and genistein concentrations were consistently higher in the Iso+LAB group, although dietary isoflavone intake did not differ among groups. Conclusions: Co-ingestion of soy isoflavones and lactobionic acid enhanced the stratum corneum water content, likely through improved absorption and metabolism of soy isoflavones, including equol production. Novelty: This study isolates the specific contribution of lactobionic acid by directly comparing low-dose soy isoflavones alone, soy isoflavones combined with LBA, and placebo, linking skin hydration changes to urinary isoflavone and equol kinetics. Keywords: soy isoflavone, lactobionic acid, stratum corneum water content, equol, skin, functional food.
Copyright (c) 2026 Kaori Homma, Ayaka Kawabata, Saki Yamauchi, Toshinari Maruo, Fumio Nanba, Kenichi Oe, Yuichi Ukawa, Kazuya Mitsuhashi, Toshio Suzuki https://creativecommons.org/licenses/by/4.0
Physiological and biochemical responses of Vicia faba L. to folic acid treatments and their relation to Aphis fabae infestation
Background: This study investigated the effects of foliar-applied folic acid (FA) on the growth and biochemical responses of faba bean (Vicia faba L.) under black bean aphid (Aphis fabae) infestation. Objective: This study aimed to evaluate the effect of foliar-applied folic acid on the growth, biochemical composition, and antioxidant defense system of faba bean (Vicia faba L.) and to determine its relationship with black bean aphid (Aphis fabae) infestation. Methods: Faba bean plants were treated with folic acid at concentrations of 0, 50, 100, and 150 mg/L under greenhouse conditions. Growth parameters, photosynthetic pigments, metabolites, and antioxidant enzyme activities were measured, and aphid infestation trials were conducted to assess plant resistance responses. Folic acid significantly improved plant growth, photosynthetic pigments and biochemical composition, with the highest concentration (150 mg/liter) producing the strongest effect. Aphid infestation markedly reduced biomass and pigment content; FA at 100–150 mg/L partially restored these parameters. FA treatments also increased secondary metabolites and antioxidant enzyme activities, infected plants showed a strong defense response, indicating a priming effect against biotic stress. Results: Folic acid application significantly improved growth parameters of both healthy and aphid-infested green bean plants, with 150 mg/L producing the highest fresh and dry weights. It partially alleviated aphid-induced stress by restoring growth performance compared with untreated infested plants. Treatment also enhanced plant water status and height, indicating improved physiological activity and hormone-like effects. These findings support the potential of folic acid as a biostimulant for sustainable crop productivity and stress tolerance. Novelty of the study: This study demonstrates a dual role of folic acid as both a growth-promoting biostimulant and defense-promoting agent against Aphis fabae in Vicia faba. Unlike previous studies focused primarily on abiotic stress, this work integrates physiological, biochemical and insect-related responses, supporting folic acid as a sustainable tool to increase crop productivity and resistance under biotic stress. Conclusion: Folic acid acts as an effective biostimulant that improves growth, photosynthetic efficiency and antioxidant defense in faba bean while reducing aphid-induced damage. These findings support its use as a sustainable strategy to enhance pest tolerance and increase crop productivity. Keywords: Vicia faba, folic acid, Aphis fabae, antioxidant enzymes, metabolites, plant resistance.
Copyright (c) 2026 Ahmed Khaleel Kafori, Mohamed Ali Triki https://creativecommons.org/licenses/by/4.0
Safety and efficacy of a proprietary Asparagus racemosus root extract on ovarian morphology, androgen balance, and insulin resistance in women diagnosed with polycystic ovary syndrome
Background: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder characterized by ovarian dysfunction, androgen imbalance, and insulin resistance (IR). Current treatments often target isolated symptoms and may have tolerability limitations, suggesting the need for safe, multi-targeted therapeutic alternatives. Asparagus racemosus (Shatavari), which contains steroidal saponins, demonstrates phytoestrogenic and metabolic regulatory activities and may offer potential benefits in PCOS. Objective: To evaluate the efficacy and safety of CL22205, a standardized A. racemosus root extract, on ovarian morphology, reproductive hormones, hyperandrogenic drive, insulin sensitivity, and anthropometric outcomes in women suffering from PCOS. Methods: In a randomized, double-blind, placebo-controlled study, 60 women (age 20–35 years) suffering from PCOS were assigned to receive either CL22205 (200 mg/day) or a placebo over a period of 84 consecutive days. The primary outcome was the change in ovarian volume from baseline. Secondary outcomes included ovarian volume, cyst size, follicle count, and menstrual cycle regularity, hirsutism score, acne severity, serum endocrine factors, insulin resistance, and anthropometric measurements. Safety was assessed through hematology, serum biochemistry, urinalysis, and monitoring of adverse events. Results: Fifty-nine participants completed the trial. CL22205 demonstrated significant reductions (p < 0.05, vs. baseline) in ovarian volume (18.7%), cyst size (39.0%), and average follicle count (19.7%), and improved menstrual regularity (10.8%) at the end of the study. Hirsutism score (41.8%) and acne severity (40.7%) decreased remarkably. CL22205 significantly increased (p < 0.05 vs. baseline) serum levels of sex hormone binding globulin, reduced total testosterone, and lowered the luteinizing hormone: follicle-stimulating hormone ratio. Post-trial, homeostatic model assessment for IR decreased by 13.2% (p < 0.0001 vs. baseline), indicating enhanced insulin sensitivity. Reductions in body weight and waist and hip circumferences further supported the metabolic benefits. No major adverse effects were observed. Conclusion: CL22205 exhibited reproductive, endocrine, and metabolic benefits with excellent tolerability, demonstrating its potential as a phytoceutical intervention for the management of PCOS. Keywords: Asparagus racemosus, Clinical trial, Hyperandrogenism, Insulin resistance, Phytoceutical, Polycystic ovary
Copyright (c) 2026 Sridevi Kondamudi, Sravanthi Sadu, Sujatha Deva, Aishwarya Yalamanchi, Amulya Yalamanchi https://creativecommons.org/licenses/by/4.0
Evaluation of the mechanism of the brain transport of nobiletin via passive and P-glycoprotein-mediated transport
Background: Nobiletin, a polymethoxyflavonoid found in citrus fruits, exhibits neuroprotective potential in disorders of the central nervous system. However, the precise mechanism governing its passage across the blood-brain barrier (BBB) remains unclear. Objective: This study aimed to elucidate the mechanism of the brain transport of nobiletin by determining its passive transport ability, P-glycoprotein (P-gp) substrate recognition, and the effect of P-gp on its brain transport. Methods: The ability of nobiletin to traverse the BBB was assessed using an artificial lipid membrane (PAMPA-BBB) to determine passive diffusion parameters. Its interaction with P-gp was examined through ATPase activation assays and bidirectional transport studies in P-gp-overexpressing cell lines (LLC-GA5-COL300) compared with control cells (LLC-PK1). The in vivo distribution of nobiletin in mouse brain and plasma was further quantified following oral administration, with and without P-gp inhibition by elacridar. Results: Nobiletin exhibited high passive transport in artificial lipid membrane permeation assay. It increased ATPase activity in P-gp-overexpressing membranes. Significant increases in basolateral-to-apical transport were observed in P-gp-expressing cells, indicating that P-gp transports nobiletin as a substrate, similar to verapamil, but not as effectively as quinidine. When orally administered to mice, the plasma and brain concentrations of nobiletin increased simultaneously and peaked at 30 min, indicating rapid distribution between the blood and brain. The brain/plasma concentration ratio at 30 min was not significantly increased upon P-gp inhibition, indicating that P-gp does not affect the brain transport of nobiletin. Novelty: This study provides the first quantitative in vivo evidence that P-gp does not functionally restrict the brain distribution of nobiletin, establishing passive diffusion as the predominant BBB transport mechanism of nobiletin. Conclusions: These results demonstrate that nobiletin efficiently crosses the BBB primarily via passive diffusion, with minimal modulation by P-gp. These findings clarify its brain transport kinetics and reinforce its potential as a neuroprotective bioactive compound for dietary and pharmaceutical development. Keywords: Nobiletin; Blood–brain barrier; P-glycoprotein; Passive transport; Brain distribution.
Copyright (c) 2026 Eriko Nakatani, Shimako Tanaka, Takayuki Yonezawa, Je Tae Woo, Shizuo Yamada, Takashi Okura https://creativecommons.org/licenses/by/4.0
Sakulora™ (Lacticaseibacillus paracasei strain Shidare) improves bowel function: A randomized, double-blind, placebo-controlled trial
Introduction and objective: Heat-killed lactic acid bacteria with postbiotic effects have emerged as promising functional food ingredients for promoting intestinal health. SakuloraTM, which consists of heat-killed Lacticaseibacillus paracasei strain Shidare (strain Shidare) isolated from weeping cherry blossom, may exert postbiotic effects on the gut microbiota. However, its impact on the intestinal environment and intestinal mobility remains unclear. Therefore, the present study investigated the efficacy of SakuloraTM on intestinal serotonin and fecal IgA concentrations in mice and bowel function in healthy adults through a randomized, double-blind, placebo-controlled trial. Methods: In the pre-clinical phase, mice were administered heat-killed strain Shidare, and intestinal serotonin and fecal IgA concentrations were assessed. Forty-four healthy adults with mild constipation were then randomly assigned to receive either SakuloraTM (containing 50 billion cells of the heat-killed strain Shidare) or a placebo daily for 2 weeks. The frequency of bowel movements in one week was used as the primary outcome. Results: In murine models, the administration of heat-killed strain Shidare significantly increased intestinal serotonin and fecal IgA concentrations. In the clinical trial, the weekly frequency of bowel movements was significantly higher in the SakuloraTM group than in the placebo group. No significant improvements were observed in the secondary endpoints, including the gut microbiota and fecal short-chain fatty acids. No serious adverse events developed throughout the study period. Novelty of the Study: The bowel movement-improving effect of the heat-killed strain Shidare was demonstrated for the first time, and its mechanism was suggested to be an increase in intestinal serotonin and IgA levels. Conclusions: SakuloraTM containing heat-killed strain Shidare effectively improved the bowel function, supporting its potential as a safe functional food ingredient for maintaining digestive health in healthy individuals. Trial Registration: UMIN-CTR: UMIN000054746 Keywords: Lacticaseibacillus paracasei; postbiotics; bowel function; intestinal environment
Copyright (c) 2026 Tsuyoshi Takara, Naoko Suzuki, Kazuo Yamamoto, Shin-ichiro Iio, Hayata Noguchi, Toshihiro Kakinuma, Asami Baba, Hiroshi Shimoda, Takumi Watanabe, Akari Yoneda, Yuriko Namatame, Tetsuro Kan, Masafumi Nagata, Shogo Takeda https://creativecommons.org/licenses/by/4.0
Biogenic silver–copper oxide nanocomposites as functional food safety agents for pathogenic microbial control in aquatic food systems
Background: Multidrug-resistant (MDR) pathogens pose a significant threat to aquatic food systems and water safety. In response, functional food science increasingly focuses on bioactive compounds derived from natural sources for food preservation and safety applications. Objectives: This study aims to investigate the antimicrobial efficacy of biogenic silver-copper-oxide nanocomposites (Ag-CuO NCs) as functional food safety agents. Methods: Biogenic Ag-CuO nanocomposites were synthesized using aqueous extracts from locally sourced botanicals at Prince Abubakar Audu University. Antimicrobial activity was evaluated against six multidrug-resistant (MDR) environmental pathogens commonly found in aquatic ecosystems (Vibrio parahaemolyticus, Escherichia coli, Salmonella enterica, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus) using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Synergistic effects with conventional food preservation methods were also assessed. Biomarker analysis included quantification of reactive oxygen species (ROS) production and assessment of membrane integrity disruption using flow cytometry and scanning electron microscopy (SEM). Results: Biogenic Ag-CuO nanocomposites demonstrated significant antimicrobial activity, with MIC values ranging from 2.5–15 μg/mL across all tested pathogens. The nanocomposites exhibited predominantly bactericidal activity. V. parahaemolyticus was the most susceptible (MIC: 2.5 μg/mL), whereas S. aureus displayed the highest resistance (MIC: 15 μg/mL). ROS quantification revealed a significant elevation in treated bacterial cells (p < 0.001), indicating oxidative stress-mediated antimicrobial mechanisms. SEM imaging confirmed cellular membrane disruption in all treated organisms. Furthermore, synergistic applications with a mild thermal treatment (50°C) enhanced antimicrobial efficacy by 3.8-fold, positioning these nanocomposites as adjuvant agents for food safety. Conclusions: Biogenic Ag-CuO nanocomposites exhibit promising functional antimicrobial properties relevant to food safety applications in aquatic food systems. Their natural derivation, dual-metal composition, and non-toxic profile at therapeutic concentrations suggest viability as bioactive food-grade safety compounds. Novelty of the Study: This study is among the first to systematically evaluate biogenic silver-copper oxide nanocomposites as functional food safety agents against multidrug-resistant aquatic pathogens, combining traditional food safety science with green nanotechnology to create novel bioactive food preservation solutions. The integration of mechanistic characterization (ROS quantification and cellular imaging), pathogen panel testing (six clinically relevant MDR organisms), and synergistic evaluation with mild thermal processing represents an original contribution advancing functional food antimicrobial applications. Keywords: functional foods, biogenic nanocomposites, antimicrobial agents, aquatic pathogens, food safety, bioactive compounds, multidrug-resistant bacteria
Copyright (c) 2026 David Adeiza Zakari, Egbeja Tsobaza Idris, Godwin Amoka Audu, Precious Adejoh Idakwoji, Joseph Abraham-Oyiguh, Hassan Amoto Abdullahi, Godwin Omuya Aliyu, Onwuatuegwu Joseph Chukwuma Taiwo, Kadiri Dickson Adejoh, Nwobodo Humphrey Afam, Ifeanyi Anthony Ezugwu, Onuh Kenneth Ikwulono, Abiodun Sunday Olusegun, Yebafa Jeremiah Akpodoitei, Abdulbasit Anoze Aliyu, Adebimpe Moyosore Adefila https://creativecommons.org/licenses/by/4.0
Antibiotic resistance profiling and histological characterization of Lactobacillus isolated from traditional dairy products
Background: Lactobacillus bacteria play a significant role in improving public health, due to their potential impact on both public health and food safety. They play a crucial role in enhancing food digestion and nutrient absorption in the intestines. This has contributed to increased public awareness of the benefits of probiotics and functional foods, and consequently, the need to evaluate their antibiotic resistance. Objectives: This research aims to study and evaluate the antibiotic resistance and histological characteristics of Lactobacillus strains isolated from conventional dairy products. Methodology: The research involved collecting samples of various dairy products available to consumers in local markets, such as milk, yogurt, and cheese. The necessary analyses were performed, and Lactobacillus bacteria were isolated using a suitable culture medium. Specific techniques were applied to isolate the desired strains. Results: The research showed high bacterial concentrations in the studied samples. The bacterial growth rate varied with the degree of dilution, indicating high bacterial density. These results demonstrate the potential for Lactobacillus bacteria to grow and thrive in diverse environments, underscoring the importance of ongoing assessment of their antibiotic resistance. Conclusion: The study's findings highlight the significance of understanding the role of Lactobacillus isolated from dairy products in antibiotic resistance, as well as the importance of continuing to investigate their impact to ensure food safety and address health challenges. Keywords: Lactobacillus, Traditional dairy products, Probiotics, Antibiotic resistance, Functional dairy foods, Histological characterization, Lactic acid bacteria, Food safety.
Copyright (c) 2026 Alaa Eid Ali ALkharabsheh, Zainab Mohammad Farhan, Ban Nadhum Abdul-Fatah, Aida Aboud Hussein Al-Hudairi, Mohamed Abouyounes, May Abdul Hafed Abdul Kader, Omar Saddam Fadhil https://creativecommons.org/licenses/by/4.0
A natural nootropic for cognitive enhancement: A case study on the standardized mango leaf extract Zynamite®
The demand for natural nootropics to enhance cognitive function has grown significantly. Mangifera indica L. (mango) leaves, with a long history of use in traditional medicine, have recently emerged as a promising candidate. Historically used as a tonic to combat fatigue and exhaustion, mango leaves are now the subject of rigorous scientific investigation. This review synthesizes the ethnobotanical background, phytochemical profile, and neuropharmacological activities of mango leaf extract and its principal bioactive compound, mangiferin. We delve into the mechanisms by which mangiferin impacts the central nervous system (CNS), including its antioxidant, anti-inflammatory, and neurotransmitter-modulating properties. A central component of this review is a detailed case study on Zynamite®, a standardized mango leaf extract. We examine preclinical and clinical evidence supporting its efficacy in enhancing cognitive domains such as reaction time, attention, and memory, particularly under conditions of stress and mental fatigue. To further optimize clinical outcomes, we detail the development of Zynamite® S, a version engineered to improve solubility and address pharmacokinetic hurdles. While previous literature has broadly discussed the diverse bioactivities of mango leaves, this article represents the first comprehensive review to specifically synthesize its effects on CNS and cognitive performance. By bridging the gap between traditional wisdom and modern science, this work provides a unique translational perspective on mango leaf extract as an evidence-based natural nootropic. Keywords: Mango Leaf Extract, Cognitive Enhancement, Solubility, Zynamite®
Copyright (c) 2026 Ana Beltrán-Arranz, David Fuentes-Ríos, Rubén Pérez-Machín, Laura López-Ríos https://creativecommons.org/licenses/by/4.0
Feiolix feijoa fruit powder improves metabolic markers in a high fat diet mouse model
Background: Feiolix®, a freeze-dried feijoa fruit powder contains ellagitannins, abscisic acid, and xyloglucans, each of which may independently and synergistically support metabolic health. Objective: To examine the dose-response effects of Feiolix® on metabolic parameters in high-fat diet-induced diabetic mice. Methods: Swiss albino mice were fed a high-fat diet for 8 weeks to induce diabetes, followed by daily oral gavage of Feiolix at five doses (0.7-11.6 mg/20 g body weight), metformin control, non-diabetic control, or continued high-fat diet for an additional 16 weeks. Results: A biphasic xenohormetic dose-response pattern was observed. The low dose (1.5 mg) demonstrated significant efficacy, significantly reducing fasting blood glucose (-10.1 mg/dL, p<0.0001 vs high-fat diet control) and triglycerides (-14.7 mg/dL, p<0.0001) with performance comparable to metformin and normal controls. Surprisingly, the mid-range 3.5 mg dose was less effective than the 1.5 mg dose for glucose and triglyceride management. The highest 11.6 mg dose showed comprehensive benefits across all metabolic parameters, significantly reducing fasting blood glucose (-30.1 mg/dL), triglycerides (-29.5 mg/dL), total cholesterol (-47.3 mg/dL), and LDL cholesterol (-20.7 mg/dL), while also promoting weight loss and improving liver histology. Conclusions: These findings demonstrate that feijoa exhibits xenohormetic effects with metabolic benefits at low doses (300 mg human equivalent) and enhanced comprehensive benefits at high doses (2300 mg human equivalent), supporting its potential as a natural intervention for metabolic dysfunction management. Novelty of the Study: This study provides evidence that freeze dried feijoa powder (Feiolix®) can act as functional food ingredient with potential therapeutic application to improve metabolic health. Keywords: feijoa; metabolism; blood glucose; cholesterol; triglycerides; body weight; liver health; dose-response; xenohormesis
Copyright (c) 2026 Doug Rosendale, Aahana Shrestha, Ashit Vora, Chhaya Godse, Starin Mckeen https://creativecommons.org/licenses/by/4.0
Development and nutritional evaluation of sorghum-chickpea-baobab based complementary foods for infants in Sudan
Background: Protein-energy malnutrition (PEM) remains a critical public health concern in Sudan, particularly among children under two years—a period marked by rapid growth and transition from exclusive breastfeeding to complementary feeding. Effective complementary foods must be rich in protein, energy, and micronutrients while maintaining acceptable sensory qualities. Objective: This study aimed to develop and evaluate sorghum-based complementary food formulations supplemented with chickpea and baobab powder to improve nutritional quality, protein digestibility, and sensory acceptability. Methods: Four blends were formulated using malted or decorticated sorghum flour, chickpea flour (20–30%), baobab powder (10%), milk powder (5%), and sugar (5%). Proximate composition, vitamin C content, and in vitro protein digestibility (IVPD) were assessed using standard AOAC methods. Sensory evaluation was conducted with 15 mothers using a five-point hedonic scale. Data were analyzed using ANOVA and Duncan’s test at p ≤ 0.05. Results: Chickpea supplementation significantly improved protein content (up to 15.56%) and IVPD (up to 71.54%). Baobab enhanced vitamin C content (up to 15.74 mg/100g). Sensory scores were highest for Blend A (20% chickpea, decorticated sorghum), particularly in color, taste, and overall acceptability. All blends showed acceptable moisture levels and enhanced nutrient density compared to a commercial formula. Conclusion: Chickpea and baobab fortification significantly improved the nutritional and sensory properties of sorghum-based complementary foods. These locally sourced formulations demonstrate strong potential as functional foods to improve infant nutrition and reduce PEM prevalence in Sudan. Novelty of the study: This study introduces a complementary food prototype integrating sorghum, chickpea, and baobab—ingredients not previously combined in this proportion for infant feeding in Sudan. Chickpea enhances protein density and digestibility, while baobab naturally enriches vitamin C, improving functional properties. Keywords: complementary food, sorghum, chickpea, baobab, protein-energy malnutrition, Sudan, infant nutrition, sensory evaluation.
Copyright (c) 2026 Rabaa Musa Hamad Ali, Alafia Basheer Alsadig Musa, Mona Moddathir Gad Almoula, Obada Adam Daowd Mahammed, Amira Gali Abdulla Adam, Hanan Elamin Ibrahim, Azhari A. Mohammed Nour, Mohamed Awad Elkarim Mohamed Ibrahim, Sultan Qasem Mashnafi, Wisal Abass Mohammed Babiker, Lobna Saad Mohammed Abd Elmeged, Soltan Jabir Algamdi https://creativecommons.org/licenses/by/4.0
Pasteurized Akkermansia muciniphila AKK ONE improves aging-related phenotypes and increases lifespan in zebrafish models
Background: Aging is a biological process characterized by progressive compositional and functional alterations in the gut microbiota. Akkermansia muciniphila, a commensal bacterium of the human intestine, has been shown to confer significant metabolic and health benefits, particularly in the context of aging-associated physiological decline. Objective: The primary objective of this study was to further evaluate the potential anti-aging effects of pasteurized Akkermansia muciniphila AKK ONE using aged zebrafish models. Methods: Three aging models were established in zebrafish through exposure to aluminum chloride hexahydrate, D-galactose, and hydrogen peroxide, respectively. Behavioral and physiological parameters were assessed, including light-dark transition time difference, total locomotor distance, movement distance within the blue region, telomere length, relative expression of the spns1 gene, and survival rate. Results: Administration of pasteurized AKK ONE significantly improved mobility as indicated by enhanced light-dark transition time difference and increased total moving distance. Additionally, after pasteurized AKK ONE treatment, the moving distance in the blue region of aged zebrafish rose compared to that of the normal control group, showing substantial improvements in learning and memory. At the epigenetic level, both telomere length and the relative expression of the spns1 gene were significantly improved after administration of pasteurized AKK ONE. Noteworthy is the increased survival rate in the pasteurized AKK ONE group. Conclusions: Pasteurized AKK ONE effectively ameliorated aging-related phenotypes in aspects of mobility, cognition, and epigenetics, and remarkably increased lifespan in aged zebrafish models. Keywords: pasteurized Akkermansia muciniphila AKK ONE, zebrafish, lifespan, aging, mobility, cognition, telomere, spns1 gene.
Copyright (c) 2026 Yangwenshan Ou, Haotian Feng, Nan Li https://creativecommons.org/licenses/by/4.0
Effects of Leu-Asp-Gln-Trp-enriched whey protein hydrolysate on mood and fatigue in healthy adults: A randomized, double-blind, placebo-controlled trial
Background: Mental health concerns and fatigue are increasingly prevalent among healthy adults. Objective: This study evaluated the effects of whey protein hydrolysate (WPH) enriched with the functional tetrapeptide Leu-Asp-Gln-Trp (LDQW) on mood state and fatigue. Methods: A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted on 112 healthy adults aged 18 to 64 years. Participants were randomly assigned to receive either an active food containing 1.0 g of MWPH (WPH with 0.1% of LDQW) or a placebo food daily for 12 weeks. The primary outcome was mood state using the Profile of Mood States-Short Form 2nd Edition (POMS2-SF), and the secondary outcome was fatigue, evaluated using the Visual Analog Scale (VAS). Results: The active group showed significant improvements in several POMS2-SF scores (Total Mood Disturbance, Depression-Dejection, Fatigue-Inertia, and Friendliness) compared with the placebo group at 12 weeks. Notably, the active group showed significant improvements in the Vigor-Activity score of POMS2-SF compared to the placebo group, at as early as 4 weeks, which persisted throughout the study. The VAS score for shoulder discomfort also significantly improved in the active group compared with the placebo group at 4 weeks and beyond. No adverse events related to the test foods were observed. Conclusions: Daily intake of the WPH enriched with LDQW improved mood state, reduced fatigue, and relieved shoulder discomfort, providing benefits for both mental and physical health. Trial registration: The study protocol was registered with UMIN-CTR (ID: UMIN000054349). Keywords: whey protein hydrolysate; mood; fatigue; shoulder discomfort; LDQW; functional peptides
Copyright (c) 2025 Mayu Nakatsuka, Kazumi Nabeshima, Ryo Sakiyama, Soichiro Sato, Manabu Nakano, Miyuki Tanaka, Masahiko Nakamura https://creativecommons.org/licenses/by/4.0
Ultra-low-dose lactulose modulates the gut microbiota in healthy adults: A double-blind, randomized, placebo-controlled crossover trial
Background: Gut health, particularly the composition and function of the gut microbiota, is increasingly recognized as essential for overall well-being. Non-digestible oligosaccharides are established prebiotics that stimulate beneficial gut bacteria; however, excessive intake may cause gastrointestinal discomfort. This study aimed to determine the minimum effective dose of lactulose using 16S rRNA gene sequencing to support safe and sustainable dietary applications. Methods: In a double-blind, randomized, placebo-controlled crossover trial, 100 healthy Japanese adults received lactulose (500 mg/day) or placebo for 28 days, separated by a 14-day washout period. The relative abundance of Bifidobacterium was analyzed using a linear mixed model with centered log-ratio transformation. Results: As a result of the analyses conducted on the PPS (Per Protocol Set, n = 78) and FAS (Full Analysis Set, n = 99), lactulose intake significantly increased the relative abundance of Bifidobacterium. Overall alpha diversity remained unchanged, although participants with low baseline alpha diversity enterotypes showed a trend toward restoration of alpha diversity. No adverse events or gastrointestinal symptoms, such as bloating or diarrhea, were observed, confirming the safety of lactulose. Conclusions: These findings provide novel evidence that even minimal doses of lactulose can beneficially modulate the gut microbiota, notably by increasing the relative abundance of Bifidobacterium without inducing laxative effects. Ultra-low-dose lactulose may serve as a practical and safe functional food ingredient to support long-term gut health, and continued research on its incorporation into functional food matrices will be important. Trial registration: The study protocol was registered with UMIN-CTR (ID: UMIN000055862). Keywords: Lactulose; Prebiotics; Bifidobacterium; Improving gut microbiota, Gastrointestinal health
Copyright (c) 2025 Ryo Sakiyama, Seiya Miyashita, Manabu Nakano, Miyuki Tanaka https://creativecommons.org/licenses/by/4.0
Glycemic benefits of a bitter melon-based multi-herbal extract supplement in adults predisposed to metabolic syndrome
Background: Herbal plants are rich in nutrients and bioactive compounds that contribute to health promotion and are associated with a reduced risk of metabolic syndrome. However, evidence from human clinical trials remains limited and inconsistent, particularly regarding the combined effects of multiple herbal species. Objective: This study aimed to evaluate the effects of consuming a dietary supplement containing extracts from various medicinal herbs on nutritional status, blood pressure, and key biochemical markers in adults predisposed to metabolic syndrome. Methods: A total of 70 adult participants aged 30-59 years who were at risk of metabolic syndrome were enrolled in a 12-week randomized, double-blind, placebo-controlled trial. Participants were randomly assigned into two groups: the experimental group (n=35), which received a bitter melon–based multi-herbal extract supplement (BMMH), and the placebo group (n=35). Pre-and post-intervention outcomes were compared, including waist circumference, body composition, glucose metabolism, lipid profiles, and inflammatory biomarkers. Dietary intake and physical activity were also assessed. Results: All seventy participants completed the study. After 12 weeks, participants who consumed BMMH extract supplement exhibited significant reductions in fasting blood glucose and HbA1c levels (p = 0.011 and p = 0.036, respectively). In addition, a significant decrease in the LDL-C to HDL-C ratio was observed (p = 0.014), whereas no comparable changes occurred in the placebo group. No statistically significant effects were observed for other lipid parameters or inflammatory markers, including IL-6, TNF-α, and hs-CRP. Conclusion: Bioactive compounds present in medicinal herbs, particularly bitter melon, may support glucose homeostasis by enhancing glucose utilization and thereby reducing blood glucose levels. These compounds may help reduce the risk of cardiovascular disease. Thus, consumption of dietary supplements derived from herbal extracts may serve as a supportive factor in improving metabolic syndrome outcomes and potentially preventing the development of non-communicable diseases. Trial registration: Thai Clinical Trials Registry TCTR20241122004 Keywords: functional foods, bioactive compounds, bitter melon, fasting blood glucose, metabolic syndrome
Copyright (c) 2026 Chanchira Phosat, Atchariya Chuenchom, Puyada Yaempannarai, Jirayu Lainampetch https://creativecommons.org/licenses/by/4.0
Assessment of toxic liver cirrhosis and its prevention through herbal hepatoprotectors with a proposed innovative strategy
Background: In contemporary medicine, effective andnosologically less harmful approaches for the prevention and treatment of liver cirrhosis remain insufficient, as indicated by the projected increase in mortality over the next decade. In recent years, the discovery and development of herbal medicine have surged. Therefore, a critical need of our time is to identify more comprehensive and novel strategies for studying liver cirrhosis to develop more effective prevention and therapy, such as those in this scientific paper. Objective: This study aims to observe the progressive dynamics of toxic liver cirrhosis using a novel preliminary diagnostic approach centered on the morphofunctional interrelationship of the liver, lungs, and kidneys and subsequently to formulate therapy strategies employing the proposed Flasil herbal combination. Methods: CCl₄-induced liver cirrhosis model was used in this prospective investigation. Mixtures (Flasil 1 and 2) prepared from active compounds of Helichrysum rubicundum (C. Koch.) flowers and S. marianum seeds grown in Armenia. At the end of the experiment, H&E staining was used to assess histological abnormalities in the liver and adjacent organs. Results: Research has demonstrated that toxic liver disease can manifest signs of pulmonary and renal disorders in the pre-cirrhotic state. Histopathological analysis showed that both Flasil formulations exhibited hepatoprotective effects while concurrently reducing pathological changes in pulmonary and renal tissues. Flasil 2 was more effective in promoting liver and kidney repair through enhanced hepatocyte regeneration, whereas Flasil 1 demonstrated greater efficacy in supporting lung tissue regeneration during the acute-to-chronic transition of liver cirrhosis. . However, non-invasive tests are needed to demonstrate both the feasibility of the proposed strategy and the different biological activities of the new Flasil combination according to the dose. Novelty: A liver-lung-kidney morphofunctional correlation tactical approach for the initial diagnosis of cirrhosis was assessed for the first time. FLASIL is the first natural product shown to affect liver-lung-kidney dysfunction in a CCl₄ model. Conclusion: This new approach (diagnosing through the liver-lung-kidney morphofunctional linkage) enables early detection and, based on it, prevention of cirrhosis by regulating its dynamics and giving varying dosages of the Flasil combination as an innovative herbal hepatoprotector. However, they necessitate the investigation of further diagnostic criteria. Keywords: liver cirrhosis, new approach, liver-lung-kidney linkage, herbal medicine, Flasil
Copyright (c) 2026 Lilit Arshakyan https://creativecommons.org/licenses/by/4.0
The second-meal effect of Undaria pinnatifida sporophylls (mekabu) in healthy young women: An open-label crossover study
Background: Postprandial hyperglycemia is an early indicator of impaired glucose tolerance and an established risk factor for the development of type 2 diabetes mellitus (T2DM). While low–glycemic index (GI) foods and soluble dietary fibers have shown efficacy in modulating postprandial glycemia, their capacity to influence glycemic responses to subsequent meals—referred to as the "second-meal effect"—remains underutilized in dietary interventions. Objective: This study aimed to investigate whether breakfast consumption of Undaria pinnatifida (mekabu), a seaweed rich in soluble fiber and sulfated polysaccharides, could attenuate postprandial glycemic response at a subsequent meal in healthy young women. Methods: An open-label, two-period, crossover study was conducted among healthy female participants. Subjects consumed a test breakfast with or without mekabu, followed by a standardized lunch. Capillary blood glucose levels were measured at multiple time points post-lunch to assess second-meal glycemic modulation. Results: The findings indicated that mekabu consumption at breakfast significantly reduced postprandial blood glucose levels after lunch, compared to the control condition. These effects may be mediated, at least in part, through delayed gastric emptying and enhanced GLP-1 secretion. Conclusion: Breakfast intake of mekabu may enhance glycemic stability over successive meals by eliciting a second-meal effect. These findings support the potential utility of mekabu as a functional dietary intervention for the early prevention of T2DM. Keywords: Mekabu (Undaria pinnatifida), Second-meal effect, Soluble dietary fiber, Postprandial glycemia, Glucagon-like peptide-1 (GLP-1), functional foods, bioactive compounds
Copyright (c) 2025 Masaki Taga, Kazuma Yohizumi, Hitomi Kobayashi, Naoki Iwamoto https://creativecommons.org/licenses/by/4.0
Microalgae and the gut microbiome: Insights from animal models to human trials
ABSTRACT: The gut microbiota is a vast consortium of microorganisms living in the gastrointestinal tract that plays essential roles in host metabolic, nutritional, and immune functions. However, this delicate ecosystem is susceptible to disruptions, or dysbiosis, which have been associated with conditions such as inflammatory bowel disease, obesity, and metabolic syndrome. The consumption of Western diets disrupts gut function; however, functional foods are essential for healthy microbiota. Microalgae, known for their ecological sustainability and rich nutritional profile, are increasingly considered promising sources of bioactive compounds, with growing evidence suggesting they may support the growth of beneficial gut microbes and help restore microbial balance. Microalgal-rich diets have shown promise by modulating fatty acid metabolism, inhibiting gut inflammation, and improving gut health. Despite previous investigations, the specific effects of microalgae on the gut microbiome remain underexplored, and the available data are dispersed. This review aims to unite and apprise the current scientific literature on the effects of microalgae-based dietary interventions on the gut microbiome by examining studies conducted in animal models, evidence from human-based approaches, including in vitro gut models and clinical trials, and identifying critical knowledge gaps in this research area. By highlighting the most relevant findings and outlining areas requiring further investigation, this review underscores the emerging potential of microalgae as microbiome-modulating agents and their promising role in next-generation functional foods for human health. Keywords: microalgae, gut microbiome, animal models, clinical trials, prebiotics
Copyright (c) 2025 Samuel Paterson, Tosin A. Olasehinde, Pilar Gómez-Cortés, Blanca Hernández-Ledesma https://creativecommons.org/licenses/by/4.0
Anti-type 2 diabetes mellitus activity of Citrus reticulata-derived materials: Mechanistic insights from integrated network pharmacology, molecular docking, and in vitro assays
Background: Citrus reticulata-derived materials (CRDMM) are representative medicinal and edible resources, yet their systematic evaluation for anti-type 2 diabetes mellitus (T2DM) potential remains to be fully elucidated. Objective: This study aimed to investigate the anti-T2DM potential of CRDMM and explore the underlying mechanisms of action using an integrated experimental and computational approach. Results: In vitro assays demonstrated significant α-glucosidase inhibitory activity across 16 CRDMM extracts, with Guangchenpi exhibiting the strongest potency (IC₅₀: 2.5–3.8 mg/mL). Network pharmacology analysis identified 10 active compounds and 74 potential targets, among which AKT1, TP53, PPARG, and PTGS2 were highlighted as core targets via protein-protein interaction analysis. Pathway enrichment suggested involvement in lipid metabolism and inflammatory pathways. Molecular docking confirmed strong binding affinities (< –7.0 kcal/mol) between key flavonoids (e.g., neohesperidin_qt and nobiletin) and the core targets. ADMET predictions indicated favorable drug-likeness, despite potential nephrotoxicity risks. Novelty: This study is the first to integrate multi-approach validation—combining in vitro bioactivity, network pharmacology, molecular docking, and ADMET profiling—to systematically reveal that CRDMM exerts anti-T2DM effects via a multi-component, multi-target mechanism. Conclusion: The results provide a scientific basis for developing CRDMM as functional food ingredients or dietary supplements for blood glucose management in T2DM. Keywords: Citrus reticulata, type 2 diabetes mellitus, α-glucosidase inhibition, network pharmacology, molecular docking, functional food, medicinal-food homology, nobiletin
Copyright (c) 2025 Hanhua Wang, Mingyue Li, Yanyue Wang https://creativecommons.org/licenses/by/4.0
Superiority of the body roundness index over BMI in linking central adiposity with vitamin D3: A cross-sectional study in Iraqi adults
Background: Body mass index is a poor measure of central adiposity. The Body Roundness Index may be a better measure, although data for Middle Eastern adults are limited. Objectives: To investigate the association of animal-fat consumption with adiposity indices as well as vitamin D3, and compare BRI with BMI as a marker of body fat in Iraqi adults. Methods: We used dietary questionnaires, anthropometry, and bioelectrical impedance to estimate visceral fat area and serum vitamin D3 in a cross-sectional study of 527 adults. Correlation and regression analyses were performed. Results: There was no association between animal-fat intake and the adiposity indices or vitamin D3. In contrast with BMI, BRI presented a quite strong inverse correlation with vitamin D3 (r = –0.497, p < 0.001). Visceral fat area was not predicted by any of the indices. Novelty explicit: In this adult sample from Iraq, BRI is more helpful than BMI for detecting central adiposity, which is associated with vitamin D3 insufficiency; as a result, BRI may be a better screening tool in a clinical and epidemiological context. Conclusion: BRI was a better indicator of metabolic risk associated with adiposity than BMI. In both clinical and epidemiological settings, it might be a beneficial screening tool for central adiposity and Vitamin D deficiency. Keywords: Body Roundness Index; Vitamin D3; Visceral fat; Body Mass Index; Adiposity.
Copyright (c) 2025 Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007 https://creativecommons.org/licenses/by-nc/4.0
Effect of homogenization and ultra-high-pressure homogenization on the activity of dairy by-products against gastrointestinal pathogens
Background: The growing emphasis on agri-food sustainability and the circular economy has promoted the valorization of dairy by-products, particularly whey, which has an estimated annual global production of approximately 200 million tons. Whey is a valuable source of proteins with nutritional and bioactive properties, and nearly half of its volume is processed into whey protein concentrate (WPC) and whey protein isolate (WPI). During WPI production, whey protein phospholipid concentrate (WPPC) is generated; however, its functional properties remain poorly characterized. The incorporation of bioactive compounds from bovine milk and its by-products into infant formulas and specialized products may contribute to gut, brain, and immune system health. Objective: This study aimed to characterize WPPC obtained from bovine whey and to evaluate its activity against Cronobacter sakazakii and rotavirus, as well as to assess the impact of conventional homogenization (CH) and ultra-high-pressure homogenization (UHPH) on this bioactivity. Methods: WPPC was obtained from industrial cheese whey through ultrafiltration and microfiltration. The resulting fractions were characterized by SDS-PAGE, laser diffraction (Mastersizer), and proteomic analysis, and were further compared with commercial WPPC. Conventional homogenization (25 MPa) and UHPH treatments (100–200 MPa) were applied using pilot plant-scale equipment. Antibacterial activity against C. sakazakii was evaluated by measuring bacterial growth and adhesion to Caco-2/TC7 cells, while antiviral activity against bovine rotavirus strain WC3 was assessed in MA104 cells using indirect immunofluorescence. Results: WPPC at a protein concentration of approximately 5 mg/mL inhibited C. sakazakii growth and adhesion to Caco-2/TC7 cells by ~40-50%, with both CH and UHPH enhancing the inhibitory activity of non-commercial WPPC by ~40%. WPPC achieved complete inhibition of rotavirus at concentrations above 0.25 mg/mL. The observed bioactivities appear to be mainly attributable to compounds with molecular weights greater than 30 kDa. Conclusion: WPPC exhibits significant antibacterial and antiviral activities, with antibacterial effects enhanced by homogenization treatments. UHPH emerges as a promising alternative to thermal pasteurization. These findings further expand current knowledge of WPPC functional properties and support its potential application as a functional ingredient in health-oriented food formulations. Keywords: cheese whey, WPPC, homogenization, ultra-high-pressure homogenization, rotavirus, Cronobacter sakazakii
Copyright (c) 2026 Laura García, Laura Carmona, Rodrigo Casado, María Dolores Pérez, Antonio J. Trujillo-Mesa, M. Manuela Hernández-Herrero, Artur X. Roig-Sagués, Laura Grasa, Lourdes Sánchez https://creativecommons.org/licenses/by/4.0
Cerebrovascular and antihyperlipidemic properties of sour cherry (Prunus cerasus) fruit
Background: Ischemic diseases are major global health burden, contributing significantly to cardiovascular and cerebrovascular disorders, with ischemic stroke being a leading cause. The main risk factors for ischemia are vascular wall damage, atherosclerosis progression, lipid metabolism disturbances, and increased platelet aggregation. Current medications targeting these mechanisms may lead to side effects, especially when they are used for prevention, driving interest in plant-derived compounds with cardiovascular and cerebrovascular benefits. Sour cherry (Prunus cerasus) has attracted attention for its high levels of polyphenols, anthocyanins, flavonoids, and organic acids, known for their blood pressure-regulating, anti-inflammatory, and sleep-modulating properties. These compounds protect the vascular system by reducing oxidative stress, inflammation, and endothelial dysfunction. Investigation of sour cherry cerebrovascular and anti-hyperlipidemic properties may contribute to integrating plant-based therapies into existing cardiovascular treatment strategies, offering new opportunities for disease prevention and management. Objectives: The purpose of this observation was to investigate the antihyperlipidemic activity and discover the new cerebrovascular effects of sour cherry fruits. Results: Obtained data evidenced that cholesterol levels in blood samples after 7 days of fruit intake were decreased by 2.74±1.52% compared with baseline parameters (day 0). Continued sour cherry fruit intake for 14 days led to further reduction in cholesterol levels by 8.1±3.30%, nearly three times exceeding the reduction level registered on day 7. Assessment of sour cherry fruits on triglyceride levels showed a significant reduction on days 7 and 14 by 17.86 ± 5.57% and 21.01 ± 9.25%, respectively, compared to baseline. No notable changes were observed in high-density lipoprotein (HDL) levels following sour cherry fruit intake. In contrast, low-density lipoprotein (LDL) levels decreased by 8.1 ± 4.24% after 14 days of consumption compared with control values. Registration of brain blood flow enabled the discovery of cerebrovascular activity in sour cherry fruits. It is noteworthy that its ability of sour cherry fruits to increase the cerebral blood flow (CBF) appears especially in case of cerebral blood flow impairment. Thus, under the normal condition, cerebral blood flow after intraperitoneal injection of 2.5 g/kg freeze-dried sour cherry fruit solution was not changed significantly. After the ligation of right common carotid artery, when CBF was decreased by 31.07±3.96% (p<0.05) intraperitoneal administration of the freeze-dried sour cherry fruits solution (2.5 g/ kg) was accompanied by the elevation of CBF, being above from occlusion levels by 13.6±5.19% ( p<0.05) at 30 minutes, and by 33.8±6.06% -at 80 minutes, compared to occlusion values. Notably, by the end of the experiment, CBF levels exceeded not only the occlusion level by 40.04±12.51%, as well as the baseline level. Conclusion: The findings of this study suggest that sour cherry fruits possess cerebrovascular and antihyperlipidemic activity, as based on their ability to improve impaired cerebral blood flow and reduce cholesterol and triglyceride levels. These results highlight the potential of sour cherry as a natural and effective plant-based agent for reducing cardiovascular disease risk factors, including hypercholesterolemia. Keywords: common carotid artery occlusion, new cerebrovascular activity, lipid spectrum changes, freeze-dried sour cherry.