Search Results (928)

Background: Elevated gamma-glutamyl transferase (GGT) is a biomarker associated with alcohol-related hepatic stress and oxidative imbalance. Although alcohol abstinence is the primary determinant of GGT normalization, adjunctive strategies may support biochemical improvement in real-world settings. Methods: This non-randomized cohort study included 197 of 1957 screened participants (10.1%), stratified according to baseline GGT into 55–99 U/L (n = 95) and ≥100 U/L (n = 102). Participants in the higher baseline subgroup underwent a multimodal intervention consisting of nutraceutical supplementation (silymarin, essential phospholipids, and a polyherbal antioxidant formulation) combined with structured psychological support aimed at promoting alcohol abstinence. The primary outcome was the change in GGT between baseline (T1) and follow-up (T2). Secondary outcomes included the proportion of participants achieving GGT reduction and the magnitude of change according to baseline severity. Clinical trial registration: ClinicalTrials.gov Identifier: NCT07603726. Results: Among participants with baseline GGT ≥ 100 U/L, GGT levels decreased from a median of 133.73 to 97.41 U/L (p < 0.001), whereas in the 55–99 U/L subgroup, median GGT changed from 67.49 to 66.51 U/L without reaching statistical significance (p = 0.072). Participants in the higher baseline subgroup demonstrated greater GGT reductions (median ΔGGT: −35.25 vs. −2.58 U/L), a higher proportion achieving GGT reduction (91.2% vs. 70.5%), and higher odds of GGT reduction at follow-up in exploratory analysis (OR = 4.32, 95% CI: 1.91–9.75). Conclusions: In this real-world cohort, reductions in GGT levels were observed, particularly among individuals with elevated baseline values (≥100 U/L) who underwent the multimodal intervention. These findings support monitoring GGT dynamics in routine clinical practice, where GGT remains a practical and accessible biomarker due to its widespread availability, low cost, and sensitivity to oxidative and alcohol-related hepatic stress. Full article

Medicinal mushrooms have become an important component of modern dietary supplementation and functional nutrition due to their diverse biological activities and long-standing use in traditional medicine. Among the most widely studied and utilized species are Ganoderma lucidum, Lentinula edodes, Grifola frondosa, Cordyceps militaris, Cordyceps sinensis, Trametes versicolor, and Inonotus obliquus. Their therapeutic potential is associated with a wide range of biologically active constituents, including polysaccharides, triterpenoids, phenolic compounds, and other secondary metabolites. Experimental and clinical studies indicate that extracts derived from these species may support immune function, modulate inflammatory responses, and exhibit antioxidant, antimicrobial, and anticancer properties. In addition to extensive in vitro and in vivo investigations, a growing number of clinical studies have evaluated the safety and potential therapeutic benefits of medicinal mushroom preparations in humans. In recent years, increasing attention has been directed toward their incorporation into nutraceutical formulations and functional foods aimed at supporting health and preventing chronic diseases. Advances in cultivation technologies and extraction methods have also contributed to improved availability and standardization of mushroom-derived products. This review provides a comprehensive overview of selected medicinal mushroom species commonly used in dietary supplements, focusing on their bioactive constituents, reported biological activities, and potential applications in contemporary medicine. Full article

Corn tortillas are consumed daily in Mexico. Alkaline extrusion is an alternative process that generates nixtamalized tortillas and preserves more bioactive compounds. Chickpea germination-extrusion may enhance the bioactive compound content. The aim was to characterize the physicochemical and antioxidant/antidiabetic properties of functional tortillas of alkaline-extruded blue corn (TC) with germinated (TG) or germinated-extruded (TGE) desi-chickpea. Likewise, the effect of simulated gastrointestinal digestion (SGD) on the bioaccessibility of bioactive compounds (phenolics, soluble protein, peptides, anthocyanins, and isoflavones) was estimated. Antioxidant capacity/cellular activity was determined by ORAC (AoxC) and in the Caco-2 cell line (CAA), while antidiabetic potential by α-amylase inhibition. The supplementation with processed chickpeas (TG/TGE) increased protein, ash, and isoflavone content (p < 0.05) compared with TC. SGD (%) released (p < 0.05) bioactive compounds from tortillas, and their bioaccessibility was among 34–70%; noticeably low phenolic bioaccessibility in TG/TGE. The AoxC was higher in TG/TGE (p < 0.05) compared with TC; in contrast, CAA was higher in TC, and both increased after SGD. TG depicted the lowest amylase inhibition; after SGD, the IC₅₀ values were 62–72-fold lower in the digests than in the tortillas. These results suggest that functional tortillas with processed chickpeas enhance nutraceutical potential. Full article

Type 2 diabetes mellitus (T2DM) is a major global health challenge that has intensified interest in multi-target nutraceuticals with potential adjunctive benefits. Ganoderma lucidum (Lingzhi/Reishi) is a medicinal mushroom traditionally used in East Asia and is increasingly investigated for its role in glycemic regulation and metabolic disturbances. This review critically synthesizes current evidence on its hypoglycemic effects, focusing on bioactive compounds, molecular mechanisms, and translational limitations. Unlike broader reviews on Ganoderma bioactivity and health-related benefits, this review specifically evaluates the alignment between taxonomic authentication, chemical standardization, preclinical mechanisms, and human clinical evidence in the context of glycemic regulation. This narrative review was based on a targeted literature search conducted in PubMed/MEDLINE, Web of Science, and Scopus for studies published up to October 2025, supplemented by Google Scholar. The included studies comprised in vitro experiments, in vivo animal models, and human clinical trials evaluating glycemic and metabolic outcomes of Ganoderma preparations. In vitro and animal studies indicate that polysaccharides, including β-(1→3)/(1→6)-glucans and proteoglycans such as FYGL, may improve insulin sensitivity via AMPK (AMP-activated protein kinase) and PI3K/Akt pathways, promote GLUT4 (glucose transporter type 4) translocation, suppress hepatic gluconeogenesis, protect pancreatic β-cells, and modulate gut microbiota. In enzyme assays and preclinical models, lanostane-type triterpenoids act primarily by inhibiting α-glucosidase and α-amylase, thereby potentially reducing postprandial glucose excursions. Despite consistent preclinical evidence, clinical findings remain heterogeneous, with the largest randomized controlled trial reporting no significant glycemic benefit. Overall, Ganoderma lucidum shows strong mechanistic plausibility but insufficient clinical evidence for antidiabetic efficacy. Future research should prioritize species authentication, chemical standardization, and adequately powered clinical trials. Full article

Cellular senescence drives aging and age-related disease through the accumulation of senescent cells and their senescence-associated secretory phenotype (SASP). Emerging evidence suggests intermittent (“hit-and-run”) senolytic interventions may improve healthspan by reducing senescent cell accumulation and the SASP. Healthy adults aged 45–79 were recruited for a decentralized, single-arm pilot study (NCT06953518) evaluating 2 days of nutraceutical supplementation (Qualia Senolytic). Fingerstick blood samples and validated quality of life (QoL) questionnaire data were collected on days 0 and 7. Primary outcomes were SASP biomarkers measured by the Olink^® Target 48 Cytokine panel, including tumor necrosis factor (TNF), interleukin-1 beta (IL-1β), interleukin-8 (CXCL8), and vascular endothelial growth factor A (VEGFA). Protein data were analyzed using linear mixed models and Wilcoxon signed-rank tests. Seventy-one adults enrolled and 53 (74.6%) provided paired protein samples. No significant changes occurred in primary outcomes. Exploratory unadjusted analyses revealed significant reductions in the established senescence chemokines CXCL9 and CXCL10, as well as CCL8 and CXCL11, and increases in interleukin-17F and oncostatin M. QoL significantly improved without safety concerns, though results are expectation-sensitive. Preliminary findings support the feasibility of this decentralized approach and identify candidate SASP biomarker signals in healthy adults warranting validation in randomized, placebo-controlled trials. Full article

Background: Muscle function determines overall health and is often impaired in metabolic syndrome and cancer, largely due to oxidative stress and inflammation. Olive mill wastewater (OMWW) is rich in bioactive polyphenols (e.g., hydroxytyrosol and verbascoside) that may hinder these potential pro-sarcopenic mechanisms, representing a potential nutraceutical to limit muscle health decline. Objective: To evaluate the effects of short-term supplementation with an OMWW-derived polyphenol extract (Oliphenolia^®, OMWW-OL) on muscle-related parameters and antioxidant biomarkers in adults at metabolic risk while maintaining dietary habits. Methods: This exploratory, hypothesis-driven secondary analysis was based on a single-arm longitudinal pilot study assessing patients at baseline (T0), after 30 days of supplementation (T1), and 30 days post-discontinuation (T2). Anthropometry, bioelectrical impedance, and biochemical assessments were performed. Results: Supplementation was associated with modest increases in skeletal muscle mass, muscle mass percentage, and wrist, arm, and calf circumferences. Fat mass decreased progressively, while total body water percentage and hydration status improved. Ferritin levels rose at T2, alongside increases in protein thiols (PSH) and Trolox equivalent antioxidant capacity (TEAC), suggesting improved iron status and reduced oxidative stress. Body weight and BMI decreased, as expected in a dietary intervention for metabolic syndrome, while muscle health showed a tendency toward improvement. Conclusions: Although the findings require cautious interpretation, short-term OMWW-OL supplementation was associated with modest but consistent directional changes in muscle-related and metabolic indicators in adults at metabolic risk. The results support hypothesis generation and highlight the need for larger studies to further explore the potential role of OMWW-OL in the context of cancer-associated sarcopenia. Full article

Chlorella and Arthrospira (spirulina) are aquatic microalgae of increasing nutraceutical interest due to their dense bioactive composition and multi-target biological activity. This narrative review provides a comparative, mechanistically integrated synthesis of molecular mechanisms and clinical evidence related to their supplementation. Current data indicate that both microalgae converge on three central regulatory axes: activation of Nrf2-dependent antioxidant responses, attenuation of NF-κB-driven inflammatory signaling, and modulation of AMP-activated protein kinase (AMPK)/protein kinase B (AKT)-mediated metabolic pathways. Spirulina demonstrates stronger mechanistic links to intracellular signaling and more consistent clinical evidence for improvements in lipid profile, insulin sensitivity, and systemic inflammation. In contrast, chlorella provides complementary effects, particularly in antioxidant capacity, blood pressure regulation, gut microbiota modulation, and detoxification-related contexts. Their bioactive components—including phycocyanin, carotenoids, polysaccharides, and peptides—act synergistically to influence mitochondrial function, immune homeostasis, and metabolic resilience. While clinical findings are generally consistent, heterogeneity in study design and product standardization limits definitive conclusions. Overall, chlorella and spirulina emerge as complementary multi-pathway biological response modulators with potential applications in preventive and integrative medicine. Full article

Background/Objectives: Cervical and lumbar radiculopathy and carpal tunnel syndrome (CTS) are common conditions that are associated with persistent pain, functional impairment, and reduced quality of life. Nutraceutical strategies targeting neuroinflammatory and oxidative stress pathways are being investigated as adjunctive approaches in pain management. This study evaluated the clinical association between supplementation with a Gastrodiae elata Blume-based nutraceutical formulation (Assonal^®) and changes in pain intensity, functional outcomes, symptom burden, and quality of life in patients with radiculopathy and CTS. Methods: A single-centre pragmatic before–after clinical study enrolled adults with cervical or lumbar radiculopathy and/or CTS. Participants received Assonal^® (two tablets daily) for two months. Pain intensity was assessed using the Numerical Pain Rating Scale (NPRS) and Visual Analogue Scale (VAS). Secondary outcomes included the Back Pain Functional Scale (BPFS), the Boston Carpal Tunnel Questionnaire (BCTQ), the Neuropathic Pain Symptom Inventory (NPSI), the EuroQol-5D-5L (EQ-5D-5L), and the Global Perceived Effect (GPE). Longitudinal within-subject changes were analysed using repeated-measures statistical tests. Results: Thirty-four participants completed the study. The observed pain intensity decreased significantly from baseline to two months (NPRS: 7.2 ± 1.3 to 3.6 ± 1.2; VAS: 7.3 ± 2.1 to 3.3 ± 1.7; p < 0.0001) and functional measures showed improvements across BPFS and BCTQ assessments, accompanied by reductions in symptom burden (NPSI). Quality of life increased significantly (EQ-5D-5L index: 0.49 ± 0.23 to 0.81 ± 0.12; p < 0.0001), and most patients reported perceived clinical improvement. Conclusions: In this exploratory real-world study, Assonal^® supplementation was associated with clinically relevant improvements in pain intensity, functional performance, and quality of life in patients with radiculopathy and CTS, suggesting the need for further investigation of these associations in future controlled clinical studies. Full article

Nowadays, it is central to generate innovations that convert agricultural by-products and food waste into valuable animal products while promoting the long-term resilience and sustainability of vulnerable animal production systems. Nutraceuticals (i.e., ‘nutrition + pharmaceutical’) are derived from foods that offer health benefits. In animal production, nutraceutical supplementation with Withania somnifera and Lepidium meyenii has shown positive effects on the endocrine, cardiopulmonary, and central nervous systems. We aimed to evaluate the possible impact of nutraceutical supplementation on rams fed a diet based on surplus feed from a highly industrialized Holstein cow production system, on corporal (live weight [LW], kg; body condition score [BCS], units), metabolic (blood glucose [GLU], mg dL⁻¹; serum protein [PRO], g 100 mL⁻¹), and sexual–testicular variables [sexual odor (ODOR, units); scrotal circumference (SC, cm); testicular volumes (TVOL, cm³); and estimated daily sperm production (EDSP, millions)]. Black Belly rams (n = 12; LW = 70.36 ± 1.2 kg; BCS = 2.96 ± 0.03 units; age = 3.8 ± 0.2 years; 25° N) were divided into 3 experimental groups: (1) WITH, supplemented with Withania somnifera (400 mg kg⁻¹ LW d⁻¹); (2) LEPI, supplemented with Lepidium meyenii (400 mg kg⁻¹ LW d⁻¹); and (3) CONT, not supplemented. The variables LW, BCS, GLU, PRO, and SC, as well as some components of TVOL, did not differ (p > 0.05) among the main effects of treatment or time; only ODOR, right transverse testicular diameter, and total testicular volume differed among treatments, generally favoring the WITH group. Furthermore, the TRT × T interaction demonstrated superior performance (p < 0.05) in the WITH group, with the largest values for LW, GLU, PRO, ODOR, SC, width of the right testicle, volume of the right testicle, total testicular volume, and EDSP. From a productive–reproductive perspective, the Robin Hood Effect—through the use of rejected dairy cattle rations as the base diet for rams—and supplemented with nutraceuticals (WITH and LEPI), emerges as a viable alternative to improve not only the productive–reproductive performance of Black Belly rams, but also other productive and socioeconomic outcomes; the latter contributing to the strengthening of producer and family well-being. Full article

Bromelain is a complex of proteolytic enzymes obtained from Ananas comosus, widely used in dietary supplements for its anti-inflammatory, immunomodulatory, anti-edema, and wound-healing properties. Despite its broad commercial use, the quality control of bromelain-based products is often limited to enzymatic activity assays, which may not be sufficient for confirming authenticity. This study aimed to evaluate the quality of bromelain-containing products. Four commercially available bromelain samples were analyzed using a multidisciplinary analytical strategy. The study results demonstrated that only one of the assessed raw materials met the declared values in terms of bromelain activity and quality. Of the other three samples, two showed no enzymatic activity, while the other revealed activity complying with the declared specification that was due to papain, rather than bromelain. The present study demonstrates that enzymatic activity alone is insufficient to validate the quality of bromelain and related finished formulations. An integrated analytical approach is essential to detect adulteration, confirming authenticity and ensuring the safety and efficacy of bromelain supplements. Such methodologies should become a regulatory priority in the nutraceutical industry to protect consumer health and ensure product integrity. Full article

Nutraceuticals are emerging as promising agents for the prevention and treatment of atherosclerosis, particularly in light of the limitations associated with current pharmacotherapies. Pomegranate-derived polyphenols, especially punicalagin (PC), possess multiple cardioprotective properties. However, their direct biological effects are constrained by poor absorption and low bioavailability. Instead, many of their actions are mediated by gut microbiota-derived metabolites known as urolithins. Despite this, the roles of PC and its metabolites in atherosclerosis remain inadequately defined. The objective of this study was to investigate the anti-atherogenic effects and underlying mechanisms of PC and its major metabolites—ellagic acid and urolithins A, B, C, and D—using in vitro and in vivo approaches. In vitro, these compounds broadly inhibited key pro-atherogenic processes in macrophages and endothelial cells, including reactive oxygen species production and inflammatory gene expression, with notable metabolite-specific differences. Urolithin A (UA), identified as the most effective compound, was further evaluated in LDL receptor-deficient mice fed a high-fat diet. UA supplementation improved peripheral blood immune cell profile, reduced atherosclerotic plaque burden and inflammation, and enhanced markers of plaque stability. RNA sequencing of the thoracic aorta revealed key molecular pathways underlying the protective actions of UA. Collectively, these findings highlight the therapeutic potential of PC-derived metabolites, particularly UA, in combating atherosclerosis and support the need for future human clinical studies. Full article

Oral joint supplements (OJSs), specifically those containing glucosamine and chondroitin sulfate, are some of the most popular feed additives fed by horse owners. However, evidence of the efficacy of these nutraceuticals in vivo is lacking. To investigate the impacts of an OJS on equine lameness, 40 geldings (18 ± 7 yr) with chronic lameness and AAEP lameness grades between 2 and 4 (as scored by a veterinary sports medicine and rehabilitation specialist) were enrolled in the study. Horses were stratified by lameness grade, BCS, and weight, and then randomly assigned to receive a placebo powder or an OJS daily for 6 wks. Stride length measurements and lameness evaluations were performed every 2 wk. There was no effect of treatment or treatment-by-day interaction for stride length, though day affected both walk (p = 0.04) and trot (p < 0.01). Only day affected lameness grade, with the lowest average score on d28 (p = 0.04). There was no evidence of supplementation improving gait symmetry over time. As such, there is no evidence to support efficacy of the tested OJS when fed for 6 wk. These results emphasize the importance of well-controlled studies and support continued development of evidence-based management strategies for equine joint health. Full article

Background/Objectives: The rapidly expanding landscape of digital technologies is transforming innovation processes across industries, and the food sector is increasingly encouraged to adopt novel tools that can enhance development workflows and support competitive positioning. In the context of Industry 4.0, it is particularly important to examine open innovation approaches that may increase the efficiency of engineers and researchers involved in the research and development of food supplements. Such approaches enable broader access to relevant scientific information, including new bioactive ingredient research and their physiological implications, potentially contributing to the development of better-informed and higher-quality products. Methods: In the present study, we evaluated the deep research capabilities of several popular large language models to assess their suitability for supporting the conceptual design of a blood glucose-optimizing food supplement intended for prediabetes management. The comparative analysis focused on the level of detail in the outputs generated by each model, the robustness of the conclusions drawn, and the capacity to produce formulation-oriented recommendations grounded in scientific literature and regulatory frameworks. Our evaluation was primarily qualitative and subjective, highlighting both the potential and limitations of these models. Moreover, the study outlines a forward-looking concept for product validation using wearable smart devices and medically certified wearable devices with continuous biometric monitoring, which could provide an innovative avenue for assessing supplement efficacy. Results: The findings indicate that large language models can support the collection, organization, and preliminary interpretation of complex scientific information. Conclusions: Nevertheless, expert input remains essential for accurate evaluation, scientific validation, and regulatory compliance, as these models cannot yet replace domain expertise or rigorous experimentation in food supplement development. Full article

Background: Menstrual migraine (MM), including pure menstrual migraine (PMM) and menstrually related migraine (MRM), is characterized by attacks occurring in close temporal association with menstruation and is often more severe, longer lasting, and less responsive to treatment than non-menstrual migraine. Prostaglandin-mediated inflammation and calcitonin gene-related peptide (CGRP) release play a key role in MM pathophysiology. Phycocyanin (PC) and palmitoylethanolamide (PEA) are nutraceutical compounds with anti-inflammatory, analgesic, and neuroprotective properties that may be beneficial as short-term perimenstrual prophylaxis. Objectives: To evaluate the effectiveness of an oral supplementation combining phycocyanin and palmitoylethanolamide as a short-term prophylaxis for menstrual migraine in a real-world clinical setting, a retrospective observational study without a control group was conducted in five Italian centers between May 2023 and June 2025. Methods: Clinical records of 800 women were reviewed, and 220 patients receiving perimenstrual supplementation with phycocyanin and palmitoylethanolamide were screened. Sixty-one women diagnosed with migraine without aura, according to the International Classification of Headache Disorders, met all inclusion criteria and were analyzed. Phycocyanin and palmitoylethanolamide were taken at a dosage of two capsules daily from five days before to five days after the onset of menstruation for three consecutive months. Outcomes during the perimenstrual window were compared with a three-month period without supplementation. Primary outcomes included migraine severity, frequency, and duration of the attacks; secondary outcomes included analgesic consumption and menstrual migraine-associated symptoms. Results: Among the 61 included patients, phycocyanin and palmitoylethanolamide supplementation was associated with a significant reduction in migraine severity across all monitored perimenstrual days (p < 0.0001). While the overall monthly frequency of migraine attacks did not change, the number of migraine days during the perimenstrual window significantly decreased from the first month of supplementation (p < 0.05). Moreover, migraine duration during the perimenstrual window was significantly reduced at one, two, and three months of phycocyanin and palmitoylethanolamide supplementation compared with baseline. Analgesic use and the number of days with migraine-associated symptoms (nausea, vomiting, photophobia/phonophobia) were also significantly reduced. Treatment was well tolerated. Conclusions: In this real-world retrospective study, perimenstrual supplementation with phycocyanin and palmitoylethanolamide was associated with reduced severity, duration, and perimenstrual frequency of menstrual migraine attacks, along with decreased analgesic use, suggesting a safe and potentially beneficial short-term prophylactic strategy for women with menstrual migraine. Full article

Objectives: To evaluate the long-term effects on retinal structure and visual function of oral bromelain and curcumin supplementation in patients with inherited retinal dystrophies (IRD) complicated by persistent cystoid macular oedema (CMO). Methods: We retrospectively studied 20 eyes with genetically confirmed IRD complicated by CMO, with refractory to systemic or local treatments performed for 6 months. We collected baseline (V1) and follow-up (V2) data from these IRD-CMO patients, who were continuously supplemented with oral bromelain and curcumin for 12 months. Outcome measures were the Snellen best-corrected visual acuity (BCVA) and central macular thickness (CMT) values, collected by spectral-domain optical coherence tomography (OCT). Based on OCT scans, we classified IRD-CMO as microcystic or macrocystic, performing this sub-grouping in two eye cohorts (n = 10). Baseline median BCVA and CMT differences in both groups were verified (Mann–Whitney test). For both CMO groups, changes from V1 to V2 in median BCVA and CMT values were evaluated (Friedman test). Results: At baseline, both the median BCVA and CMT values were significantly different in both groups (p < 0.01 and p < 0.001). Between V1 and V2, in the microcystic CMO group, a slightly improved median BCVA was found, whereas the median CMT was reduced; however, this did not reach statistical significance (p = 0.6 and p = 0.2, respectively). In the macrocystic CMO group, a significant stable median BCVA was found from V1 to V2, with concomitant significant reduction in median CMT (p < 0.05 for both comparisons). Conclusions: Retinal structural improvement and visual function preservation were observed after oral bromelain and curcumin supplementation in macrocystic IRD-CMO. It is likely that the vasogenic component in macrocystic CMO is more responsive to nutraceutical molecules than the degenerative microcystic component. Full article