Nutraceuticals

Tyrosol, a phenolic compound derived from olive products, exhibits anti-inflammatory, neuroprotective, and cardiometabolic properties, whereas creatine is a well-established ergogenic aid with documented benefits for muscular performance and emerging evidence for cognitive support. This 5-week randomized, double blind, placebo-controlled trial examined the effects of Tyrosol, creatine, their combination, and placebo on resistance and aerobic exercise performance and psychomotor vigilance in healthy adults. Participants (n = 48; 18–50 years) consumed their assigned supplement for 4 weeks, after which changes in upper and lower body strength, submaximal resistance performance, aerobic capacity, lactate responses, plyometric performance, and acute cognitive function were assessed. The Tyrosol + Creatine condition produced the most consistent improvements in upper body resistance performance, particularly for higher load, higher volume bench press work. In contrast, neither the Tyrosol-alone group, the creatine-alone group, nor the placebo group achieved this effect, which suggests there is a synergistic effect between Tyrosol and creatine. No significant effects were observed for intermediate resistance loads, isometric lower body strength, grip strength, aerobic endurance, lactate responses, plyometric outcomes, or acute psychomotor vigilance. Collectively, these findings support the use of short-term co-supplementation with Tyrosol and low-dose creatine (without a loading phase) as a potentially beneficial strategy to enhance upper-body training quality in specific tests and improve upper-body strength endurance. Full article

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Despite their often-asymptomatic progression and complex therapeutic management, a substantial proportion of CVDs is preventable through early intervention and lifestyle modification. However, effective pharmacological strategies to fully reduce disease burden and associated risk factors remain limited. Polyphenols are a structurally diverse class of bioactive compounds widely distributed in plant-based foods, characterized by multiple phenolic and hydroxyl groups that confer potent redox-modulating properties. Increasing evidence indicates that dietary polyphenols exert cardioprotective effects through antioxidant, anti-inflammatory, and endothelial-modulating mechanisms. Experimental studies (in vitro and in vivo) have demonstrated that polyphenols regulate key molecular pathways involved in oxidative stress, inflammation, and vascular function, including PI3K/Akt/eNOS, AMPK/SIRT1, and Nrf2 signaling. In parallel, epidemiological and clinical evidence support their association with improvements in blood pressure, glycemic control, lipid profiles, and body weight, critical determinants of cardiovascular risk. Importantly, the biological response to polyphenol intake is highly variable and influenced by genetic background, metabolism, gut microbiota composition, and bioavailability constraints. This review provides an updated and integrative analysis of the molecular mechanisms underlying the cardioprotective effects of polyphenols, emphasizing their role in endothelial function and nitric oxide bioavailability. Additionally, it highlights recent advances in polyphenol-based nutraceuticals, discusses translational limitations, and outlines future perspectives for their application in cardiovascular disease prevention and management. Full article

Oilseed consumption in Morocco has seen enhanced relevance due to its nutrient and functional value. This research paper was undertaken to establish the most consumed oilseeds in the country and to compare their chemical profiles, nutritional contents and health-promoting properties. Two-hundred and fifty people spread out in various regions of Morocco were surveyed to obtain comprehensive information on the consumption patterns of the participants. The findings revealed that the percentage who consumed oilseeds was 91.2%, and the frequency of consumption was at a very low level, with the overall majority consuming the food less than once a week. Flax, sesame, sunflower, pumpkin, chia, anise, garden cress, black cumin, fennel, and fenugreek oilseeds were the most frequently consumed. At the same time, it is possible to note that the analysis of the available scientific evidence gave information about the chemical composition and the nutritional qualities of these oilseeds, which make their use of great advantage in the case of cardiovascular health, digestive system and skin health. Conclusively, although the consumption of oilseeds is still inconsistent, the research indicates that more of them can be consumed both nationally and internationally, especially with the help of nutritional education, awareness, and availability of fortified product campaigns. Full article

Silymarin (Silybum marianum (L.) Gaertn. extract) is a widely used botanical for liver disease, yet clinical results remain inconsistent. Most mechanistic work uses supraphysiological aglycones, whereas humans are exposed predominantly to phase II conjugates that are strongly protein-bound and routed by transporters toward bile and the intestinal mucosa. We reframe silymarin activity through a spatial pharmacology lens, proposing three post-intake windows: early (0–2 h) conjugate-dominant exposure with localised β-glucuronidase-mediated reactivation; intermediate (2–8 h) enterohepatic recirculation pulses; and late (8–48 h) microbial catabolite contributions. Each window engages distinct signalling modules—Keap1/NRF2, NF-κB, and AMPK-mTOR-TFEB—via transient redox events (quinone cycling, micro-H₂O₂ relays) and proteostatic remodelling (autophagy/mitophagy). We synthesise human pharmacokinetic and clinical evidence—with emphasis on MASLD and alcohol-associated liver disease—and show how formulation, meal timing, and microbiome metabotype determine which windows are engaged. Finally, we propose minimum reporting standards and falsifiable hypotheses to reduce between-study heterogeneity and enable precision use of silymarin. Full article

In this study, the pharmacokinetic (PK) characteristics of oleuropein present in the olive tree (Olea europaea) were determined. We developed and validated a highly sensitive ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method to quantify oleuropein and its aglycone derivative, thereby establishing their pharmacokinetic properties in vitro and in vivo. Quantification of oleuropein and oleuropein aglycone was performed using selected reaction monitoring (SRM) with heated electrospray ionization in negative ion mode, employing mass transitions of m/z 275.06 and 307.137 for the respective analytes, and methylparaben as the internal standard. The calibration curve for both exhibited a range from 1 ng/mL to 1000 ng/mL, utilizing a total of 10 calibrator standards. The method demonstrated superior sensitivity, precision, and reproducibility, facilitating accurate quantification of analytes over a wide concentration range in biological matrices. To develop a pharmacokinetic profile, C57BL/6 male mice were administered oleuropein at a dose of 100 mg/kg body weight via oral gavage, and plasma levels were examined by LC-MS/MS. Oleuropein pharmacokinetics were evaluated exclusively, as plasma levels of oleuropein aglycone remained below the limit of quantification throughout the 24 h sampling period. Mass analysis of plasma samples identified multiple glucuronidated and sulfated metabolites, establishing Phase II metabolism as the dominant pathway governing the systemic disposition of oleuropein. In addition, the metabolic stability of the compounds was also investigated in mouse liver microsomes and S9 fractions to define the in vivo stability of oleuropein and oleuropein aglycone. Full article

Roselle beverage residue (RBR), a by-product of Hibiscus sabdariffa L. processing, retains bioactive compounds, including soluble and insoluble dietary fiber and polyphenols. Its antihyperglycemic effect in type 2 diabetes mellitus (T2DM) has been previously demonstrated; however, its role in lipid metabolism remains unknown. This study assessed the preventive and therapeutic potential of RBR on dyslipidemia and hepatic steatosis in a rodent model of late-stage T2DM characterized by hyperglycemia and hypoinsulinemia. Male Wistar rats with T2DM induced by a high-fat and high-fructose diet combined with streptozotocin received 6% RBR supplementation as either a preventive intervention (starting at week 1 in healthy rats or week 9 in insulin-resistant rats) or a therapeutic intervention (starting at week 14 in diabetic rats). After 17 weeks, RBR supplementation significantly reduced serum triglycerides and total cholesterol, attenuating hepatic lipid accumulation regardless of the timing of intervention. Hepatic Acadm expression, involved in fatty acid β-oxidation, was significantly upregulated in rats treated with RBR from week 1 and 9, whereas no significant modulation was observed for genes related to fatty acid synthesis or uptake. These findings suggest that RBR supplementation may contribute to improving lipid metabolism and hepatic steatosis in a rat model of late-stage T2DM. Full article

This study aimed to explore the efficacy of oral supplementation with 11 probiotic strains, combined in the strain mix Probatech™ (Centro Sperimentale del Latte S.r.l Strada Provinciale per Merlino, 326839 Zelo Buon Persico (LO), Italy) and delivered through the food supplement PROBAFLOR and how it plays a positive role in maintaining normal intestinal function, providing benefits in healthy adult subjects. A 16-week, randomized, double-blind, placebo-controlled clinical study was conducted starting with 60 participants. Participants were randomly assigned to either the probiotic or placebo group. Participants were asked to provide one faecal sample at the beginning of the study, another one after 12 weeks of supplementation and the final one after 16 weeks. Amplicon 16S rRNA gene sequencing and GC-MS Short-Chain Fatty Acid (SCFA) profiling were performed on the faecal samples. Participants filled out questionnaires to assess their gastrointestinal health and psychological well-being. The overall mean GIQLI scores increased in both groups over time. The increases were significant within both groups but not between groups. Following the administration of PROBAFLOR, Shannon and Simpson diversity indices showed a significant increase at day 90 (week 12) (p < 0.05), demonstrating that the intervention effectively enhanced gut microbiota diversity. A shift in the intestinal microbiota towards SCFA-producing families and genera was observed. Moreover, the change in total and single SCFAs was significantly different between probiotic and placebo groups at the end of the supplementation period. Once-daily consumption of the PROBAFLOR probiotics formula regulated gut microbiota balance by modulating SCFA production. It may be beneficial for gut health, improving defecation habits and satisfaction, normalizing stool frequency, and promoting bacterial metabolism. Full article

Natural by-products (NBPs), including pomace, peels, stems, and skins, account for over 50% of materials generated during fresh fruit processing. Most of these are discarded or landfilled, contributing to environmental pollution. NBPs are rich in bioactive compounds, including polyphenols and flavonoids, suggesting their potential as functional ingredients for health promotion. Accordingly, twelve types of NBPs from Korea were extracted with 70% ethanol. Each extract was comparatively evaluated at a uniform concentration for antioxidant, tyrosinase inhibition, and elastase inhibition activities. Anti-inflammatory and antimicrobial activities were additionally evaluated to identify extracts with superior overall activity profiles. Based on these findings, four extracts exhibiting the highest activities were combined, and the NBP complex was further tested for its antioxidant, anti-inflammatory, and antimicrobial effects. Although certain individual NBPs extracts showed strong activities, the NBP complex exhibited enhanced overall effects. These findings indicate that selected NBPs, both individually and in combination, possess significant potential as health-promoting functional ingredients. The study provides scientific evidence supporting the valorization of fruit processing residues into value-added products while addressing environmental concerns associated with their disposal. Full article

Oxidative stress and environmental factors impair spermatogenesis and testicular function. The gut–testis axis has emerged as an important regulator of male reproductive health, influencing spermatogenesis beyond traditional endocrine control. This study evaluated the efficacy of a combination of Carob (Ceratonia siliqua), Bifidobacterium longum GA24, and ribonucleotides (MIX) on in vitro models of the gut–testis axis (co-culture Caco-2/HSerC on Transwell^® system). At the intestinal level, MIX increased Caco-2 cell viability, improved tight junction levels, regulated ROS production, and increased butyrate synthesis beyond physiological values, highlighting improved intestinal barrier function and integrity. In the gut–testis model, HSerC cells subjected to H₂O₂ 300 μM showed 1.5-fold increased viability, 81% reduction in ROS, increased ATP (+1.7-fold) and NO (+1.8-fold). The MIX combination reduced the apoptotic markers BAX (−1.6-fold), caspase-3 (−1.84-fold), and Cyto-C (−1.52-fold), and the inflammatory mediators TNFα and IL-6. MIX enhanced Sertoli cell maturation markers, increasing AR by 6-fold, p27 by 1.64-fold, and SGP-2 by 2.5-fold, and modulated hormonal-related markers by increasing testosterone and FSHR expression. These findings indicate that MIX may positively modulate the gut–testicular axis, supporting the intestinal barrier, testicular health, and spermatogenesis. Full article

Dietary fiber (DF) has a profound influence on human health mainly by modulating the gut microbiota. This review provides an overview of DF derived from cereals, legumes, fruits, vegetables, fungi, and seaweeds, specifically addressing the relationship between microbial utilization and source-specific structural characteristics (such as linking patterns, conformation, solubility, and fermentability). Due to these structural properties, different DFs display selective microbial responses that favor fermentation and the production of short-chain fatty acids (SCFAs). These microbial responses and fermentation-derived metabolites associated with DF intake may contribute to reduced risk of obesity, diabetes, inflammatory bowel disease, and other chronic disorders. This review does not address the trial heterogeneity, dose response, safety, and conflicting evidence, and much of the available evidence is largely observational and heterogeneous. Future studies should focus on dose–response trials of defined DF structures with standardized microbiome and metabolomic endpoints, including validation in human interventions. This review summarizes the DF source and structure, selective changes in the microbiota across various study types, including in vitro, animal models, and human studies, and how these relate to overall health. Full article

Chrysanthemum indicum L. (C. indicum), a perennial herb widely distributed across East Asia, has long been utilised in traditional medicine and as a functional food ingredient. Contemporary research has revealed a chemically diverse phytochemical profile, dominated by flavonoids, phenolic acids, sesquiterpene lactones, essential oils, carotenoids, and polysaccharides, which collectively underpin its broad pharmacological potential. Experimental studies demonstrate that extracts and isolated constituents of C. indicum exert pronounced antioxidant, anti-inflammatory, antimicrobial, hepatoprotective, cardioprotective, and anticancer effects in vitro and in vivo, often through modulation of key molecular pathways such as NF-κB, NLRP3 inflammasomes, AMPK–SIRT1, and Nrf2 signalling. Emerging pharmacokinetic evidence indicates variable oral bioavailability and metabolic transformation of major bioactive compounds, highlighting formulation challenges that may influence therapeutic efficacy. Toxicological studies suggest a generally favourable safety profile at traditionally used doses, although long-term and clinical safety data remain limited. Regulatory positioning varies internationally, with applications spanning traditional herbal preparations, dietary supplements and functional foods. Despite promising preclinical findings, significant challenges persist, including chemical standardisation, bioavailability optimisation, mechanistic clarification and the paucity of well-designed clinical trials. This review critically synthesises current knowledge on the botany, phytochemistry, pharmacological activities, pharmacokinetics, safety considerations and regulatory landscape of C. indicum, identifying key research gaps and outlining future directions to support its evidence-based development as a therapeutic and dietary agent. Full article

Recent advances in chiral analytical chemistry have revealed that fermented and natural foods contain substantial amounts of D-amino acids (D-AAs), the mirror-image counterparts of L-amino acids, leading to their recognition as nutraceutical components with potential health relevance. Although clinical evidence provides only limited support for their therapeutic efficacy, commercial expectations have outpaced scientific validation, and recent safety concerns emphasize the need for critical evaluation. In this review, we integrate findings from food chemistry, microbiology, biochemistry, physiology, and clinical research to provide a critical overview of dietary D-AAs. We examine how dietary exposure, microbial metabolism, host clearance capacity, and redox status collectively shape their context-dependent biological effects. We highlight the mechanistic linkage between D-amino acid oxidase (DAAO)-mediated hydrogen peroxide (H₂O₂) generation and organ-specific vulnerability, thereby clarifying the molecular basis of their “double-edged sword” actions. Within this interdisciplinary framework, we propose that D-AAs function as context-dependent “contronymic” molecules in cellular communication. By distinguishing physiological regulation, experimental modulation, and clinical application, this review aims to support evidence-based nutraceutical strategies and safety assessments that harness the potential benefits of D-AAs while minimizing associated risks. Full article

Estrogen suppress food intake, and soy isoflavones exhibit estrogen-like activities. However, the specific isoflavone components responsible for appetite regulation and their underlying neuroendocrine mechanisms remain unclear. We investigated whether the major soy isoflavones daidzein and genistein differentially influence feeding behavior and hypothalamic appetite-regulating neuropeptides in female rats. Ovariectomized (OVX) and sham-operated female rats were fed a control diet or diets supplemented with daidzein or genistein (150 mg/kg diet) for one or two weeks under ad libitum conditions. A separate OVX group received subcutaneous estradiol. Hypothalamic expression of orexigenic and anorexigenic neuropeptides was quantified during the dark (active) and light (inactive) phases. Daidzein, but not genistein, significantly reduced food intake, body weight gain, and body fat in both OVX and intact females, whereas estradiol decreased these parameters only in OVX rats. Among all hypothalamic neuropeptides examined, urocortin was the only gene that responded to dietary daidzein, showing a significant increase exclusively during the light phase of Week 1. Neither NPY nor CRH expression was altered by daidzein. The temporal pattern of urocortin induction closely paralleled the reduction in food intake, suggesting a potential mechanistic link. Daidzein exerts a female-specific anorectic effect that cannot be explained solely by estrogenic activity. The selective upregulation of hypothalamic urocortin during the light phase represents a novel neuroendocrine response to dietary daidzein and may contribute to its suppression of food intake. These findings provide new insight into the sex-specific metabolic actions of dietary isoflavones. Full article

Evidence suggests that gut dysbiosis may contribute to acute myocardial infarction (AMI) and its complications, including reduced physical performance and muscle weakness. We hypothesized that probiotic supplementation could improve muscle strength during post-AMI recovery. In a randomized, controlled, triple-blind clinical trial, adults and older adults undergoing myocardial revascularization received either a multistrain probiotic formulation (Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, Lacticaseibacillus acidophilus, and Bifidobacterium lactis) or placebo for 90 days. The primary outcome was handgrip strength (HGS). Forty-five participants completed the study. No significant between-group differences were observed in the main analysis. However, in an exploratory subgroup of men aged 50 years and older with low baseline HGS (n = 30), probiotic supplementation led to a greater improvement in non-dominant HGS after 90 days compared with placebo (mean difference: +4.6 kg/f; p = 0.04). A baseline-adjusted ANCOVA confirmed a significant baseline-by-treatment interaction for the non-dominant hand (β = +0.33; 95% CI: +0.02 to +0.62; p = 0.038), indicating greater improvements among participants with lower initial strength. Although the primary analysis yielded null results, these exploratory findings indicate a potential benefit of probiotic supplementation in a clinically vulnerable subgroup of revascularized men with low baseline strength. Larger and prospectively powered trials are warranted to confirm these observations. Trial registration: RBR-6ztyb7. Full article