Nutraceuticals

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

Background: Nutraceuticals are increasingly used in clinical practice for their anti-inflammatory, antiproliferative, and antioxidant properties. This study aimed to evaluate the safety and efficacy of a fixed nutraceutical combination containing chondroitin sulfate, α-lipoic acid, astaxanthin, lycopene, escin, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in improving pain and quality of life in patients with chronic knee osteoarthritis (OA). Methods: This observational study included patients with chronic knee OA who were referred to the ambulatory pain clinic at Dulbecco University Hospital, Catanzaro, Italy. Participants received one tablet daily for three months. Quality of life was assessed using the 36-Item Short Form Health Survey (SF-36), and adverse drug reactions (ADRs) were evaluated using the Naranjo scale. Results: Fifty patients (20 men and 30 women; mean age, 63.6 ± 11.4 years; range, 26–88 years; mean body mass index, 26.9 ± 3.7 kg/m²) were enrolled. Pain symptoms demonstrated a statistically significant improvement over time (p < 0.01). No ADRs were reported during the study period. Conclusions: The fixed nutraceutical combination improved pain and quality of life in patients with chronic knee OA and demonstrated an excellent safety profile. Full article

Morus alba L., a member of the Moraceae family, is known for its positive effects on human health, linked to the presence of different classes of secondary metabolites, including flavonoids, stilbenoids, and alkaloids, found in different parts of the plant. Stilbenoids, in particular, are mainly present at the root cortex level and, owing to their valuable activities, have attracted scientific interest in recent years. Since roots are a non-renewable source, in this study, M. alba in vitro callus cultures were established. The biomass with the appropriate growth and texture was selected for juice extraction, and the total phenol, flavonoid, and proanthocyanidin contents, along with the antioxidant activity, were estimated in the juices. The analyses throughout the callus growth cycle revealed the juice of 14-day-old calli to be the richest, resulting in the most active. In this juice, the LC-MS/MS-DAD analysis unveiled the presence of seventeen stilbenoids. Together with the data obtained by the nutritional analysis, the results showed that M. alba cell cultures have the potential to be utilised for producing innovative healthy food materials, bridging the gap between the ever-increasing natural-based-product demand and the need for more environmental, social, and economic development. Full article

The objective of this study was to investigate the effect of reactive extrusion (thermomechanical and chemical process) on the chemical composition, techno-functional properties, glucose and cholesterol adsorption capacity, and bioactive compound profile of spent coffee grounds (SCG). SCG was extruded using citric acid or alkaline hydrogen peroxide as reagents, and a control sample was extruded without reagents. Treatment with citric acid resulted in the highest levels of total dietary fiber (79.6 g/100 g) and insoluble fiber (76.2 g/100 g), especially cellulose, and significantly improved glucose (32.7 mmol/L) and cholesterol (4.5 mg/g) adsorption at neutral pH. Treatment with alkaline hydrogen peroxide increased water retention capacity (3.9 g/g). Although chemical treatments reduced total polyphenol and antioxidant activity, they effectively broke down the lignocellulosic matrix, thereby increasing fiber availability and functionality. Extrusion without reagents (processes induced by mechanical and thermal factors) favored the retention of caffeine and chlorogenic acids, increasing soluble fiber and maintaining antioxidant capacity. Therefore, reactive extrusion is a technological strategy that aligns with the principles of the circular economy, offering an environmentally friendly alternative to landfill disposal and adding value to spent coffee grounds by transforming lignocellulosic residue into functional ingredients with broad application potential. Full article

Arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, serves as a metabolic precursor for prostaglandins (PGs) such as PGE₂ and PGF_2α, which have been implicated in the regulation of skeletal muscle adaptations to resistance exercise. On this basis, AA supplementation has been proposed as a potential ergogenic aid in resistance training, under the hypothesis that increasing endogenous AA availability through supplementation may enhance PGs synthesis, thereby potentially influencing muscle remodeling and recovery process. However, AA remains a relatively underexplored candidate. This review aimed to summarize and critically evaluate the current evidence regarding the effects of AA supplementation in the context of resistance exercise. The limited available studies provide preliminary mechanistic observations suggesting that AA supplementation may be associated with changes in muscle strength and anaerobic performance and with modulation of the acute inflammatory response to exercise, without affecting chronic inflammation. Conversely, findings related to body composition and muscle hypertrophy remain inconsistent and a significant effect has not been consistently observed. Despite these preliminary insights, the current body of evidence is insufficient and heterogeneous, precluding the recommendation of routine clinical or practice-based use. Future well-designed, long-term investigations are warranted to clarify the efficacy, optimal dosage, and timing of AA supplementation, as well as its safety profile and potential applications across populations differing in age, sex, nutritional status, and training background. Full article

Fermented foods and prebiotics are increasingly studied for their potential therapeutic roles in metabolic disorders. In this study, 52 male Wistar rats maintained on a high-fat, high-sucrose (HFS) diet were supplemented for 8 weeks with either water kefir (providing approximately 10⁵ CFU per rat per day), olive leaf polyphenols (equivalent to 1.6 mg oleuropein daily), or a combination of both. Both interventions ameliorated HFS-diet induced weight gain, accompanied by reductions in subcutaneous and mesenteric fat, without additive effects when combined. Moreover, olive polyphenols decreased liver weight, suggesting a potential protective effect against hepatic steatosis through Fasn modulation. These metabolic improvements were accompanied by enhanced gut microbiota diversity. Together, these findings highlight water kefir and olive leaf polyphenols as potential dietary strategies for the management of obesity, hepatic steatosis, and dyslipidemia. Full article

Mixed dementia, most often caused by the coexistence of Alzheimer’s disease and vascular dementia pathologies, presents unique preventive and therapeutic challenges that may be addressed through dietary and nutraceutical interventions. Current evidence demonstrates that diets emphasizing polyphenol-rich foods like olive oil, berries, and leafy greens exert neuroprotective effects by reducing oxidative stress, inflammation, and amyloid pathology while improving cerebrovascular function. Specific bioactive compounds, including resveratrol, curcumin, quercetin, epigallocatechin gallate, N-acetylcysteine, and Huperzine A, among some others, have demonstrated therapeutic potential through their multimodal mechanisms targeting the pathogenic pathways of Alzheimer’s disease and vascular dementia, including Aβ and tau pathology, neuroinflammation, oxidative stress, and neurovascular dysfunction. However, our limited appreciation of the pharmacokinetics and pharmacodynamics of natural compounds and the inadequate extent of clinical studies underscore the need for further research. This review synthesizes current knowledge on diet and nutraceutical compounds that may be of value in the prevention and treatment of mixed Alzheimer’s disease and vascular dementia. We focus on their molecular mechanisms of action relevant to the dual pathophysiological basis of mixed Alzheimer’s disease and vascular dementia. Full article

Nutraceuticals are food-based products that provide health benefits beyond basic nutrition and play an increasingly important role in preventive healthcare. Ensuring their quality, safety, and efficacy is critical as the global market expands. A systematic literature search was conducted in Scopus, Web of Science, and PubMed using keywords such as ‘nutraceuticals,’ functional foods,’ and ‘quality control,’ with studies selected based on their focus on methods for standardization, characterization, and quality assessment. This review summarizes current analytical approaches, including spectroscopic, chromatographic, and techniques for elemental analysis, highlighting their applications in compound identification, quantification, detection of adulterants, and overall quality control. Emerging challenges and future trends, such as the integration of chemometrics and real-time analytical strategies, are also discussed, providing a comprehensive perspective on the evolving field of nutraceutical analysis. Full article

The interrelationship between iron metabolism and vitamin D has attracted increasing attention; however, nutritional knowledge regarding the relationship between iron and vitamin D remains scarce. We hypothesized that a continuous increase in dietary vitamin D intake would enhance biological iron levels through the regulation of hepcidin, and we investigated whether dietary vitamin D levels alter iron dynamics and blood cell status. Twenty-five male Wistar rats aged 7 and 8 weeks were used in experiments 1 (14 days) and 2 (4 days), respectively. Rats were divided into control and vitamin D-supplemented diet groups (14C vs. 14A in Experiment 1; 4C vs. 4A in Experiment 2) and fed the experimental diet ad libitum. In Experiment 2, no significant differences were observed in serum and liver iron levels, total iron-binding capacity, and serum transferrin saturation between groups; however, hepcidin (HAMP) mRNA expression was lower in the 4A group. By contrast, the 14A group showed significantly higher serum and liver iron levels and higher HAMP mRNA expression than the 14C group. These results indicate that high-dose dietary vitamin D alters iron metabolism in rats, characterized by transient suppression of hepatic hepcidin expression and increased liver iron, suggesting modulation of iron regulatory pathways. Full article

Background: Oxidative stress is a key contributor to many chronic diseases. Natural biocompounds with antioxidant activity are of growing therapeutic interest. Brassica macrocarpa, a plant from the Brassicaceae family, has shown in vitro safety and antioxidant potential due to its rich content of glucosinolates and phenolics. However, in vivo, its effects remain poorly characterized. This study aimed to evaluate the in vivo safety and biological effects of Brassica macrocarpa leaf extract in zebrafish embryos and to assess its potential to counteract copper sulphate (CuSO₄)-induced oxidative stress. Methods: Zebrafish embryos were exposed to Brassica macrocarpa extract at concentrations from 125 to 2000 µg/mL. Embryonic mortality and malformations were monitored daily to determine sub-lethal concentrations (125–500 µg/mL) for further behavioural and biochemical analysis. Antioxidant properties were tested in a CuSO₄-induced oxidative stress model. Results: No teratogenic effects were observed over 96 h. Larvae showed normal swimming and no behavioural changes. Pre-treatment with the extract significantly reduced CuSO₄-induced ROS and NO production, modulated antioxidant enzyme (SOD, CAT) activity, and lowered lipid peroxidation and protein oxidation, slightly affecting DNA damage. Conclusions: Brassica macrocarpa extract in vivo appears safe at sub-lethal doses and shows promising antioxidant effects, suggesting its potential role in managing oxidative stress-related conditions. Full article

Curcumin is widely used for its antioxidant and anti-inflammatory properties, but its poor oral bioavailability has driven the development of advanced formulations such as CAVACURMIN^®, a γ-cyclodextrin-based curcumin complex with enhanced absorption. Given recent regulatory scrutiny of high-bioavailability curcumin products, we evaluated the subacute oral safety of CAVACURMIN^® in Wistar rats. Animals received 2000 mg/kg/day (low dose) or 3500 mg/kg/day (high dose) for 28 days, with controls receiving vehicle or γ-cyclodextrin alone. No mortality or systemic toxicity occurred, except for one incidental death unrelated to treatment. Transient post-dosing signs (salivation, bedding displacement) were attributed to local sensory or irritant effects. Clinical chemistry showed modest, non-adverse variations—including decreased urea (up to −25% in males) and increased albumin (up to +9% in females)—that were not associated with pathological or clinical abnormalities. All other parameters, including body weight, food intake, haematology, organ weights (except for a small, non-adverse liver-weight increase in high-dose females), and gross pathology, were comparable to controls. These findings demonstrate that CAVACURMIN^® was well tolerated at doses up to 3500 mg/kg/day and provide a basis for subsequent OECD 408-compliant 90-day toxicity studies. Full article

Neurological and neurodegenerative diseases encompass a wide range of conditions affecting the central nervous system, leading to progressive dysfunction and damage. These diseases, such as Alzheimer’s, Parkinson’s, and some cerebral organic acidurias, often result in debilitating symptoms impacting motor control, cognitive function, and sensory processing. Research into their complex etiologies, including the role of energy and redox homeostasis, is crucial for developing effective diagnostics and therapeutic interventions. Despite the current lack of effective treatments for many neurological and neurodegenerative disorders, nutraceuticals are garnering significant interest. These food-derived compounds offer benefits beyond basic nutrition, primarily due to their ability to modulate intracellular processes that are known to be disrupted in these diseases. This study reviews the neuroprotective potential of several nutraceuticals, specifically creatine, acetyl-L-carnitine, melatonin, and resveratrol, as promising adjuvants to therapeutic interventions in neurological and neurodegenerative diseases. Full article