Nutraceuticals

Bacteriocins from lactic acid bacteria have attracted considerable attention as natural alternatives to conventional antimicrobial agents. Weissellicin LM85, a bacteriocin purified from Weissella confusa LM85, has been less extensively studied in terms of its mechanism of action and potential applications. In this study, purified weissellicin LM85 exhibited potent inhibitory effects against Gram-positive bacteria, with minimum inhibitory and bactericidal concentrations determined against Micrococcus luteus MTCC106. Time-kill assays and fluorescence staining indicated a concentration-dependent reduction in cell viability, accompanied by membrane disruption. Further analyses revealed potassium ion efflux, dissipation of membrane potential (Δψ) and pH gradient (ΔpH), genomic DNA fragmentation, and pronounced morphological alterations in target cells. These findings are strongly suggestive of membrane-targeted bactericidal activity, likely involving pore-forming effects. In addition, weissellicin LM85 inhibited both growth and biofilm formation of Salmonella enterica subsp. enterica serovar Typhimurium ATCC13311 and Staphylococcus aureus subsp. aureus ATCC25923. Mechanistic analyses revealed the disruption of cell membrane integrity, leakage of potassium ions, cytoplasmic contents, and non-specific DNA degradation, indicating a multifaceted antibacterial mode of action. These findings highlight weissellicin LM85 as a promising natural antimicrobial with potential applications in food preservation and the control of foodborne pathogens and biofilm-associated infections. Further studies on cytotoxicity and in vivo efficacy are required to advance its practical application. Full article

Protein supplements are popular nutritional supplements consumed primarily by physically active individuals with increased protein demands. Despite the increasing consumer demand for protein supplements in Greece, detailed and comparative data on the nutritional profile of such products is scarce. The purpose of this study was to determine the nutritional quality of protein powder supplements available in the Greek market and to compare animal- with plant-based products. Data was extracted from the websites of the major retailers (n = 28). In total, 216 products were identified and grouped as animal- and plant-based, depending on the protein origin. Animal-based products were predominantly (84.0%) produced from whey. Protein content was significantly higher (p < 0.05) in animal-based products, providing 43.5% of the reference intake (RI) for men and 53.2% for women per serving. The content of essential amino acids (EAAs), branched amino acids (BCAAs) and alanine (Ala) was significantly higher (p < 0.05) in animal-based products (median: 11.0, 5.3 and 1.2 g/serving) compared with plant-based alternatives (median: 8.4, 4.0 and 1.0 g/serving size). Plant-based protein supplements contained significantly higher (p < 0.05) content of fiber, fat and salt and were more energy-dense per 100 g. Mean serving size was larger for animal-based products (29.9 ± 0.4 g) compared with the plant-based ones (28.1 ± 0.5 g). Animal-based supplements were more expensive to purchase by 4.3 € per kg. Overall, animal-based protein powder supplements show a more desirable nutritional profile regarding protein content and quality. Results of this study can serve as a tool for consumers to make informed and healthy choices and for health professionals to provide effective and personalized guidance based on the nutritional content of products. Full article

The olive fruit is recognized for being a significant source of phenolic compounds, including hydroxytyrosol (H-tyr), tyrosol (Tyr), oleuropein (Ole), and verbascoside (Verb). The maturity index (MI) significantly influences the phenolic profile, which is a cultivar-specific trait. A study was conducted to assess the evolution of the phenolic profile in seven olive cultivars during ripening: ‘Galega vulgar’ (Gv), ‘Azeiteira’ (Az), ‘Cobrançosa’ (Cob), ‘Picual’ (Pic), ‘Carrasquenha’ (Car), ‘Redondil’ (Red), and ‘Arbequina’ (Arb). The results indicate a declining trend in total phenolic compounds (TPC) across all cultivars, with Cob and Car exhibiting the highest values, over 60 g GAE kg⁻¹ at T1 and above 30 g GAE kg⁻¹ at T7, respectively. In Ole quantitation, Red demonstrated the highest values, recording 39 g kg⁻¹ in T1 and 15 g kg⁻¹ at T7, with per olive fruit unit measurements ranging from 19.7 mg at T1 to 22.7 mg at T7. These findings underscore olive fruit as an exceptional source of bioactive compounds and their advantageous health-promoting effects, which might be utilized as a functional food source, validating the unique phenolic profiles of each cultivar in relation to ripening. Full article

The human gut microbiota helps maintain metabolic balance, supports immune function, and defends against opportunistic pathogens that can disrupt the microbiota ecosystem. An imbalance or dysbiosis in microbial composition is linked to various diseases, including inflammatory bowel disease, metabolic syndromes, and neurodegenerative disorders. Using microbiota modulation with prebiotics and postbiotics is a practical approach to address these imbalances. Prebiotic compounds are defined as substrates that promote metabolic activity and restore microbial patterns. Postbiotics include short-chain fatty acids (SCFAs), microbial cell lysates, and extracellular compounds. This research aims to investigate how the gut microbiota can be modulated in vitro using the prebiotic ColonX and a postbiotic derived from Kombucha fermentation within a controlled GIS1 in vitro system. These products demonstrate potential for modulation, as they support selective bacterial growth and enhance microbial diversity. Prebiotics help stabilize gut pH, while postbiotics play a crucial role in biofilm formation. Together, they provide an innovative approach to treating dysbiosis and enhancing overall gut health. The findings highlight the importance of utilizing prebiotics and postbiotics to modulate gut microbiota in chronic diseases characterized by dysbiosis. This paper is especially relevant for elderly populations, as gut dysbiosis is common, and microbiota modulation supports healthy aging. Full article

Urinary tract infections (UTIs) are common and create significant clinical challenges. Most UTIs are caused by uropathogenic Escherichia coli (UPEC) and affect 50 to 70% of women at some point in their lives. Of this population, 25% will have a recurrent urinary tract infection (rUTI) within 3 to 12 months of the first episode. High rates of rUTIs may occur because UPEC can enter a non-proliferative or quiescent state within the urothelium of the bladder. This state allows UPEC to evade the host’s immune response and antibiotic treatment. We utilized a library of plant extracts derived from the URI Heber W. Youngken Jr. Medicinal Garden to determine if they reversed UPEC quiescence with a novel in vitro quiescence assay using the classic UPEC endemic lineage ST73 strain CFT073. We found an overall active extract hit rate of 69% (79/114 active) and that active extracts contained high levels of polyphenolic compounds. Further testing showed that polyphenols with adjacent hydroxyl groups on a benzene ring (catechol moiety) were the most effective and potent in reversing quiescence. The ability to reverse quiescence was also linked to the compound’s ability to bind iron (e.g., epigallocatechin gallate and rosmarinic acid were the most potent reversing agents—0.1 mM—and they both had the strongest iron-binding activity as determined via CAS assay). These findings reveal a new class of metabolites that can reverse quiescence in UPEC strains. Full article

DHMBA, a novel antioxidant derived from oyster, exhibits dual properties that block oxidative stress by acting as a radical scavenger in various cells. DHMBA has been shown to play a pharmacological role by exerting anti-macrophage and anti-cancer effects. Gallic acid, which is widely distributed in edible plants, exhibits a potent antioxidant activity. In this study, we compared the effects of DHMBA and gallic acid using inflammatory macrophages (RAW264.7 cells) and human lung cancer cells (A549 cells) in vitro. In these cells, we demonstrated that DHMBA at comparatively lower concentrations (1 or 10 µM) significantly affected cell proliferation and stimulated cell death, resulting in a decrease in cell number. Gallic acid at 1 and 10 μM did not affect the proliferation or death of RAW264.7 and A549 cells. DHMBA may be a potent antioxidant that regulates cell function. Despite having the same molecular weight, the chemical structure of DHMBA and gallic acid exerted different effects. Notably, the combined DHMBA and gallic acid with comparatively lower concentrations (1 and 10 μM) showed potent effects in suppressing the proliferation of RAW264.7 and A549 cells. However, this combination did not induce a significant effect on cell death. Thus, the effects of DHMBA were potentiated in the presence of the antioxidant gallic acid. This finding suggests a potential effect induced by the combined antioxidants. This study provides a new strategy for disease prevention using the strong antioxidants DHMBA and gallic acid. Full article

Major depressive disorder (MDD) is the most common mood disorder among adults. Despite the wide use of pharmacological agents by those with MDD, the evidence indicates that only a small fraction of patients benefits, and many individuals using antidepressant therapy relapse. Side effects are numerous with antidepressants, which can be a factor in patient medication compliance. Along with psychotherapy and fine-tuning lifestyle components, another emerging option in treating MDD is the use of bioactive natural products known as nutraceuticals. We present the scientific findings specific to select nutraceuticals (e.g., omega-3 fatty acids, S-adenosyl-methionine, folate-based compounds, and vitamin D) either as a monotherapy or as adjunctive therapy to a pharmaceutical antidepressant, for treatment of MDD. Many studies demonstrate that nutraceuticals result in a decrease in depressive symptoms with fewer side effects as traditional medications and have the potential to improve the result of antidepressants, especially in individuals experiencing resistance to medication. From a therapeutic perspective, a holistic approach incorporating psychotherapy, pharmacological therapy, and lifestyle factors (inclusive of nutraceutical use) appears most logical and could provide for enhanced treatment efficacy. Full article

Pistacia terebinthus L. which has been traditionally used in diet and medicine, remains underexplored in Greece, particularly regarding its chemical composition and antioxidant activity. The current study aims to comparatively evaluate the chemical profile of cold-pressed terebinth fruit oils, obtained from wild trees growing in the Greek Island of Chios (North East Aegean Sea), harvested during three years (2019, 2020 and 2021). The oils’ lipid profile was dominated by oleic acid (C18:1 cis-9) (42–45%) followed by palmitic acid (C16:0) (24–30%) and linoleic acid (C18:2 cis-9,12) (19–22%). Their phenolic acid content, expressed as anacardic acids—known for their bioactive properties—was quantified via q-¹H-NMR and found to be markedly high (1.91–2.98 mmol/kg oil). Total phenolic content (TPC) of the fruit extract showed interesting high value (185.92 ± 2.61 mg GAE/g) accompanied by strong antioxidant activity (DPPH, exhibiting > 80% inhibition at a concentration of 100 µg/mL) which was positively correlated with TPC. Additionally, the fruits demonstrated a rich nutritional profile, particularly in crude fibers (38.9%) and essential minerals (K, Mg, and Zn), along with low sodium content, suggesting notable dietary benefits. The cold-pressed oil exhibited high lipid content and low specific extinction coefficients (K₂₃₂, K₂₇₀), indicating minimal oxidation and confirming the oil’s freshness. These findings highlight the potential of P. terebinthus fruit oil as a high-value functional raw material with nutritional and antioxidant properties. Comparable to olive oil in lipid quality, Greek turpentine fruit and oil could play a promising role towards further applications in the food, cosmetic and pharmaceutical sectors. Full article

The leaves and stems of Bauhinia guianensis Aubl. are used in traditional Amazonian phytotherapy for the treatment of pain and inflammation. This study investigates the anti-inflammatory and antinociceptive effects of hydroethanolic extracts from B. guianensis Aubl. leaves and stems (HELBg and HESBg, respectively) in vivo models of inflammation and hyperalgesia. Danio rerio experimental animals were submitted to the acute inflammation test, induced by intraperitoneal (ip.) administration of carrageenan 20 μg/animal (abdominal edema); the groups were previously treated orally with saline solution 2 μL/animal (SS), dimethyl sulfoxide 2 μL/animal (DMSO), indomethacin 10 mg/kg, HELBg 100 mg/kg and HESBg 100 mg/kg, n = 12 per experimental group to evaluate the inhibition of edema and alteration histopathology of the liver, intestine and kidney of these animals. The antinociceptive effect was observed from the body curvature index and the behavioral responses of Danio rerio, after an experimental protocol for the induction of hyperalgesia, by ip. administration of 10 μL/animal of 2.5% acetic acid; the animals were orally treated orally with saline solution 2 μL/animal (SS), dimethyl sulfoxide 2 μL/animal (DMSO), morphine 2.5 mg/kg, HELBg 100 mg/kg and HESBg 100 mg/kg, and n = 5 per experimental group. In carrageenan-induced edema, the group treated with HESBg inhibited edema formation over the 3 h of the experiment. Maximum edema was inhibited by 54% (p < 0.05) when compared to the control group. Both HELBg and HESBg prevented body curvature index changes (t_(df=3,8) = 6.96 and t_(df=3,8) = 6.61, respectively, both p < 0.0001). In the behavioral parameters sensitive to antinociceptive pharmacological modulation, due to the abdominal constriction induced by acetic acid, the administration of HELBg and HESBg resulted in an improvement in swimming activity, with the following results: increase in distance covered (F_(df=3,16) = 6.50 and F_(df=3,16) = 7.72, respectively, both p < 0.0001), decrease in freezing time (F_(df=3,16) = 2.04 and F_(df=3,16) = 1.28, respectively, both p < 0.0059), increase in the number of ascents to the upper area of the tank (F_(df=3,16) = 33.02 and F_(df=3,16) = 35.62, respectively, both p < 0.0009) and decreased time spent in that area (F_(df=3,16) = 101.19 and F_(df=3,16) = 103.59, respectively, both p < 0.0038). It is reasonable to suppose that both extracts modulated the variations induced by carrageenan and acetic acid through the inhibition of prostaglandin biosynthesis, thereby decreasing the release of inflammatory mediators, the sensitization of peripheral nociceptors, and, consequently, the perception of pain. These results suggest that HELBg and HESBg have anti-inflammatory and antinociceptive activities, likely of peripheral origin and associated with the inhibition of prostaglandin biosynthesis. Full article

Psoriasis is a chronic inflammatory autoimmune skin disease with current treatments often causing significant side effects. This study systematically evaluated the therapeutic potential and mechanisms of polyphenolic compounds in psoriasis treatment. Following PRISMA guidelines, we searched PubMed, Google Scholar, and ScienceDirect databases between January 2008 and September 2023. Studies investigating polyphenolic effects on psoriasis through in vitro, animal, or clinical models were included. Twenty-five studies met inclusion criteria: nine in vitro studies, eleven animal studies, and five clinical trials. Curcumin was most extensively studied, demonstrating 30–60% reductions in inflammatory markers (TNF-alpha, IL-17, IL-22) and significant PASI score improvements. Mechanistic analysis revealed polyphenols primarily target NF-kappaB pathway inhibition and IL-17/Th17 axis suppression, addressing fundamental inflammatory processes in psoriatic pathophysiology. However, limited clinical evidence represents a significant implementation barrier. Polyphenols show potential as adjunctive therapies to conventional topical and systemic treatments. Future research should prioritize large-scale randomized controlled trials with standardized formulations and combination therapy investigations to establish clinical efficacy and overcome bioavailability challenges. Full article

Sesame oil extraction byproduct (SOEB) contains a high percentage of protein (49.81 g/100 g), making it a suitable plant-based source for producing protein hydrolysates with nutraceutical potential. In this study, albumins, globulins, glutelins, and prolamins fractions were extracted and characterized from SOEB. These fractions were then enzymatically hydrolyzed with alcalase, yielding high soluble protein content (>90%) and hydrolysis degrees ranging from 34.66 to 45.10%. The hydrolysates were fractionated by molecular weight (<5 kDa, 3–5 kDa, 1–3 kDa, and <1 kDa). These fractions demonstrated potential for inhibiting the DPPH radical (25.19–95.79%) and the α-glucosidase enzyme (40.14–55.63%), particularly the fractions with molecular weight <1 kDa. We identified 28 peptides, with molecular weights between 332.20 and 1096.63 Da, which showed potent antioxidant activities (IC₅₀ = 90.18 µg/mL), as well as inhibitory effects on key enzymes such as α-glucosidase (IC₅₀ = 61.48 µg/mL), dipeptidyl peptidase IV (IC₅₀ = 12.12 µg/mL), and pancreatic lipase (IC₅₀ = 6.14 mg/mL). These results demonstrate the antioxidant, antihyperglycemic, antidiabetic, and anti-obesity potential of SOEB peptides, highlighting their use in the formulation of new functional foods or nutraceuticals. Full article

Opuntia dillenii has gained considerable scientific attention as a potential natural source of antioxidants. This systematic review compiles and evaluates current evidence regarding its antioxidant activity. A PRISMA-guided literature search was conducted using PubMed, Scopus, and Web of Science, identifying 37 eligible studies. These studies employed two main methodological approaches: chemical-based assays and biological models. Chemical assays, including radical scavenging and reducing power assays, demonstrated a broad range of antioxidant activity influenced by factors such as the extraction method, plant part, plant maturity, and geographic origin. Polysaccharides, betalains, and polyphenols were consistently identified as primary contributors to these effects. Biological models further supported the antioxidant properties of O. dillenii extracts. In animal studies, administration of the extracts significantly improved oxidative stress biomarkers, increasing glutathione levels, reducing malondialdehyde concentrations, and enhancing the activity of antioxidant enzymes, particularly in the liver and other digestive tissues like the colon, stomach, and pancreas. Cellular studies using hepatocyte, macrophage, enterocyte, and neuronal cell lines produced comparable results, confirming the antioxidant effects. In conclusion, O. dillenii exhibits promising antioxidant potential across various experimental models. However, the absence of human clinical trials highlights the need for further research to establish its efficacy and safety as a nutraceutical product. Full article

Plant-derived pharmaceuticals represent a highly compelling area of research and continue to attract significant interest from countries, regions, scientific communities, and pharmaceutical companies worldwide. Among these, α- and β-amyrins have been identified as high-value triterpenoid compounds with a broad spectrum of potential therapeutic properties, including anti-inflammatory, antidiabetic, antiatherosclerotic, analgesic, antigout, neuroprotective, anti-Parkinsonian, anticancer, antibacterial, and anti-HIV activities. Relevant information and data were obtained through comprehensive searches of major scientific databases, including Web of Science, Elsevier, and the National Library of Medicine. This study highlighted the pharmaceutical potential of α- and β-amyrins, supported by specific evidence from in vivo, in vitro, and clinical trials. Various extraction methods for α- and β-amyrins are discussed, followed by recommendations for future directions in the development of these compounds as pharmaceutical agents and functional food ingredients. This review highlights the therapeutic of α- and β-amyrin compounds in the prevention and treatment of various serious diseases worldwide, potentially opening new opportunities and directions for the pharmaceutical industry. Full article

The marine seaweed Undaria pinnatifida belongs to the large group of brown macroalgae (Ochrophyta) and is valued both as a nutritious food and a source of pharmaceutical compounds. It has been widely consumed in East Asia as part of the traditional diet and is generally regarded as a “healthy longevity food.” Consequently, it represents one of the most promising natural sources of biomedicinal and bioactive products. This review aims to synthesize current scientific evidence on the pharmacologically active compounds of U. pinnatifida, emphasizing their mechanisms of action and therapeutic potential in neurodegenerative and chronic diseases. This narrative review is based on a comprehensive literature search of peer-reviewed articles from scientific databases, focusing on studies addressing the pharmacological properties of U. pinnatifida and its major bioactive constituents. Recent research highlights that compounds such as fucoxanthin (a carotenoid), fucosterol (a sterol), fucoidan (a polysaccharide), alginate, and dietary fiber found in U. pinnatifida possess significant potential for developing treatments for conditions including goitre, urinary diseases, scrofula, dropsy, stomach ailments, and hemorrhoids. Moreover, these compounds exhibit remarkable pharmacological properties, including immunomodulation, antitumor, antiviral, antioxidant, antidiabetic, anti-inflammatory, anticoagulant, antithrombotic, and antibacterial activities, all with low toxicity and minimal side effects. Additionally, U. pinnatifida shows promise in the treatment or prevention of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as neuropsychiatric conditions like depression, supported by its antioxidant effects against oxidative stress and neuroprotective activities. Numerous in vitro and in vivo studies have confirmed that U. pinnatifida polysaccharides (UPPs), particularly fucoidans, exhibit significant biological activities. Thus, accumulating evidence positions UPPs as promising therapeutic agents for a variety of diseases. Full article

Short-chain fatty acids (SCFAs) are metabolites derived from the fermentation of dietary fibre by gut bacteria. SCFAs function as essential regulators of host-microbiome interactions by participating in numerous physiological and pathological processes within the gastrointestinal (GI) tract. In recent years, the depletion of SCFAs has been increasingly linked to the pathogenesis of GI diseases. In this review, we summarize the current understanding of the therapeutic mechanisms of SCFAs in GI diseases, including inflammatory bowel disease, irritable bowel syndrome, metabolic dysfunction-associated steatotic liver disease, and acute pancreatitis. We next highlight potential therapeutic approaches that increase the endogenous production of SCFAs, including prebiotics, probiotics, and fecal microbiota transplantation. We conclude that, although SCFAs are promising therapeutic agents, further research is necessary due to variability in treatment efficacy, inconsistent clinical outcomes, and a limited understanding of SCFAs’ mechanisms of action. Full article

This study aimed to evaluate the impregnation process of apple slices with bioactive compounds (BCs) that were obtained from the richest antioxidant fruit powder extracts. Acaí, beetroot, blueberry, cranberry, dragon fruit, and pomegranate powders were assessed on their main BCs, antioxidant capacity (AC), and reducing power (RP) before and after heat treatment to select the extract with the highest and most stable BCs and AC. The effect of pH (3–7) and the total soluble solids (TSSs) (5–15%) on the BCs and AC of selected fruit powder extracts were also evaluated to decide which one should be used to impregnate apple slices. Results indicate that the pomegranate extract presented the highest BCs, AC, and RP among the fruit powders tested, even after heat treatment. Moreover, the TSSs did not affect the BCs from the pomegranate extract; however, pH affected the stability, showing higher values of BCs as the pH was reduced. Apple slices impregnated with pomegranate extract (pH 2) showed an increase in their total phenolic compounds, total anthocyanins, AC, and RP at 25.94, 3085.00, 19.80, and 56.94%, respectively, compared to control apple slices. This study indicates that reducing the pH of pomegranate extracts may increase their antioxidant compounds, showing a higher impregnation of them on apple slices. Full article

Inflammation, oxidative stress, and androgen activity are key features in benign prostate hyperplasia (BPH). Risks associated with the long-term use of 5α-reductase inhibitors have led to the search for alternative therapies, including food supplements. This study investigates the effectiveness of the combination of pollen extracts, namely Graminex^®G96^® (G) and Teupol 25P (T), towards oxidative stress and inflammation on human macrophages and benign prostate hyperplasia cells (BPH-1), both of which are LPS stimulated. The Nrf2-dependent antioxidant intracellular cascade as well as the NF-ĸB-driven inflammatory cascades were analyzed. The anti-proliferative effect of G and T, alone and in association, were evaluated on prostatic adenocarcinoma cells (PC-3) and BPH-1 cells. Finally, the inhibitory activity of GT on 5α-reductase was investigated in PC-3 cells by measuring epiandrosterone amounts, with the 5α-reductase inhibitor finasteride administered for comparison. All experiments were conducted in triplicate; data are presented as mean values ± standard deviations. Statistical analysis was performed using one-way analysis of variance. Our work demonstrates that GT promotes Nrf2-dependent antioxidant responses and counteracts the NF-ĸB-driven pathway in macrophages. GT is effective in counteracting the expression of pro-inflammatory cytokines and the generation of reactive oxygen species by promoting HO-1-dependent antioxidant responses in BPH-1 cells. GT reduces PC-3 and BPH-1 proliferation when associated with finasteride through a statistically significant inhibition of 5α-reductase activity. Data obtained in vitro and in silico demonstrate the potential efficacy of a multitargeted approach in the treatment of BPH. Full article

Endometrial stromal cells (EnSCs) undergo decidualization in response to progesterone. Decidualization facilitates spiral artery remodeling, immune tolerance in the endometrium, and fetal cell invasion and placentation—all essential for successful embryo implantation. Therefore, we aimed to investigate whether ergothioneine (EGT) plays a role in reproduction, particularly in decidualization and implantation. In this study, we found that solute carrier family 22 member 4 (SLC22A4), a specific transporter of EGT—a functional food ingredient with strong anti-aging properties—is upregulated in decidualized EnSCs. The effects of EGT were examined using uterine tissues from patients, primary cultured EnSCs, EnSC cell lines, and co-cultures with a fetal cell line. We observed a significant increase in SLC22A4 expression in secretory-phase human uterine tissue, decidualized EnSCs, and EnSC cell lines. We also found that EGT regulates insulin-like growth factor binding protein 1 expression, which promotes placentation. In co-cultures of EnSC and fetal cell lines, EGT upregulated ectonucleoside triphosphate diphosphohydrolase 1 and major histocompatibility complex, class I, G expression in fetal cell lines—both critical for placentation. These findings suggest that EGT is crucial to regulating decidualization and its markers, particularly insulin-like growth factor-binding protein 1, which contributes to placentation. Full article

Ergothioneine is a diet-derived antioxidant with emerging evidence of neuroprotective benefits, but no dose-ranging study has evaluated its effects in healthy older adults. In this 16-week randomized, double-blind, placebo-controlled trial, 147 adults aged 55–79 with subjective memory complaints received ergothioneine (10 mg or 25 mg/day ErgoActive^®) or placebo. The primary outcome was the change in composite memory (CNS Vital Signs). Secondary outcomes included other cognitive domains, subjective memory and sleep quality, and blood biomarkers. At baseline, participants showed slightly above-average cognitive function (neurocognitive index median = 105), with plasma ergothioneine levels of median = 1154 nM (interquartile range = 889.9). Plasma ergothioneine increased by ~3- and ~6-fold for 10 mg, and ~6- and ~16-fold for 25 mg, at weeks 4 and 16, respectively (p < 0.001). 25 mg ergothioneine showed a within-group improvement in composite memory at week 4 (p < 0.05), although this was not sustained. Reaction time improved in both groups, dependent on time. Other domains showed null or limited effects. Subjective prospective memory and sleep initiation improved dose-dependently, with significant effects at 25 mg (p < 0.05). Liver function improved and a within-group increase in telomere length was noted. In conclusion, ergothioneine supplementation was safe and well tolerated, with evidence suggesting some benefits in this cohort of healthy older adults. Longer trials in individuals with lower baseline ergothioneine or cognitive function are warranted. Full article