Nutraceuticals

The solid-state fermentation (SSF) of agro-industrial by-products such as okara, pomegranate peel, and cranberry pomace presents a sustainable approach to enhance the release of bioactive compounds. This study investigated the effects of different microbial cultures—Rhizopus oligosporus, Aspergillus oryzae, Streptococcus thermophilus, and a co-culture of R. oligosporus and S. thermophilus—on the bioconversion of bioactive compounds in 100% okara, okara with 2% pomegranate peel, and okara with 1% cranberry pomace. The objective was to assess whether co-culture fermentation with molds and S. thermophilus augments the release of bioactive compounds in okara-based fermentations through synergistic enzymatic activity. Over a period of 72 h, isoflavone transformation (daidzin, daidzein, genistin, and genistein), pH evolution, and water activity were assessed. The co-culture system exhibited improved bioconversion, leading to significant (p < 0.01) increases in daidzein and genistein in pure okara compared to the starting material. The highest polyphenol content (0.908 mg/g) and antioxidant capacity (24.9 mg Trolox eq/g) were recorded in 100% okara. However, pomegranate peel inhibited β-glucosidase activity, delaying the release of isoflavone aglycones. These findings confirm that co-culture fermentation is an effective strategy for enhancing the bioactive properties of okara-based fermentations. This facilitates the release of bioactive aglycones and supports the upcycling of agro-industrial by-products into functional food ingredients. Future research should focus on optimizing fermentation parameters to further enhance the release of bioactive compounds. Full article

This feasibility study investigates the relationship between functional food consumption and mental well-being, focusing on natural foods traditionally linked to mental health benefits. This research also examines consumer preferences to identify key characteristics that novel functional foods designed to enhance mental well-being should possess. Additionally, this study lays the groundwork for a clinical trial exploring the effects of a novel functional food on mental health and well-being. Data were collected through an online bilingual survey (Greek/English) from 362 participants across Greece and Cyprus, using an adapted Functional Food Frequency Questionnaire (FFFQ) featuring 30 foods with documented effects on cognitive function and mood regulation. The survey included validated scales measuring mental well-being, health-related quality of life (HRQoL), sleep quality, and food choice motives, along with demographic and anthropometric data. Analysis revealed significant associations between functional food consumption and mental health outcomes, particularly in HRQoL, sleep quality, and body mass index (BMI). Most functional foods consumed were natural and aligned with the Mediterranean dietary pattern, such as fruits, vegetables, nuts, herbal infusions, and honey, all demonstrating positive effects on mental and physical health. Consumer preferences showed a strong inclination toward functional foods that balance sensory appeal with health benefits, including milk-based and plant-based beverages, protein bars, and granola bars. Ingredients like St. John’s wort and Greek mountain tea were identified as potentially beneficial for mental well-being, consistent with their established efficacy in psychological health. A significant majority of participants (66.9%) expressed interest in participating in clinical trials, highlighting the need for further research into the efficacy of functional food components. This study provides a foundation for future clinical trials examining the impact of novel functional food formulations on mental and physical health, addressing the growing consumer demand for products that enhance psychological resilience and well-being. Full article

In these times and with the pace of life that we have developed, many people need help falling asleep due to poor sleep hygiene, among other reasons. Thus, in mild cases, it is recommended to use natural therapies, such as phytotherapy, avoiding in the first instance the use of drugs. Melatonin is considered a versatile molecule widely used today. It is included as a main ingredient in dietary supplements that are, in some cases, accompanied by medicinal plants as botanical mixes, generating beneficial products for sleep disorders among other conditions. The dietary phytotherapeutic supplements evaluated in this work contain various concentrations of melatonin and other products, resulting in different effects on sleep therapy. The aim of this work is to reveal the quantitative differences that exist between the melatonin contents labeled in the products and those analyzed. The degradation rate of this hormone at three years in the phytotherapeutic supplements is also studied in order to re-evaluate the expiration dates of these products. In conclusion, the mixture between synthetic melatonin and different botanical mixes is very common in the supplements studied here and aimed at improving sleep. However, the most natural thing would be to be able to use only plants with sufficient phytomelatonin content to eliminate the inclusion of chemically synthesized melatonin in preparation. We propose the use of a particular raw plant material with excellent characteristics for this purpose. Full article

Lyophilized organ extracts from livestock such as beef or elk are widely commercially proposed as animal-sourced nutraceuticals. Such preparations contain blends of vitamins and nutrients that may be employed for general or specific dietary supplementation. The first objective of this study was to develop an optimized and function-oriented manufacturing process for stabilized organ-specific extracts of American buffalo (Bison bison). The second objective of the study was to perform functional benchmarking of the obtained stabilized extracts by focusing on antioxidant attributes, which are key properties of nutraceuticals. Methodologically, a two-step lyophilization process, hard-shell capsule formulation, and process quality control elements were adapted from pharmaceutical technology practices. Stabilized extracts (300 mg capsules) were derived from the spleen, heart, liver, kidneys, lungs, and thymus of grass-fed and grass-finished American bison (born and raised in a tempered climate in Geneva, Switzerland). Functional benchmarking of the obtained extracts was performed using orthogonal methods of antioxidant activity determination (TEAC, FRAP, and H₂O₂ challenge assays). Firstly, the developed biomass transformation process enabled the considered organs to be effectively stabilized while reaching the desired quality attributes. Secondly, functional characterization of the formulated extracts revealed significant and organ-specific antioxidant attributes, wherein liver-derived materials were found to be the most potent. Thirdly, key quality and functional parameters (residual moisture levels and TEAC) were found to be stable over 12 months of storage following extract preparation. Overall, the present study provides an evidence-based technical/functional rationale for the preparation and control of American bison organ-specific lyophilized extracts to be included in nutraceutical preparations. Full article

The aim of the present study was to investigate the phenolic composition and the efficacy of an innovative formulation based on Mg, Vitamin B6, and water extracts from Vitex agnus-castus, Crocus sativus, Melissa officinalis, Betula pendula, and Betula pubescens developed as an effective tool to face neuroinflammation and depression symptoms occurring in premenstrual syndrome (PMS). The formulation was analyzed through colorimetric and liquid chromatography methods for determining the content in phenols and flavonoids. Additionally, scavenging/reducing properties were investigated via 2,2-diphenyl-1-picrylhydrazyl (DPPH,) 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and horseradish peroxidase assays. The biocompatible limits were determined via allelopathy, the brine shrimp lethality test, and Daphnia magna cardiotoxicity assay. The formulation was then assayed in an experimental model constituted by isolated mouse cortex specimens exposed to K⁺ 60 mM Krebs–Ringer buffer, a toxic depolarizing stimulus able to reproduce the burden of inflammation/oxidative stress and the increased serotonin (5-hydroxytryptamine, 5-HT) impoverishment occurring in different neurological and psychiatric conditions, including depression. The results of the phytochemical analysis showed that the formulation is rich in benzoic acids, namely gentisic acid (155.31 µg/mL) and phenylethanoid compounds, namely hydroxytyrosol (39.79 µg/mL) that support the antioxidant effects measured via DPPH (IC₅₀: 1.48 mg/mL), ABTS (IC₅₀: 0.42 mg/mL), and horseradish peroxidase (IC₅₀: 2.02 mg/mL) assays. The ecotoxicological models indicated the formulation as non-toxic, permitting the identification of a biocompatible concentration (1000 µg/mL) to be used in isolated mouse cortex exposed to K⁺ 60 mM Krebs–Ringer buffer. In this model, the gene expression of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), estrogen receptor-1 (ESR1), prolactin receptor (PRLR), brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) was determined by real-time PCR. In the isolated mouse cortex, the formula reduced COX-2, IL-6, SERT, ESR1, and PRLR gene expression and increased BDNF and IL-10 gene expression. Overall, the study corroborated the use of the formulation as an innovative tool to contrast inflammation, oxidative stress, and neurotransmitter impairment associated with PMS. Full article

This study investigates the effects of xylitol, a natural sugar alcohol, on tumor progression in syngeneic mouse cancer models. Xylitol is known for its dental health benefits, but emerging evidence suggests broader biological roles, including potential anti-cancer properties. We explored xylitol’s impact on two mouse cancer models: 4T1 mammary carcinoma and B16F10 melanoma. Xylitol’s efficacy in inhibiting cancer cell lines and modulating tumor progression was assessed using immunocompetent female mice. The experiments involved intratumoral and peritumoral administration of a 20% xylitol solution in two mouse strains: BALB/c (4T1 mammary carcinoma) and C57BL/6 (B16F10 melanoma). Tumor volume, histopathology, and metabolomic analyses were conducted to gauge xylitol’s influence. The study revealed that xylitol administration initially reduced tumor growth in the B16F10 melanoma model, accompanied by alterations in tumor metabolism. However, similar effects were not observed in the 4T1 mammary carcinoma model, and melanoma tumor growth re-commenced in the melanoma model after stroma deterioration caused xylitol solution leakage. These findings suggest that xylitol may have potential as an adjunct therapy in cancer treatment, specifically in melanoma. The differential response between the two cancer models underscores the complexity of cancer biology and the need for further investigation into xylitol’s mechanisms of action and its role in cancer therapy. Full article

The use of plants for therapeutic purposes is an ancestral practice that dates back to the earliest times in the history of mankind. Even today the exploitation of plants for medicinal purposes plays a big role for the communities, especially in Africa, despite advances in modern medicine. According to the World Health Organization, about 80% of the population in developing countries use plants for their primary health care. In Niger, the use of medicinal plants is a foundation of traditional medicine across all ages. It remains a very common practice, especially in rural areas. This practice concerns all ages of life, including mother–child care. In infants and young children, mothers use plants as fortifiers for their prophylactic or curative powers, or to facilitate growth and weight gain, and also to fight major causes of infant morbidity and mortality. Mothers also use medicinal plants for their galactogenic power to stimulate lactation. This is even more important in rural areas where breastfeeding is the main source of infant nutrition. Over the years, these medicinal plants have been the subject of chemical and biological investigations to back up their therapeutic potential and virtues. This study aims to summarize current knowledge on the most commonly used medicinal plants in Niger in mother–child care. This helps emphasize the validation of ancestral medicinal plants through the scientific evaluation of the bioactive components and mechanisms. Elements of sustainability are discussed in future developments. Full article

Kale (Brassica oleracea) is recognized as a ‘superfood’ among leafy vegetables due to its high carotenoid content and potential health benefits. This study aims to optimize ultrasound-assisted extraction (UAE) to enhance the recovery of carotenoids and other phytochemicals from upcycled kale using response surface methodology. The optimized extraction parameters for carotenoids, i.e., aqueous ethanol as solvent, temperature, and extraction time at a fixed solid-to-solvent ratio, were established using the central composite design. The optimized extraction method was compared with other reported extraction methods for total phenolic content (TPC) and total antioxidant capacity (ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging). Ultra-high-performance liquid chromatography–electrospray ionization–mass spectrometry (UPLC-ESI-MS) analysis was also performed. Under the optimized UAE conditions of 100% ethanol at 57 °C for 30 min, total carotenoid content of 392 µg/g dry weight (DW) was observed, though the predicted carotenoid content was 550 µg/g DW. Under these conditions, TPC, FRAP, and DPPH were 10.5 mg gallic acid equivalents/g DW, 13.9 µmole Trolox equivalence/g DW, and DPPH radical scavenging activity as IC₅₀ of 2.04 ± 0.31 mg/mL, respectively. The UPLC-ESI-MS analysis showed the highest total phytochemicals recovered through microwave-assisted extraction, followed by UAE, compared to other tested extraction methods. In conclusion, the established optimized UAE process significantly enhanced the yield and quality of recovered phytochemicals from upcycled kale. Full article

The present study aimed to qualitatively assess the influence of Chenopodium quinoa Willd. varieties (INIAP-Tunkahuan, INIAP-Pata de Venado varieties and Chimborazo genotype), phenological stages (40, 60, and 80 days), and places of cultivation (Pichincha and Chimborazo Ecuadorian provinces) on the leaf and seed phenolic composition and biological properties. Their nutraceutical potential was assessed through qualitative analyses of (i) their polyphenols by high-performance thin-layer chromatography (HPTLC); and (ii) their free radical scavenging (quenching of 2,2-diphenyl-1-picrylhydrazyl free radical, DPPH^•) and α-amylase inhibitory properties (iodine visualization of starch hydrolysis) by HPTLC–bioautography. Compared to seeds, the quinoa leaf methanolic extracts present a high content of polyphenols with free radical scavenging activity, and compounds with an α-amylase inhibitory property; both biological activities indicate a remarkable potential of quinoa leaves, which may be relevant for the treatment of diabetes but also for the chemoprevention and/or treatment of pathologies related to oxidative stress. In quinoa leaves harvested after 80 days of cultivation, regardless of the place of production and the variety, a high content of bioactive compounds was observed. Future research is undoubtedly needed to further promote quinoa leaves as a dietary vegetable or to develop them into a nutritional supplement. This would empower quinoa smallholders in Andean regions to promote the sustainable development of this culture in its places of origin. Full article

Fruits and vegetables are sources of natural nutraceuticals. They contain a variety of bioactive compounds such as vitamins, minerals, dietary fibers and other phytochemicals that contribute to their health-promoting properties and disease prevention. A wide variety of fruits and vegetables should be eaten to ensure that an individual’s diet includes a combination of phytonutraceuticals and to obtain all their health benefits. This study aimed to compare the antioxidant potential and cardiovascular benefits within a restricted sample of ten fruits and ten vegetables, previously reported as largely consumed in Portugal. With data available from the literature, antioxidant potential scales were established. Additionally, a set of seven criteria, including high antioxidant capacity (FRAP values above 1), presence of n-3 fatty acids, saturated fat, cholesterol, trans fatty acids, fiber and sodium was used to create comparative scales of their potential cardiovascular benefits. The main results showed that the fruits that simultaneously exhibited the highest antioxidant potential values and the highest cardiovascular potential benefit were lemon, grapes, and melon; among vegetables, the top rankings were found to be tomato and onion. These products have been recognized as interesting sources of natural nutraceuticals for the food and pharmaceutical industries. In the future, similar approaches are desirable to translate complex scientific data into practical, simple and user-friendly information for food literacy initiatives, including nutrition education materials, about the relative level of the potential cardiovascular benefits of a wide diversity of food products. Full article

Skin aging is intrinsic and extrinsic. Intrinsic, or chronological, skin aging is an inevitable process of chronological and physiological alterations. The factors contributing to extrinsic skin aging involve sunlight, nutrients, and stress. Thus, extrinsic aging is thought to be superimposed over intrinsic aging and depends on the intensity and duration of environmental exposure and skin type (e.g., dry skin, oily skin, or eczema). The most significant extrinsic aging factor is UV radiation, which causes cellular senescence in a process known as photoaging. This study aimed to illuminate the mechanism whereby solubilized elastin peptide lotion (EL) from the bulbus arteriosus of yellowtail (Seriola quinqueradiata) prevents skin photoaging in hairless mice. EL reduced wrinkle formation, epidermal skin thickness, and Ki67 (cell growth marker) mRNA expression in skin tissues from ultraviolet B (UVB)-irradiated mice. EL treatment also reduced glyoxalase-1 (key enzyme of glucose metabolism) levels in skin tissue. Although no significant differences in collagen and elastin contents were found in dermal areas, matrix metalloproteinase-12 (wrinkle-related marker) expression was reduced following EL application. Furthermore, skin DPP-IV/CD26 (new senescence marker) levels decreased following EL treatment in photoaging model mice. These results suggest that EL moderates skin damage caused by UVB irradiation by regulating senescence-related molecule expression. Full article

This study aimed to investigate whether beta-alanine supplementation (BA) improves performance and rating of perceived exertion (RPE) and reduces the respiratory exchange ratio (RER) during a CrossFit^® workout. Fourteen participants were randomized in a double-blind design to either BA or placebo, with 12 participants (7 males, 5 females, 32 ± 9.2 y) completing the study. Participants performed two tests, separated by three weeks of supplementing with either 6.4 g/day of BA or placebo. Performance tests involved time to complete an adapted CrossFit^® “Fran” Workout of the Day: 21-15-9 repetition scheme alternating between dumbbell thrusters and kipping pull-ups. No significant differences between the BA group and the placebo group were observed for performance time improvement (−13.4 s vs. −12.9 s, p = 0.97), change in mean RER (0.06 vs. 0.05, p = 0.84), or change in RPE (10-point scale) (−0.4 vs. −0.07, p = 0.56). There was a group × time × time during test interaction for RER (p = 0.021). Compared to pre-testing, post-testing RER was higher at the 25% time point of the test for the BA group and at the 75% and 100% time points in the placebo group (p < 0.05). Beta-alanine did not show significant ergogenic effects during an adapted version of the CrossFit^® workout “Fran”, although it might have helped with the buffering of acidity later in the test, based on RER. Full article

Several studies have explored the effects of single or binary mixtures of sweeteners on both healthy individuals and those with diabetes. However, there is limited research on the impact of a combination of four sweeteners supplemented with dietary minerals. Steviol glycosides, extracted from Stevia rebaudiana, offer a zero-calorie sweetness that exerts minimal influence on blood glucose levels. When combined with other sweeteners, they can reduce the required quantity of each component thus mitigating the potential side effects. Furthermore, the incorporation of chromium picolinate into sweeteners may enhance insulin sensitivity and glucose metabolism and diminish insulin resistance in both diabetic and non-diabetic individuals. This study aimed to evaluate the effects of commercial mixed sweeteners (acesulfame-K, sucralose, sorbitol, and steviol glycoside) supplemented with chromium picolinate (MSSC) on diabetes-related markers and complications in healthy and type 2 diabetic rats (T2D). Over six weeks, diabetic rats received daily oral administration of MSSC at a standard dosage. The results demonstrated that MSSC significantly reduced weight loss in diabetic rats, lowered fasting blood glucose levels, enhanced hexokinase activity, and improved pancreatic antioxidative capacities. Additionally, MSSC treatment led to notable reductions in serum triglycerides, cholesterol, malondialdehyde (MDA), and LDL cholesterol levels. The treatment also modulated specific renal function parameters, and moderately reversed the necrotic architectures of the liver and pancreatic β cells. These results indicate that long-term administration of MSSC may alleviate certain diabetic complications without adverse effects on non-diabetic individuals. Further clinical studies are strongly recommended to evaluate the safety and efficacy of MSSC in diverse populations. Full article

Rheumatoid arthritis is an autoimmune pathology that follows a chronic course characterized by the involvement of the synovial membrane of joints all over the body. Clinically, the disease is characterized by persistent and painful immune-mediated inflammation, which culminates in bone deformations and joint movement limitation. Alternative therapies, such as garlic, ginger, curcumin, and resveratrol, are beneficial given their anti-inflammatory properties. These alternative therapies are a secondary option for treating the clinical manifestations of rheumatoid arthritis, helping to improve the patient’s quality of life further and preventing future complications. Full article

The bioavailability of vitamin C, or ascorbic acid, depends on limiting transport mechanisms that may be bypassed by liposome-encapsulation. The goal for this study was to evaluate the uptake, antioxidant, and immune-modulating effects of liposome-encapsulated vitamin C (LEC) using Lypo-Spheric^® technology, compared to three controls: ascorbic acid (AA), the phospholipid fraction composing the liposome, and placebo. A double-blinded placebo-controlled cross-over study design involved twelve healthy participants attending four clinic visits. At each visit, a baseline blood draw was performed, followed by consumption of 1 g LEC, 1 g AA, the phospholipid component of LEC, or placebo. Additional blood draws were performed at 2, 4, and 6 h. Consuming LEC and AA increased blood levels of vitamin C; the levels were significantly higher after consuming LEC at all timepoints when compared to AA (p < 0.01). LEC consumption increased serum antioxidant capacity (p < 0.01 at 2 h) and protection. Consuming LEC increased IFN-γ levels at 6 h, while consuming the phospholipid fraction rapidly decreased inflammatory cytokines IL-6, MCP-1, and MIP-1α at 2 h. Consuming LEC provided enhanced vitamin C bioavailability and antioxidant protection compared to AA. Consuming the phospholipids had anti-inflammatory effects. The results suggest that LEC provides antioxidant and immune benefits above AA, useful in preventive medicine. Full article

The purpose of this study was to determine whether a combined L-arginine and L-citrulline beverage can enhance total nitric oxide (NOx), as well as physiological (cardiopulmonary metrics) and perceptual (rate of perceived exertion) responses to a repeated bout of high-intensity exercise among university soccer players. Thirty male soccer players were included in a randomized double-blind, placebo-controlled, parallel design. Participants performed two bouts of high-intensity running, spaced two hours apart. Forty minutes before the second bout only, participants consumed a 500 mL beverage containing 6 g L-arginine and 6 g L-citrulline (n = 15) or placebo (n = 15). Blood NOx concentration was measured immediately before and after both bouts. There was no significant increase in NOx or significant interaction effects for physiological, performance, or perceptual variables between the L-arginine/L-citrulline and placebo groups. The peak volume of oxygen uptake of the L-arginine/L-citrulline group was significantly higher in the second compared with the first exercise bout (54.92 ± 4.81 vs. 50.54 ± 9.22 mL/kg/min; p = 0.01). In the second bout of exercise, time to exhaustion in the L-arginine/L-citrulline group increased by 8.5% (~60 s) compared to the first. In conclusion, these results suggest that a single dose of L-arginine/L-citrulline beverage did not increase NOx yet seemed to impact aerobic metabolism in university soccer players. Full article

There is increasing interest in Australian finger lime (Citrus australasica) due to its nutritional and bioactive potential. In this study, polar extracts from five finger lime cultivars were investigated for their potential bioactivity using a range of assays: antioxidant capacity (total phenolic content (TPC), ferric reducing antioxidant power (FRAP), and cupric reducing antioxidant capacity (CUPRAC)), total monomeric anthocyanin content (TMAC), anti-diabetic activity (α-glucosidase and α-amylase inhibition), anti-Alzheimer activity (acetylcholinesterase inhibition), Skin-whitening activity skin-brightening activity (tyrosinase inhibition), and anti-inflammatory activity (COX-2 inhibition). Commercial Tahitian lime was used as a “control” (comparison). The TPC ranged from 328 to 779 mg GAE/100 g dry weight (DW) in the pulp (compared to 1043 mg GAE/100 g for Tahitian lime) and from 755 to 1048 mg GAE/100 g in the peel (1704 mg GAE/100 g for Tahitian lime). A similar range of variation was seen for FRAP, ranging from 114 to 436 mg TE/100 g DW in the pulp (422 mg TE/100 g for Tahitian lime) and 259 to 495 mg TE/100 g DW in the peel (491 mg TE/100 g for Tahitian lime). Similarly, the TFC was generally lower in finger lime pulp (100–392 mg QE/100 g DW) compared to Tahitian lime (312 mg QE/100 g). The polar extracts did not show any significant inhibition of α-glucosidase, α-amylase, tyrosinase, or COX-2. One finger lime variety showed moderate (>50%) inhibition of acetylcholinesterase (AChE) at the highest concentration screened (~1500 mg/L), as did Tahitian lime. Additionally, in silico docking against acetylcholinesterase suggested that some of the polyphenols present, including catechin, quercetin-3-glucoside, and cyanidin-3-glucoside, could potentially dock to AChE and inhibit it. This is the first time the species has been investigated for many of these bioactive properties, and also the first time in silico docking has been performed to explore which potential compounds from this species could provide its bioactivity. Although little bioactivity was generally found across the applied bioassays, these findings nevertheless provide important basic data for future research and any claims about the potential health benefits of Australian finger lime. Full article