Acute effects of a chewable beetroot-based supplement on cognitive performance: a double-blind randomized placebo-controlled crossover clinical trial.

BACKGROUND: Dietary nitrate (NO3-) has been shown to be useful as an ergogenic aid with potential applications in health and disease (e.g., blood pressure control). However, there is no consensus about the effects of dietary NO3- or beetroot (BR) juice supplementation on cognitive function. OBJECTIVE: The aim of this study was to evaluate the effects of a single dose of a chewable BR-based supplement on cognitive performance. METHODS: A double-blind randomized placebo-controlled two-period crossover clinical trial was carried out based on the extension of the CONSORT guidelines for randomized crossover trials. A total of 44 participants (24 F; 20 M; 32.7 [12.5] years; 66.3 [9.0] kg; 170 [9.2] cm; 22.8 [1.4] kg/m2) were randomly allocated to receive first either four BR-based chewable tablets (BR-CT) containing 3 g of a Beta vulgaris extract (RedNite®) or four tablets of a placebo (maltodextrin). A 4-day washout period was used before crossover. Ninety minutes after ingestion of the treatments, a neuropsychological testing battery was administered in each period. The trial was registered at clinicaltrials.gov NCT05509075. RESULTS: Significant improvements with moderate effect size were found on memory consolidation at the short and long term only after BR-CT supplementation via the Rey Auditory Verbal Learning Test immediate (+ 20.69%) and delayed (+ 12.34%) recalls. Likewise, enhancement on both frontal lobe functions (+ 2.57%) and cognitive flexibility (+ 11.16%) were detected after BR-CT. There was no significant change (p < 0.05) on verbal memory of short-term digits, working memory and information processing speed. Mixed results were found on mood and anxiety through the Beck Depression Inventory-II (BDI-II) and the State-Trait Anxiety Inventory (STAI-Y1 and STAI-Y2); however, sequence and period effects were seen on STAI-Y2. CONCLUSIONS: The acute administration of a chewable BR-based supplement improves certain aspects of cognitive function in healthy females and males, particularly memory capacity and frontal skills.

The Effect of Beta-Carotene on Cognitive Function: A Systematic Review.

ß-carotene is a powerful antioxidant and dietary precursor of vitamin A whose role in maintaining mental health and cognitive performance, either alone or in combination with other dietary compounds, has been a topic of recent research. However, its effectiveness is still unclear. This systematic review, conducted according to the PRISMA guideline and assisted by the MySLR platform, addressed this issue. A total of 16 eligible original research articles were identified. Dietary intake or ß-carotene serum levels were associated with improved measures of cognitive function in 7 out of 10 epidemiological studies included. In intervention studies, ß-carotene consumption alone did not promote better cognitive function in the short term, but only in a long-term intervention with a mean duration of 18 years. However, all but one intervention study suggested the beneficial effects of ß-carotene supplementation at doses ranging from 6 mg to 50 mg per day in combination with a multicomplex such as vitamin E, vitamin C, zinc, or selenium for a period of 16 weeks to 20 years. Despite the current limitations, the available evidence suggests a potential association between ß-carotene dietary/supplementary intake and the maintenance of cognitive function. The ß-carotene most probably does not act alone but in synergy with other micronutrients.

Effect of Soy Protein Supplementation on Muscle Adaptations, Metabolic and Antioxidant Status, Hormonal Response, and Exercise Performance of Active Individuals and Athletes: A Systematic Review of Randomised Controlled Trials.

BACKGROUND: Protein supplements are important to maintain optimum health and physical performance, particularly in athletes and active individuals to repair and rebuild their skeletal muscles and connective tissues. Soy protein (SP) has gained popularity in recent years as an alternative to animal proteins. OBJECTIVES: This systematic review evaluates the evidence from randomised controlled clinical trials of the effects of SP supplementation in active individuals and athletes in terms of muscle adaptations, metabolic and antioxidant status, hormonal response and exercise performance. It also explores the differences in SP supplementation effects in comparison to whey protein. METHODS: A systematic search was conducted in PubMed, Embase and Web of Science, as well as a manual search in Google Scholar and EBSCO, on 27 June 2023. Randomised controlled trials that evaluated the applications of SPs supplementation on sports and athletic-related outcomes that are linked with exercise performance, adaptations and biomarkers in athletes and physically active adolescents and young adults (14 to 39 years old) were included, otherwise, studies were excluded. The risk of bias was assessed according to Cochrane's revised risk of bias tool. RESULTS: A total of 19 eligible original research articles were included that investigated the effect of SP supplementation on muscle adaptations (n = 9), metabolic and antioxidant status (n = 6), hormonal response (n = 6) and exercise performance (n = 6). Some studies investigated more than one effect. SP was found to provide identical increases in lean mass compared to whey in some studies. SP consumption promoted the reduction of exercise-induced metabolic/blood circulating biomarkers such as triglycerides, uric acid and lactate. Better antioxidant capacity against oxidative stress has been seen with respect to whey protein in long-term studies. Some studies reported testosterone and cortisol fluctuations related to SP; however, more research is required. All studies on SP and endurance performance suggested the potential beneficial effects of SP supplementation (10-53.3 g) on exercise performance by improving high-intensity and high-speed running performance, enhancing maximal cardiac output, delaying fatigue and improving isometric muscle strength, improving endurance in recreational cyclists, increasing running velocity and decreasing accumulated lactate levels; however, studies determining the efficacy of soy protein on VO2max provided conflicted results. CONCLUSION: It is possible to recommend SP to athletes and active individuals in place of conventional protein supplements by assessing their dosage and effectiveness in relation to different types of training. SP may enhance lean mass compared with other protein sources, enhance the antioxidant status, and reduce oxidative stress. SP supplementation had an inconsistent effect on testosterone and cortisol levels. SP supplementation may be beneficial, especially after muscle damage, high-intensity/high-speed or repeated bouts of strenuous exercise.

Diet and miRNA: Epigenetic Regulator or a New Class of Supplements?

It is well recognized that diet components are important genomic regulators considering that food intake influences cytokines such as leptin, ghrelin, adiponectin, and NPY, which regulate gene expression in response to different nutritional programs, particularly regarding the caloric balance. However, the single nutrients, both the macro-nutrients, the fatty acids, and above all the micronutrients, show an essential capacity also for epigenetic regulation; in this sense, vitamins and their derivatives polyphenols are the main actors.

The efficacy and tolerability of pollen extract in combination with hyaluronic acid and vitamins in the management of patients affected by chronic prostatitis/chronic pelvic pain syndrome: a 26 weeks, randomized, controlled, single-blinded, phase III study.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains a challenging clinical condition to manage. Here, we evaluate the efficacy and tolerability of a new treatment option (suppositories) containing pollen extract in combination with hyaluronic acid and vitamins in the management of patients with CP/CPPS. METHODS: In this prospective, randomized, controlled, single-blinded, phase-III study we enrolled CP/CPPS patients between March and December 2019. Participants were randomized (1:1) to the following treatment groups: 1) pollen extract suppositories 1 daily for 10 days; or 2) ibuprofen 600 mg 1 tablet in the morning for 10 days. At the enrolment time and at the follow-up evaluations (3, 6 months), all patients completed baseline questionnaires ([National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] and Quality of Well-Being [QoL]) and underwent urological examination and microbiological evaluation. The primary endpoint was the quality-of-life assessment with Patients' Reported Outcomes (PROs). RESULTS: One hundred and eighty-seven patients were screened. Finally, one hundred and twenty-four patients (mean age 34.6±3.9 years) were randomly allocated to the new pollen extract treatment (N.=63) or ibuprofen (N.=61) groups. At the end of follow-up examinations 56/63 group 1 patients (88.8%) showed a significant reduction of the NIH-CPSI total score, compared with 17/61 (27.8%) in group 2 (P<0.0001). Group 1 patients also reported a higher improvement in terms of PROs, when compared with the control group and group 1 patients reported a significant reduction of leucocyte count at the Meares-Stamey Test (-12; -4; P<0.001). Only mild adverse events were reported in the two groups and adverse events were less frequent in the pollen extract suppositories group. CONCLUSIONS: The combination of pollen extract with hyaluronic acid and vitamins is more effective than ibuprofen in improving symptoms and Quality of Life in patients affected with CP/CPPS and has less side effects.

Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the Differences among Acute, Healed, and Negative COVID-19 Patients? A Multicenter Real-Practice Study.

Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D3 serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March-September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D3 (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p > 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D3 levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D3 levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D3 levels (<1 ng/mL) and in a subset supplemented with 1α,25(OH)2D3. Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH)2D3 (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH)2D3 might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.

Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects.

Vestibular disorders may generate complex signs and symptoms, which may alter patients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/usefulness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) pharmacodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs.

Sarcopenia: Etiology, Nutritional Approaches, and miRNAs.

Sarcopenia, an age-related decline in skeletal muscle mass and function, dramatically affects the quality of life. Although there is a consensus that sarcopenia is a multifactorial syndrome, the etiology and underlying mechanisms are not yet delineated. Moreover, research about nutritional interventions to prevent the development of sarcopenia is mainly focused on the amount and quality of protein intake. The impact of several nutrition strategies that consider timing of food intake, anti-inflammatory nutrients, metabolic control, and the role of mitochondrial function on the progression of sarcopenia is not fully understood. This narrative review summarizes the metabolic background of this phenomenon and proposes an integral nutritional approach (including dietary supplements such as creatine monohydrate) to target potential molecular pathways that may affect reduce or ameliorate the adverse effects of sarcopenia. Lastly, miRNAs, in particular those produced by skeletal muscle (MyomiR), might represent a valid tool to evaluate sarcopenia progression as a potential rapid and early biomarker for diagnosis and characterization.

Effects of Long-Term Storage on Radical Scavenging Properties and Phenolic Content of Kombucha from Black Tea.

Kombucha is a fermented beverage. Its consumption has significantly increased during the last decades due to its perceived beneficial effects. For this reason, it has become a highly commercialized drink that is produced industrially. However, kombucha is still also a homemade beverage, and the parameters which, besides its organoleptic characteristics, define the duration of its potential beneficial properties over time, are poorly known. Therefore, this study aimed to determine the effect of 9-month storage at 4 °C with 30-day sampling on the pH, total phenolic, and flavonoid contents, free radical scavenging properties of kombucha fermented from black tea. Our results highlighted that, after four months, the phenolic content decreased significantly from the initial value of 234.1 ± 1.4 µg GAE mL-1 to 202.9 ± 2.1 µg GAE mL-1, as well its antioxidant capacity tested by two in vitro models, DPPH, and ABTS assays. Concomitantly, the pH value increased from 2.82 to 3.16. The novel findings of this pilot study revealed that kombucha from sugared black tea can be stored at refrigerator temperature for four months. After this period the antioxidant properties of kombucha are no longer retained.

Effect of Addition of Pectins from Jujubes (Ziziphus jujuba Mill.) on Vitamin C Production during Heterolactic Fermentation.

Soluble fibers, including pectins from apple and lemon, are commonly used as prebiotic and to prepare functional foods. The present study aimed to investigate the physicochemical and functional properties of pectins extracted from jujubes (Ziziphus jujuba Mill.). Pectins were extracted from jujubes at three stages of harvesting and characterized by FTIR and SEM analyses. Whole milk inoculated with kefir grains was supplemented by 0.25 mg·mL-1 of pectins. The pH value and vitamin C content were evaluated after 24 and 48 h of fermentation. Pectins from jujubes at the first harvesting stage (PJ1K) showed the lowest methoxylation degree. The addition of pectins enhanced the production of vitamin C during heterolactic process. This result was found to depend on jujube harvesting stage as PJ1K stimulated the growth of yeasts in kefir grains yielding to the highest amount of vitamin C (0.83 ± 0.01 µg·mL-1) compared to other samples (0.53-0.60 µg·mL-1) at 24 h. Lactic acid bacteria diminish pH rapidly with respect to control (4.13 ± 0.05), according to the stage of maturation, reducing its initial value by 38.3% in PJ1K. Besides being an excellent prebiotic, pectins from jujubes could be used to enrich kefir with vitamin C.

Quercetin, Epigallocatechin Gallate, Curcumin, and Resveratrol: From Dietary Sources to Human MicroRNA Modulation.

Epidemiologic studies suggest that dietary polyphenol intake is associated with a lower incidence of several non-communicable diseases. Although several foods contain complex mixtures of polyphenols, numerous factors can affect their content. Besides the well-known capability of these molecules to act as antioxidants, they are able to interact with cell-signaling pathways, modulating gene expression, influencing the activity of transcription factors, and modulating microRNAs. Here we deeply describe four polyphenols used as nutritional supplements: quercetin, resveratrol, epigallocatechin gallate (ECGC), and curcumin, summarizing the current knowledge about them, spanning from dietary sources to the epigenetic capabilities of these compounds on microRNA modulation.

Improved Efficacy of Pregabalin by Restoring Plasma Vitamin D Levels in Migraine: a Case Report.

Migraine appears to be the most common neurological syndrome in primary care. Pain in migraine is mediated by the release of inflammatory mediators at the level of nerves and blood vessels. The antioxidant and neuroprotective effects of vitamin D in the central nervous system suggest that deficiency of this vitamin can be involved in migraine. Moreover, low serum levels of vitamin D correlates with a higher incidence of chronic pain, including migraine and in co-administered with anti-migraine treatment reduces the frequency of migraine attacks. We report a 46-year old woman affected by migraine, anxiety and mild depressive mood (MSQ score: 24; BDI score: 34; VAS score: 8) that partially improved with pregabalin treatment (VAS: 5). Laboratory findings documented low serum levels of vitamin D (25-hydroxy-vitamin D: 12 ng/mL; normal range: 20-100 ng/mL; 1-25 di-hydroxy-vitamin D: 19 ng/mL, normal range: 25-66 ng/mL). The treatment with 10,000 UI vitamin D during pregabalin therapy induced an improvement of clinical symptoms (pain, anxiety and depression) and of the quality of life. This case report suggest that in chronic migraine patient with anxiety and mild mood depression in treatment with pregabalin a supplementation of vitamin D improvement the clinical symptoms of migraine and a modulation of inhibitoy synaptic neurotransmission may explain this effect in our migraine patient.

Capsaicin Analogues Derived from n-3 Polyunsaturated Fatty Acids (PUFAs) Reduce Inflammatory Activity of Macrophages and Stimulate Insulin Secretion by ß-Cells In Vitro.

In this study, two capsaicin analogues, N-eicosapentaenoyl vanillylamine (EPVA) and N-docosahexaenoyl vanillylamine (DHVA), were enzymatically synthesized from their corresponding n-3 long chain polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both dietary relevant components. The compounds significantly reduced the production of some lipopolysaccharide (LPS)-induced inflammatory mediators, including nitric oxide (NO), macrophage-inflammatory protein-3α (CCL20) and monocyte chemoattractant protein-1 (MCP-1 or CCL2), by RAW264.7 macrophages. Next to this, only EPVA increased insulin secretion by pancreatic INS-1 832/13 ß-cells, while raising intracellular Ca2+ and ATP concentrations. This suggests that the stimulation of insulin release occurs through an increase in the intracellular ATP/ADP ratio in the first phase, while is calcium-mediated in the second phase. Although it is not yet known whether EPVA is endogenously produced, its potential therapeutic value for diabetes treatment merits further investigation.

Variation in Immune-Related microRNAs Profile in Human Milk Amongst Lactating Women.

BACKGROUND: Human Milk (HM) is a biological fluid representing the first nutrient for newborns. It directly impacts the development of the infant's immune system. In this concern, specific microRNAs (miRNAs) such as hsa-miR-21, hsa-miR-181a, hsa-miR-150 and hsa-miR-223 are known to be involved in the innate and acquired immune response. OBJECTIVE: Herein, these miRNAs were evaluated in frozen and pasteurized samples of human colostrum and HM in order to elucidate the distribution and the expression profile of these biological mediators in both biological fluids. METHODS: Using quantitative approach qRT-PCR, we analyzed immune-related microRNAs in both, colostrum and HM. RESULTS: Our study provided evidence of a comparable profile of immune specific miRNAs in colostrum and HM. Although we detected all the four miRNAs tested, we point out the prevalence of hsamiR- 181a and hsa-miR-223 indicative to act on T and granulocytes cell populations as selective targets. Therefore, these biomolecules could affect newborn's immune homeostasis at early stages of life. While, variation in immune-related miRNAs was found in HM amongst lactating women, it was not evidenced in colostrum. Of interest, pasteurization procedure did not alter the distribution or the expression profile of the miRNAs tested in both colostrum and HM. Herein, we also proposed a simple method to determine the quantity of these biomolecules in biological fluids. CONCLUSION: Considering, this evidence the variation in immune-related miRNAs should be take into account and could be relevant for preterm and hospitalized infants who usually received pasteurized HM from donors.

From the hive: Honey, a novel weapon against cancer.

Nowadays there is a folk medicine branch called apitherapy that aims to treat diseases with bee products, including honey. Honey has long been known for its medicinal and health promoting properties. It encloses numerous types of phytochemicals with high phenolic and flavonoid content, which contribute to its antioxidant and anti-inflammatory activities. Varieties and variants of polyphenols in honey showed antiproliferative property against several types of cancer. This review focuses on the latest discoveries about the key role of honey in different stages of carcinogenesis, initiation, proliferation and progression, both in vitro and in vivo, as well as on its adjuvant effect in cancer therapy. Although a possible application of honey and its active compounds as drugs against cancer is still far away from clinical practice, scientific results highlight that they could be used as immune booster for patients undergoing chemotherapy. They showed protective effects against the common exasperating and disabling side effects, mostly mucositis.

Biochemical and chemical characterization of Cynara cardunculus L. extract and its potential use as co-adjuvant therapy of chronic myeloid leukemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Ancient mediterranean diet was characterized by consuming the spontaneous forms of Cynara cardunculus L. (CCL), commonly called artichoke. Cultivated and/or spontaneous forms of CC studies have demonstrated that methanol extract of CCL flower and/or cynaropicrin showed remarkable anti-proliferative activity in vitro models of leukocyte cancer cell. AIM OF THE STUDY: Chronic myeloid leukemia (CML) is associated with a reciprocal translocation of the long arms of chromosomes 9 and 22 generating the BCR/ABL fusion gene, translated in the p210BCR/ABL oncoprotein kinase. This chimeric protein is the target of a kinase inhibitor, imatinib, but the development of mutations in the ABL kinase domain resulting in drug resistance and several approaches to overcoming resistance have been study. In this concern, we investigated the effect of CCL extract on human K562 CML and K562 imatinib resistant (IMAR) cell proliferation and on p210BCR/ABL expression. MATERIALS AND METHODS: Chemical characterization of the CCL extracts was performed by GC/MS analysis and semipreparative RP-HPLC chromatography. Structural characterization of compounds was assessed by 1H-13C NMR and LC/MS analysis. The effects of CCL extracts on the proliferation of K562 CML human cell line and K562 IMAR were screened by MTT assay. The p210BCR/ABL mRNA and protein expressions were analyzed by qRT-PCR and Western blot techniques respectively. RESULTS: We demonstrate that CCL extract affect cell viability of both K562 CML human cell line and K562 IMAR. The biocomponents of CCL were chemical characterized and we identify cynaropicrin and its deacyl derivative having the capability to down-regulate the p210BCR/ABL oncoprotein. CONCLUSIONS: Our study suggests that the use of those molecules could represent a novel and promising strategy to potentiate the ability of imatinib or of its analogues to induce cancer growth arrest in CML and to delay or overcome the resistance of CML to chemotherapy.

Expression and Subcellular Localization of Retinoic Acid Receptor-α (RARα) in Healthy and Varicocele Human Spermatozoa: Its Possible Regulatory Role in Capacitation and Survival.

Varicocele, an abnormal tortuosity and dilation of veins of the pampiniform plexus, is the most common identifiable and correctable cause of male infertility. It is now becoming apparent that signaling through vitamin A metabolites, such as all-trans retinoic acid (ATRA), is indispensable for spermatogenesis and disruption of retinoic acid receptor-α (RARα) function may result in male sterility and aberrant spermatogenesis. Herein, we investigated by Western blot and immunogold electron microscopy the expression profiles and subcellular localization of RARα in healthy and varicocele human sperm; in addition, we analyzed the effects of ATRA on cholesterol efflux and sperm survival utilizing enzymatic colorimetric CHOD-PAP method and Eosin Y technique, respectively. In varicocele samples, a strong reduction of RARα expression was observed. Immunogold labeling evidenced cellular location of RARα also confirming its reduced expression in "varicocele" samples. Sperm responsiveness to ATRA treatment was reduced in varicocele sperm. Our study showed that RARα is expressed in human sperm probably with a dual role in promoting both cholesterol efflux and survival. RARα might be involved in the pathogenesis of varicocele as its expression is reduced in pathologic samples. Thus, ATRA administration in procedures for artificial insemination or dietary vitamin A supplementation might represent a promising therapeutic approach for the management of male infertility.

Dietary fatty acid composition differently influences retinoylation reaction in rat testes mitochondria.

All-trans-retinoic acid (atRA) is incorporated covalently into proteins of rat testes mitochondria. In this study, the effect of three diets with different fatty acid composition on the retinoylation of proteins of rat testes mitochondria has been investigated. Different groups of rats were fed on a basal diet supplemented with 15% of either coconut oil (CO), olive oil (OO) or fish oil (FO). We found that, when compared with CO, the binding of retinoic acid was decreased in FO- and OO-fed rats. Mitochondrial phospholipids composition was differently influenced by dietary treatments; minor changes were observed in fatty acid composition of phospholipids. Few differences were observed in the Arrhenius plots among the three groups of rats. Kinetic analysis revealed a decrease in the V (max) value in FO- and OO- as compared with CO-fed rats. No difference among the three groups were observed in the K ( M ) value. The retinoylation reaction was inhibited by 13-cis-RA and 9-cis-RA.