Safety Of Dietary Supplements Research Articles

Prebiotics for Induction and Maintenance of Remission in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD. A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events. Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn's disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics. Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.

Ginseng-DF ameliorates intestinal mucosal barrier injury and enhances immunity in immunosuppressed mice by regulating MAPK/NF-κB signaling pathways.

Dietary fiber (DF) has a good application prospect in effectively restoring the integrity of the intestinal mucosal barrier. Ginseng-DF has good physicochemical properties and physiological activity and shows positive effects in enhancing immunity. The aim of this study was to investigate the protective effect of Ginseng-DF on intestinal mucosal barrier injury induced by cyclophosphamide (CTX) in immunosuppressed mice and its possible mechanism. The effects of Gginseng-DF on immune function in mice were studied by delayed-type hypersensitivy, lymphocyte proliferation assay and NK cytotoxicity assay, the T lymphocyte differentiation and intestinal barrier integrity were analyzed by flow cytometry and western blot. Ginseng-DF (2.5% and 5%) could attenuate the inhibition of DTH response by CTX, promote the transformation and proliferation of lymphocytes, and stimulate NK effector cell activity. At the same time, Ginseng-DF could restore the proportion of CD4+/CD8+ T lymphocytes induced by CTX to different extents, improved spleen tissue damage, promoted the secretion of immunoglobulin IgG, and enhanced body immunity. More importantly, Ginseng-DF could up-regulate the contents of TNF-α, IFN-γ, IL-6 and IL-1β in serum and intestine of immunosuppressed mice to maintain the balance between Th1/Th2 cytokines, and improve the permeability of intestinal mucosal barrier. Meanwhile, Ginseng-DF could reduce intestinal epithelial cell apoptosis and improve intestinal adaptive immunity in CTX-induced immunosuppressed mice by regulating MAPK/NF-κB signaling pathway. Ginseng-DF can be used as a safe dietary supplement to enhance body immunity and reduce intestinal mucosal injury caused by CTX.

Metabolic brain imaging with glucosamine CEST MRI: in vivo characterization and first insights

The utility of chemical exchange saturation transfer (CEST) MRI for monitoring the uptake of glucosamine (GlcN), a safe dietary supplement, has been previously demonstrated in detecting breast cancer in both murine and human subjects. Here, we studied and characterized the detectability of GlcN uptake and metabolism in the brain. Following intravenous GlcN administration in mice, CEST brain signals calculated by magnetization transfer ratio asymmetry (MTRasym) analysis, were significantly elevated, mainly in the cortex, hippocampus, and thalamus. The in vivo contrast remained stable during 40 min of examination, which can be attributed to GlcN uptake and its metabolic products accumulation as confirmed using 13C NMR spectroscopic studies of brain extracts. A Lorentzian multi-pool fitting analysis revealed an increase in the hydroxyl, amide, and relayed nuclear Overhauser effect (rNOE) signal components after GlcN treatment. With its ability to cross the blood-brain barrier (BBB), the GlcN CEST technique has the potential to serve as a metabolic biomarker for the diagnosis and monitoring various brain disorders.

The Development and Efficacy of a High School Athlete Education Program for Safe Nutritional Supplement Use

Many high school athletes report using nutritional supplements. Due to a lack of education at the high school level, the use of safe for sports third-party tested nutritional supplements may be limited. To determine the impact of a short online nutritional supplement education program on safe dietary supplement behavior a cross-sectional repeated measures design was used. Therefore, a convenience sample of 106 high school athletes (14–19 years old) was recruited to measure pre-post education difference for nutritional supplement use and third-party tested (TPT) supplements. Additionally, it was analyzed if nutritional supplement related Theory of Planned Behavior (TPB) constructs were associated with athlete choices. The most popular supplements included protein powder (65%), caffeine from beverages (45%), and different types of vitamins (ranging from 38–44%). Consistent use of (safe) third-party tested individual supplements was low, ranging from 35–77% for the most frequently reported supplements. The combined TPB determinants explained 26% of the variance of the intention to use safe supplements (F3, 102 = 13.03, p < 0.001, Adj R2 = 0.26). The self-reported intention to use third-party tested supplements increased significantly (+7%–36% per individual supplement) after following the education program (Z = −3.288, p = 0.001) resulting in an intentional use of 54–94% TPT supplements. In conclusion, education resulted in more high school athletes reporting future third-party tested supplements use, and TPB construct scores did not change over time but could explain a substantial part of the variance of safe supplement use intentions.

Preparation of astaxanthin-loaded composite micelles with coaxial electrospray technology for enhanced oral bioavailability and improved antioxidation capability.

Astaxanthin (AST) is approved by the US Food and Drug Administration (FDA) as a safe dietary supplement for humans. As a potent lipid-soluble keto-carotenoid, it is widely used in food, cosmetics, and the pharmaceutical industry. However, its low solubility limits its powerful biological activity and its application in these fields. This study aims to develop a delivery system to address the low solubility and bioavailability of AST and to enhance its antioxidant capacity. Astaxanthin-loaded composite micelles were successfully prepared via coaxial electrospray technology. Astaxanthin existed in the amorphous state in the electro-sprayed formulation with an approximate particle size of 186.28 nm and with a polydispersity index of 0.243. In this delivery system, Soluplus and copovidone (PVPVA 64) were the main polymeric matrix for AST, which then released the drug upon contact with aqueous media, resulting in an overall increase in drug solubility and a release rate of 94.08%. Meanwhile, lecithin, and Polyethylene glycol-grafted Chitosan (PEG-g-CS)could support the absorption of AST in the gastrointestinal tract, assisting transmembrane transport. The relative bioavailability reached about 308.33% and the reactive oxygen species (ROS) scavenging efficiency of the formulation was 44.10%, which was 1.57 times higher than that of free astaxanthin (28.10%) when both were at the same concentration level based on astaxanthin. Coaxial electrospray could be applied to prepare a composite micelles system for the delivery of poorly water-soluble active ingredients in functional food, cosmetics, and medicine. © 2023 Society of Chemical Industry.

P24-076-23 Forging a Way Forward for Safe Dietary Supplement Use: Development of a Mobile App

P24-076-23 Forging a Way Forward for Safe Dietary Supplement Use: Development of a Mobile App

Dietary Supplements for Weight Loss.

The Federal Drug Administration has approved, following rigorous testing, 6 pharmacologic agents and one drug in device form for the management of overweight and obesity. Myriad products that purport to act on physiological mechanisms leading to weight loss also pervade the market with minimal regulatory oversight. Systematic reviews and meta-analyses of these products and their ingredients fail to establish any as meaningfully effective at the clinical level. Moreover, safety concerns prevail with adulteration, hypersensitivity reactions, and recognized adverse reactions. Lifestyle, pharmacologic, and bariatric surgical treatments are increasingly available, effective, and safe management tools for practitioners who should council patients, many of whom are susceptible to misinformation, on the lack effective and safe dietary supplements for weight loss.

Can exercise prevent the age‐related decline in adaptive homeostasis? Evidence across organisms and tissues

Can exercise prevent the age‐related decline in adaptive homeostasis? Evidence across organisms and tissues

Narrative Review: The FDA's Perfunctory Approach of Dietary Supplement Regulations Giving Rise to Copious Reports of Adverse Events.

Background: The Food and Drug Administration (FDA) originated from the passage of the 1906 Pure Food and Drugs act aimed to rein in the long-standing abuse in the consumer product marketplace. The act was passed to prohibit interstate commerce of misbranded and adulterated foods, drinks, drugs. Thus, promoting the FDA's mission to protect the public health by regulating human and veterinary drugs, biological products, medical devices, food supply, cosmetics, and tobacco to ensure safety, efficacy, and security. Progressing further in 1994, the Dietary Supplement Health and Education Act (DSHEA) was established designating specific label requirements, providing regulatory framework, and authorizing the FDA to promulgate good manufacturing practices for dietary supplements. This act defined and classified "dietary supplements" and "dietary ingredients" as food requiring all over the counter products (OTC) products to consist of labeling that is easy to understand and meets the FDA quality, effectiveness, and safety standards. However, under the umbrella of OTC products, the FDA fell short in its regulation of the expansive dietary supplement market. The objective of this study is to discern how the lack of efficacy in the FDA's regulations of OTC dietary supplements inevitably inspired more harm than benefit. Methods: This review comprised of case studies including young adolescents and adult consumers who experienced adverse events from the use of dietary supplements. Products which showed highest prevalence in adverse event reports through the Food and Drug Administration CFSAN Adverse Event Reporting System (CAERS) included but not limited to; Vitamin E (vitamin derivative), Beta-sitosterol (plant sterol) Yohimbine, Kava Kava Kratom, Garcinia Cambogia, (herbal products) and OxyElite Pro (marketed weight loss product). The primary endpoint was evaluating the FDA's regulations on dietary supplement safety protocols. The secondary endpoint was assessing the actions of the FDA in response to these case events. Results: Overall, between 2004 to 2021, a total of 79,071 adverse events related to the use of dietary supplements were reported to the Center for Food Safety and Applied Nutrition. Vitamin E products for example, marketed for decades for their antioxidant benefits in turn have shown significant evidence of toxicity and an increased risk of bleeding outweighing its potential benefit. The FDA's response was simply implementing a label guideline update, yet this update had evidence of minimal effect as the number of cases gradually continued to increase. Likewise, herbal products such as Kava Kava, Yohimbine, Kratom, and Garcinia Cambogia, in addition to weight regulating products, such as OxyElite Pro and HydroxyCut, have been linked to organ failure, hepatic, renal, cardiac toxicity, and death respectively. The FDA merely responded through instating public consumer warnings of their effects with consumption and limited recalls of certain products. Conclusion: With the easy accessibility of these products, the general public is more inclined to its use without proper guidance and monitoring from their healthcare team, posing as a major concern for possible interactions, contraindications and unfavorable outcomes. With proper implementation of stringent regulations post findings from increased studies on efficacy and safety, cases of adverse events could have been reduced significantly or averted completely. The FDA's minimalistic efforts consisting of only post-marketing monitoring and retrospective actions of label modifying have time and time again shown flaws as seen in the growing series of reports. By emending the over-the-counter supplement review process to reflect that of prescription medication, the magnitude of adverse events can be diminished. The process should include preclinical research in addition to clinical research, FDA thorough examination of data prior approval and post marketing surveillance.

Screening of Spirulina Components for Anti-Parkinson's and Anti-Alzheimer's Activity byin Silico Methods and Docking Studies.

Spirulina platensis was first isolated from Lake Texcoco by Aztecs in the sixteenth century. In 2012, spirulina was considered to be safe dietary supplement by the Food and Drug Administration (FDA). Spirulina is a cyanophytic microalgae that is often considered as single cell protein. It contains many essential amino acids, proteins, fatty acids, antioxidant pigments, carotenoids, and cyanogenic pigments, that is, phycocyanobilins and phycocyanins (Eriksen, Appl Microbiol Biotechnol, 80(1):1-4, 2008). Components of spirulina are investigated for many health benefits and for pharmaceutical uses (Karkos et al., Spirulina in clinical practice: evidence-based human applications). Spirulina has been found to have a role in growth, immunity (Wu et al., Arch Toxicol, 90(8):1817-40, 2016), antioxidant (Wu et al., Arch Toxicol, 90(8):1817-40, 2016), antiviral (Ayehunie et al., J Acquir Immune Defic Syndr Hum Retrovirol, 18(1):7-12, 1998), antitoxicologic, anti-cancerogenic (Hirahashi et al., Int Immunopharmacol, 2(4):423-34, 2002), antidiabetic (Layam and Reddy, Diabetol Croat, 35(2):29-33, 2006), and neuroprotective properties. In this study, we focused on spirulina components in anti-Parkinson's and anti-Alzheimer's activity. Four potential targets, two for each activity, that is, structure of parkinE3 ligase (PDB ID:4I1H) and structure of BACE bound to 5-(3-(5-chloropyridin-3-yl)phenyl)-5-cyclopropyl-2-imino-3-methylimidazolidin-4one (PDBI D:4DJx) for anti-Parkinson's activity and structure of human MAO B in complex with selective inhibitor safinamide (PDB ID:2V5Z) and crystal structure of human BACE-1 in complex with CNP520(PDB ID:6EQM) for anti-Alzheimer's activity, have been selected. The in silico results and scoring of virtual screening, that is, molecular docking, were compared with commonly used marketed drugs such as levodopa for Parkinson's disease (PD) and rivastigmine (Rösler et al., BMJ, 318(7184):633-40, 1999) for Alzheimer's disease.

Processes in Doping System: Quantification Reports in Mixed Martial Arts Fighters

Mixed martial arts (MMA) has always been surrounded by controversy due to the unusual muscle development of its participants, so it is crucial to know the strategies that have been implemented to reduce doping cases. The main purpose of this paper is to describe the various cases of doping detected by USADA in UFC MMA participants. In addition, strategies that are being developed to reduce cases of positive doping are proposed. From the UFC USADA database, doping cases were extracted, obtaining the substance or substances involved; the formula, physiological effect and the athletes involved; the dates of the sampling; if it was out of competition or in-competition and the sanction time. The substances that were most involved were found to be Ostarine (22), Clomiphene (9), Diuretics (10) and Stanozolol (9). Some sanctions were diminished because they were treated with contamination of supplements (cases of Ostarine) and cases of contamination of meat (Clomiphene). When contaminated supplements were reported, they were added to the list of high-risk supplements maintained as part of USADA’s online dietary supplement safety education and awareness resource—Supplement 411. There were also cases in which positive doping could be avoided through the early report of therapeutic use exemptions. The methodology that the USADA has implemented allows us to register the athletes with positive doping, check the risk of the supplements before being bought and provide a teaching portal. These efforts are necessary to implement in all countries in which MMA is practiced, avoiding the participation of doped martial artists.

Soluble dietary fiber and cellulose from Saccharina japonica by-product ameliorate Loperamide-induced constipation via modulating enteric neurotransmitters, short-chain fatty acids and gut microbiota

The effects of soluble dietary fiber (SDF) and cellulose (IDF) from Saccharina japonica by-product and their differences in improving constipation were further clarified in the present study. We demonstrated that SDF was mainly made up of d-mannuronic acid and d-mannose while IDF consisted of d-glucose , which is different from other reported dietary fibers of terrestrial plants. In this research, both SDF and IDF improved fecal-related indicators, gastrointestinal transit rate and histological morphology in Lop-induced mice. Moreover, they could increase the level of antioxidant enzymes (SOD and GSH-Px), restore the expression of enteric neurotransmitters, and maintain the function of ZO-1, JAM-1 as well as Occludin. Interestingly, SDF and IDF had a significant up-regulated effect on the proportion of Muribaculacea, Prevotellaceaen and Lachnospiraceae, which are critical to preserving intestinal immune homeostasis. Besides, they promoted the biosynthesis of short-chain fatty acids (SCFAs). The overall index showed that SDF is more effective for constipation due to its better water retention capacity. Thus, they can be used as a safe dietary supplement for the treatment of chronic or occasional constipation in humans.

Evaluation of Effectiveness and Safety of Microcin C7 in Weaned Piglets.

The effects and safety of dietary supplementation with Microcin C7 (C7) were evaluated in 216 weaned piglets. The pigs were given a control corn−soybean meal basal diet or C7 diet (control diet supplemented with 250, 500, 750, 1000, or 5000 mg C7/kg diets). Compared with the control group, the 500 mg/kg C7 supplementation group had better intestinal morphological indicators (p < 0.05), which may help maintain intestinal epithelial function and increase the growth performance (p < 0.05) and apparent total tract digestibility (p < 0.05). The diarrhea indexes of the 250, 500, and 750 mg/kg groups were significantly lower than that of the control group at 0−28 d (p < 0.05), and the 500 mg/kg group had the lowest diarrhea indexes (linear and quadratic, p < 0.05). A comprehensive analysis showed that microbial structure was significantly correlated with the degree of diarrhea, and the diarrhea-alleviating effect of C7 may be related to its selective regulation of specific microbial taxa. The 250 and 500 mg/kg C7 supplementation also significantly improved several immune indices of piglets (p < 0.05). Compared with the control diet, 5000 mg/kg C7 supplementation had no significant adverse effect on all parameters. Overall, the 250−500 mg/kg dose had the best effect, and the highest dose (5000 mg/kg) posed no toxicity risk. Therefore, C7 appears safe for use as an alternative to antibiotic growth promoters in weaned piglets.

A novel Atlantic salmon (Salmo salar) bone collagen peptide delays osteoarthritis development by inhibiting cartilage matrix degradation and anti-inflammatory

Nowadays, the biological activity of collagen peptides has been revealed, but the effect of Atlantic salmon (Salmo salar) bone-derived collagen peptide (CPs) on osteoarthritis remains unclear. In this study, CPs was identified as a small molecular weight peptide rich in Gly-X-Y structure. Meanwhile, interleukin-1β (IL-1β)-induced hypertrophic chondrocytes and partial medial meniscectomy (pMMx) surgery model in rats were performed. In IL-1β stimulated chondrocytes, CPs significantly increased the type-II collagen content, reduced the type-X collagen abundance and chondrocytes apoptosis. Meanwhile, CPs reversed the increased expression of matrix metalloproteinase, metalloproteinase with thrombospondin motifs and RUNX family transcription factor 2 in chondrocytes induced by IL-1β. In vivo, CPs increased pain tolerance of rats and without organ toxicity at 1.6 g/kg.bw. CPs significantly decreased the levels of COMP and Helix-II in serum. Furthermore, a significant decrease of IL-1β in synovial fluid and cartilage tissue were observed by CPs intervention. From Micro-CT, CPs (0.8 g/kg.bw) significantly decreased Tb.sp and SMI value. Meanwhile, the expression of tumor necrosis factor and interleukin-6 were reduced by CPs administration both in vitro and in vivo. Together, CPs showed potential to be a novel and safe dietary supplement for helping anti-inflammatory and cartilage regeneration, ultimately hindering osteoarthritis development. However, the clear mechanism of CPs’s positive effect on osteoarthritis needs to be further explored.

Dietary Supplements Use among Serbian Undergraduate Students of Different Academic Fields.

The rising popularity of dietary supplements as a part of self-care practice increases interest in monitoring their usage in the general and specific population groups. This study investigated the prevalence and patterns of dietary supplement use among Belgrade University undergraduate students and its variations across different academic study fields. Of the 914 online survey students, 55.7% used dietary supplements during the past year. Female gender, eating behavior, and academic field were significant predictors of dietary supplement use. For all students, the most commonly used dietary supplements were vitamins and minerals, alone or in combination. Magnesium, vitamin C, and B vitamins were the most frequently supplemented micronutrients. The reasons for using, place of purchase, and source of information regarding dietary supplements significantly varied among students of different fields of study. Adverse effects related to dietary supplement use, including gastrointestinal symptoms, skin flushing, dizziness, and heart palpitation, were reported in 4.5% of students. Insufficient knowledge about these products was self-reported by 16.5% of users, more common among non-medical students. Thus, public health interventions are needed to improve students’ knowledge regarding rational and safe dietary supplement use.

Calm Down With Kava: What Clinicians Need to Know.

Kava is a neuroactive medicinal herb that can induce pharmacological effects when ingested. As an herbal remedy, kava exhibits sedative, anesthetic, euphoriant, and entheogenic effects. Kava is used as a relaxant, pain reliever, and remedy for anxiety and insomnia. In the United States, kava is marketed as a safe dietary supplement. Kava's popularity is on the rise due to heightened awareness and interest in natural plant-based health alternatives. Although meta-analyses and systematic reviews of kava use in treating anxiety are favorable, results remain inconsistent. Due to poor quality control, diversity of kava products, and lack of standardization, health care professionals, such as nurses, advanced practice nurses, physicians, physician assistants, and pharmacists, need to be familiar with the pharmacology, possible polydrug interactions, and management of kava use as a remedy for anxiety-related conditions. The purpose of the current article is to provide an overview of kava and its use as a remedy for psychological issues, such as anxiety and nervousness. [Journal of Psychosocial Nursing and Mental Health Services, 60(12), 17-24.].

Nicotinamide Riboside Supports Brain Health: Assessing the Evidence

ObjectivesAlterations in neurobiology are linked to mild cognitive decline and various diseases including Alzheimer's Disease (AD), ALS, and Autism Spectrum Disorder (ASD). Declines in brain health are associated with neuroinflammation, nicotinamide adenine dinucleotide (NAD+) deficits, and are often accompanied by changes in memory and social behaviors. The NAD+ precursor, nicotinamide riboside (NR) is a clinically proven, safe dietary supplement in humans. The objective of this review is to evaluate the effectiveness of NR on improving brain function and neurobiology in preclinical models, to support translation into future clinical studies.MethodsPeer-reviewed, published preclinical studies evaluating NR on various parameters of brain health and neurodegeneration were reviewed. Complimentary endpoints associated with multiple studies were identified to conclude potential mechanisms of action across multiple disease models and justify translation into human studies.ResultsA total of 20 preclinical studies have been published evaluating NR on various aspects of brain health in cell culture and rodent models. NR was evaluated in preclinical models of AD, ALS, Gulf War Illness, ASD, obesity-induced cognitive decline, alcohol-induced depression, and maternal supplementation, amongst others. Though various doses of NR were tested, 400 mg/kg/day (estimated at 1300 mg/day for an adult human) was most frequently utilized dose. NR increased NAD+ levels in the brain of mice following oral supplementation in seven separate studies. Multiple studies demonstrated NR-induced improvements in cognitive performance, behavior, and slowing of disease progression. The mechanisms of NR-induced augmentations were repeatedly associated with decreased neuroinflammation, potentially through a decrease in the cGAS–STING pathway, attenuation of neuronal degradation, reduction in amyloid-β, increase in brain-derived neurotrophic factor, and an increase in sirtuins.ConclusionsAs the safety of NR has been demonstrated in multiple clinical studies, and oral NR supplementation has been shown to be successful in multiple preclinical models of neurodegeneration and brain function, there is ample evidence to support clinical evaluation of NR as a support for brain health.Funding SourcesThe authors are employees of ChromaDex.

0801 Melatonin Induced Autoimmune Hepatitis in the Setting of the Management of REM Sleep Behavior Disorder

Abstract Introduction Melatonin is a neurohormone that serves a key role in human circadian physiology. It is widely used in the United States as an over-the-counter (OTC) sleep aid for managing insomnia, circadian rhythm disorders, and parasomnias. The US Food and Drug do not regulate it as a dietary supplement. However, insufficient data currently exist about formulations and overall safety for long-term usage. While serious adverse events with melatonin are rare, we describe a patient in whom clinical, laboratory, and biopsy features of autoimmune-mediated hepatitis developed in temporal association with time-release melatonin (MLTR) therapy for the treatment of dream enactment behaviors in the setting of REM-sleep behavior disorder (RBD). Report of Cases: A 78-year-old female was referred to our clinic to manage disruptive dream enactment in the setting of RBD. The patient had been previously treated with Clonazepam, Diazepam, and Temazepam but remained refractory. Management with MLTR at 5 mg achieved clinical improvement and titration over a month up to 10 and 15 mg fully controlled dream enactment. Unfortunately, during this time, the patient developed swollen and erythematous joints and abdominal pain. Liver biopsy demonstrated lymphoplasmacytic infiltrate with rosette formation consistent with autoimmune hepatitis consistent with idiosyncratic drug-induced hepatitis associated with elevated liver function enzymes [AST 184 (H) (NL &amp;lt;39U/L), ALT 395 (H) (NL&amp;lt;56 U/L), Bilirubin, Direct= 0.3 (H) (NL&amp;lt;=0.2 mg/dL)]. Melatonin was discontinued achieving complete resolution of symptoms and normalization of liver function indicating its causal association with hepatitis. Conclusion This unusual report of melatonin-induced autoimmune hepatitis is uncommon but points to intriguing immunostimulatory effects of melatonin. Our case highlights an important and sometimes overlooked attribute of melatonin that prescribers and patients must recognize. While melatonin is often viewed as a safe dietary supplement, its use, particularly among people with autoimmune disorders, should be documented and monitored with care. Support (If Any)

Cardio-respiratory and phenotypic rescue of dystrophin/utrophin-deficient mice by combination therapy.

Duchenne muscular dystrophy (DMD) is a systemic progressive muscular disease caused by frame-disrupting mutations in the DMD gene. Although exon-skipping antisense oligonucleotides (AOs) are clinically approved and can correct DMD, insufficient muscle delivery limits efficacy. If AO activity can be enhanced by safe dietary supplements, clinical trials for efficacy can be undertaken rapidly to benefit patients. We showed previously that intravenous glycine enhanced phosphorodiamidate morpholino oligomer (PMO) delivery to peripheral muscles in mdx mice. Here, we demonstrate that the combination of oral glycine and metformin with intravenous PMO enhances PMO activity, dystrophin restoration, extends lifespan, and improves body-wide function and phenotypic rescue of dystrophin /utrophin double knock-out (DKO) mice without any overt adverse effects. The DKO mice treated with the combination without altering the approved administration protocol of PMO show improved cardio-respiratory and behavioral functions. Metformin and glycine individually are ineffective in DMD patients, but the combination of PMO with clinically-approved oral glycine and metformin might improve the efficacy of the treatment also in DMD patients. Our data suggest that this combination therapy might be an attractive therapy for DMD and potentially other muscle diseases requiring systemic treatment with AOs.

Issues of Safety of Herb Mixes and Food Supplements Contaminated with Tropane Alkaloids: A Review

Background: Nutritional supplements, herbal assemblages, and herbal teas are of particular interest in the global market of specialized food products, with the issues of a safe use becoming particularly relevant in the light of the reports on their potential contamination with tropane alkaloids, which content ranges from 0.01 % to 3 % depending on the type of raw materials. Objective: Analysis of the safety of dietary supplements, herbs and herbal teas contaminated with tropane alkaloids, based on data currently presented in domestic and international scientific publications. Materials and methods: We reviewed and analyzed literature sources found in Scopus, PubMed and RSCI databases for tropane alkaloids. The initial sample included 49 articles, of which 19 articles were excluded following a primary analysis. The selection criteria included the presence of classification of tropane alkaloids, their contents in herbs and foods, methods of detection, and potential human health effects. We selected 30 full-text publications meeting the above criteria. The study results were systematized by the type of intervention. Results: The analysis showed that the content of tropane alkaloids in some herbal teas by the sum of atropine and scopolamine can exceed the established level of a single safe intake (0.016 µg/kg body weight). Since scopolamine is a derivative of hyoscyamine (atropine), safety of foods and raw materials should be assessed by their content of atropine that will allow effective monitoring of contamination with tropane alkaloids of all types of the specified food products for the purpose of their safe use. Conclusion: For the safe use of herbal preparations and plant-based dietary supplements, it is recommended to monitor these types of food products for the presence of tropane alkaloids in them. It is advisable to develop a method for their analysis using high-performance liquid chromatography coupled with mass spectrometry.