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Assessment of adverse reactions to α-lipoic acid containing dietary supplements through spontaneous reporting systems.
Gatti, M, Ippoliti, I, Poluzzi, E, Antonazzo, IC, Moro, PA, Moretti, U, Menniti-Ippolito, F, Mazzanti, G, De Ponti, F, Raschi, E
Clinical nutrition (Edinburgh, Scotland). 2021;(3):1176-1185
Abstract
BACKGROUND & AIMS Alpha-lipoic acid (ALA)-containing dietary supplements are widely used in clinical practice, although their safety assessment is under-investigated. We characterize the safety profile of ALA-containing products by analysing spontaneous reports of suspected adverse reactions (ARs). METHODS Suspected ARs to ALA-containing products were extracted from the Italian Phytovigilance System (IPS), and scrutinized in terms of seriousness and causality (through WHO UMC system), with a specific focus on important (IMEs) and designated medical events (DMEs). To characterize the reporting profile from an international perspective, the WHO-VigiBase was also queried. RESULTS From March 2002 to February 2020, out of 2147 total reports, 116 reports concerning 212 ARs to ALA-containing products were collected. Women were involved in 68.1% of cases. Skin (44.9%) and gastrointestinal disorders (10.8%) were the most frequently represented ARs. Causality assessment resulted as definite (15), probable (35), possible (24), unlikely (5), and unclassifiable (37). In 70% of cases, events occurred within 30 days of ALA use. Forty-five reports were serious (38.8%), being insulin autoimmune syndrome the most frequently reported (N = 10). IMEs were recorded in 20 cases, including four DMEs (3 angioedema and one anaphylactic shock). Similar distribution emerged from the 5641 reports in the WHO-VigiBase. CONCLUSIONS The remarkable reporting of unpredictable skin, immune and hepatic ARs, coupled with seriousness, strong causality and early onset, calls for a) careful risk-benefit assessment of ALA-containing products by regulators; b) awareness and monitoring by clinicians and c) continuous vigilance of their safety profile through valuable spontaneous reporting systems such as IPS.
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Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial.
Wauters, L, Slaets, H, De Paepe, K, Ceulemans, M, Wetzels, S, Geboers, K, Toth, J, Thys, W, Dybajlo, R, Walgraeve, D, et al
The lancet. Gastroenterology & hepatology. 2021;(10):784-792
Abstract
BACKGROUND Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. METHODS In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (≥18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computer-generated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulans MY01 and Bacillus subtilis MY02, 2·5 × 109 colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0·7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04030780. FINDINGS Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40·1 years [SD 14·4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1·95 [95% CI 1·07-4·11]; p=0·028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product. INTERPRETATION In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets. FUNDING MY HEALTH.
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The landscape of hepatobiliary adverse reactions across 53 herbal and dietary supplements reveals immune-mediated injury as a common cause of hepatitis.
Zhu, J, Chen, M, Borlak, J, Tong, W
Archives of toxicology. 2020;(1):273-293
Abstract
Recent evidence suggests herbal-induced liver injury (HILI) to account for 20% of cases among the U.S. Drug-Induced-Liver-Injury-Network. To define injury patterns of HILI, we reviewed the clinical data of 413 patients exposed to 53 HDS products by considering the evidence for HILI and its grades of severity. Outstandingly, females developed HILI more rapidly (p = 0.018) and the time to recovery was significantly increased (p = 0.0153). > 90% of reported cases were severe and half of HDS products caused acute liver failure (ALF) requiring liver transplantation or resulted in fatal outcomes. Liver biopsies of 243 patients defined 13 histological features; two-thirds of products elicited immune-mediated hepatitis and included 154 Hy's law positive cases. The histological injury patterns were confirmed among unrelated patients, while accidental re-challenges evidenced culprits as causative. Furthermore, one-fifth of patients presented elevated autoantibody titres indicative of autoimmune-like HILI, and one-third of the products were linked to chronic hepatitis and cholestatic injuries not resolving within 6 months. Lastly, INR and TBL are critical laboratory parameters to predict progression of severe HILI to ALF. Our study highlights the need for a regulatory framework to minimize the risk for HILI. Better education of the public and a physician-supervised self-medication plan will be important measures to abate risk of HILI.
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Herbal supplements interactions with oral oestrogen-based contraceptive metabolism and transport.
Hlengwa, N, Muller, CJF, Basson, AK, Bowles, S, Louw, J, Awortwe, C
Phytotherapy research : PTR. 2020;(7):1519-1529
Abstract
The increased use of herbal supplements as complementary or alternative medicines has become a clinical conundrum due to the potential for herb-drug interactions. This is exacerbated by an increased supply of new herbal supplements in the market claiming various health advantages. These herbal supplements are available as over-the-counter self-medications. Herbal supplements are generally perceived as efficacious without side effects commonly associated with conventional drugs. However, despite regulations, claims related to their therapeutic effects are mostly unsupported by scientific evidence. These products often lack suitable product quality controls, labelled inadequately and with batch to batch variations, potentially compromising the safety of the consumer. Amongst health practitioners, the greatest concern is related to the lack of chemical characterization of the active compounds of the herbal supplements. The interaction between these different active components and their concomitant effects on other conventional drugs is generally not known. This review will focus on herbal supplements with the potential to effect pharmacokinetic and pharmacodynamic properties of oestrogen-based oral contraceptives. The use of herbal supplements for weight management, depression, and immune boosting benefits were selected as likely herbal supplements to be used concomitantly by women on oral contraceptives.
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A randomized, double-blind, placebo-controlled clinical trial, evaluating the garlic supplement effects on some serum biomarkers of oxidative stress, and quality of life in women with rheumatoid arthritis.
Moosavian, SP, Paknahad, Z, Habibagahi, Z
International journal of clinical practice. 2020;(7):e13498
Abstract
AIM: Rheumatoid arthritis (RA), is a prevalent immune-inflammatory disease, which is associated with disabling pain. Oxidative stress might play a role in RA pathogenesis and outcomes. According to the antioxidant properties of garlic, the current study was performed to evaluate the garlic supplement effects on some serum levels of oxidative stress biomarkers, and quality of life in patients with rheumatoid arthritis. METHODS Seventy women with RA participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The patients were randomly divided into two groups, receiving two tablets of either 500 mg garlic or placebo daily for 8 weeks. Serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA) and quality of life were determined at baseline and end of week 8. A health assessment questionnaire (HAQ) was used to evaluate the quality of life related to health. RESULTS Of 70 patients enrolled in the trial, 62 subjects were included in the final analysis. At the end of the study, there was a significant increase in serum levels of TAC in the garlic group as compared with the placebo group (26.58 ± 77.30 nmol of Trolox equivalent/ml vs 16.11 ± 0.92 nmol of Trolox equivalent/mL; P = .026). In addition, MDA levels were significantly decreased in the intervention group compared with the control group (-0.82 ± 1.99 nmol/mL vs 0.36 ± 2.57 nmol/mL; P = .032). Pain after activity and HAQ scores decreased in the garlic group compared with the placebo (-11.96 ± 13.43 mm vs -0.06 ± 13.41 mm; P < .001, 0.17 ± 20 vs 0.05 ± 0.15; P < .001, respectively). CONCLUSIONS The findings suggest that garlic supplementation for 8 weeks resulted in significant improvements in oxidative stress, HAQ in women with RA.
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Evaluation of the effects of pycnogenol (French maritime pine bark extract) supplementation on inflammatory biomarkers and nutritional and clinical status in traumatic brain injury patients in an intensive care unit: A randomized clinical trial protocol.
Malekahmadi, M, Moradi Moghaddam, O, Islam, SMS, Tanha, K, Nematy, M, Pahlavani, N, Firouzi, S, Zali, MR, Norouzy, A
Trials. 2020;(1):162
Abstract
BACKGROUND Traumatic brain injury (TBI) is one of the major health and socioeconomic problems in the world. Immune-enhancing enteral formula has been proven to significantly reduce infection rate in TBI patients. One of the ingredients that can be used in immunonutrition formulas to reduce inflammation and oxidative stress is pycnogenol. OBJECTIVE The objective of this work is to survey the effect of pycnogenol on the clinical, nutritional, and inflammatory status of TBI patients. METHODS This is a double-blind, randomized controlled trial. Block randomization will be used. An intervention group will receive pycnogenol supplementation of 150 mg for 10 days and a control group will receive a placebo for the same duration. Inflammatory status (IL-6, IL- 1β, C-reactive protein) and oxidative stress status (malondialdehyde, total antioxidant capacity), at the baseline, at the 5th day, and at the end of the study (10th day) will be measured. Clinical and nutritional status will be assessed three times during the intervention. The Sequential Organ Failure Assessment (SOFA) questionnaire for assessment of organ failure will be filled out every other day. The mortality rate will be calculated within 28 days of the start of the intervention. Weight, body mass index, and body composition will be measured. All analyses will be conducted by an initially assigned study arm in an intention-to-treat analysis. DISCUSSION We expect that supplementation of 150 mg pycnogenol for 10 days will improve clinical and nutritional status and reduce the inflammation and oxidative stress of the TBI patients. TRIAL REGISTRATION This trial is registered at clinicaltrials.gov (ref: NCT03777683) at 12/13/2018.
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Nutritional supplementation of vitamin A and health-related outcomes in patients with multiple sclerosis: A protocol for a systematic review and meta-analysis of randomized clinical trials.
Nunes, ACF, Piuvezam, G
Medicine. 2019;(25):e16043
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Abstract
BACKGROUND Multiple sclerosis (MS) is a chronic immune mediated disease which affects the central nervous system (CNS), having a substantial financial, functional, and quality of life (QOL) impact on these people. The vitamin A supplementation has been studied as a therapeutic possibility for in MS. Therefore, the objective of this protocol is to build an outline for a future systematic review, which will provide up-to-date available evidence about the clinical impact of nutritional supplementation of vitamin A in the outcomes related to the symptoms in patients with this pathology. METHODS The search will be performed in the following databases: PubMed, Embase, Scopus, cinahl, Scielo, Web of Science, the Cochrane Library and Science Direct, randomized clinical trials published until May 2019 that evaluate the relationship of the supplementation of vitamin A and health-related outcomes in patients with MS will be included. Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) will be used to outline the protocol, and PRISMA to the systematic review. Undergraduate handbook of quality of evidence and strength of recommendations for decision making in health (GRADE) will be used to assess the quality of evidence and the strength of the recommendation, and the JADAD scale to assess the internal validity of selected studies. For the extraction of all the data found a database in Microsoft Excel will be created. For the summary of the findings the Cochrane Collaboration Handbook recommendations will be used, and for the meta-analysis standard statistical techniques the RevMan software will be used. RESULTS In this study, we hope to find a considerable number of articles presenting evidence about the effectiveness of vitamin A supplementation in patients with MS. CONCLUSION Currently, many lines of evidence have been produced when it comes to the use of food supplements. This systematic review proposal might provide recent, important, and trusted information for better treatment of patients. RECORD OF SYSTEMATIC REVIEW This review was recorded in the International Register of Prospective Systematic Reviews (PROSPERO) on the January 30, 2019 (registration: CRD42019121757). Available at: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019121757.
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Drug-Induced Liver Injury: Highlights of the Recent Literature.
Real, M, Barnhill, MS, Higley, C, Rosenberg, J, Lewis, JH
Drug safety. 2019;(3):365-387
Abstract
Drug-induced liver injury (DILI), herbal-induced liver injury, and herbal and dietary supplement (HDS)-induced liver injury are an important aspect of drug safety. Knowledge regarding responsible drugs, mechanisms, risk factors, and the diagnostic tools to detect liver injury have continued to grow in the past year. This review highlights what we considered the most significant publications from among more than 1800 articles relating to liver injury from medications, herbal products, and dietary supplements in 2017 and 2018. The US Drug-Induced Liver Injury Network (DILIN) prospective study highlighted several areas of ongoing study, including the potential utility of human leukocyte antigens and microRNAs as DILI risk factors and new data on racial differences, the role of alcohol consumption, factors associated with prognosis, and updates on the clinical signatures of autoimmune DILI, thiopurines, and HDS agents. Novel data were also generated from the Spanish and Latin American DILI registries as well as from Chinese and Korean case series. A few new agents causing DILI were added to the growing list in the past 2 years, including sodium-glucose co-transporter-2 inhibitors, as were new aspects of chemotherapy-associated liver injury. A number of cases reported previously described hepatotoxins confirmed via the Roussel Uclaf Causality Assessment Method (RUCAM; e.g., norethisterone, methylprednisolone, glatiramer acetate) and/or the DILIN method (e.g., celecoxib, dimethyl fumarate). Additionally, much work centered on elucidating the pathophysiology of DILI, including the importance of bile salt export pumps and immune-mediated mechanisms. Finally, it must be noted that, while hundreds of new studies described DILI in 2017-2018, the quality of such reports must always be addressed. Björnsson reminds us to remain very critical of the data when addressing the future utility of a study, which is why it is so important to adhere to a standardized method such as RUCAM when determining DILI causality. While drug-induced hepatotoxicity remains a diagnosis of exclusion, the diverse array of publications that appeared in 2017 and 2018 provided important advances in our understanding of DILI, paving the way for our improved ability to make a more definitive diagnosis and risk assessment.
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Additional effect of perioperative, compared with preoperative, immunonutrition after pancreaticoduodenectomy: A randomized, controlled trial.
Miyauchi, Y, Furukawa, K, Suzuki, D, Yoshitomi, H, Takayashiki, T, Kuboki, S, Miyazaki, M, Ohtsuka, M
International journal of surgery (London, England). 2019;:69-75
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BACKGROUND We have reported that perioperative and preoperative immunonutrition reduced infectious complications in patients undergoing pancreaticoduodenectomy; however, it is unclear whether perioperative immunonutrition has additional effects compared with preoperative immunonutrition. The present study evaluated whether perioperative, compared with preoperative, immunonutrition has additional effects on cell-mediated immunity and the infection rate after pancreaticoduodenectomy. MATERIALS AND METHODS This was a prospective, randomized clinical trial conducted in our institution. Oral supplementation enriched with arginine, ω-3 fatty acids, and dietary nucleotides was given by enteral infusion to 30 patients before and after surgery (perioperative group); 30 patients received the same enriched formula before surgery and standard enteral nutrition following surgery (preoperative group). The primary endpoint was concanavalin (Con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation on postoperative day (POD) 7, which is an index of cell-mediated immunity; the secondary endpoint was the postoperative infection rate. RESULTS There were no significant differences in Con A- or PHA-stimulated lymphocyte proliferation on POD 7 between the groups. There was no significant difference in the postoperative infection rate between the two groups. In the post hoc subgroup analysis, with respect to the effect on the infection rate, a significant interaction was found only between a long operative time and perioperative immunonutrition. CONCLUSIONS There were no additional effects of perioperative, compared with preoperative, immunonutrition on postoperative immunity and infectious complications in patients undergoing pancreaticoduodenectomy.
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Preventive and Therapeutic Role of Functional Ingredients of Barley Grass for Chronic Diseases in Human Beings.
Zeng, Y, Pu, X, Yang, J, Du, J, Yang, X, Li, X, Li, L, Zhou, Y, Yang, T
Oxidative medicine and cellular longevity. 2018;:3232080
Abstract
Barley grass powder is the best functional food that provides nutrition and eliminates toxins from cells in human beings; however, its functional ingredients have played an important role as health benefit. In order to better cognize the preventive and therapeutic role of barley grass for chronic diseases, we carried out the systematic strategies for functional ingredients of barley grass, based on the comprehensive databases, especially the PubMed, Baidu, ISI Web of Science, and CNKI, between 2008 and 2017. Barley grass is rich in functional ingredients, such as gamma-aminobutyric acid (GABA), flavonoids, saponarin, lutonarin, superoxide dismutase (SOD), K, Ca, Se, tryptophan, chlorophyll, vitamins (A, B1, C, and E), dietary fiber, polysaccharide, alkaloid, metallothioneins, and polyphenols. Barley grass promotes sleep; has antidiabetic effect; regulates blood pressure; enhances immunity; protects liver; has anti-acne/detoxifying and antidepressant effects; improves gastrointestinal function; has anticancer, anti-inflammatory, antioxidant, hypolipidemic, and antigout effects; reduces hyperuricemia; prevents hypoxia, cardiovascular diseases, fatigue, and constipation; alleviates atopic dermatitis; is a calcium supplement; improves cognition; and so on. These results support that barley grass may be one of the best functional foods for preventive chronic diseases and the best raw material of modern diet structure in promoting the development of large health industry and further reveal that GABA, flavonoids, SOD, K-Ca, vitamins, and tryptophan mechanism of barley grass have preventive and therapeutic role for chronic diseases. This paper can be used as a scientific evidence for developing functional foods and novel drugs for barley grass for preventive chronic diseases.