밀크씨슬 (실리마린)

Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions.

1. Planta Med. 2012 Sep;78(13):1458-77. doi: 10.1055/s-0032-1315117. Epub 2012 Aug 1. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Hermann R(1), von Richter O. Author information: (1)Clinical Research Appliance, Radolfzell, Germany. robert.hermann@cr-

Coadministration of milk thistle and indinavir in healthy subjects.

2. Pharmacotherapy. 2003 Jul;23(7):866-70. doi: 10.1592/phco.23.7.866.32723. Coadministration of milk thistle and indinavir in healthy subjects. DiCenzo R(1), Shelton M, Jordan K, Koval C, Forrest A, Reichman R, Morse G. Author information: (1)University of Buffalo School of Pharmacy and Pharmace

Silymarin-alpha lipoic acid and metabolic dysfunction-associated steatotic liver disease: Insights and methodological considerations.

1. World J Hepatol. 2025 Sep 27;17(9):110162. doi: 10.4254/wjh.v17.i9.110162. Silymarin-alpha lipoic acid and metabolic dysfunction-associated steatotic liver disease: Insights and methodological considerations. Martínez-Sánchez FD(1), Martínez-Vázquez SE(1), Gutiérrez-Monterrubio R(1), Muñoz-Martínez S(2), Garcia-Juarez I(3). Author information: (1)Department of Gastroenterology and Hepatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan 14080, CDMX, Mexico. (2)Department of Gastroenterology and Hepatology, ABC Medical Center, Tlalpan 14080, CDMX, Mexico. (3)Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan 14080, CDMX, Mexico. drinter77@gmail.com. The trial by Cano Contreras et al examined a proprietary formulation containing Silybum marianum and alpha-lipoic acid (SM-ALA), combined with a Mediterranean diet, in patients with metabolic dysfunction-associated steatotic liver disease. While some metabolic benefits were observed, limitations such as the absence of an SM-ALA-only group, the lack of histological data, and a small sample size reduce the validity of the findings. Future research should follow clinical trial standards for pharmacological studies, including phase 1/2 testing, validated outcomes, and transparency. ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved. DOI: 10.4254/wjh.v17.i9.110162 PMCID: PMC12476725 PMID: 41024889 Conflict of interest statement: Conflict-of-interest statement: The authors declare no competing interests.

Evaluating Bioactive-Substance-Based Interventions for Adults with MASLD: Results from a Systematic Scoping Review.

2. Nutrients. 2025 Jan 26;17(3):453. doi: 10.3390/nu17030453. Evaluating Bioactive-Substance-Based Interventions for Adults with MASLD: Results from a Systematic Scoping Review. Handu D(1), Stote K(2), Piemonte T(1). Author information: (1)Academy of Nutrition and Dietetics, Chicago, IL 60606, USA. (2)Department of Allied Health Sciences, State University of New York, Empire State University, Saratoga Springs, NY 12866, USA. Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition affecting a broad population. This review aimed to identify and summarize the current evidence on bioactive-substance-based interventions for adults with MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), covering publications from 2000 to 2023. Methods: A search was conducted across six databases (MEDLINE, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Food Science Source, and SPORTDiscus) for randomized controlled trials and other study types (e.g., prospective cohort studies and systematic reviews), reflecting the scoping nature of this review. The search was limited to studies in adults (>18 years old), with an intervention of interest and at least one comparator group. Results: A total of 4572 articles were retrieved, with 201 full-text articles screened for eligibility. Of these, 131 primary studies and 49 systematic reviews were included in the scoping review. The most studied bioactive substances were Curcumin (Turmeric) (n = 25), Silymarin (Milk Thistle) (n = 17), Resveratrol (n = 10), Coffee (n = 7), Green Tea (n = 5), and Berberine (n = 5 each). Moreover, 46 studies reported on 36 other bioactive substances with 2 or fewer articles each. Among the included systematic reviews, 13 focused on Curcumin, 12 on Coffee or Tea, 10 on bioactive substance combinations, 6 on Resveratrol, and 2 each on Silymarin and Artichoke Leaf. The included studies showed substantial heterogeneity in reported outcomes, which primarily focused on hepatic health, body weight, adverse events, glycemic control, blood lipids, and body composition. Conclusions: This scoping review highlights a range of bioactive substances used in the treatment of MASLD. While evidence is abundant for bioactive substances like Curcumin and Silymarin, further research and synthesis of findings is necessary to establish the clinical efficacy of all bioactive substances. DOI: 10.3390/nu17030453 PMCID: PMC11820841 PMID: 39940310 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest related to this work. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results [197,198,199,200,201,202,203].

Nutraceutical composition (yeast β-glucan, prebiotics, minerals, and silymarin) predicts improvement of sleep quality and metabolic parameters: A randomized pilot study.

3. Clin Nutr ESPEN. 2024 Oct;63:476-490. doi: 10.1016/j.clnesp.2024.06.033. Epub 2024 Jul 2. Nutraceutical composition (yeast β-glucan, prebiotics, minerals, and silymarin) predicts improvement of sleep quality and metabolic parameters: A randomized pilot study. Santamarina AB(1), Nehmi Filho V(2), Freitas JA(2), Silva BFRBD(3), Gusmão AF(4), Olivieri EHR(4), Souza E(5), Silva SLD(6), Miranda DA(7), Demarque DP(8), Oliveira EDS(8), Otoch JP(9), Pessoa AFM(2). Author information: (1)Laboratório de Produtos e Derivados Naturais, Laboratório de Investigação Médica-26 (LIM-26), Departamento de Cirurgia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 01246903, Brazil; Pesquisa e Desenvolvimento Efeom Nutrição S/A, São Paulo, SP 03317-000, Brazil; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos, SP 11015-020, Brazil. Electronic address: alinesantamarina@gmail.com. (2)Laboratório de Produtos e Derivados Naturais, Laboratório de Investigação Médica-26 (LIM-26), Departamento de Cirurgia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 01246903, Brazil; Pesquisa e Desenvolvimento Efeom Nutrição S/A, São Paulo, SP 03317-000, Brazil. (3)Laboratório de Produtos e Derivados Naturais, Laboratório de Investigação Médica-26 (LIM-26), Departamento de Cirurgia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 01246903, Brazil; Laboratório Interdisciplinar em Fisiologia e Exercício, Universidade Federal de São Paulo (UNIFESP), Santos, SP 11015-020, Brazil. (4)International Research Center, A.C. Camargo Cancer Center, São Paulo, SP 01508-010, Brazil. (5)Ambulatório Monte Azul, São Paulo, SP 05801-110, Brazil. (6)Pesquisa e Desenvolvimento Efeom Nutrição S/A, São Paulo, SP 03317-000, Brazil. (7)Departamento de Fisiologia, Escola Paulista de Medicina/Universidade Federal de São Paulo, São Paulo, SP 04023062, Brazil. (8)Laboratório de Farmacognosia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil. (9)Laboratório de Produtos e Derivados Naturais, Laboratório de Investigação Médica-26 (LIM-26), Departamento de Cirurgia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 01246903, Brazil; Pesquisa e Desenvolvimento Efeom Nutrição S/A, São Paulo, SP 03317-000, Brazil; Hospital Universitário da Universidade de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 05508-000, Brazil. BACKGROUND & AIMS: The search for integrative and natural therapies that favor homeostasis to boost sleep and diet quality took place for young adult populations as a non-pharmacological strategy for long-term good quality of life. Thus, the present pilot study aims to investigate the effects of 90-day consumption of a nutraceutical composition on the neuro-immune-endocrine axis, providing better sleep quality and health improvement. METHODS: For this, from March 2021 to June 2021, twenty-two Brazilian young adult volunteers (women and men) with BMI between 18.5 and 34.9 kg/m2 were divided into three distinct supplementation groups: NSupple; NSupple plus_S, and NSupple plus. Briefly, the supplement compositions included yeast β-glucan, prebiotics, and minerals in different concentrations associated or not with the herbal medicine silymarin. Neither nutritional nor physical activity interventions were performed during this pilot study period. The anthropometrics measures, questionnaires answer data, and harvest blood for metabolic, inflammatory, and hormonal tests were collected at baseline time (day zero-T0) and day 90 (T90) post-supplementation. RESULTS: Our results highlight that the supplementation reduced body mass index (BMI), Waist-to-height ratio (WHtR), waist circumference, AST/ALT ratio, alkaline phosphatase, and HbA1c. Post-supplementation the IL-6 and IL-10 levels and the sleep, humor, and quality of life scores were suggested to improve. Sleep quality improvement seems to predict the reduction of adiposity-related body measures. CONCLUSION: In sum, the nutraceutical supplementation might be related to anthropometric, metabolic, and endocrine parameters after 90 days reflecting on perception of humor, sleep, and life quality enhancement. However, it is important to recognize the limitation of the data presented considering that this was a pilot study. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04810572 registered on 20th February 2021. Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.clnesp.2024.06.033 PMID: 39012843 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest This study received funding from EFEOM Nutrition S.A. The funder had the following involvement with the study: financial support for experimental protocol development and financial resources for analysis performed. All authors declare no other competing interests.

Nutraceutical blends predict enhanced health via microbiota reshaping improving cytokines and life quality: a Brazilian double-blind randomized trial.

4. Sci Rep. 2024 May 15;14(1):11127. doi: 10.1038/s41598-024-61909-3. Nutraceutical blends predict enhanced health via microbiota reshaping improving cytokines and life quality: a Brazilian double-blind randomized trial. Santamarina AB(1)(2), de Freitas JA(1)(2), Franco LAM(3), Nehmi-Filho V(1)(2), Fonseca JV(4), Martins RC(3), Turri JA(5), da Silva BFRB(1)(6), Fugi BEI(1)(7), da Fonseca SS(1)(7), Gusmão AF(8), Olivieri EHR(8), de Souza E(9), Costa S(4), Sabino EC(3), Otoch JP(1)(2)(10), Pessoa AFM(11)(12). Author information: (1)Laboratório de Produtos e Derivados Naturais, Laboratório de Investigação Médica-26 (LIM-26), Departamento de Cirurgia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, 01246903, Brazil. (2)Pesquisa e Desenvolvimento Efeom Nutrição S/A, São Paulo, SP, 03317000, Brazil. (3)Laboratório de Parasitologia Médica (LIM-46), Departamento de Doenças Infecciosas e Parasitárias, Universidade de São Paulo Instituto de Medicina Tropical de São Paulo, São Paulo, SP, 05403-000, Brazil. (4)Laboratório de Investigação Médica em Protozoologia, Bacteriologia e Resistência Antimicrobiana (LIM-49)Departamento de Doenças Infecciosas e Parasitárias, Universidade de São Paulo Instituto de Medicina Tropical de São Paulo, São Paulo, SP, 05403-000, Brazil. (5)Grupo de Pesquisa em Economia da Saúde, Departamento de Ginecologia e Obstetrícia, Universidade de São Paulo Faculdade de Medicina, São Paulo, SP, 01246903, Brazil. (6)Laboratório Interdisciplinar em Fisiologia e Exercício, Universidade Federal de São Paulo (UNIFESP), Santos, SP, 11015-020, Brazil. (7)Graduação em Nutrição, Faculdade de Saúde Pública, Universidade de São Paulo, São Paulo, SP, 01246904, Brazil. (8)International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, 01508-010, Brazil. (9)Ambulatório Monte Azul, São Paulo, SP, 05801-110, Brazil. (10)Faculdade de Medicina da, Universidade de São Paulo, Hospital Universitário da Universidade de São Paulo, São Paulo, SP, 05508-000, Brazil. (11)Laboratório de Produtos e Derivados Naturais, Laboratório de Investigação Médica-26 (LIM-26), Departamento de Cirurgia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, 01246903, Brazil. anabiorq@usp.br. (12)Pesquisa e Desenvolvimento Efeom Nutrição S/A, São Paulo, SP, 03317000, Brazil. anabiorq@usp.br. Nutraceutical interventions supporting microbiota and eliciting clinical improvements in metabolic diseases have grown significantly. Chronic stress, gut dysbiosis, and metainflammation have emerged as key factors intertwined with sleep disorders, consequently exacerbating the decline in quality of life. This study aimed to assess the effects of two nutraceutical formulations containing prebiotics (fructooligosaccharides (FOS), galactooligosaccharides (GOS), yeast β-glucans), minerals (Mg, Se, Zn), and the herbal medicine Silybum marianum L. Gaertn., Asteraceae (Milk thistle or Silymarin). These formulations, namely NSupple (without silymarin) and NSupple_Silybum (with silymarin) were tested over 180 days in overweight/obese volunteers from Brazil's southeastern region. We accessed fecal gut microbiota by partial 16S rRNA sequences; cytokines expression by CBA; anthropometrics, quality of life and sleep, as well as metabolic and hormonal parameters, at baseline (T0) and 180 days (T180) post-supplementation. Results demonstrated gut microbiota reshaping at phyla, genera, and species level post-supplementation. The Bacteroidetes phylum, Bacteroides, and Prevotella genera were positively modulated especially in the NSupple_Silybum group. Gut microbiota modulation was associated with improved sleep patterns, quality-of-life perception, cytokines expression, and anthropometric parameters post-supplementation. Our findings suggest that the nutraceutical blends positively enhance cardiometabolic and inflammatory markers. Particularly, NSupple_Silybum modulated microbiota composition, underscoring its potential significance in ameliorating metabolic dysregulation. Clinical trial registry number: NCT04810572. 23/03/2021. © 2024. The Author(s). DOI: 10.1038/s41598-024-61909-3 PMCID: PMC11096337 PMID: 38750102 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no competing interests.

Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis.

5. Ann Hepatol. 2024 Mar-Apr;29(2):101174. doi: 10.1016/j.aohep.2023.101174. Epub 2023 Oct 29. Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis. Li S(1), Duan F(2), Li S(2), Lu B(3). Author information: (1)The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou 450000, China. (2)The First Affiliated Hospital of Henan University of TCM Zhengzhou 450000, China. (3)Henan University of Chinese Medicine, Zhengzhou 450046, China. Electronic address: lbp1921@sohu.com. INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant. RESULTS: A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]). CONCLUSIONS: Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research. Copyright © 2023 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved. DOI: 10.1016/j.aohep.2023.101174 PMID: 38579127 [Indexed for MEDLINE] Conflict of interest statement: Declaration of interests None.

Adjunctive silymarin supplementation and its effects on disease severity, oxidative stress, and inflammation in patients with Alzheimer's disease.

6. Nutr Neurosci. 2024 Oct;27(10):1077-1087. doi: 10.1080/1028415X.2023.2301163. Epub 2024 Feb 14. Adjunctive silymarin supplementation and its effects on disease severity, oxidative stress, and inflammation in patients with Alzheimer's disease. Navabi SM(1), Elieh-Ali-Komi D(2)(3), Afshari D(4), Goudarzi F(5), Mohammadi-Noori E(6), Heydari K(7), Heydarpour F(8), Kiani A(5). Author information: (1)Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran. (2)Institute of Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. (3)Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany. (4)Department of Neurology, College of Medicine, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. (5)Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. (6)Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. (7)Department of Clinical Pharmacy, Faculty of Pharmacy, Islamic, Azad, University of Tehran, Tehran, Iran. (8)Social Development and Health Promotion Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. BACKGROUND: Brain tissue in Alzheimer's patients is exposed to oxidative stress. Silymarin is an adjunct drug that has anti-inflammatory and antioxidant properties. OBJECTIVE: This study aimed to evaluate the effect of silymarin on biomarkers of oxidative stress, inflammation, and disease severity in Alzheimer's patients. METHODS: This randomized, single-blind clinical trial study was performed on 33 patients with Alzheimer's disease (AD) whose disease was confirmed by DSM-5 criteria and by brain imaging. Patients in the case group received three 250 mg silymarin capsules daily (each containing 150 mg silymarin), as an adjunctive medication in addition to the routine medication regimen. In the placebo group (control), patients received the same amount of placebo. All patients underwent Mini Mental State Exam (MMSE) and a panel of blood tests including malondialdehyde, neopterin, catalase, paraoxonase-1, total oxidative status, and total antioxidant capacity to reevaluate the changes pre/postintervention at the end of the trimester. RESULTS: The catalase and MDA serum levels after the adjunctive silymarin treatment decreased significantly (Catalasebefore silymarin = 9.29 ± 7.02 vs Catalaseafter silymarin = 5.32 ± 2.97, p = 0.007 and MDAbefore silymarin = 4.29 ± 1.90 vs MDAafter silymarin = 1.66 ± 0.84, p < 0.001) while MMSE increased notably (MMSEbefore silymarin = 10.39 ± 6.42 vs MMSEafter silymarin = 13.37 ± 6.81, p < 0.001). CONCLUSION: Silymarin can be effective as an adjunct drug and a powerful antioxidant in reducing oxidative stress and improving the course of AD. DOI: 10.1080/1028415X.2023.2301163 PMID: 38353101 [Indexed for MEDLINE]

Feasible feeding strategies for sustainable management of serve heat stress conditions: Effect of Milk Thistle extract on growth performance and health status of newly weaned rabbits.

7. J Anim Physiol Anim Nutr (Berl). 2024 May;108(3):778-791. doi: 10.1111/jpn.13930. Epub 2024 Feb 4. Feasible feeding strategies for sustainable management of serve heat stress conditions: Effect of Milk Thistle extract on growth performance and health status of newly weaned rabbits. Hassan MAE(1), Ragab MA(1), Shazly SA(1), Ahmed ME(1), El-Kholany ME(1), El-Raghi AA(2). Author information: (1)Agriculture Research Center, Animal Production Research Institute (APRI), Ministry of Agriculture, Dokki, Giza, Egypt. (2)Department of Animal, Poultry, and Fish Production, Faculty of Agriculture, Damietta University, Damietta, Egypt. The trail aimed to explore the effect of dietary supplementation of Milk Thistle (MT) extract on growth performance and health status of growing rabbits exposed to serve heat stress condition, considering the economic efficiency of supplementation. A total of 96 weaned male rabbits were divided into 4 groups (24 rabbits/group). The first group received the basal diet without any supplementation and served as a control (MT0), while 2nd, 3rd and 4th groups supplemented with MT at levels of 5 (MT5), 10 (MT10) and 15 (MT15) g/kg diet, respectively, for 10 consecutive weeks. Both of growth performance and feed utilisation were significantly enhanced by the dietary treatment, the optimum dose of MT was 12 g/kg diet for average daily gain, specific growth rate and performance index. However, it was 13 g/kg diet for feed conversation ratio. The polynomial regression analysis showed that the lowest values of rectal temperature and respiration rate were observed at doses of 11 and 13 g/kg diet respectively. The dressing percentage and the relative weights of liver and total edible giblets were significantly improved by the treatment (p = 0.0416, 0.0112 and 0.0032, respectively), maximising in the MT10 group. The MT10 and MT15 groups showed higher erythrocytes and leucocytes counts and lower levels of urea, creatinine and total cholesterol compared to the control (p < 0.05). Liver functions significantly enhanced in aforementioned two treated groups, the liver ultrastructure represented normal cytoplasmic organelles, and nucleus and mitochondria in MT10 group, while the MT15 group showed hepatocytes with dilated nucleus with most cytoplasmic organelles appeared well organised and normal except few small cytoplasms vacuolated. The levels glutathione, superoxide dismutase, catalase and total antioxidant capacity as well as immunoglobulin M, and immunoglobulin G significant improved in the MT-Treated groups compared to the control (p < 0.05). Economically, MT supplemented diets improved the net revenue of fattened rabbits during the summer season. In conclusion, the supplementation of MT extract at levels of 10 or 15 g/kg diet enhanced growth performance, feed utilisation, dressing percentage, hemato-biochemical attributes, immunity and redox balance of heat stressed growing rabbits during the hot season. © 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd. DOI: 10.1111/jpn.13930 PMID: 38311824 [Indexed for MEDLINE]

Efficacy of silymarin in patients with non-alcoholic fatty liver disease - the Siliver trial: a study protocol for a randomized controlled clinical trial.

8. Trials. 2023 Mar 10;24(1):177. doi: 10.1186/s13063-023-07210-6. Efficacy of silymarin in patients with non-alcoholic fatty liver disease - the Siliver trial: a study protocol for a randomized controlled clinical trial. de Avelar CR(1), Nunes BVC(2), da Silva Sassaki B(2), Dos Santos Vasconcelos M(2), de Oliveira LPM(2), Lyra AC(3), Bueno AA(4), de Jesus RP(2). Author information: (1)Department of Nutrition Sciences, Federal University of Bahia, Bahia, 32 Araújo Pinho Street, Canela, Salvador, Bahia, 40.110-150, Brazil. contato@camilaavelar.com.br. (2)Department of Nutrition Sciences, Federal University of Bahia, Bahia, 32 Araújo Pinho Street, Canela, Salvador, Bahia, 40.110-150, Brazil. (3)Gastrohepatology Service, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Bahia, Brazil. (4)College of Health, Life and Environmental Sciences, University of Worcester, Worcester, WR2 6AJ, UK. BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases globally. Pharmacological treatments for NAFLD are still limited. Silymarin, a compound extracted from Silybum marianum, is an herbal supplement traditionally used in folk medicine for liver disorders. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the efficacy of silymarin supplementation in the adjuvant treatment of NAFLD in adult patients. METHOD: This is a randomized double-blind placebo-controlled clinical trial recruiting adult NAFLD patients in therapy on an outpatient basis. Participants are randomized to an intervention (I) or control (C) group. Both groups receive identical capsules and are followed for 12 weeks. I receives 700mg of silymarin + 8mg vitamin E + 50mg phosphatidylcholine daily, while C receives 700mg maltodextrin + 8mg vitamin E + 50mg phosphatidylcholine daily. Patients undergo a computerized tomography (CT) scan and blood tests at the beginning and end of the study. Monthly face-to-face consultations and weekly telephone contact are carried out for all participants. The primary outcome assessed will be change in NAFLD stage, if any, assessed by the difference in attenuation coefficient between liver and spleen, obtained by upper abdomen CT. DISCUSSION: The results of this study may provide a valuable opinion on whether silymarin can be used as adjuvant therapy for the management or treatment of NAFLD. The data presented on the efficacy and safety of silymarin may provide more foundation for further trials and for a possible use in clinical practice. TRIAL REGISTRATION: This study has been approved by the Research Ethics Committee of the Professor Edgard Santos University Hospital Complex, Salvador BA, Brazil, under protocol 2.635.954. The study is carried out according to guidelines and regulatory standards for research involving humans, as set out in Brazilian legislation. Trial registration - ClinicalTrials.gov : NCT03749070. November 21, 2018. © 2023. The Author(s). DOI: 10.1186/s13063-023-07210-6 PMCID: PMC10000352 PMID: 36899430 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no competing interests.

Novel nutraceutical supplements with yeast β-glucan, prebiotics, minerals, and Silybum marianum (silymarin) ameliorate obesity-related metabolic and clinical parameters: A double-blind randomized trial.

9. Front Endocrinol (Lausanne). 2023 Jan 27;13:1089938. doi: 10.3389/fendo.2022.1089938. eCollection 2022. Novel nutraceutical supplements with yeast β-glucan, prebiotics, minerals, and Silybum marianum (silymarin) ameliorate obesity-related metabolic and clinical parameters: A double-blind randomized trial. Nehmi-Filho V(1)(2), Santamarina AB(3), de Freitas JA(1)(2), Trarbach EB(4), de Oliveira DR(1)(5), Palace-Berl F(1), de Souza E(6), de Miranda DA(7), Escamilla-Garcia A(8), Otoch JP(1)(2)(8), Pessoa AFM(1)(2)(9). Author information: (1)Natural Products and Derivatives Laboratory (LIM-26), Department of Surgery, University of São Paulo Medical School, São Paulo, SP, Brazil. (2)Research and Development Efeom Nutrition S/A, São Paulo, SP, Brazil. (3)Department of Biosciences, Federal University of São Paulo (UNIFESP), Santos, SP, Brazil. (4)Laboratory of Cellular and Molecular Endocrinology (LIM25), Division of Endocrinology and Metabology, Clinics Hospital, University of São Paulo Medical School, São Paulo, SP, Brazil. (5)Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, United States. (6)Monte Azul Ambulatory, São Paulo, SP, Brazil. (7)Departament of Physiology, Escola Paulista de Medicina/Universidade Federal de São Paulo, São Paulo, SP, Brazil. (8)University Hospital of the University of São Paulo, University of São Paulo Medical School, São Paulo, SP, Brazil. (9)Natural Products Committee, Brazilian Academic Consortium for Integrative Health (CABSIN), São Paulo, Brazil. PURPOSE: It is known that obesity has a multifactorial etiology that involves genetic and environmental factors. The WHO estimates the worldwide prevalence of 1.9 billion overweight adults and more than 650 million people with obesity. These alarming data highlight the high and growing prevalence of obesity and represent a risk factor for the development and aggravation of other chronic diseases, such as nonalcoholic fatty liver disease (NAFLD) that is frequently considered the hepatic outcome of type 2 diabetes. The use of non-pharmacological therapies such as food supplements, nutraceuticals, and natural integrative therapies has grown as an alternative tool for obesity-related diseases compared to conventional medications. However, it is a still little explored research field and lacks scientific evidence of therapeutic effectiveness. Considering this, the aim is to evaluate whether a new nutraceutical supplement composition can improve and supply essential mineral nutrients, providing an improvement of obesity-related metabolic and endocrine parameters. METHODS: Sedentary volunteers (women and men) with body mass index (BMI) ≤34.9 kg/m2 were divided into two groups: Novel Nutraceutical Supplement_(S) (n = 30) and Novel Nutraceutical Supplement (n = 29), differing in the absence (S) or presence of silymarin, respectively. Volunteers were instructed to take two capsules in the morning and two capsules in the evening. No nutritional intervention was performed during the study period. The data (anthropometrics and anamneses) and harvest blood (biochemistry and hormonal exams) were collected at three different time points: baseline time [day 0 (T0)], day 90 (T90), and day 180 (T180) post-supplementation. RESULTS: In the anthropometric analysis, the waist circumference in middle abdomen (WC-mid) and waist circumference in iliac crest (WC-IC) were reduced. Also, the waist-to-height ratio (WHt R) and waist-to-hip ratio (WHR) seem to slightly decrease alongside the supplementation period with both nutraceutical supplements tested as well as transaminase enzyme ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR)], a known as a biomarker of NAFLD, and endocrine hormones cortisol and thyroid-stimulating hormone (TSH) at 90 and 180 days post-supplementation. CONCLUSIONS: In a condition associated with sedentary and no nutritional intervention, the new nutraceutical supplement composition demonstrated the ability to be a strong and newfangled tool to improve important biomarkers associated with obesity and its comorbidities. Copyright © 2023 Nehmi-Filho, Santamarina, de Freitas, Trarbach, de Oliveira, Palace-Berl, de Souza, de Miranda, Escamilla-Garcia, Otoch and Pessoa. DOI: 10.3389/fendo.2022.1089938 PMCID: PMC9912840 PMID: 36778595 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Effects berberine-silymarin on liver enzymes: A systematic review and meta-analysis of randomized controlled trials.

10. Clin Nutr ESPEN. 2022 Jun;49:181-186. doi: 10.1016/j.clnesp.2022.01.037. Epub 2022 Feb 15. Effects berberine-silymarin on liver enzymes: A systematic review and meta-analysis of randomized controlled trials. Mohtashaminia F(1), Amini MR(2), Sheikhhossein F(3), Djafarian K(3), Shab-Bidar S(4). Author information: (1)Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran. (2)Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (3)Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran. (4)Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran. Electronic address: s_shabbidar@tums.ac.ir. BACKGROUND & AIMS: Despite controversies, no study has systematically summarized findings from earlier studies on the effect of berberine (BBR)-silymarin on liver enzymes. Therefore, the current systematic review and meta-analysis aimed to investigate the effect of berberis aristate and Silybum marianum on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in adults. METHODS: Relevant studies, published up to June 2021, were searched through PubMed/Medline, Scopus, ISI Web of Science, EMBASE and Google Scholar. The mean differences and standard deviations were pooled using a random-effects model. The studies' quality was evaluated using the Cochrane Risk of Bias Tool. RESULTS: Out of 80 citations, 5 trials that enrolled 549 participants were included. Berberis aristate and Silybum marianum resulted in no statistically significant change in ALT (weighted mean differences (WMD): -0.39 mg/dl; 95% CI: -1.67 to 0.89, P = 0.55), and AST (WMD: -0.44 mg/dl; 95% CI: -2.02 to 1.14, P = 0.58). CONCLUSION: We did not find any significant reduction in liver enzymes following BBR-silymarin consumption in adults. Further clinical trials with high quality according to the challenges mentioned seem to be helpful to use BBR-silymarin as a supplement for improving liver function. Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. DOI: 10.1016/j.clnesp.2022.01.037 PMID: 35623810 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declared no conflicts of interest.

Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases.

11. Phytother Res. 2018 Nov;32(11):2202-2213. doi: 10.1002/ptr.6171. Epub 2018 Aug 6. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Abenavoli L(1), Izzo AA(2), Milić N(3), Cicala C(2), Santini A(2), Capasso R(4). Author information: (1)Department of Health Sciences, University Magna Graecia, Catanzaro, Italy. (2)Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy. (3)Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. (4)Department of Agricultural Sciences, University of Naples Federico II, Naples, Italy. Milk thistle (MT; Silybum marianum), a member of the Asteraceae family, is a therapeutic herb with a 2,000-year history of use. MT fruits contain a mixture of flavonolignans collectively known as silymarin, being silybin (also named silibinin) the main component. This article reviews the chemistry of MT, the pharmacokinetics and bioavailability, the pharmacologically relevant actions for liver diseases (e.g., anti-inflammatory, immunomodulating, antifibrotic, antioxidant, and liver-regenerating properties) as well as the clinical potential in patients with alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, drug-induced liver injury, and mushroom poisoning. Overall, literature data suggest that, despite encouraging preclinical data, further well-designed randomized clinical trials are needed to fully substantiate the real value of MT preparations in liver diseases. © 2018 John Wiley & Sons, Ltd. DOI: 10.1002/ptr.6171 PMID: 30080294 [Indexed for MEDLINE]

Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A Triple-blinded randomized controlled clinical trial.

12. Phytomedicine. 2018 May 15;44:39-44. doi: 10.1016/j.phymed.2018.03.050. Epub 2018 Mar 19. Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A Triple-blinded randomized controlled clinical trial. Ebrahimpour-Koujan S(1), Gargari BP(2), Mobasseri M(3), Valizadeh H(4), Asghari-Jafarabadi M(5). Author information: (1)Students' Research Committee, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. (2)Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: bahrampg@yahoo.com. (3)Department of Internal Medicine, Tabriz University of Medical Science. Tabriz. Iran. (4)Research Center for Pharmaceutical Nanotechnology and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. (5)Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran. OBJECTIVE: This randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on glycemic indices and serum lipid profile in type 2 diabetes mellitus (T2DM) patients. METHODS: 40 T2DM patients (twenty male and twenty female), 25-50 years of age and on stable medication, were recruited for the present paralleled, randomized, triple-blinded, placebo-controlled clinical trial. The participants were randomly assigned to the silymarin or placebo groups, in which the patients either received 140 mg of silymarin, thrice daily (n = 20) or placebo (n = 20) for 45 days. Anthropometric and dietary intake data were collected at the baseline and end of the trial. Fasting blood samples were collected, and glycemic indices and lipid profile were determined at baseline, as well as the end of the study. RESULTS: Silymarin supplementation led to significant reduction in fasting blood sugar, serum insulin, homeostatic model assessment for insulin resistance, serum triglyceride and triglyceride to high-density lipoprotein cholesterol ratio as compared to the placebo, by 11.01, 14.35, 25.92, 23.7 and 27.67% respectively. There was significant increase in high-density lipoprotein cholesterol levels and quantitative insulin sensitivity check index in the silymarin group as compared to the placebo group, by 6.88 and 5.64% respectively, (p < 0.05). Total cholesterol and low-density lipoprotein cholesterol concentrations significantly decreased in the silymarin group as compared to the baseline, by 7.93 (p = 0.001) and 7.15% (p = 0.02), respectively. CONCLUSION: Silymarin supplementation may improve the glycemic indices and lipid profiles of T2DM patients. More studies are needed to validate the adjunct use of silymarin for metabolic control of T2DM patients. Copyright © 2018 Elsevier GmbH. All rights reserved. DOI: 10.1016/j.phymed.2018.03.050 PMID: 29895491 [Indexed for MEDLINE]

Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study.

13. Clin Ther. 2018 Jan;40(1):103-113.e1. doi: 10.1016/j.clinthera.2017.11.013. Epub 2017 Dec 19. Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study. Li WY(1), Yu G(2), Hogan RM(3), Mohandas R(4), Frye RF(1), Gumpricht E(5), Markowitz JS(6). Author information: (1)Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida. (2)Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida; Drug Clinical Trial Institution, Subei People's Hospital, Yangzhou, Jiangsu, China. (3)Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, Florida. (4)Department of Medicine, Nephrology and Hypertension Section, Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, Florida; Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, Florida. (5)Isagenix International LLC, Gilbert, Arizona. (6)Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida. Electronic address: jmarkowitz@cop.ufl.edu. PURPOSE: The purpose of this study was to compare the bioavailability between 2 milk thistle-containing dietary supplements, Product B and IsaGenesis, in healthy volunteers. METHODS: Bioavailability between Product B, originally formulated as a powdered capsule, and IsaGenesis, reformulated as a soft gel, were compared by measuring silybin A and silybin B as surrogate pharmacokinetic markers for differences in absorption and bioavailability. For this randomized, open-label, crossover pharmacokinetic study, 12 healthy volunteers consumed a single-dose serving of each supplement separated by at least a 7-day washout period. Serial blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and analyzed via LC-MS/MS. FINDINGS: Rapid absorption and elimination of silybin A and silybin B have been observed after oral administration of both Product B and IsaGenesis. However, the absorption rate and extent, as indicated by mean the Cmax and mean plasma AUC, were significantly higher for the IsaGenesis soft gel formulation. The dose-corrected mean Cmax was 365% and 450% greater for silybin A and B, respectively, relative to powdered Product B. The time to Tmax was reached, on average, at least 1 hour earlier with IsaGenesis relative to Product B for both silybin A and silybin B. IMPLICATIONS: The IsaGenesis soft gel formulation provided substantially greater absorption and bioavailability of silybin A and silybin B relative to the powdered Product B supplement. ClinicalTrials.gov Identifier: NCT02529605. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved. DOI: 10.1016/j.clinthera.2017.11.013 PMCID: PMC6037411 PMID: 29273470 [Indexed for MEDLINE]

Semen quality, antioxidant status and reproductive performance of rabbits bucks fed milk thistle seeds and rosemary leaves.

14. Anim Reprod Sci. 2017 Sep;184:178-186. doi: 10.1016/j.anireprosci.2017.07.014. Epub 2017 Jul 23. Semen quality, antioxidant status and reproductive performance of rabbits bucks fed milk thistle seeds and rosemary leaves. Attia YA(1), Hamed RS(2), Bovera F(3), Abd El-Hamid AEE(4), Al-Harthi MA(1), Shahba HA(2). Author information: (1)Department of Arid Land Agriculture, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah, 21589, Saudi Arabia. (2)Animal Production Research Institute, Ministry of Agriculture, ARC, Dokki, 12816, Gizza, Egypt. (3)Department of Veterinary Medicine and Animal Production, University of Napoli Federico II, 80137, Napoli, Italy. Electronic address: bovera@unina.it. (4)Animal and Poultry Production Department, Faculty of Agriculture, Damanhour University, Damanhour, 22516, Egypt. The study aimed to investigate the effects of milk thistle seeds (MTS) and rosemary leaves (RL) both at 5 and 10g/kg diet on reproductive performance, semen quality and blood metabolites of rabbit bucks. A total of 35 rabbit bucks were randomly distributed into five experimental groups (7 bucks/group). All the groups were fed the same basal diet. The 1st group (control) did not have MTS and RL in its basal diet. The 2nd and 3rd groups were supplemented with MTS at 5 and 10g/kg, respectively. The 4th and 5th groups were fed the basal diet supplemented with RL at 5 and 10g/kg, respectively. The sperm concentration (SC), total sperm output (TSO), live sperm (LS), total live sperm (TLS) and total motile sperm (TMS) were significantly greater in the bucks fed MTS at 10 and RL at 5g/kg diet than the control group. Bucks fed MTS at 10g/kg diet had higher fertility than the control. Also, RL 5g/kg group showed higher testosterone and fertility than the control, but the MTS 10g/kg group showed the highest value for both parameters. In conclusion, MTS and RL at 10 and 5g/kg, respectively, significantly improved the semen quality and the fertility and MTS also increased the economic efficiency of rabbit bucks. Copyright © 2017 Elsevier B.V. All rights reserved. DOI: 10.1016/j.anireprosci.2017.07.014 PMID: 28765034 [Indexed for MEDLINE]

Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements.

15. Drug Metab Dispos. 2016 Feb;44(2):162-71. doi: 10.1124/dmd.115.066902. Epub 2015 Oct 5. Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements. Sprouse AA(1), van Breemen RB(2). Author information: (1)University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois. (2)University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois breemen@uic.edu. The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug-botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John's wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug-botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug-botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics. DOI: 10.1124/dmd.115.066902 PMCID: PMC4727115 PMID: 26438626 [Indexed for MEDLINE]