Citrus Bergamia and Cynara Cardunculus Reduce Serum Uric Acid in Individuals with Non-Alcoholic Fatty Liver Disease

Background and Objectives: Hyperuricemia and liver steatosis are risk factors for cardiovascular diseases and mortality. The use of natural compounds could be a safe and effective alternative to drugs for the treatment of fatty liver and hyperuricemia. Polyphenolic fraction of Citrus Bergamia in association with the extract of Cynara Cardunculus, as nutraceutical, is able to reduce body weight, hepatic steatosis and markers of oxidative stress. Then, we performed a secondary analysis of a double-blind placebo-controlled trial to examine the effects of this nutraceutical on serum uric acid levels in adults with fatty liver. Materials and Methods: The study included 94 individuals with hepatic steatosis. For six weeks, the intervention group was given a nutraceutical (300 mg/day) comprising a Bergamot polyphenol fraction and Cynara Cardunculus extract. The control group received a daily pill of placebo. Serum uric acid, lipids, glucose and anthropometric parameters were assessed at baseline and after 6 weeks. Results: We found a greater reduction in serum uric acid in the participants taking the nutraceutical rather than placebo (−0.1 ± 0.7 mg/dL vs. 0.3 ± 0.7 mg/dL, p = 0.004), and especially in those with moderate/severe hepatic steatosis also after adjustment for confounding variables. In addition, we analysed the two groups according to tertiles of uric acid concentration. Among participants taking the nutraceutical, we found in those with the highest baseline serum uric acid (>5.4 mg/dL) the greater reduction compared to the lowest baseline uric acid (−7.8% vs. +4.9%; adjusted p = 0.04). The stepwise multivariable analysis confirmed the association between the absolute serum uric acid change and nutraceutical treatment (B = −0.43; p = 0.004). Conclusions: A nutraceutical containing bioactive components from bergamot and wild cardoon reduced serum uric acid during 6 weeks in adults with fatty liver. Future investigations are needed to evaluate the efficacy of this nutraceutical in the treatment of hyperuricaemia.

[1]  A. Pujia,et al.  A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease , 2022, Journal of translational medicine.

[2]  A. Salmi,et al.  Ultrasound and FibroScan® Controlled Attenuation Parameter in patients with MAFLD: head to head comparison in assessing liver steatosis , 2022, Endocrine.

[3]  A. Pujia,et al.  Bergamot Polyphenol Extract Reduces Hepatocyte Neutral Fat by Increasing Beta-Oxidation , 2022, Nutrients.

[4]  M. Farag,et al.  Therapeutic Potential of Artichoke in the Treatment of Fatty Liver: A Systematic Review and Meta-Analysis. , 2022, Journal of medicinal food.

[5]  T. Luedde,et al.  An elevated FIB-4 score predicts liver cancer development: a longitudinal analysis from 29,999 NAFLD patients: Reply to: "EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis- 2021 update". , 2021, Journal of hepatology.

[6]  Haifeng Yu,et al.  Relationship between serum uric acid level and nonalcoholic fatty liver disease in type 2 diabetes patients , 2021, Medicine.

[7]  C. Borghi,et al.  The Impact of Uric Acid and Hyperuricemia on Cardiovascular and Renal Systems. , 2021, Cardiology clinics.

[8]  H. Yasunaga,et al.  Relation of Serum Uric Acid and Cardiovascular Events in Adults Aged 20-49 Years. , 2021, The American journal of cardiology.

[9]  M. Friedrich-Rust,et al.  Easl Clinical Practice Guidelines (Cpgs) On Non-Invasive Tests For Evaluation Of Liver Disease Severity And Prognosis- 2020 Update. , 2021, Journal of hepatology.

[10]  R. Savino,et al.  Effect of a novel functional tomato sauce (OsteoCol) from vine-ripened tomatoes on serum lipids in individuals with common hypercholesterolemia: tomato sauce and hypercholesterolemia , 2021, Journal of translational medicine.

[11]  M. Trauner,et al.  Accuracy of non-invasive liver stiffness measurement and steatosis quantification in patients with severe and morbid obesity. , 2021, Hepatobiliary surgery and nutrition.

[12]  R. Newson,et al.  Incident gout and weight change patterns: a retrospective cohort study of US adults , 2020, Arthritis Research & Therapy.

[13]  K. Node,et al.  Uric acid and cardiovascular disease: A clinical review. , 2020, Journal of cardiology.

[14]  A. Fonseca,et al.  Bariatric surgery during the evolution of fatty liver–A randomized clinical trial comparing gastric bypass and sleeve gastrectomy based on transient elastography , 2020, Clinical obesity.

[15]  Xiuhua Guo,et al.  Hyperuricemia precedes non-alcoholic fatty liver disease with abdominal obesity moderating this unidirectional relationship: Three longitudinal analyses. , 2020, Atherosclerosis.

[16]  D. Foti,et al.  Randomized Clinical Trial: Bergamot Citrus and Wild Cardoon Reduce Liver Steatosis and Body Weight in Non-diabetic Individuals Aged Over 50 Years , 2020, Frontiers in Endocrinology.

[17]  Minhui Li,et al.  Bioactive Compounds from Plant-Based Functional Foods: A Promising Choice for the Prevention and Management of Hyperuricemia , 2020, Foods.

[18]  Ting Bao,et al.  Association between Serum Uric Acid and Nonalcoholic Fatty Liver Disease in Nonobese Postmenopausal Women: A Cross-sectional Study , 2020, Scientific Reports.

[19]  L. Jacobsson,et al.  Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors , 2020, Nature Reviews Rheumatology.

[20]  F. Wei,et al.  Higher Serum Uric Acid Level Predicts Non-alcoholic Fatty Liver Disease: A 4-Year Prospective Cohort Study , 2020, Frontiers in Endocrinology.

[21]  M. Volterrani,et al.  The synergistic effect of Citrus bergamia and Cynara cardunculus extracts on vascular inflammation and oxidative stress in non-alcoholic fatty liver disease , 2020, Journal of traditional and complementary medicine.

[22]  Hiroshi Suzuki,et al.  Inhibitory effect of Citrus flavonoids on the in vitro transport activity of human urate transporter 1 (URAT1/SLC22A12), a renal re-absorber of urate , 2020, npj Science of Food.

[23]  G. Parati,et al.  Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years , 2019, Hypertension.

[24]  Jin-Long Wu,et al.  Effect of lemon water soluble extract on hyperuricemia in a mouse model. , 2019, Food & function.

[25]  T. Eleftheriadis,et al.  Dietary Antioxidant Supplements and Uric Acid in Chronic Kidney Disease: A Review , 2019, Nutrients.

[26]  A. Cicero,et al.  Safety and tolerability of available urate-lowering drugs: a critical review , 2019, Expert opinion on drug safety.

[27]  R. Andrade,et al.  Higher levels of serum uric acid influences hepatic damage in patients with non-alcoholic fatty liver disease (NAFLD). , 2019, Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva.

[28]  Wen-Wen Chen,et al.  Examining the use of allopurinol: Perspectives from recent drug injury relief applications. , 2019, Journal of the Formosan Medical Association = Taiwan yi zhi.

[29]  C. Mignogna,et al.  Bergamot Polyphenols Boost Therapeutic Effects of the Diet on Non-Alcoholic Steatohepatitis (NASH) Induced by “Junk Food”: Evidence for Anti-Inflammatory Activity , 2018, Nutrients.

[30]  D. Del Rio,et al.  Consumption of orange fermented beverage improves antioxidant status and reduces peroxidation lipid and inflammatory markers in healthy humans. , 2018, Journal of the science of food and agriculture.

[31]  L. Gong,et al.  Gender-specific association of serum uric acid levels and cardio-ankle vascular index in Chinese adults , 2018, Lipids in Health and Disease.

[32]  L. Gong,et al.  Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults , 2017, Lipids in Health and Disease.

[33]  K. Wijarnpreecha,et al.  Hyperuricemia is associated with nonalcoholic fatty liver disease activity score in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis , 2017, European journal of gastroenterology & hepatology.

[34]  F. Perez-Ruiz,et al.  Potency on lowering serum uric acid in gout patients: a pooled analysis of registrative studies comparing febuxostat vs. allopurinol. , 2017, European review for medical and pharmacological sciences.

[35]  C. Torti,et al.  Protein and vitamin B6 intake are associated with liver steatosis assessed by transient elastography, especially in obese individuals , 2017, Clinical and molecular hepatology.

[36]  A. G. Alkushi Biological Effect of Cynara cardunculus on Kidney Status of Hypercholesterolemic Rats , 2017, Pharmacognosy magazine.

[37]  A. Ferramosca,et al.  Antioxidant dietary approach in treatment of fatty liver: New insights and updates , 2017, World journal of gastroenterology.

[38]  Xiuxin Deng,et al.  Lemon fruits lower the blood uric acid levels in humans and mice , 2017 .

[39]  G. Sesti,et al.  Uric Acid Is Associated With Inflammatory Biomarkers and Induces Inflammation Via Activating the NF-&kgr;B Signaling Pathway in HepG2 Cells , 2017, Arteriosclerosis, thrombosis, and vascular biology.

[40]  C. Byrne,et al.  Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents. , 2017, Journal of hepatology.

[41]  L. Appel,et al.  DASH diet and change in serum uric acid over time , 2017, Clinical Rheumatology.

[42]  H. Hmouda,et al.  Drug-induced hyperuricaemia and gout. , 2016, Rheumatology.

[43]  N. Malara,et al.  The treatment of hyperuricemia. , 2016, International journal of cardiology.

[44]  Carolina Muscoli,et al.  Regulation of uric acid metabolism and excretion. , 2016, International journal of cardiology.

[45]  H. Tilg,et al.  EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. , 2016, Journal of hepatology.

[46]  Wei Wang,et al.  Chemical Evidence for Potent Xanthine Oxidase Inhibitory Activity of Ethyl Acetate Extract of Citrus aurantium L. Dried Immature Fruits , 2016, Molecules.

[47]  European Association for the Study of the Liver,et al.  EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease , 2016, Obesity Facts.

[48]  N. Schlesinger,et al.  SAT0318 Lemon Juice Reduces Serum Uric Acid Level Via Alkalization of Urine in Gouty and Hyperuremic Patients- A Pilot Study , 2015 .

[49]  Zhenzhong Wang,et al.  Study on the anti-gout activity of chlorogenic acid: improvement on hyperuricemia and gouty inflammation. , 2014, The American journal of Chinese medicine.

[50]  Y. Moriwaki Effects on Uric Acid Metabolism of the Drugs except the Antihyperuricemics , 2014 .

[51]  J. Singh Racial and Gender Disparities Among Patients with Gout , 2013, Current Rheumatology Reports.

[52]  R. Burini,et al.  High plasma uric acid concentration: causes and consequences , 2012, Diabetology & Metabolic Syndrome.

[53]  V. de Lédinghen,et al.  Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. , 2010, Ultrasound in medicine & biology.

[54]  M. Meydani,et al.  Dietary Polyphenols and Obesity , 2010, Nutrients.

[55]  Yan Shi Caught red-handed: uric acid is an agent of inflammation. , 2010, The Journal of clinical investigation.

[56]  F. Haidari,et al.  Orange Juice and Hesperetin Supplementation to Hyperuricemic Rats Alter Oxidative Stress Markers and Xanthine Oxidoreductase Activity , 2009, Journal of clinical biochemistry and nutrition.

[57]  S. Sarawek,et al.  Flavonoids of Cynara scolymus possess potent xanthinoxidase inhibitory activity in vitro but are devoid of hypouricemic effects in rats after oral application. , 2008, Planta medica.

[58]  Dong-Mei Zhang,et al.  Hypouricemic action of selected flavonoids in mice: structure-activity relationships. , 2007, Biological & pharmaceutical bulletin.