Intervention Review

Antioxidant supplements for liver diseases

  1. Goran Bjelakovic1,*,
  2. Lise Lotte Gluud2,
  3. Dimitrinka Nikolova3,
  4. Marija Bjelakovic4,
  5. Aleksandar Nagorni5,
  6. Christian Gluud3

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 16 MAR 2011

Assessed as up-to-date: 1 FEB 2011

DOI: 10.1002/14651858.CD007749.pub2

Database Title

Additional Information

How to Cite

Bjelakovic G, Gluud LL, Nikolova D, Bjelakovic M, Nagorni A, Gluud C. Antioxidant supplements for liver diseases. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No.: CD007749. DOI: 10.1002/14651858.CD007749.pub2.

Author Information

  1. 1

    and Department of Internal Medicine - Gastroenterology and Hepatology, Medical Faculty, University of Nis, Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Nis, Serbia

  2. 2

    Gentofte University Hospital, Department of Internal Medicine, Hellerup, Denmark

  3. 3

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

  4. 4

    Medical Faculty, University of Nis, Institute of Anatomy, Nis, Serbia

  5. 5

    Medical Faculty, University of Nis, Department of Internal Medicine - Gastroenterology and Hepatology, Nis, Serbia

*Goran Bjelakovic, Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, and Department of Internal Medicine - Gastroenterology and Hepatology, Medical Faculty, University of Nis, Zorana Djindjica 81, Nis, 18000, Serbia. goranb@junis.ni.ac.rs.

Publication History

  1. Publication Status: New
  2. Published Online: 16 MAR 2011

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Background

Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal.

Objectives

To assess the benefits and harms of antioxidant supplements for patients with liver diseases.

Search strategy

We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science to January 2011. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials.

Selection criteria

We considered for inclusion randomised trials that compared antioxidant supplements (beta-carotene, vitamin A, C, E, and selenium) versus placebo or no intervention for autoimmune liver diseases, viral hepatitis, alcoholic liver disease, and cirrhosis (any aetiology).

Data collection and analysis

Four authors independently selected trials for inclusion and extracted data. Outcome measures were all-cause mortality, liver-related mortality, liver-related morbidity, biochemical indices at maximum follow-up in the individual trials as well as adverse events, quality-of-life measures, and cost-effectiveness. For patients with hepatitis B or C we also considered end of treatment and sustained virological response. We conducted random-effects and fixed-effect meta-analyses. Results were presented as relative risks (RR) or mean differences (MD), both with 95% confidence intervals (CI).

Main results

Twenty randomised trials with 1225 participants were included. The trials assessed beta-carotene (3 trials), vitamin A (2 trials), vitamin C (9 trials), vitamin E (15 trials), and selenium (8 trials). The majority of the trials had high risk of bias and showed heterogeneity. Overall, the assessed antioxidant supplements had no significant effect on all-cause mortality (relative risk [RR] 0.84, 95% confidence interval [CI] 0.60 to 1.19, I2 = 0%), or liver-related mortality (RR 0.89, 95% CI 0.39 to 2.05, I2 = 37%). Stratification according to the type of liver disease did not affect noticeably the results. Antioxidant supplements significantly increased activity of gamma glutamyl transpeptidase (MD 24.21 IU/l, 95% CI 6.67 to 41.75, I2 = 0%).

Authors' conclusions

We found no evidence to support or refute antioxidant supplements in patients with liver disease. Antioxidant supplements may increase liver enzyme activity.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Antioxidant supplements for liver disease

Beta-carotene, vitamin A, vitamin C, and vitamin E cannot be recommended for treatment of liver diseases.

An imbalance between too much oxidative stress and too little antioxidative defence has been suggested to cause a variety of liver diseases. Therefore, antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) could have a potential role in patients with liver disease. The evidence on whether antioxidant supplements are effective in treatment of liver diseases is contradictory.

In this review treatment with antioxidant supplements of alcoholic, autoimmune, hepatitis B or hepatitis C virus liver diseases, or liver cirrhosis is assessed. The review includes 20 randomised clinical trials. In total, 1225 participants were randomised to antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. The low number of randomised participants increases the risk of random errors ('play of chance'). Trial quality was low and accordingly the risk of systematic errors ('bias') was high.

Based on the conducted randomised clinical trials, convincing evidence that beta-carotene, vitamin A, vitamin C, and vitamin E or their combinations are beneficial for treatment of alcoholic, autoimmune, hepatitis B or hepatitis C virus liver diseases, or liver cirrhosis could not be found.

 

Resumen

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  2. Abstract
  3. Plain language summary
  4. Resumen

Antecedentes

Suplementos de antioxidantes para las enfermedades hepáticas

Varias enfermedades hepáticas se han asociado con estrés oxidativo. Por lo tanto, los antioxidantes se han indicado como fármacos terapéuticos posibles para varias enfermedades hepáticas. Las pruebas que apoyan estas indicaciones son contradictorias.

Objetivos

Evaluar los efectos beneficiosos y perjudiciales de los suplementos de antioxidantes para los pacientes con enfermedades hepáticas.

Estrategia de búsqueda

Se hicieron búsquedas en Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded y en Conference Proceedings Citation IndexScience hasta enero 2011. Se revisaron las bibliografías de publicaciones pertinentes y se les escribió a expertos y compañías farmacéuticas para encontrar ensayos adicionales.

Criterios de selección

Se consideraron para su inclusión ensayos con asignación aleatoria que compararan suplementos de antioxidantes (betacaroteno, vitamina A, C, E y selenio) versus placebo o ninguna intervención para las enfermedades hepáticas autoinmunes, las hepatitis virales, la hepatopatía alcohólica y la cirrosis (cualquier etiología).

Obtención y análisis de los datos

Cuatro autores seleccionaron de forma independiente los ensayos para su inclusión y extrajeron los datos. Las medidas de resultado fueron mortalidad por todas las causas, mortalidad relacionada con hepatopatía, morbilidad relacionada con hepatopatía, índices bioquímicos al seguimiento máximo en los ensayos individuales así como los eventos adversos, las medidas de calidad de vida y la relación costeefectividad. En los pacientes con hepatitis B o C también se consideró la respuesta virológica sostenida y al final del tratamiento. Se realizaron metanálisis de efectos aleatorios y de efectos fijos Los resultados se presentaron como riesgos relativos (RR) o diferencias de medias (DM), ambos con intervalos de confianza (IC) del 95%.

Resultados principales

Se incluyeron 20 ensayos con asignación aleatoria con 1 225 participantes. Los ensayos evaluaron el betacaroteno (tres ensayos), la vitamina A (dos ensayos), la vitamina C (nueve ensayos), la vitamina E (15 ensayos) y el selenio (ocho ensayos). La mayoría de los ensayos tuvo un alto riesgo de sesgo y mostró heterogeneidad. En general, los suplementos de antioxidantes evaluados no tuvieron efectos significativos sobre la mortalidad por todas las causas (riesgo relativo [RR] 0,84, intervalo de confianza [IC] del 95%: 0,60 a 1,19; I2 = 0%) ni sobre la mortalidad relacionada con hepatopatía (RR 0,89, IC del 95%: 0,39 a 2,05; I2 = 37%). La estratificación según el tipo de enfermedad hepática no afectó notoriamente los resultados. Los suplementos de antioxidantes aumentaron significativamente la actividad de la gammaglutamiltranspeptidasa (DM 24,21 UI/l, IC del 95%: 6,67 a 41,75; I2 = 0%).

Conclusiones de los autores

No se encontraron pruebas para apoyar o refutar el uso de suplementos de antioxidantes en pacientes con enfermedades hepáticas. Los suplementos de antioxidantes pueden aumentar la actividad de las enzimas hepáticas.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano

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